Objective: Traditional denoising algorithms perform less due Limited Directional Selectivity problem and do not adequately capture directional information in pixels. Traditional algorithms' edge representation and texture details are insufficient for the earlier detection of DH. Limited Directional Selectivity leads to inaccurate diagnosis and classification of Disc Herniation (DH) stages. The DH stages are (i) Degeneration (ii) Prolapse (iii) Extrusion and (iv) Sequestration. Moreover, detection of DH size below 2mm using MR image is the major problem.

Methods: To solve the above problem, spinal cord MR images fed to the proposed Parrot optimization tuned Denoising Convolutional Neural Network (Po- DnCNN) algorithm for perspective enhancement of nucleus pulposus region in the spinal cord, vertebrae. The perspective enhancement of Spinal cord image led to the accurate classification of stages and earlier detection of DH by using the proposed Hippopotamus optimization- Fast Hybrid Vision Transformer (Ho–FastViT) algorithm. For this study, spinal cord MR images are obtained from the Grand Challenge website – SPIDER dataset.

Results: The proposed Po-DnCNN method and Ho-FastViT results are analysed quantitatively and qualitatively based on the edge, contrast, classification of the stage, and enhancement of the projected nucleus pulposus region in the spinal cord and vertebrae. The predicted DH results using the proposed method are compared with the manual Pfirrman Grade value of the spinal card method.

Conclusion: Proposed method is better than traditional methods for earlier detection of DH. Po-DnCNN and Ho-FastViat methods give high accuracy of about 98% and 97% compared to traditional methods.

Methods: The present perspective is based on a consensus meeting that gathered the insights of six consultant cardiologists. All experts were affiliated with academic institutions representing the UAE's different geographical areas.

Findings and Conclusion: Data regarding the prevalence of dyslipidemia in the UAE and its associated ethnic differences are lacking. It is suggested that there needs to be more adherence to international recommendations for screening lipid profiles in primary care centers, which may lead to underestimating the burden of dyslipidemia. As CVD presents at a younger age in the UAE, screening for lipid profile at 35 is recommended, regardless of CVD risk. The panel emphasized that most dyslipidemia patients in the UAE are categorized as high or very high-risk groups for CVD; however, current risk assessment tools have not been validated in the UAE population and may not be tailored to the Middle Eastern and Asian populations. International guidelines have recommended the high-intensity statins-ezetimibe combination for high and very high-risk patients; the experts stated that the high-intensity statins-ezetimibe combination could be initiated in high-risk groups in the UAE. Several barriers to effectively controlling dyslipidemia in the UAE have been identified, including non-adherence, limited awareness about screening and management recommendations, and physician inertia toward achieving the recommended therapeutic goals.

Objective: This study aimed to explore the influence of dating violence on lifestyle and the risk of T2DM in women university students from Mexico.

Methods: The study employed a cross-sectional and correlational design. The study population consisted of women university students. The sample size included 255 participants. Women aged 18 to 39 with current dating relationships and residency in Mexicali, Baja California, Mexico, were included. Data collection was conducted from February to May 2023. Correlations and multiple linear regression models were conducted.

Results: A total of 255 women participated, with an average age of 21.6 years (SD = 3.2), and 32.2% had a history of intrafamily violence during childhood. 58.8% of the participants exhibited some level of risk of T2DM, and 56.7% of the lifestyle was mostly categorized as poor/fair. Detachment was the most prevalent type of dating violence, followed by coercion. Dating violence was correlated with lifestyle (r = -.430) and the risk of T2DM (r = .321). In the multiple linear regression model, dating violence influenced the risk of T2DM.

Conclusion: Women who reported higher levels of dating violence have a less healthy lifestyle and a greater risk of T2DM. It is important to consider dating violence to improve lifestyle and prevent T2DM in Mexican women university students.

Objective: Our goal is to train general practitioners on holistic patient management, with the aim of increasing patient satisfaction and treatment adherence, reducing side effects, and improving quality of life in patients with poor tolerance to metformin-IR.

Materials and Methods: We designed an educational program for physicians called SlowDiab, aimed at establishing a holistic patient approach. In this context, adult patients with T2DM who experienced gastrointestinal discomfort with metformin-IR were enrolled and switched to metformin- ER. Data on glycemic control were collected at baseline and 2 months after switching. A survey was carried out on patients to assess their level of satisfaction.

Results: In 69 enrolled patients (mean (min-max) age, 68.2 (41-90)), side effects decreased after switching from 61.8% to 16.2% (p < 0.01), and the mean perceived burden of adverse events on a scale of 1 to 10 also decreased (6.17 vs. 3.82; p < 0.05). Among patients previously intolerant to metformin-IR, 74.3% reported no longer experiencing any side effects after the switch. The mean number of tablets taken daily (2.28 vs. 1.66; p < 0.01) and mean plasma glycated hemoglobin (HbA1c) values (7.0% vs. 6.7%; p < 0.05) decreased, while 93.8% of patients were satisfied with the treatment change. Moreover, 84.2% reported an improvement in glycemic control after the switch.

Conclusion: In a real-life setting, an educational program for general practitioners confirmed that metformin ER reduces side effects and improves pill burden, therapeutic adherence, and patient satisfaction compared to metformin IR.

Objective: Here, we give a comprehensive overview of this quickly developing theranostic application that includes all relevant imaging, diagnostic, therapeutic, and monitoring elements for the management of diabetes and diabetes neuropathy.

Methods: The data for the current study was gathered by searching PubMed and Google Scholar. Several research and review publications from various publishers, including Springer Nature, Bentham Science, PLOS one, MDPI, and ACS Publishing Centre, were evaluated to compile the data.

Result: Recent developments in theranostics have shown promise as alternate management approaches for diabetes and ailments linked to diabetes. Numerous nanotechnology-built biosensors, including multiwalled carbon nanotubes, copper nanowires, zinc oxide tetrapods, and nanoparticle- embedded contact lenses, offer benefits in monitoring diabetic neuropathy.

Conclusion: The potency, usability, and dependability of insulin substitutes have been demonstrated by a variety of innovative methods for the management of diabetes, which includes nanotechnology approaches using Gene-Based Nanoparticles (siRNA), Liposomes, Exosomes/ Extracellular Vesicles, Neuromodulation, and Inhalable Nanoparticles. Over the past few years, the development of various theranostic nanoparticles for Diabetic neuropathy has experienced an unprecedented expansion. Even though much work needs to be done to precisely evaluate the genuine benefits provided by these particles, such as issues with nanotoxicity, theranostic nanoparticles will have a significant impact on the field of nanomedicine.

Aims: The study aimed to assess the role of baseline anamnestic information, clinical parameters, instrumental examination, and serum biomarkers in predicting adverse outcomes of COVID-19 in a hospital setting of Internal Medicine.

Methods: Fifty-two inpatients consecutively admitted to the Unit of Internal Medicine “Baccelli,” Azienda Ospedaliero – Universitaria Policlinico of Bari (February 1 - May 31, 2021) due to confirmed COVID-19 were grouped into two categories based on the specific outcome: good prognosis (n=44), patients discharged at home after the acute phase of the infection; poor prognosis, a composite outcome of deaths and intensive care requirements (n=8). Data were extracted from medical records of patients who provided written informed consent to participate.

Results: The two study groups had similar demographic, anthropometric, clinical, and radiological characteristics. Higher interleukin 6 (IL-6) levels and leucocyte count, and lower free triiodothyronine (fT₃) levels were found in patients with poor than those with good prognosis. Higher IL-6 levels and leucocyte count, lower fT₃ concentration, and pre-existing hypercholesterolemia were independent risk factors of poor outcomes in our study population. A predicting risk score, built by assigning one point if fT₃ < 2 pg/mL, IL-6 >25 pg/mL, and leucocyte count >7,000 n/mm³, revealed that patients totalizing at least 2 points by applying the predicting score had a considerably higher risk of poor prognosis than those scoring <2 points (OR 24.35 (1.32; 448), p = 0.03). The weight of pre-existing hypercholesterolemia did not change the risk estimation.

Conclusion: Four specific baseline variables, one anamnestic (pre-existing hypercholesterolemia) and three laboratory parameters (leucocyte count, IL-6, and fT3), were significantly associated with poor prognosis as independent risk factors. To prevent adverse outcomes, the updated 4-point score could be useful in identifying at-risk patients, highlighting the need for specific trials to estimate the safety and efficacy of targeted treatments.

Methods: Searches were made in PubMed Central, EMBASE, MEDLINE, SCOPUS, CENTRAL, WHO trial registry and Clinicaltrials.gov up to December 2022. Meta-analysis was executed using the random-effects model. Pooled hazard ratio (HR)/risk ratio (RR) was reported with 95% confidence intervals (CIs).

Results: In total, 13 studies were included in the analysis. Most were multi-country studies and had a higher risk of bias. Regarding the efficacy parameters, pooled HR for progression-free survival was 0.79 (95%CI: 0.67-0.92), pooled RR for complete response was 1.54 [95%CI: 1.14 to 2.09], partial response was 1.18 [95%CI: 0.87-1.61], overall response was 1.20 [95%CI: 0.93-1.56], stable disease was 1.09 [95%CI: 0.78-1.53], progressive disease was 0.80 [95%CI: 0.74 to 0.87], and clinical benefit was 1.08 [95%CI: 0.80-1.49]. For safety parameters, pooled RR for hyperglycemia was 4.57 [95%CI: 3.15-6.62], and gastrointestinal toxicity was 1.82 [95%CI: 1.56 to 2.14].

Conclusion: PI3K inhibitors had better efficacy than the present standard of concern for patients with breast cancer, especially among patients with PIK3CA mutations. Hence, clinicians and oncologists can provide this drug for the target population with extra caution for diabetes patients.

Introduction: DN has become one of the most prevalent complications of clinical hyperglycemia, with individual-specific variations in the disease spectrum that leads to fatal consequences. Diverse etiologies involving oxidative and nitrosative stress, activation of polyol pathway, inflammasome formation, Extracellular Matrix (ECM) modifications, fibrosis, and change in dynamics of podocyte functional and mesangial cell proliferation adds up to the clinical complexity of DN. Current synthetic therapeutics lacks target-specific approach, and is associated with the development of inevitable residual toxicity and drug resistance. Phytocompounds provides a vast diversity of novel compounds that can become an alternative therapeutic approach to combat the DN.

Methods: Relevant publications were searched and screened from research databases like GOOGLE SCHOLAR, PUBMED and SCISEARCH. Out of 4895 publications, the most relevant publications were selected and included in this article.

Result: This study critically reviews over 60 most promising phytochemical and provides with their molecular targets, that can be of pharmacological significance in context to current treatment and concomitant research in DN.

Conclusion: This review highlights those most promising phytocompounds that have the potential of becoming new safer naturally-sourced therapeutic candidates and demands further attention at clinical level.

Methods: Raw data from microarray chips with GEO accession GSE49541 were downloaded from the Gene Expression Omnibus database, and the R package (Affy and Limma) was applied to investigate differentially expressed genes (DEGs) involved in the progress of low- (mild 0-1 fibrosis score) to high- (severe 3-4 fibrosis score) fibrosis stage NAFLD patients. Subsequently, significant DEGs with pathway enrichment were analyzed, including gene ontology (GO), KEGG and Wikipathway. In order to then explore critical genes, the protein-protein interaction network (PPI) was established and visualized using the STRING database, with further analysis undertaken using Cytoscape and Gephi software. Survival analysis was undertaken to determine the overall survival of the hub genes in the progression of NAFLD to hepatocellular carcinoma.

Results: A total of 311 significant genes were identified, with an expression of 278 being upregulated and 33 downregulated in the high vs. low group. Gene functional enrichment analysis of these significant genes demonstrated major involvement in extracellular matrix (ECM)-receptor interaction, protein digestion and absorption, and the AGE-RAGE signaling pathway. The PPI network was constructed with 196 nodes and 572 edges with PPI enrichment using a p-value < 1.0 e-16. Based on this cut-off, we identified 12 genes with the highest score in four centralities: Degree, Betweenness, Closeness, and Eigenvector. Those twelve hub genes were CD34, THY1, CFTR, COL3A1, COL1A1, COL1A2, SPP1, THBS1, THBS2, LUM, VCAN, and VWF. Four of these hub genes, namely CD34, VWF, SPP1, and VCAN, showed significant association with the development of hepatocellular carcinoma.

Conclusion: This PPI network analysis of DEGs identified critical hub genes involved in the progression of fibrosis and the biological pathways through which they exert their effects in NAFLD patients. Those 12 genes offer an excellent opportunity for further focused research to determine potential targets for therapeutic applications.

Methods: The methodology includes the preparation of granules from the okra gum and neem extract, which is compressed into tablets. The nanoparticle dispersion of Pioglitazone is prepared by using the 2% w/v polyvinyl pyrrolidone (PVP) and 1% sodium lauryl sulphate (SLS), which are then sprayed on the drug-free tablet substrate. This process enhances the area of the Pioglitazone particles and thereby increases the bioavailability of the drug. The spraying of the nanoparticles on the surface of the substrate reduces the aggregation of the particles, which is a drawback of nanoparticles.

Results: The results show that the release rate is increased 2.14 times compared with the pure drug by depositing Pioglitazone nanoparticles on a tablet substrate composed of the okra mucilage and alcoholic extract of Neem. It also shows that there is a remarkable reduction in the glucose levels in vivo when compared with the product formulated by employing the traditional wet granulation technique.

Conclusion: This study concluded that the addition of herbal antidiabetic molecules as excipients can improve the therapeutic effect significantly. Better antidiabetic activity may be obtained with the deposition of hydrophobic antidiabetic drugs on herbal antidiabetic components.

Methods: The present systematic review was conducted using the PRISMA guidelines. Scopus, ScienceDirect, Google Scholar, and PubMed were the main databases used for retrieving information from inception to March 2022.

Results: From the findings obtained, Z. officinale can be regarded as a therapeutic species showing significant improvement in clinical studies on glycemic parameters (Fasting blood glucose (FBG), hemoglobin A1C (HbA1c), and insulin resistance). In addition, the bioactive compounds of Z. officinale act via several mechanisms as revealed by in vitro and in vivo studies. Overall, these mechanisms were by increasing glucose-stimulated insulin secretion, sensitising insulin receptors and raising glucose uptake, translocation of GLUT4, inhibition of advanced glycation end product-induced increase of reactive oxygen species, regulation of hepatic gene expression of enzymes associated with glucose metabolism, regulation of the level of pro-inflammatory cytokines, amelioration of the pathological injuries of kidneys, protective effect on the morphology of β-cells as well as its antioxidant mechanisms, among others.

Conclusion: Z. officinale and its bioactive compounds displayed promising results in in vitro and in vivo systems, nevertheless, it is highly recommended that human trials be conducted on these compounds since clinical studies are the core of medical research and considered the final stages of the drug development process.

Objective: The objective of this study was to assess the impact of consuming lycopene and tomatoes on various cardiovascular risks factors such as lipid profile, glycemic control markers, blood pressure, inflammation, oxidative stress, and body weight.

Methods: A systematic literature search was carried out using electronic databases, including PubMed, Web of Science, and Scopus, up to November 2022 to identify eligible Randomized Control Trials (RCTs) evaluating the effect of lycopene and tomato consumption on cardiovascular risk factors. Heterogeneity tests of the selected trials were performed using the I² statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference (WMD) with a 95% confidence interval (CI).

Results: Out of 27,438 records initially identified, a total of 34 studies met the eligibility criteria and were included in this meta-analysis. The results showed that lycopene consumption was associated with a significant reduction in malondialdehyde (MDA) levels, indicating a potential benefit in reducing oxidative stress. However, lycopene and tomato consumption did not have significant effects on other cardiovascular risk factors such as triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), Intercellular Adhesion Molecule 1 (ICAM-1), c-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), body weight, and body mass index (BMI).

Conclusion: Overall, the findings showed that lycopene and tomato consumption did not affect cardiovascular risk factors. However, lycopene supplementation may result in a significant improvement in MDA levels. With the view to confirming these results, further studies with long-term duration and different doses are needed.

Aim: This study aims to explore the effects of oxidative stress combined with an inflammatory response on left carotid artery stenosis with coronary artery disease in patients.

Methods: We, therefore, tested the hypothesis that levels of markers of oxidative stress and inflammation are associated with coexistent severe carotid and coronary artery stenosis in patients. We measured the circulating levels of malondialdehyde (MDA), oxidized low-density lipoprotein (OX-LDL), homocysteine (Hcy), F2- isoprostanes (F2-IsoPs), tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), prostaglandin E2 (PG-E2) and interferon-gamma (IFN-γ) in patients with combined carotid and coronary artery severe stenosis. We also assessed the relationships among oxidative stress, inflammation, and severe stenosis of the carotid with a coronary artery in patients.

Results: Levels of MDA, OX-LDL, Hcy, F2-IsoPs, TNF-α, hs-CRP, PG-E2, and IFN-γ were remarkably increased (P < 0.001) in patients with combined carotid and coronary artery severe stenosis. High levels of oxidative stress and inflammation may be related to severe stenosis of the carotid with coronary arteries in patients.

Conclusion: Our observations indicated that measurements of oxidative stress and inflammatory markers may be valuable for the assessment of the degree of carotid with coronary artery stenosis. The biomarkers of oxidative stress and inflammatory response may become therapeutic targets for carotid artery stenosis with coronary artery stenosis in patients.

Objective: The present study aims to review the radioprotective potentials of silymarin/silibinin in the prevention/reduction of ionizing radiation-induced adverse effects on healthy cells/tissues.

Methods: Based on PRISMA guidelines, a comprehensive and systematic search was performed for identifying relevant literature on the “potential protective role of silymarin/silibinin in the treatment of radiotherapy-induced toxicities” in the different electronic databases of Web of Science, PubMed, and Scopus up to April 2022. Four hundred and fifty-five articles were obtained and screened in accordance with the inclusion and exclusion criteria of the current study. Finally, 19 papers were included in this systematic review.

Results: The findings revealed that the ionizing radiation-treated groups had reduced survival rates and body weight in comparison with the control groups. It was also found that radiation can induce mild to severe adverse effects on the skin, digestive, hematologic, lymphatic, respiratory, reproductive, and urinary systems. Nevertheless, the administration of silymarin/silibinin could mitigate the ionizing radiation-induced adverse effects in most cases. This herbal agent exerts its radioprotective effects through anti-oxidant, anti-apoptosis, anti-inflammatory activities, and other mechanisms.

Conclusion: The results of the current systematic review showed that co-treatment of silymarin/silibinin with radiotherapy alleviates the radiotherapy-induced adverse effects in healthy cells/tissues

Objective: The objective is developing an integrated mathematical model of the insulin signaling network based on Brännmark's model, which can simulate the signaling events more comprehensively with the added key components.

Methods: In this study, a thorough mathematical model of the insulin signaling network was developed by expanding the previously validated model and incorporating the glycogen synthesis module. Parameters (69 parameters) of the integrated model were evaluated by a genetic algorithm by fitting the model predictions to eighty percent of experimental data from the literature. Twenty percent of the experimental data were used to evaluate the final optimized model.

Results: The time-response curves indicate that the GS phosphorylation reaches its maximum in response to 10^-7 M insulin after 4 min, while the maximum phosphorylated GSK3 is attained within ~50 min. The doseresponse curves for the GSP and GSK3 of the insulin signaling intermediaries in response to the increased concentration of insulin, after 10 min, in the input from 0-100 nM exhibits a decreasing trend, whereas an increasing trend was observed for the GS and GSK3P. The GSK and GS phosphorylation sensitivity was enhanced by increasing the initial insulin concentration level from 0.001 to 100 nM. However, the sensitivity of GSK3 to insulin concentration changes (from 0.001 to 100 nM) was 3-fold higher than GS sensitivity.

Conclusion: Considerably, the trends of all signaling components simulated by the expanded model shows high compatibility with experimental data (R2 ≥ 0.9), which approves the accuracy of the proposed model. The proposed mathematical model can be used in many biological systems and combined with the whole-body model of the blood glucose regulation system for a better understanding of the causes and potential treatment of type 2 diabetes. Although, this model is not a complete description of insulin signaling, yet it can make profound contributions to improvements regarding other important components and signaling branches such as epidermal growth factor (EGF) signaling, as well as signaling in other cell types in the model structure of future works.

Gut microbiota modulation and stem cell therapy may be considered a highly promising field that could add up towards the improvement of different diseases, increasing the outcome and efficacy of each other through mutual interplay or interaction between both therapies. Importantly, more investigations are required to reveal the cross‐talk between microbiota modulation and stem cell therapy to pave the way for the development of new therapies with enhanced therapeutic outcomes.

This review provides an overview of dysbiosis in various diseases and their management. It also discusses microbiota modulation via antibiotics, probiotics, prebiotics, and fecal microbiota transplant to introduce the concept of dysbiosis correction for the management of various diseases. Furthermore, we demonstrate the beneficial interactions between microbiota modulation and stem cell therapy as a way for the development of new therapies in addition to limitations and future challenges regarding the applications of these therapies.

Objective: This research sought to investigate the potential diagnostic and therapeutic targets for recurrent arrhythmias in patients with coronary restenosis and reocclusions after coronary stenting.

Methods: We examined whether oxidative stress, proinflammatory microparticles, and proinflammatory cytokines could have effects that lead to recurrent arrhythmias in elderly patients with coronary restenosis and reocclusions. We measured the levels of malondialdehyde (MDA), CD31 + endothelial microparticle (CD31 EMP), CD62E + endothelial microparticle (CD62E + EMP), high-sensitivity C-reactive protein (hs-CRP), interleukin- 1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α), as well as oxidized low-density lipoprotein (OX-LDL), and assessed the effects of relationship between oxidative stress, proinflammatory microparticles, and proinflammatory cytokines on recurrent atrial and ventricular arrhythmias in elderly patients with coronary restenosis and reocclusions after coronary stenting.

Results: The levels of CD31 + EMP, CD62E + EMP, MDA, hs-CRP, IL-1β, IL-6, IL-8, TNF-α and OX-LDL were found to be increased significantly in coronary restenosis + recurrent atrial arrhythmia group compared to without coronary restenosis and coronary restenosis + without recurrent atrial arrhythmia groups, respectively (P < 0.001). Patients in the coronary reocclusion + recurrent ventricular arrhythmia group also exhibited significantly increased levels of CD31 + EMP, CD62E + EMP, MDA, hs-CRP, IL-1β, IL-6, IL-8, TNF-α and OXLDL compared to without coronary reocclusion and coronary reocclusion + without recurrent ventricular arrhythmia groups, respectively (P < 0.001).

Conclusion: Proinflammatory microparticles, proinflammatory cytokines, and oxidative stress might act as potential targets for recurrent arrhythmias in patients with coronary restenosis and reocclusions after coronary stenting.

Methods: 382 newly-diagnosed NAFLD adolescents, aged 9-16 years old, were enrolled and divided into three subgroups according to the APNtertile. Simple and multiple linear regression analyses were performed to assess the correlation between HOMA-IR and APN in boys and girls, respectively.

Results: The HOMA-IR values tended to decrease in boys according to APN tertiles: 5.6(4.4-7.3) vs. 5.2(4.6-6.9) vs. 4.9(4.1-5.8) (p<0.01), and there was a significant difference in the HOMA-IR values among three APN tertile subgroups in girls (p<0.01). Univariate analysis showed that body mass index, waist circumference, weight-to-height ratio, fasting blood glucose, insulin, triglyceride, and APN were significantly associated with HOMA-IR in boys (p<0.05). In girls, body mass index, fasting blood glucose, insulin, total cholesterol, triglyceride, and APN were significantly associated with HOMA-IR (p<0.05).APN was found to be a significant determinant for HOMA-IR only in boys (β=-0.147, p<0.01).

Conclusion: Our findings showed that APN was an independent and significant determinant for increased HOMA-IR in boys with NAFLD. Further studies are needed to explore the underlying mechanisms.

Objective: Accordingly, the current review aims to depict the role of resveratrol in the regulation of different signaling pathways that are involved in the reactive oxygen species (ROS) production, inflammatory processes, autophagy, and mitochondrial dysfunction, as critical contributors to DN pathophysiology.

Results: The pathogenesis of DN can be multifactorial; hyperglycemia is one of the prominent risk factors of DN development that is closely related to oxidative stress. Resveratrol, as a well-defined polyphenol, has various biological and medicinal properties, including anti-diabetic, anti-inflammatory, and anti-oxidative effects.

Conclusion: Resveratrol prevents kidney damages that are caused by oxidative stress, enhances antioxidant capacity, and attenuates the inflammatory and fibrotic responses. For this reason, resveratrol is considered an interesting target in DN research due to its therapeutic possibilities during diabetic disorders and renal protection.

Objectives: Owing to the present remarkable anti-diabetic effects with no or few side effects of lipids, the aim of this study was to assess the state-of-the-art research on anti-diabetic effects of lipids via the modulation of angiogenesis.

Methods: To study the effects of lipids in diabetes via modulation of angiogenesis, we have searched the electronic databases including Scopus, PubMed, and Cochrane.

Results: The promising anti-diabetic effects of lipids were reported in several studies. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil (FO) were reported to significantly induce neovasculogenesis in high glucose (HG)-mediated endothelial progenitor cells (EPCs) with neovasculogenesis dysfunction in type 2 diabetic mice. Linoleic acid, mono-epoxy-tocotrienol- α (MeT3α), and ginsenoside Rg1 facilitate wound closure and vessel formation. N-Palmitoylethanolamine (PEA), α-linolenic acid (ALA), omega-3 (ω3) lipids from flaxseed (FS) oil, ω-3 polyunsaturated fatty acids (PUFA), lipoic acid, taurine, and zeaxanthin (Zx) are effective in diabetic retinopathy via suppression of angiogenesis. Lysophosphatidic acid, alkyl-glycerophosphate, crocin, arjunolic acid, α-lipoic acid, and FS oil are involved in the management of diabetes and its cardiac complications. Furthermore, in two clinical trials, R-(+)-lipoic acid (RLA) in combination with hyperbaric oxygenation therapy (HBOT) for treatment of chronic wound healing in DM patients, as well as supplementation with DHA plus antioxidants along with intravitreal ranibizumab were investigated for its effects on diabetic macular edema.

Conclusion: Proof-of-concept studies presented here seem to well shed light on the anti-diabetic effects of lipids via modulation of angiogenesis.

Objective: The aim of the study was to review in depth the current literature regarding exercise treatment of metabolic syndrome neuropathy in humans and animal models, highlight the diverse mechanisms by which exercise exerts beneficial effects, and examine adherence limitations, safety aspects, modes and dose of exercise.

Results: Rodent models that recapitulate the organismal milieu of prediabetic metabolic syndrome and the phenotype of its neuropathy provide a strong platform to dissect exercise effects on neuropathy pathogenesis. In these models, exercise reverses hyperglycemia and consequent oxidative and nitrosative stress, improves microvascular vasoreactivity, enhances axonal transport, ameliorates the lipotoxicity and inflammatory effects of hyperlipidemia and obesity, supports neuronal survival and regeneration following injury, and enhances mitochondrial bioenergetics at the distal axon. Prospective human studies are limited in scale but suggest exercise to improve cutaneous nerve regenerative capacity, neuropathic pain, and task-specific functional performance measures of gait and balance. Like other heath behavioral interventions, the benefits of exercise are limited by patient adherence.

Conclusion: Exercise is an integrative therapy that potently reduces cellular inflammatory state and improves distal axonal oxidative metabolism to ameliorate features of neuropathy in metabolic syndrome. The intensity of exercise need not improve cardinal features of metabolic syndrome, including weight, glucose control, to exert beneficial effects. https://www.benthamscience.comarticle/117604 https://www.benthamscience.comarticle/116520 https://www.benthamscience.comarticle/115540Introduction: Animal models have been widely used to investigate the etiology and potential treatments for diabetic peripheral neuropathy. What we have learned from these studies and the extent to which this information has been adapted for the human condition will be the subject of this review article.

Methods: A comprehensive search of the PubMed database was performed, and relevant articles on the topic were included in this review.

Results: Extensive study of diabetic animal models has shown that the etiology of diabetic peripheral neuropathy is complex, with multiple mechanisms affecting neurons, Schwann cells, and the microvasculature, which contribute to the phenotypic nature of this most common complication of diabetes. Moreover, animal studies have demonstrated that the mechanisms related to peripheral neuropathy occurring in type 1 and type 2 diabetes are likely different, with hyperglycemia being the primary factor for neuropathology in type 1 diabetes, which contributes to a lesser extent in type 2 diabetes, whereas insulin resistance, hyperlipidemia, and other factors may have a greater role. Two of the earliest mechanisms described from animal studies as a cause for diabetic peripheral neuropathy were the activation of the aldose reductase pathway and increased non-enzymatic glycation. However, continuing research has identified numerous other potential factors that may contribute to diabetic peripheral neuropathy, including oxidative and inflammatory stress, dysregulation of protein kinase C and hexosamine pathways, and decreased neurotrophic support. In addition, recent studies have demonstrated that peripheral neuropathy-like symptoms are present in animal models, representing pre-diabetes in the absence of hyperglycemia.

Conclusion: This complexity complicates the successful treatment of diabetic peripheral neuropathy, and results in the poor outcome of translating successful treatments from animal studies to human clinical trials.

Discussion: This review focuses on the general information about nitrous oxide, its types and mechanism of action and the fact that overview of inadequate NOS activity for cardio protective benefits was often studied for cardiovascular treatments.

Conclusion: We concluded that the natural plant NO is essential for cardiovascular activity to target site with desired concentration. Moreover, the researchers focused on evidence that suggested that nitrate supplementation could help regulate blood pressure, limit progression of atherosclerosis, and improve myocardial contractility in both healthy individuals and those with cardiovascular diseases.

Results: Only 46 out of 67 patients accomplished the criteria at the end of the study. There was no general improvement in the glycemic control evaluated by HbA1c (9.4 ± 2.4 vs 9.4 ± 2.6, p=NS) after VD supplementation. However, a post-hoc analysis, based on HbA1c variation, identified patients who had HbA1c reduced at least 0.6% (group 1, N = 13 (28%)). In addition, a correlation between 25(OH)D levels with HbA1c and total insulin dose at the end of the study was observed (r = -0.3, p<0.05; r=-0.4, p<0.05, respectively), and a regression model demonstrated that 25(OH)D was independent of BMI, duration of T1DM and final total insulin dose, being capable of determining 9.2% of HbA1c final levels (Unstandardized B coefficient = −0.033 (CI 95%: −0.064 to −0.002), r2 = 0.1, p <0.05).

Conclusion: Our data suggest that VD is not widely recommended for glycemic control. Nevertheless, specific patients might benefit from this approach.]]> https://www.benthamscience.comarticle/113172 Objective: The current study aimed to analyze the protective effects of metformin on streptozocin- induced diabetic rats in T1DM in hepatic tissues.

Methods: In the present study, male Wistar rats (n=24) were randomly assigned into 2 groups (n=12 for each control and test), and metformin (100 mg/kg/day) was given for 7 weeks. Afterward, diabetes was induced by streptozocin (STZ) at a single dose of 150 mg/kg. Blood glucose was examined daily before and after STZ induction. The animals were euthanized by cervical dislocation 5 days after streptozocin injection, after which liver and pancreas were harvested from each rat.

Results: The biochemical analyses revealed that metformin resulted in significantly reduced plasma glucose levels and higher pancreatic insulin levels in the test group. Using a restrictive cut-off of at least 2-FC and an adjusted p-value (q-value) of ≤0.05, a sum of 747 genes for the metformin group were shown to be differentially regulated compared to controls (320 Down and 427 Up), by which they were obtained from the liver. Furthermore, the evidence is attained that metformin may hinder the loss of critical β-cells by reducing inflammatory and apoptosis signaling, promoting fatty acid β-oxidation, and inducing metabolism.

Conclusion: Collectively, this study has demonstrated a decrease in blood glucose levels and a rise in insulin-levels and thus consequent prophylactic effects in metformin-given STZ-induced diabetic rats.]]> https://www.benthamscience.comarticle/116620Background: Metabolic and clinical disorders forming the complex of interrelated abnormalities is known as metabolic syndrome (METs).

Objective: Our goal was to assess the dependence of serum arylsulfatase (AS) and acid phosphatase (ACP) activities on anthropometric and biochemical parameters in patients with METs.

Methods: In 142 patients with METs (IDF criteria), consisting of different components in different sequences (hypertension, diabetes, lipid disorders), and in 65 healthy participants, basic biochemical parameters were determined in laboratory tests. The activity of serum hydrolases was determined using Bessey’s (ACP) and Roy’s (AS) methods.

Results: The AS activity is correlated with waist-to-hip ratio (WHR) (more strongly in women and in most advanced METs), BMI (in men), and triglycerides (TG) (in women, participants with I degree obesity, and those with three METs components). The ACP activity correlated with the WHR of patients with II degree obesity, TG in those with III degree of obesity, and total cholesterol (TC) in those with four METs components.

Conclusion: Increased AS activity in patients with METs compared to lower AS activity in the control group may be due to decreased lysosomal function and related to the amount of adipose tissue. Low activity of ACP in the blood serum of patients with METs compared to high activity of ACP in the control group may indicate exhaustion of the lysosomal apparatus and loss of hydrolytic activity. The increase in TG and TC in groups with an increasing number of METs-defining components may be due to the abnormal lysosomal degradation of these compounds.

Methods: Database research was carried out on Medline, Embase, Cochrane Library, country-specific journals, and following-up WHO reports published between December 25, 2019 - May 25, 2020.

Results: Till 25 May 2020, coronavirus cases were 5,307,298, with 347,070 deathsand 2,314,849 recovered cases. According to the WHO reports, most COVID-19 deaths seen are in people who suffered from other chronic diseases characterized by phospholipidosis and phosphatidylglycerol deficiency, including hypertension, liver, heart, and lung diseases and diabetes. Phospholipases A2 (PLA2) catalyze the cleavage of fatty acids esterified at the sn-2 position of glycerophospholipids leading to enhanced inflammation and lung damage. Also, cytosolic phospholipase A2α inhibitors may reduce the accumulation of viral proteins and RNA. In addition, administration of exogenous phospholipid surfactant may help COVID-19 infected patients with ARDS to remove inflammatory mediators.

Conclusion: The present study showed a relation between phosphatidylglycerol deficiency in COVID-19 infected patients with ARDS and/or chronic diseases and their mortality. These findings also showed an important approach for the prevention and treatment of COVID-19 infections by using cytosolic phospholipase A2α inhibitors and exogenous administration of a specific phospholipid surfactant.]]> https://www.benthamscience.comarticle/112319 https://www.benthamscience.comarticle/110034 https://www.benthamscience.comarticle/112253 https://www.benthamscience.comarticle/112315Introduction: Silent coronary heart disease is frequently undetected in type 2 diabetes mellitus (DM2) and pre-diabetes determined by glucose intolerance (GI). Pulse wave velocity (PWV) and albumin-creatinine ratio (ACR) have been considered markers of cardiovascular mortality, coronary heart disease and chronic renal failure.

Aim: To evaluate the incidence of coronary artery disease (CAD) and the relationship between urinary albumin-creatinine ratio, glomerular filtration rate (GFR) and PWV in type 2 DM with silent CAD.

Methods: We analyzed 92 individuals (44 male), 49 (60±7y) type 2 DM non-insulin dependents and 43 prediabetics (43±4y), with Grade I-II hypertension and no symptoms of CAD.

All type 2 DM patients were under antidiabetic treatment with A1C hemoglobin between 5.5 and 6.5%.

Every patient underwent a myocardial perfusion SPECT scan. In those subjects with ischemic patterns, coronary angiography was performed. In addition, PWV, glomerular filtration rate, and ACR were evaluated. Statistics: mean±SEM, and ANOVA among groups.

Results: 48.59% of DM2 and 25.58% of GI patients had silent coronary artery had silent coronary artery disease and higher ACR, PWV and reduced GFR. Higher ACR and PWV and reduced GFR. DM2 and GI showed a negative relationship between GFR and ACR. Moreover, this relation was also observed in different levels of GFR (>60 ml/min and <60ml.min (p<0.05) in patients with CAD, suggesting a cardio-renal interaction in DM2.

Conclusion: Higher PWV, lower GFR and ACR predict the incidence of CAD in DM2. Dysglycemic individuals also represent a group of higher risk for coronary artery disease with similar predictors as in DM2. Diabetic and prediabetics still develop renal microalbuminuria. Thus, PWV seems to represent a reliable marker of renal impairment and coronary artery disease.

Recently, the Sodium Glucose Co-transporter type 2 inhibitors (SGLT2 inhibitors) used for the treatment of heart failure patients with or without diabetes has been a breakthrough in the field of medicine.

This review describes the established pathophysiology of diabetic cardiomyopathy and SGLT2 inhibitors, their mechanisms of action, and benefits in this group of patients.

Methods: Relevant studies were identified by PubMed, Google Scholar and Science Direct. Reference lists of retrieved articles were also reviewed. The most relevant and up-to-date information was incorporated.

Results: There is a wide range of drugs that can induce lithiasis. While the risk of developing lithiasis is high with some drugs (ceftriaxone, atazanavir, somatostatin analogues), it is lower or even questionable with others. Some drugs precipitate in the bile and may account for up to 100% of the weight of the stone.

Conclusion: Cholelithiasis can be induced by a wide range of drugs with different mechanisms of action. The aim of the article is to draw attention to this lesser known fact and the need to take into account the risk of developing lithiasis prior to therapy initiation.

Objective: The aim of this study was to examine whether plasma lipid peroxidation, antioxidant capability, leptin levels are associate selected LEP -2548 A/G and LEPR Q223R polymorphisms in mestizo and indigenous obesity Mexican population.

Methods: We identified and characterized 50 overweight or obese subjects and 50 healthy, normal- weight volunteers with indigenous Tepehuana or Mexican mestizo ethnicity from Durango, Mexico. LEP -2548 A/G and LEPR Q223R polymorphisms were determined by genotyping. Concentrations of leptin, antioxidant capacity (CA) and lipoperoxidation (LIPX) were determined in fast conditions on plasma with Enzyme-Linked ImmunoSorbent Assay (ELISA) in all participants.

Results: The highest genotype frequency was the heterozygous LEPR, which was associated with lipid peroxidation levels in normal-weight Tepehuan populations. A positive correlation was observed (r = 0.5; p <0.01) between LEP polymorphism and lipoperoxidation in normal weight Tepehuan subjects. On the other hand, the LEPR polymorphism was associated with the level of lipoperoxidation (r = 0.13; P <0.05) in mestizo populations of normal weight. Conclusion: It is probable that there is a synergistic effect for obesity, where the presence of oxidative stress and single nucleotide polymorphisms (SNP) of leptin and its receptor contributes to the generation of pathological subcutaneous fat of obesity, together with the environmental conditions of the populations.

Objective: The aim of this study was to evaluate salivary antioxidants and oxidative stress markers in GDM.

Methods: Twenty pregnant women with GDM and 20 healthy pregnant women with normal blood glucose test participated in this study. Five mL of unstimulated saliva samples were collected. Spectrophotometric assay was carried out for sialo-chemical analysis. Stata software was used for data analysis.

Results: The GDM group exhibited no significant difference in salivary total antioxidant capacity and malondialdehyde compared to the healthy control group. All antioxidants markers, the uric acid, total antioxidant, peroxidase and catalase, decreased in GDM group that the difference of peroxidase and catalase was statistically significant. All of oxidative stress markers, the salivary malondialdehyde, total oxidative stress and total thiol, increased in GDM group. GDM group exhibited significantly higher salivary total oxidative stress levels.

Conclusion: Catalase level was significantly lower and total oxidative stress was significantly higher. These two markers might have significant importance and might exhibit early changes compared to other factors in GDM. Some salivary antioxidants might have diagnostic, prognostic or therapeutic implications in GDM. Other studies with large sample size on salivary and blood samples need to be done to confirm these properties and salivary samples using instead of blood samples in GDM biomarkers changes.

Methods: This systematic review investigated the bioactive compounds reported to possess activities against type 2 diabetes. Three (3) databases, PubMed, ScienceDirect and Google Scholar were searched for research articles published between January 2010 and October 2020. A total of 6464 articles were identified out of which 84 articles were identified to be elligible for the study.

Result and Discussion: From the data extracted, it was found that quercetin, Kaempferol, Rosmarinic acid, Cyanidin, Rutin, Catechin, Luteolin and Ellagic acid were the most cited bioactive compounds which all falls within the class of polyphenolic compounds. The major sources of these bioactive compounds includes citrus fruits, grapes, onions, berries, cherries, broccoli, honey, apples, green tea, Ginkgo biloba, St. John's wort, green beans, cucumber, spinach, tea, Rosmarinus officinalis, Aloe vera, Moringa oleifera, tomatoes, potatoes, oregano, lemon balm, thyme, peppermint, Ocimum basilicum, red cabbage, pears, olive oil and walnut.

Objective: This article aims to summarize metformin’s anticancer effects through reviewing its literatures and patents, with a focus on its potential to be repurposed for cancer therapy.

Methods: Various databases were examined using keywords, ‘Metformin’ and ‘Cancer’. Research articles were collected through the PubMed database, clinical trials were obtained from the Clinical Trials database, and patents were collected through the Google Patents database.

Results: Metformin shows antineoplastic activity in various models. These anticancer properties appear to synergize with existing chemotherapeutics, which allows a reduction in drug dosage without losing potency while minimizing adverse effects. Numerous patents on metformin have been filed which claim various combination therapies, delivery methods, and uses for cancer therapy, displaying an increasing interest in metformin’s anticancer potential.

Conclusion: Preclinical studies, along with early phase clinical trials, have examined the antitumor properties of metformin on a variety of cancers. Metformin’s anticancer effects are well documented, demonstrating a great promise in improving current cancer therapies. However, there is a significant lack of late phase clinical trials, specifically those involving nondiabetic cancer patients, and therefore further research in this area is required.

Methods: Article reviews, systematic reviews, prospective studies, retrospective studies, randomized, double-blind, and placebo-controlled trials in humans recently published were selected and analyzed. A total of 368 articles were collated and submitted to the eligibility analysis. Subsequently, 215 studies were selected to compose the content part of the paper, and 153 studies composed the narrative review.

Results: Studies suggest a possible role of melatonin in metabolic diseases such as obesity, T2DM and metabolic syndrome. Intervention studies using this hormone in metabolic diseases are still unclear regarding the possible benefit of it. There is so far no consensus about the possible role of melatonin as an adjuvant in the treatment of metabolic diseases. More studies are necessary to define possible risks and benefits of melatonin as a therapeutic agent.]]> https://www.benthamscience.comarticle/111116Background: Having in mind that diabetes mellitus (DM) and obesity are some of the greatest health challenges of the modern era, diabetic cardiomyopathy (DCM) is becoming more and more recognized in clinical practice.

Main Text: Initially, DM is asymptomatic, but it may progress to diastolic and then systolic left ventricular dysfunction, which results in congestive heart failure. A basic feature of this DM complication is the absence of hemodynamically significant stenosis of the coronary blood vessels. Clinical manifestations are the result of several metabolic disorders that are present during DM progression. The complexity of metabolic processes, along with numerous regulatory mechanisms, has been the subject of research that aims at discovering new diagnostic (e.g. myocardial strain with echocardiography and cardiac magnetic resonance) and treatment options. Adequate glycaemic control is not sufficient to prevent or reduce the progression of DCM. Contemporary hypoglycemic medications, such as sodium-glucose transport protein 2 inhibitors, significantly reduce the frequency of cardiovascular complications in patients with DM. Several studies have shown that, unlike the above-stated medications, thiazolidinediones and dipeptidyl peptidase-4 inhibitors are associated with deterioration of heart failure.

Conclusion: Imaging procedures, especially myocardial strain with echocardiography and cardiac magnetic resonance, are useful to identify the early signs of DCM. Research and studies regarding new treatment options are still “in progress”.

Objective: This review aims to identify and summarize the effect of novel anti-diabetic agents (glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter -2 inhibitors) on endothelial (EF) and platelet function (PF) and evaluate the consistency with the results of cardiovascular outcomes studies.

Methods: We performed a structured search of the PubMed database for peer-reviewed research of the literature between 1981 and 2020 regarding the effect of DM and novel antidiabetic agents on EF and PF.

Results: We analyzed data regarding the effect of novel anti-diabetic agents on EF and PF as well as the pathophysiological interplay between DM, PF, and EF. The available studies use different methods to evaluate these outcomes and the results of different studies are rather conflicting as a result of different study designs, combinations of drugs tested, small study samples and patient population heterogeneity.

Conclusion: The currently available data do not unequivocally support a consistent effect of novel antidiabetic agents on EF and PF. Further study is required ideally for the validation of the results with clinical outcomes.

Background: Diabetic Retinopathy (DR) is a frequent complication of Diabetes mellitus and it has a decisive impact on the quality of life, as it is one of the biggest causes of blindness in the adult population. Levels of microRNA-9 have been shown to be related to diabetes but little is known about its involvement with DR in humans.

Objective: To analyze the relationship between the methylation profile of miR-9-1 or miRs -9-1/-9-3 and DR.

Methods: 103 patients diagnosed with diabetes for 5 to 10 years were analyzed. The data were categorized according to clinical, biochemical, lifestyle and anthropometric parameters. DNA extracted from leukocyte samples was used to determine the methylation profile of miRs-9-1 and -9-3 using a specific methylation PCR assay.

Results: miR-9-1 methylation was related to diabetic retinopathy, indicating that methylation of this miR increases the chances of presenting retinopathy up to 5 times. In our analyses, diabetics with lower levels of creatinine and CRP showed significant reductions (99% and 97%) in presenting DR. Methylation of both miRs-9-1 and 9-3 methylated increases the chances of presenting DR by 8 times; in addition, a sedentary lifestyle can increase the risk for the same complication by up to 6 times.

Conclusion: Our results suggest that both methylation of miR-9-1 and e miRs-9-1 / 9-3 favors DR in patients with diabetes in a period of 5 to 10 years of diagnosis.

Methods: Literature has been collected through SciFinder, Web of Science, Google Scholar, Pubmed, and a library. This review shares updated information on the botany, distribution, health benefits, phytochemistry and pharmacology of Mung bean seeds.

Results: Bioactive components of mung bean seeds exhibited a wide array of activities such as anticancer, antihyperlipidemic, antihypertensive, antidiabetic, anti-microbial, antioxidant, treatment of alcoholism, reducing obesity, increasing muscular strength, rheumatism, piles, liver and neurological diseases. This curative potential highlighted its various beneficial outcomes in the field of drug research and increasing scientific interest in the identification of bioactive compounds responsible for various pharmacological activities. This legume is gaining importance for its use in the pharmaceutical, food and cosmetic products.

Conclusion: Existing literature authenticates the potential benefits of mung bean seeds from nutritional as well as medicinal perspective. This food grain needs to be explored for identification, isolation, and characterization of bioactive compounds against varied ailments.

Background: The fat-soluble molecule, vitamin D, has gained great importance ever since its pleiotropism has been recognized. Its efficacy could be attributed to the presence of vitamin D receptors in most of the body tissues. Vitamin D plays a significant role in cell proliferation, differentiation, and immune modulation. It modulates the T and B cells resulting in the suppression of the immunoglobulins, autoimmunity, and inflammation.

Methods: We performed a literature search with the objective to highlight the role of vitamin D in peripheral vascular disease and peripheral neuropathy, which are the major risk factors for DFU, as well as evidences of its role in wound healing and management of DFU.

Results: Preclinical and clinical studies have shown that vitamin D influences multiple phases of wound healing and thereby accelerates the process. It modulates various cells involved in proliferation and remodelling phases. Vitamin D also enhances the expression of antimicrobial peptides that help to eliminate the microbes, as well as suppress the proinflammatory responses while enhancing the anti-inflammatory responses.

Conclusion: This review concludes vitamin D to have a protective role in the immune and vascular system, improve glycaemic outcomes, and wound healing. Therefore, vitamin D could be a preferred adjuvant in the management of DFU.