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Medicine & Pharmacology, General Medical Research; air pollution; coal-fired thermal power plant; oil thermal power plant; geocoded; lung cancer; bladder cancer; north-eastern Italy
Online: 25 May 2017 (08:40:54 CEST)
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We assessed lung and bladder cancer risk in people living near a coal-oil-fired thermal power plant in an area of north-eastern Italy covered by a population-based cancer registry. Incidence rate ratios (IRR) by sex, age, and histology were computed according to tertiles of residential exposure to benzene, nitrogen dioxide (NO2), particular matter (PM10), and sulfur dioxide (SO2) among 1076 incident cases of lung and 650 cases of bladder cancers. In men of all ages and in women under 75 years of age, no significant associations were observed. Conversely, in women aged ≥ 75 years significantly increased risks of lung and bladder cancer were related to high exposure to benzene (IRR for highest vs. lowest tertile: 2.00 for lung cancer and 1.94 for bladder cancer) and NO2 (IRR: 1.72 for lung cancer; and 1.94 for bladder cancer). In these women, a 1.71-fold higher risk of lung cancer was also related to high exposure to SO2. The findings of this descriptive study indicate that air pollution may have a role with regard to the risk of lung and bladder cancers, limited to women aged ≥ 75 years. Such increased risk warrants further analytical investigations.
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Medicine & Pharmacology, Nutrition; constitutive androstene receptor; cytochrome P450, fibrosis; gender difference; high-fat-cholesterol (HFC) diet; necrosis; stroke-prone spontaneously hypertensive 5/Dmcr rats; sulfotransferase, pregnane X receptor; UGP-glucuronosyltransferase
Online: 23 May 2017 (07:54:46 CEST)
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During middle age, women are less susceptible to nonalcoholic steatohepatitis (NASH) than men. Thus, we investigated the underlying molecular mechanisms behind these sexual differences using an established rat model of NASH. Mature female and male stroke-prone spontaneously hypertensive 5/Dmcr rats were fed control or high-fat-cholesterol (HFC) diets for 2, 8, and 14 weeks. Although HFC-induced hepatic fibrosis was markedly less severe in females than in males, only minor gender differences were observed in expression levels of cytochrome P450 enzymes (CYP)7A1, CYP8B1 CYP27A1, and CYP7B1, and multidrug resistance-associated protein 3, and bile salt export pump, which are involved in fibrosis-related bile acid (BA) kinetics. However, the BA detoxification-related enzymes UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) 2A1, and the nuclear receptors constitutive androstene receptor (CAR) and pregnane X receptor (PXR), were strongly suppressed in HFC fed males, and were only slightly changed in HFC-diet fed females. Expression levels of the farnesoid X receptor and its small heterodimer partner were similarly regulated in a gender-dependent fashion following HFC feeding. Hence, the pronounced female resistance to HFC-induced liver damage likely reflects sustained expression of the nuclear receptors CAR and PXR and the BA detoxification enzymes UGT and SULT.
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Medicine & Pharmacology, Nutrition; β-hydroxy-β-methylbutyrate, anti-inflamatory cytokines, resistance exercise
Online: 23 May 2017 (07:30:43 CEST)
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The aim of this study was to investigate the effect of β-Hydroxy-β-methylbutyrate (HMB) supplementation on anti-inflammatory cytokines including IL-4, IL-10 and TGF-β during an acute bout of resistance exercise (RE) in young resistance trained men. Ten resistance-trained men in a randomized, double-blind, placebo-controlled and crossover study, were administered a 7-day HMB supplementation (3×1 g.d-1 of HMB) and placebo (3×1 g.d-1 of Maltodextrin) with a 7 days washout period. After supplementation periods, subjects performed three sets of bench press, lat pull down, leg extension, leg curl, biceps curl, triceps curl and shoulder press to failure with 85% of one repetition to maximum (1RM). Blood samples were obtained before- (Pre), immediately post- (IP) and 1 hour-post RE (1h P) to assess serum concentrations of IL-4, IL-10 and TGF-β1. The data were analyzed using 2 (treatment: HMB and PL) × 3 (time points: Pre, IP and 1hP) repeated measures analysis of variance (ANOVA) followed by the Bonferroni post hoc test with a significant level of p<0.05. Serum IL-4 was significantly higher at IP resistance exercise in HMB compared to placebo. Circulating IL-4 and TGF-β1 were significantly raised at IP compared to Pre in both HMB and placebo treatments. No significant differences between treatments were observed for IL-10 and TGF-β1at any time points. In conclusion, HMB supplementation increased the circulating level of IL-4 during RE in resistance-trained men, which may attenuate inflammation and facilitate adaptation to RE.
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Medicine & Pharmacology, Ophthalmology; dry eye; lacrimal gland; lipids and lipidomics; Meibomian gland; ocular surface disorders; proteins and proteomics; tear film
Online: 22 May 2017 (07:54:47 CEST)
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The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome, because the tear film represents the interface between the eye and the environment. Despite having a multifactorial origin, the main risk factors for the emergence of the ocular disease are female gender and advanced age. Likewise, morphological changes in several glands and in chemical composition of their secretions such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors to maintain a condition of good health of the ocular anterior segment. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic infiammation that reflex on the ocular surface. However, it is one of the most commonly encountered disease in clinical practice and many other causes related to daily life and to lengthen the average life will contribute to the beginning. This review will consider how and what disorders of the ocular surface are responsible for a widespread pathology so. In the end, the most appropriate and new therapies will be briefly exposed according to the specific pathology.
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Medicine & Pharmacology, Nutrition; dietary substitution; CVD; saturated fatty acids; protein; monounsaturated fatty acids; polyunsaturated fatty acids; dairy fat; refined carbohydrates; whole grains
Online: 18 May 2017 (04:01:53 CEST)
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Dietary recommendations to decrease the risk of cardiovascular disease (CVD) have focused on reducing intake of saturated fatty acids (SFA) for more than 50 years. While the 2015-2020 Dietary Guidelines for Americans advise substituting both monounsaturated and polyunsaturated fatty acids for SFA, evidence supports other nutrient substitutions that will also reduce CVD risk. For example, replacing SFA with whole grains, but not refined carbohydrates, reduces CVD risk. Replacing SFA with protein, especially plant protein may also reduce CVD risk. While dairy fat (milk, cheese) is associated with a slightly lower CVD risk compared to meat, dairy fat results in a significantly greater CVD risk relative to unsaturated fatty acids. As research continues, we will refine our understanding of dietary patterns associated with lower CVD risk.
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Medicine & Pharmacology, Pharmacology & Toxicology; Aronia melanocarpa berries; bone biomechanical properties; cadmium; chokeberries; female rats; polyphenols; procollagen; protection
Online: 16 May 2017 (07:45:30 CEST)
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The hypothesis that consumption of Aronia melanocarpa berries (chokeberries) extract, recently reported by us to improve bone metabolism in female rats at low-level and moderate chronic exposure to cadmium (1 and 5 mg Cd/kg diet for up to 24 months), may increase the bone resistance to fracture was investigated. Biomechanical properties of the neck (bending test with vertical head loading) and diaphysis (three-point bending test) of the femur of rats administered 0.1% aqueous chokeberry extract (65.74% of polyphenols) or/and Cd in the diet (1 and 5 mg Cd/kg) for 3, 10, 17, and 24 months were evaluated. Moreover, procollagen I was assayed in the bone tissue. The low-level and moderate exposure to Cd decreased procollagen I concentration in the bone tissue and weakened biomechanical properties of the femoral neck and diaphysis. Chokeberry extract administration under the exposure to Cd improved the bone collagen biosynthesis and femur biomechanical properties. The results allow for the conclusion that consumption of chokeberry products under exposure to Cd may improve the bone biomechanical properties and protect from fracture. This study provides support for Aronia melanocarpa berries being a promising natural agent for the skeleton protection under low-level and moderate chronic exposure to Cd.
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Medicine & Pharmacology, General Medical Research; squamous cell carcinoma (SCC), Grainyhead-like 3 (Grhl3), interfollicular epidermis (IFE), supra-basal epidermis, involucrin (IVL), cancer-initiating cell (CIC), cancer stem cell (CSC).
Online: 12 May 2017 (18:15:31 CEST)
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Non-melanomatous skin cancers (NMSCs), which include basal and squamous cell carcinoma (BCC and SCC respectively), represent a significant burden on the population as well as an economic load to the health care system, yet treatments of these preventable cancers remain ineffective. Although primary prevention is possible through minimising sunlight exposure, the World Health Organisation estimates that between 2 and 3 million new cases of NMSCs are diagnosed each year, accounting for 1 in 3 of all newly diagnosed cancers. Furthermore, studies have estimated there has been a 2-fold increase in the incidence of NMSCs between 1960s and 1980s. The increase in cases of NMSCs as well as the lack of effective treatments makes the need for novel therapeutic approaches all the more necessary. To rationally develop more targeted treatments for NMSCs, a better understanding of the cell of origin, in addition to the underlying pathophysiological mechanisms that govern the development of these cancers, is urgent. NMSCs are generally thought to arise from specific types of stem cells that become the source of clonal expansion of tumourigenic cells. Previous research on SCC has alluded to these stem cells being localised in the basal compartment of the skin, which ordinarily houses the progenitor cells that contribute towards wound healing and normal cell turnover of overlying epidermal skin layers. More recent research has suggested that commitment to differentiation, which requires exiting the basal, progenitor-cell compartment, is a reversible mechanism. Genetic modifications engage differentiated cells into dedifferentiation, converting them into cancer-initiating cells (CICs) and thereby promoting a tumourigenic environment. Here we explore the most recent developments in the understanding of skin SCC cell of origin, and discuss a case study illustrating the loss of the Grainy-head like 3 (GRHL3) transcription factor in suprabasal layers, which confers a tendency towards tumour development and thereby challenging the “stem cell” theory of tumourigenesis.
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Medicine & Pharmacology, Oncology & Oncogenics; sulforaphane; withaferin; breast cancer; HDAC1; DNMTs; chemoprevention; epigenetics
Online: 12 May 2017 (05:19:02 CEST)
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With cancer often classified as a disease that has an important epigenetic component, natural compounds that have the ability to regulate the epigenome become ideal candidates for study. Humans have a complex diet, which illustrates the need to elucidate the mechanisms of interaction between these bioactive compounds in combination. The natural compounds withaferin A (WA), from the Indian winter cherry, and sulforaphane (SFN), from cruciferous vegetables, have numerous anti-cancer effects and some report their ability to regulate epigenetic processes. Our study is the first to investigate the combinatorial effects of low physiologically achievable concentrations of WA and SFN on breast cancer cell proliferation, histone deacetylase1 (HDAC1) and DNA methyltransferases (DNMTs). No adverse effects were observed on control cells at optimal concentrations. There was synergistic inhibition of cellular viability in MCF-7 cells and a greater induction of apoptosis with the combinatorial approach than with either compound administered alone in both MDA-MB-231 and MCF-7 cells. HDAC expression was down-regulated at multiple levels. Lastly, we determined the combined effects of these bioactive compounds on the pro-apoptotic BAX and anti-apoptotic BCL-2 and found decreases in BCL-2 and increases in BAX. Taken together, our findings demonstrate the ability of low concentrations of combinatorial WA and SFN to promote cancer cell death and regulate key epigenetic modifiers in human breast cancer cells.
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Medicine & Pharmacology, Nutrition; cancer; carotenoid; chemoprevention; Cucurbita; cytotoxicity; DNA-protection; tumor cells
Online: 11 May 2017 (17:31:47 CEST)
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Zucchini (Cucurbita pepo subsp. pepo) is a seasonal vegetable with high nutritional and medical value. Many useful properties of this fruit are attributed to its bioactive compounds. Zucchini fruits (“Yellow” and “Light Green” varieties) and four distinctive components (lutein, β-carotene, zeaxanthin and dehydroascorbic acid)were selected. Firstly it was determinated the lutein, β-carotene, zeaxanthin and dehydroascorbic acid content in these fruits and then, in order to measure the safety and suitability of their use different assays were carried out: (i) Genotoxicity and antigenotoxicity tests to determine the safety and DNA-protection against hydrogen peroxide; (ii) cytotoxicity and (iii) DNA fragmentation assay to evaluate the proapoptotic effect. Results showed that: (i) all the substances were non-genotoxic, (ii) all the substances were antigenotoxic except the highest concentration of lutein, (iii) “Yellow” Zucchini epicarp and mesocarp exhibited the highest cytotoxic activity (IC50 > 0.1 mg/mL and 0.2 mg/mL, respectively) and iv) “Light Green” Zucchini skin and pulp induced internucleosomal DNA fragmentation . To sump up, Zucchini fruit could play a positive role in human health and nutrition due to this fruit and its components were safe, able to inhibit significantly the H2O2-induced damage and exhibit antiproliferative and pro-apoptotic properties toward HL60 tumour cells. The information generated from this research should take into account to select potential accessions for breeding programs purposes.
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Medicine & Pharmacology, Oncology & Oncogenics; heterocyclic amines (HCAs); meat intake; colorectal cancer; colorectal adenomas; cancer prevention
Online: 9 May 2017 (06:13:18 CEST)
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Several evidences suggest that the positive association between meat intake and colorectal adenoma (CRA) and cancer (CRC) risk is mediated by mutagenic compounds generated during cooking at high temperature. A number of epidemiological studies have estimated the effect of meat-related mutagens intake on CRC/CRA risk with contradictory and sometime inconsistent results. A literature search was carried out (PubMed, Web of Science and Scopus) to identify articles reporting the relationship between the intake of meat-related mutagens (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine: PhIP, 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline: MeIQx, 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline: DiMeIQx, benzo(a) pyrene: (B(a)P) and “meat derived mutagenic activity”: MDM) and CRC/CRA risk. A random-effect model was used to calculate the risk association. Thirty-nine studies were included in the systematic review and meta-analysis. Polled CRA risk (15229 cases) was significantly increased by intake of PhIP (OR=1.20; 95%CI:1.13,1.28; p<0.001), MeIQx (OR=1.14; 95%CI:1.05,1.23; p=0.001), DiMeIQx (OR=1.13; 95%CI:1.05,1.21; p=0.001), B(a)P (OR=1.10; 95%CI:1.02,1.19; p=0.017) and MDM (OR=1.17; 95%CI:1.07,1.28; p=0.001). A linear and curvilinear trend was observed in dose-response meta-analisis between CRA risk in association with PhIP and MDM, MeIQx, respectively. CRC risk (21344 cases) was increased by uptake of MeIQx (OR=1.14; 95%CI:1.04,1.25; p=0.004), DiMeIQx (OR=1.12; 95%CI:1.02,1.22; p=0.014) and MDM (OR=1.12; 95%CI:1.06,1.19; p<0.001). No publication bias could be detected whereas heterogeneity was in some cases rather high. Mutagenic compounds formed during cooking of meat at high temperature may be responsible of its carcinogenicity.
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Medicine & Pharmacology, Obstetrics & Gynaecology; Hochu-ekki-to; immune modulation; polycystic ovarian syndrome
Online: 9 May 2017 (04:11:56 CEST)
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The traditional herbal medicine, Hochu-ekki-to, has been shown to have preventive effects on viral infection and stress. This study aimed to evaluate the clinical effects of Hochu-ekki-to on two stress-related rat models of polycystic ovarian syndrome. Female Sprague-Dawley rats were divided into control and treatment groups, the latter of which were subjected to stress induced by exposure to adrenocorticotropic hormone (ACTH) or cold temperatures. After these stress inductions, rats were orally treated with dissolved Hochu-ekki-to once per day for 7 days. Rats subjected to the two different stressors exhibited upregulation of steroid hormone receptors (in ovaries) and reproductive hormones (in blood), and consequent stimulation of abnormal follicle development accompanied by elevation of Hsp 90 expression (in ovaries). Treatment with Hochu-ekki-to for 7 days after stress induction increased immune functions, reduced the stress-induced activation of Hsp 90, and normalized the levels of the tested steroid hormone receptors and reproductive hormones. Our findings suggest that stress stimulations may promote the activation of Hsp 90 via the dysregulation of steroid hormone receptors and reproductive hormones, but that post-stress treatment with Hochu-ekki-to improves reproductive and immune functions in the ovaries of stressed rats.
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Medicine & Pharmacology, Pathology & Pathobiology; Toxoplasma gondii; neurophysiology; host-parasite interaction, neuroimmune, testosterone, dopamine, catecholamine, glutamatergic
Online: 8 May 2017 (18:34:39 CEST)
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Although the parasite Toxoplasma gondii is one of the most pervasive neurotropic pathogens in the world, the host-parasite interactions during CNS infection and consequences of neurological infection are just beginning to be unraveled. The chronic stages of infection have been considered dormant, although several studies have found correlations of infection with an array of host behavioral changes. These may facilitate parasite transmission and impact neurological diseases. During infection, in addition to the presence of the parasites within neurons, host-mediated neuroimmune and hormonal responses to infection are also present. T. gondii induces numerous changes to host neurons during infection and globally alters host neurological signaling pathways, as discussed in this review. Understanding the neurophysiological changes in the host brain is imperative to understanding the parasitic mechanisms and to delineate the effects of this single-celled parasite on health and its contribution to neurological disease.
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Medicine & Pharmacology, Other; economic evaluation; mathematical modeling; HIV vaccines; pre-exposure prophylaxis; cost-effectiveness
Online: 8 May 2017 (12:13:45 CEST)
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This economic evaluation aims to support policy-making on the combined use of pre-exposure prophylaxis (PrEP) with HIV vaccines by evaluating the potential cost-effectiveness of implementation that would support the design of clinical trials for assessment of combined product safety and efficacy. The target study population is a cohort of men who have sex with men (MSM) in the United States. Policy strategies considered include standard HIV prevention, daily oral PrEP, HIV vaccine, and their combination. We constructed a Markov model based on clinical trial data and published literature. We used a payer perspective, monthly cycle length, a lifetime horizon, and a 3% discount rate. We assumed a price of $500 per HIV vaccine series in the base case. HIV vaccines dominated standard care and PrEP. At current prices,PrEP was not cost-effective alone or in combination. A combination strategy had the greatest health benefit but was not cost-effective (ICER=$463,448/QALY) as compared to vaccination alone. Sensitivity analyses suggest a combination may be valuable for higher-risk men with good adherence. Vaccine durability and PrEP drug prices were key drivers of cost-effectiveness. Results suggest that boosting potential may be key to HIV vaccine value.
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Medicine & Pharmacology, Other; autologous; buffy coat; growth factor level; platelet-rich fibrin; thrombocyte concentrate
Online: 4 May 2017 (08:37:59 CEST)
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Fibrin rich of platelets (PRF®) of Choukroun represents a new step in the therapeutic concept of platelet gel with a simplified processing and biochemical changes little artificial. A valid method of preparation of the PRF must effectively separate the plates by erythrocytes and concentrate without damaging or lysing the plates themselves. In this study the experimental design is to standardize the production of L-PRF in horse directing it to human production. Our hypothesis is that the L-PRF is easy to produce in the horse, without modifications of the human protocol, thus allowing a better standardization of the human protocol. A new device for the preparation and the standardization of L-PRF clots and membranes is the L-PRF Wound Box®. The optical microscopy, most cell bodies were highlighted concentrated in the proximal portion of each membrane, the last 1/4 was observed at the center; the distal part had only residual traces of cell bodies. The L-PRF will form constantly when the phases described above are strictly adhered to. The success of the art L-PRF depends entirely on the speed of blood collection and transfer in centrifuge within a minute and by a temperature of centrifugation and compression is higher than 21°C (between 21 and 30°C). Our experiments on the horse will no doubt be able to improve our understanding on wound healing, in particularly in chronic skin lesions therapy.
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Medicine & Pharmacology, Gastroenterology; microparticles, biomarkers, hepatocellular carcinoma
Online: 3 May 2017 (09:53:22 CEST)
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Circulating microparticles (MPs) are novel potential biomarkers in cancer patients. Their role in hepatocellular carcinoma (HCC) is under intensive investigation. In this study we tested the hypothesis that MPs expressing the antigen HepPar1 are increased in the blood of subjects with HCC and may serve as markers of early recurrence after liver resection (LR). We studied fifteen patients affected by HCC undergoing LR and used flow cytometry to assess the number of circulating HepPar1+ MPs. Ten subjects without HCC (five with liver cirrhosis and 5 with healthy liver) were used as controls. After LR, HCC patients were followed-up for early recurrence, which occurred in seven cases. The number of circulating HepPar1+ MPs was significantly higher in subjects affected by HCC, compared to individuals without cancer (p<0.01). We also found that, among HCC patients, the number of circulating HepPar1+ MPs, measured before LR, was significantly higher in those who displayed early recurrence compared to those without recurrence (p=0.02). Of note, other types of circulating MPs, such as those derived from endothelial cells (CD144+) or those produced by the activated endothelium (CD144+/CD62+) were not associated with HCC, neither could predict HCC recurrence. HepPar1+ MPs deserve further investigation as novel biomarkers of disease and prognosis in HCC patients.
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Medicine & Pharmacology, Nutrition; gluten; celiac disease; antibodies; Ménière’s disease; vertigo
Online: 2 May 2017 (05:49:26 CEST)
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Background: Meniere's disease (MD) has been recently linked to gluten assumption. Approximately 75% of MD patients show positive skin test to food and about 50% of the positive responses are specific to the gliadin acid extract fraction. Aim of this study was to investigate the humoral immune responses to wheat antigens and related autoantigens in MD patients. Methods. We assessed the reactivity of sera from 28 patients with definite MD and 100 healthy controls against a repertoire of 51 antigens usually associated with immune reaction to gluten. Results. MD patients showed an increase of anti-wheat IgA, anti-cerebellar peptide IgA and anti-glutamic acid decarboxylase (GAD) 65 IgM compared to healthy controls. In particular, the increase of anti-wheat IgA and GAD 65 IgM has been confirmed in a subgroup of MD patients symptomatically responding to a gluten free diet (GFD). Conclusion. In MD patients, an increase of the antibody production against gluten biomarkers was observed; in particular, anti-wheat IgA seems to be associated to clinical response to GFD.
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Medicine & Pharmacology, Pharmacology & Toxicology; medicinal plants; flavonoids; hypoglycemic; hypolipidemic; antiatherogenic
Online: 27 April 2017 (04:13:10 CEST)
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Celtis iguanaea is popularly used in the treatment of diabetes mellitus. However, thorough chemical and pharmacological investigations regarding its activity are lacking. In this study, we investigated the effects of the hydroalcoholic extract from C. iguanaea (CI) on markers of cardiovascular diseases and the glucose metabolism in cholesterol-fed rats. Therefore, hypercholesterolemic rats (1% cholesterol) were orally treated with CI (150, 300, or 600 mg/kg) or simvastatin (4 mg/kg) (n = 6) once a day for 30 days along with a hypercholesterolemic diet. A control group (C) was given saline solution. CI showed significant decreases in serum levels of total cholesterol, LDL-cholesterol, HMG-CoA-reductase, IL-1, IL-6, TNF-α, and IFN-γ when compared to group C (p ˂ 0.05). Hypoglycemic effects were observed along with a decrease of the activity of sucrase (CI 600), maltase (CI 150, CI 300), and an increase in muscle glycogen levels (CI 300). Antioxidant effects were observed in plasma, and the histopathological analysis showed a significant decrease in the liver fat area for CI compared to group C (p < 0.001). Our results suggest that the biological effects of CI could be related to the presence of flavonoids that possibly exert antioxidant, enzymatic inhibitory, and insulin-mimetic effects.
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Medicine & Pharmacology, Other; Peroxiredoxin (PRDX) 4, chronic inflammatory disease, metabolic syndrome, human PRDX4 transgenic mice (Tg), animal model.
Online: 26 April 2017 (17:57:38 CEST)
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The peroxiredoxin (PRDX) family, a new family of proteins with a pivotal antioxidative function, is ubiquitously synthesized and abundantly identified in various organisms. In contrast to the intracellular localization of other family members (PRDX1/2/3/5/6), PRDX4 is the only known secretory form and protects against oxidative damage by scavenging reactive oxygen species in both the intracellular (especially the endoplasmic reticulum) compartments and the extracellular space. Recently, we generated unique human PRDX4 (hPRDX4) transgenic (Tg) mice on a C57BL/6J background and investigated the critical and diverse protective roles of PRDX4 against diabetes mellitus, atherosclerosis, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) as well as evaluated its role in the intestinal function in various animal models. Our published data have shown that PRDX4 helps prevent the progression of metabolic syndrome by reducing local and systemic oxidative stress and synergistically suppressing steatosis, inflammatory reactions, and/or apoptotic activity. These observations suggest that Tg mice may be a useful animal model for studying the relevance of oxidative stress on inflammation and the dysregulation of lipid/bile acid/glucose metabolism upon the progression of human metabolic syndrome, and that specific accelerators of PRDX4 may be useful as therapeutic agents for ameliorating various chronic inflammatory diseases.
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Medicine & Pharmacology, Allergology; ranolazine; atrial fibrillation; prevention; pharmacological cardioversion; meta-analysis
Online: 25 April 2017 (07:48:26 CEST)
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Introduction Recent evidence from relatively small randomized controlled trials would seem to support a useful role of ranolazine for the prevention and treatment of atrial fibrillation (AF). The present study is aimed at providing information about the possible beneficial anti-arrhythmic properties of ranolazine. In particular, the meta-analysis carried out in this study focuses on the application of ranolazine to prophylaxis and treatment of atrial fibrillation.Methods Both randomized controlled trials (RCTs) and non randomized observational studies concerning the effects of ranolazine on AF were included in the meta-analysis. In each of the considered studies, a comparison was made between a group of patients taking ranolazine and a second group treated instead with another antiarrhythmic therapy , or assigned to placebo. Efficacy outcomes were the risk of new- onset AF, the probability of conversion to sinus rhythm of patients with recent occurrence(≤ 48 h)of AF and the time to conversion to sinus rhythm. Safety endpoints were death, adverse events, QTc prolongation and hypotension.Results Ten studies ( 8 RCTs and 2 nonrandomized observational studies) were gathered on the whole. Ranolazine was effective in preventing the occurrence of AF when compared to controls (RR= 0.60; 95% CI: 0.43–0.83; p = 0.002). Subgroup analysis showed a more pronounced preventive effect of ranolazine against AF in the postoperative setting of coronary artery bypass grafting(CABG) surgery (RR= 0.39; 95% CI: 0.18-0.83; p=0.02) when compared to non- postoperative AF (RR= 0.76; 95% CI: 0.63-0.92; p=0.04). Ranolazine enhanced the chances of successful cardioversion when added to intravenous amiodarone compared to amiodarone alone (RR 1.18; 95% CI: 1.05–1.33; p = 0.004) and significantly decreased the time to cardioversion(SMD= −10.35 h; 95% CI: −18.13 hours to − 2.57 hours; p < 0.001). Overall risks of death, adverse events, and QTc prolongation were shown to be similar in the comparison between patients treated with ranolazine and controls. Conclusions Ranolazine given orally at appropriate doses showed the property to significantly quicken the conversion of AF to sinus rhythm when combined with the iv amiodarone, compared to iv amiodarone alone . Furthermore, in patients in sinus rhythm, ranolazine proved to reduce the frequency of new onset AF as well as of its recurrences, especially in patients undergone CABG surgery, known to be at high risk of developing postoperative AF. In addition, ranolazine use seems to be safe and associated with relatively few adverse events.
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Medicine & Pharmacology, Dentistry; early childhood caries; mouth pain; malnutrition; ecuador; community-based intervention
Online: 24 April 2017 (05:43:03 CEST)
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Malnutrition and dental caries in early childhood remain persistent and intertwined global health challenges, particularly for indigenous and geographically-remote populations. To examine the prevalence and associations between early childhood dental caries, parent-reported mouth pain and malnutrition in the Amazonian region of Ecuador, we conducted a cross-sectional study of the oral health and nutrition status of 1,407 children from birth through age 6 in the “Alli Kiru” program (2011-2013). We used multivariate regression analysis to examine relationships between severe caries, parent-reported mouth pain measures, and nutritional status. The prevalence of dental caries was 65.4%, with 44.7% of children having deep or severe caries, and 33.8% reporting mouth pain. The number of decayed, missing and filled teeth dmft) increased dramatically with age. Malnutrition was prevalent, with 35.9% of children stunted, 1.1% wasted, 7.4% underweight, and 6.8% overweight. As mouth pain increased in frequency, odds for severe caries increased. For each unit increase in mouth pain frequency interfering with sleeping, children had increased odds for underweight (AOR: 1.27; 95% CI: 1.02 – 1.54) and decreased odds for overweight (AOR: 0.76; 95% CI: 0.58 – 0.97). This relationship was most pronounced among 3-6 year-olds. Early childhood caries, mouth pain and malnutrition were prevalent in this sample of young children. Parent-reported mouth pain was associated with severe caries, and mouth pain interfering with sleeping was predictive of poor nutritional status. We demonstrate the utility of a parsimonious parent-reported measure of mouth pain to predict young children’s risk for severe early childhood caries and malnutrition, which has implications for community health interventions.
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Medicine & Pharmacology, Psychiatry & Mental Health studies; emotion and will; music therapy; five phases; five phases music therapy; psychology
Online: 24 April 2017 (05:37:45 CEST)
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Music therapy has served as complementary and alternative medicine for various neurological disorders. Five Phases Music Therapy (FPMT) employs the theory of five phases and five music scales or tones (Gong (do), Shang (ri), Jue (mi), Zhi (so) and Yu (la)) to analyze and treat mind-body illness. In Chinese Medicine (CM) the five music scales are used to connect the human body and the universe, summarize personalities and constitution and analyze the influences of climatic changes on health. FPMT has a self-contained theory and routine of practice application. Large amount of clinical and fundamental reports has been available and clinical benefits have been obtained. However more systemic clinic research esp. Evidence-based and random controlled trials must be performed to validate and optimize it’s routines and biological and neurological mechanism must be further explored. It’s reasonable to believe that the introduction of FPMT to the world outside China may attract more attentions to use this effective music therapy.
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Medicine & Pharmacology, Nutrition; alcoholic fatty liver disease; PARP; PJ34; triglyceride
Online: 24 April 2017 (05:30:53 CEST)
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The specific role of nicotinamide adenine dinucleotide (NAD) in hepatic triglyceride (TG) accumulation in alcoholic fatty liver disease (AFLD) were unclear. Poly ADP ribose polymerase (PARP) is a NAD-consuming enzyme and its specific role in the pathogenesis of AFLD is still elusive. In current investigation, we found that chronic alcohol exposure enhanced hepatic PARP expression and activity and lowered hepatic NAD+ level. PARP activity inhibitor PJ34 decreased the intracellular TG content in hepatocyte. Moreover, PJ34 suppressed the gene expression of DGAT1 and DGAT2 and elevated the intracellular NAD+ level in hepatocyte. These mechanistic observation was validated in alcohol-fed mice injected with PJ34 intraperitoneally. PJ34 injection attenuated hepatic TG accumulation in alcohol-fed mice. Further, the gene expression of hepatic SERBP-1c, DGAT1 and DGAT2 were lowered by PJ34 injection, while the hepatic NAD+ level was augmented by PJ34 injection in alcohol-fed mice. At last, the nicotinamide riboside supplementation alleviated hepatic TG accumulation in alcohol-fed mice. These data indicate that applying PARP specific inhibitor PJ34 by intraperitoneal injection attenuated hepatic NAD+ depletion and TG accumulation in alcohol-fed mice, which might be a potential candidate for AFLD therapy.
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Medicine & Pharmacology, Oncology & Oncogenics; breast cancer; surgical tissues; gel-based proteomics; mass spectrometry; protein clustering
Online: 24 April 2017 (05:14:06 CEST)
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The present investigation has been conducted on one hundred tissue fragments of breast cancer, collected and immediately cryopreserved following the surgical resection. The fragments were selected from patients with invasive ductal carcinoma of the breast, the most common and potentially aggressive type of mammary cancer, with the objective to increase the knowledge of breast cancer molecular markers, useful for diagnostic and prognostic categorization of patients, in assessing post-surgical therapeutic regimes. The proteomic screening, by 2D-IPG and mass spectrometry, allowed us to identify two main classes of protein clusters: proteins expressed ubiquitously at high levels in all patients, and proteins expressed sporadically among the same patients. Within the group of ubiquitous proteins, glycolytic enzymes and proteins with anti-apoptotic activity were predominant. Among the sporadic ones, proteins involved in cell motility, molecular chaperones and proteins involved in the detoxification appeared prevalent. The data of the present study indicates that the primary tumor growth is generally supported by two concurrent pathways: the inhibition of apoptosis and the stimulation of cellular proliferation. The second phase of the evolution of the tumor can be prematurely scheduled by the occasional presence of proteins involved in cell motility and in the defenses of the oxidative stress. To our knowledge this report on large-scales proteomics of breast cancer is currently a unique approach in the literature that offers the opportunity to evaluate the presence and recurrence of proteins to be used as prognostic indicators and susceptibility to metastasis in patients operated on for invasive ductal carcinoma of the breast.
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Medicine & Pharmacology, Pathology & Pathobiology; aging; age-related disease; mortality rate; positive feedback loop; vicious cycle
Online: 18 April 2017 (02:45:04 CEST)
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Age-related diseases (ARDs) are the leading cause of death worldwide, and contribute to 90% of mortality in developed countries. Interestingly, the mortality rates of individual ARDs increase exponentially with age. Processes described by the exponential growth function typically involve a branching chain reaction or, more generally, a positive feedback loop. Here I propose that each ARD is mediated by one or several positive feedback loops (vicious cycles). I then identify critical vicious cycles in five major ARDs: atherosclerosis, hypertension, diabetes, Alzheimer’s and Parkinson’s. I also propose that the progression of ARDs can be halted by selectively interrupting the vicious cycles and suggest the most promising targets. An evolutionary perspective is also offered.
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Medicine & Pharmacology, Nutrition; Parboiled rice, medium-grain white rice, cold stored, reheating, blood glucose concentration chewing time, satiety, palatability.
Online: 17 April 2017 (05:35:10 CEST)
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Background: Globally, hot cooked refined rice is consumed in large quantities and is a major contributor to dietary glycaemic load. This study aimed to compare the glycaemic potency of hot and cold stored parboiled rice to widely available medium grain white rice. Method: Twenty-eight healthy volunteers participated in a three treatment experiment where postprandial blood glucose was measured over 120 minutes after consumption of 140g of rice. Three rice samples were freshly cooked medium-grain white rice, freshly cooked parboiled rice, and parboiled rice stored overnight at 4 ºC. All rice was served warm at 65 ºC. Chewing time was recorded. Results: The 24-hours cold-stored and reheated parboiled rice resulted in a 42% and 12% lower blood glucose concentration trajectory than freshly cooked medium-grain white rice and freshly cooked parboiled rice. Chewing time for 10g cold stored parboiled rice was 6 seconds (25%) longer and was considered more palatable, visually appealing and better tasting than freshly cooked medium grain (all P<0.05). Conclusions:. For regular consumers of rice reheating cooked rice after cold storage would lower the dietary glycaemic load and long term may reduce risk for type 2 and gestational diabetes. More trials are needed to identify the significance.
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Medicine & Pharmacology, Pediatrics; extended newborn screening; ethnic screening differences; Roma ethnicity
Online: 14 April 2017 (08:31:47 CEST)
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Authors present The First Results of the National Extended Newborn Screening (ENS) in Slovakia in the majority (M) and the Roma (R ) ethnic populations. The follow-up of the ethnicity has been introduced in Newborn Screening for Cystic Fibrosis (NSCF) and after to entire ENS program comprising of 23 Hereditary Metabolic Disorders (HMD). Results: In 2013-2015, a total of 165,648 newborns were investigated in ENS, 23,321 of them (15,3%) were the R ethnic group, a total of 313 positive cases were discovered (total ENS prevalence = 1:529, M=1:758, R=1:198). In the R ethnic group, there was slightly higher prevalence in cong. hypothyreosis (CH), only one case of CF, and no cases of CAH in the R ethnic group. The ENS prevalence of HMD detected by MS/MS was expressively higher in the R ethnic group than in M group (M=1:1670 vs. R=1:234, OR:7,13). Significant differences in the prevalence of individual types of HMD were found. Whereas the PKU and spectrum of aminoaciduria and organic acidurias dominate in the M group, the fatty acids oxidation disorders (MCAD, SCAD) and carnitine defects (CUD) were frequent in the R newborn group. Conclusion: Despite the presented results are preliminary, the ethnic approach to ENS is enabling the recording of the ethnic differences in the screening prevalence of individual disorders, which would be missing during unitary approach.
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Medicine & Pharmacology, Pathology & Pathobiology; Ochratoxin A, insulin, glucagon, glucose, rat plasma, pathology, immunohistochemistry
Online: 13 April 2017 (11:46:19 CEST)
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In this study, diabetogenic effects of long term Ochratoxin A (OTA) administration in rats were investigated and its role in the etiology of diabetes mellitus (DM) was examined utilizing 42 female Wistar rats for these purposes. The rats were divided into 3 different study and control groups according to the duration of the OTA administration. Rats received 45 μg OTA daily in their feed for 6, 9 and 24 weeks study groups. Three control groups without any treatment were also used in the same periods. Blood and pancreatic tissue samples were collected during the necropsy at the end of 6, 9 and 24 weeks. Plasma values of insulin, glucagon and glucose in study and control groups were determined. Pancreatic lesions were evaluated by histopathological examination; then insulin and glucagon expression in these lesions were determined by immunohistochemical methods. Statistically significant decrease in insulin levels in contrast to increases in glucagon and glucose levels in blood were observed. Slight degeneration in Langerhans islet cells were observed at the histopathological examination in all OTA treated groups. Immunohistochemistry of pancreatic tissue revealed decreased insulin and increased glucagon expression. This study demonstrated that OTA may cause pancreatic damage in Langerhans islet and predispose rats to DM.
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Medicine & Pharmacology, Gastroenterology; survivin; high expression; gastrointestinal cancer; prognostic
Online: 11 April 2017 (10:51:06 CEST)
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Previous studies on the prognostic impact of survivin expression in gastrointestinal (GI) cancer have yielded inconsistent results. This study was initiated to assess the relationship between survivin expression and overall survival (OS) or disease free survival (DFS) in GI cancer patients. We applied system literature searches on EMBASE, PubMed, Web of science, and the Cochrane library to conduct this up-to-date meta-analysis. Thirty studies with totally 3622 GI cancer patients were collected. The prevalence of high survivin expression in GI cancer was 0.57 (95% CI: 0.51-0.63). High survivin expression was significantly associated with shorter OS (HR 1.57, 95% CI: 1.42-1.74) and DFS (HR 1.38, 95% CI: 1.21-1.58). Subgroup analysis also showed significant association between high survivin expression and poorer OS or DFS in gastric cancer or colorectal cancer. In summary, our study indicated that high survivin expression was related to poor prognosis in GI cancer. Well-designed studies with large sample and more convincing data are needed to confirm our conclusion.
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Medicine & Pharmacology, General Medical Research; iron deficiency anemia; osteoporosis; ferrum infusion; blood transfusion
Online: 10 April 2017 (06:32:56 CEST)
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The cause-effect relationship between iron deficiency anemia (IDA) and osteoporosis has not been established in the general population. Thus, the current longitudinal study determined the role of IDA as a risk factor for osteoporosis by analyzing a large nationwide population-based sample. In a sample of 1,000,000 randomly sampled individuals from the 1998-2012 Taiwan National Health Insurance Research Database, patients with IDA (case group [n=35,751]) and individuals without IDA (control group [n=178,755]) were compared. Patients who were <20 years of age and who had pre-existing osteoporosis prior to the diagnosis of IDA were excluded. Each patient with IDA was age- and gender-matched to 5 individuals without IDA. The diagnoses of IDA and osteoporosis (coded using ICD-9CM) were further confirmed with blood test results and X-ray bone densitometry to ensure the accuracy of the diagnoses. Osteoporosis occurred more often among patients with IDA compared to individuals without IDA (2.27% vs. 1.32%, p<0.001). Cox proportional hazard analysis revealed that the risk for osteoporosis was significantly higher in the case than the control group (hazard ratio [HR]=1.74; 95% CI=1.61-1.88) and remained similar after adjustment for covariates (adjusted HR=1.81; 95% CI=1.67-1.97). Compared with individuals without IDA, the risk for osteoporosis was even higher for patients with IDA who received intravenous ferrum therapy (adjusted HR=2.21; 95% CI=1.85-2.63). In contrast, the risk for osteoporosis was reduced for patients with IDA who received a blood transfusion (adjusted HR=1.47; 95% CI=1.20-1.80). As a predictor, prior IDA is a significant and independent risk factor for development of osteoporosis. In contrast to blood transfusion treatment, the use of intravenous ferrum may further increase the risk for future osteoporosis.
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Medicine & Pharmacology, Nutrition; lysine; skeletal muscle; transcriptome; gene expression; microarray; pig
Online: 10 April 2017 (06:30:13 CEST)
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Nine crossbred finishing barrows randomly assigned to 3 dietary treatments were used to investigate the effects of dietary lysine on muscle growth related metabolic and signaling pathways. Muscle samples were collected from the longissimus dorsi of individual pigs after feeding the lysine-deficient, lysine-adequate, or lysine-excess diet for 5 weeks, and the total RNA was extracted afterwards. Affymetrix Porcine Gene 1.0 ST Array was used to quantify the expression levels of 19,211 genes. A total of 674 transcripts were differentially expressed (P ≤ 0.05); 60 out of 131 transcripts (P ≤ 0.01) were annotated in the NetAffx database. Ingenuity pathway analysis showed that dietary lysine deficiency may lead to (1) increased muscle protein degradation via the ubiquitination pathway as indicated by the up-regulated DNAJA1, HSP90AB1 and UBE2B mRNA, (2) reduced muscle protein synthesis via the up-regulated RND3 and ZIC1 mRNA, (3) increased serine and glycine synthesis via the up-regulated PHGDH and PSPH mRNA, and (4) increased lipid accumulation via the up-regulated ME1, SCD, and CIDEC mRNA. Dietary lysine excess may lead to (1) decreased muscle protein degradation via the down-regulated DNAJA1, HSP90AA1, HSPH1, and UBE2D3 mRNA, and (2) reduced lipid biosynthesis via the down-regulated CFD and ME1 mRNA.
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Medicine & Pharmacology, Other; carnitine palmitoyltransferase deficiency; CPT1A; fatty acid oxidation disorders; transaminitis; Ashkenazi Jewish; neonatal screening
Online: 10 April 2017 (06:23:32 CEST)
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An 18 month-old male was evaluated after presenting with disproportionate transaminitis in the setting of acute gastroenteritis. He had marked hepatomegaly on physical exam that was later confirmed with an abdominal ultrasound. Given this clinical picture, suspicion for a fatty acid oxidation disorder was raised. Further investigation revealed that his initial newborn screen was positive for carnitine palmitoyltransferase 1A (CPT1A) deficiency - a rare autosomal recessive disorder of long-chain fatty acid oxidation. Confirmatory biochemical testing in the newborn period showed carnitine levels to be unexpectedly low with a normal acylcarnitine profile. Thus, it was considered to be a false-positive newborn screen and metabolic follow up was not recommended. Repeat biochemical testing during this hospitalization revealed a normal acylcarnitine profile. The only abnormalities noted were a low proportion of acylcarnitine species from plasma, an elevated free-to-total carnitine ratio, and mild hypoketotic medium chain decarboxylic aciduria on urine organic acids. Gene sequencing of CPT1A revealed a novel homozygous splice site variant that confirmed his diagnosis. CPT1A deficiency has a population founder effect in the Inuit and other Arctic groups, but has not been previously reported in persons of Ashkenazi Jewish ancestry.
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Medicine & Pharmacology, Nursing & Health Studies; adolescents; depression; insomnia; mobile phone; Japanese
Online: 7 April 2017 (04:33:14 CEST)
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Adolescents spend an increasing amount of time on mobile phones. The aim of this study was to assess the relationship between duration of mobile phone use and insomnia and depression in senior high school students. The cross-sectional study was conducted on 295 senior high school students in Japan. Mobile phones were owned by 98.6% of students; 58.6% of students used mobile phones for more than 2 h daily and 10.5% used them for 5 h daily. The risk of insomnia was significantly high in students who used mobile phones for 5 h or more (OR: 3.89 [95% CI: 1.21-12.49]). There was no significant association between depression and duration of mobile phone use. However, individuals who spent 120 min or more using mobile phones for social network services (OR: 3.63 [1.20-10.98]) and online chats (OR: 3.14 [1.42-6.95]) were at risk for depression. Excessive mobile phone use is associated with unhealthy sleep habits and insomnia. Moreover, the excessive use of the social network services and online chats are related to depression rather than duration of mobile phone use. Adolescents should use mobile phones appropriately to avoid sleep disturbances and the impairment of mental health.
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Medicine & Pharmacology, Sport Sciences & Therapy; latin dance, tai chi, knee proprioception
Online: 6 April 2017 (06:08:48 CEST)
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To study the influence of Latin dance and Tai Chi on knee joint proprioception and balance. Method: All experiments were performed in the Beijing Normal University School of Physical Education and Sport Biomechanics Laboratory. An isokinetic test system (Biodex system 4, BS4) and a balance testing system (Biodex Balance System, BBS)from the United States Biodex medical system were used to test related indexes. Results: In the LOS test, the overall score of Latin group is much better than sedentary group. In the ASL test, Latin group have a better balance ability in anterior and posterior direction and overall score than sedentary group(p＜0.05); TAI CHI group have a better balance ability than sedentary group in anterior and posterior direction(p＜0.05)and right and left direction (p＜0.01). When the knee joint was at 15, 30, and 45degree positions, the Tai Chi exercise group was much better than sedentary group (P < 0.05), and the 45 degree position in the Tai Chi group was much better than that in the Latin dance group (P < 0.01).When the knee joint was at the 30 degree position, the quadriceps force sense was significantly better in the Tai Chi group than in the Latin dance and sedentary groups. In a test of the four angles, the hamstring force sense in the Tai Chi exercise group was obviously better than that in the sedentary group (P < 0.05); at the 15 degree position, the Tai Chi group was significantly better than the Latin group (P < 0.05); and at 30 degree position, the hamstring force sense of the Latin group was obviously better than that of the sedentary group (P < 0.05).
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Medicine & Pharmacology, Pharmacology & Toxicology; ostreolysin A/pleurotolysin B; equinatoxins; pore-forming proteins; biological effects
Online: 5 April 2017 (15:36:57 CEST)
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Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.
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Medicine & Pharmacology, Allergology; fibromyalgia; drugs; NMDA receptor; ketamine; memantine.
Online: 3 April 2017 (16:43:53 CEST)
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Activation of the N-methyl D-aspartate receptor (NMDAR) results in increased sensitivity of spinal cord and brain pathways that process sensory information, particularly that which relates pain. The NMDAR shows increased activity in fibromyalgia and hence modulation of the NMDAR is a target for therapeutic intervention. A literature review of interventions impacting on the NMDAR shows a number of drugs to be active on the NMDAR mechanism in fibromyalgia patients, with variable clinical effects. Low-dose intravenous ketamine and oral memantine both show clinically useful benefit in fibromyalgia. However, consideration of side-effects, logistics and cost need to be factored into management decisions regarding use of these drugs in this clinical setting. Overall benefits with current NMDAR antagonists appear modest and there is a need for better strategy trials to clarify optimal dose schedules and to delineate potential longer –term adverse events. Further investigation of the role of the NMDAR in fibromyalgia and the effect of other molecules that modulate this receptor appear important to enhance treatment targets in fibromyalgia.
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Medicine & Pharmacology, Pharmacology & Toxicology; valproic acid; doxorubicin; reactive oxygen species; autophagy; cell death; caveolae endocytosis pathway
Online: 31 March 2017 (12:08:53 CEST)
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We evaluated the mono- and combination-therapy effects of valproic acid (VPA) and doxorubicin (DOX) in hepatocellular carcinoma (HCC) and identified a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the coefficient of drug interaction confirmed the significant synergistic effect of the combination treatment. Concurrently, the synergistic apoptotic cell death caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear staining and western blot analysis of caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species (ROS) generation and autophagy, which were clearly attenuated by ROS and autophagy inhibitors, respectively. Furthermore, as an indication of the mechanism underlying the synergistic effect, we observed that DOX internalization, which was induced in the VPA and DOX combination-treated group, occurred via by the caveolae-mediated endocytosis pathway. Taken together, our study uncovered the potential effect of the VPA and DOX combination treatment with regard to cell death, including induction of cellular ROS, autophagy, and the caveolae-mediated endocytosis pathway. Therefore, these results present novel implications in drug delivery research for the treatment of HCC.
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Medicine & Pharmacology, General Medical Research; social determinants; epigenetics; exposome; public health policy; resilience; allostatic load; adaptation
Online: 31 March 2017 (11:35:57 CEST)
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Globally, humans are struggling with the double threat of communicable and non-communicable diseases, which are presenting new challenges to public health. Public health problems are generally studied and addressed at primary, secondary and tertiary levels. Most effective results are seen with primary interventions. Public health is becoming more aware of the importance of environment-gene interactions in the ontology of health and disease using epigenetics. Epigenetics is the study of altered gene expression without change in base pairs. Be it physical, social, behavioral, or economic factors; they all influence quality of life and health of individuals and populations. That environments are changing the human health phenotype and these changed phenotypes are heritable is of concern for the future of the human race. Knowing the causes of non-communicable human diseases using epigenetics will contribute to the development of new policies to encourage prevention using primary public health initiatives. Research and application of epigenetics shows great promise for improving population health. Continued advances in epigenetics will enhance how we understand and address the way environments are affecting the human health phenotype. For some time, health systems have been and continue to be tertiary in nature. Epigenetic changes can provide information necessary to better understand how social determinants of health can be used to build societies focused on equitable health for all people, rather than continuing to focus on treatment of diseases in the tertiary phase that leads to health disparities. Understanding mechanisms of social determinants of disease, will allow society to evolve in a health-oriented rather than a disease-oriented world. For this reason, we must enhance and apply epigenetics (physical, social, behavioral, economic) research to policy development. We will discuss how bringing social determinants together with biology can be used as new tools for public health policy.
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Medicine & Pharmacology, Dermatology; biodiversity; skin allergy; benchmark skin health values; effect of synthetic cosmetics on skin; 21st century skin ailments; measure skin health; healthy skin ecosystem; healthy skin bacteria; damaged skin bacteria; perfect skin
Online: 31 March 2017 (08:52:14 CEST)
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There is a skin allergy epidemic in the western world, and the rate of deterioration has increased significantly in the past 5-10 years. It is probable that there are many environmental contributing factors, yet some studies have linked it primarily to the rise in the use of synthetic chemical ingredients in modern cosmetics. Our challenge, therefore, was to find a mechanism to determine the effect these substances have on skin health, and whether they really are a primary cause of long term damage to the skin. The first problem is the lack of any definitive way to measure skin health. Motivated by the overwhelming evidence for a link between deficient gut flora and ill health, we decided to look at whether our skin microbiota could similarly be used as an indicator of skin health. Our research illustrates how it is microbiota diversity alone that can predict whether skin is healthy or not, after we revealed a complete lack of conclusive findings linking the presence or abundance of particular species of microbe to skin problems. This phenomenon is replicated throughout nature, where high biodiversity always leads to healthy ecosystems. ‘Caveman’ skin, untouched by modern civilisation, was far different to ‘western’ skin and displayed unprecedented levels of bacterial diversity. The less exposed communities were to western practices, the higher the skin diversity, which is clear evidence of an environmental factor in the developed world damaging skin. For the first time we propose benchmark values of diversity against which we can measure skin to determine how healthy it is. This gives us the ability to be able to predict which people are more likely to be prone to skin ailments, and start to test whether cosmetic ingredients and products are a main cause of the skin allergy epidemic.
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Medicine & Pharmacology, General Medical Research; acute lung injury; fasudil, Rho kinase; endothelial function; inflammation
Online: 31 March 2017 (08:30:54 CEST)
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Fasudil, a potent Rho kinase (ROCK) inhibitor, can ameliorate LPS-induced acute lung injury (ALI) in mice, but the mechanism remains obscure. In this study, a mice model of ALI was established by intra-tracheal instillation of LPS. Histological changes, cytokine levels, lung permeability, and endothelial apoptosis were determined to evaluate the effects of fasudil on lung injury. The cellular and molecular biological mechanisms were explored by culturing human pulmonary microvascular endothelial cells (PMECs). The results showed that fasudil reduced LPS-induced lung inflammation, pulmonary hyperpermeability, and endothelial apoptosis in mice. In cultured human PMECs, fasudil inhibited LPS-induced caspse-3 cleavage and cell apoptosis. It also decreased LPS-induced hyperpermeability of human PMECs monolayer by reversing the down-regulation of intercellular junctions. Moreover, fasudil inhibited LPS-induced overexpression of chemokines and intercellular adhesion molecule (ICAM)-1 in human PMECs, which in turn suppressed neutrophil chemotaxis and neutrophil-endothelial adhesion. Further molecular researches showed fasudil inhibited LPS-induced activation of ROCK, NF-κB, and p38 in human PMECs. Our findings demonstrated that fasudil alleviated LPS-induced ALI by protecting endothelial function via inhibiting endothelial apoptosis, maintaining endothelial barrier integrity, and reducing endothelial inflammation. These effects of fasudil could be attributed to the inhibition of ROCK and its downstream NF-κB and p38 signaling pathways.
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Medicine & Pharmacology, Oncology & Oncogenics; 18S rRNA; fungi; mycobiome; carcinoma; High-Throughput Nucleotide Sequencing; microbiome; mouth; squamous cell
Online: 30 March 2017 (05:37:37 CEST)
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Background: Studies employing next-generation sequencing (NGS) show that the oral fungal community (mycobiome) is far more complex than hitherto thought. However, the role of the oral mycobiome in health and disease, including oral carcinogenesis, has not been explored. Objective: To characterize the mycobiome associated with oral squamous cell carcinoma (OSCC). Methods: Tissue biopsies [cases: 25 OSCC; controls: 27 intra-oral fibro-epithelial polyp (FEP)] were collected from oral and maxillofacial units in Sri Lanka. Total DNA was extracted and subjected to sequencing of the fungal ITS2 region using Illumina’s 2x300 bp chemistry. High quality, non-chimeric merged reads were classified to species level using a BLASTN-algorithm with UNITE’s named species sequences as reference. Downstream analyses were performed using QIIME and LEfSe. Results: 364 species representing 160 genera and 2 phyla (Ascomycota and Basidiomycota) were identified, with Candida and Malassezia making up 48% and 11% of the average mycobiome, respectively. However, only 5 species and 4 genera were detected in ≥50% of the samples. The species richness and diversity were significantly lower in OSCC. At the genus level, Candida, Hannaella and Gibberella were overrepresented in OSCC while Alternaria and Trametes were more abundant in FEP. Species-wise, C. albicans, C. etchellsii and Hannaella luteola-like species were enriched in OSCC while Malassezia restricta, Aspergillus tamarii, Alternaria alternate, Cladosporium halotolerans, and Hanseniaspora uvarum-like species were the most significantly abundant in FEP. Conclusions: A dysbiotic mycobiome dominated by C. albicans was found in association with OSCC. Whether this dysbiosis plays a role in oral carcinogenesis warrants further investigation.
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Medicine & Pharmacology, Pediatrics; Activin-A; HIE; MRI; apparent diffusion coefficient; neonates
Online: 28 March 2017 (03:07:20 CEST)
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Background: Early identification and prevention of hypoxic ischemic encephalopathy (HIE) may reduce neonatal mortality and morbidity. Objective: We aimed to correlate between urinary Activin-A and MRI (conventional and Diffusion-weighted) and the severity of HIE in full-term neonates. Methods: Forty-five full-term neonates with HIE admitted to NICU and 15 normal neonates were enrolled into the study. The concentration of urinary Activin-A was determined using enzyme immunoassay kits and MRI were done. Correlations between urinary Activin-A and MRI with the degree of HIE were done. Results: Urinary Activin-A levels were significantly higher in neonates with HIE than controls (P<0.001). It was positively correlated with the clinical grading of HIE and a cutoff value of 0.08µg/l on day-1 after birth had a sensitivity of 98.6% and specificity of 97.1% for prediction of HIE. DW-MRI detected HIE with a high sensitivity (85%) compared to the low sensitivity of conventional MRI (35%). An ADC value of ≤ 0.8 was the best sensitivity-specificity cutoff point for detecting severe ischemic injury. DW-MRI imaging was positively correlated with Urinary Activin-A and both of them were positively correlated with the clinical grades of HIE (P < 0.001). Conclusions: DW-MRI imaging is correlated well with urinary Activin-A in full-term neonates with HIE and both of them are correlated with the degree of HIE. Early determination of urinary Activin-A combined with DW-MRI imaging can early detect HIE and its severity in full-term neonates with HIE.
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Medicine & Pharmacology, Gastroenterology; alcohol; liver cirrhosis; selenium; interleukin-6; growth differentiation factor-15
Online: 27 March 2017 (16:12:33 CEST)
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According to some authors, the serum selenium level is strongly associated with the severity of liver diseases including liver cirrhosis. The aim of the study was to determine the relationship between the concentration of selenium and pro-inflammatory and profibrotic cytokines – interleukin-6 (IL-6) and growth differentiation factor 15 (GDF-15) in patients with alcoholic liver cirrhosis. The parameters studied were determined in serum of 99 alcoholic liver cirrhosis patients divided based on the severity of disease according to the Child-Turcotte-Pugh criteria. In patients with liver cirrhosis, the serum selenium concentration was statistically lower whereas serum IL-6 and GDF-15 concentrations were higher than those in the control group. Moreover, the concentration of selenium negatively correlated with the levels of GDF-15 and IL-6. The above results may indicate a role of selenium deficiency in the pathogenesis and progression of alcoholic liver disease.
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Medicine & Pharmacology, Obstetrics & Gynaecology; melatonin; antioxidants; RNS; ROS; embryo development; DNA integrity; DNA oxidation; gene expression
Online: 27 March 2017 (10:04:31 CEST)
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Oxidative and nitrosative stress are a common problem when manipulating gametes in vitro. In vitro development in mammalian embryos is highly affected by culture conditions, especially by reactive oxygen species (ROS) and reactive nitrogen species (RNS), because its absence or over production causes embryo arrest and changes in gene expression. Melatonin in gamete co-incubation during IVF has deleterious or positive effects depending on the concentration used in culture medium, demonstrating the delicate balance that must exist between antioxidant and pro-oxidant activity. Further research is needed to better understand the possible impact of melatonin on the different IVP steps in domestic animals, especially in seasonal breeds where this neuro-hormone system highly regulates its reproduction physiology.
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Medicine & Pharmacology, Oncology & Oncogenics; Isoxazole moiety; Thieno[2,3-d]pyrimidine derivatives; Synthesis; Anticancer activity
Online: 24 March 2017 (17:52:30 CET)
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Under the guidance of our previous achievements, and in order to extend this small molecular library. In current work, other 21 novel structures of thieno[2,3-d]pyrimidines containing isoxazole-moiety (1a-1u) were firstly synthesized and the cytotoxicity to A549, HCT116 and MCF-7 cell lines was evaluated using the MTT method. The results showed that most target compounds exhibited good to excellent cytotoxicity to A549, HCT116 and MCF-7 cell lines, especially 6-Methyl-4-{[3-(4-chlorophenyl)-isoxazol-5-yl-]-methoxy-}-thieno[2,3-d]-pyrimidine (1e) exhibited a broad-spectrum and the most potent cytotoxicity to A549, HCT116 and MCF-7 cell lines (IC50s: 2.79, 6.69 and 4.21×10-3 μM, respectively) as compared with the reference drug gefitinib (IC50s: 17.90, 21.55 and 20.68 μM, respectively). 1e can be seen as the best drug candidates for development of anticancer drugs.
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Medicine & Pharmacology, Veterinary Medicine; veterinary; allergic dermatitis; low level laser therapy
Online: 24 March 2017 (10:32:49 CET)
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Background: The prevalence of atopic dermatitis in domestic animals is one of the problems of modern veterinary. Treating with standard techniques using chemotherapeutic agents not always leads to a positive result of therapy; moreover, many drugs produce adverse side effects. Methods: Low level laser therapy, in particular, intravenous laser blood illumination (ILBI) has a pronounced and long-lasting impact on the immune system of animals. The combined technique including ILBI-635 (635 nm, 2 mW, 5 min) and LUVBI® (365 nm, 2 mW, 3 min) every other day provides a positive change in clinical status of cats with allergic dermatitis after the 3rd-4th treatment session. Results: The increased level of erythrocytes and hemoglobin was identified in the course of treatment, and it indirectly indicates increased blood transport activity, which improves trophic provision and microcirculation. A double reduction of leukocytes and a significant decrease of neutrophil cells indicate the immunomodulatory effect of LILI (low-intensity laser illumination). The increase in the percentage of lymphocytes and the decrease of eosinophils and monocytes against the background of basophil concentrations deviations within physiological concentration result in the reduction of inflammatory mediators expression that induce itching. The reduction of total IgE concentration 32 times against control on the 7th day of treatment correlates with the decrease in the quantitative content of peripheral blood eosinophils, indicating the decrease in severity of an allergic process. Conclusion: LLLT is recommended against the background of standard drug therapy to achieve quick clinical outcome together with a long-lasting prolonged effect.
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Medicine & Pharmacology, Cardiology; sildenafil ; phosphodiesterase-5 inhibitors; chronic heart failure; meta-analysis
Online: 22 March 2017 (18:12:47 CET)
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Background: In patients with pulmonary arterial hypertension, substantial clinical benefits have been reported with the use of phosphodiesterase-5 inhibitors(PDE5i) . Moreover, some studies would have proven useful effects of PDE5i also on the clinical picture of the pulmonary hypertension(PH) secondary to left-sided chronic heart failure(CHF). Methods: We performed a meta-analysis comprising randomized controlled trials ( RCTs) which had compared PDE5i ( mostly sildenafil) with placebo in CHF patients. Results: 14 studies, including 928 patients overall , were admitted to the meta-analysis. In heart failure with reduced left ventricular ejection fraction(HFREF), PDE5i, compared to placebo, significantly improved the composite of death and hospitalization (OR= 0.28; 95% CI: 0.10 to 0.74). They also improved peak VO2 (difference in means[MD]: 3.76; 95% CI: 3.27 to 4.25), six-minutes walk distance ( (6MWD)( MD, 22.7 meters ; 95% CI, 8.19 to 37.21) and pulmonary arterial systolic pressure (MD: -11.52 mmHg; 95% CI: -15.56 to -7.49). Conversely, in CHF with preserved left ventricular ejection fraction ( HFpEF), PDE5i were shown not to yield any beneficial effect concerning the investigated endpoints. Conclusions: In HFREF, PDE5i were shown to improve the composite of death and hospitalization, as well as exercise capacity and pulmonary hemodynamics. Conversely, in HFpEF, no significant clinical, ergospirometric or hemodynamic betterment was achieved using PDE5i treatment.
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Muhammad Abu-Elmagd,
Mansour A Alghamdi,
Magdy Shamy,
Mamdouh I Khoder,
Max Costa,
Mourad Assidi,
Roaa Kadam,
Haneen Alsehli,
Mamdooh Gari,
Peter Natesan Pushparaj,
Gauthaman Kalamegam,
Mohammed Al-Qahtani
Medicine & Pharmacology, General Medical Research; Particulate matter; BM-MSCs; cell proliferation; cell death; qRT-PCR; IPA
Online: 20 March 2017 (16:33:56 CET)
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Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with an array of acute and chronic diseases, in humans. However, their specific effects on the stem cells remain unclear. Here, we report the effects of PM collected from Jeddah city on bone marrow mesenchymal stem cells (BM-MSCs) on proliferation, cell death, related gene expression and systems biological analysis aiming to understand the underlying mechanisms. Two different sizes (PM2.5-10) were tested in vitro at various concentrations (15 to 300 µg/ml) and durations (24 to 72 h). PMs induced cellular stress including membrane damage, shrinkage and death. Lower concentrations of PM2.5 increased BM-MSCs proliferation, while higher concentrations decreased it. PM10 decreased BM-MSCs proliferation in a concentration-dependant manner. The X-Ray Fluorescence spectrometric analysis showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis (IPA) and hierarchical clustering analyses showed that heavy metals were associated with signalling pathways involving cell stress/death, cancer and chronic diseases. qRT-PCR results showed differential regulation of the apoptosis genes (BCL2, BAX); upregulation of inflammation associated genes (TNF-a and IL-6) and downregulation of cell cycle regulation gene (P53). We conclude that PM could affect different cellular functions and predispose to debilitating diseases.
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Medicine & Pharmacology, Other; diabetes; education; environmental tobacco smoke; smoker
Online: 20 March 2017 (09:09:44 CET)
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Background: Smoking, including environmental tobacco smoke (ETS) exposure is a well-known risk factor for diabetes. Low socioeconomic status, especially lack of education, also is a risk factor for diabetes. Therefore, we assessed the association of education and smoking status, including ETS exposure, with the prevalence of diabetes. Methods: Data were from the 2007–2013 Korea National Health and Nutritional Evaluation Survey (KNHANES). Multivariable logistic regression examined associations between various lifestyle and health factors and prevalence of diabetes while controlling for potential confounding variables. Subgroup analysis was performed according to smoking status to determine factors associated with diabetes. Results: Of 19,303 individuals analyzed, 1,325 (11.4%) had diabetes. Greater average age, male sex, lower educational level, unemployment, and coexisting health problems were significantly associated with diabetes. Individuals with only elementary, middle, or high school level education had significantly greater odds ratios (p<0.05) compared to college graduates; smokers and nonsmokers exposed to ETS had significantly greater OR (p<0.05) than nonsmokers unexposed to ETS. Subgroup analysis of diabetics according to smoking status revealed significant associations (p<0.05) for diabetic nonsmokers exposed to ETS with female sex, single status, elementary level education, urban residence, National Health Insurance (NHI), hypertension, no alcohol intake, and no moderate physical activity. For diabetic smokers, there were significant associations (p<0.05) with elementary education, urban residence, lack of moderate physical activity, no alcohol intake, and NHI. Conclusions: The results suggested that smoking status, including ETS exposure, was associated with a higher prevalence of diabetes especially in populations with less education. Thus, we should direct efforts for controlling diabetes toward individuals with lower levels of education, and those who are smokers and nonsmokers exposed to ETS.
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Medicine & Pharmacology, Nutrition; pancreatic cancer; alcohol intake; folate intake; case-control study
Online: 20 March 2017 (08:29:00 CET)
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Pancreatic cancer is one of the most fatal common cancers affecting both men and women, representing about 3 percent of all new cancer cases in the United States. In this study, we aimed to investigate the association of pancreatic cancer risk with alcohol consumption as well as folate intake. We performed a case-control study of 384 patients diagnosed with pancreatic cancer from May 2004 to December 2009 and 983 primary care healthy controls. Our findings showed no significant association between risk of pancreatic cancer and either overall alcohol consumption or type of alcohol consumed (drinks/day). Our study showed dietary folate intake was modestly but significantly inversely associated with pancreatic cancer (OR=0.99, P <.0001). The current study supports the hypothesis that pancreatic cancer risk is reduced with higher food-based folate intake.
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Medicine & Pharmacology, Pharmacology & Toxicology; machine learning; random forest; estrogen receptor; Tox21 data challenge 2014; QSAR prediction model
Online: 17 March 2017 (04:49:28 CET)
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Many agonists for the estrogen receptor are known to disrupt endocrine functioning. We have developed a computational model that predicts agonists for the estrogen receptor ligand-binding domain in an assay system. Our model was entered into the Tox21 Data Challenge 2014, a computational toxicology competition organized by the National Center for Advancing Translational Sciences. This competition aims to find high-performance predictive models for various adverse-outcome pathways, including the estrogen receptor. Our predictive model, which is based on the random forest method, delivered the best performance in its competition category. In the current study, the predictive performance of the random forest models was improved by strictly adjusting the hyperparameters to avoid overfitting. The random forest models were optimized from 4,000 descriptors simultaneously applied to 10,000 activity assay results for the estrogen receptor ligand-binding domain, which have been measured and compiled by Tox21. At this time, our model delivers the highest predictive power on estrogen receptor agonists in the world. Furthermore, analysis of the optimized model revealed some important features of the agonists, such as the number of hydroxyl groups in the molecules.
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Medicine & Pharmacology, Pathology & Pathobiology; Extracellular vesicles (EVs); Peptidylarginine deiminases (PADs); Chlor-amidine (Cl-Am); cancer; neurodegeneration; deimination; cytoskeleton; induced pluripotent stem cells (iPSCs); histone H3; epigenetics
Online: 16 March 2017 (17:54:15 CET)
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Extracellular vesicle (EV) release, which occurs in most eukaryotic cells, has recently been associated with peptidylarginine deiminase (PAD)-driven protein deimination. Evidence points to the involvement of deiminated cytoskeletal proteins and changes in histone deimination. Both PADs and EVs are associated with various pathologies including cancers, autoimmune and neurodegenerative diseases. The elevated PAD expression observed in cancers may contribute to increase in EV shedding observed from cancer cells, contributing to cancer progression. Similarly, elevated PAD expression observed in neurodegenerative diseases may cause increased EV shedding and spread of neurodegenerative EV cargo, contributing to disease progression and pathologies. Pharmacological inhibition of PAD-mediated deimination using pan-PAD inhibitor Cl-amidine, reduced cellular EV release in prostate cancer cells, rendering them significantly more susceptible to chemotherapeutic drugs. Studies on models of central nervous system damage have demonstrated critical functional roles for PADs and neuroprotective effects using PAD inhibitors in vivo, while human neurodegenerative iPSC in vitro models showed evidence of increased protein deimination. Besides using refined PAD inhibitors to selectively manipulate EV biogenesis for novel combination therapies in cancer treatment, we also speculate how EV biogenesis could be targeted via the newly identified PAD-pathway to ameliorate neurodegenerative disease progression.
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Medicine & Pharmacology, Behavioral Neuroscience; autism spectrum disorders; fragile X syndrome (FXS); sleep disorder; melatonin
Online: 15 March 2017 (07:40:49 CET)
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Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.
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Medicine & Pharmacology, Gastroenterology; lifestyle factors; chronic inflammatory diseases; treatment result; treatment response; diet; meat intake; dietary pattern; food; mucosa associated bacteria; epithelium-associated bacteria; microbiome; fibre intake; personalized medicine; mucus; sulphate-reducing bacteria; mucin-degrading bacteria; Western style diet; anti-TNF
Online: 15 March 2017 (07:29:13 CET)
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We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.
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Medicine & Pharmacology, Other; Zika Virus, Antiviral, Marine Algae
Online: 14 March 2017 (18:34:37 CET)
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For many years marine algae has been subject of numerous researches and as a source of natural products with antiviral activity, such as terpenes, alkaloids and sulphated polysaccharides. However, the anti-Zika virus (ZIKV) potential of algae has not been studied. In this study we evaluated extracts seven species of the three major classes of seaweeds (Phaeophyceae, Chlorophyceae and Rhodophyceae) against ZIKV. All seaweeds tested are native of the Brazilian coast, except for Kappaphycus alvarezii that can be cultivated. ZIKV a mosquito-borne flavivirus, has become a public health problem. In recent years there has been an increase in the number of cases and a strong association between ZIKV outbreak and the spread of cases of Guillain-Barré Syndrome and microcephaly. All seaweed extracts tested in this work inhibits ZIKV replication in a dose-dependent manner. Caulerpa racemosa, Kappaphycus alvarezii and Osmundaria obtusiloba extracts were able to inhibit viral replication at low concentrations with EC50 values ranging from 1.38 to 1.98 µg/mL. We observed that O. obtusiloba presented a significant virucidal effect. Our results suggest that extracts of C. racemosa, K. alvarezii and O. obtusiloba presented very promising results, being excellent candidates for further studies, demonstrating that marine algae are an interesting source for the development of novel anti-ZIKV agents.
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Medicine & Pharmacology, Oncology & Oncogenics; breast cancer; dense breasts; dual-modality imaging; FFDM; ABUS
Online: 14 March 2017 (09:24:58 CET)
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Although mammography has been the gold standard for early detection of breast cancer, if a woman has dense breast tissue, a false negative diagnosis may occur. Breast ultrasound, whether hand-held or automated, is a useful adjunct to mammography but adds extra time and cost. The primary aim was to demonstrate that our second-generation Aceso system, which combines full-field digital mammography (FFDM) and automated breast ultrasound (ABUS) in a single platform, is able to produce improved quality images that provide clinically meaningful results. Aceso was first tested using two industry standards: a CDMAM phantom to assess the FFDM images; and the CIRS 054GS phantom to evaluate the ABUS images. In addition, 25 women participated in a clinical trial: 14 were healthy volunteers while 11 were patients referred by the breast clinic at Groote Schuur Hospital. The CDMAM phantom results showed the FFDM results were better than EUREF’s standard of “acceptable” and were approaching “achievable”. The ABUS results showed lateral and axial spatial resolution of 0.5 mm and adequate depth penetration of 80 mm. Our second-generation Aceso system, with its improved quality of clinical FFDM and ABUS images, has demonstrated its potential for early detection of breast cancer in a busy clinic.
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Medicine & Pharmacology, Nutrition; salt; sodium; potassium; intake; MedDietScore; Greece
Online: 14 March 2017 (08:56:43 CET)
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A reduction in population sodium (as salt) consumption is one of the most cost-effective strategies to reduce the burden of cardiovascular disease and it is a global health priority. High potassium intake is also recommended to reduce cardiovascular disease. To establish effective policies for setting targets and monitoring effectiveness within each country, the current level of consumption should be known. Greece lacks data on actual sodium and potassium intakes. The aim of the present study was therefore to assess dietary salt (using sodium as biomarker) and potassium intakes in a sample of healthy adults in northern Greece and to determine whether adherence to a Mediterranean diet is related to different sodium intakes or sodium-to-potassium ratio. A cross-sectional survey was carried out in Thessaloniki greater metropolitan area (northern Greece) (n=252, aged 18-75 years, 45.2% males). Participants’ dietary sodium and potassium intakes were determined by 24h urinary sodium and potassium excretions. In addition, we estimated their adherence to Mediterranean diet by the use of an 11-item MedDietScore (range 0-55). The mean sodium excretion was 175 (SD 72) mmol/day, equivalent to 4,220 (1,745) mg of sodium or 10.7 (4.4) g of salt per day and potassium excretion was 65 (25) mmol/day, equivalent to 3,303 (1,247) mg/day. Men had higher sodium and potassium excretions compared to women. Only 5.6% of the sample had salt intake <5g/d, which is the target intake recommended by the WHO. Mean sodium-to-potassium intake ratio was 1.34 (0.51). There was no significant difference in salt or potassium intake or their ratio across MedDietScore quartiles. No significant relationships were found between salt intake and adherence to Mediterranean diet, suggesting that the perception of the health benefits of the Mediterranean diet does not hold when referring to salt consumption. These results suggest the need for a larger nation-wide survey on salt intake in Greece and underline the importance of continuation of salt reduction initiatives in Greece.
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Medicine & Pharmacology, Nursing & Health Studies; systematic review; forest therapy; depression; adults
Online: 14 March 2017 (08:45:56 CET)
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The purpose of this study was to systematically review forest therapy programs designed to decrease the level of depression among adults and subsequently identify the gaps in the literature. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The authors independently screened full-text articles from various databases using the following criteria: 1) intervention studies assessing the effects of forest therapy on depression in adults aged 18 years and over; 2) studies including at least one control group or condition; 3) been peer-reviewed; and 4) been published either in English or Korean before July 2016. The Scottish Intercollegiate Guideline Network (SIGN) measurement tool was used to assess the risk of bias in each trial. In the final sample, a total of 28 articles (English: 13, Korean: 15) were included in the present systematic review. This review concluded that forest therapy is one of the emerging and effective interventions for decreasing the level of depression in adults. However, the studies included in this review lacked methodological rigor. Future studies assessing the long-term effect of forest therapy on depression using rigorous study designs are needed.
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Medicine & Pharmacology, Other; electronic cigarette; e-cigarette; smoking; adolescent; frequency; tobacco
Online: 14 March 2017 (07:56:50 CET)
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Introduction The prevalence of adolescent electronic cigarette (e-cigarette) use has increased in most countries. This study determines the relation between the frequency of e-cigarette use and the frequency and intensity of cigarette smoking. Furthermore, it evaluates the association between the reasons for e-cigarette use and the frequency of its use. Materials and Methods Participants were 68,043 middle and high school students aged 13–18 years from the 2015 Korean Youth Risk Behavior Web-Based Survey. Of the 68,043 participants, we analyzed 6,655 adolescents with an experience of e-cigarette use. Results The prevalence of ever using and current (past 30 days) use of e-cigarettes was 10.1% and 3.9%, respectively. Of the ever e-cigarette users, approximately 40% used e-cigarettes for ≥1/month and 8.1% used e-cigarettes daily. Daily e-cigarettes users were 10 times greater among daily cigarette smokers than among cigarette users for <1/month (18.1% vs. 1.8%) and 16 times more prevalent among those smoking ≥20 cigarettes/day than among those smoking <1 cigarette/month (38.9% vs. 2.4%). The most common reason for e-cigarette use was curiosity (22.9%), followed by less harmful than conventional cigarettes (18.9%), smoking cessation (13.1%), and indoor use (10.7%). Curiosity was the most common reason among less frequent e-cigarette users; however, smoking cessation and indoor use were the most common reasons among more frequent users. Conclusions Results showed a positive relation between frequency or intensity of conventional cigarette smoking and frequency of e-cigarette use among Korean adolescents, and frequency of e-cigarette use differed according to the reason for the use of e-cigarettes.
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Medicine & Pharmacology, Oncology & Oncogenics; mucositis; radiotherapy; chemotherapy; pathophysiology; management; melatonin
Online: 9 March 2017 (04:46:30 CET)
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The current treatment for cervico-facial cancer involves radio and/or chemotherapy. Unfortunately, cancer therapies can lead to local and systemic complications such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract. Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. However, melatonin, whose role in the treatment of mucositis has recently been investigated, offers an effective alternative therapy in the prevention and/or management of radio and/or chemotherapy-induced mucositis. This review focuses on the pathobiology and management of mucositis in order to improve the quality of cancer patients’ lives.
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Medicine & Pharmacology, Oncology & Oncogenics; bacteria; bacteriome; carcinoma; microbiome; mouth; smokeless; snuff; tobacco
Online: 6 March 2017 (07:18:27 CET)
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Smokeless tobacco (ST) products vary significantly in their oral carcinogenicity. Much is known about the differences in chemical, but not bacterial, constituents of these products. In this study, we explore the composition and function of the bacteriome in ST products from 4 countries using q-PCR and 16S rRNA-based next generation sequencing. The bacterial load (16S rRNA copies/gram) was lowest in Swedish snus (3.4E+6) and highest in Yemeni shammah (6.6E+11). A total of 491 species-level taxa, many of which are potentially novel, belonging to 178 genera and 11 phyla were identified. Species richness and diversity were highest for Swedish snus and lowest for Yemeni shammah. Bacillus, Paenibacillus, and Oceanobacillus spp. were the most abundant in American snuff; species of Pseudomonas, Massilia, Propionibacterium, Puniceispirillum and Gloeothece predominated in Swedish snus. In Sudanese toombak, Facklamia, Desemzia, Atopostipes and Lysinibacillus spp. accounted for the majority of the bacteriome. Yemeni shammah exclusively contained Bacillus spp. PICRUSt functional prediction showed that genes encoding cadmium/zinc and nickel transport systems were enriched in the presumptively “high carcinogenicity” products. The bacteriome of ST products thus differed qualitatively, quantitatively and functionally. The relevance of these differences, particularly with respect to nickel and cadmium, to oral carcinogenesis warrants further investigation.
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Medicine & Pharmacology, Oncology & Oncogenics; 16S rRNA; bacteria; bacteriome; carcinoma; High-Throughput Nucleotide Sequencing; microbiome; mouth; squamous cell
Online: 6 March 2017 (04:47:15 CET)
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Studies on the possible association between bacteria and oral squamous cell carcinoma (OSCC) remain inconclusive, largely due to methodological variations/limitations. The objective of this study was to characterize the species composition as well as functional attributes of the bacteriome associated with OSCC. DNA obtained from 20 fresh OSCC biopsies (cases) and 20 deep-epithelium swabs (matched control subjects) were sequenced for the V1-V3 region using Illumina’s 2x300 bp chemistry. High quality, non-chimeric merged reads were classified to species level using a prioritized BLASTN-algorithm. Downstream analyses were performed using QIIME, PICRUSt, and LEfSe. Fusobacterium nucleatum subsp. polymorphum was the most significantly overrepresented species in the tumors followed by Pseudomonas aeruginosa and Campylobacter sp. Oral taxon 44, while Streptococcus mitis, Rothia mucilaginosa and Haemophilus parainfluenzae were the most significantly abundant in the controls. Functionally, genes involved in bacterial mobility, flagellar assembly, bacterial chemotaxis and LPS synthesis were enriched in the tumors while those responsible for DNA repair and combination, purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, ribosome biogenesis and glycolysis/gluconeogenesis were significantly associated with the controls. This is the first epidemiological evidence for association of F. nucleatum and P. aeruginosa with OSCC. Functionally, an “inflammatory bacteriome” is enriched in OSSC.
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Medicine & Pharmacology, Dentistry; Poly (lactic acid); chitosan; calcium silicate; tissue engineering; osteogenesis
Online: 1 March 2017 (17:03:43 CET)
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Electrospinning is the versatile technique to generate large quantities of micro- or nano-fibers from a wide variety of shapes and sizes of polymer. Natural bone is a hierarchically composites with the dispersion of inorganic ceramic along organic polymer. The aim of this study, the electrospun poly (lactic acid) (PLA) mats coated with chitosan (CH) and calcium silicate (CS) powder were fabricated. The morphology, chemical composition, and surface properties of CS/CH-PLA composites were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. In vitro, the CS/CH-coated PLA mats increased the formation of apatite on the surface when soaking in cell cultured medium. During culture, the adhesion and proliferation of the human mesenchymal stem cells (hMSCs) cultured on CS/CH-PLA were significantly promoted relative to those on PLA. Collagen I and fibronectin levels and promoted cell adhesion were observed upon an increase in CS content. Further, compared to PLA mats without CS/CH, CS10 and CS15 mats markedly enhanced the proliferation of hMSCs as well as their osteogenesis properties, which was characterized by bone-related gene expression. Our results demonstrated that the biodegradable and electroactive CS/CH-PLA mats had potential application as an ideal candidate for bone tissue engineering. Together, findings from this study clearly demonstrated that PLLA-C2S composite scaffold may function as an ideal candidate for bone tissue engineering.
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Medicine & Pharmacology, Other; ghrelin; serotonin N-acetyltransferase; tryptophan 5-hydroxylase 1; melatonin; pineal gland; photoperiod; sheep
Online: 28 February 2017 (11:13:01 CET)
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Several studies suggests that ghrelin (GHRL) has neurobiological effects that extend beyond control of food intake. Our previous results confirmed that GHRL modulates the secretory activity of the pineal gland (PG) through nocturnal melatonin (MEL) secretion in sheep, the seasonally reproductive animals. Here we investigated the effects of GHRL (10 ng/ml) on the expression of enzymes limiting synthesis of MEL, including tryptophan 5-hydroxylase 1 (TPH1), serotonin N-acetyltransferase (AA-NAT) and its phosphorylated form p31T-AA-NAT in sheep PG explants (n = 72) during the 4-hour incubation in a gas-liquid interface, at a short (SD) and long (LD) photoperiods. After each hour of incubation selected explants were frozen in liquid nitrogen and stored at -80°C for subsequent analysis (real-time PCR, western-blotting, ELISA). Results show that GHRL regulates nightly MEL secretion in a TPH1-independent manner. The factor modulating GHRL activity was photoperiod. During SD photoperiod GHRL significantly reduced the expression of p31T-AA-NAT, AA-NAT and inhibited MEL secretion from PG explants. Whereas, during LD photoperiod no effect of GHRL on MEL secretion and expression of examined enzymes was noted. Studies indicate that GHRL directly affects PG under in vitro conditions and causes MEL secretion in animals which exhibit seasonality in reproductive and metabolic processes.
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Medicine & Pharmacology, Nutrition; ovalbumin, allergy; advanced glycation; fructose; fructositis; receptor for advanced glycation end products; inflammation; asthma; chlorogenic acid; Ilex paraguariensis; high fructose corn syrup
Online: 28 February 2017 (10:41:10 CET)
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One mechanism by which fructose could exert deleterious effect in metabolism and inflammation is via its potency vis-à-vis de Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin to test the hypothesis that indeed AGEs are formed by fructose during simulated digestion of an ubiquitous food protein with intrinsic allergenic potential and under model physiological conditions. Methods: OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100 mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370 nm, Emission: λ 440nm. Results: AGE adducts form between fructose and OVA which can be found in peptide fractions (< 5 kDa) at times (30 min) and concentration ranges (10 mM) plausibly found in the intestines, whereas no reaction occurs with glucose. The reaction is inhibited by chlorogenic acid at concentrations compatible with those found in the gut. The reaction is inhibited by AG, a specific antiglycation agent. Conclusion: Our proof of principle study shows that fructose-AGE formation on an ubiquitous allergenic protein indeed occurs in one hour and thereby may pave the way for the study of yet another mechanism by which the excess fructose in our Western diets is contributing to disease: intestinal AGE formation, absorption and RAGE engagement.
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Medicine & Pharmacology, Oncology & Oncogenics; MicroRNA; cancer associated fibroblasts; cell-cell communication; transformation; epigenetic
Online: 28 February 2017 (10:29:27 CET)
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Tumor microenvironment including cancer-associated fibroblasts (CAF) has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell – tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles. There is evidence that miRs have very similar roles in activating hepatic (HSC) and pancreatic stellate cells (PSC) as part of precancerous fibrotic diseases. In summary, deregulated miRs affect various intracellular functional complexes, such as transcriptional factors, extracellular matrix, cytoskeleton, EMT/MET regulation, soluble factors, tyrosine kinase and G-protein signaling, apoptosis and cell cycle & differentiation, but also formation and composition of the extracellular microenvironment. These processes result in the clinical appearance of desmoplasia involving CAFs and fibrosis characterized by deregulated stellate cells. In addition, modulated release of soluble factors can act as (auto)activating feedback loop for transition of NFs into their pathological counterparts. Furthermore, epigenetic communication between CAFs and cancer cells may confer to cancer specific functional readouts and transition of NF into their pathological counterparts. MiR related epigenetic regulation with many similarities should be considered as key factor in development of cancer and fibrosis specific environment.
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Medicine & Pharmacology, Urology; LUTS; stress urinary incontinence; perimenopause; pelvic floor
Online: 27 February 2017 (17:41:42 CET)
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Stress urinary incontinence (SUI) influences the quality of life of women. The research applied ICIQ LUTS qol (The International Consultation Incontinence Questionnaire Lower Urinary Tract Symptoms quality of life) as a tool to measure the quality of life (QOL) of patients with stage 1 SUI in many areas. 140 perimenopausal women who participated in a urodynamic test at Department of Gynecology, Endocrinology and Gynecologic Oncology, Pomeranian Medical University, Police, Poland in the years 2013-2015 were enrolled in the study. Patients were divided into two groups: A and B. Two questionnaires were applied: the author’s original questionnaire and the standardized ICIQ LUTS qol. Gymnastic plans were recommended 4 times per week for the period of 3 months. The plan for group A included the exercises of pelvic floor muscles (PFM) with the simultaneous tension of the transverse abdominal muscle (TrA) and for group B included the exercises of PMF without TrA. The evaluation of the quality of life of patients with stage 1 SUI with the use of ICIQ LUTS qol among patients from groups A and B after therapy showed a significant improvement in most areas. More impact is observed in the physiotherapy of both PFM with TrA.
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Medicine & Pharmacology, General Medical Research; human antibody; invasion; lung cancer; therapeutic target; VCAM-1; VCAM-1-D6
Online: 15 February 2017 (10:45:16 CET)
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Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.
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Medicine & Pharmacology, Nutrition; advanced glycation end products; fructose; glucose; lipogenesis; sphingolipids; NLRP3; Nrf2; mitochondrial dysfunction; oxidative stress
Online: 14 February 2017 (08:38:14 CET)
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The rapid increase in metabolic diseases occurred in the last three decades in both industrialized and developing countries has been related to the rise in sugar-added foods and sweetened beverages consumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as consequence of a high dietary sugars intake. Animal models of high sugars consumption, in particular fructose, have reported AGEs accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations. The in vitro observation that fructose is one of the most rapid and effective glycating agent when compared to other sugars has prompted the investigation of the in vivo fructose-induced glycation. In particular, the widespread employment of fructose as sweetener has been ascribed by many experimental and observational studies for the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet-derived AGEs have been demonstrated to interfere with many cell functions such as lipid synthesis, inflammation, antioxidant defences, and mitochondrial metabolism. Moreover, emerging evidences also in humans suggest that this impact of dietary AGEs on different signalling pathways can contribute to the onset of organ damage in liver, skeletal and cardiac muscle, and brain, affecting not only metabolic control, but global health. Indeed, the here reviewed most recent reports on the effects of high sugars consumption and diet-derived AGEs on human health suggest the need to limit the dietary sources of AGEs, including added sugars, to prevent the development of metabolic diseases and related comorbidities.
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Medicine & Pharmacology, Psychiatry & Mental Health studies; suicide; network analysis; symptoms; personalized treatment
Online: 13 February 2017 (11:04:49 CET)
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Although suicide is a major public health issue worldwide, we understand little of the onset and development of suicidal behavior. Suicidal behavior is argued to be the end result of the complex interaction between psychological, social and biological factors. Epidemiological studies resulted in a range of risk factors for suicidal behavior, but we do not yet understand how their interaction increases the risk for suicidal behavior. A new approach called network analysis can help us better understand this process as it allows to visualize and quantify complex association between many different symptoms or risk factors. A network analysis of data contain information on suicidal patients can help us understand how risk factors interact and how their interaction is related to suicidal thoughts and behaviour. A network perspective has been successfully applied to the field of depression and psychosis, but not yet to the field of suicidology. In this theoretical article, I will introduce the concept of network analysis to the field of suicide prevention, and offer directions for future applications and studies.
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Kazufumi Nakamura,
Hiromi Matsubara,
Satoshi Akagi,
Toshihiro Sarashina,
Kentaro Ejiri,
Norifumi Kawakita,
Masashi Yoshida,
Toru Miyoshi,
Atsuyuki Watanabe,
Nobuhiro NIshii,
Hiroshi Ito
Medicine & Pharmacology, Cardiology; pulmonary arterial hypertension; prostacyclin; nanoparticle; drug delivery system
Online: 13 February 2017 (09:27:09 CET)
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Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost)-incorporated nanoparticles and imatinib, a PDGF-receptor tyrosine kinase inhibitor, -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of PAH and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for treatment of PAH.
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Medicine & Pharmacology, Pediatrics; congenital hypothyroidism; incidence; neonatal screening; thyroid-stimulating hormone; cutoff level
Online: 8 February 2017 (10:54:10 CET)
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Lower cutoff levels in screening programs have led to an increase in the proportion of detected cases with transient hypothyroidism, leading to increase of the overall incidence of primary congenital hypothyroidism (CH) in several countries. We have performed retrospective evaluation on the data from 251,008 (96.72%) neonates screened for thyroid-stimulating hormone (TSH) level in dried blood spot specimens taken 48 hours after birth, between 2002 and 2015, using DELFIA method. A TSH value of 15 mIU/L was used as the cutoff point until 2010 and 10 mIU/L thereafter. Primary CH was detected in 127 newborns (1/1976) of which 81.1% had permanent and 18.9% had transient CH. The incidence of primary CH was increased from 1/2489 until to 2010 to 1/1585 thereafter (p=0.131). However, the incidence of permanent CH was slightly increased (p=0.922), while the transient CH incidence had 8-fold increasing after lowering the TSH cutoff level (p<0.001). In cases with permanent CH, we observed lower frequency for thyroid dysgenesis (82.7 vs. 66.7%) and higher frequency for normal in-situ thyroid gland (17.3 vs. 33.3%), for the period with reduced TSH cutoff value. Our findings support the impact of lower TSH cutoff on the increasing incidence of congenital hypothyroidism.
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Medicine & Pharmacology, General Medical Research; alpha-synuclein; Parkinsons disease; dementia with Lewy bodies; multiple system atrophy; tunelling nanotube; glymphatic system; cell-to-cell spread
Online: 7 February 2017 (03:24:21 CET)
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Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.
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Medicine & Pharmacology, Nutrition; Vitamin D, Knowledge, Attitude, Practice, Validity, Reliability
Online: 1 February 2017 (16:39:41 CET)
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The aim of this study was to develop a valid and reliable questionnaire to assess vitamin D-related knowledge, attitude and practice (KAP) in Iranian adults who may be at increased risk of vitamin D deficiency. This study was conducted on 527 subjects, aged ≥20 years from Public health care centers in Tehran, Iran. Based on results of literature review and in-depth interviews, the 38-item vitamin D-related KAP questionnaire with four subscale was developed: 1) general knowledge; 2) nutritional knowledge; 3) attitudes; 4) behaviors. Validity of the developed vitamin D-KAP questionnaire was assessed, utilizing face, content, and construct validity methods. Internal consistency was calculated to assess reliability of the current developed questionnaire. A total of 572 (54.1% female) adults, aged 30.2±7.9 years, participated in the study. All items were perceived as relevant and comprehendible by participants. Content validity was confirmed by the panel of experts. The internal consistency, as measured by Cronbach’s alpha coefficients, exceeded the minimum reliability standard of 0.60 for four subscales. The EFA suggested a four-factor construct and the results of the CFA indicated acceptable fit indices for the proposed model. No ceiling effects were observed except for general knowledge (1.2%). Floor effects detected were 0, 1.1, 2.4, and 8.7% for practice, attitude, general knowledge, and nutrition knowledge, respectively. General knowledge had the highest score (79.59±14.52) and nutrition knowledge, the lowest score (42.58±20.40) among the four sub-scales. Results confirm the initial validity and reliability of the vitamin D-related knowledge, attitude and practice questionnaire. Further investigations in different urban and rural population are recommended.
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Medicine & Pharmacology, Pharmacology & Toxicology; Danggui-Shaoyao-San, chronic restraint stress, learning and memory, anxiety/depression, structural plasticity
Online: 31 January 2017 (15:30:41 CET)
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Background: Clinical trails have revealed that patients with depression generally accompanied with learning and memory impairment, which critically impact on individual’s health and development. Danggui-Shaoyao-San (DSS), a famous Chinese complex prescription, significantly overcame depression and relieved cognitive disorder based on previous research and publication. However, its effectsand potential mechanism against chronic restraint stress (CRS) remained unknown. Methods: CRS animal model was established and mice were divided to six groups while they were oral administrated with Danggui-Shaoyao-San at doses of 1.25, 2.5 and 5 g/kg for 14 days. Emotional and cognitive performances were detected by behavior tests, meanwhile neural plasticity and its molecular mechanism were examined by Dil staining, western blot and immunofluorescence. Results: DSS treatment dose-dependently improved locomotion ability in open filed test, overcame depression behavior in forced swimming test and elevated plus maze test, enhanced learning and memory ability in Morris water maze test. CRS decreased number of total spines and mushroom spines, while DSS treatment dose-dependently restored these by Dil staining. Expression of BDNF and GluR1 were significantly down-regulated in CRS group, which were significantly normalized by DSS. Conclusions: DSS treatment dose-dependently reversed CRS-induced cognitive impairments by inducing structural remodeling of neurons.
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Medicine & Pharmacology, Nutrition; nutritional intervention; menopausal women; vitamin D3-fortified yogurts; serum 25OHD dose response; seasonality interaction
Online: 31 January 2017 (12:01:31 CET)
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A 24 week-controlled trial was conducted in menopausal women (mean age:61.5) to assess serum 25-hydroyvitaminD (s25OHD) evolution in relation to three interdependent determinants: doses of supplemented (Suppl.) vitamin D3 (VitD3); baseline status; seasonality. Participants were randomized into 3 groups (Gr): Gr.Suppl.0, time-controls maintaining dietary habits; Gr.Suppl.5 and Gr.Suppl.10 consuming one and two 125 g servings of VitD3-fortified yogurts with 5 and 10 µg daily doses, respectively. The 16 intervention-weeks lasted from early-January to mid-August, the 8 follow-up-weeks from late-August to mid-October. Before enrollment, subjects were randomized into two s25OHD strata: “Low stratum (LoStr)“: 25-50 nmol/L; “High stratum (HiStr)“: >50-75 nmol/L. All enrolled participants remained compliant until study end: Gr.Suppl.0 (n=45), Gr.Suppl.5 (n=44) Gr.Suppl.10 (n=44). Over the 16 intervention and 8 follow-up weeks, s25OHD increased in both supplemented groups, more in Gr.Suppl.10 than Gr.Suppl.5. The constant rate of s25OHD per supplemental VitD3 microgram was greater in LoStr than HiStr. s25OHD increase was greater with late (mid-March) than early (mid-January) inclusion. In conclusion, this randomized trial demonstrates: -a dose-dependent s25OHD improvement related to fortified yogurt consumption; -an inversely baseline-dependent increase in s25OHD; -a seasonal effect that highlights the importance of vitamin D3 supplementation during winter, even at 5µg/d, in healthy menopausal women.
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Medicine & Pharmacology, Clinical Neurology; csf; shunt; filtration; neurodegenerative; neuroimmunology; alzheimer; parkinson; guillain-barre; device; ventriculo-peritoneal shunt
Online: 30 January 2017 (14:22:03 CET)
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Liquorpheresis (CSF filtration) comprises a therapeutical approach that has been
proposed to treat several neurological conditions where antibodies, inflammatory
mediators or abnormal peptides are the cause or play an important role in the
pathogenesis of the disease. CSF replacement may be an alternative approach not
explored so far.
Here, we review previous experiences in the use of liquorpheresis in autoimmune and
degenerative neurological diseases. Then we describe previous developments and
provide some new technical innovations in order to design bidirectional CSF shunting
systems. These systems can be complemented either with a deposit of artificial CSF or
with a CSF filter, allowing CSF replacement or liquorpheresis respectively. Both options
would lead to mechanical dilution of the patient’s CSF.
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Medicine & Pharmacology, Oncology & Oncogenics; theranostics ; nuclear medicine ; personalized medicine
Online: 22 January 2017 (04:29:27 CET)
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The importance of personalized medicine is growing, since there is an urged need to avoid unnecessary and expensive treatments. In nuclear medicine, the theranostic approach is an established tool for a specific molecular targeting in means of diagnostics and therapy. The visualisation of potential targets can help to predict if a patient would benefit from a particular treatment or not. Thanks to the quick development of radiopharmaceuticals and diagnostic techniques, the use of theranostic agents is constantly rising. In this article important milestones of nuclear therapies and diagnostics in the context of theranostics are highlighted. It begins with the well-known radioiodine therapy in patients with thyroid cancer and then guides through different approaches for the treatment of advanced cancer with targeted therapies. The aim of this review is to provide a summary of background knowledge, current applications and advantages of targeted therapies and imaging in nuclear medicine practice.
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Medicine & Pharmacology, Nutrition; 22:6 docosahexaenoic acid; ω-3 fatty acids; offspring of obese mothers; offspring of lean mothers; insulin-dependent skeletal muscle glucose uptake
Online: 20 January 2017 (04:59:25 CET)
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Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.
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Medicine & Pharmacology, Dentistry; periodontitis; PMX-53; miniature swines
Online: 19 January 2017 (01:52:00 CET)
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Periodontitis is a chronic inflammatory disease which results in the destruction of the tooth’ s supporting tissues and the alveolar bone resorption. The complement becomes a major link between infection and inflammatory pathology including periodontitis. Gingipians as important virulence factors of P. gingivalis have the activity of C5 convertase, could cleave C5 into fully functional C5a to activate C5aR. The above process could be blocked by the C5aR antagonist (PMX-53) to suppress local periodontal inflammation, and then achieves the purpose of treatment of periodontitis. Nanoparticles incorporated within gelatin are promising carrier system for drug delivery in recent years. This study aimed to investigate whether gelatin nanoparticles loaded with PMX-53 prevents alveolar bone resorption in miniature swines model of periodontitis. Four miniature swines were placed ligatures around the maxillary and mandibular fourth premolar and first molar on both sides for seven weeks to induce periodontitis. Then, animals were assigned randomly to four groups: minocycline-treated group, gelatin with PMX53-treated group, gelatin-treated group and a sham control group. They were treated with 1ml related drugs respectively, into gingival sulcusl for 4 times at one-week intervals. We showed that local treatments with gelatin nanoparticles loaded with PMX-53 could inhibit alveolar bone loss of periodontitis. Our study revealed that gelatin nanoparticles loaded with PMX-53 prevented alveolar bone resorption miniature swines model of periodontitis. In addition, provided proof-of-concept for local targeting of gelatin nanoparticles loaded with PMX-53 as a powerful candidate for the treatment of periodontitis.
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Medicine & Pharmacology, Oncology & Oncogenics; IQGAP1; glioblastoma multiforme (GBM); scaffold protein; podosome/invadosome
Online: 16 January 2017 (10:30:48 CET)
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Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signaling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumors, suggesting a role for this protein in cell proliferation, transformation and invasion. IQGAP1 has been identified as a marker of amplifying cancer cells in GBMs. To determine the involvement of IQGAP1 in the onco-biology of GBM, we performed immunohistochemical confocal microscopic analysis of the IQGAP1 protein in human GBM tissue samples using cell type-specific markers. IQGAP1 immunostaining and subcellular localization was heterogeneous; the protein was located in the plasma membrane and, at variable levels, in nucleus and/or cytosol. Moreover, IQGAP1 positive staining was found in podosome/invadopodia-like structures. IQGAP1+ staining was observed in neurons (Map2+ cells), in cancer stem cells (CSC; nestin+) and in several macrophages (CD31+ or Iba1+). Our results indicate that the IQGAP1 protein is involved in normal cell physiology as well as oncologic processes.
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Medicine & Pharmacology, Nutrition; osteoarthritis; rheumatoid arthritis; medicinal plants; herbs
Online: 11 January 2017 (07:56:32 CET)
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Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and an efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even many of them have been proved effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarise the available scientific information on these joint-friendly medicinal plants, which have been already tested in human studies: Arnica montana, Boswelliaspp., Curcuma spp., Equisetum arvense, Harpagophytumprocumbens, Salix spp., Sesamumindicum, Symphytumofficinalis, Zingiberofficinalis, Panaxnotoginseng, Whitaniasomnifera.
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Medicine & Pharmacology, Pharmacology & Toxicology; Aflatoxins; Peanuts; Aspergillus species
Online: 9 January 2017 (09:40:46 CET)
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Aflatoxin contaminates foods including peanuts. Aflatoxin is a carcinogenic toxin mainly produced bty Aspergillus flavus. Other Aspergillus species that rarely produce aflatoxins are A. nomius and A. niger. Aflatoxin is associated with liver failure, hepatocellular carcinoma (HCC) and death. Recent studies have shown that peanuts in Kenya are highly contaminated with aflatoxins but information gaps exist on the characterization of the Aspergillus species that produce aflatoxins in peanuts in Kenya. Therefore, this gap necessitated the determination of the Aspergillus species producing aflatoxins in peanuts from the main growing districts of Busia and Kisii Central districts. One hundred and two (102) peanuts samples were collected from farmers’ in each district Aspergillus species were isolated from the peanut samples by using the dilution plate technique on modified Rose Bengal agar. Phenotypical characterization of the identified Aspergillus section flavus isolates from the peanuts samples was determined using the procedure of Mellon and Cotty. This study identified five (5) Aspergillus species as contaminants in peanuts analyzed in this study. They were Aspergillus flavus L-strain, Aspergillus flavus S-strain, Aspergillus parasiticus, Aspergillus niger and Aspergillus tamari. Overall, the occurrence of Aspergillus flavus L- strain and A. flavus S- strain were significantly higher than other species identified (H = 15.55, df = 4, P = 0.004) in peanuts from the two districts. However, A. flavus S-strain was the most dominant species identified in the study with a mean occurrence of 45.1%. Aspergillus flavus L- strain was the most common isolate (58.8%) in peanuts from Busia district while A. flavus S- strain was the most common strain (60.2%) in peanuts from Kisii Central district. Overall, the occurrence of Aspergillus flavus L strain and A. flavus S strain were significantly higher than other species identified (H = 15.55, df = 4, P = 0.004) in peanuts from the two districts. However, A. flavus S-strain was the most dominant species (F=3.15, df =25, P=0.031) with an overall mean occurrence of 45.1%. The confirmation of occurrence of other species that produce toxins such as A. niger and A. tamarii which also produces cyclopiazonic acid suggests the need to screen peanuts for other carcinogenic mycotoxins.
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Medicine & Pharmacology, Clinical Neurology; iPad; tablet computers; Stroke; neuro-rehabilitation
Online: 5 January 2017 (09:56:53 CET)
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Neuro-rehabilitation services are essential in reducing post-stroke impairments, enhancing independence, and improving recovery in hospital and post-discharge. However these services are therapist-dependent and resource intensive. Patients’ disengagement and boredom in stroke units are common which adversely affect functional and psychological outcomes. Novel techniques such as use of iPads™ are increasingly researched to overcome such challenges. The aim of this review is to determine the feasibility, effectiveness, acceptability, and barriers to the use of iPads™ in stroke neuro-rehabilitation. Four databases and manual literature search were used to identify published studies using the terms “iPad”, “Stroke”, and “neuro-rehabilitation”. Studies were included in accordance with the review selection criteria. A total of 16 articles were included in the review. The majority of the studies focused on iPads use in speech and language therapy. Although of small scale, the studies highlighted that iPads are feasible, have the potential to improve rehabilitation outcomes, and can improve patient’s social isolation. Patients’ stroke severity and financial limitations are some of the barriers highlighted in this review. This review presents preliminary data supportive for the use of iPad technology in stroke neuro-rehabilitation. However, further research is needed to determine impact on rehabilitation goals acquisition, clinical efficacy, and cost-efficiency.
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Medicine & Pharmacology, Other; Rheumatoid Arthritis; thematic analysis; Outcomes assessment; Qualitative Research; Patient reported outcome measures
Online: 3 January 2017 (11:32:52 CET)
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Background. The Stanford Health Assessment Questionnaire-Disability Index (HAQ) is widely used to measure functional ability in persons with Rheumatoid Arthritis (RA). The instrument was developed with limited involvement from persons with RA, and their perception of the instrument has not been studied in depth. The aim of this study was to explore how persons with RA experience the use of the HAQ in care.
Methods. Forty persons with RA were purposefully recruited to participate in semi-structured interviews. The interviews were then analyzed qualitatively using thematic analysis.
Results. The participants questioned the relevance of the HAQ but nevertheless experienced that the instrument had a profound effect on their understanding of health and how care is delivered. The analysis resulted in three themes: Problems with individual items, meaning of the summative score, and effects on care and health perceptions.
Conclusions. To make the HAQ relevant to persons with RA, it needs to be revised or to include an option to select items most meaningful to the respondent. To ensure relevance, the HAQ update should preferably be co-created by researchers, clinicians and persons with RA.
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Medicine & Pharmacology, Clinical Neurology; Haemophilus influenza; Neisseria meningitidis; meningitis; vaccine efficacy evaluation; immunization schedule.
Online: 2 January 2017 (18:14:59 CET)
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Meningitis is a severe disease associated with death in children under five with highest rates of infections under age of one. Vaccines for Neisseria meningitides and Haemophilus influenza are used to prevent the main causative agents of meningitis. Administration of H. influenzae type b (Hib) vaccine is recommended at 2, 4 and 6 months with a booster dose at 18 months. N. meningitidis has two commercially available vaccines, the pure polysaccharide is recommended at 24 months meanwhile the protein-conjugated vaccines at 12 months. We sought in this study to examine if coadministering the vaccines for the two main meningitis causing bacteria might be synergistic as a preliminary step towards the possibility of shuffling immunization schedule. So, we coadministered Hib vaccine with commercially available vaccines either quadrate (ACWY) polysaccharide meningococcal (Men) or conjugated meningococcal (Nim) vaccines in Balb/C mice (n = 6/group) and compared to each vaccine administered separately and controls. Thirty-five days post immunization, we measured specific antibodies titers. Hib vaccine increased Men antibody titers significantly for serotypes Y and W. When Hib vaccine was coadministrated with Nim, antibody titer for Y, W and A significantly increased. For serotype C, there was no significant difference in antibody titers among immunized groups. As for effect of meningococcal vaccines on Hib, Men significantly increased Hib antibody titers while Nim had no effect. Collectively, our data suggested that coadministration of Hib and Men or Nim vaccines was safe and had synergistic effect on immune responses elicited to both vaccines. Further studies are needed before immunization schedule modifications. Such immunization schedule recommendation should provide better protection against this life-threatening disease in young children.
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Medicine & Pharmacology, Nutrition; pito; beverage; bacteria; coliform; Lower Prampram; Ghana
Online: 2 January 2017 (10:55:07 CET)
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Pito is a traditionally brewed alcoholic beverage in some African countries. It is gaining much prominence and the patronage among the youth. Therefore, samples of the drink were collected every week for six weeks from three different popular brewing sites at Lower Prampram in the Ningo-Prampram District of Accra, Ghana. The samples were processed and examined for bacteria and fungi using the Standard Plate Count (SPC) technique. A total of six different bacteria and a fungus were isolated. The bacteria were Escherichia coli, Klesiella pneumoniae, Shigella spp, Enterobacter aerogenes, Staphylococcus aureus and Pseudomonas aeroginosa, whiles the fungus was Saccharomyces cerevisiae. Total viable counts as well as individual isolates counts in all the pito samples were found to be less than 104 cfu/ml. It is noteworthy that, Saccharomyces cerevisiae, the only fungus isolated is known to be associated with fermentation and the microbes isolated from the pito samples were found to be within the permissible limits. However, these potentially pathogenic microbes, if found in unacceptable limits, from the fermenting samples could merit public health attention. Therefore, periodic screening of pito and their brewers, coupled with education on the maintenance of recommended guidelines concerning food and drink production is encouraged.
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Medicine & Pharmacology, Other; acute pharyngitis; rational use of drugs; incidence; prevalence
Online: 30 December 2016 (07:37:07 CET)
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According to Indonesia’s result of Basic Health Research of 2013, prevalence of acute respiratory infection in 2007 and 2013 were not different (25.5% and 25.0%, respectively). Identifying the cause of acute pharyngitis is a key point in determining the optimal treatment. The main purpose is to evaluate the rational use of drugs and its irrational impact as well as the correlation of the drug use with the incidence and prevalence of acute pharyngitis. This study was a descriptive and observational study, carried out retrospectively and concurrently at two community health centers located in Bandung and Cimahi, Indonesia. There were 80.01% over prescription of antibiotics, with a total of 8.98% is non-treatment option, and 62.43% irrational used of corticosteroids. The incidence and prevalence of acute pharyngitis at one health center in Bandung were 2.45% and 2.31%, respectively, with irrationality rate of 83.82%. Those recorded at one health center in Cimahi were 2.11% of incidence and 2.00% of prevalence with irrational rate of 91.29%. It can be concluded that there were still irrational use of medicines in the treatment of acute pharyngitis in community health center. The higher incidence and prevalence might indicate the declining health services quality.
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Medicine & Pharmacology, Other; pharmacy graduates; preparedness; patient care; Indonesia
Online: 30 December 2016 (06:12:04 CET)
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Pharmacists’ roles in providing patient care remain limited in Indonesia, hence this study aimed to determine the preparedness of pharmacy graduates from one university in Indonesia to deliver patient care. Pharmacy graduates (both registered pharmacists [104] and recent graduates eligible for registration [45]) were sent a validated self-administered survey. The survey sought their perceptions about whether they had acquired 16 patient care related attributes. Further, it sought their opinion on the desirability of having those attributes. Data were analysed using SPSS version 22.0. Sixteen of 104 (15.4%) registered pharmacists and 40 of 45 (88.9%) recent pharmacy graduates participated in the study. More than 50% of participants in both groups were female and most participants were aged in their 20s. Of the recent pharmacy graduates the majority perceived they had at least partially acquired four of 16 list attributes. Male and female recent graduates had significantly different beliefs about their leadership ability (p=0.004). In comparison, most registered pharmacists perceived they had 10 out of the 16 listed attributes. The findings of this study suggested that pharmacy graduates should be better prepared to deliver patient care, and that curriculum redesign with expansion of experiential learning is required.
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Medicine & Pharmacology, Sport Sciences & Therapy; accelerometers; MVPA; health; adults
Online: 29 December 2016 (10:33:36 CET)
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The main goal of the study was to obtain objective measures of the impact of a complete pre-season of amateur football on the players’ physical activity parameters. 17 amateur football players (24.47 ± 4.53 years) enrolled in the same team agreed to participate. They were asked to wear one accelerometer on the right hip during each training practice. Moderate-to-Vigorous physical activity (MVPA), steps and metabolic-equivalent (METs), among other parameters, were obtained and analyzed. Results showed that players spent an average 54.86% of each training session in MVPA levels, for a total of 100.33 minutes every week (3 training sessions per week). Therefore, this group of amateur football players did not meet the requirements to obtain health benefits from their physical activity program: amateur football. This finding could be considered noteworthy because there are thousands of adults worldwide who play amateur football to maintain a healthy lifestyle. They should be aware that their weekly training load is not enough to help them meet the necessary requirements. They either need more practice time (90-minute sessions) or more sessions. The pre-season training program was rated as “somewhat hard” by the participants, and quadriceps and hamstrings were mentioned as the most exerted muscles
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Medicine & Pharmacology, Pharmacology & Toxicology; 2S-UTP; 4S-UTP; P2Y12 receptors; ADP; platelet aggregation
Online: 28 December 2016 (10:46:04 CET)
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Platelet P2Y12 is an important ADP receptor that is involved in agonist-induced platelet aggregation and is a valuable target for the development of anti-platelet drugs. Here we characterise the effects of thio-analogues of uridine triphosphate (UTP) on ADP-induced platelet aggregation. Using human platelet-rich plasma we demonstrate that UTP inhibits P2Y12 but not P2Y1 receptors and antagonises 10 μM ADP-induced platelet aggregation in a concentration-dependent manner with an IC50 value of ~250 μM. An 8-fold higher platelet inhibitory activity was observed with a 2-thio analogue of UTP (2S-UTP), with an IC50 of 30 μM. The 4-thio analogue (4S-UTP) with an IC50 of 7.5 μM was 33-fold more effective. A 3-fold decrease in inhibitory activity, however, was observed by introducing an isobutyl group at the 4S- position. A complete loss of inhibition was observed with thio-modification of the γ phosphate of the sugar moiety, which yields an enzymatically stable analogue. The interaction of UTP analogues with P2Y12 receptors was verified by P2Y12 receptor binding and cAMP assays. These novel data demonstrate for the first time that 2- and 4-thio analogues of UTP are potent P2Y12 receptor antagonists that may be useful for therapeutic intervention.
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Medicine & Pharmacology, Allergology; wheat allergy; specific immunoglobulin E; children; gluten-related disorders
Online: 28 December 2016 (10:37:23 CET)
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IgE-mediated wheat allergy is a gluten-related disorder. Wheat is one of the five most common food allergens in children. However, the natural history of IgE-mediated wheat allergy has seldom been described in the research literature. This study presents the current state of knowledge about the IgE-mediated wheat allergy in children.
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Medicine & Pharmacology, Pharmacology & Toxicology; furfuryl alcohol; β- myrcene; carcinogens; occurrence
Online: 25 December 2016 (08:21:19 CET)
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For decades, compounds present in foods and beverages have been implicated in the etiology of human cancers. The International Agency for Research on Cancer (IARC) continues to classify such agents regarding their potential carcinogenicity in humans based on new evidence from animal and human studies. Furfuryl alcohol and β-myrcene belong to these potential human carcinogens due to be evaluated. The major source of furfuryl alcohol in foods is thermal processing and ageing of alcoholic beverages while β-myrcene occurs naturally as a constituent of essential oils of plants such as hops, lemongrass and derived products. This study aimed to summarize the occurrence of furfuryl alcohol and β-myrcene in foods and beverages using data from own nuclear magnetic resonance (NMR) analysis and literature review. The highest content of furfuryl alcohol was found in coffee beans (>100 mg/kg) and in some fish products (about 10 mg/kg) while among beverages, wines contained between 1–10 mg/L with 8 mg/L in pineapple juice. The content of β-myrcene was highest in hops. In conclusion, the data about the occurrence of the two agents is either very old or based on single sample analysis, and currently judged as insufficient for exposure and risk assessment. The results of this study point out the food and beverage groups that may be considered for future monitoring of furfuryl alcohol and β-myrcene.
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Medicine & Pharmacology, Dermatology; antibacterial activity, cinnamon, honey, checkerboards method, synergistic activity
Online: 23 December 2016 (18:37:59 CET)
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Propionibacterium acnes and Staphylococcus epidermidis are the major skin bacteria that cause the formation of acne. The present study was conducted to investigate antibacterial activity of ethanolic extract of cinnamon bark, honey and their combination against acne bacteria. The antibacterial activity of extract of cinnamon bark and honey were investigated against P. acnes and S. epidermidis using disc diffusion method. Minimum Inhibitory Concentration (MIC) and minimal bactericidal concentration (MBC) were performed using Clinical and Laboratory Standard Institute (CLSI) methods. The interaction combination between extract of cinnamon bark and honey was determined by using a checkerboards method. The results showed that he MIC of extract of cinnamon bark and honey against P. acne were 256 µg/mL and 50% v/v, respectively, while against S. epidermidis were 1024 µg/mL and 50% v/v, respectively. The MBC of extract of cinnamon against P. acnes and S. epidermidis were more than 2048 µg/mL, whereas the MBC for honey against P. acnes and S. epidermidis were 100%. The combination of cinnamon bark extract and honey against against P. acnes and S. epidermidis, showed additive activity with the FICI value 0.625. Therefore, the combination of extract of cinnamon bark and honey has potential activity against acne causing bacteria.
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Medicine & Pharmacology, Nutrition; β-glucans; entero-endocrine system; intestinal hormones; microbiota; nutritional intervention
Online: 23 December 2016 (13:37:44 CET)
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Recent interest in intestinal hormones has risen with the idea that they modulate glucose tolerance and food intake through a variety of mechanisms, and such hormones like peptide YY (PYY), ghrelin, glucagon-like peptide (GLP)-1 and 2, and cholecystokinin (CKK) are therefore excellent therapeutic candidates for the treatment of diabetes and obesity. Furthermore, in the recent years, multiple studies suggest that the microbiota is critically important for normal host functions, while impaired host microbiota interactions contribute to the pathogenesis of numerous common metabolic disorders. In this study, we considered the nutraceutical effects of β-glucans added to pasta at the concentration of 6g\100g. Ten participants have been recruited and hematochemical analyses and intestinal hormones tests have been performed before and after 30 days of pasta intake. Stool specimens have been studied for Lactobacillus Fermentum, Lactobacillus acidophilus, Lactobacillus salivarius, Bifidobacterium longum, and Enterococcus faecium presence before and after 30 days of nutritional intervention. After 30 days of regular intake of pasta enriched by β-glucans results have been evaluated. In conclusion, pasta prepared from barley flour enriched with β-glucans at 6% exhibit promising responses on glucose metabolism, on intestinal hormones responses and on microbiota modification.
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Medicine & Pharmacology, Nutrition; antibiotic; bacteroidetes; dietary emulsifier; firmicutes; food additive; gut microbiota; non-nutritive sweetener; proteobacteria
Online: 23 December 2016 (11:21:40 CET)
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Gut bacteria play an important role in several metabolic processes and human diseases, such as obesity and its co-morbidities, like fatty liver disease, insulin resistance/diabetes and cardiovascular events. Among several factors, dietary patterns, probiotics, prebiotics, synbiotics, antimicrobials and non-dietary factors, such as stress, age, exercise and climatic conditions, can dramatically impact the human gut microbiota diversity and equilibrium. However, the effect of minor food constituents, including food additives and trace contaminants, on human gut microbiota has received less attention. Consequently, the present review aimed to provide an objective perspective of the current knowledge regarding the impacts of minor food constituents on human gut microbiota and consequently, on human health.
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Medicine & Pharmacology, Oncology & Oncogenics; breast cancer; brain metastases; clonal evolution; precision medicine; genomics; tumour microenvironment
Online: 22 December 2016 (09:57:33 CET)
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Brain metastases are highly evolved manifestations of breast cancer arising in a unique microenvironment, giving them exceptional adaptability in the face of new extrinsic pressures. The incidence is rising in line with population ageing, and use of newer therapies that stabilise metastatic disease burden with variable efficacy throughout the body. Historically, there has been a widely held view that brain metastases do not respond to circulating therapeutics because the blood-brain-barrier (BBB) restricts their uptake. However, emerging data are beginning to paint a far more complex picture where the brain acts as a sanctuary for dormant, subclinical proliferations that are initially protected by the BBB, but then exposed to dynamic selection pressures as tumours mature and vascular permeability increases. Here, we review key experimental approaches and landmark studies that have charted the genomic landscape of breast cancer brain metastases. These findings are contextualised with the factors impacting on clonal outgrowth in the brain: intrinsic breast tumour cell capabilities required for brain metastatic fitness, and the neural niche, which is initially hostile to invading cells but then engineered into a tumour-support vehicle by the successful minority. We also discuss how late detection, abnormal vascular perfusion and interstitial fluid dynamics underpin the recalcitrant clinical behaviour of brain metastases, and outline active clinical trials in the context of precision management.
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Medicine & Pharmacology, Oncology & Oncogenics; apoptosis; gynecologic cancer; lipopolysaccharide; proliferation; Toll-like receptor
Online: 20 December 2016 (11:12:07 CET)
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Toll-like receptor 4 (TLR4) is a member of the TLR family. Members of the TLR family play an important role in innate immune responses and are induced by recognition of pathogen-associated molecular patterns. They are also involved in cell proliferation and apoptosis in cancer. We investigated the role of TLR4 in apoptotic cell death in gynecological cancer cells; gynecological cancer is associated with infertility and spontaneous abortion. To examine the effect of TLR4 activation on apoptotic signaling in cancer cells, cultured primary cancer cells were treated with the TLR4 agonist lipopolysaccharide (LPS). The morphology of cancer cells was compared with normal myometrial cells. Enhanced growth rate and loss of contact inhibition with cellular overlap was observed in the cancer cells. The molecular mechanism analysis revealed differential expression of tumor suppressor genes in LPS-treated cancer cells. The expression of apoptosis-related caspase-3 was increased significantly in cancer cells with TLR4 activation after exposure to LPS. Taken together, these results suggest the pro-apoptotic activity of TLR4 as a potential therapeutic target for the treatment of gynecological cancers.
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Medicine & Pharmacology, Pharmacology & Toxicology; aging; bioactive nutrients; dietary; nutrigenomics; Oxiinflammaging
Online: 19 December 2016 (09:37:23 CET)
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The increase in the average lifespan and the consequent proportional growth of the elderly segment of society has furthered the interest in studying ageing processes. Ageing may be considered a multifactorial process derived from the interaction between genetic and environmental factors including lifestyle. There is ample evidence in many species that the maximum age attainable (maximum lifespan potential, MLSP) is genetically determined and several mitochondrial DNA polymorphisms are associated with longevity. Many studies have shown that most of the phenotypic characteristics observed in the aging process are the result of the occurrence, with age, of a low grade chronic pro-inflammatory status called "inflammaging", partially under genetic control. The term indicate that aging is accompanied by a low degree of chronic inflammatory, an up-regulation of inflammatory response and that inflammatory changes are common to many age-related diseases. Therefore, the theory of oxidation-inflammation was proposed as the main cause of aging. Accordingly, the chronic oxidative stress, that appears with age, affects all cells and especially those of the regulatory systems, such as the nervous, endocrine, and immune systems and the communication between them. This prevents an adequate homeostasis and, therefore, the preservation of health. It was also proposed that the immune system plays a key role in the aging process, specifically in the rate of aging, since there is a relationship between the redox state and functional capacity of immune cells and longevity of individuals. Moreover, the role of the immune system in senescence could be of universal application. A confirmation of the central role of the immune system in oxi-inflamm-aging is that the administrationintake? of adequate amounts of antioxidants in the diet improves immune function, decreases their oxidative stress, and consequently increases longevity. The promotion of healthy lifestyles is one of the major goals of governments and international agencies all over the world. Human molecular processes are influenced by both physiological pathways and exogenous factors which include, for instance, those originating from diet. Dietary intake has substantive effects on molecular processes of metabolic health. Nutrients can directly regulate physiological changes in human body. In fact, in addition to have an energetic and structural value, nutritional intake provides bioactive molecules which are selectively able to modulate specific metabolic pathways, noticeably affecting cardiovascular and neoplastic diseases development or progress. Numerous bioactive nutrients are being progressively identified and their chemopreventive effects are being described at clinical and molecular mechanism levels. Systematic analyses comprise all “omics” technologies (such as transcriptomics, proteomics and metabolomics) and the goal is to investigate bioactive molecules effects derived from the diet. Nutrigenomic knowledge on physiologic status and disease risk will provide both developments of better diagnostic procedures and of new therapeutic strategies specifically targeted on nutritionally relevant processes. The present review was aimed to understand the molecular mechanisms underlying beneficial effects of bioactive nutrients and nutrigenomics on age-related diseases.
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Medicine & Pharmacology, Oncology & Oncogenics; lung cancer; adenovirus; E1b; UV-irradiation; genomics
Online: 19 December 2016 (09:33:20 CET)
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Adenoviruses (Ads) have been extensively manipulated for the development of cancer selective replication, leading to cancer cell death or oncolysis. Clinical studies using E1-modified oncolytic Ads have shown that this therapeutic platform was safe, but with limited efficacy, indicating the necessity of targeting other viral genes for manipulation. To improve the therapeutic efficacy of oncolytic Ads, we treated the entire Ad genome repeatedly with UV-light and have isolated AdUV which efficiently lyses cancer cells as reported previously [1]. In this report, we show that no mutations were observed in the early genes (E1 or E4) of AdUV while several mutations were observed within the Ad late genes which have structural or viral DNA packaging functions. This study also reported the increased release of AdUV from cancer cells. In this study, we found that AdUV inhibits tumor growth following intratumoral injection. These results indicate the potentially significant role of the viral late genes, in particular the DNA packaging genes, to enhance Ad oncolysis.
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Medicine & Pharmacology, General Medical Research; Coccidioides immitis; Coccidioides posadasii; Coccidioidomycosis; vaccine; immunology; fungi; T-cell mediated immunity
Online: 15 December 2016 (07:24:05 CET)
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Coccidioidomycosis (Valley Fever) is a disease caused by inhalation of Coccidioides spp. This neglected tropical disease of the Americas has substantial public health impact despite its geographic restriction to desert areas of the southwestern U.S., Mexico, Central and South America. The incidence of this infection in California and Arizona has been increasing over the past fifteen years. The burden of disease in outside the U.S. remains poorly understood. Several large cities are within the endemic region in the U.S. Coccidioidomycosis accounts for 25,000 hospital admissions per year in California. While most cases of coccidioidomycosis resolve spontaneously, up to 40% are severe enough to require anti-fungal treatment, and a significant number disseminate beyond the lungs. Disseminated infection, especially involving the meninges, is fatal without appropriate treatment. Infection with Coccidioides spp. is protective against a second infection, so vaccination seems biologically plausible. This review of efforts to develop a vaccine against coccidioidomycosis focuses on vaccine approaches and the difficulties in identifying protein antigen/adjuvant combinations that protect in experimental mouse models. Although the quest for a vaccine has not yet resulted in a clinically useful product, scientific efforts of vaccine development pave the way for future success.