ARTICLE | doi:10.20944/preprints202106.0144.v1
Subject: Keywords: Diabetic; Diabetic Mellitus; Diabetic Prediction; PIMA diabetic dataset; Female diabetic Patients; Machine Learning
Online: 4 June 2021 (15:25:16 CEST)
Diabetics or Diabetic Mellitus is a metabolic disorder of blood sugar levels in the human body. It is a major non-communicable disease and involved many serious health risk issues. This disease is rapidly increasing in India. It is a chronic condition and it occurs when a body doesn't produce enough insulin hormone to control the blood sugar level. In this study, different variables have been analyzed that cause the diabetics, and different machine learning algorithms are used to predict whether an unknown sample is diabetes or not. For this purpose, PIMA diabetic detection for Female patients was used. Here 10 different classification model is used for prediction. Finally, the detailed performance analysis of the different variables of the PIMA dataset and also the classification model are discussed.
ARTICLE | doi:10.20944/preprints202211.0274.v1
Subject: Medicine & Pharmacology, Ophthalmology Keywords: telemedicine; diabetic retinopathy; diabetic macular edema; epidemiology; COVID-19
Online: 15 November 2022 (04:40:58 CET)
(1) Background: Diabetic retinopathy (DR) is a complication of diabetes mellitus (DM) and the COVID-19 pandemic has affected screening programmes. The aim of present study was to determine the impact of the COVID-19 pandemic on the screening of diabetes patients in our Health Care Area (HCA); (2) Methods: A retrospective study of patients with DM who had attended the DR screening programme between January 2015 and June 2022. We studied attendance, DM metabolic control and DR incidence. (3) Results: Screening for DR decreased in the first months of the pandemic. Incidence of mild and moderate DR remained stable throughout the study, and we observed a little increase in severe-DR, proliferative-DR and neovascular glaucoma, during 2021 and 2022. (4) Conclusions: The COVID-19 pandemic caused a reduction in the number of patients screened for DM, although its effect on DR seems limited, with a similar number of patients with DR throughout 2015 to 2022, despite the number of patients with severe-DR and proliferative-DR increased in 2021 and 2022.
ARTICLE | doi:10.20944/preprints202111.0303.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: Microvascular complications; Cardiac autonomic neuropathy; Diabetic peripheral neuropathy; Diabetic nephropathy; Diabetic retinopathy; patient profiles; machine learning
Online: 17 November 2021 (11:54:23 CET)
Microvascular complications are one of the key causes of mortality among type-2 diabetic patients. This study was sought to investigate the use of a novel machine learning approach for predicting these complications from patient demographic, clinical, and laboratory profiles only. A total of 96 Bangladeshi participants having type-2 diabetes were recruited during their routine hospital visits. All patient profiles were assessed by using a Chi-squared (2) test to statistically determine the most important markers in predicting four microvascular complications; namely cardiac autonomic neuropathy (CAN), diabetic peripheral neuropathy (DPN), diabetic nephropathy (NEP), and diabetic retinopathy (RET). A machine learning approach based on random forest (RF) and support vector machine (SVM) was then developed to ensure automated clinical testing for microvascular complication in diabetic patients. The highest prediction accuracies were obtained by RF using diastolic blood pressure, Albumin-Creatinine ratio, and gender for CAN testing (98.67%), Microalbuminuria, smoking history, and hemoglobin A1C for DPN testing (67.78%), Albumin-Creatinine ratio for NEP testing (100%), and hemoglobin A1C, Microalbuminuria, and smoking history for RET testing (84.38%). This study suggests machine learning as a promising automated tool for predicting microvascular complications in diabetic patients using their profiles, which could help prvent those patients from further microvascular complications leading to early death.
ARTICLE | doi:10.20944/preprints201908.0285.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: oral health , pre-diabetic, diabetic, oral systemic, screening, H1A1c, Findrisk , periodontal
Online: 27 August 2019 (11:58:44 CEST)
Pre-diabetes is a serious health condition where blood sugar levels are higher than normal, but not high enough yet to be diagnosed as type 2 diabetes. Pre-diabetes puts one at an increased risk of developing type 2 diabetes and heart disease Methodology: A cross-sectional study was carried out on 384 patients aged 20-70 years old, attending the dental clinics to assess the risk for diabetes, using the FINDRISC questionnaire, HbA1c blood test and a periodontal examination. Results: The mean age of participants was 38.90±10.74. 32.3% were categorized as no risk, 46.6% low risk, while 19% and 2.1% moderate and high risk of developing diabetes respectively. Tests for serum HbA1c Level showed 46.1 % had normal HbA1c followed by 18.0% and 3.6 % were pre-diabetic and diabetic respectively. 19.3% of participants had periodontal pockets measuring more than 4mm and 15.9% measuring more than 6mm. Conclusion: The study has proven to be useful in identifying patients at high-risk of developing diabetes. Controlling and managing periodontal disease could be a new aspect to include in the standards for diabetes care. Dental settings could be a successful platform to carry out the screening and risk stratification of pre-diabetic patients.
ARTICLE | doi:10.20944/preprints201809.0153.v1
Online: 10 September 2018 (06:26:55 CEST)
Background: diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause for end stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. The mesenchymal stem cells (MSCs) derived exosomes are currently considered as a new promising therapy in chronic renal injury. However, the renal protective mechanism of exosomes on DN has not been completely understood. We examined the potential role of MSCs derived exosomes in enhancement of autophagy activity and its effect on DN. In our study we used five groups of rats; control, DN, DN treated with exosomes, DN treated with 3-methyladenine (3-MA) and chloroquine (inhibitors of autophagy) and DN treated with 3-methyladenine (3-MA) and chloroquine and exosomes groups. We assessed renal functions, morphology and fibrosis. Moreover, autophagy markers; mTOR, Beclin-1, light chain-3 (LC3-II), and LC3-II/LC3-I ratio were detected. Additionally, electron microscopy was used for detection of autophagosomes. Results: Exosomes markedly improved the renal functions and showed histological restoration of renal tissues with significant increase in LC3 and Beclin-1 besides the significant decrease in mTOR and fibrotic markers expression in renal tissue. All previous effects were partially abolished by the autophagy inhibitor, chloroquine and 3-MA. Conclusions: we conclude that autophagy induction by exosomes could attenuate DN in a rat model of streptozotocin-induced diabetes mellitus.
REVIEW | doi:10.20944/preprints202301.0096.v1
Subject: Medicine & Pharmacology, Other Keywords: Diabetes Mellitus; Diabetic Complications; Pyroptosis; Bibliometrics
Online: 5 January 2023 (03:37:02 CET)
Objective: To visualize and analyze the published literature on diabetes and pyroptosis based on a bibliometric approach, so as to provide a comprehensive picture of the hot research directions and dynamic progress in this field. Methods: This study was based on the web of science core collection database to conduct a comprehensive search of the published literature in the field of diabetes and Pyroptosis from January 1985 to August 2022, including the published research literature in this field, as well as a visual analysis of the number of citations, year of publication, journal, author, research institution, country, and research topic. Results: A total of 139 literature on research related to diabetes and cellular scorch from 2011 to 2022 were retrieved, with a total of 3009 citations and a maximum of 255 citations for a single article, which had a first authorSchmid-Burgk, JL The first author of this article is from Germany; among 20 publishing countries, China leads with 100 articles; among 222 publishing institutions, Harbin Medical University leads with 18 articles and 184 citations; among 980 authors, Chen, X from China tops the list of high-impact authors with 5 articles and 29 citations; Among the 98 journals, "CELL DEATH DISEASE" ranked first in both volume and high impact journals with 4 articles and 29 citations; among 349 keywords, "pyroptosis" ranked first with a cumulative frequency of 65 times. The cluster analysis was divided into three categories, chronic complications of diabetes and pyroptosis (67 articles), diabetes and pyroptosis (60 articles), and diabetes combined with other diseases and pyroptosis (12 articles), and the number of articles related to diabetes and its chronic complications increased rapidly from 2019, among which, diabetic cardiomyopathy (27 articles) had the highest number of articles. Conclusions: Based on a comprehensive analysis of published literature in the field of diabetes and pyroptosis from 2011-2022, this study achieved a visual analysis of studies with significant and outstanding contributions to the field, thus framing a picture showing the development and changes in the field. At the same time, this study provides research information and direction for clinicians and investigators to conduct diabetes and pyroptosis related research in the future.
CASE REPORT | doi:10.20944/preprints202207.0045.v1
Online: 4 July 2022 (09:32:17 CEST)
Management of diabetic foot ulcers (DFUs) presents challenges to even the most experienced wound care providers. Because of the chronic, non-healing nature of many DFUs, advances in the treatment and care of this disease process are particularly relevant. This case study aims to report the efficacy of the application of dehydrated amniotic membrane allograft (DAMA) to a diabetic foot ulcer. The patient in this study is a 44-year-old male who presented with an aggressive infection on his right foot, which resulted in an open wound of 18 months duration. This patient received weekly applications of dual-layer DAMA over seven weeks. Upon examination at the initial application, the wound was classified as a Wagner grade 3 with necrosis of the underlying muscle. Upon inspection at the final visit, the wound was closed entirely. The results that were shown include improvements in the size, depth, edges, necrotic tissue amount, and epithelization of the wound. This case study demonstrates that the ap-plication of DAMA has the potential to augment the body’s natural DFU healing response; however, future nonrandomized and randomized controlled trials are needed to establish its efficacy further.
ARTICLE | doi:10.20944/preprints202211.0159.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: care wound; wound diabetic; honey; staphylococcus aureus
Online: 9 November 2022 (01:07:32 CET)
Background : Diabetic wounds are very easy to experience complications in the form of infection due to bacterial invasion, and sugar conditions blood which tall encourage the growth of bacteria.Bacteria that can cause infection in diabetic wounds wrong one is staphylococci aureus . Wound diabetes can treated with honey. Honey contains antibacterial , antioxidant and hydrogen peroxide properties that help kill bacteria dangerous. Objective : The purpose of this study was to determine the effect of the wound dressing contains honey against bacterial colonization Staphylococcus aureus on wound diabetic . Methods : The research design used is pre-experimental with o ne-group pre-test and post-test design . Sampling method using consecutive sampling as many as 7 respondents. Results : Analysis data use test dependent t-test and obtained score p value 0.000 ( p value < = 0.05), so could concluded there is influence care wound use honey to colonization bacteria Staphylococcus aureus in wounds diabetic Diabetes Mellitus patients in the region work Public health center Banjarmasin . Conclusion : best Use honey as product care wound because nature the antibacterial which could prevent infection and speed up process healing wound .
REVIEW | doi:10.20944/preprints202202.0353.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: Diabetic; Chronic Kidney Disease; Metformin; Acidosis Lactate
Online: 28 February 2022 (09:28:33 CET)
Background: Diabetes Mellitus is a metabolite disorder with parameters of high blood sugar levels. In the management of diabetes can be used the drug metformin is the gold of choice to achieve a therapeutic effect and rarely causes side effects of the drug, but it still has debate view. However, if used in excessive doses for patients with kidney disease, it will be contraindicated with side effects such as lactic acidosis. Objective: This study aims to evaluate the side effect of Metformin for diabetic kidney diseases (DKD) patients. Method: This study used the Narrative Review Method that was obtained from 2011 to 2021, in the English language from PubMed, Google Scholar, and Cochrane Library. Results: Metformin is at the forefront of the treatment of type 2 diabetes mellitus (DM2). Metformin is likely to have lactic acidosis-related adverse effects in chronic kidney disease (CKD) patients, such as increased arterial lactate. Lactic acidosis is defined as an increase in arterial lactate with an indicator of more than five mmol/L and an arterial blood pH of less than 7.35. Metformin-induced lactate levels are considered to be below the parameters. DKD risk factors can be conceptually classified as several susceptibility factors, initiation factors, and developmental factors. The two most prominent risk factors are hyperglycemia and hypertension. Conclusion: Metformin can increase lactate levels in CKD patients but is still below the parameters of lactic acidosis. This study may have some weaknesses and requires further prospective research to validate the results.
COMMUNICATION | doi:10.20944/preprints202106.0364.v2
Subject: Medicine & Pharmacology, Other Keywords: Diabetic foot infection; Sonication Method; Microbiological diagnosis.
Online: 24 November 2021 (11:51:36 CET)
We hypothesized that biofilm production occurs on stainless steel when incubated with tissue specimens in thioglycolate broth media (TBM). In a diabetic foot infection (DFI) cohort, applying the Kirschner wire and conventional methods were more sensitive than applying only the latter (CI 90%; 0.167 versus 0.375).
ARTICLE | doi:10.20944/preprints201809.0282.v1
Online: 16 September 2018 (10:02:14 CEST)
Background. Nanotechnology is promising field for generating new applications. A green synthesis of nanoparticles through biological methods using plant extract have a reliable and ecofriendly approach to improve our global environment. Methods. Silver nanoparticles (AgNPs) were synthesized using aqueous extract of Anagalis arvensis L and silver nitrate and were physicochemically characterized. Results. The stability of AgNPs toward acidity, alkalinity, salinity and temperature showed that they remained stable at room temperature for more than two months. The SEM and TEM analysis of the AgNPs showed that they have a uniform spherical shape with an average size in the range of 40–78 nm. Further 1-Dibhenyl-2-Picrylhydrazl radical in Anagalis arvensis L.mediated AgNPs showed a maximum activity of 98% at concentration of 200μg/mL. Hydrogen peroxide scavenging assay in Anagalis arvensis L. mediated AgNPs showed a maximum activity of 85% at concentration of 200μg/mL. Reducing power of Anagalis arvensis L.Ag NPs exhibited a higher activity of 330 μg/mL at concentration of 200 μg/mL. These NPs have cytotoxic effects against brine shrimp (Artemia salina) nauplii with a value of 53% LD 178.04μg/mL. Conclusion. The AgNPs synthesized using Anagalis arvensis L. extract demonstrate a broad range of applications.
ARTICLE | doi:10.20944/preprints202003.0060.v1
Subject: Medicine & Pharmacology, Other Keywords: Alcaligenes faecalis; Diabetic foot ulcer; extensive-drug resistant
Online: 4 March 2020 (10:34:23 CET)
Background: Diabetic foot ulcers are an increasingly common complex problem and are associated with a very considerable health care burden. Diabetic foot ulcer with Alcaligenes faecalis infection is rarely reported in the literature. We report a case series of diabetic foot ulcer with Alcaligenes faecalis infection treated at our facility. Methods: We conducted a retrospective analysis of all patients with diabetic foot ulcer with Alcaligenes faecalis infection seen from January 2014 to April 2019. We analyzed the clinical characteristics, ulcer lesion classification, comorbidities, prior intravenous antibiotic use within three months, wound culture, antibiotics sensitivity test, and clinical outcomes of these patients. Results: Eight cases of diabetic foot ulcer with Alcaligenes faecalis infection were seen in five males and three females. The mean age was 54.6 years. All patients had other comorbidities, and all ulcer lesions were of chronic duration ( more than 14 days ). All wound cultures revealed polymicrobial infection, with two cases of diabetic foot with extensive-drug resistant Alcaligenes faecalis infection found in 2019. All patients needed intravenous antibiotic therapy and surgical interventions for the chronic ulcer lesion. The wound failed to heal in three patients. Conclusions: All diabetic foot ulcers with Alcaligenes faecalis infection were of chronic duration ( more than 14 days ) and had polymicrobial infection. Extensive-drug resistant Alcaligenes faecalis emerged in 2019. Definitive antibiotic therapy is necessary for all infected wounds and should be based on both the culture results and susceptibility data. All patients will need appropriate wound care, and most will need rapid surgical intervention for an optimal outcome.
ARTICLE | doi:10.20944/preprints201810.0489.v1
Subject: Physical Sciences, Other Keywords: diabetes mellitus; blood glucose; kidney; diabetic neuropathy; pancreas
Online: 22 October 2018 (10:45:08 CEST)
This present study was designed to find out whether the acankoreagenin showed the antidiabetic and renoprotective effects in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats. Type I diabetes was induced by a single intraperitoneal injection of STZ (70 mg/kg). At the end of the experiment, rats were euthanized and serum/plasma was separated for the determination of glucose, insulin, glycated hemoglobin A1c (HbA1c), C-peptide, biochemical parameters, and kidney function. One kidney was used for determining glutathione, superoxide dismutas, malondialdehyde, and tumor necrosis factor-alpha levels. The other kidney and pancreas were used for histopathological studies and immunohistochemical measurement of transforming growth factor beta (TGF-β) or NF-κB. Acankoreagenin (2 mg/kg) treatments led to a significant reduction in blood glucose assessed via oral glucose tolerance test (OGTT) in diabetic rats at 2 h. The treatment also resulted in improved body weight, decreased HbA1c, restored lipid profile, and renal oxidative stress. By inhibiting NF-κB, the release of proinflammatory cytokines was suppressed and by inhibiting TGF-β, the renal fibrosis was suppressed in STZ-induced diabetic rat model. Histopathological injury was also observed in pancreatic and renal tissues. These findings support the beneficial effect of acankoreagenin treatment in DN, which could be attributed to its antidiabetic and renoprotective effects.
REVIEW | doi:10.20944/preprints201704.0059.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: Keywords: vitamin D deficiency; diabetic retinopathy; meta-analysis.
Online: 11 April 2017 (06:16:22 CEST)
Background: Diabetic retinopathy (DR) is one of the most prominent pathological microvascular complications in diabetes. A series of studies reported that vitamin D deficiency was associated with increased prevalence of retinopathy in diabetic patients but the results were inconsistent. In this study we focused on evaluating the relationship between vitamin D deficiency and DR by conducting a meta-analysis of observational studies. Methods: Systematic computerized searches were performed in PubMed, MEDLINE, and the Cochrane Library for relevant original articles till November 20, 2016. The pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated to assess the associated value of vitamin D deficiency to the risk of DR. 9 studies including 6332 participants were subjected to final analysis. Results: The results indicated that vitamin D deficiency increases the risk of DR (OR = 1.57, 95% CI 1.32-1.87) with a little heterogeneity (I2 = 23%). In addition, the subgroup analysis demonstrated that there were obvious heterogeneities in T2DM (I2 = 47.8%). Sensitivity analysis showed that the results were relatively stable and reliable. Conclusion: our meta-analysis demonstrated that vitamin D deficiency could increase the risk of DR.
REVIEW | doi:10.20944/preprints202209.0165.v1
Subject: Engineering, Biomedical & Chemical Engineering Keywords: Diabetic foot; Diabetic neuropathies; Peripheral arterial disease; Foot ulcer; Gait; Walking; Postural balance; Wearable electronic devices; Gait analysis; Digital technology
Online: 13 September 2022 (09:28:22 CEST)
People with diabetic foot frequently exhibit poor gait and balance. However, there is no review to inform digital biomarkers of poor gait and balance related to diabetic foot, measurable by wearables outside traditional gait laboratories. Such information could assist in designing remote patient monitoring platform to track changes in gait and balance dysfunction among people with diabetic foot for timely referral and intervention. Accordingly, we conducted a web-based review using PubMed. Our search was limited to human subjects and English-written papers published in peer-reviewed journals. We identified 20 papers in this review. We found preliminary evidence of digital biomarkers of gait and balance dysfunction in people with diabetic foot, measured by wearables, such as slow gait speed, large gait variability, unstable gait initiation, and large body sway. However, due to heterogeneities in included papers in terms of study design, movement tasks, and small sample size, more studies are recommended to confirm this preliminary evidence. Additionally, based on our review, we recommend establishing appropriate strategies to successfully implement wearable-based assessment into clinical practice for diabetic foot care.
ARTICLE | doi:10.20944/preprints202111.0219.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Diabetic Ketoacidosis; Mental health; Type 1 diabetes; Transition; Glycemia
Online: 12 November 2021 (12:04:43 CET)
The transition of people from paediatric to adult diabetes services is associated with worsening glycaemia and increased diabetes-related hospitalisation. This study compared the clinical characteristics of those with and without mental health conditions among attenders at a diabetes young adult clinic diabetes before and after changes in service delivery. Retrospective review of 200 people with diabetes attending a Sydney public hospital over eight years corresponding to the period before (2012-2016) and after (2017-2018) restructuring of a clinic for young adults aged 16-25 years. Characteristics of those with and without mental health conditions (depression, anxiety, diabetes related distress, eating disorders), were compared. Among clinic attenders (type 1 diabetes n=184, 83.2%), 40.5% (n=89) had a mental health condition particularly, depression (n=57, 64%), which was higher among Indigenous than non-Indigenous people (5.6% vs 0.8% p=0.031) but similar between diabetes type. Over eight years, those with, compared with those without a mental health condition had higher HbA1c at the last visit (9.4%[79 mmol/mol] vs 8.7% [71 mmol/mol], p=0.027), the proportion with diabetic ketoacidosis (DKA 60.7% vs 42.7%,p=0.009), smoking (38.4 vs 13.6%,p=0.009), retinopathy (9.0 vs 2.3%,p=0.025), multiple DKAs (28.4 vs 16.0%,p=0.031) were significantly higher. Having a mental health condition was associated with 2.02 (95% Confidence intervals 1.1-3.7) fold increased risk of HbA1c ≥ 9.0%[75mmol/mol]. Changes to the clinic were not associated with improvements in mental health condition (39.0% vs 32.4%, p=0.096). In conclusion, we found that mental health conditions, particularly depression, are common in this population and are associated with diabetes complications. Diabetes type and clinic changes did not affect the reported mental health conditions. Additional strategies are required to reduce complication risks among those with mental health conditions. .
COMMUNICATION | doi:10.20944/preprints202007.0654.v1
Subject: Life Sciences, Biochemistry Keywords: Anti-diabetic; hyperglycaemia; hypoglycaemic; Vernonia amygdalina; Type-2 diabetes
Online: 27 July 2020 (00:32:27 CEST)
Nine components (C1-C9) were isolated from chloroform fraction of fractionated methanol extracts of Vernonia amygdalina leaves (FMEVA) by column chromatography. All the components C1 to C9 were purified and screened for hypoglycaemic activities in type-2 diabetic rats. The most potent hypoglycaemic component was elucidated on the basis of extensive spectroscopic (1D-, 2D-NMR, GC-MS, FTIR) data analysis. The Component C5 was found to be the most potent hypoglycaemic in reducing blood glucose by 12.55 ± 3.55% at 4 h post-oral administration, when compared to the positive (18.07 ± 1.20%) and negative (-1.99 ± 0.43%) controls. The spectroscopic data analysis reveals that the isolated compound has a structure consistent with 11β,13-dihydrovernolide. The isolated compound is part of the hypoglycaemic components present in V. amygdalina leaves that is responsible for the anti-diabetic activities. Further research is needed in the development of this compound or its derivatives for pharmaceutical use.
ARTICLE | doi:10.20944/preprints201909.0343.v1
Subject: Biology, Animal Sciences & Zoology Keywords: uric acid levels; aloxan; diabetic rat; Muntingia calabura L.
Online: 30 September 2019 (08:02:58 CEST)
Background and objectives: This study were designed to determine uric acid concentration and renal histopathology of M. calabura L. stem bark extract in diabetic rats and to compare the natural product of M. calabura L. stem bark extract with allopurinol. Materials and Methods: A completely randomized design was used for the experiment which consisted of 6 treatment groups, each consisting of 4 rats, as follows: 1) NR, normal rat; 2) KN, diabetic rat (negative control); 3) KP, diabetic rats given allopurinol 10 mg/kg body weight; 4) EM150, diabetic rats given the test extract 150 mg/kg body weight/day; 5) EM300, diabetic rats given the test extract 300 mg/kg body weight/day; and 6) EM450, diabetic rats given the test extract 450 mg/kg body weight/ day. Results: The results showed that M. calabura L. stem bark extract decrease (p<0.05) uric acid levels in diabetic rats and no specific damage to renal proximal tubular cells was seen. Conclusions: It was concluded that M. calabura L. stem bark extract has a potential as an antihyperuricemic in diabetic rats. The recommended does was 300 mg/kg body weight to provide a significant effect on reducing the uric acid level in diabetic rats. Our findings support the use of this plant as a treatment for gout and other inflammatory diseases.
ARTICLE | doi:10.20944/preprints201804.0350.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: 1-DNJ; diabetic cardiomyopathy; fibrosis; N-glycosylation; α1,6-fucosylation
Online: 27 April 2018 (06:13:25 CEST)
The traditional Chinese drug Bombyx Batryticatus mori.L (BBm) which is also named the white stiff silkworm has been widely used in Chinese clinics for thousands of years. It is famous for its antispasmodic and blood circulation promoting effects. Cardiomyocyte hypertrophy, interstitial cell hyperplasia and myocardial fibrosis are closely related to the N-glycosylation of key proteins. To examine the alterations of N-glycosylation that occur in diabetic myocardium during the early stage of the disease and clarify the therapeutic effect of 1-DNJ extracted from BBm, we used the db/db mouse model and an approach based on hydrophilic chromatography solid-phase extraction integrated with an LC-MS/MS identification strategy to perform a site-specific N-glycosylation analysis of left ventricular cardiomyocyte proteins. AGEs, hydroxyproline, CTGF and other serum biochemical indicators were measured with ELISA. In addition, the α1,6-fucosylation of N-glycans was profiled with LCA lectin blots and FITC-labelled lectin affinity histochemistry. The results indicated that 1-DNJ administration obviously downregulated myocardium protein N-glycosylation in db/db mice. The expression levels of serum indicators and fibrosis-related cytokines were reduced significantly by 1-DNJ in a dose-dependent manner. The glycan α1,6-fucosylation level of the db/db mouse myocardium was elevated, and the intervention effect of 1-DNJ administration on N-glycan α1,6-fucosylation was significant. To verify this result, the well-known TGF-β/smad2/3 pathway was selected, and core α1,6-fucosylated TGFR-βⅡ was analysed semi-quantitatively with western blotting. The result supported the conclusions obtained from LCA lectin affinity histochemistry and lectin blot analysis. The expression level of FUT8 mRNA was also detected, and the results showed that 1-DNJ administration did not cause obvious inhibitory effects on FUT8 expression. Therefore, the mechanism of 1-DNJ to relieve the DCM-associated fibrosis can be concluded as the inhibition of N-GlcNAc formation and the reduction of substrate concentration.
ARTICLE | doi:10.20944/preprints202112.0445.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: omega-3; polyunsaturated fatty acids; painful diabetic neuropathy; metabolism; metabolomics
Online: 28 December 2021 (10:58:38 CET)
Background: Omega-3 polyunsaturated fatty acids (PUFAs) are increasingly reported to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. Specifically, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms. However, the molecular mechanism behind omega-3 PUFAs ameliorating pDN symptoms is lacking. Therefore, we sought to determine the distinct cellular pathways that omega-3 PUFAs dietary supplementation promotes in reducing painful neuropathy in type 2 diabetes mellitus (DM2) patients. Methods: Forty volunteers diagnosed with type 2 diabetes were enrolled in the "En Balance-PLUS" diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1,000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data was analyzed using random forest, hierarchical cluster, ingenuity pathway analysis, and metabolic pathway mapping. Results: We found that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (-11%), glycine (+11%) and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253 %) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species (p = 4.38 × 10-4, z-score = -1.96), peroxidation of lipids (p = 2.24 × 10-5, z-score = -1.944), Ca2+ transport (p = 1.55 × 10-4, z-score = -1.969), excitation of neurons (p = 1.07 ×10-4, z-score = -1.091), and concentration of glutathione (p = 3.06 × 10-4, z-score = 1.974). Conclusion: The reduction of pro-inflammatory and oxidative stress pathways following omega-3 PUFAS supplementation is consistent with using omega-3 PUFAs as a complementary dietary strategy as part of the overall treatment of painful diabetic neuropathy.
REVIEW | doi:10.20944/preprints202108.0030.v1
Subject: Medicine & Pharmacology, Ophthalmology Keywords: Artificial Intelligence; Neural Networks; Deep Learning; Diabetic Retinopathy; Diabetes Mellitus
Online: 2 August 2021 (12:26:52 CEST)
Diabetic retinopathy is the most common microvascular complication of diabetes mellitus and one of the leading causes of blindness globally. Due to the progressive nature of the disease, earlier detection and timely treatment can lead to substantial reductions in the incidence of irreversible vision-loss. Artificial intelligence (AI) screening systems have offered clinically acceptable and quicker results in detecting diabetic retinopathy from retinal fundus and optical coherence tomography (OCT) images. Thus, this systematic review and meta-analysis of relevant investigations was performed to document the performance of AI screening systems that were applied to fundus and OCT images of patients from diverse geographic locations including North America, Europe, Africa, Asia, and Australia. A systematic literature search on Medline, Global Health, and PubMed was performed and studies published between October 2015 and January 2020 were included. The search strategy was based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, and AI-based investigations were mandatory for studies inclusion. The abstracts, titles, and full-texts of potentially eligible studies were screened against inclusion and exclusion criteria. Twenty-one studies were included in this systematic review; 18 met inclusion criteria for the meta-analysis. The pooled sensitivity of the evaluated AI screening systems in detecting diabetic retinopathy was 0.93 (95% CI: 0.92-0.94) and the specificity was 0.88 (95% CI: 0.86-0.89). The included studies detailed training and external validation datasets, criteria for diabetic retinopathy case ascertainment, imaging modalities, DR-grading scales, and compared AI results to those of human graders (e.g., ophthalmologists, retinal specialists, trained nurses, and other healthcare providers) as a reference standard. The findings of this study showed that the majority AI screening systems demonstrated clinically acceptable levels of sensitivity and specificity for detecting referable diabetic retinopathy from retinal fundus and OCT photographs. Further improvement depends on the continual development of novel algorithms with large and gradable sets of images for training and validation. If cost-effectiveness ratios can be optimized, AI can become a financially sustainable and clinically effective intervention that can be incorporated into the healthcare systems of low-to-middle income countries (LMICs) and geographically remote locations. Combining screening technologies with treatment interventions such as anti-VEGF therapy, acellular capillary laser treatment, and vitreoretinal surgery can lead to substantial reductions in the incidence of irreversible vision-loss due to proliferative diabetic retinopathy.
ARTICLE | doi:10.20944/preprints202106.0268.v1
Subject: Medicine & Pharmacology, Allergology Keywords: diabetic retinopathy; mesenchymal stem cells; neural precursor cells; stem cell.
Online: 9 June 2021 (13:44:48 CEST)
This study aimed to evaluate cell therapy with human neural precursor cells (hNPCs) in diabetic retinopathy (DR) Wistar rats, induced to diabetes by intraperitoneal injection with streptozotocin. Wharton's Jelly Mesenchymal stem cells (WJ-MSCs) were isolated, expanded, and seeded onto a biopolymer substrate without growth factors to develop neurospheres to obtain the hNPCs, characterized by immunocytochemistry. The animals were divided into three groups; non-diabetic (ND) n = four; diabetic without treatment (DM) n = nine; and diabetic with cell therapy (DM + hNPCs) n = nine. After eight weeks of diabetes induction and verified DR, intravitreal injection of hNPCs (1 x 106 cel/µL) was performed in the DM + hNPCs group. Optical Coherence Tomography (OCT) and Electroretinography (ERG) evaluations were done before and after diabetes induction and after cell therapy. Eye enucleation occurred four weeks after treatment for the histopathological and immunohistochemistry analyses. In the treated group, there was the repair of the retinal structures and their arrangements. hNPCs increased the thickness of neuroretina layers, especially in the ganglion cell and photoreceptor layers. The results indicate that hNPCs reduced DR progression by a neuroprotective effect and promoted retinal repair, making them potential candidates for regeneration of the neuroretinal tissue.
ARTICLE | doi:10.20944/preprints202005.0493.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: Convolutional Neural Networks; Dental Diagnosis; Image Recognition; Diabetic Retinopathy detection
Online: 31 May 2020 (18:55:43 CEST)
Retinopathy is a human eye disease that causes changes in retinal blood vessels that leads to bleed, leak fluid and vision impairment. Symptoms of retinopathy are blurred vision, changes in color perception, red spots, and eye pain. In this paper, a new methodology based on Convolutional Neural Networks (CNN) is developed and proposed to diagnose and give a decision about the presence of retinopathy. The CNN model is trained by different images of eyes that have retinopathy and those which do not have retinopathy. The performance of the proposed model is compared with the related methods of DREAM, KNN, GD-CNN and SVM. Experimental results show that the proposed CNN performs better.
ARTICLE | doi:10.20944/preprints201803.0030.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: 1-DNJ; diabetic cardiomyopathy; fibrosis; N-glycosylation; α 1,6-Fucosylation
Online: 5 March 2018 (04:08:49 CET)
The Chinese drug Bombyx Batryticatus mori.L which also named as the white stiff silkworm is widely used in clinics, due to the significant antispasmodic and promotional blood circulation effects. In addition, its hypoglycemic effect is also recognized in recent years. From a pathological point of view, the enzymatic glycosylation and non-enzymatic glycation both have important roles in regulating properties of proteins and are associated with Diabetes. With the db/db mouse model, we examined the alterations of N-glycosylation of diabetic myocardium at primary stage and clarify the differences in glycosylation of myocardium before and after with 1-DNJ treatment. Hydrophilic chromatography solid phase extraction enrichment and LC-MS/MS identification was applied to profile the alternations in protein glycosylation. Meanwhile, N-glycan α1, 6-fucosylation alterations were profiled with LCA lectin blot and FITC-labelled lectin affinity histochemistry. Our results showed that AGES, hydroxyproline, CTGF and other serum indicators and fibrosis related cytokines expressional levels were reduced significantly by 1-DNJ in a dose-dependent manner. In order to verify this result, the well-known pathway of TGF-β/smad2/3 was picked out and α1, 6-core fucosylated TGFR-βⅡwas semi-quantified with western blot method. The result sustained the conclusion from LCA lectin affinity histochemistry and lectin blot analysis. The expressional level of α1, 6-fucosyltransferase mRNA was increased in the myocardium of db/db mice, however, the 1-DNJ administration did not show obvious inhibitory effect on FU8 expression. This unexpected result can be interpreted as 1-DNJ plays the roles by reducing the concentration of substrate rather than inhibiting α1，6-fucose glycosyltransferase expression. Meanwhile, 1-DNJ crude extract from BBm with some flavonoids accompany can also play the roles of anti-oxidant, and all the chemicals protect the diabetic myocardium from hyperglycemia damage commonly.
REVIEW | doi:10.20944/preprints201907.0265.v2
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: Aging; Alzheimer’s disease; brain insulin resistance; db/db diabetic mouse model; diabetic cognopathy; insulin resistance; metabolic syndrome; mixed dementia; obesity; type 2 diabetes mellitus
Online: 9 September 2019 (06:12:15 CEST)
Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease-dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments associated with metabolic factors and increases the cellular vulnerability to develop the age-related increased risk of LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. aging (chronic age-related diseases); ii. metabolic (hyperglycemia - advanced glycation end-products and its receptor (AGE/RAGE) interactions and hyperinsulinemia – insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen-nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis - vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.
ARTICLE | doi:10.20944/preprints202301.0333.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: diabetic foot osteomyelitis; biofilm; antimicrobial resistance; adverse effects; rifampicin; fluoro-quinolones
Online: 18 January 2023 (10:00:52 CET)
The choice of antibiotic regimens to use in patients presenting with diabetic foot osteomyelitis and their duration differs according to the situation. Antibiotics play a more important role in the medical option where no infected bone has been resected while their role is reduced but not negligible in the case of surgical options. Some studies have reported the presence of biofilm structures in bone samples taken from patients with diabetic foot osteomyelitis which raises the question of the place of anti-biofilm antibiotic regimens in this setting. During the last two decades, clinical studies have suggested a potential benefit for anti-biofilm antibiotics, mainly rifampicin against staphylococci and fluoroquinolones against gram-negative bacilli. No data from randomized controlled studies have however been reported so far. The present work provides a summary of the available data on the question of the place of anti-biofilm antibiotics for the treatment of diabetic foot osteomyelitis but also the potential limitations of such treatments.
ARTICLE | doi:10.20944/preprints202111.0153.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: Diabetic Retinopathy; Fundus Images; Retina,; Support vector machine; K-Means Clustering.
Online: 8 November 2021 (14:59:13 CET)
The complication of people with diabetes causes an illness known as Diabetic Retinopathy (DR). It is very widespread among middle-aged and older people. As diabetes progresses, patients' vision may deteriorate and cause DR. People to lose their vision because of this illness. To cope with DR, early detection is needed. Patients will have to be checked by doctors regularly, which is a waste of time and energy. DR can be divided into two groups: non-proliferative (NPDR) while the other is proliferative (PDR). In this study, machine learning (ML) techniques are used to diagnose DR early. These are PNN, SVM, Bayesian Classification, and K-Means Clustering. These techniques will be evaluated and compared with each other to choose the best methodology. A total of 300 fundus photographs are processed for training and testing. The features are extracted from these raw images using image processing techniques. After an experiment, it is concluded that PNN has an accuracy of about 89%, Bayes Classifications 94%, SVM 97%, and K-Means Clustering 87%. The preliminary results prove that SVM is the best technique for early detection of DR.
Subject: Medicine & Pharmacology, Cardiology Keywords: Diabetic Cardiomyopathy; Hyperglycemia; Ischemia/Reperfusion Injury; Metabolism; Mitochondria; Remote Conditioning; Exercise
Online: 17 March 2020 (08:52:25 CET)
Metabolic syndrome, diabetes and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is responsible for the most severe signs and symptoms. An important strategy for reducing the incidence of cardiovascular disease is regular exercise. Remote ischemic conditioning has some similarity with exercise, and can be induced by short periods of ischemia and reperfusion of a limb, and it can be performed in people who cannot exercise. There is abundant evidence that exercise is beneficial in diabetes and ischemic heart disease, but there is a need to elucidate the specific cardiovascular effects of emerging and unconventional forms of exercise in people with diabetes. Also, remote ischemic conditioning may be considered among the options to induce beneficial effects in these patients. The characteristics and interactions of diabetes and ischemic heart disease, and the known effects of exercise and remote ischemic conditioning in the presence of metabolic syndrome and diabetes, are analyzed in this brief review.
ARTICLE | doi:10.20944/preprints202108.0279.v1
Subject: Keywords: Glaucoma; Diabetic Retinopathy; Convolution Neural Network (CNN); Vision Loss; Blindness; Machine Learning
Online: 12 August 2021 (15:36:51 CEST)
In the last few decades, glaucoma became the second biggest leading cause of irreversible vision loss. Because of its asymptotic growth, it is not properly diagnosed until the relatively late stage. To stop the severe damage by glaucoma it is needed to detect glaucoma in its early stages. Surprisingly diabetes also be the greatest cause of glaucoma. In the modern era, artificial intelligence makes great progress in the medical image processing field. Image analysis based on machine learning gives a huge success in diagnosis glaucoma without any misdiagnosis. The aim of this proposed paper is to create an automated process that can detect glaucoma and diabetic retinopathy. Here various Machine Learning models are used and results of these methods are presented.
ARTICLE | doi:10.20944/preprints201901.0245.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: Osteomeles Schwerinae; diabetic retinopathy (DR); spontaneously diabetic Torii (SDT) rat; human retinal microvascular endothelial cells (HRMECs); advanced glycation end products (AGEs); retinal apoptosis; oxidative stress; mitochondrial function; adjunctive effect; combination therapy
Online: 24 January 2019 (08:37:29 CET)
Retinal apoptosis plays a critical role in the progression of diabetic retinopathy (DR), a common diabetic complication. Currently, the tight control of blood glucose levels is the standard approach to prevent or delay the progression of DR. However, prevalence of DR among diabetic patients remains high. Focusing on natural nutrients or herbal medicines that can prevent or delay the onset of diabetic complications, we administered an ethanol extract of the aerial portion of Osteomeles Schwerinae (OSSCE), a Chinese herbal medicine, over a period of 17 weeks to spontaneously diabetic Torii (SDT) rats. OSSCE was found to ameliorate retinal apoptosis through the regulation of advanced glycation end products (AGEs) accumulation, oxidative stress, and mitochondrial function via inhibition of NF-κB activity, in turn through the downregulation of PKCδ, P47phox, and ERK1/2. We further demonstrated in 25 mM glucose-treated human retinal microvascular endothelial cells (HRMECs) that hyperoside (3-O-galactoside-quercetin), quercitrin (3-O-rhamnoside-quercetin), and 2''-O-acetylvitexin (8-C-(2''-O-acetyl-glucoside)-apigenin) were the active components of OSSCE that mediated its pharmacological action. Our results provide evidence that OSSCE is a powerful agent that may directly mediate a delay in development or disease improvement in patients of DR.
ARTICLE | doi:10.20944/preprints202212.0397.v2
Subject: Medicine & Pharmacology, Other Keywords: antibiotic therapy; diabetic foot infections; non-beta-lactam antibiotics; skin commensals; treatemet failures; associations with treatment failures
Online: 20 January 2023 (15:13:51 CET)
In diabetic foot infections (DFI), the clinically virulence of skin commensals are generally pre-sumed to be of low virulence. In this single-center study, we divided the wound isolates into two groups: skin commensals (coagulase-negative staphylococci, micrococci, corynebacteria, cutibacteria); and, pyogenicpathogenic pathogens, and followed the patients for ≥ 6 months. In this retrospective study among 1,018 DFI episodes (392 [39%] with osteomyelitis), we identified skin commensals as the sole culture isolates (without accompanying pyogenicpathogenic patho-gens) in 54 cases (5%). After treatment (antibiotic therapy [median of 20 days], hyperbaric oxy-gen in 98 cases [10%]), 251 episodes (25%) were clinical failures. Group comparisons between those growing only skin commensals and controls found no difference in clinical failure (17% vs 24 %, p=0.23) or microbiological recurrence (11% vs 17 %, p=0.23). The skin commensals were mostly treated with non-beta-lactam oral antibiotics. In multivariate logistic regression analysis, isolation of only skin commensals was not associated with failure (odds ratio 0.4, 95% confi-dence interval 0.1-3.8). Clinicians might wish to consider these isolates as potential pathogens when selecting a targeted antibiotic regimen, which may equally base on oral non-beta-lactam antibiotic agents susceptible to the corresponding skin pathogens.
REVIEW | doi:10.20944/preprints202212.0208.v1
Subject: Medicine & Pharmacology, Ophthalmology Keywords: Proliferative diabetic retinopathy; recurrent vitreous hemorrhage; diabetes duration; anemia; posterior vitreous; retinal laser photocoagulation
Online: 12 December 2022 (14:59:08 CET)
(Background) the aim was to determine related factors to recurrent vitreous hemorrhage (RVH) in a sample of proliferative diabetic retinopathy (PDR) patients. (Methods) A retrospective, review-based study. We studied 183 eyes from 121 type 2 diabetes patients with PDR. We recorded diabetes duration, history of hypertension, retinal photocoagulation status, the posterior vitreous status, the mean HbA1c, mean hemoglobin, the renal function, and the systemic complications related to diabetes. We also recorded the use of ranibizumab prior to vitrectomy and the following surgical variables: the application of segmentation and diathermy on fibrovascular proliferative tissue, the use of silicone oil, and the occurrence of surgical complications, to study which independent variables were significantly related to the presence of RVH. (Results) Duration of diabetes (P= 0.028), hemoglobin (P=0.02), status of the posterior vitreous (P=0.03), retinal photocoagulation (P=0.002) and use of segmentation surgery technique (P=0.003) have significant link to the presence of RVH. In addition, patients with diabetic polyneuropathy, myocardial infarction and ischemia in lower limbs had more vitreous hemorrhage events (p<0.001). (Conclusions) Patients with PDR and with longer diabetes duration, anemia, attached posterior vitreous, deficient retinal photocoagulation, and previously cardiovascular events, were more prone to RVH.
ARTICLE | doi:10.20944/preprints201805.0318.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: microencapsulation; polyphenols; freeze-drying; antioxidant activity; in vitro dialyzability; in vitro anti-diabetic potential
Online: 23 May 2018 (08:11:46 CEST)
Microencapsulation of polyherbal formulation (PHF) extract was carried out by freeze drying method, by employing gum arabic (GA), gelatin (GE), and maltodextrin (MD) with their designated different combinations as encapsulating wall materials. Antioxidant components (i.e total phenolic contents (TPC),Total flavonoids contents (TFC), and total condensed contents (TCT)), antioxidant activity (i.e. DPPH, β-carotene & ABTS+ assays), moisture contents, water activity (aw), solubility, hygroscopicity, glass transition temperature (Tg), particle size, morphology, in vitro alpha-amylase and alpha-glucosidase inhibition and bioavailability ratios of the powders were investigated. Amongst all encapsulated products, TB (5% GA and 5% MD) and TC (10% GA) has proven to be the best treatments with respect to the highest preservation of antioxidant components and their antioxidant potential by DPPH and β-carotene assays and noteworthy for an ABTS+ assays, in addition, the aforesaid treatments also demonstrated lower moisture content, aw, particle size and higher solubility, hygroscopicity and glass transition temperature (Tg). All freeze dried samples showed irregular (asymmetrical) microcrystalline structures. Furthermore, TB and TC also illustrated the highest in vitro anti-diabetic potential due to great potency for inhibiting alpha-amylase and alpha-glucosidase activities. In the perspective of bioavailability, TA, TB and TC demonstrated the excellent bioavailability ratios (%).Futhermore, the phytochemo-profiling of ethanolic extract of PHF was also revealed to find out the bioactive compounds.
REVIEW | doi:10.20944/preprints202212.0287.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: green tea; EGCG; oxidative stress; acute kidney injury; chronic kidney disease; kidney stones; diabetic nephropathy
Online: 15 December 2022 (15:48:03 CET)
Kidney diseases are a global health problem, and their frequency is continuously increasing. Available treatments provide limited kidney protection. The protective effect of the green tea polyphenol epigallocatechin-3-gallate (EGCG) in several diseases have been extensively investigated. Experimental and clinical studies have shown that the antioxidant, anti-inflammatory, and anti-apoptotic properties of EGCG are promising for the treatment and/or prevention of kidney diseases. This review analyzes the available evidence on the effects, and the likely protective mechanisms of action, of EGCG in a broad spectrum of kidney diseases, including acute kidney injury, drug-induced nephrotoxicity, kidney stone disease, diabetic nephropathy, chronic kidney disease, and kidney fibrosis.
ARTICLE | doi:10.20944/preprints201809.0529.v1
Subject: Life Sciences, Biotechnology Keywords: hemodialysis; end stage renal disease; diabetes; motor performance; gait; balance; wearable; aging; frailty; diabetic peripheral neuropathy
Online: 27 September 2018 (04:19:43 CEST)
Motor functions are deteriorated by aging. Some conditions may magnify this deterioration. To examine whether hemodialysis (HD) process would negatively impact gait and balance beyond diabetes condition among mid-age adults (48-64 years) and older adults (65+ years). One hundred and ninety-six subjects (age=66.2±9.1 years, body-mass-index=30.1±6.4 kg/m2, female=56%) in 5 groups were recruited: mid-age adults with diabetes undergoing HD (Mid-age HD+, n=38) and without HD (Mid-age HD-, n=40); older adults with diabetes undergoing HD (Older HD+, n=36) and without HD (Older HD-, n=37); and non-diabetic older adults (Older DM-, n=45). Gait parameters (stride velocity, stride length, gait cycle time, and double support) and balance parameters (ankle, hip, and center of mass sways) were quantified using validated wearable platforms. Groups with diabetes had overall poorer gait and balance compared to the non-diabetic group (p<0.050). Among people with diabetes, the HD+ had significantly worsened gait and balance when comparing to the HD- (Cohen’s effect size d=0.63-2.32, p<0.050). Between-group difference was more pronounced among older adults with the largest effect size observed for stride length (d=2.32, p<0.001). Results suggested that deterioration in gait speed among the HD+ was correlated with age (r=-0.440, p<0.001), while this correlation was diminished among the HD-. Interestingly, results also suggested that poor gait in the Older HD- related to poor balance, while no correlation was observed between poor balance and poor gait among the Older HD+. Using objective assessments, results confirmed that the presence of diabetes can deteriorate gait and balance, and this deterioration can be magnified by HD process. Among non-HD people with diabetes, poor static balance described poor gait. However, among people with diabetes undergoing HD, age was a dominate factor describing poor gait irrespective of static balance. Results also suggested feasibility of using wearable platforms to quantify motor performance during routine dialysis clinic visits. These objective assessments may assist in identifying early deterioration in motor function, which in turn may promote timely intervention.
REVIEW | doi:10.20944/preprints201807.0454.v1
Subject: Life Sciences, Biochemistry Keywords: Carica papaya; fermented papaya preparation (FPP); free radical scavenging; antioxidant; oxidative stress; anti-diabetic; anti-carcinogenic
Online: 24 July 2018 (11:39:50 CEST)
The simplistic morphological characteristics of the Carica papaya, papaya or ‘pawpaw’ should not be the cause for underestimating its potential as a nutraceutical. The market for papaya has been expanding at a staggering rate, partly due to its applicability as a biofortified product, but mostly for its phytochemical properties and traditional health benefits. Recent characterization studies have showed that the entirety of papaya or using a formulation of fermented papaya promotion (FPP) displays effective free radical scavenging abilities, thought to be influenced by its phenolic, carotenoids, flavonoid or amino acid profile. Aiming at reducing the impact of free radical-induced oxidative damage in the human system, the antioxidant properties of FPP have been found to potently target a broad spectrum of diseases ranging from neurological impairments such as senile dementia to systemic diseases, to its interference at the cellular level and support of normal biological ageing processes. FPP has thus been extensively investigated for its ability to exert cellular protective effects and reduce oxidative stress via mitigation of genetic damage, lipid peroxidation and enzymatic inactivation in diseases. Oxidative stress reduction strategies using FPP and its holistic approach in disease prevention and management, with a focus on diabetes, cancer and cognitive health, contributes unequivocally to wellness in an aging population.
ARTICLE | doi:10.20944/preprints202110.0417.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Diabetic wound; Achyranthes aspera; wound healing; burn wound; cotton; pellet granuloma; carrageenan-induced paw edema; Acute toxicity
Online: 27 October 2021 (14:16:41 CEST)
Introduction: Wound healing is a multifaceted biological process, and diabetic wounds add more complexity to it. In diabetic wounds, the combination of chloroform fractions of Achyranthes aspera L. (A.aspera) leaves with β-Glucans has not been investigated. The additive effect of these two (A.aspera + β-Glucans) would benefit the inflammatory phase of diabetic wounds, as improper treatment will lead to chronic injuries. Therefore, the goal of this research work was to assess the in-vivo wound healing and anti-inflammatory effects of a combination of chloroform fractions of A.aspera leaves and β-Glucans in a variety of wound models in STZ-induced diabetic rats. Methods: Preliminary phytochemical analyses of A.aspera were conducted to identify various phytoconstituents in the test extract. Acute and sub-acute dermal toxicity tests of A.aspera were carried out on mice and rats, respectively, to see whether there were any abnormalities. Excision and incision wound models, cotton pellet-induced granuloma models, rat paw edema and burn wounds were used to test wound healing and anti-inflammatory actions. To induce diabetes, streptozotocin (STZ) was administered intraperitoneally at a dosage of 65 mg/kg (i.p.). A.aspera (10% w/w) and β-Glucans (2% w/w) ointments were tested separately and in combination for wound healing activities. Silver sulfadiazine (1 % w/w) ointment was used to treat the positive control groups. Excision wound model rats that had been treated with basic ointment were used as negative controls, as were incision wound model rats that had not been treated. A.aspera (400 mg/kg, po) and β-Glucans (30 mg/kg, po) were tested separately and in combination for anti-inflammatory efficacy. Positive control groups were given indomethacin (10 mg/kg, po) for cotton pellet-induced granuloma and rat paw oedema models. Negative controls for both anti-inflammatory activity models were provided 2% Tween 80. The groups were made up of six rats, and the treatments were given topically and orally to assess wound healing and anti-inflammatory effects. The levels of hydroxyproline and hexosamine and the antioxidant enzymes (SOD and CAT) in the granulation tissue were measured in excision wound model. Healed excision wound skin was examined histopathologically. Results: The A.aspera and β-Glucans combination resulted in a significant percentage of wound contraction and a shorter epithelialization time (P<0.01). The combination was found to be the most effective, with the highest percentage of edema reduction (55 %; p<0.01). The combination also exhibited favourable hydroxylamine, hexosamine and anti-oxidant profiles supported by histopathology data. Conclusion: This research showed that the immunomodulatory effect of β-Glucans had significantly enhanced the wound healing, anti-inflammatory, and anti-oxidant potential of A.aspera in diabetic wounds.
ARTICLE | doi:10.20944/preprints202101.0478.v1
Subject: Medicine & Pharmacology, Allergology Keywords: ocular drug delivery system; topical liposomes; posterior segment of the eye; safety and toler-ability; biologic activity; diabetic macular edema
Online: 25 January 2021 (10:48:51 CET)
Intravitreal injections (IVTs) of corticosteroids as triamcinolone acetonide (TA) are frequently used for the treatment of many vitreous and retinal disorders. However, IVTs are related to severe ocular complications. Lately, a topical ophthalmic TA loaded liposomes formulation (TALF) was designed to transport TA into the posterior segment of the eye when instilled in the ocular surface. To evaluate the safety, tolerability, and biologic activity of TALF, an animal study and a phase I clinical assay was performed. Moreover, four patients with diabetic macular edema (DME) were treated with TALF in order to explore the biologic activity of the formulation. No inflammation, lens opacity, swelling or intraocular pressure rising were recorded after the instillation of TALF in any of the animal or clinical study. Mainly, mild and transient adverse events such as dry eye (30%) and burning (30%) were reported. TALF improves significantly visual acuity and diminishes central foveal thickness in patients with DME. The current data demonstrate the safety, tolerability, and biologic activity of TALF. It seems that TALF can be used topically to treat vitreous and retinal diseases that respond to TA such as DME, avoiding the use of corticosteroids IVTs and its associated hazards.
REVIEW | doi:10.20944/preprints201709.0027.v1
Subject: Life Sciences, Biotechnology Keywords: EVs; endothelial-derived microparticles; platelet-derived microparticles; non-invasive biomarkers; miRNAs signature; diabetes associated complications; micro-macrovascular damage; diabetic nephropathy
Online: 8 September 2017 (09:38:47 CEST)
Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. Almost all cell types release EVs, thus they are naturally present in all body fluids. Among the several potential applications, EVs could be used as drug delivery vehicles in disease treatment, in immune therapy because of their immunomodulatory properties and in regenerative medicine. In addition to general markers, EVs are characterized by the presence of specific biomarkers (proteins, miRNAs) that allow the identification of their cell- or tissue-origin. For these features, they represent a potential powerful diagnostic tool to monitor state and progression of specific diseases. As regards, a large body of studies supports the idea that endothelial derived (EMPs) together with platelet-derived microparticles (PMPs) are deeply involved in the pathogenesis of diseases characterized by micro- and macrovascular damages, including diabetes. Existing literature suggests that the detection of circulating EMPs and PMPs and their specific miRNA profile may represent a very useful non-invasive signature to achieve informations about the onset of peculiar disease manifestations. In this Review, we discuss the possible utility of EVs in the early diagnosis of diabetes-associated microvascular complications, specifically related to kidney.
ARTICLE | doi:10.20944/preprints202206.0129.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: Diabetic retinopathy; Oxidative stress; Advanced glycation end products (AGEs); Antioxidant enzymes; Vascular endothelial growth factor; B-vitamins; Vitamin-C; Vitamin- E
Online: 8 June 2022 (12:40:07 CEST)
Excessive intracellular glucose in insulin independent tissues including nerve, nephron, lens and retina invites mishandling of metabolism of glucose resulting in a background of increased oxidative stress, advanced glycation end products (AGE) formation, lipid peroxidation and failure of antioxidant defense systems in type 2 diabetes mellitus (T2DM). All these detrimental biochemical anomalies ultimately attack biological membranes and especially capillary beds of retina and glomerulus of kidney, resulting in break-down of inner blood-retinal i.e. initiation of diabetic retinopathy (DR). If these disarrays are corrected to a large extent, development of DR can be avoided or delayed. In this prospective clinical trial, 185 patients with T2DM who received B-vitamins, vitamin-C, and E along with anti-diabetic medication for five years, demonstrated a slower rate of the development of DR and reduced abnormal biochemical mediators like reactive oxygen species (ROS), malondialdehyde (MDA), AGE, and vascular endothelial growth factor (VEGF) compared to 175 T2DM individuals who were treated with only anti-hyperglycemic drugs.