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.

Objective: This paper aims to discuss the mechanism of actions, pathways, and metabolites triggered due to the development of neuropathy and nephropathy post-long-haul diabetes in patients. The therapeutic targets are also highlighted, proving to be a potential cure for such conditions.

Methods: Research works were searched from international and national databases with keywords like “diabetes,” “diabetic nephropathy,” “NADPH,” “oxidative stress,” “PKC,” “Molecular mechanisms,” “ cellular mechanisms,” “complications of diabetes,” and “factors.” The databases searched were PubMed, Scopus, Directory of open access journals, Semantic Scholar, Core, Europe PMC, EMBASE, Nutrition, FSTA- Food Science and Technology, Merck Index, Google Scholar, PubMed, Science Open, MedlinePlus, Indian citation index, World Wide Science, and Shodhganga.

Results: Pathways causing protein kinase C (PKC) activation, free radical injury, oxidative stress, and aggravating the conditions of neuropathy and nephropathy were discussed. In diabetic neuropathy and nephropathy, neurons and nephrons are affected to the extent that their normal physiology is disturbed, thus leading to further complications and conditions of loss of nerve sensation in diabetic neuropathy and kidney failure in diabetic nephropathy.

Current treatment options available for the management of diabetic neuropathy are anticonvulsants, antidepressants, and topical medications, including capsaicin. According to AAN guidelines, pregabalin is recommended as the first line of therapy, whereas other drugs currently used for treatment are gabapentin, venlafaxine, opioids, amitriptyline, and valproate.

Drug targets for treating diabetic neuropathy must suppress the activated polyol pathways, kinase C, hexosamine, and other pathways, which amplify neuroinflammation. Targeted therapy must focus on the reduction of oxidative stress and proinflammatory cytokines and suppression of neuroinflammation, NF-κB, AP-1, etc.

Conclusion: Potential drug targets must be considered for new research on the treatment of neuropathy and nephropathy conditions.]]> https://www.benthamscience.comarticle/135222Objective: The potential mechanism underlying the protective effect of Astragaloside IV (AS-IV) co-treatment with 1, 25-dihydroxy-vitamin D (Vit-D) on neuropathy in diabetic high-fat rats was investigated.

Methods: The rat diabetic hyperlipidemia (DH) model was established via streptozotocin and a high-fat diet (HFD). After co-treatment (of AS-IV and Vit-D at respective doses of 50 mg/kg via oral gavage and 30000 IU/kg via intramuscular injection), blood glucose levels, markers of inflammation and oxidative stress, as well as apoptosis and histopathology were evaluated with appropriate techniques.

Results: Co-treatment could effectively reduce blood glucose levels substantially (p< 0.01), improve weight loss, and decrease oral glucose tolerance. Reduced respective sensory and motor nerve conduction velocities in rats were substantially improved (p<0.01) after co-treatment. Also, we observed obvious improvement in DH-induced injured nerve fiber myelin structure and other organ pathologies in co-treated rats. Besides, we observed up-regulated expressions of peroxisomal-proliferator activated receptor-alpha (PPAR-α) and Vit-D receptors (VDR) (p< 0.01) through the western blotting technique. Using the same technique, we also discovered reduced levels of interleukin (IL)1 beta, IL-6, and tumor necrosis factor-alpha, coupled with increased IL-10 and superoxide dismutase levels (p< 0.01). Importantly, co-treatment could effectively exert antioxidative and anti-inflammatory effects. Also, co-treatment resulted in the up-regulation of PPAR-α and VDR expressions, inhibition of the renin–angiotensin–aldosterone system, and promotion of β-cell sensitivity to insulin.

Conclusion: The combined application of AS-IV and Vit-D exhibited health effects such as anti-oxidation, regulation of inflammatory factors, and promotion of cell repair, which may be considered as the mechanisms underlying treatment of diabetic peripheral neuropathy and improvement in biochemical indicators.

Objectives: This study aimed to investigate ocular blood flow in eyes with or without diabetic macular edema using arterial spin labeling.

Methods: This cross-sectional study included 118 eyes of 65 patients with diabetic retinopathy analyzed between November 2018 and December 2019. We included a total of 53 eyes without diabetic macular edema (mean [SD] age, 57.83 [7.23] years; 29 men [54.7%]) and 65 eyes with diabetic macular edema (mean [SD] age, 60.11 [7.63] years; 38 men [58.5%]). Using a 3.0-T magnetic resonance imaging, participants were imaged with arterial spin labeling with multiple post-labeling delays.

Results: The mean ocular blood flow at post-labeling delays of 1.5 and 2.5 s was significantly lower in eyes with diabetic macular edema among patients with diabetic retinopathy compared with the remaining subgroups (P=0.022 and P <0.001, respectively). The mean ocular blood flow exhibited a significant decrease in eyes with diabetic macular edema when the post-labeling delay was set at 2.5 s in the nonproliferative and proliferative diabetic retinopathy groups, compared with the remaining subgroups (P=0.005 and P=0.002, respectively). The cutoff points of ocular blood flow at post-labeling delays of 1.5 s and 2.5 s were 9.40 and 11.10 mL/100 g/min, respectively.

Conclusion: Three-dimensional pseudocontinuous arterial spin labeling can identify differences in the ocular blood flow of patients with diabetic eyes with and without diabetic macular edema.

Case Presentation: A 55-year-old female patient presented with right elbow pain. An oval mass was seen near the medial epicondyle on the radiograph. A dynamic ultrasound examination was performed to reveal the relationship between the bone mass and the surrounding tissues, especially the ulnar nerve. Due to the well-circumscribed mass, a diagnosis of os subepicondylare mediale, a rare sesamoid bone, was made in light of current literature.

Conclusion: When a bone mass is seen in patients presenting with elbow pain, it will be useful to know and consider the sesamoid bones. In addition, ultrasonography should be performed in addition to radiography for a localized sesamoid bone in the medial region and adjacent to the ulnar nerve. Thus, the relationship of the sesamoid bone with existing and potential complaints can be revealed and correct diagnosis-treatment approaches can be applied.

Objective: The main objective of the present study was to evaluate the effect of this newly developed special laser shoe PBM on neuropathic pain and plantar pressure profile in individuals with type 2 diabetes mellitus with neuropathy.

Methods: We included 60 participants with diabetic peripheral neuropathy of both genders and age more than 20 years. Participants were treated with PBM by a specially designed novel Laser Shoe. Outcomes were clinical variables like Vibration Perception Threshold (VPT), Visual Analogue Scale (VAS), Michigan neuropathy screening instrument A&B, Ankle-Brachial Index (ABI), and Static dynamic gait parameters.

Results: Participants were with an average age of 62, and the average duration of diabetes was 11 years. Analysis showed a significant difference in VPT, VAS, Michigan neuropathic screening inventory, and ankle-brachial index (P < 0.05).

Conclusion: We conclude that Novel laser shoe photobiomodulation using 'Laser Shoe' effectively reduces peripheral neuropathic pain. It is also effective in reducing average and maximum plantar pressure. Reduction in neuropathic pain and improvement in plantar pressure distribution can reduce further complications.

Background: Diabetic Peripheral Neuropathy (DPN) is the most common and debilitating complication of Type 2 Diabetes Mellitus (T2DM).

Methods: Newly diagnosed T2DM patients visiting the outpatient department were recruited. Detailed demographic parameters, histories, physical examinations, and biochemical investigations were carried out. Patients were screened for DPN using the Diabetic Neuropathy Symptom (DNS) score, the revised Disability Neuropathy Score (NDS), Vibration Perception Threshold (VPT) using a biosthesiometer, and the 10 g SW Monofilament Test (MFT).

Results: A total of 350 newly diagnosed T2DM patients (mean age 46.4±13.6 years) were included. The prevalence of DPN was found to be 34% using the combined DNS and NDS scores. VPT was moderately impaired in 18.3% and severely impaired in 12% patients, while MFT revealed a loss of protective sensation in 35.4% patients. After logistic regression analysis, DPN was significantly associated with increasing age (OR 1.08, 95%CI 1.06-1.11), increasing HbA1C levels (OR 1.23, 95%CI 1.05-1.42), increasing TSH levels (OR 1.23, 95%CI 1.05-1.44), presence of hypertension (OR 2.78, 95%CI 1.51-5.11), and reduced BMI (OR 0.9, 95%CI 0.84- 0.99). The sensitivity and specificity of detecting DPN by combining VPT and MFT were 91.6% and 84.2%, respectively.

Conclusion: The prevalence of DPN was high even in newly diagnosed T2DM and associated significantly with increasing age, HbA1C levels, TSH levels, hypertension, and reduced BMI. Earlier screening for DPN, along with aggressive control of glycemia, blood pressure, and hypothyroidism, may be beneficial.

Methodology: In addition to traditional therapies with insulin and oral anti-diabetics, researchers have developed new approaches for treatment, including stem cell (SC) therapy, which exhibits promising outcomes. Besides its significant role in treating type one DM (T1DM) and type two DM (T2DM), it can also attenuate diabetic complications. Furthermore, the development of insulin- producing cells can be achieved by using the different types of SCs, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and multiple types of adult stem cells, such as pancreatic, hepatic, and mesenchymal stem cells (MSC). All these types have been extensively studied and proved their ability to develop insulin-producing cells, but every type has limitations.

Conclusion: This review aims to enlighten researchers about recent advances in stem cell research and their potential benefits in DM and diabetic complications.

Background: Diabetic foot ulcer (DFU) is a multifactorial disorder that involves chronic inflammation, oxidative stress and neuropathy. Current treatment therapies involving the use of growth factors and skin substitutes being costly, are out of reach for the majority of patients. The present research explored the usefulness of a combination of tetrahydrocurcumin and folic acid-loaded nanostructured lipidic carriers in DFU.

Objectives: To develop and validate a QbD-assisted method for simultaneous analysis of tetrahydrocurcumin (THC) and folic acid (FA). Applicability of the above method to determine total drug content (TDC) and entrapment efficiency (EE) of nanostructured lipid carriers (NLCs) loaded with THC and FA.

Methods: A high-performance liquid chromatographic (HPLC) method was developed, optimized and validated using Box-Behnken design for improved method performance. Chromatographic separation was conducted on a Supelco 250 x 4.6 mm (5 μm) column with optimized mobile phase composition containing tetrahydrofuran: citric acid buffer pH 3.5 (50:50) at a flow rate of 0.4 mL.min-1 and diode array detection between 210 and 360 nm.

Results: The method developed in a concentration range of 1 to 100 μg.mL^-1 was found to be linear (R² 0.999, p≤0.001), accurate (99.10-101.70%) and precise with high recovery values in intra and inter-day results. The system adaptability and robustness evaluation revealed that the percent recovery ranged from 96.90 to 102.80%, and the percent relative standard deviation (%RSD) values were less than 2%. Moreover, the method was further applied for the determination of TDC (86±6% and 96±8%) and drug EE (81±21% and 73±13%) for THC and FA, respectively.

Conclusion: The investigation indicated the applicability of the developed and validated method for the estimation of THC and FA in the developed nanostructured lipidic carriers.]]> https://www.benthamscience.comarticle/140548 https://www.benthamscience.comarticle/137581Background: Diabetes neuropathy is a frequent ailment that has a substantial impact on patients by increasing the risk of falls and causing discomfort. The lower extremities are where diabetic neuropathy patients first feel pain. This discomfort could seem like a pinprick, an electric shock, or something else.

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.

Method: According to the PRISMA guideline, a systematic search was accomplished to identify all relevant scientific papers on “the role of resveratrol against cisplatin-induced ototoxicity” in different electronic databases up to May 2021. Fifty-five articles were screened based on a predefined set of inclusion and exclusion criteria. Eight eligible studies were finally included in the current systematic review. The in-vitro findings revealed that cisplatin administration significantly decreased the HEI-OC1 cell viability compared to the untreated cells; however, resveratrol co-treatment (in a dose-dependent manner) could protect HEI-OC1 cells against cisplatin-induced decrease in cell viability.

Results: Furthermore, the in-vivo finding showed a decreased value of DPOAE, and increased values of ABR threshold, ABR-I, ABR-IV, and ABR I-IV interval in cisplatin-treated animals; in contrast, resveratrol co-administration demonstrated an opposite pattern on these parameters.

Conclusion: Thus, it can be mentioned that resveratrol co-treatment alleviates cisplatin-induced ototoxicity. Mechanically, resveratrol exerts its otoprotective effects through various mechanisms such as anti-oxidant, anti-apoptosis, and anti-inflammatory.

Objectives: The objective of this review was to relate the consumption of probiotic bacteria and its effects on inflammatory diseases, including obesity, type II diabetes and celiac disease.

Methods: A search was carried out in English, between the years 2011 and 2022, for research articles and clinical trials with humans and in vivo studies. Research showed improvement in cardiovascular risk markers, and improvement in insulin sensitivity, lipid profile and plasma atherogenic index, in obesity with the use of probiotics. In type II diabetes, decreased levels of fasting glucose, glycated hemoglobin, insulin and glycemic index, and increased levels of peptide 1, superoxide dismutase and glutathione peroxidase were observed.

Results: In addition to cellular protection of the islets of Langerhans and positive alteration of TNF- α and IL-1β markers. Improvement in the condition of patients with celiac disease was observed, since the neutralization of the imbalance in serotonin levels was observed, reducing the expression of genes of interest and also, a decrease in cytokines.

Conclusion: Therefore, the use of probiotics should be encouraged.

Objective: This review aims to summarize recent advances in the development of treatment strategies for FRDA, with a focus on potential drug candidates and their mechanisms of action.

Methods: A comprehensive literature search was conducted using various authentic scientific databases to identify studies published in the last decade that investigated potential treatment strategies for FRDA. The search terms used included “Friedreich's ataxia”, “treatment”, “drug candidates”, and “mechanisms of action”.

Results: To date, only one drug got approval from US-FDA in the year 2023; however, significant developments were achieved in FRDA-related research focusing on diverse therapeutic interventions that could potentially alleviate the symptoms of this disease. Several promising drug candidates have been identified for the treatment of FRDA, which target various aspects of frataxin deficiency and aim to restore frataxin levels, reduce oxidative stress, and improve mitochondrial function. Clinical trials have shown varying degrees of success, with some drugs demonstrating significant improvements in neurological function and quality of life in FRDA patients.

Conclusion: While there has been significant progress in the development of treatment strategies for FRDA, further research is needed to optimize these approaches and identify the most effective and safe treatment options for patients. The integration of multiple therapeutic strategies may be necessary to achieve the best outcomes in FRDA management.

Objective: This study aimed to identify and analyze the main interventions used to improve static balance in patients with DM.

Methods: For the selection of articles, a bibliographic search was performed using PubMed, Scopus, Web of Science, Embase, and Cochrane databases. Only clinical trials that investigated the effect of training on static balance in adults with type 2 DM were selected, and 34 studies were included.

Results: The search resulted in the identification of 2681 articles, and of these, 31 were eligible for the study. The identified interventions were proprioceptive, aerobic, resistance training on platforms, in virtual reality, and Tai Chi. The main results obtained were an increase in time in the one-leg stance, Romberg test, and tandem position, a significant increase in the Berg Balance Scale score and balance index, and a reduction in the variables of postural sway.

Conclusion: There are a variety of effective training methods for improving static balance, and the choice of intervention to be applied goes beyond proven effectiveness, depending on reproducibility and/or financial cost.

Objective: The aim of this systematic review was to investigate the association between diabetes microvascular complications, including retinopathy, neuropathy, nephropathy, and gut microbiota composition.

Methods: A systematic search was carried out in PubMed, Scopus, and ISI Web of Science from database inception to March 2023. Screening, data extraction, and quality assessment were performed by two independent authors. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment.

Results: About 19 articles were selected from 590 retrieved articles. Among the included studies, nephropathy has been studied more than other complications of diabetes, showing that the composition of the healthy microbiota is changed, and large quantities of uremic solutes that cause kidney injury are produced by gut microbes. Phyla, including Fusobacteria and Proteobacteria, accounted for the majority of the variation in gut microbiota between Type 2 diabetic patients with and without neuropathy. In cases with retinopathy, an increase in pathogenic and proinflammatory bacteria was observed.

Conclusion: Our results revealed that increases in Bacteroidetes, Proteobacteria and Fusobacteria may be associated with the pathogenesis of diabetic nephropathy, neuropathy, and retinopathy.

In view of the detrimental role of intestinal dysbiosis in the development of diabetes-related complications, gut microbiota assessment may be used as a biomarker in the future and interventions that modulate the composition of microbiota in individuals with diabetes can be used to prevent and control these complications.

Method: The features used to predict the complications are identified and categorised by scrutinising the standards of electronic health records.

Result: Overall, 102 research articles have been reviewed, resulting in 59 frequent features being identified. Nineteen attributes are recognised as a standard in all four considered complications, which are age, gender, ethnicity, weight, height, BMI, smoking history, HbA1c, SBP, eGFR, DBP, HDL, LDL, total cholesterol, triglyceride, use of insulin, duration of diabetes, family history of CVD, and diabetes. The existence of a well-accepted and updated feature set for health analytics models to predict the complications of diabetes mellitus is a vital and contemporary requirement. A widely accepted feature set is beneficial for benchmarking the risk factors of complications of diabetes.

Conclusion: This study is a thorough literature review to provide a clear state of the art for academicians, clinicians, and other stakeholders regarding the risk factors and their importance.

Objectives: To produce a specific molecule with potent therapeutic properties, it is now common methods to combine at least two pharmacophores. This facilitates interaction with several targets, enhances biological functions, or eliminates adverse effects associated with them.

Conclusion: The synthesis of benzimidazole-1,3,4-oxadiazole hybrid compounds has recently involved the use of several synthetic techniques, all of which are detailed in the literature along with the advantages and disadvantages. It has been noted that the structure-activity relationship relates their pharmacological actions to their molecular structure. In order to set the stage for future research, the study aims to provide researchers with an effective toolbox and an understanding of benzimidazole and 1,3,4-oxadiazole hybrid compounds.

Aims: This study was performed to evaluate the neuroprotective effect in diabetes by enhancing antioxidant defense against oxidative stress, which exhibits a neuroprotective effect in streptozotocin- induced diabetic rats.

Objectives: The objective of this study was to elucidate the therapeutic potential of bioactive compounds of Swertia chirayita for diabetic complications.

Methods: The present work focused on isolating the bioactive from the leaves of Swertia absinthe for acute toxicity studies, assessing its protective effects against diabetes and diabetic neuropathy as well as its mode of action in STZ-induced Wistar rats. The local area of Moradabad is the place from where the leaves of Swertia chirayita were gathered. Mangiferin was isolated and identified using spectroscopic techniques, such as UV, HPLC, 1H NMR, C13 NMR, MAS, and FTIR. Mangiferin was administered in doses of 15 and 30 mg/kg to test its effect on experimentally induced diabetes. The sciatic nerves of all groups were examined histopathologically. The protective effect of the drug against diabetes and diabetic neuropathy was demonstrated by measures, such as blood glucose level, body weight, food intake, thermal hyperalgesia, grip strength, spontaneous locomotor test, and lipid profile analysis. Sciatic nerve cells of the treated groups showed less inflammation, degeneration, and necrosis.

Results: The results of this study confirmed that mangiferin alleviated diabetic neuropathic pain, possibly by reducing inflammatory cytokines (TNF-α, TGF-β1, IL-1β, and IL-6), strong antioxidant activity, and NGF in sciatic nerves. It may be a therapeutic agent.

Conclusion: Our results suggested that active phytochemicals of Swertia chirayita showed preventive and curative effects against STZ-induced diabetic neuropathy in rats, which might be due to its antioxidant, anti-inflammatory, and anti-apoptotic properties.

Several online databases including PubMed, Google Scholar, and Science Direct have been searched for gathering the information covered in this review. Empirical studies demonstrated that most of these natural compounds exhibited therapeutic properties through their immunomodulatory and anti-inflammatory potential supplemented often with anti-microbial, anti-neoplastic, and anti- oxidant activities. Overall, plant-based natural products discussed here are capable of modulating the immune system to minimize or completely suppress the pro-inflammatory markers, scavenge free radicals (ROS), prevent bacteria, fungal, and virus-derived skin infections and often regress skin cancer through the induction of apoptosis. The challenges and opportunities associated with the application of plant-based immunomodulators for skin applications and their safety considerations are also discussed here. The present study indicated that immunomodulatory plant natural products being biologically validated ligands against various biological targets manifested in inflammatory skin diseases, offer an effective, safe and affordable treatment for such disorders affecting skin health. However, further clinical evaluations are needed to substantiate these findings.

Objective: Here, we propose that the human body exclusively employs mechanisms of adaptation to protect itself during an adverse event. For this purpose, two control systems are defined, namely the autonomic and the neural control systems. The autonomic control system responds via inflammatory and immune responses, while the neural control system regulates neural signaling, via plastic adaptation. Both systems are proposed to regulate a network of temporal and causative connections which unravel the complex nature of diabetic complications.

Results: A significant result of this approach infers that both systems make DN reversible, thus opening the door to novel therapeutic applications.

Methods: Human umbilical cord mesenchymal stem cells were assessed for adipogenic differentiation, osteogenic differentiation, and proliferation ability. Vonfry and a hot disc pain tester were used to evaluate tactile sensation and thermal pain sensation in mice. Hematoxylin-eosin and TUNEL staining were performed to visualize sciatic nerve fiber lesions and Schwann cell apoptosis in diabetic mice. Western blotting was used to detect expression of the apoptosis-related proteins Bax, B-cell lymphoma-2, and caspase-3 in mouse sciatic nerve fibers and Schwann cells. Real-Time Quantitative PCR was used to detect mRNA levels of the C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 2, C-X-C motif chemokine ligand 9, and C-X-C motif chemokine ligand 10 in mouse sciatic nerve fibers and Schwann cells. Enzyme-linked immunosorbent assay was used to detect levels of the inflammatory cytokines, interleukin- 1β, interleukin-6, and tumor necrosis factor-α in serum and Schwann cells.

Results: The adipogenic differentiation capacity, osteogenic differentiation capacity, and proliferation ability of human umbilical cord mesenchymal stem cells were enhanced after interferon-gamma treatment. Real-Time Quantitative PCR revealed that interferon-gamma promoted expression of the adipogenic markers, PPAR-γ and CEBP-α, as well as of the osteogenic markers secreted phosphoprotein 1, bone gamma-carboxyglutamate protein, collagen type I alpha1 chain, and Runt-related transcription factor 2. The results of hematoxylin-eosin and TUNEL staining showed that pathological nerve fiber damage and Schwann cell apoptosis were reduced after the injection of interferon-gamma-treated human umbilical cord mesenchymal stem cells. Expression of the apoptosis-related proteins, caspase-3 and Bax, was significantly reduced, while expression of the anti-apoptotic protein B-cell lymphoma-2 was significantly increased. mRNA levels of the cell chemokines, C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 2, C-X-C motif chemokine ligand 9, and C-X-C motif chemokine ligand 10, were significantly reduced, and levels of the inflammatory cytokines, interleukin-1β, interleukin-6, and tumor necrosis factor-α, were decreased. Tactile and thermal pain sensations were improved in diabetic mice.

Conclusion: Interferon-gamma treatment of umbilical cord mesenchymal stem cells enhanced osteogenic differentiation, adipogenic differentiation, and proliferative potential. It can enhance the ability of human umbilical cord mesenchymal stem cells to alleviate damage to diabetic nerve fibers and Schwann cells, in addition to improving the neurological function of diabetic mice.

Objective: Abuse of alcohol does not occur suddenly. People becoming addicted to various alcoholic beverages is a problem that results from months and years of irresponsible drinking. The process of recovering from the issue in turn includes targeted, particular methods for raising awareness of the negative effects of alcohol usage.

Conclusion: Due to the heightened risks for one's bodily and mental health along with the social issues it generates, alcohol consumption results in these costs. We discuss the three areas of the epidemiology of alcohol's impact on health and diseases, the public health approach for treating problems related to alcohol use, and advancements in alcohol science.

Methods: The effect of naringenin on the apoptosis of CAL-27 cells and its mechanism were studied by cell counting kit-8, mitochondrial membrane potential assay with JC-1, Annexin V-- FITC apoptosis detection, cell cycle, and apoptosis analysis, Reactive Oxygen Species assay and Western blot.

Results: The results showed that naringenin significantly induced apoptosis in CAL-27 cells in a dose-dependent manner. Mechanistically, naringenin-induced apoptosis was mediated through the upregulation of Bid and downregulation of Bcl-xl, which led to increased generation of ROS.

Conclusion: The findings suggested that naringenin may represent a promising candidate for the treatment of oral cancer by inducing apoptotic cell death via modulation of the Bid and Bcl-xl signaling pathways.

Methods: The present consensus was based on the three-step modified Delphi method. The modified Delphi method is based on a series of voting rounds and in-between meetings of the expert panel to reach agreements on the statements that did not reach the consensus level during voting. The panel group comprised professors and consultants in endocrinology (both adult and pediatric). Other members included experts in the fields of cardiovascular medicine, nephrology, ophthalmology, and vascular surgery, affiliated with academic institutions in Egypt.

Result: In PwDM who intend to fast during Ramadan, risk stratification is crucial to optimize patient outcomes and prevent serious complications. The present consensus provides risk assessment of those living with diabetes according to several factors, including the type of diabetes, presence, and severity of complications, number of fasting hours, and other socioeconomic factors. According to their risk factors, patients were classified into four categories (very high, high, moderate, and low risk).

Conclusion: Future research is warranted due to the controversial literature regarding the impact of fasting on certain comorbidities.

Objective: To systematically review the scientific literature and provide a comprehensive summary on the neuroprotective action and the mechanisms involved in the cytoprotective effects of TUDCA.

Methods: A systematic review was conducted in accordance with the PRISMA (The Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Systematic literature search of United States National Library of Medicine (PubMed), Web of Science, Embase, Scopus and Cochrane Library was performed, which covered all original articles published up to July 2022. The terms, “TUDCA” in combination with “retina”, “retinal protection”, “neuroprotection” were searched. Possible biases were identified with the adopted SYRCLE’s tool.

Results: Of the 423 initially gathered studies, 24 articles met inclusion/exclusion criteria for full-text review. Six of them were in vitro experiments, 17 studies reported in vivo data and one study described both in vitro and in vivo data. The results revealed the effect of TUDCA on different retinal diseases, such as retinitis pigmentosa (RP), diabetic retinopathy (DR), retinal degeneration (RD), retinal ganglion cell (RGC) injury, Leber’s hereditary optic neuropathy (LHON), choroidal neovascularization (CNV), and retinal detachment (RDT). The quality scores of the in vivo studies were ranged from 5 to 7 points (total 10 points), according to SYRCLE’s risk of bias tool. Both in vitro and in vivo data suggested that TUDCA could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and function, and its mechanism of actions might be related with inhibiting apoptosis, decreasing inflammation, attenuating oxidative stress, suppressing endoplasmic reticulum (ER) stress, and reducing angiogenesis.

Conclusion: This systematic review demonstrated that TUDCA has neuroprotective effect on in vivo and in vitro models of retinal disorders, reinforcing the currently available evidence that TUDCA could be a promising therapeutic agent in retinal diseases treatment. However, well designed clinical trials are necessary to appraise the efficacy of TUDCA in clinical setting.

Objectives: This study aimed to investigate the possible mechanism of CLY in relation to DFU using network pharmacology and molecular docking.

Materials and Methods: Firstly, relevant targets of CLY against DFU were obtained from TCMSP, Swiss Target Prediction database and GEO database. Then, topological analysis was employed by Cytoscape to screen the top 6 core active ingredients and the top 8 hub targets. Furthermore, the OmicShare Tools were applied for gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis. Finally, the results of network pharmacology were verified by molecular docking method.

Results: CLY has 61 active compounds and 361 targets after de-duplication, and the top 8 hub targets were EGFR, TP53, CCND1, IL-1B, CREBBP, AR, PTGS2 and PGR. GO enrichment analysis is mainly related to signal transducer activity, receptor activity, and molecular transducer activity. KEGG pathway analysis indicated that these shared targets were primarily focused on AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, IL-17 signaling pathway, and JAK-STAT signaling pathway. Molecular docking results showed that physciondiglucoside, 2-cinnamoyl-glucose and kinobeon A were well bound with EGFR, IL-1B, AR and PTGS2.

Conclusion: This study demonstrated that CLY has anti-oxidative stress and anti-inflammatory effects in the treatment of DFU through various constituents, multiple targets, and multiple pathways, which provides a valuable point of reference for future investigations on CLY.

Methods: The pathogenesis and development of diabetic neuropathies may be explained by a wide variety of molecular pathways, hexosamine pathways, such as MAPK pathway, PARP pathway, oxidative stress pathway polyol (sorbitol) pathway, cyclooxygenase pathway, and lipoxygenase pathway. Although diabetic neuropathies can be treated symptomatically, there are limited options for treating the underlying cause.

Result: Various pathways and screening models involved in diabetic neuropathies are discussed, along with their possible outcomes. Moreover, both medicinal and non-medical approaches to therapy are also explored.

Conclusion: This study highlights the probable involvement of several processes and pathways in the establishment of diabetic neuropathies and presents in-depth knowledge of new therapeutic approaches intended to stop, delay, or reverse different types of diabetic complications.

Methods: Data analysis was performed using Statistical Package for the Social Sciences, SPSS 23rd version. Frequency and percentages were used to display categorical variables. Minimum, maximum, mean, and standard deviation were used to test numerical variables. Independent t-test and ANOVA test were both utilized to test the factors associated with knowledge and attitude toward the use of SGLT-2 inhibitors.

Results: A total of 65 participants were included in the study. 26.2% had a low knowledge level, 30.8% had a moderate knowledge level, and 43.1% had a high knowledge level of sodium-glucose cotransporter 2 inhibitors. 9.2% had a low attitude level, 43.1% had a moderate attitude level, and 47.7% had a high attitude level toward sodium-glucose cotransporter 2 inhibitors. Age, professional status, years of experience, and specialty were significantly associated with attitude but not with the knowledge of sodium-glucose cotransporter 2 inhibitors prescription.

Conclusion: While the study cohort scored high in the knowledge and attitude domains of the survey, a large proportion failed to answer very essential questions in type 2 diabetes management. An educational awareness program needs to be carried out to strengthen the physicians’ knowledge of SGLT2 inhibitors prescription.]]> https://www.benthamscience.comarticle/135366 https://www.benthamscience.comarticle/134512 https://www.benthamscience.comarticle/131545Background: Diabetes mellitus leading to foot ulcer is a serious complication, and it is considered a global epidemic. Neuropathyand high blood glucose levels are the primary causes of foot ulcers. Fifteen percent of people with diabetes develop foot ulcers, and these foot disorders are the main cause of lower extremity amputation among such patients.

Introduction: Complications of diabetic foot, affecting the lower extremities are common and quite complex and life-threatening. This review focuses on the life-threatening factors associated with diabetic foot ulcers and also the diagnosing and preventive measures. Neuropathy assessment and the range of foot ulcers were accurately examined.

Conclusion: Novel therapies focusing on the vascularity of the lower limbs, infection control, and ischemic control are being developed to mainly treat nonhealing ulcers.

Objective: Considering the emerging search for new therapies for the control of DN and the growing commercial interest in the probiotics market, this study aimed to provide patents on the use of probiotics in the control of DN.

Methods: This is a patent prospection performed in the Espacenet Patent database, using the association of keywords and IPC related to probiotics in medical preparations and foods, from 2009 to December 2022.

Results: Results have shown that in 2020, there was a boom in patent filing in the area. Asian countries accounted for more than 50% of all 48 inventions (n = 48), with Japan as the only applicant in 2021. Products being developed in recent years point to effects that may represent an advancement in DN treatment, such as reduced concentration of pro-inflammatory mediators, metabolites and neurotransmitters release, and hypoglycemic potential. All effects were more related to the Lactobacillus and Bifidobacterium genera, associated with more than one property mentioned.

Conclusion: The mechanisms attributed to the microorganisms suggest the therapeutic potential of probiotics in the non-pharmacological treatment of pain. New applications for probiotics have resulted from great research interest by academia, but also reflect commercial interests despite the paucity of clinical trials. Thus, the present work supports the evolution of research to explore the benefits of probiotics and their clinical use in DN.

Methodology: The databases, PubMed, ResearchGate, Scopus, Web of Science, Science Direct, CINAHL, and Cochrane were searched using relevant keywords for the study. Full articles in English since 2000, including keywords “Prevalence”, “Diabetic peripheral neuropathy”, “Diabetic foot”, and “MENA region” were reviewed in two phases. All authors screened the titles and abstracts of the articles individually, which was followed by a screening of full texts. A consensus was made among all the authors for the final selection of the articles based on the eligibility criteria.

Results: Ten selected articles on the prevalence of DPN were reviewed in the first phase of the study, which reported varying prevalence rates among the different countries of the MENA region ranging from 9% to 61%. In the second phase, only two articles on DF prevalence were shortlisted. They reported the prevalence of DF as 4.6% and 18.1% in Jordan and Sudan, respectively.

Conclusion: The prevalence of DPN in the MENA region is varied within a short period of time and the reported prevalence of DF is limited. This study projects a strong need of establishing early screening strategies for DPN and DF to prevent further complications and decrease healthcare burden.

Further cautions are required when paresthesia is acute (within days) in onset, rapidly progressive, severe, asymmetric, proximal, multifocal, or associated with predominant motor signs (limb weakness) or severe dysautonomia. Acroparesthesia may reveal Guillain-Barré syndrome or vasculitis, requiring rapid management.

Acroparesthesia is a predominant symptom of polyneuropathy, typically distal and symmetric, often due to diabetes. However, it can occur in other diseases such as vitamin B12 deficiency, monoclonal gammopathy of undetermined significance, or Fabry’s disease. Mononeuropathy, mainly carpal tunnel syndrome, remains the most common cause of acroparesthesia.

Ultrasonography contributes to the diagnosis of nerve entrapment neuropathy by showing nerve enlargement, hypoechogenic nerve, and intraneural vascularity. Besides, it can reveal its cause, such as space-occupying lesions, anatomical nerve variations, or anomalous muscle. Ultrasonography is also helpful for entrapment neuropathy treatment, such as ultrasound-guided steroid injection or carpal tunnel release.

The management of acroparesthesia depends on its causes.

This article aimed to review and summarize current knowledge on acroparesthesia and its causes.

We also propose an algorithm for the management of acroparesthesia.

Objective: Considering the therapeutic value of the plant, focus on using current technology to quantify and confirm the pharmacological effects with in vitro and in vivo assays was felt and to shed light on in silico investigations.

Results: Relevant analytical tools for characterizing and quantifying phytoconstituents in the plant, along with emphasis on well-established pharmacological screening experiments on parts and whole plant extracts, commercially available formulations of H.spinosa have been elaborated. It has been discussed how to further validate the pharmacological effects using insilico methods and predictions from ADME/T analyses. H. spinosa based Phyto fabricated nanoparticle systems with gold and silver have broadened the use of plant extract as a metal. carrier which minimizesmetal. toxicity to further boost its synergistic effects in response to the growing need for targeted medicine delivery systems.

Conclusión: In light of the necessity to investigate a specific mechanism of action for each of the specific phytoconstituents contained in the plant, the present review summarizes the phytochemical and pharmacological importance of the plant in chronic illness.]]> https://www.benthamscience.comarticle/136674 https://www.benthamscience.comarticle/130676Background: Toenail onychomycosis is common in patients with diabetes and it can increase the risk of secondary infections and foot complications. Despite several studies investigating the prevalence and associated factors of toenail onychomycosis from different parts of the world, there are no data from Jordan.

Objective: To determine the prevalence and the associated factors of toenail onychomycosis among patients with diabetes in Jordan.

Methods: A cross-sectional study was conducted on 375 patients with diabetes at the National Centre for Diabetes, Endocrinology, and Genetics in Amman, Jordan. Several socio-demographic and health-independent variables including foot self-care practices were collected. Toenail onychomycosis was assessed by a specimen culture and microscopic examinations. Descriptive and inferential statistics were used for data analysis.

Results: The prevalence of toenail onychomycosis was 57.6% (n=216). Multiple logistic regression revealed four significant associated factors; the presence of neuropathy (β=1.87, p=0.02), being an ex-smoker (β=2.69, p=0.01), being treated by both insulin and oral hypoglycemics drugs (β=1.32, p=0.03), and using antibiotics in the last year (β=1.78, p=0.02).

Conclusion: The prevalence of toenail onychomycosis among patients with diabetes in Jordan is high. Regular foot screening and podiatric care are recommended especially among patients with diabetic neuropathy, current treatment by insulin and oral hypoglycemics drugs, previous history of smoking, and previous use of antibiotics.

Objective: To analyze the incidence, prevalence, and risk factors associated with diabetic foot in people with type 2 Diabetes Mellitus.

Method: Systematic literature review. Searches in MedLine via PubMed, LILACS, Web of Science, Scopus CINAHL, and Cochrane Library databases were performed. Inclusion of 52 studies. The R program, Metan packages, was used to calculate the meta-analysis. Given the heterogeneity of studies, the random effect was used to calculate the meta-analysis of risk factors.

Results: The meta-analysis showed that the prevalence of diabetic foot was 14% in a hospital setting and 5% in a community setting. The overall prevalence and incidence were 9% and 4%, respectively. Significant risk factors included time of DM (odds ratio [OR] =1.46, confidence interval [CI], 0.36-2.57, P = 0.009), smoking (OR = 1.46, CI, 1.16 -1.85, P< .001), glycated hemoglobin (OR = 0.96, CI, 0.50; 1.42, P< .001), peripheral arterial disease (OR = 3.38, CI, 2.07; 5.53, P < .001) and peripheral neuropathy (OR = 5.88, CI, 2.39-14.45, P<.001).

Conclusion: Multidisciplinary monitoring, educational strategies, periodic foot examination for alterations, and early identification of risk factors are essential to prevent ulceration and reduce the disease burden.

Materials and Methods: Gamma-mangostin (γ-mangostin), a xanthone derived from Garcinia mangostana, possesses cytoprotective properties in various pathological conditions. In this study, we employed S16Y cells as a representative Schwann cell model to investigate the protective effects of γ-mangostin against the toxicity induced by tert-Butyl hydroperoxide (tBHP). Different concentrations of γ-mangostin and tBHP were used to determine non-toxic doses of γ-mangostin and toxic doses of tBHP for subsequent experiments. MTT cell viability assays, cell flow cytometry, and western blot analysis were used for evaluating the protective effects of γ-mangostin.

Results: The results indicated that tBHP (50 μM) significantly reduced S16Y cell viability and induced apoptotic cell death by upregulating cleaved caspase-3 and cleaved PARP protein levels and reducing the Bcl- X_L/Bax ratio. Notably, pretreatment with γ-mangostin (2.5 μM) significantly mitigated the decrease in cell viability caused by tBHP treatment. Furthermore, γ-mangostin effectively reduced cellular apoptosis induced by tBHP. Lastly, γ-mangostin significantly reverted tBHP-mediated caspase-3 and PARP cleavage and increased the Bcl-X_L/Bax ratio.

Conclusion: Collectively, these findings highlight the ability of γ-mangostin to protect Schwann cells from apoptotic cell death induced by oxidative stress.

Objectives: This study aimed to investigate the effects of Ang-(1-7) on high glucose-induced islet β-cell dedifferentiation by activating the phosphatidylinositol-3-kinase/Protein kinase B/ Forkhead box transcription factor O1 (PI3K/Akt/FoxO1) signaling pathway.

Methods: The mouse islet β-cell line MIN6 cells were passaged and cultured and randomly divided into five groups: control (Con) group, high glucose (HG) group, HG with Ang-(1-7) group, HG with Ang-(1-7) and specific MasR antagonist A-779 group, and HG with Ang-(1-7) and PI3K inhibitor LY294002 group. After 48 hours, glucose-stimulated insulin secretion (GSIS) was detected by Enzyme-Linked Immunosorbent Assay (ELISA). The mRNA and protein expression levels of β-cell-specific factors (Pancreatic duodenal homeobox-1 (Pdx1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A(MafA)) and endocrine progenitor cell-specific factors (Octamer binding transcription factor 4(Oct4), Nanog) were measured by Real Time-PCR and Western blot. The factors of protein expression levels of PI3K/Akt/FoxO1 signaling pathway (Akt, p-Akt, Fox- O1, p-FoxO1) were determined by Western blot.

Results: We observed for the first time that high glucotoxicity can induce dedifferentiation of pancreatic islet β-cell, causing a decrease in insulin secretion levels and expression of Pdx1, MafA, p-- FoxO1, and p-Akt and an increase in expression of Oct4 and Nanog. After Ang-(1-7) intervention, insulin secretion levels and expression of Pdx1, MafA, p-FoxO1 and p-Akt were increased, and the levels of Oct4 and Nanog were reduced. However, A-779 and LY294002 could reverse this effect. During these processes, the total Akt and total FoxO1 expression did not change significantly.

Conclusion: Ang-(1-7) may prevent high glucose-induced pathological dedifferentiation of pancreatic β-cell by activating the PI3K/Akt/FoxO1 signaling pathway.

Objective: In this work, we aimed to summarize the interesting results from preclinical and clinical studies that assessed the effects of natural alkaloids (berberine, nigelladine A, piperine, trigonelline, capsaicin, nuciferine, evodiamine, mahanine, and magnoflorine) on impaired insulin sensitivity and worsened insulin resistance, which play a pivotal role in the pathogenesis of type 2 diabetes.

Methods: In the current review, PubMed, ScienceDirect, Springer, and Google Scholar databases were used. The inclusion criteria were based on the following keywords and phrases: insulin sensitivity, insulin resistance, alkaloids and insulin resistance, alkaloids and type 2 diabetes, mechanisms of action, and alkaloids.

Results: The outcomes reported in this review demonstrated that the selected alkaloids increased insulin sensitivity and reduced insulin resistance in vitro and in vivo evidence, as well as in clinical trials, through improving insulin-signaling transduction mainly in hepatocytes, myocytes, and adipocytes, both at cellular and molecular levels. Insulin signaling components (InsR, IRS-1, PI3K, Akt, etc.), protein kinases and phosphatases, receptors, ion channels, cytokines, adipokines, and microRNAs, are influenced by alkaloids at transcriptional and translational levels, also in terms of function (activity and/or phosphorylation). Multiple perturbations associated with insulin resistance, such as ectopic lipid accumulation, inflammation, ER stress, oxidative stress, mitochondrial dysfunction, gut microbiota dysbiosis, and β-cell failure, are reversed after treatment with alkaloids. Furthermore, various indices and tests are employed to assess insulin resistance, including the Matsuda index, insulin sensitivity index (ISI), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT), which are all enhanced by alkaloids. These improvements extend to fasting blood glucose, fasting insulin, and HbA1c levels as well. Additionally, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Homeostasis Model Assessment of β-cell function (HOMA-β) are recognized as robust markers of insulin sensitivity and β-cell function, and it is noteworthy that alkaloids also lead to improvements in these two markers.

Conclusion: Based on the findings of the current review, alkaloids may serve as both preventive and curative agents for metabolic disorders, specifically type 2 diabetes. Nonetheless, there is an urgent need for additional clinical trials to explore the potential benefits of alkaloids in both healthy individuals and those with type 2 diabetes. Additionally, it is crucial to assess any possible side effects and interactions with antidiabetic drugs.

Aim: This study aimed to investigate whether newer second-line glucose-lowering treatments are associated with an alternative risk of developing diabetic retinopathy in people with type 2 diabetes.

Methods: A nationwide cohort of people with type 2 diabetes on second-line glucose-lowering treatment regimens in 2008-2018 was extracted from the Danish National Patient Registry. Adjusted time to diabetic retinopathy was estimated with a Cox Proportional Hazards model. The model was adjusted for age, sex, diabetes duration, alcohol abuse, treatment start year, education, income, history of late-diabetic complications, history of non-fatal major adverse cardiovascular events, history of chronic kidney disease, and history of hypoglycaemic episodes.

Results: Treatment regimens of metformin + basal insulin (HR: 3.15, 95% CI: 2.42-4.10) and metformin + glucagon-like peptide-1 receptor agonist (GLP-1-RA, HR: 1.46, 95% CI: 1.09-1.96) were associated with an increased risk of diabetic retinopathy compared with metformin + dipeptidyl peptidase-4 inhibitors (DPP-4i). Treatment with metformin + sodium–glucose cotransporter-2 inhibitor (SGLT2i, HR: 0.77, 95% CI: 0.28-2.11) was associated with the numerically lowest risk of diabetic retinopathy compared with all regimens investigated.

Conclusion: Findings from this study indicate that basal insulin and GLP-1-RA are suboptimal second- line choices for people with type 2 diabetes at risk of developing diabetic retinopathy. However, many other considerations concerning the choice of second-line glucose-lowering treatment for type 2 diabetes patients should be taken into account.

Objective: One of the oldest plant families that have been used medicinally is the Apiaceae family. One of the most important genera of this family is Ferula, which has 170 different species and is distributed in hot and dry regions of the earth and has various therapeutic properties. The purpose of this article is to review the anti-diabetic effects of the Ferula genus on diabetes.

Methods: In this review article, key science databases, including Science Direct, PubMed, and Google Scholar, were searched to find information on Ferula genus using a combination of different keywords, including diabetes, hyperglycemia, and alpha-glucosidase inhibition.

Results: A total of 9 types of Ferula have been reported in the articles that have anti-diabetic properties.

Conclusion: The review of the conducted research shows that the genus Ferula has a high potential in reducing blood sugar and other aspects of diabetes, and additional research should be performed in this field.

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.

Methods: Based on predetermined criteria, a bibliographical search was performed on May 31, 2022, by searching the following databases: ISI Web of Science, Embase, PubMed, and the Cochrane Library. Statistical analysis was conducted to assess renal protection and safety of SGLT2i by using Cochrane Review Manager Version 5.3.

Results: Thirty randomised controlled trials fulfilled the inclusion criteria and were eligible for this meta-analysis. Our study found that the SGLT2i can sustainably reduce the urine albumin/creatinine ratio (UACR) at different time points and prevent the progression to macroalbuminuria. Before 24 weeks, SGLT2i can decrease the estimated glomerular filtration rate (eGFR) compared to the control group. Interestingly, after 24 weeks, SGLT2i can continuously maintain the increase in eGFR when compared with the control group. Furthermore, SGLT2i can reduce the event rates of incident or worsening nephropathy, a decline in estimated eGFR of ≥ 50%, doubling of serum creatinine level, acute renal failure and renal failure. Interestingly, the renoprotective effects of SGLT2i are independent of its glycemic effects. SGLT2i can reduce the morbidity rate of any related adverse events, any related severe adverse events and SGLT2i have not increased the event rates of urinary tract infection, bone fractures, amputation, and acute pancreatitis when compared with the control group.

Conclusion: SGLT2i can protect renal function and are safe drug for CKD. SGLT2i are promising therapeutic agents for CKD patients.

Objective: The present study aims to review and identify the appropriate clinical measures for dual task gait evaluation in T2DM.

Methods: Electronic databases of PubMed, CINAHLPlus and scholarly platforms were searched to identify the relevant articles. Review has included studies which have subjects with T2DM, dual task testing as a part of evaluation, has used clinical measures to assess dual task gait and was available in English.

Results: 16 articles met the inclusión criteria. Four studies used cognitive timed up and go test (TUG), four studies used walking while talking test; one study used extended TUG; one study used walking and remembering test;one study used instrumented TUG along with manual TUG and arithmetic subtractions; two studies used inertial sensors for gait evaluation along with backword counting; one study used two dimensional video analysis for gait along with verbal fluency task and calculation; one study used TUG with arithmetic additions task; one study used Manual TUG and arithmetic subtraction task while walking on GAITRITE walkway.

Conclusion: The studies show a lack of valid and reliable clinical measures for dual task gait evaluation in T2DM.

Methods: The present retrospective cross-sectional study aims to describe the experience on the clinical profile, morbidity profile, and comorbidities of Type1 DM in children below 15 years of age admitted to the SAQR and Fujairah hospitals in the Northern part of United Arab Emirates (UAE) from 1st January 2017 to 31st December 2019. The study material was the digital medical records of children below 15 years who got admitted to emergency and pediatric wards with type 1 Diabetes mellitus (T1DM) in SAQR and Fujairah hospitals.

Results: Total admissions during the study period were 98. At the time of diagnosis, 12.2% of children were below five years of age, whereas 87.75% were more than five years. All 98 children were UAE nationals, of which 52% were males and 48% were females. 50% of our study population has a strong family history of either type 1 or type 2 diabetes mellitus, of which 12.2% of siblings of the study population had T1DM. The first symptoms in 58% and 57% of children were polyuria and polydipsia. Among 90% of children under follow-up for three years, one child developed microalbuminuria, three developed systolic hypertension, and 8% were lost to follow-up.

Conclusion: The present study highlights the need for future prospective studies in the UAE to know the actual burden of the disease with an emphasis on early screening.

Objective: The objective of this systematic review was to analyze the various studies involving photobiomodulation therapy on neuropathic pain and plantar pressure distribution in diabetic peripheral neuropathy.

Methods: We conducted a systematic review (PubMed, Web of Science, CINAHL, and Cochrane) to summarise the evidence on photobiomodulation therapy for Diabetic Peripheral Neuropathy with type 2 diabetes mellitus. Randomized and non-randomized studies were included in the review.

Results: This systematic review included eight studies in which photobiomodulation therapy showed improvement in neuropathic pain and nerve conduction velocity. It also reduces plantar pressure distribution, which is a high risk for developing foot ulcers.

Conclusion: We conclude that photobiomodulation therapy is an effective, non-invasive, and costefficient means to improve neuropathic pain and altered plantar pressure distribution in diabetic peripheral neuropathy.

Methods: A cross-sectional study was conducted to evaluate the general health of patients with diabetes mellitus type 2. The participants of the present study were randomly selected from rural and urban areas. The diabetic patients visiting community pharmacies in these areas were invited to participate in this study after explaining the goal of the study. A self-reported questionnaire in the Arabic version of the medical outcome survey, the Short-Form (36-item), was conducted. However, uneducated patients were interviewed by trained pharmacists in the community pharmacies.

Results and Discussion: Two hundred confirmed DM patients were enrolled in this study with a mean age of (50.65 ± 8.914 years). 142 (71%) were male and the remaining 58 (29%) were female. The scores of all domains of SF-36 were significantly lower (p < 0.05) in female patients in comparison to that recorded in men. In addition, diabetic patients aged more than 50 years showed significantly lower scores of most domains of SF-36 (p < 0.05) except for emotional well-being (p > 0.05). The multivariate linear regression analysis demonstrated that gender, age, and treatment type were independent of health status based on the SF-36 survey, while emotional well-being, social functioning, and pain were exceptional.

Conclusion: The outcomes of this study showed a negative correlation between diabetes mellitus and the health status as measured by SF-36. Furthermore, excluding emotional well-being, social functioning, and pain domains, the other parameters of gender, age, and treatment type showed a significant correlation with health status.