Background Although high-density lipoprotein has cardioprotective effects, the association between serum high-density lipoprotein cholesterol (HDL-C) and hypertension is poorly understood. Objective We investigated whether low and high concentrations of HDL-C are associated with hypertension using a large healthcare dataset. Methods In a community-based cross-sectional study of 1,493,152 Japanese people aged 40–74 years who underwent a health checkup, blood pressures and clinical parameters, including nine HDL-C concentrations (20–110 mg/dL or over) were investigated. Results A crude U-shaped relationship was observed between the nine HDL-C concentrations and blood pressure in males (n = 830,669), while a left-to-right inverted J-shaped relationship was observed in females(n = 662,483). An age-adjusted logistic regression analysis showed J-shaped relationships (left-to-right inversion in females) between HDL-C and odds ratios for hypertension (≥140/90 mmHg), with lower limits of 60–79 mg/dL in males and 90–99 mg/dL in females, which were unchanged after adjusting for smoking, habitual exercise, alcohol consumption, and pharmacotherapy for hypertension, dyslipidemia, and diabetes. However, further adjustment for body mass index and serum triglyceride concentration revealed latent positive linear associations between HDL-C and hypertension, although the association between extremely high HDL-C (≥100 mg/dL) and hypertension was attenuated in non-alcohol drinkers. Conclusion Both low and extremely high HDL-C concentrations are associated with hypertension. The former association may be dependent on excess fat mass, which is often concomitant with low HDL-C, whereas the latter association may be dependent on frequent alcohol consumption.

The effects of octadecylamide of alginic acid (amidated alginate) and tetrahydrolipstatin on serum and hepatic cholesterol, and the faecal output of fat and sterols were compared in rats. Amidated alginate is a sorbent of lipids, tetrahydrolipstatin is inhibitor of pancreatic lipase. Rats were fed diets containing cholesterol and palm fat at 10 and 70 g/kg, respectively. Palm fat was provided by coconut meal. Amidated alginate at 40 g/kg diet significantly decreased serum total cholesterol, LDL and hepatic cholesterol, hepatic lipids, and increased faecal output of fat and coprostanol. Tetrahydrolipstatin at 300 mg/kg diet significantly decreased LDL cholesterol, hepatic lipids and increased faecal output of fat. The intake of feed was not significantly influenced, however the weight gains in rats fed amidated alginate was lower than in rats of the control group. Both amidated alginate and tetrahydrolipstatin modified fatty acid profile in excreta lipids. Concentrations of saturated fatty acids were decreased and that of unsaturated fatty acids were increased. Despite different mode of action, amidated alginate and tetrahydrolipstatin were equally efficient in the removing dietary fat from the body.

The aim of our study was a comprehensive comparative assessment of the effect of consumption of 1 and 2% cholesterol as part of a standard diet with and without regular moderate physical activity on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. The animals were randomly divided into 5 groups according to body weight and Open Field test results: Control (n=10), 1% Chol (n=10), 2% Chol (n=10), 1% Chol + RUN (n=10) and 2% Chol + RUN. The cholesterol was additionally added in the amount of 1g or 2g/100g, respectively, to the diet of animals. The rats of experimental groups 1% Chol + RUN and 2% Chol + RUN were subjected to regular (2 days a week) physical activity on a Treadmill. In rats of four experimental groups, when compared to the Control, a response of 39 indicators was revealed. The largest number of changes in biomarkers - 29 (statistically significant, p

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.

With the ever-increasing rate, obesity has become an epidemiological problem throughout the globe comprising about 39% of the world population as of now. Among several reasons, disruption of the gut microbial ecosystem might contribute to the pathogenesis of metabolic disorders, including obesity, metabolic syndrome, type 2 diabetes, and other associated comorbidities. Though the mechanisms related to dysbiosis are unclear, diet might play a modulating role where different dietary approaches manipulate microbial richness and abundance as well as stability. For instance, shifting of Firmicutes and Bacteroidetes ratio in the gut might have a role in association with the dietary approaches and ingestion duration. Along with altered gut microbial composition, microbial metabolites such as short-chain fatty acids (SCFA) after ingestion of non-digestible dietary starches may have an impact on host metabolism by regulating lipogenesis, gluconeogenesis, and inflammation with potential associations to health and obesity. The dietary approaches like carbohydrates, fibre, protein, and/or fat diet at various arrangements can make a shift in the composition of gut microbiota if introduced for a short period. However, the unique pattern of the gut microbes usually remains the same along with the longer period of habitual diet. Though the short-term dietary intervention or circadian rhythm influences a transient change in gut microbes, other than habitual diet, the understanding related to long-term dietary change-induced permanent alterations is minimum. Alternatively, the usage of prebiotics, probiotics as well as postbiotics could be beneficial to overcome dysbiosis. This review highlights the current knowledge and the interaction between the human intestinal microbiota and diet as a modifying factor, in obesity allowing the scientists to uncover novel targets and tools to use as customized therapy.

In humans and animal models, intermittent fasting (IF) interventions promote body weight loss, improve metabolic health, and are thought to lower cardiovascular disease risk. However, there is a paucity of reports on the relevancy of such nutritional interventions in the context of dyslipidemia and atherosclerotic cardiovascular diseases. The present study assessed the metabolic and atheroprotective effects of intermittent fasting intervention (IF) in atherosclerosis-prone apolipoprotein E-deficient (Apoe-/-) mice. Groups of male and female Apoe-/- mice were fed a regular (chow) or atherogenic (high-fat, high-cholesterol, HFCD) diet for 4 months, either ad libitum or in an alternate-day fasting manner. The results show that IF intervention improved glucose and lipid metabolism independently of sex. However, IF only decreased body weight gain in males fed chow diet and differentially modulated adipose tissue parameters and liver steatosis in a diet composition-dependent manner. Finally, IF prevented spontaneous aortic atherosclerotic lesions formation in mice fed chow diet, irrespective of sex but failed to reduce HFCD-diet-induced atherosclerosis. Overall, the current work indicates that IF interventions can efficiently improve glucose homeostasis and treat atherogenic dyslipidemia, but a degree of caution is warranted with regard to the individual sex and the composition of the dietary regimen.

Although many policosanols from different sources, such as sugar cane, rice bran, and insects, have been marketed worldwide, there has been no comparative study of the in vivo efficacy using a hyperlipidemic animal model. This study compared the efficacy of treating dyslipidemia with four different policosanols, including one sugar cane wax alcohol from Cuba (Raydel®) and three policosanols from China (Xi’an Natural sugar cane, Xi’an Realin sugar cane, and Shaanxi rice bran) in hyperlipidemic zebrafish. After 12 weeks of consumption of each policosanol (final 0.1% in diet, wt/wt) and high cholesterol diet (HCD, final 4%, wt/wt) in a tetrabit, the Raydel policosanol group and Xi’an Natural policosanol group showed the highest survivability of approximately 81%, whereas the Xi’an Realin policosanol group and Shaanxi policosanol group showed 57% and 67% survivability, respectively. Among five HCD groups, the Raydel policosanol group showed the lowest serum total cholesterol (TC, p<0.001 versus HCD control) and triglyceride (TG, p<0.001 versus HCD control) with the highest percentage of high-density lipoproteins (HDL)-C in TC. The Raydel policosanol group also showed the lowest serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels with the least infiltration of inflammatory cells and interleukin-6 production in hepatocytes. In the ovary, the Raydel policosanol group also showed the highest contents of mature vitellogenic oocytes with the lowest production of reactive oxygen species and cellular apoptosis in ovarian cells. In the testis, the Raydel policosanol group also showed the healthiest morphology for spermatogenesis with the least interstitial area and reactive oxygen species (ROS) production in testicular cells. In conclusion, 12 weeks of Raydel policosanol consumption resulted in remarkable improvement of the blood lipid profile, amelioration of inflammation in the liver, and enhancement of the cell morphology in the ovary and testis with the highest survivability under the HCD.

Large epidemiological studies show U-shaped relationships between high-density lipoprotein cholesterol (HDL-C) levels and all-cause mortality in individuals without atherosclerotic cardiovascular diseases (ASCVD). Association in those with ASCVD by sex is unclear. We examined the association between HDL-C levels and 10-year all-cause mortality in subjects (≥40 years of age) with ASCVD using the 2010 National Health Insurance Service and the National Death Registry of Korea. We categorized HDL-C levels into three groups (low: <40 mg/dL for males, <50 mg/dL for females; high: 40-90 mg/dL for males, 50-90 mg/dL for females; extremely high: >90 mg/dL) and 10 mg/dL intervals. We conducted a sex-stratified and adjusted Cox proportional hazards analysis. Out of 1,711,548 individuals (54% female, mean age 61.4 years), 10-year mortality was observed in 218,252 (12.8%). Males had a higher mortality rate than females (16.2% vs 9.8%; P<0.001). When adjusting for age, body mass index, LDL-cholesterol, triglycerides, hypertension, diabetes, smoking, and alcohol consumption, the low and extremely high HDL-C groups had significantly higher hazard ratios for 10-year mortality compared to the high HDL-C group in males [1.183 (1.166-1.199), 1.359 (1.288-1.434)] and in females [1.153 (1.138-1.169), 1.095 (1.029-1.167)]. The frequency distribution bars for the 10-year mortality rate showed sex-specific nadirs of 50-59 mg/dL in males and 70-79 mg/dL in females. In this ASCVD cohort, the extremely high HDL-C (>90 mg/dL) group had 35.9% and 9.5% higher 10-year mortality risk than the high HDL-C group for males and females, respectively. There was a slightly U-shaped relationship between baseline HDL-C levels and 10-year mortality rate, with earlier inflection in males than in females.

Populations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH among three strains of rats, i.e., two hypertensive strains comprising spontaneously hypertensive rats and the stroke-prone spontaneously hypertensive 5/Dmcr, and the original Wistar Kyoto rats as the normotensive control. We investigated histopathological changes and molecular signals related to inflammation in the liver after feeding with the HFC diet for 8 weeks. The diet induced severe lobular inflammation and fibrosis in the livers of the hypertensive rats, whereas it only caused mild steatohepatitis in the normotensive rats. Increased activation of proinflammatory signaling (transforming growth factor-β1/mitogen-activated protein kinases pathway) was observed in the hypertensive strains fed with the HFC diet. In addition, the HFC diet suppressed the nuclear factor erythroid 2-related factor 2 pathway in the hypertensive rats and led to lower increases in the hepatic expression of heme oxygenase-1, which has anti-oxidative and anti-inflammatory activities. In conclusion, these signaling pathways might play crucial roles in the development of hypertension-associated NASH.

One of the mechanisms used in the management and cure of atherosclerosis is reverse cholesterol transfer (RCT), which plays a vital role in the export of cholesterol from peripheral cells. Cholesterol efflux from macrophages in the subintima of the vessel wall is a critical part of RCT. ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) are involved in the transfer of cholesterol from arterial macrophages to extracellular high-density lipoprotein cholesterol (HDL). The HDL then transports esterified cholesterol to the liver for elimination. An important factor in the reverse cholesterol transport and excretion of extracellular cholesterol is HDL. Atherogenesis can be prevented by altering the processes of RCT and cholesterol efflux, and this might lead to novel treatment options for cardiovascular disease. Research of novel modifying variables for RCT and cholesterol efflux is necessary. A better understanding of RCT's molecular processes has been gained via research, allowing for the creation of new treatments that make use of RCT's potential for pharmacological improvement. The purpose of this review is to provoke discussion on the potential impact of selected flavonoids on cholesterol efflux on the progression of atherosclerosis (Fig. 1.).

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of DR. It mainly includes hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, which plays a key role in the pathological changes of DR.High-sucrose diets(HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of AGEs and VEGF, causes plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. Early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes, and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss, and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies we give, patients can change their poor eating habits timely, avoid the retinopathy that can be avoided theoretically, and obtain a excellent outcome.

High fat-diet (HFD) feeding is known to induce metabolic dysregulation, however less is known on its impact in promoting the hypercoagulable state. The current study aimed to evaluate platelet-monocyte aggregate (PMA) formation following short-term HFD feeding. This is particularly important for understanding the link between inflammation and the hypercoagulable state during the early onset of metabolic dysregulation. To explore such a hypothesis, mice were fed a HFD for 8 weeks, with body weights as well as insulin and blood glucose levels monitored on weekly basis during this period. Basal hematological measurements were determined and the levels of spontaneous peripheral blood PMAs were assessed using whole blood flow cytometry. The results showed that although there were no significant differences in body weights, mice on HFD displayed impaired glucose tolerance and markedly raised insulin levels. These metabolic abnormalities were accompanied by elevated baseline PMA levels as an indication of hypercoagulation. Importantly, it was evident that baseline levels of monocytes, measured using the CD14 monocyte marker were significantly decreased in HFD-fed mice when compared to controls. In summary, the current evidence shows that in addition to causing glucose intolerance, such as that identified in a prediabetic state, HFD-feeding can promote undesirable hypercoagulation, the major consequence implicated in the development of cardiovascular complications.

Early-life exposure to high-fat diet (HF) can program metabolic and cognitive alterations in adult offspring. Although the hippocampus plays a crucial role in memory and metabolic homeostasis, few studies reported the impact of maternal HF on this structure. We assessed the effects of maternal HF during lactation on physiological, metabolic and cognitive parameters in young adult offspring mice. To identify early-programming mechanisms in hippocampus, we developed a multi-omics strategy in male and female offspring. Maternal HF induced a transient increased body weight at weaning, a mild glucose intolerance only in 3-month-old male mice with no change in plasma metabolic parameters in adult male and female offspring. Behavioral alterations revealed by Barnes maze test were observed both in 6-month-old male and female mice. Multi-omics strategy unveiled sex-specific transcriptomic and proteomic modifications in the hippocampus of adult offspring. These studies that were confirmed by regulon analysis, showing that, although genes whose expression was modified by maternal HF were different between sexes, the main pathways affected were similar with mitochondria and synapses as main hippocampal targets of maternal HF. The effects of maternal HF reported here may help to better characterize sex-dependent molecular pathways involved in cognitive disorders and neurodegenerative diseases.

Ozonated sunflower oil (OSO) is well known functional oil with its antioxidant, antimi-crobial, anti-allergic, and skin-moisturizing properties. However, studies on the effects of OSO on high-cholesterol diet (HCD)-induced metabolic disorders have been scarce. In the current study, we aimed to determine the anti-inflammatory effects of OSO on lipid me-tabolism in adult hypercholesterolemic zebrafish and its embryo. Microinjection of OSO (final 2%, 10 nL) into zebrafish embryos under presence of carboxymethyllysine (CML, 500 ng) protected acute embryo death upto 61% survival, while sunflower oil (final 2%) showed much less protection around 42% survival. The microinjection of OSO was more effective than SO to inhibit reactive oxygen species (ROS) production and apoptosis in the CML induced embryo toxicity. Intraperitoneal injection of OSO under presence of CML protected acute death from CML-induced neurotoxicity with improved hepatic inflamma-tion, less detection of ROS and interleukin (IL)-6, and lowering blood total cholesterol (TC) and triglyceride (TG), while SO-injected group did not protect the CML-toxicity. Long-term supplementation of OSO (final 20%, wt/wt) with HCD for 6 months resulted higher sur-vivability than HCD alone group or HCD+SO group (final 20%, wt/wt) with significant lowering of plasma TC and TG levels. The HCD+OSO group showed the least hepatic in-flammation, fatty liver change, ROS, and IL-6 production. In conclusion, short-term treat-ment of OSO by injection exhibited potent anti-inflammatory activity against acute neuro-toxicity of CML in zebrafish and its embryo. Long-term supplementation of OSO in diet also revealed the highest survivability and blood lipid-lowering effect through potent an-ti-oxidant and anti-inflammatory activity.

Background: Several preventive strategies to reduce dyslipidaemia, have been suggested of which dietary modification features as an important one. Addition of almonds in our daily diets has been proposed to beneficially impact the lipid profile. This review critically examines the available evidence assessing the effect of almonds on dyslipidaemia in the South Asian (particularly Indian) context. Methods: An extensive review comprising of epidemiological studies, clinical trials, meta-analyses and systematic reviews was conducted from published literature from across the world. Studies examining the effect of almonds on different aspects of dyslipidaemia viz. high LDL-C, low HDL-C, triglyceridaemia, high total cholesterol levels have been included. Results: Dyslipidaemia is a major risk factor for coronary heart disease and strategies to manage dyslipidaemia have been shown to reduce the incidence of CVD. Although there are proven pharmacological therapies to help manage this condition, there are not many nutritional interventions which can impact dyslipidaemia. Almonds have been shown to reduce LDL-C which is a known risk factor for CHD, in several studies and the effect of almonds has been well documented in systematic reviews and meta-analysis of clinical trials. Conclusions: Addition of almonds in the diet has been shown to not only to reduce LDL-C levels, but also to maintain HDL-C levels. This review informs about the use of this simple nutritional strategy which may help manage known major risk factors for heart disease such as high LDL-C and low HDL-C levels especially in the context of South Asians.

Obesity and metabolic disorders can be risk factors for the onset and development of neurodegenerative diseases. The aim of the present study was to investigate the protective effects on dysmetabolism and neurodegeneration of a natural dietary supplement (NDS), containing Curcuma longa, silymarin, guggul, chlorogenic acid and inulin, on the brains of high fat diet (HFD)-fed mice. A decreased expression of FACL-4, CerS-1 and CerS-4, reduced cholesterol concentration, increased IR expression and insulin signaling activation, were found in brains of NDS-treated HFD mice, suggesting that NDS is able to prevent brain lipid accumulation and central insulin resistance. In the brains of NDS-treated HFD mice, the levels of RNS, ROS and lipid peroxidation, the expression of p-ERK, H-Oxy, i-NOS, HSP60, NF-kB, GFAP, IL-1β, IL-6, and CD4 positive cell infiltration were lower than in untreated HFD mice, suggesting antioxidant and anti-inflammatory effects of NDS. The decreased expression of p-ERK and GFAP in NDS-treated HFD mice was confirmed by immunofluorescence. Lastly, a lower number of apoptotic nuclei was found in cortical sections of NDS-treated HFD. All these data indicate that NDS exerts neuroprotective effects in HFD mice by reducing brain fat accumulation, oxidative stress and inflammation and improving brain insulin resistance.

Bioactive peptides are related to the prevention and treatment of many diseases. GPETAFLR is an octapeptide which was isolated from lupine (Lupinus angustifolius L.) and showed anti-inflammatory properties. The aim of this study was to evaluate the potential activity of GPETAFLR to prevent non-alcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-induced obese mice. C57BL/6J mice were fed a standard diet or an HFD. Two of the groups fed the HFD diet were treated with GPETAFLR in their drinking water at 0,5 mg/kg/d or 1 mg/kg/d. To determine the ability of GPETAFLR to improve the onset and progression of NAFLD, histological studies, hepatic enzyme profile, inflammatory cytokine and lipid metabolism-related genes and proteins were analyzed. Our results suggest that HFD-induced inflammatory metabolic disorders were alleviated by treatment with GPETAFLR. In conclusion, dietary lupine consumption could repair HFD-induced hepatic damage, possibly via modifications in the liver’s lipid signalling pathways.

Although it is known that the gut microbiota (GM) can be modulated by diet, the efficacy of specific dietary interventions in determining its composition and diversity in obese patients remains to be ascertained. The present work aims to evaluate the impact of a moderately hypocaloric Mediterranean diet on the GM of obese and overweight patients (OB). The GM of 23 OB patients (F/M= 20/3) was compared before (T0) and after 3 months (T3) of the nutritional intervention (NI). Fecal samples were analyzed by Illumina MiSeq sequencing of the 16S rRNA gene. At baseline, the GM characterization confirmed the typical obesity-associated dysbiosis. After 3 months of NI, patients presented a statistically significant reduction of the body weight and fat mass, along with changes in the relative abundance of many microbial patterns. In fact, we observed an increased abundance in several Bacteroidetes taxa (i.e. Sphingobacteriaceae, Sphingobacterium, Bacteroides spp., Prevotella stercorea) and depletion of many Firmicutes taxa (i.e. Lachnospiraceae members, Ruminococcaceae and Ruminococcus, Veillonellaceae, Catenibacterium, Megamonas). In addition, the phylum Proteobacteria showed an increased abundance, while the genus Sutterella, within the same phylum, decreased after the intervention. Metabolic pathways, predicted by bioinformatic analyses, showed a decrease in membrane transport and cell motility after NI. The present study extends our knowledge of the GM profiles in OB, highlighting the potential benefit of a moderate caloric restriction in counteracting the gut dysbiosis.

Emerging evidence has indicated the involvement of extra-hypothalamic kisspeptin and GnRHR in reproductive function. In this study, we evaluate if maternal exposure to the pesticide chlorpyrifos (CPF) and/or a high-fat diet (HFD) have an impact on the expression of kisspeptin and GnRHR in reproductive organ of offspring’s rats. 16 Pregnant rats are divided into 4 groups, control group (n=4), CPF group (4 rats exposed daily to 1/mg/kg/day), HFD group (4 rats randomly fed a 5,25 kcal/g HFD), co-exposed group (4 rats exposed to CPF and HDF). At postnatal development PND60, males and female offspring were sacrificed. The reproductive organs (ovary and testis) were removed and histological, immunohistological analysis and in silico quantification (software Tissuefax, HistoQuest) was assessed to investigate the impact of different treatment on kisspeptin and GnRHR expression in reproductive organs. The main outcomes of the study showed a significant decrease in rat offspring’s body weight in CPF group from PND30 andPND60 (p&lt;0.05 and p&lt;0.01, respectively). Histological analysis shows a significant increase in atretic follicle and abnormal testis structure with germ cell desquamation at CPF exposed group. The immunodetection quantification of protein shows a significant decrease in GnRHR and kisspeptin in HFD and CPF exposed group, respectively in testis rat offspring. Perinatal exposure to CPF and HFD exposure affect the reproduction function of rat offspring.

Hepato-renal dysfunctions associated with hyperlipidemia necessitates continuous search for natural remedies. This study thus, evaluated the effect of dietary chitosan on diet-induced hyperlipidemic rats. Thirty male Wistar rats (90 ± 5.2) g were randomly allotted into six (6) groups (n=5): Normal diet, High-fat diet (HFD), Normal diet + 5% chitosan. The three other groups received HFD, supplemented with 1%-, 3%-, and 5% of chitosan. The feeding lasted for 8 weeks, after which the rats were sacrificed. The liver and kidneys were harvested for Analyses. Hepatic alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activity, and renal biomarkers (ALT, AST, urea, and creatinine) were assayed spectrophotometrically. Additionally, expression of hepatic and renal CD43 and p53 was estimated immunohistochemically. Hyperlipidemia caused a significant (p<0.05) decrease in the hepatic (AST, ALT, and ALP) and renal (AST and ALT) activities, while renal urea and creatinine increased. Furthermore, the HFD group showed an elevated level of hepatic and renal CD43 while p53 expression decreased. However, groups supplemented with chitosan showed improved hepatic and renal biomarkers, as well as corrected the aberrations in the expressions of p53 and CD43. Conclusively, dietary chitosan could effectively improve kidney and liver functionality via abatement of inflammatory responses.

Abstract Cholesterol has ruled the history of atherosclerotic cardiovascular diseases (CVD) for decades, and the transport of cholesterol by lipoproteins has become a cornerstone of our view of etiology of the disease. Discovery of the lipoprotein-specific transport of lipid oxidation products (LOP) has opened a new and exciting area in research of CVD by revealing strong connections between atherogenic LOP, lipoprotein transport functions and CVD. This review goes through the evidence in support of the lipoprotein-specific LOP transport and speculates of possible consequences of the proposed role of lipoprotein LOP transport as a risk factor. Association of lipoprotein LOP with known risk factors of CVD are largely parallel with those of cholesterol, and due to the common transport and cellular intake mechanisms the elucidation of independent effects of either cholesterol or LOP is difficult. Yet, unlike cholesterol, LOP can directly initiate and boost atherogenic processes. It therefore appears inevitable that increasing knowledge of the lipoprotein-specific LOP transport will affect the present view of the role of cholesterol in aetiology and as a risk factor of CVD.

The gut microbiota plays a crucial role in childhood obesity, and diet is a dominating driver. The effects of fructo-oligosaccharides (FOS), as a dietary fiber, on the composition and metabolism of gut microbiota in healthy children was investigated by vitro fermentation system with a reformative YCFA medium (rich in tryptic hydrolysates of meat). The 16S rRNA sequencing technology was utilized to analyze the varieties of gut microbiota. Measurement of short chain fatty acids (SCFAs) and gases were used by the gas chromatograph. Majorbio Cloud Platform and MetOrigin, as the interactive cloud server, perform the microbiota analysis, the metabolic pathway enrichment analysis, the statistical correlations, and biological relationships using network visualization. We found that the FOS group significantly regulated the composition and metabolism of gut microbiota. The co-metabolism network showed that 3 metabolites were related to 6 differential bacteria and 8 metabolism pathways. These findings suggest that dietary fiber could regulate the composition of gut microbiota and its metabolites in a better direction, but when dietary fiber participates in precision nutrition formula, it may be relevant for precision obesity, may help identify windows of opportunity for the dietary intervention of childhood obesity.

With rising rates of human obesity, the study aimed to determine the relationship between maternal diet-induced obesity and offspring morphometrics and behaviour in mice. Pregnant and lactating female mice fed a diet high in fat and sugar (HFHS) commonly consumed by human populations showed decreased food, calorie, and protein intake but increased adiposity at the expense of lean mass. The pre-weaning body weight of HFHS offspring was reduced for the first postnatal week but not thereafter with HFHS female offspring having higher body weights by weaning, due to continuing higher fractional growth rates. Post-weaning, there were minor differences in offspring food and protein intake. Maternal diet, however, affected fractional growth rate and total body fat content of male but not female HFHS offspring. Maternal diet did not affect offspring locomotor activity or social behaviour in either sex. Both male and female HFHS offspring displayed reduced anxiety-related behaviours with sex differences in particular aspects of the elevated plus maze task. In the novel object recognition task, performance was impaired in male but not female HFHS offspring. Collectively, the findings demonstrate that maternal obesity alters the growth, adiposity, and behaviour of male and female offspring, with sex-specific differences.

G-protein coupled receptors (GPCRs) are membrane proteins that convey extracellular signals to the cellular milieu. They represent a target for more than 30 % of currently marketed drugs. Here we review the effects of membrane cholesterol on the function of GPCRs of Class A. We review both the specific effects of cholesterol mediated via its direct high-affinity binding to the receptor and non-specific effects mediated by cholesterol-induced changes in the properties of the membrane. Cholesterol binds to many GPCRs at both canonical and non-canonical binding sites. It allosterically affects ligand binding to and activation of GPCRs. Also, it changes the oligomerization state of GPCRs. In this review, we consider a perspective of the potential for the development of new therapies that are targeted at manipulating the level of membrane cholesterol or modulating cholesterol binding sites on to GPCRs.

The present study examined and compared the effects of high- and low-molecular weight (MW) chitosan, a nutraceutical, on intestinal and liver lipid metabolism in rats fed with high-fat diet. Both high- and low-MW chitosan decreased liver weight, elongated small intestine, improved the dysregulation of blood lipids and liver fat accumulation, and increased fecal lipid excretion in high-fat diet-fed rats. Supplementation of both high- and low-MW chitosan significantly inhibited the decreased phosphorylated AMP-activated protein kinase (AMPK)α and peroxisome proliferator-activated receptor (PPAR)α protein expressions and the increased lipogenesis/cholesterogenesis-associated protein expressions (sterol regulatory element binding protein (SREBP)1c, SREBP2, and PPARγ) and the decreased apolipoprotein (Apo)E and microsomal triglyceride transfer protein (MTTP) protein expressions in the livers of high-fat diet-fed rats. Both high and low-MW chitosan supplementation could also suppress the increased MTTP protein expression and the decreased angiopoietin-like protein (Angptl)4 protein expression in the intestines of high-fat diet-fed rats. Comparison between high and low-MW chitosan, high-MW chitosan has a higher efficiency than low-MW chitosan on the inhibition of intestinal lipid absorption and the increase of hepatic fatty acid oxidation, which can improve liver lipid biosynthesis and accumulation.

Giant unilamellar vesicles (GUVs) are membrane model used to study membrane properties. Electroformation is one of the methods used to produce GUVs. During electroformation protocol dry lipid film is formed. Drying of the lipid film induce Cholesterol (Chol) demixing artifact, in which Chol forms anhydrous crystals, where these crystals does not participate in formation of vesicles. This leads to a lower Chol concentration in the vesicle bilayers compared to the Chol concentration in the initial lipid solution. To address this problem, we propose novel electroformation protocol that includes rapid solvent exchange, plasma cleaning and spin-coating methods to produce GUVs. We tested the protocol focusing on vesicles with high Chol content using different spin-coating durations and vesicle types deposition. Additionally, we compared the novel protocol using completely dry lipid film. The optimal spin-coating duration for vesicles made out of phosphatidylcholine/Chol mixture was 30 s. Mulitlamellar vesicles (MLVs), large unilamellar vesicles (LUVs) obtained by extrusion of MLVs through 100 nm membrane pores and LUVs obtained by extrusion of previously obtained LUVs through 50 nm membrane pores were deposited on electrode for 1.5/1 Chol/phosphatidylcholine lipid mixture and the results were compared. Electroformation using all three deposited vesicle types gave a high GUVs yield, but deposition of LUVs obtained by extrusion of MLVs through 100 nm membrane pores gave the most reproducible results. Using deposition of these LUVs, we produced GUVs with high yield for 6 different Chol concentrations (from 0 % to 71.4%). Using protocol that includes dry lipid film GUVs yield was lower and Chol demixing artifact was induced, proving that the lipid film should never undergo drying when Chol content is high.

A brown seaweed consumed worldwide, Fucus vesiculosus, has been used to prevent atherosclerosis and hypercholesterolemia, among other uses, however, the mechanisms of action that lead to these effects are not yet fully understood. An F. vesiculosus aqueous extract, prepared as a soup was characterized as rich in sev-eral bioactive compounds, mainly phlorotannin and peptides. This work aims to study the in vitro effect of this extract on the expression of different proteins involved in the synthesis and transport of cholesterol in HepG2 cells, though a proteomic analysis, western blot and qRT-PCR. The results demonstrated that, in liver cells, the extract decreases the expression of 4 proteins involved in cholesterol biosynthesis process and also decrease the expression of two important transporters proteins of cholesterol, NPC1L1 and ABCG5, as well as decrease the NPC1L1 mRNA levels. Our study demonstrates some mechanisms of action of bioactive com-pounds from F. vesiculosus that may explain its previously reported hypocholesterolemic effect.

Hypercholesterolemia plays a fundamental role in the development and progression of atherosclerosis. Current guidelines for treating dyslipidemia target low-density lipoprotein-cholesterol (LDL-C). Despite advances in the pharmacotherapy of atherosclerosis, the most successful agents used to treat this disease – statins – remain insufficient in the primary or secondary prevention of acute myocardial infarction. Advancing therapy for hypercholesterolemia with emerging new drugs, either as monotherapy or in combination, is expected to improve cardiovascular outcomes.

Cholesterol is a lipid-derived substance found in lipoproteins and cell membranes. It is also one of the main sources for the production of bile acids, vitamin D, and steroid hormones. Today, foods are evaluated by consumers not only according to their taste and nutritional content but also according to their effects on consumer health. For example, many consumers choose foods according to their cholesterol level. The cholesterol in the food can directly affect the blood cholesterol level when consumed, which can lead to cardiovascular diseases. High levels of cholesterol can lead to diet-related human diseases such as cardiac arrest, paralysis, type II diabetes cerebral hemorrhage. In societies with high living standards, interest in and consumption of foods that lower or have low cholesterol levels have increased recently. Accordingly, efforts to increase the variety of foods with reduced cholesterol levels are on the rise. This has indirectly insulted in accurate measurement of cholesterol levels in blood and food being of great importance. Classical chemical, enzymatic, colorimetric, polarographic, chromatographic, spectrophotometric methods, and enzymatic, nonenzymatic, and electrochemical sensors and biosensors are used for the determination of cholesterol in foods. The purpose of this review is to reveal and explore current and future trends in cholesterol detection methods in foods. The review will summarize the most appropriate and standard methods for measuring cholesterol in biological components and foods.

Oxysterols have been implicated in the pathogenesis of cardiovascular diseases. Serum levels of oxysterols could be positively correlated with cholesterol absorption and synthesis. However, physiological regulation of various serum oxysterols is largely unknown. The aim of this study was to investigate the relationship between clinical factors and cholesterol metabolism markers, and identify oxysterols associated with cholesterol absorption and synthesis in patients with coronary artery disease. Subjects (n=207) who underwent coronary stenting between 2011 and 2013 were studied cross-sectionally. We measured lipid profiles including serum oxysterols. As for the serum biomarkers of cholesterol synthesis and absorption, oxysterol levels were positively correlated with campesterol and lathosterol. Covariance structure analysis revealed that dyslipidemia and statin usage had a positive correlation with “cholesterol absorption”. Statin usage also had a positive correlation with “cholesterol synthesis” Several oxysterols associated with cholesterol absorption and/or synthesis. In conclusion, we elucidated the potential clinical factors that may affect cholesterol metabolism, and the associations between various oxysterols with cholesterol absorption and/or synthesis in patients with coronary artery disease.

The translocator protein (TSPO) is a transmembrane protein present in the three domains of life. Its functional quaternary structure consists of one or more subunits. In mouse, the dimer-to-monomer equilibrium is shifted in vitro towards the monomer by adding cholesterol, a natural component of mammalian membranes. Here, we present a coarse-grained molecular dynamics study on the mouse protein in the presence of a physiological content and of an excess of cholesterol. The latter turns out to weaken the interfaces of the dimer by clusterizing mostly at the inter-monomeric space and pushing the contact residues apart. It also increases the compactness and the rigidity of the monomer. These two factors might play a role for the experimentally observed incremented stability of the monomeric form with increased content of cholesterol. Comparison with simulations on bacterial proteins suggests that the effect of cholesterol is much less pronounced for the latter than for the mouse protein.

Excessive high fat diet (HFD) consumption can induce food addiction which is believed to involve the communication between the hypothalamus and mesolimbic dopaminergic neurons, originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc). These brain regions are densely populated with opioid receptors, raising the possibility that these receptors, and particularly mu opioid receptors (MORs), are involved in mediating reward induced by palatable foods. This study sought to investigate the involvement of MORs in high fat diet (HFD)-induced reward and if there is any difference between male and female subjects in this response. We also assessed if exposure to HFD would potentiate the rewarding action of oxycodone, a relatively selective MOR agonist. The place conditioning paradigm was used to determine if conditioning for a short time (STC, 2 h) or long time (LTC, 16 h) with HFD induces reward or alters the rewarding action of oxycodone. Male and female C57BL/6J mice as well as MOR knockout and wildtype mice of both sexes were tested for basal place preference on day 1 and then conditioned with HFD in one chamber and regular chow diet (RCD) in another chamber and tested for place preference again after three sets of STC and again after a set of LTC. Each set consisted of two conditioning with RCD and two conditioning with HFD. Controls were conditioned with RCD in both conditioning chambers. Following the last place preference test, mice were treated with oxycodone and conditioned in the HFD-paired chamber and saline in the RCD-paired chamber for one hour once a day to explore the possibility if the HFD could alter oxycodone reward. The result showed that HFD induced conditioned place preference (CPP) in both male and female subjects following the LTC. This response was further potentiated after oxycodone conditioning. The latter response was mediated via MORs, as it was blunted in MOR knockout mice. However, HFD-induced CPP was observed following LTC in only female MOR knockout mice, suggesting for sexual dimorphism in this response.

The rates of obesity and obesity-related diseases continue to increase worldwide, classifying obesity as a global epidemic. Endogenous opioids have been implicated in influencing feeding behavior; however, the role of each opioid peptide is still only partially characterized. Therefore, we assessed the role of the proopiomelanocortin (POMC)-derived peptide beta-endorphin (β-END) in long-term high-fat diet (HFD) feeding and glucose homeostasis and assessed if sex-related differences exist in these processes. Male and female mice lacking the ability to produce β-END and their respective controls were subjected to a 12-week HFD consumption to determine the role of the opioid peptide in food intake and glucose homeostasis. Body weight and food intake were measured weekly for twelve weeks. At weeks 6 and 12, plasma glucose levels were measured using an oral glucose tolerance test. Here, we report that male β-END deficient mice gained more weight and consumed more calories than their wildtype controls; however, this difference was not observed in the female mice. Regardless of genotype, female mice consumed more calories per body weight when compared to male mice despite their smaller body weights. Moreover, our findings suggest differences in glucose homeostasis between the wildtype and knockout mice and that these were only observed at week six but not at week 12. Overall, our study suggests that endogenous β-END may play a role in controlling body weight, feeding behavior, and glucose homeostasis and that sex-related differences may exist in this regard.

Background and Aim: Serum alkaline phosphatase (ALP) activity has been associated with ath-erosclerotic cardiovascular disease (ASCVD). We aimed to investigate the association of ALP with ASCVD in patients with dyslipidemia. Methods: Retrospective cohort study including consecutive adults with dyslipidemia followed-up for ≥3 years (from 1999 to 2022) in the outpatient Lipid Clinic of Ioannina University General Hospital, Greece. The primary endpoint was the association between baseline ALP and incident ASCVD after adjusting for traditional risk factors (i.e. sex, age, hypertension, diabetes, smoking, dyslipidemia), baseline ASCVD and lipid-lowering treatment. ALP levels were stratified by ter-tiles as follows: low:<67 U/L, middle: 67-79 U/L, high: ≥79 U/L. Results: Overall, 1178 subjects were included; 44% were males and their median age was 57 years (range 49-65). During a 6-year median follow-up (interquartile range IQR: 4-9), 78 new ASCVD events (6.6%) occurred. A statistically significant association between baseline ALP levels and incident ASCVD was demonstrated (Odds Ratio, OR: 6.99, 95% Confidence Interval, CI: 2.29-21.03, p=0.001). Subjects in the highest ALP tertile had the highest odds for ASCVD when compared with those in the lowest tertile (OR: 2.35; 95% CI: 1.24-4.41, p=0.008). Conclusions: The present study demonstrated that ALP is associated with ASCVD development in patients with dyslipidemia.

The deficiency of Survival Motor Neuron (SMN) protein causes Spinal Muscular Atrophy (SMA), a rare neuromuscular disease that affects different organs. SMN is a key player in RNA metabolism regulation. An intriguing aspect of SMN function is its relationship with plasma membrane-associated proteins. Here, we provide a first demonstration that SMN affects the ATP-binding cassette transporter A1, (ABCA1), a membrane protein critically involved in cholesterol homeostasis. In human fibroblasts, we showed that SMN associates to ABCA1 mRNA, and impacts its subcellular distribution. Consistent with the central role of ABCA1 in the efflux of free cholesterol from cells, we observed a cholesterol accumulation in SMN-depleted human fibroblasts. These results were also confirmed in a SMA type I patient-derived fibroblasts. These findings not only validate the intimate connection between SMN and plasma mem-brane-associated proteins, but also highlight a contribution of dysregulated cholesterol efflux in SMA pathophysiology.

The 2015 Dietary Guidelines for Americans recommends that individuals should eat as little dietary cholesterol as possible. However, current dietary cholesterol intake and its food sources have not been well-characterized. We examined dietary cholesterol intake by age, sex, race, and food sources using 24-hour dietary recall data from a nationally representative sample of 5047 adults aged 20 years or older who participated in NHANES (2013–2014 survey cycle). We also reported trends in cholesterol intake across the past 7 NHANES surveys. Mean dietary cholesterol intake was 293 mg/day (348 mg/day for males and 242 mg/day for females) in the 2013–2014 survey cycle; 39% of adults had dietary cholesterol intake above 300 mg/day (46% for males and 28% for females). Meat, eggs, grain products, and milk were the highest four food sources of cholesterol, contributing to 96% of the total consumption. Both average cholesterol intake and food source varied by age, sex, and race (each p < 0.05). Mean cholesterol intake of the overall population had been relatively constant at ~290 mg/day from 2001–2002 to 2013–2014 (p-trend = 0.98). These results should inform public health efforts in implementing dietary guidelines and tailoring dietary recommendations.

Chitosan treatment results in significantly lower serum LDL cholesterol concentrations. To assess the working mechanism of chitosan, we measured serum surrogate markers of cholesterol absorption (campesterol, sitosterol, cholestanol), synthesis (lathosterol, lanosterol, desmosterol), and degradation to bile acids (7α-hydroxy-cholesterol, 27-hydroxy-cholesterol) corrected for cholesterol concentration (R_sterols). Over 12 weeks, 116 obese subjects (BMI 31.7, range 28.1 – 38.9 kg/m²) were studied under chitosan (n=61) and placebo treatment (n=55). The participants were briefly educated regarding improvement of nutrition quality and energy expenditure. Daily chitosan intake was 3200 mg. Serum LDL cholesterol concentration decreased significantly more (P=0.0252) under chitosan (-8.67 ± 18.18 mg/dl, 5.6%) than under placebo treatment (-1.00 ± 24.22 mg/dl, 0.9%). This reduction was not associated with the expected greater decreases in markers of cholesterol absorption under chitosan treatment. Also, increase in markers of cholesterol synthesis and bile acid synthesis under chitosan treatment was not any greater than under placebo treatment. In conclusion, a significant selective reduction of serum LDL cholesterol under chitosan treatment is neither associated with a reduction of serum surrogate markers of cholesterol absorption nor with an increases of markers for cholesterol and bile acid synthesis.

Sugar-sweetened beverages are associated with metabolic dysfunction, particularly in those with increased risk factors. Artificial sweeteners (AS) are often promoted as a healthier alternative, yet findings remain conflicting as to their effects on metabolic function. Further, there is a lack of data exploring the interaction between AS and high-fat diets (HFD). We therefore examined the effects of HFD and the AS Acesulfame-potassium (Ace-K) on glucose intolerance and adipose tissue physiology in male and female C57BL/6 mice. 40 mice were randomised to receive either a) a control diet (CDCon; standard control diet/water), b) control diet and Ace-k (CDAS; CD/7.5mM AS in drinking water), c) HFD (HFCon; HFD (45%kcal from fat)/water), or d) HF and AS (HFAS; HFD/7.5mM AS in drinking water) for 6 weeks. A HFD increased body weight in male and female mice independently of AS supplementation. AS induced sex-specific effects protecting against HFD-induced hyperglycaemia and adipocyte hypertrophy in male mice and reducing inflammatory gene expression in the adipose tissue. Conversely in females, AS induced hyperinsulinemia in HFD mice and increased expression of immune-related genes. These findings suggest that supplementation of HFD with AS exacerbates metabolic dysfunction in female mice. This work supports the importance of studying sexually dimorphic responses to an altered nutritional environment and highlights the need for further investigation into the intake of AS, particularly in those already at risk of metabolic disease such as the obese or overweight.

Gut microbiota dysfunction is a key factor affecting chronic kidney disease (CKD) susceptibility. Puerariae Lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote gut microbiota homeostasis, however, its role in renoprotection remains unknown. This study aimed to investigate the efficacy and potential mechanism of PLR to alleviate CKD. An 8-week 2% NaCl-feeding murine model was applied to induce CKD and evaluate the therapeutic effect of PLR supplementary. After gavage for 8 weeks, PLR significantly alleviated CKD-associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by reducing inflammatory response and down-regulating the canonical Wnt / β-catenin pathway. Further, PLR rescued gut microbiota dysbiosis and protected high salt-induced gut barrier dysfunction. We found enrichment of Akkermansia and Bifidobacterium after PLR intervention, the relative abundance of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that the positive effect of PLR on CKD was at least partially exerted through gut microbiota reestablishment and down-regulation of the Wnt / β-catenin pathway. Our study provides evidence for new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.

Age-related hearing loss (ARHL) is the most common sensory disorder in the elderly. It is associated with aging and hair cell death due to oxidative stress-induced mitochondrial dysfunction. Although transgenic mice and long-term cultures for induction of aging have been used to study ARHL, there are presently no ARHL animal models stimulated by intermittent environmental change for aging. In this study, an ARHL animal model was established by inducing continuous oxidative stress to promote short-term aging of cells, determined based on the expression of the hearing loss-induced phenotype and aging related factors in the short term. The incidence of hearing loss was significantly different among the groups subjected to intermittent hypoxic environment, high-fat diet (HFD), and injection with D-galactose. Continuous oxidative stress and HFD were factors that accelerated cellular aging. Increase in UCP2 affected oxidative stress and mitochondrial dysfunction. CDH23, SLC26A4, KCNQ4, Myo7a, and Myo6, which are ARHL-related factors, were modified by oxidative stress in cells of the hearing organ. We found that intermittent hypoxic, HFD, and galactose injection accelerated cellular aging in the short term. Thus, we anticipate that the development of this hearing loss animal model, which reflects intermittent environmental changes, will benefit future research on ARHL.

Background: The mechanisms underlying the effect of estradiol (E2) on low-density lipoprotein cholesterol (LDL-C) levels are not completely understood, although a role for proprotein con-vertase subtilisin/kexin type 9 (PCSK9) has been proposed. We aimed to investigate the association between levels of E2, PCSK9 and lipid parameters in premenopausal women undergoing in vitro fertilization (IVF). Methods: Healthy women undergoing IVF in the Department of Obstetrics and Gynecology of the University General Hospital of Ioannina were recruited. Levels of E2, pro-protein convertase subtilisin/kexin type 9 (PCSK9), total cholesterol (TCHOL), high-density lip-oprotein cholesterol (HDL-C), LDL-C, and triglycerides (TGs) were measured 10 days after ovarian depression (E2min) and 7 days after ovarian stimulation (E2max). Results: A total of 34 consecutive healthy women aged 38 (26-46) years old who underwent a full IVF cycle were included. E2 levels increased by 329.6% from E2min to E2max (108 [47-346] to 464 [241-2471] pg/mL, p<0.05). At the same time, serum PCSK9 levels significantly decreased by 30.8% (245 ± 80 to 170 ± 64 ng/mL, p<0.05). No significant changes in TCHOL, LDL-C, TGs and HDL-C were found (-0.4%, -3.8%, -2.2%, and +5.3%, p >0.05). Conclusions: The increase in endogenous E2 production during an IVF cycle was associated with a significant decrease in serum PCSK9 levels during a 7-day period.

Administration of crude polysaccharides extract from natural product is a promising gut microbiota-targeted approach to preventing obesity and associated metabolic disorders. Dietary restrictions can change the type and number of gut bacteria, which is an important factor in delaying the onset and burden of diseases. This study aimed to investigate the effects of high-yield crude polysaccharides from Cordyceps militaris (CMP) on high-fat diet (HFD) mice model and the gut microbiota community assembly, and to identify whether selenium (Se) addition would improve CMP action mode during cultivation. We found that the CMP treatment ameliorated adipose and liver pathologic morphology and fat accumulation in obese mice, while, SeCMP intervention was not superior than CMP in body mass gain, but notably decreasing serum triglyceride level increased by HFD. The upregulated expression of gene Cyp7a1 in liver and protein UCP1 in brown adipose tissue (BAT) preliminary indicated that the effect might relate to bile acids (BAs) metabolism pathway and thermogenesis. In addition, CMP showed a drastic decrease in the gut microbes which positively correlated with dyslipidemia parameters. Our result reveals the potential of CMP to be used as functional food in the prevention of diet-induced adipose and liver steatosis, so does SeCMP has outstanding capacity of improving dyslipidemia.

The Nanosecond Pulsed Electric Field (nsPEF) or Nano Pulsed Stimulation (NPS) is a cutting-edge technology that applies a series of high-voltage electric field pulses of extremely short duration, typically on the order of nanoseconds, to cells. This technique induces the formation of nanopores and activate ionic channels, thereby altering cellular activity. Recent simulations suggest that nsPEF also triggers a novel phenomenon, Protein-mediated Electroporation, whereby pores are formed through the voltage-sensing domain of ionic channels. In this study, we employed Molecular Dynamics simulations and machine learning techniques to investigate the Voltage Sensing Domain (VSD) of a cardiac channel under nsPEF stimulation. Specifically, we characterized VSD structures that form pores helping for the understanding of the physical chemistry underlying the defibrillation effect of nsPEF. Our analysis involved the clustering of 142 replicas simulated for 50 ns under the nsPEF stimulus. Subsequently, we identified the representative structures of each cluster and calculated the free energy between them. Our results demonstrate that although VSD structures are ubiquitous among ionic channels, they exhibit distinct responses to nsPEF stimuli. These findings have significant implications for the development of novel nsPEF-based therapies for cardiac diseases.

The objective of this experiment was to study the effect of feeding pellet containing high sulfur (PELFUR) diet and fresh cassava root (FCR) to Thai native beef cattle on feed use efficiency, ruminal characteristics, and blood metabolites. Four male Thai native beef cattle (150 ± 15.0 kg of body weight (BW)) were allocated with a 2 × 2 factorial arrangement in a 4 × 4 Latin square design. Factor A was FCR supplementation at 15 and 20 g/kg of BW. Factor B was the sulfur level in the PELFUR ration at 15 and 30 g/kg of dry matter (DM). No interaction effect was found among FCR supplementation and PELFUR in terms of feed intake and nutrient intake (p > 0.05). Cyanide intake was significantly increased based on FCR supplementation (p < 0.05), whereas sulfur intake was increased by level addition of PELFUR levels (p < 0.05). There were interaction effects among FCR supplementation and PELFUR on digestibility coefficients of DM and organic matter (OM) (p < 0.05). FCR supplementation at 20 g/kg BW with PELFUR 30 g/kg demonstrated the highest digestibility of DM and OM. Moreover, interactions were observed between FCR and PELFUR for bacterial populations (p < 0.01). The populations of bacteria were highest in FCR supplementation at 20 g/kg BW with PELFUR 30 g/kg at various feeding times. An interaction effects from among feeding FCR with PELFUR was found on blood thiocyanate concentrations at various feeding times (p < 0.01). The highest mean values of blood thiocyanate were observed when feeding FCR at 20 g/kg BW with PELFUR at 30 g/kg. No interaction effect was found between FCR and PELFUR on total volatile fatty acids (VFA) and their profiles (p >0.05). However, the proportions of the total VFA at 0 and 4 h post-feeding were increased when FCR at 20 g/kg BW was supplemented (p < 0.01). FCR at 20 g/kg BW could enhance propionate (C3) at 4 h post-feeding when compared with FCR at 15 g/kg BW (p < 0.01). Moreover, supplementation of PELFUR at 30 g/kg increased the total VFA at 0 and 4 h post-feeding, whereas the concentration of C3 at 4 h post-feeding was enhanced (p < 0.05). However, no significant changes were found for any parameters among treatments and between the main effect of FCR and PELFUR supplementation (p > 0.05). In conclusion, feeding of two combinations (FCR 20 g/kg BW with PELFUR 30 g/kg) could promote the nutrient digestibility, the bacterial populations, and the rate of disappearance of cyanide without having any adverse effect on rumen fermentation.

Sterol homeostasis in mammalian cells and tissues involves balancing three fundamental processes: de novo sterol biosynthesis; sterol import (e.g., from blood-borne lipoproteins); and sterol export. In complex tissues, composed of multiple different cell types (such as the retina), import and export also may involve intra-tissue, inter-cellular sterol exchange. Disruption of any of these processes can result in pathologies that impact the normal structure and function of the retina. Here, we provide a brief overview of what is known currently about sterol homeostasis in the vertebrate retina and offer a proposed path for future experimental work to further our understanding of these processes, with relevance to the development of novel therapeutic interventions for human diseases involving defective sterol homeostasis.

Background: Lipid disorders are one of risk factors for cardiovascular diseases. The aim of the study was to determine the lipid profile in early childhood in the group of Polish children born small for gestational age (SGA). Materials and Methods: The study included 140 children (93 SGA and 47 controls) aged 5 to 11 years. All children underwent a physical examination and blood tests for the glucose and lipid profile. SGA group was divided in subgroups: symmetrical and asymmetric intrauterine growth restriction (IUGR). Results: Blood sample analysis revealed higher levels of total cholesterol levels (SGA group 190.61 +/- 24.66 mg/dl vs control 143.23 +/- 23.90; p&lt;0.001). The analysis of particular fractions of cholesterol showed significantly higher mean values of triglycerides, LDL-cholesterol as well as lower mean values of HDL-cholesterol in children born as SGA. Children in both groups did not differ significantly according to weight and body mass index. A statistically significantly higher glucose concentration was obtained in the group of children with IUGR with symmetrical type of IUGR. Conclusions: Children born SGA even in their early childhood, without overweight or obesity, have abnormal lipid profile, which may be a risk factor of cardiovascular diseases in adulthood.

Breast cancer is the most common cancer in women. Cardiovascular diseases are common complications after chemotherapy due to the effect of the drug on lipid levels. This study aimed to explore the changes in lipid profiles in patients with breast cancer under chemotherapy. Methods: In this prospective study, 50 patients with breast cancer participated. Three biochemical-lipid hematological tests were performed: total cholesterol (TC), triglycerides (TG), High-Density Lipoprotein (HDL-C), and Low-Density Lipoprotein (LDL-C) before initiation (pre-chemotherapy), at the start (1st follow-up), and at the completion (2nd follow-up) of the first cycle of chemotherapy. Statistical significance was set at p&lt;0.05. Analyses were conducted using SPSS Statistical Software (version 22.0). Results: Mean TC values increased significantly at 2nd follow-up. TG values decreased significantly from 1st to 2nd follow-up. HDL-C was significantly lower at 1st follow-up compared to pre-chemotherapy and 2nd follow-up reaching similar to the initial levels. LDL-C values were significantly higher at 2nd follow-up compared to pre-chemotherapy measurement. Significantly positive correlations of BMI with pre-chemotherapy LDL-C, 1st follow-up TC, 1st follow-up LDL-C, 2nd follow-up TC, and 2nd follow-up LDL-C were found. Conclusions: There is a statistically significant increase in the levels of TC and LDL-C in breast cancer patients during chemotherapy. This study was not registered.

Milk fat globule membrane (MFGM) is a complex tri-layer membrane that wraps droplets of lipids in milk. In recent years, it has attracted widespread attention due to its excellent bioactive functions and nutritional value. The milk fat globule membrane contains a diverse array of bioactive lipids, including cholesterol, phospholipids, and sphingolipids, which play pivotal roles in mediating the bioactivity of the milk fat globule membrane. We sequentially summarize the main lipid types in milk fat globule membrane in this comprehensive review and outline the characterization methods used to employed them. In this comprehensive review, we sequentially describe the types of major lipids found in the milk fat globule membrane and outline the characterization methods employed to study them. Additionally, we compare the structural disparities among glycerophospholipids, sphingolipids, and gangliosides, while introducing the formation of lipid rafts facilitated by cholesterol. The focus of this review revolves around an extensive evaluation of current research on lipid isolates from the milk fat globule membrane, as well as products containing milk fat globule membrane lipids, with respect to their impact on human health. Notably, we emphasize clinical trials encompassing a large number of participants. The summarized bioactive functions of milk fat globule membrane lipids encompass regulation of human growth and development, influence on intestinal health, inhibition of cholesterol absorption, enhancement of exercise capacity, and anti-cancer effects. By offering a comprehensive overview, the aim of this review is to provide valuable insights into the diverse biologically active functions exhibited by lipids in milk fat globule membrane.

Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a proteolytic enzyme that indirectly regulates serum LDL cholesterol by destroying LDL receptors. In clinical studies, the main role of the proprotein convertase subtilisin/Kexin type9 (PCSK9) inhibitor in cholesterol regulation was elucidated. It is produced in the liver but is also present in the kidney and intestine. It prevents HMGCo from synthesizing cholesterol. SREBP-2 is a reductase that is induced by statins. In a dose-dependent manner, increasing SREBP-2 levels enhanced LDL-R and PCSK9 gene expression. At the minimum, two procedures have been developed to overcome the plasma level of PCSK9. This is the LDLR test, polyclonal antibodies, and sentience oligonucleotide. Lower dosage statin treatment with a proprotein convertase subtilisin/Kexin type9 inhibitor will be most efficient in lowering LDL and avoiding statin adverse effects. In multiple long-term trials, statins have been found to reduce cardiovascular mortality by 30% and stroke incidence by 20%. In this way, we conclude the role of PCSK9 in hypercholesterolemia.

Diabetes is a major risk factor for tuberculosis (TB). Diabetes increases the risk of progression from latent tuberculosis infection (LTBI) to active pulmonary TB and TB patients with diabetes are at greater risk of more severe disease and adverse TB treatment outcomes compared to TB patients without co-morbidities. Diabetes is a complex disease characterized not only by hyperglycemia but also various forms of dyslipidemia. However, the relative contribution of these underlying metabolic factors to increased susceptibility to TB are poorly understood. This review summarizes our current knowledge on epidemiology and clinical manifestation of TB and diabetes comorbidity. We subsequently dissect the relative contribution of body mass index, hyperglycemia, elevated cholesterol and triglycerides on TB disease severity and treatment outcomes. Lastly, we discuss the impact of selected glucose and cholesterol lowering treatments frequently used in the management of diabetes on TB treatment outcomes.

At the end of mitosis the Mitotic Exit Network (MEN) pathway triggers complex tasks which mainly include the spindle disassembly and the nuclear envelopes assembly. In the course of telophase, which often lasts less than an hour and corresponds to only about 2% of the entire cell cycle’s duration, spatial and temporal cues are integrated to ensure that cytokinesis occurs after the genome has partitioned between mother and daughter cells. From the end of anaphase through telophase, sequential components of a Ras-like GTPase signaling pathway are controlled by a set of different spatial and temporal signals. Successful propagation of these signals through multi-step transduction requires a remarkable sequential coordination. By considering that cells lacking proper MEN function fail to exit from mitosis, I argue that in a hybrid genome impaired coordination between two diverged MENs is prone to result in critical mitotic defects, from late anaphase through telophase. The so-called HyMEN model of hybrid incompatibility depicted here can be regarded as an extension of the Bateson-Dobzhansky-Muller model of speciation, centered on the MEN.

This study presents a meta-analysis of studies that investigate the effectiveness of chitosan administration on lifestyle-related disease in murine models. A total of 34 published studies were used to evaluate the effect of chitosan supplementation. The effect sizes for various items after chitosan administration were evaluated using the standardized mean difference. Using Cochran’s Q test, the heterogeneity of effect sizes was assessed, after which a meta-ANOVA and –regression test was conducted to explain the heterogeneity of effect sizes using the mixed-effect model. Publication bias was performed using Egger’s linear regression test. Among the items evaluated, blood triglyceride and HDL-cholesterol showed the highest Q statistics and I2 values, respectively. Other than blood HDL-cholesterol, total cholesterol, and triglyceride in feces, most items evaluated showed a negative effect size with high significance in the fixed- and random-effect model (p<0.0001). In the meta-ANOVA and -regression test, administering chitosan and resistant starch was revealed to be most effective in lowering body weight. In addition, chitosan supplementation proved to be an effective solution for TNF-α inhibition. In conclusion, chitosan has been shown to be somewhat useful in improving symptoms of lifestyle-related disease. Although there are some limitations in the results of this meta-analysis due to the limited number of animal experiments conducted, chitosan administration nevertheless shows promise in enhancing the quality of human life.

Previous incidental findings of an increase of suicidal risk among subjects with low cholesterol levels have drawn attention to the role of lipids in suicidal behavior. To date, multiple lines of evidence acquired from clinical studies have confirmed an association between low cholesterol levels and suicidal behavior, but the involvement of dimensional traits including impulsivity and aggression in this association remains elusive. In this narrative review, we aimed to address and synthesize the literature regarding the involvement of lipids in the neurobiology of suicidal behavior and its underlying psychological substrates, impulsivity and aggression. An electronic database search was performed using different combinations of relevant keywords. Both preclinical and clinical studies matching the scope of this article were reviewed and filtered through an inspection of the abstracts to recruit the most suitable articles that contributed essential and substantial findings to the literature. Although subject characteristics and study designs vary across studies, current research has demonstrated that impulsivity and aggression might have shared neurobiologic substrates involved in altered serotonergic neurotransmission. Despite the association between low serum lipid levels and suicidal behavior being well documented, the involvement of lipid subtypes in the pathophysiology of impulsive and aggressive traits remains elusive. Further work is warranted to recognize the roles of lipids in neuronal membrane functions and serotonin metabolism, promote a greater appreciation of identifying biomarkers that could be used to determine at-risk individuals, and develop potential interventions to disrupt the pathogenesis of behavioral phenotypes of suicide.

Managing blood cholesterol levels is important for the treatment and prevention of diabetes, cardiovascular disease, and obesity. An easy-to-use, portable cholesterol blood test will accelerate more frequent testing by patients and at-risk populations. We aim to evaluate the performance of smartphone-based point-of-care cholesterol blood tests as compared to that of hospital-grade laboratory tests. We used smartphone systems that are already familiar to many people. Because smartphone systems can be carried around everywhere, blood can be measured easily and frequently. We compared the results of cholesterol tests with those of existing clinical diagnostic laboratory methods. We found that smartphone-based point-of-care lipid blood tests are as accurate as hospital-grade laboratory tests (N=116, R>0.97, P<0.001 for all 3 cholesterol blood tests: total cholesterol, high density lipoprotein, and triglyceride). Our system will be useful for those who need to manage blood cholesterol levels to motivate them to track and control their behavior.

Lipid composition in the cellular membranes plays an important role in maintaining the struc-tural integrity of cells and in regulating cellular signaling that controls functions of both mem-brane-anchored and cytoplasmic proteins. ATP-dependent ABC and P4-ATPase lipid transport-ers, two integral membrane proteins, are known to contribute to lipid translocation across the li-pid bilayers on the cellular membranes. In this review, we will highlight current knowledge about the role of cholesterol and phospholipids of cellular membrane in regulating cell signaling and how lipid transporters participate this process.

All over the world birds’ eggs are an important and valuable component of the human diet. The study aimed to compare the content of lipid components and their nutritional value as well as iron and zinc levels in chicken and quail eggs commonly available on the market. In egg lipids, unsaturated acids were dominated, especially oleic acid, the content of which was about 40% of total fatty acids (TFA). Linoleic acid was the major polyunsaturated fatty acid. Compared to other products of animal origin, eggs were characterized by favourable values of lipid quality indices, especially index of atherogenicity, thrombogenicity and hypocholesterolemic to hypercholesterolemic ratio. In the present study, no differences in the content of tested nutrients between eggs from different production methods (organic, free-range, barn, cages), as well as inter-breed differences were noticed. Cluster analysis showed that eggs enriched in n3 PUFA (according to producers’ declaration) differ from other groups of chicken eggs. However, only in eggs from one producer, the amount of EPA and DHA exceed 80 mg per 100 g, entitling to use the nutrition claim on the package. Quail eggs differed from chicken eggs in FA profile; they also had much higher iron and cholesterol levels.

Weight loss solutions are on the rise, and there is growing interest in natural alternatives to the pharmaceuticals in the market, which are not devoid of relevant side effects. To this end, the objective of the current study is to assess the effects of a botanical-based blend comprised of lemon verbena and hibiscus extracts in weight management, body fat, appetite, lipid, and glucose profiles, in an overweight population, for 90 days. As a result, the volunteers presented significant weight loss in absence of diet, which coincided with decreased body fat. Body fat was assessed by anthropometry, electrical bioimpedance and DEXA scan. Cholesterol levels were also significantly decreased. Satiety assessment revealed that the product contributed to increased feeling of fullness and satisfaction after a meal, compared to the placebo group, which could contribute to the weight loss observed. Blood glucose and blood pressure levels remained unchanged, which was expected as the volunteers were normoglycemic and their blood pressure was in the healthy range. In conclusion, daily supplementation of a botanical-based blend contributes to weight loss in overweight individuals, in absence of diet, while not affecting other parameters that are in the healthy range. This product could be a candidate alternative or add-on to other weight loss products, as part of a healthy lifestyle.

The use of antibiotics as growth promotors or for the prevention of some poultry diseases has face global concern and serious criticism. Their addition to poultry feed show hazardous effects including development of antimicrobial resistance and the potential harmful effect on humans’ health. To eliminate these threats, there is increasing interest to search for natural alternatives. Plant derivatives such as garlic (Allium sativum L.) and its derivatives are nowadays extensively used in poultry production system. Dietary supplementation of broilers and layers with garlic induced improvement of production parameters, carcass quality, and intestinal integrity. Modulation of the immune response against important viral diseases and increasing the immune organs body weight ratio resulting from supplementation of poultry with garlic. Moreover, garlic showed modulation of gut health through the antibacterial and antiparasitic activities. Treatment with garlic also can mitigate the oxidative stress and reduce the free radicals production. Reduction of cholesterol level, but improvement of some liver and blood parameters were also reported following dietary inoculation of garlic. This review was designed to search on the impact of garlic as feed additives on performance, immunity, gut health, antioxidant status, and blood parameters of poultry.

Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease. Dyslipidemia in T2D is typically characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels. There is a significant gap in the literature regarding dyslipidemia in rural parts of Africa, where lipid profiles may not be routinely captured through standard surveillance activities. This study aimed to characterize the prevalence and demographic profile of dyslipidemia in T2D patients in the rural community of Ganadougou, Mali. We performed a cross-sectional study of 104 subjects with T2D in Ganadougou between November 2021 and March 2022. Demographic and lipid profiles were collected through cross-sectional surveys and blood tests. The overall prevalence of dyslipidemia in T2D patients was 87.5% (91/104), which did not differ by sex (p = .368). High low-density lipoprotein cholesterol (LDL-C) was the most common lipid abnormality (78.9%, [82/104]). Dyslipidemia was associated with age and hypertension status (p = .013 and p = .036, respectively). High total and high LDL-C parameters were significantly associated with hypertension (p = .029 and p = .006, respectively). In low-resource settings such as rural Mali, there is a critical need to improve infrastructure for routine dyslipidemia screening to guide its prevention and intervention approaches. The high rates of dyslipidemia observed in Gandadougou, consistent with concomitant increases in cardiovascular diseases in Africa suggest that lipid profile assessments should be incorporated into routine medical care for T2D patients in African rural settings.

Metabolic changes are an important component of tumor cell progression. Tumor cells adapt to environmental stresses via changes to carbohydrate and lipid metabolism. Autophagy, a physiological process in mammalian cells that digests damaged organelles and misfolded proteins via lysosomal degradation is closely associated with metabolism in mammalian cells acting as a meter of cellular ATP levels. In this review, we discuss the changes in glycolytic and lipid biosynthetic pathways in mammalian cells and their impact on carcinogenesis via the autophagy pathway. Also, we discuss the impact of these metabolic pathways on autophagy in lung cancer.

Recent COVID-19 outbreak has come into prominence the pathogenetic mechanisms underlying the Biology and Biochemistry of viral infections. COVID-19 illness is brought about by infection with the severe acute respiratory syndrome coronavirus SARS-CoV-2 [1,2], an enveloped positive single stranded RNA virus (ssRNA+). From a lipidomics viewpoint, there is a variety of mechanisms involving virus infection that encompass virus entry, disturbance of host cell lipid metabolism, and the role played by diverse lipids in regard to the infection effectiveness. All these aspects have currently been tackled separately as independent issues and focusing on the function of proteins. Here we review the role of cholesterol and other lipids in in ssRNA+ and SARS-COV-2 infection.

Hypercholesterolemia accelerates atherosclerosis, and extensive research has been undertaken to ameliorate this abnormality. Plant sterols have been shown to inhibit cholesterol absorption and lower plasma cholesterol level since the 1950s. This ingredient has recently been reappraised as a food additive that can be taken daily in a preclinical period to prevent hypercholesterolemia, considering that cardiovascular-related diseases are the top cause of death globally even with clinical interventions. Intestinal cholesterol handling is still elusive, making it difficult to clarify the mechanism for plant sterol-mediated inhibition. Notably, although the small intestine absorbs cholesterol, it is also the organ that excretes it abundantly, via trans-intestinal cholesterol efflux (TICE). In this review, we show a model where the brush border membrane (BBM) of intestinal epithelial cells stands as the dividing ridge for cholesterol fluxes, making cholesterol absorption and TICE inversely correlated. With this model, we tried to explain the plant sterol-mediated inhibitory mechanism. As well as cholesterol, plant sterols diffuse into the BBM but are effluxed back to the lumen rapidly. We propose that repeated plant sterol shuttling between the BBM and lumen promotes cholesterol efflux, and plant sterol in the BBM may disturb the trafficking machineries that transport cholesterol to the cell interior.

Glaucoma is a group of ocular diseases that causes irreversible blindness worldwide and is characterized by a multifactorial degeneration of optic nerve and retinal ganglion cells (RGCs), leading to vision loss. One of the significant risk factors in glaucoma pathogenesis is glia-driven neuroinflammation. Impairment of mitochondrial dynamics and bioenergetics is associated with glaucomatous neurodegeneration and is linked to neuroinflammation. Apolipoprotein A-I binding protein (AIBP) binds to toll-like receptor 4 (TLR4) and facilitates the removal of excess cholesterol from the plasma membrane in activated cells, suggesting the regulation of cholesterol-driven inflammation by inhibiting the TLR4-associated lipid rafts. AIBP is localized in mitochondria and regulates mitophagy by ubiquitination of mitofusin 1 and 2. We observed elevated intraocular pressure-induced AIBP deficiency in glaucomatous neurodegeneration. We also observed that AIBP deficiency activated TLR4 in Müller glia, triggered mitochondrial dysfunction in both RGCs and Müller glia and impaired visual function. In mouse models of glaucoma, AIBP treatment protects RGCs by reducing inflammatory responses. Here, our review focuses on investigating the role of AIBP in the retina and examining the underlying mechanism by which AIBP contributes to the pathogenesis of glaucoma, aiming to provide new insight into the therapeutic potential for the treatment of glaucoma.

The number of people with gluten-related illnesses has been increasing and the available treatments include the introduction of a gluten-free diet. In the bakery industry, there are problems with gluten-free products, namely the important characteristics that this component gives to doughs and the low nutritional value they present. A disease that has also increased in recent years is diabetes mellitus, which is characterized by a lack of insulin and the effectiveness of its action (type 1 diabetes) or tissue insensitivity to the hormone (type 2 diabetes). In terms of treatments, there are several approaches: inhibition of digestive enzymes (α-amylase and α-glucosidase) or techniques based on mechanisms of action (stimulation of insulin production and release, insulin transport and decreased glucose absorption). Hyperglycemia is also associated with the production of reactive oxygen species, which leads to cell apoptosis. On the other hand, there was also an association with high levels of cholesterol in the body, which contributed to the development of other types of diseases. In this sense, macroalgae have been studied as a source of natural compounds and used as food supplements, due to their protein, amino acid and mineral content, and the anti-diabetic effect in controlling the glycemic index, oxidative stress and cholesterol have already been demonstrated. Seaweed emerges as a promising source of bioactive nutraceuticals for individuals with coeliac disease, diabetes, and hyperglycemia. The rising prevalence of gluten-related illnesses calls for effective treatments, and seaweed's potential in enhancing the nutritional value of gluten-free products is noteworthy. Additionally, its demonstrated anti-diabetic effects, including glycemic index control, oxidative stress reduction, and cholesterol management, make it a valuable dietary supplement. Further research is needed to explore the specific bioactivities of seaweed compounds and their mechanisms of action. Integrating seaweed-based nutraceuticals into diets could complement traditional treatments, offering potential health benefits to those with coeliac disease and diabetes.

Approximately one-third of mankind is chronically exposed to the carcinogenic aflatoxin M1 contained in milk and dairy products and there is no ready to use procedure for decontamination purposes applicable in milk technology. Since β-cyclodextrin is frequently used in food industry, its effect on aflatoxin M1 concentration was investigated during cholesterol removal. So, milk samples were spiked with aflatoxin M1 at the average level 0.89 µg/kg and cholesterol removal was carried out by 2.0% (w/w) β-cyclodextrin addition. As found, average cholesterol concentration decreased by 92.3% while aflatoxin M1 concentration decreased to 0.53 µg/kg, i. e. by 39.1% after the treatment. The procedure itself is easy, inexpensive, and ready to use in milk processing technology on current production lines without any investments, thus fully applicable with a high potential of full aflatoxin M1 milk decontamination efficiency and such way to strengthen considerably the food safety issues associated with milk and dairy products on global level.

Background: Residents of a large area of North-Eastern Italy were exposed for decades to high concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) via drinking water. Despite the large amount of evidence in adults of a positive association between serum PFAS and metabolic outcomes, studies focusing on children and adolescents are limited. We evaluated the associations between serum PFAS concentrations and lipid profile, blood pressure and body mass index (BMI) in highly exposed adolescents and children. Methods: A cross-sectional analysis was conducted in 6669 adolescents (14-19 years) and 2693 children (8-11 years) enrolled in the health surveillance program of the Veneto Region. Non-fasting blood samples were obtained and analyzed for perfluorooctanoic acid (PFOA) perfluorooctane sulfonate (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), total cholesterol (TC) high-density lipoprotein cholesterol (HDL-C) and triglycerides. Low-density lipoprotein cholesterol (LDL-C) was calculated. Systolic and diastolic blood pressure (BP) were measured and BMI z-score accounting for age and sex was estimated. The associations between ln-transformed PFAS (and categorized into quartiles) and continuous outcomes were assessed using generalized additive models. Analyses were stratified by gender and adjusted for potential confounders. Results: Among adolescents, significant associations were detected between all investigated PFAS and TC, LDL-C, and to a fewer extent HDL-C. Among children, PFOS and PFNA had significant associations with TC, LDL-C and HDL-C, while PFOA and PFHxS had significant associations with HDL-C only. Increased serum concentrations of PFAS, particularly PFOS, were associated with decreased BMI z-score. No statistically significant associations were observed between PFAS concentrations and BP. Conclusions: Our study supports a consistent association between PFAS concentration and serum lipids, stronger for PFOS and PFNA and with a greater magnitude among children compared to adolescents, and a negative association of PFAS with BMI.

IIAEK (Ile-Ile-Ala-Glu-Lys, lactostatin) is a novel pentapeptide from bovine milk β-lactoglobulin which lowers cholesterol levels. However, the molecular mechanisms underlying the suppression of intestinal cholesterol absorption by IIAEK are unknown. Therefore, we evaluated the effects of IIAEK on intestinal cholesterol metabolism in Caco-2 cells in a human intestinal model. We found that IIAEK significantly reduced the expression of intestinal cholesterol metabolism-associated genes, particularly that of the ATP-binding cassette transporter A1 (ABCA1) protein. Subsequently, we chemically synthesized a novel molecular probe, IIXEK, which can visualize a complex of target proteins interacting with photoaffinity-labeled IIAEK by fluorescent substances. Photoaffinity labeling and MS analysis with IIXEK for the rat small intestinal mucosa and intestinal lipid raft fractions of Caco-2 cells, we identified intestinal alkaline phosphatase (IAP) as a specific molecule interacting with IIAEK and discovered IIAEK common binding amino acid sequence, GFYLFVEGGR. Transfection of IAP siRNA counteracted the decrease in ABCA1 mRNA levels in Caco-2 cells. IIAEK significantly increased IAP mRNA and protein levels, and significantly decreased ABCA1 mRNA and protein levels in Caco-2 cells. In conclusion, we found that IIAEK targets IAP to improve cholesterol metabolism via a novel signaling pathway with a specific activation of IAP and down-regulation of intestinal ABCA1.

Meta-analysis of plant sterol supplement studies suggests an 8% lowering of LDL cholesterol for 2 to 2.5g/day of plant sterols. Cereal foods have been rarely tested and one study showed a lower LDL lowering of 5.4% with 1.6g of plant sterol in breakfast cereal. We aimed to test a breakfast wheat biscuit with 2g of plant sterols in a single serve of two wholegrain wheat breakfast cereal biscuits. Fifty volunteers with a total cholesterol of >5.5mmol/L were recruited for a randomised crossover study with two 4-week periods with no washout of which 45 successfully completed the study. After exclusion of four outliers the difference in LDL cholesterol between standard wholegrain wheat breakfast cereal biscuit and plant sterol-enriched wholegrain wheat breakfast cereal biscuit was 0.23 mmol/L or 5.6% (P=0.001) with a 95% confidence interval of 2.4-8.9%. Men and daily cereal consumers had greater responses 9.8% vs 3.6% and 7.2% vs 3.8% respectively (P<0.05). The LDL lowering effect of 2g of plant sterol enriched from one serve of wholegrain wheat breakfast cereal biscuit was not significantly different from other food products delivering 2-2.5g of plant sterols daily. Regular cereal consumers have a better response.

Excessive body fat is a major contributor to obesity, which is related to high blood, total cholesterol and triglycerides. Lemons (Citrus limon) are renowned for their antioxidant and lipid-lowering properties. First, Sugar-free fermentation demonstrated better results lower sugar content and was identified as the preferred fermentation method. Next, the effect of two doses of sugar-free fermented lemon peel juice (SF-FLPJ) on obesity was investigated. Sprague Dawley (male rats) were randomly divided into 4 groups and fed a standard feed or high-fat diet (HFD) to induce fatness for eight weeks. The two groups of rats fed an HFD were administered SF-FLPJ at 0.45 or 0.9 g/kg body weight daily for eight weeks. The obese rats administered 0.9 g/kg (body weight/day) of SF-FLPJ exhibited significant reductions in body fat mass and percentage; they also had lower blood cholesterol and triglyceride levels than the other groups. Additionally, the rats displayed diminished liver fat accumulation. The results suggest that SF-FLPJ can be a supplement in managing body fat, contributing positively to addressing obesity within the context of health management, and reduce obesity-associated issues.

Cholesterol siRNA conjugates attract attention because they allow the delivery of siRNA into cells without the use of transfection agents. In this study, we compared the efficacy and duration of silencing induced by cholesterol conjugates of selectively and totally modified siRNAs and their heteroduplexes of the same sequence and explored the impact of linker length between the 3' end of the sense strand of siRNA and cholesterol on the silencing activity of “light” and “heavy” modified siRNAs. All 3'-cholesterol conjugates were equally active under transfection, but the conjugate with a C3 linker was less active than those with longer linkers (C8 and C15) in a carrier-free mode. At the same time, they are significantly inferior in activity to the 5'-cholesterol conjugate. Shortening the sense strand carrying cholesterol by 2 nucleotides from the 3'-end did not have a significant effect on the activity of the conjugate. Replacing the antisense strand or both strands with fully modified ones has a significant effect on silencing as well as improving the duration in transfection-mediated and carrier-free modes. A significant 78% suppression of MDR1 gene expression in KB-8-5 xenograft tumors developed in mice promises an advantage from the use of fully modified siRNA cholesterol conjugates in combination chemotherapy.

The purpose of this work was to investigate whether two-months supplementation with 100% sea buckthorn juice (SBJ) would modify blood lipids, LDL subfractions and other markers of cardiovascular risk in hypercholesterolemic women. A group of 28 hypercholesterolemic non-medicated adult women with a mean age of 50.58 ± 5.76 years consumed 50 mL of 100% SBJ daily for two-months. We observed a significant reduction of body weight (BW; p < 0.05), body mass index (BMI; p < 0.05), body fat mass (BFM; p < 0.001) and visceral fat area (VFA; p < 0.001), on the contrary, a significant increase of skeletal muscle mass (SMM; p < 0.05) and fat-free mass (FFM; p < 0.05). Supplementation with 100% SBJ significantly increased the level of high-density lipoprotein (HDL; p < 0.05), reduced the level of low-density lipoprotein (LDL; p < 0.05), atherogenic LDL subfractions (LDL3–7; p < 0.05) and improved LDL/HDL ratio (p < 0.001). After the SBJ consumption, significant reduction of C-reactive protein (CRP; p < 0.001), orosomucoid (ORM; p < 0.001) and interleukin 6 (IL-6; p < 0.05) were found. In conclusion, consumption of SBJ showed an indication of beneficial effects on cardiovascular risk factors in hypercholesterolemic women.

The metabolism of lipoproteins, which regulates the transit of the lipid to and from tissues, is crucial to maintaining cholesterol homeostasis. Cardiac remodeling is referred to as a set of molecular, cellular, and interstitial changes that, following injury, affect the size, shape, function, mass, and geometry of the heart. Acetyl coenzyme A (acetyl CoA), which can be made from glucose, amino acids, or fatty acids, is the precursor for the synthesis of cholesterol. In this article, authors explain concepts behind cardiac remodeling, its clinical ramifications, and the pathophysiological roles played by numerous various components, such as cell death, neurohormonal activation, oxidative stress, contractile proteins, energy metabolism, collagen, calcium transport, inflammation, and geometry. The levels of cholesterol are traditionally regulated by two biological mechanisms at the transcriptional stage. First, the SREBP transcription factor family regulates the transcription of crucial rate-limiting cholesterogenic and lipogenic proteins, which in turn limits cholesterol production. Immune cells become activated, differentiated, and divided, during an immune response with the objective of eradicating the danger signal. In addition to creating ATP, which is used as energy, this process relies on metabolic reprogramming of both catabolic and anabolic pathways to create metabolites that play a crucial role in regulating the response. Because of changes in signal transduction, malfunction of the sarcoplasmic reticulum and sarcolemma, impairment of calcium handling, increases in cardiac fibrosis, and progressive loss of cardiomyocytes, oxidative stress appears to be the primary mechanism that causes the transition from cardiac hypertrophy to heart failure. De novo cholesterol production, intestinal cholesterol absorption, and biliary cholesterol output are consequently crucial processes in cholesterol homeostasis. In the article's final section, the pharmacological management of cardiac remodeling is explored. The route of treatment is explained into different steps: including, promising, and potential strategies. This chapter offers a brief overview of the history of the study of cholesterol absorption as well as the different potential therapeutic targets.

The Ras family of proteins is tethered to the inner leaflet of the cell membranes which play an essential role in signal transduction pathways that promote cellular proliferation, survival, growth, and differentiation. KRas-4B, the most mutated Ras isoform in different cancers, has been under extensive study for more than two decades. Here we have focused our interest on the influence of cholesterol on the orientations that KRas-4B adopts with respect to the plane of the anionic model membranes. How cholesterol in the bilayer might modulate preferences for specific orientation states is far from clear. Herein, after analyzing data from in total 4000 ns-long MD simulations for four KRas-4B systems, properties such as the area per lipid and thickness of the membrane as well as selected radial distribution functions, penetration of different moieties of KRas-4B, and internal conformational fluctuations of flexible moieties in KRas-4B have been calculated. It has been shown that high cholesterol content in the PM favors OS1, exposing the effector-binding loop for signal transduction in the cell from the atomic level. We confirm that high cholesterol in the PM helps KRas-4B mutant stay in its constitutively active state, which suggests that high cholesterol intake can increase mortality and may promote cancer progression for cancer patients. We propose that during the treatment of KRas-4B-related cancers, reducing the cholesterol level in the PM and sustaining cancer progression by controlling the plasma cholesterol intake might be taken into account in anti-cancer therapies.

Oligonucleotides are key compounds widely used for research, diagnostics, and therapeutics. The rapid increase in oligonucleotide-based applications, together with the progress in nucleic acids research, led to the design of nucleotide analogs that when being part of these oligomers enhance their efficiency, bioavailability, or stability. One of the most useful nucleotide analogs are the first-generation bridge nucleic acids (BNA), also known as locked nucleic acids (LNA), which were used in combination with ribonucleotides, deoxyribonucleotides, or other analogs to construct oligomers with diverse applications. However, there is still room to improve their efficiency, bioavailability, stability, and, importantly, toxicity. A second generation BNA, BNANC (2'-O,4'-aminoethylene bridged nucleic acid), has been recently made available. Oligomers containing these analogs not only showed less toxicity when compared to LNA-containing compounds but in some cases also exhibited higher specificity. Although there are still few applications where BNANC-containing compounds were researched, the results are very promising warranting more efforts in incorporating these analogs for other applications. Furthermore, newer BNA compounds will be introduced in the near future offering great hope to oligonucleotide-based fields of research and applications.

A warning sign for impending cardio-vascular events is not fully established. In the process to plaque rupture, formation of vulnerable plaque is important, and oxidized cholesterols play important role in its progression. Furthermore, the significance of vasa vasorum penetrating medial smooth muscle layer and rich in atheromatous lesion should be paid attention. Cardio-ankle vascular index (CAVI) is new arterial stiffness index of the arterial tree from the origin of the aorta to the ankle. CAVI reflects functional stiffness in addition to structural stiffness. Rapid rise of CAVI means medial smooth muscle cell contraction, and strangling vasa vasorum. We reported rapid rise of CAVI in peoples after big earthquake, following high frequency of cardiovascular events. And we met several cases who showed rapid rise of CAVI a few weeks or months before suffering cardiovascular events. To explain these sequences of events, we proposed a hypothesis; A rapid rise of CAVI means medial smooth muscle contraction, strangling vasa vasorum, leading ischemia, necrosis of vulnerable plaque, then, the plaque ruptures. In individuals having high CAVI, further rapid rise of CAVI might be a warning sign for impending cardiovascular events. In such case, treatments to decrease CAVI had better to be taken soon.

Postprandial hyperlipidemia showing postprandial increase in serum triglyceride (TG) is atherogenic and associated with the development of coronary artery disease (CAD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed, however, this test is very time-consuming and is difficult to perform. Ele-vated serum TG levels reflect an increase in TG-rich lipoproteins (TRL) such chylomi-crons (CM), very low-density lipoproteins (VLDL) and their remnants (CM remnant [CMR] and VLDL remnant [VLDLR]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurements of apo B48 which is a constituent of CM and CMR, non-fasting TG which includes TG content in all lipoproteins including CM and CMR, non-high-density lipoprotein-cholesterol (non-HDL-C) which includes TRL and low-density lipoprotein, and remnant cholesterol, are useful to suspect the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an in-ducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with post-prandial hyperlipidemia have various atherogenic properties such as induction of in-flammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss and exercise, positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, bezafibrate, ezetimibe and eicosapentaenoic acid have shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glu-cagon like peptide 1 analogues, have shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments.

Hypertension (HT) is a very common risk factor and a frequent cause of morbidity and mortality worldwide mainly due to much increase in overweight (OW) and obesity that manifests in various forms of cardiovascular disease (CVD). There are a number of factors that may cause overweight hypertension (OHT). However, we planned to conduct the present work to study the HT and OHT men for finding the variation, interrelationship and association of important cytokines mainly serum leptin (Lep) and tumor necrosis factor-alpha (TNF-α), serum testosterone (ST), total cholesterol (TC) and inflammatory status by measuring interleukin-6 (IL-6). Three groups of subjects, the normal controls (NC; n:98; age range: 51-60 years), HT (n: 97; age range: 51-60 years) subjects, and OHT (n: 97; age range: 51-60 years) subjects were studied. Comparisons for Lep, ST, TNF-α, IL-6 and TC levels for the subject groups showed significant variations. The ST indicated significant difference only for NC vs. OHT. The IL-6 gave significant difference for NC vs. OHT and HT vs. OHT. The one-way ANOVA showed significant difference among groups for BMI, TC, IL-6, TNF-α, ST and Lep levels. Significant positive linear correlation for all groups among Lep, TNF-α, IL-6 and TC were found. The ST against TC for HT and OHT groups presented non-significant negative linear correlations. The ST showed significant negative linear correlation with other variables. Conclusively, the present study uncovers the interactive impact of serum leptin, TNF-α, testosterone, total cholesterol and IL-6 in hypertensive and overweight-related hypertensive men.

Multi-board electronic cases with high density and high power modules are widely used in industrial power supply management. With the improvement of case performance and miniaturization requirements, heat dissipation becomes one of the important factors to be considered in the design process. First,The existing small electronic thermal design methods focus on heat dissipation structure or heat source layout optimization,and ignores on-load test for modeling analysis. Second,The selected power module has on-load power consumption, resulting in relatively low calorific value and the effectiveness of thermal design cannot be verified. Third, The thermal lacks Intelligent monitoring and feedback control mechanism. In order to solve these problems, this paper designs a kind of heat dissipation case with intelligent temperature control based on high-power and high-density power supply array. Based on the extremely miniaturization design principle, we adopt the composite heat dissipation mode based on conduction and supplemented by forced air cooling . The case is made of magnesium and aluminum alloy with a perforated design. Finally, we compare and analyze with the existing cooling design. The results show that the case is smaller in volume, and the cooling performance parameters are slightly better than the existing case. Under the condition of high-density and high-power design, The output power of the whole system is not less than 10kw and the lowest packing-level density is not less than 47w/cm2 with high reliability, portability and practicability. It also provides technical support and prototype support for the standardized design of similar power arrays.

Infertility affects millions worldwide, posing a significant global health challenge. The proteomic analysis of follicular fluid provides a comprehensive view of the complex molecular landscape within ovarian follicles, offering valuable information on the factors influencing oocyte development and on the overall reproductive health. The follicular fluid is derived from the plasma and contains various proteins that can have different roles in oocyte health and infertility and this fluid is a critical microenvironment for the developing oocytes as well. Using HPLC/MS method we investigated the protein composition of the follicular fluid and after classification we did relative quantification of the identified proteins in the pregnant (P) and non-pregnant (NP) groups. Based on the protein-protein interaction analysis ALB and ApoA1 was found to be hub proteins and the quantitative comparison of the P and NP groups resulted significantly lower concentration of ApoA1 and HDL-cholesterol in the P group. As both molecules are involved in the cholesterol transport, we also investigated their role in the development of oocytes and in the prediction of fertility.

G-protein coupled receptors (GPCRs), one of the largest superfamilies of cell-surface receptors, are heptahelical integral membrane proteins that play critical roles in virtually every organ system. G-protein-coupled receptors operate in membranes rich in cholesterol, with an imbalance in cholesterol level within the vicinity of GPCR transmembrane domains affecting the structure and/or function of many GPCRs, a phenomenon that has been linked to several diseases. These effects of cholesterol could result in indirect changes by altering the mechanical properties of the lipid environment or direct changes by binding to specific sites on the protein. There are a number of studies and reviews on how cholesterol modulates class A GPCRs, however, this area of study is yet to be explored for class C GPCRs, which are characterized by a large extracellular region and often form constitutive dimers. This review highlights specific sites of interaction, functions, and structural dynamics involved in the cholesterol recognition of the class C GPCRs. We summarize recent data from some typical family members to explain the effects of membrane cholesterol on the structural features and functions of Class C GPCRs and speculate on their corresponding therapeutic potential.

Niemann-Pick type C (NPC) disease is a childhood autosomal recessive inherited rare neuro-degenerative disease, characterized by the accumulation of cholesterol and glycosphingolipids, implicating the autophagy-lysosome system. Inhibition of soluble epoxide hydrolase (sEH), an enzyme that metabolizes epoxy fatty acids (EpFAs) to 1,2-diols, exerts beneficial effects in mod-ulating inflammation and autophagy, critical features of the NPC disease. This study aimed to evaluate the effects of UB-EV-52 a sEH inhibitor (sEHi) in the Npc mouse model by administering for 4 weeks (5 mg/kg/day). Behavioral and cognitive assays (open field test (OF), elevated plus maze (EPM), novel object recognition test (NORT) and object location test (OLT) demonstrated that treatment produced an improvement in short- and long-term memory as well as in spatial memory. Moreover, the treatment with UB-EV-52 increased body weight and the lifespan by 25% and re-duced gene expression of the inflammatory markers (i.e. Il-1β and Mcp1) and improved oxidative stress (OS) markers (iNOS and Hmox1) in the treated Npc mice group. Regarding the autophagic markers, we surprisingly found significantly reduced levels of the ratio LC3B-II/LC3B-I and a significant reduction of brain protein levels of lysosomal-associated membrane protein-1 (LAMP-1) in Npc mice treated group compared to non-treated. Lipid profile analysis showed a significant reduction in lipid storage in the liver and some slight changes in brain tissue in treated Npc mice compared to non-treated groups. Thus, Our results suggest that the pharmacological inhibition of sEH ameliorates most of NPC’s characteristic traits in mice, demonstrating that sEH can be considered a potential therapeutic target for this condition.

Patients with schizophrenia (SCZ) are at high risk of cardiovascular disease (CVD) due to an inherited predisposition, a sedentary life style and the use of antipsychotic medications. Several approaches have been taken to minimize this risk but results continue to be unsatisfactory. A potential alternative is prescribing Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs decrease platelet aggregation and reduce the risk of coronary heart disease in patients with depression. We therefore aim to investigate whether there is evidence that supports the use of SSRIs to reduce the risk for CVD in SCZ. A systematic review of the literature revealed five published reports relating to the impact of SSRIs on CV risk in SCZ. Three trials assessed the influence on metabolic parameters of fluvoxamine when combined with clozapine. Two of those studies found improvements with fluvoxamine. Of the other two reports, one indicates SSRIs as a group caused minimal but statistically significant increments in total cholesterol, LDL and triglyceride. The second report suggests that when SSRIs are combined with antipsychotics, the metabolic impact depends on the antipsychotic prescribed. While there are promising results, further studies are needed to establish the impact of SSRIs on CV risk in SCZ.

Super-high (x400) magnification dermoscopy (D400) is a new non-invasive imaging technique that has been shown to add information for the differential diagnosis of melanocytic lesions in a pilot study. Our study aimed to confirm if D400 can add details for the discrimination of clinically atypical nevus and melanoma. This is a retrospective observational, multicentric study enrolling patients who received an x20 (D20) and x400 (D400) magnification dermoscopic examination of pigmented skin lesions. Dermoscopic images were retrospectively evaluated by three observers for the presence/absence of nine D20 and twenty D400 dermoscopic features defined in the previous pilot study. Univariate and multivariate analyses were carried out to find predictors of benign and malignant behaviors. At D20 atypical pigment network, blue-whitish veil, atypical vascular pattern, regression, and homogenous pattern were more frequent in melanoma than in nevi (p&lt;0.001). At D400 melanoma showed more frequently than benign lesions melanocytes with an irregular arrangement and irregular in shape and size (p&lt;0.001). Network with edged papillae was more frequent in benign lesions than melanomas (p&lt;0.001). Our study confirms that D400 can identify melanocytes with an irregular arrangement and irregular in shape and size in melanomas, adding information to the conventional D20 examination.

Chitosan (CTS) is widely used in agriculture as a soil amendment, plant growth regulator and promoter of cold resistance. However, the effects of CTS on strawberry seedlings under the combined stress of high-temperature and high-light are unclear. In this study, Xuelixiang strawberry was used as a test material, and 100 mg·kg-1 CTS solution was sprayed onto the leaves. We measured the chlorophyll content, membrane peroxidation, reactive oxygen species content, antioxidant enzyme content, AsA-GSH cycle activity and other related indicators of strawberry seedling leaves under the combined stress of high-temperature and high-light and found that CTS can increase the contents of antioxidants, increase the contents of osmotic adjustment substances, increase the activity of antioxidant enzymes activity,; remove reactive oxygen species over time, reduce the damage of reactive oxygen species to photosynthetic organs and cell membranes, and improve the photosynthesis efficiency of leaves of strawberry plants under high-temperature and high-light stress, thereby reducing damage to strawberry seedlings caused by high-temperature and high-light.

In-situ injection of steam for heating of the subsurface is an efficient method for the recovery of oil and gas from oil shale where permeability typically evolves with temperature. We reported measurements on Jimusar oil shales(Xinjiang, China) at different temperatures to 600℃ and under recreated in situ triaxial stresses to obtain permeability evolution with temperature and stress. Permeability of tight oil shales evolves with temperature to a threshold temperature and peak temperature. The threshold temperature was subjected to triaxial stresses. For Jimusar oil shale, the threshold temperature ranges from 200℃ to 250℃ at ground stress of buried depth of 500m and from 350℃ to 400℃ at buried depth of 1000m. The peak temperature was almost not subjected to triaxial stress and the range is from 450℃ to 500℃ for all Jimusar samples. Pyrolysis plays an important role in permeability evolution and fundamentally changes permeability tendency and magnitude. At high temperature permeability exhibits a little reduction due to stress effect but still remains a high level due to pyrolysis. The above results show that oil shale mass can change from tight porous media into highly permeable media and oil & gas can easily flow through oil shale stratum.

High-strength wastewaters from a variety of sources, including the food industry, domestic septage and landfill leachate, are often hauled to municipal wastewater treatment plants (WWTPs) for co-treatment. Due to their high organic loadings, these wastewaters can cause process upsets in both the WWTP’s liquid and solids treatment trains and consume organic treatment capacity, leaving less capacity available to service customers in the catchment area. A novel pre-treatment method, the Waste Activated Sludge-High Rate (WASHR) process, is proposed to optimize the co-treatment of high-strength wastewaters. The WASHR process combines the contact stabilization and sequencing batch reactor processes. It utilizes waste activated sludge from the municipal WWTP as its biomass source, allowing rapid start-up. Bench scale treatment trials of winery wastewater confirm the WASHR process can reduce loadings on the downstream WWTP’s liquid treatment and solids treatment trains. A case study approach is used to confirm the economic viability and environmental sustainability of the WASHR process compared to direct co-treatment using life cycle cost analyses and greenhouse gas emissions estimates.

Next Generation Sequencing (NGS), now widely used in the clinical setting, offers an efficient and comprehensive molecular approach for patients with Familial hypercholesterolemia (FH). Although the dominant form of disease is mostly due to low-density lipoprotein receptor (LDLR) small-scale pathogenic variants, approximately 10% of molecularly defined FH cases are due to Copy Number Variations (CNVs). Here, we report a novel large deletion of the LDLR gene involving exons 4–18, identified by bioinformatic analysis of NGS data in an Italian family. A long PCR strategy was employed for breakpoint region analysis where an insertion of 6 nucleotides (TTCACT) was found. Two Alu sequences, identified within intron 3 and exon 18, could underlie the identified rearrangement by a Nonallelic Homologous Recombination (NAHR) mechanism. NGS proves to be a powerful tool used to precisely identify CNVs, in addition to small-scale variants in FH-related genes. At this purpose, the use and implementation of this cost-effective, efficient molecular approach meets the clinical need for personalized diagnosis in FH cases.

The salt marshes, lying at the land-sea temperate interface, furnish a plethora of ecosystems services such as biodiversity niche support, ocean-climate change regulation, ornithology recreo-tourism or plant gathering by hand. They undergo significant worldwide losses due to their conversion into crop fields and to their spatial compression between the rising sea-level and the armoring shoreline. Their monitoring however requires to use a suite of remote sensing sensors to embrace the regional scale while capturing the plant details. This research innovatively adopts a multiscale approach using a cascading spaceborne and airborne process, from the 10-m Sentinel-2, through the 3-m Dove, to the 0.03-m unmanned airborne vehicle (UAV) imageries. The high to very high temporal resolution of the Sentinel-2 and Dove enabled to cover twenties and tens of km2 over five and four years, respectively, in the form of normalized difference vegetation index (NDVI) classes, associated with microphytobenthos, low, medium and high salt marsh vegetation, including the opportunistic Elyma genus. The NDVI was then modelled at the UAV scale (a few km2) using a three-layered NN prediction, providing the final near-infrared (NIR), and the intermediate red, green and blue reflectance imageries, calibrated/validated/tested with the Dove reflectance imageries (R2NIR=0.98, R2red=0.88, R2green=0.84, and R2blue=0.90). The 100fold increase in pixel size allowed to detect the decimeter-scale objects of the tidal flats and salt marshes, to enlarge the NDVI class ranges, and hold great promise to model other spectral bands at the UAV scale for further deeply enhancing the salt marsh mapping.

The cornerstone of molecular magnetism is a detailed understanding of the relationship between structure and magnetic behaviour, i.e. the development of magneto-structural correlations. Traditionally, the synthetic chemist approaches this challenge by making multiple compounds that share a similar magnetic core but differ in peripheral ligation. Changes in the ligand framework induce changes in the bond angles and distances around the metal ions which are manifested in changes to magnetic susceptibility and magnetisation data. This approach requires the synthesis of series of different ligands and assumes that the chemical/electronic nature of the ligands and their coordination to the metal, the nature and number of counter ions and how they are positioned in the crystal lattice, and the molecular and crystallographic symmetry have no effect on the measured magnetic properties. In short, the assumption is that everything outwith the magnetic core is innocent, which is a huge oversimplification. The ideal scenario would be to have the same complex available in multiple structural conformations, and this is something that can be achieved through the application of external hydrostatic pressure, correlating structural changes observed through high pressure single crystal X-ray crystallography with changes observed in high pressure magnetometry, in tandem with high pressure inelastic neutron scattering (INS), high pressure electron paramagnetic resonance (EPR) spectroscopy and high pressure absorption/emission/Raman spectroscopy. In this review, which summarises our work in this area over the last 15 years, we show that the application of pressure to molecule-based magnets can (reversibly): (1) lead to changes in bond angles, distances and Jahn-Teller orientations; (2) break and form bonds; (3) induce polymerisation/depolymerisation; (4) enforce multiple phase transitions; (5) instigate piezochromism; (6) change the magnitude and sign of pairwise exchange interactions and magnetic anisotropy and (7) lead to significant increases in magnetic ordering temperatures.

In response to a perceived epidemic of coronary heart disease, Ancel Keys introduced the lipid-heart hypothesis in 1953 which asserted that high intakes of total fat, saturated fat, and cholesterol lead to atherosclerosis and that consuming less fat and cholesterol, and replacing saturated fat with polyunsaturated fat, would reduce serum cholesterol and consequently the risk of heart disease. Keys proposed an equation that would predict the concentration of serum cholesterol (DChol.) from consumption of saturated fat (DS), polyunsaturated fat (DP), and cholesterol (DZ): ΔChol. = 1.2(2ΔS − ΔP) + 1.5ΔZ. However, the Keys equation conflated natural saturated fat and industrial trans-fat into a single parameter and considered only linoleic acid as the polyunsaturated fat. This ignored the widespread consumption of trans-fat and its effects on serum cholesterol and promoted an imbalance of omega-6 to omega-3 fatty acids in the diet. Numerous observational, epidemiological, interventional, and autopsy studies have failed to validate the Keys equation and the lipid-heart hypothesis. Nevertheless, these have been the cornerstone of national and international dietary guidelines which have focused disproportionately on heart disease and much less so on cancer and metabolic disorders, which have steadily increased since the adoption of this hypothesis.

Objective: The objective of our study was to explore the potential benefits of combining moderate alcohol consumption with regular vigorous physical activity on HDL-cholesterol levels and its potential positive impact on cardiovascular health. Material and method: The study comprised two groups: group A (102 patients) who consumed 1 gram of alcohol per day, specifically red wine, and increased their exercise levels in addition to their standard medical treatment, and group B (108 patients) who adhered only to their standard medical treatment. The patients were monitored for a year, during which various clinical parameters were observed. Results:Our study showed that moderate alcohol consumption, particularly red wine, along with increased physical activity levels, was associated with enhancements in exercise tolerance and elevated levels of HDL-cholesterol. Our findings suggest the efficacy of the intervention in improving lipid profiles, with the group that consumed alcohol as part of their treatment scheme, generally experiencing more pronounced positive effects. Statistically significant differences between groups in terms of angina evolution, AMI recurrence, or arrhythmias evolution were not found. However, there were important differences in terms of EF improvement and quality of life, with the alcohol consuming group displaying greater improvements in both aspects. Conclusions:In conclusion, our study emphasizes the potential benefits of combining moderate alcohol consumption, specifically red wine, with increased physical activity levels for improving exercise tolerance and enhancing HDL-cholesterol levels. However, further research and clinical trials are essential to fully understand the mechanisms and optimize the integration of these lifestyle elements for improved cardiovascular health outcomes.

Objective: The objective of our study was to explore the potential benefits of combining moderate alcohol consumption with regular vigorous physical activity on HDL-cholesterol levels and its potential positive impact on cardiovascular health. Material and method: The study comprised two groups: group A (102 patients) who consumed 1 gram of alcohol per day, specifically red wine, and increased their exercise levels in addition to their standard medical treatment, and group B (108 patients) who adhered only to their standard medical treatment. The patients were monitored for a year, during which various clinical parameters were observed. Results:Our study showed that moderate alcohol consumption, particularly red wine, along with increased physical activity levels, was associated with enhancements in exercise tolerance and elevated levels of HDL-cholesterol. Our findings suggest the efficacy of the intervention in improving lipid profiles, with the group that consumed alcohol as part of their treatment scheme, generally experiencing more pronounced positive effects. Statistically significant differences between groups in terms of angina evolution, AMI recurrence, or arrhythmias evolution were not found. However, there were important differences in terms of EF improvement and quality of life, with the alcohol consuming group displaying greater improvements in both aspects. Conclusions:In conclusion, our study emphasizes the potential benefits of combining moderate alcohol consumption, specifically red wine, with increased physical activity levels for improving exercise tolerance and enhancing HDL-cholesterol levels. However, further research and clinical trials are essential to fully understand the mechanisms and optimize the integration of these lifestyle elements for improved cardiovascular health outcomes.

Cardiovascular diseases (CVDs) represent the leading cause of global mortality with 1,7 million deaths a year. One of the alternative systems to drug therapy to minimize the risk of CVDs is represented by alpha-linolenic acid (ALA), an essential fatty acid of the Omega-3 series, known for its cholesterol-lowering effect. The main purpose of this review is to analyze the effects of ALA and investigate the relevant n-6/n-3 ratio in order to maintain functionally beneficial effects. Concerning the lipid-lowering preventive effects, ALA may favorably affect the values of LDL-C and triglycerides in either adult and pediatric populations and it has a positive and protective effect against hypertension, suggesting that ALA is an useful diet-related antihypertensive compound. According to the 2009 EFSA statement, dietary ALA may contribute to reducing the risk of CVDs, thanks to anti-hypertensive, anti-atherosclerotic and cardio-protective effects.

In the face of the newly emergent COVID-19 pandemic, researchers around the world are racing to identify efficacious drugs capable of preventing or treating its infection. They are doing that by testing already available and approved antimicrobials for their rapid repurposing against COVID-19. Using the data emerging on the comparable efficacy of various compounds having different mechanisms of action and indications, I suggest in this report, their potential mechanistic convergence. Specifically, I highlight the lysosome as a key possible therapeutic target for COVID-19, proposing one of the lysosomal storage disorders, Niemann-Pick type C disease (NPC), as a prototypical condition with inherent resistance or an “unfavorable” host cell environment for viral propagation. The included reasoning evolves from previously generated data in NPC, along with the emerging data on COVID-19. The aim of this report is to suggest that pharmacological induction of a “transient” NPC-like lysosomal dysfunction, could hold answers for targeting the ongoing COVID-19 pandemic.

Val-Phe-Val-Arg-Asn (VFVRN) has been identified and screened from lipid-lowering chickpea peptides (ChPs) by using a pharmacokinetic model in our previous experiment. The present study was conducted to investigate its effects and mechanisms on lipid metabolism. A high-fat diet C57BL/6J mice model and 3T3-L1 preadipocyte cell model were used. VFVRN was found to significantly decrease the levels of some blood lipids. The expressions of LDL receptor (LDLR), peroxisome proliferator-activated receptors (PPAR)α, liver X receptor (LXR)α, cholesterol 7α-hydroxylase (CYP7A1) and AMP-activated protein kinase (p-AMPK) in liver were up-regulated by VFVRN treatment. The expressions of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), fatty acid synthetase (FAS), 1-aminocyclopropane-1-carboxylate synthetase (ACC), sterol regulatory element-binding protein (SREBP)-1c and SREBP-2 in liver were significantly (P<0.05) down-regulated. Additionally, the expressions of PPARα and PPARγ in adipose tissues were up-regulated by VFVRN significantly (P<0.05). VFVRN might also contribute to transintestinal cholesterol efflux (TICE) by up-regulating the expressions of LXRα and ATP binding cassette G5/8 transporters (ABGC5/8). Moreover, VFVRN promoted 3T3-L1 preadipocyte apoptosis by up-regulating the expressions of BaX, cleaved Caspase-3 and down-regulating Bcl-2. VFVRN had potent effects in reversing metabolic disorders of blood and liver in a high-fat diet mice model, as well as to promote the apoptosis of 3T3-L1 preadipocytes.

Rocks are materials with a wide variety of structures and properties. These can be unprocessed conglomerates of conglomerated minerals as well as crystallized outcrop or metamorphic rocks. Their processing, especially shaping, poses many technological difficulties. Therefore, it is very important to answer the question of how these natural materials yield to high-pressure water jet and abrasive water. It is equally important to determine the effect of key process parameters such as pressure, water nozzle diameter and feed rate on cutting efficiency. The first two parameters determine the water output and power of the jet, while the third determines the jet erosion time per unit volume of material. Their interdependence, using appropriate evaluation indicators, allows to determine the energy intensity of processing and directions for its minimization.

In the recent concrete industry, high fluidity concrete is being widely used for the pouring of dense reinforced concrete. Normally, in the case of high fluidity concrete, it includes high binder contents, so it is necessary to replace part of the cement through admixtures such as fly ash to procure economic feasibility and durability. This study shows the mechanical properties and field applicability of high fluidity concrete that using mass of fly ash as alternative materials of cement. The high fluidity concrete mixed with 50% fly ash was measured to manufacture concrete that applies low water/binder ratio to measure the mechanical characteristics as compressive strength and elastic modulus. Also, in order to evaluate the field applicability, high fluidity concrete containing high volume fly ash was evaluated that fluidity, compressive strength, heat of hydration and drying shrinkage of concrete.

The main objective was to analyze the influence of silicon content on high-temperature oxidation of low-alloy steels. Samples of AISI 1045, AISI 5160, and AISI 9254 steels, with different silicon contents, were oxidized at an isothermal temperature of 1000°C for times of 20 minutes, 40 minutes, and 60 minutes. The oxide layers formed mainly contain hematite, magnetite wustite, and fayalite. The average thickness of the oxide layer can decrease with an increase in silicon content below 1% but can increase for contents greater than 1% due to the difference in density between fayalite and iron oxides. Silicon tends to accumulate on the surface of steel and form a SiO2 film in the early stages of oxidation, which can control the oxidation process. The eutectic compound FeO+Fe2SiO4 forms at the oxide-steel interface, and its thickness increases with oxidation time and the silicon content present. The SiO2 film tends to decrease with oxidation time and silicon content.

Chemical flooding methods are used to recover the remaining oil after water flooding, and surfactant-polymer (SP) flooding is an important chemical flooding technology. It is of great significance to design and screen high-performance oil displacement agents in order to overcome the increasingly challenging high temperature (&gt;70 ℃) and high salinity (>10,000 mg/L) reservoirs. Based on the characteristics of high temperature (70 ℃) and high salinity (151,000 mg/L) in the Qinghai Gasi reservoir, the performance of the SP flooding system was studied. This study considered interfacial tension, emulsification, viscosity, compatibility, and oil displacement efficiency. The selected formula demonstrated high resistance to both salinity (151,000 mg/L) and temperature (70 ℃), characterized by a low oil-water interfacial tension (10-2 mN/m) and high viscosity (18.13 mPa.s). After water flooding achieved an oil recovery rate of 64.64%, the subsequent replacement rate of crude oil increased by 26.95%, confirming that SP flooding can be used as a technology for enhancing oil recovery in high-temperature, high-salinity reservoirs represented by Qinghai Gasi reservoirs.

Intended for the high voltage gain and wide-range operation of DC/DC converters for photovoltaic energy storage systems, a topology for four-phase interleaved DC/DC converters for photovoltaic power generation is proposed. This topology increases output voltage for output in series, and reduces the input current ripple by paralleling the input. Compared with traditional boost converter topology, the proposed topology reduces the output current and output voltage ripple, reduces the stress of the switching device, and reduces the withstanding voltage of the output capacitor under the premise of ensuring the boost ratio. Experimental results show that the maximum efficiency of the converter reaches 95.37%. Compared with traditional boost converters, the proposed converter offers obvious advantages in efficiency under the conditions that the output voltage and load are variable.