Diabetic Conditions Research Articles

Critical review on Naga Bhasma

Rasa Shastra in Ayurveda focuses on metals and minerals categorized as Rasa, Maharasa, Uprasa, Dhatu, Ratna, Visha, etc., and is valued for its potent therapeutic effects compared to herbal drugs. Naga, a type of Putiloha in Dhatu Varga, is utilized for medicinal purposes to treat various ailments like Diabetes, Obesity, Joint issues, eye and skin conditions, and Anemia. The process of drug preparation explained in Rasa Shastra involves Samskara, which alters the characteristics of the drugs. The purification process, known as Shodhana, must be done on all medications before they are used in any mixture or undergo further processes like Jarana and Marana. In the field of Rasa Shastra, Jarana can be seen in various forms such as Parada Samskara, Gandhaka/Bali Jarana, and Putilohas Jarana. This article examines Jarana of the Putiloha. The preparation of Bhasma is a multistep and intricate process. The steps vary significantly depending on the type of herbal, metallic, or mineral media used in the Marana process. Naga (Lead) was grouped with heavy metals such as mercury, arsenic, and cadmium. It’s exposure can result in neurological disorders and issues with other body systems. Naga Bhasma is a preparation that includes Lead as its main ingredient. Lead and its compounds are harmful to human health. The presence of unique healing qualities in Naga Bhasma suggests that the Ayurvedic procedures used in its creation result in significant transformations in Naga. These processes eliminate its toxicity and add exceptional medicinal properties to Naga Bhasma.

Stochastic Learning Strategy with Varying Regularization Activation Layer-Based Diabetes Prediction Using Multilayer Perceptron

Diabetes makes people more susceptible to disorders like heart disease, kidney disease, Parkinson’s, cataracts, respiratory issues, and other illnesses. Numerous tests are employed to capture essential data for diagnosing diabetes, and the assessment is then used to decide the most appropriate course of action. Nevertheless, it is still challenging to identify the precise traits essential for the emergence of diabetes. Finding the critical factors that influence the target diabetes condition is the primary goal of this research. The Stochastic Learning Strategy with Varying Regularization Logistic Activation Multilayer Perceptron (MLP) model has been implemented with the Indian Diabetes patient dataset extracted from the UCI database repository. Data preprocessing was accomplished for the patients of the Indian diabetes dataset. This research tries to extract the correlation and distribution of all features from the Indian Diabetes Patient dataset. All classifiers demonstrate an accuracy of less than 80% when applied to the Indian Diabetes patient dataset with and without feature scaling, except the Random Forest classifier, which is found to have an accuracy of 78%, which is not the best. The Indian Diabetes patient dataset is fitted with MLP with various learning rates such as Constant learning, Constant momentum and Constant Nesterov momentum learning rate, Invasive Scaling, Invasive Scaling momentum and Invasive Scaling Nesterov momentum learning rate, Adaptive learning, Adaptive momentum and Adaptive Nesterov momentum learning rate for various activation layers like ReLU (Rectified Linear Unit), Identity, tanh and logistic activation layer and the performance is analyzed. The MLP with a logistic activation layer under the Adaptive momentum Learning rate strategy is examined with varying regularization parameter alpha to strengthen the prediction accuracy. The proposed Stochastic Learning Strategy with Varying Regularization Logistic Activation MLP model was further analyzed with the performance metrics precision, recall, FScore, runtime and accuracy and the experimental results exhibit 97% accuracy for MLP with logistic activation layer under Adaptive momentum Learning rate toward predicting the diabetes disease.

Influence of medical conditions on the diagnostic accuracy of plasma p-tau217 and p-tau217/Aβ42.

Blood-based biomarkers (BBMs) can enable early detection of brain amyloid beta (Aβ) pathology in cognitively unimpaired individuals. However, the extent to which common medical conditions affect biomarker performance remains unclear. Participants (n=348) included individuals without cognitive impairment. We studied how brain Aβ associated with BBMs (Aβ42/40, phosphorylated tau [p-tau] 181 and 217, p-tau217/Aβ42, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]) and optimal BBM thresholds for predicting brain Aβ positivity and whether they are obscured by the presence of common medical conditions. Plasma Aβ42/40, p-tau181, p-tau217, and GFAP, but not NfL, were significantly associated with brain Aβ. P-tau217/Aβ42 showed the best discriminative performance (area under the curve: 0.91). The strength of p-tau217-brain Aβ associations were obscured by diabetes and cardiovascular conditions. These results suggest BBMs may help detect early Aβ pathology but suggest caution in their use due to common medical conditions that could affect accuracy. Plasma Aβ42/40, p-tau181, p-tau217, and GFAP but not NfL showed significant associations with brain Aβ. BBMs were more strongly associated with the level of brain Aβ in those without diabetes and cardiovascular conditions. P-tau217/Aβ42 showed the best performance (AUC=0.91) in discriminating Aβ presence with an optimal cut-off of>1.2, followed by p-tau217 at>0.46 pg/mL, with performance slightly improving when excluding participants with cardiovascular conditions.

E3 ubiquitination ligase XIAP lightens diabetes-induced cognitive impairment by inactivating TXNIP-ERS-mediated neuronal injury.

Diabetes-induced cognitive dysfunction (DCD) is a neurological disorder associated with diabetes, characterized by cognitive impairment driven by neuronal injury from chronic high glucose (HG) exposure. This study aims to elucidate the role and mechanisms of the X-linked inhibitor of apoptosis protein (XIAP)/thioredoxin-interacting protein (TXNIP) in hippocampal neuron cell death and cognitive function within DCD models. A diabetic rat model was established using a high-fat/sucrose diet and streptozotocin injection. Primary hippocampal neurons were stimulated with HG to mimic diabetic conditions. Cognitive and memory functions were assessed using the Morris water maze (MWM) and novel object recognition test (ORT).

Immunomodulation with M2 macrophage–derived extracellular vesicles for enhanced titanium implant osseointegration under diabetic conditions

Immunomodulation with M2 macrophage–derived extracellular vesicles for enhanced titanium implant osseointegration under diabetic conditions

Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations

Retinal neurodegeneration (RN), an early marker of diabetic retinopathy (DR), is closely associated with Müller glia cells (MGs) in diabetic subjects. MGs play a pivotal role in maintaining retinal homeostasis, integrity, and metabolic support and respond to diabetic stress. In lower vertebrates, MGs have a strong regenerative response and can completely repair the retina after injuries. However, this ability diminishes as organisms become more complex. The aim of this study was to investigate the gliotic response and reprogramming potential of the human Müller cell line MIO-M1 cultured in normoglycemic (5 mM glucose, NG) and hyperglycemic (25 mM glucose, HG) conditions and then exposed to sustained high-glucose and glucose fluctuation (GF) treatments to mimic the human diabetic conditions. The results showed that NG MIO-M1 cells exhibited a dynamic activation to sustained high-glucose and GF treatments by increasing GFAP and Vimentin expression together, indicative of gliotic response. Increased expression of SHH and SOX2 were also observed, foreshadowing reprogramming potential. Conversely, HG MIO-M1 cells showed increased levels of the indexes reported above and adaptation/desensitization to sustained high-glucose and GF treatments. These findings indicate that MIO-M1 cells exhibit a differential response under various glucose treatments, which is dependent on the metabolic environment. The in vitro model used in this study, based on a well-established cell line, enables the exploration of how these responses occur in a controlled, reproducible system and the identification of strategies to promote neurogenesis over neurodegeneration. These findings contribute to the understanding of MGs responses under diabetic conditions, which may have implications for future therapeutic approaches to diabetes-associated retinal neurodegeneration.

An Immunomodulatory Hydrogel Featuring Antibacterial and Reactive Oxygen Species Scavenging Properties for Treating Periodontitis in Diabetes.

Periodontal disease is a multifactorial, bacterially induced inflammatory disorder characterized by progressive destruction of periodontal tissues. Additionally, diabetes mellitus exacerbates periodontitis, resulting in expedited resorption of periodontal bone. However, methods such as mechanical debridement, anti-inflammatory medications, and surgical approaches often fail to eradicate local infections and inflammation, complicating the reconstruction of periodontal tissue structures. Consequently, there is an urgent need to devise a novel strategy for managing diabetic periodontal conditions. Here, a multifunctional controlled-release drug delivery system (GOE1) is developed by encapsulating self-assembled nanoparticles (consisting of chlorhexidine acetate and epigallocatechin-3-gallate) into a hydrogel matrix composed of gelatin methacryloyl and oxidized hyaluronic acid. In vitro experiments demonstrate that the GOE1 hydrogel possesses good antimicrobial, antioxidant and anti-inflammatory properties, and transgenic sequence genomics further illustrates that IL-17-producing RAW 264.7 macrophages are critical for mediating M1/M2 macrophage transition and provide favorable immune microenvironment. In addition, in vivo experiments reveal that GOE1 significantly ameliorates periodontal tissue inflammation and reduces the loss of alveolar bone by reducing inflammatory infiltration and collagen destruction. Overall, the GOE1 hydrogel offers a promising therapeutic option for managing diabetic periodontitis.

Kidney physiopathologic changes in diabetic Golden-Syrian hamsters (Mesocricetus auratus) fed with hypercaloric diet

Diabetic nephropathy is the single major cause of end stage renal failure. The increase of visceral adipose tissue may lead to glomerular hypertrophy and chronic kidney disease. The objective is to determine renal changes in diabetic Golden-Syrian Hamster (Mesocricetus auratus) supplemented with a hypercaloric diet. Methods: One group of animals (n=10) was fed with a standard diet (SD), and the other group (n=10) was fed with a hypercaloric diet (HCD) for 1 month. Afterwards, both groups were treated with three doses of Streptozotocin. Hyperglycemia was determined throughout 73 days. The animal’s weight, blood and kidney tissues were obtained for analysis. Results: Diabetic animals fed with HCD diet manifested hyperglycemia (250-350 mg/dL) with significant weight loss (40g) and important glomerular filtration rate decrement (0.491mL/min). Regarding to renal fibrosis, all animals showed an increase of glomerular, interstitial, and cortical extracellular matrix (36.3, 75.2 and 70.7%, respectively). Diabetic animals that were SD-fed showed only mild hyperglycemia and slight increase of glomerular, interstitial, and cortical extracellular matrix. A group of animals (n=5) that was fed exclusively with HCD was also included in the study. Conclusions: Our finding suggests that HCD fed can accelerate the progression of chronic kidney disease in a diabetic condition.

Influence of Alkaline Reduced Water Supplementation on Glucose and Lipid Metabolism in Non-Diabetic and Diabetic Rats

Background: With the global increase in metabolic disorders, identifying effective dietary strategies is crucial for enhancing health outcomes. While various health advantages of alkaline reduced water (ARW) have been documented, its specific impacts on glucose and lipid metabolism in both healthy and diabetic conditions are still not well understood. Methods: This study investigates how ARW affects carbohydrate and lipid metabolism in male Wistar rats, which were induced to develop glucose metabolism disorders through subcutaneous injections of nicotinamide and streptozotocin (STZ). The rats were allocated into four groups: one group received distilled water, another ARW, with similar arrangements for both non-diabetic and diabetic rats. Throughout the six-week experiment, the rats had unrestricted access to food and water. At the end of the study, blood and tissue samples were collected post-euthanasia for further analysis. Results: Non-diabetic rats consuming ARW experienced significant decreases in plasma glucose, triglycerides, cholesterol, insulin, leptin, and TBARS levels, along with reduced activities of hepatic hexokinase and intestinal sucrase. Meanwhile, there were increases in hepatic antioxidant enzyme activities, such as glutathione peroxidase and glucose-6-phosphate dehydrogenase, although glutathione levels decreased. In diabetic rats, ARW supplementation notably reduced plasma glucose and the glucose area under the curve, lowered hepatic glucose-6-phosphatase and intestinal disaccharidase activities, and raised hepatic GSH levels. Conclusions: These findings suggest that ARW supplementation significantly enhances glucose and lipid metabolism and boosts antioxidant activity in both non-diabetic and diabetic rats, indicating its potential as a therapeutic aid for managing metabolic disorders.

Medication Management Initiatives Using Wearable Devices: Scoping Review.

Wearable devices (WDs) have evolved beyond simple fitness trackers to sophisticated health monitors capable of measuring vital signs, such as heart rate and blood oxygen levels. Their application in health care, particularly medication management, is an emerging field poised to significantly enhance patient adherence to treatment regimens. Despite their widespread use and increasing incorporation into clinical trials, a comprehensive review of WDs in terms of medication adherence has not been conducted. This study aimed to conduct a comprehensive scoping review to evaluate the impact of WDs on medication adherence across a variety of diseases, summarizing key research findings, outcomes, and challenges encountered. Adhering to PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines, a structured search was conducted across MEDLINE, Web of Science, and Embase databases, covering the literature from January 1, 2010, to September 30, 2022. The search strategy was based on terms related to WDs and medication adherence, specifically focusing on empirical studies to ensure the inclusion of original research findings. Studies were selected based on their relevance to medication adherence, usage of WDs in detecting medication-taking actions, and their role in integrated medication management systems. We screened 657 articles and identified 18 articles. The identified studies demonstrated the diverse applications of WDs in enhancing medication adherence across diseases such as Parkinson disease, diabetes, and cardiovascular conditions. The geographical distribution and publication years of these studies indicate a growing interest in this research area. The studies were divided into three types: (1) studies reporting a correlation between data from WDs or their usage and medication adherence or drug usage as outcomes, (2) studies using WDs to detect the act of medication-taking itself, and (3) studies proposing an integrated medication management system that uses WDs in managing medication. WDs are increasingly being recognized for their potential to enhance medication management and adherence. This review underscores the need for further empirical research to validate the effectiveness of WDs in real-life settings and explore their use in predicting adherence based on activity rhythms and activities. Despite technological advancements, challenges remain regarding the integration of WDs into routine clinical practice. Future research should focus on leveraging the comprehensive data provided by WDs to develop personalized medication management strategies that can improve patient outcomes.

Exploring the anti-inflammatory and anti-apoptotic properties of phloroglucinol on pancreatic cells in diabetic models: In silico and in vivo study

Pancreatic cell damage in diabetes mellitus is closely linked to inflammation and apoptosis. This study aimed to investigate the protective effects of phloroglucinol on pancreatic cells in a streptozotocin-induced diabetic model by assessing its anti-inflammatory and anti-apoptotic mechanisms. Phloroglucinol ligand and the structures of Bax, Bcl-2, and caspase-3 proteins were sourced from the PubChem database. Molecular docking was performed using Autodock Tools and docking results were analyzed with PyRx software. In addition, during the in vivo study, the BALB/c mice were grouped into four categories: healthy control, untreated streptozotocin-induced diabetic, and streptozotocin-induced diabetic treated with two doses of oral phloroglucinol at 100 mg/kg and 200 mg/kg body weight. After 28 days, pancreatic tissues were collected for flow cytometric analysis of NF-κB, IL-6, TNF-α, and apoptotic markers (Bax, Bcl-2, and caspase-3). The docking simulations revealed specific binding interactions: phloroglucinol interacted with Bcl-2 via amino acid residues of ALA90 and TYR139, with Bax via ALA42, LEU45, ALA46, LEU47, PRO130, and ILE133, and with caspase-3 through ARG64, SER120, GLN161, CYS163, and ARG207. The binding affinities for Bax, Bcl-2, and caspase-3 were -5.0, -4.7, and -4.9 kcal/mol, respectively. In vivo, results showed that streptozotocin significantly elevated inflammatory cytokines NF-κB, TNF-α, and IL-6, along with apoptotic markers in pancreatic cells (p<0.05) compared to healthy controls. Phloroglucinol administration at 200 mg/kg significantly reduced TNF-α, NF-κB and IL-6 levels. Phloroglucinol also prevented streptozotocin-induced pancreatic cell damage through anti-apoptotic effects by downregulating Bax and caspase-3 and upregulating Bcl-2. These findings suggest that phloroglucinol may offer protective benefits in diabetic conditions by modulating apoptotic and inflammatory pathways.

Alpha-ketoglutarate supramolecular network accelerates diabetic wound healing through exudates management and neovascularization

Healing of chronic wounds such as diabetic foot ulcers is a critical clinical challenge due to the failure management of excess exudates, persistent inflammatory responses, and vascular microcirculatory disturbances by most traditional wound dressings. To promote the wound healing under diabetic pathological environment, a supramolecular network, polyethyleneimine/polyacrylic acid/alpha-ketoglutarate (PEI/PAA/αKG) with bioactive and metabolic αKG was developed herein for exudates management and vascular microcirculatory reconstruction. Once deposited onto the wound area, the PEI/PAA/αKG supramolecular powder would quickly adsorb the exudates and in-situ gel to form a robust protective barrier for sustainably managing the wound exudates during the healing process. Owing to the reversible H-bonding and electrostatic interactions in the network, bioactive αKG monomer could responsively dissociate from the supramolecular network in a pH-dependent manner to promote the chronic diabetic wound healing. The collagen deposition, soft tissue regeneration, and neovascularization of the healing wound were all obviously enhanced under the mediation of PEI/PAA/αKG supramolecular hydrogel. It was further confirmed that the outstanding effect of PEI/PAA/αKG on angiogenesis under diabetic condition results from the function of αKG on cellular oxidative stress regulation. The present method of materializing therapeutic molecules provides a potential strategy to solve the problem of metabolic molecules in biomedical application.

Effect of Hibiscus sabdariffa L. leaf flavonoid-rich extract on Nrf-2 and HO-1 pathways in liver damage of streptozotocin-induced diabetic rats.

This study investigated the effects of flavonoid-rich extract from Hibiscus sabdariffa L. (Malvaceae) leaves on liver damage in streptozotocin-induced diabetic rats by evaluating various biochemical parameters, including the molecular gene expressions of Nrf-2 and HO-1 as well as histological parameters. The extract was found to significantly reduce liver damage, as evidenced by lower levels of fragmented DNA and protein carbonyl concentrations. Oxidative stress markers, including malondialdehyde (MDA) level, were also significantly (p<0.05) decreased, while antioxidant biomarkers, like reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) were enhanced. Additionally, the extract improved the activities of key liver enzymes, including phosphatases and transaminases, and increased albumin levels. Importantly, the study demonstrated that H.sabdariffa extract effectively regulated the expression of Nrf-2 and HO-1, suggesting a significant role in mitigating liver damage. These findings highlight its potential as a therapeutic agent for liver protection in diabetic conditions.

Designing a Structured Insulin Pump Program Pathway and Reducing Wait Times in the Diabetes Clinic at BC Children’s Hospital

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes an initiative to optimize the insulin pump initiation process at a Canadian children’s hospital.

Effect of Different Extraction Techniques on Phenolic Profile and Phytochemical Potential of Gymnema inodorum Leaf Extract.

The therapeutic potential of plant extracts has attracted significant interest, especially regarding indigenous species with health-promoting properties. Gymnema inodorum, native to Northern Thailand, is recognized for its rich phytochemical profile; however, the impact of various extraction techniques on its phenolic composition and bioactivity remains underexplored. Optimizing extraction methods is essential to enhance the pharmacological efficacy of this plant's bioactive compounds. This study investigated the influence of four extraction methods-ethanol maceration, ethanol reflux, aqueous decoction, and microwave-assisted extraction-on the bioactive profile of G. inodorum leaves, with a focus on the phenolic content and biological activities. Antioxidant activities were evaluated using DPPH, ABTS, and FRAP assays, while the total phenolic and flavonoid contents were quantified by colorimetric methods. High-Performance Liquid Chromatography (HPLC) quantified gymnemic acid and key phenolic compounds. Among the methods, ethanol reflux yielded the highest antioxidant activities (DPPH and ABTS scavenging), with a total phenolic content of 82.54 mg GAE/g and flavonoid content of 31.90 mg QE/g. HPLC analysis identified sinapic acid, myricetin, and p-hydroxybenzoic acid as major phenolics. Furthermore, the ethanol reflux extract displayed potent anti-diabetic activity, with IC50 values of 13.36 mg/mL for α-amylase and 7.39 mg/mL for α-glucosidase, as well as strong anti-inflammatory activity (IC50 of 1.6 mg/mL) and acetylcholinesterase inhibition (IC50 of 1.2 mg/mL). These findings suggest that ethanol reflux extraction is a highly effective method for producing bioactive-rich G. inodorum extracts, with substantial pharmacological potential for developing herbal remedies and nutraceuticals, particularly in enhancing therapeutic approaches for diabetes and other health-related conditions.

Understanding the Role of Social Determinants in Shaping Chronic Disease Outcomes: A Comprehensive Review

This review explores the influence of social determinants of health (SDH) on chronic disease outcomes, focusing on the interconnected roles of socioeconomic status, physical environment, community context, education, healthcare access, and behavioral determinants. Chronic diseases—such as cardiovascular disease, diabetes, and respiratory conditions—pose a significant public health challenge, with social determinants increasingly recognized as critical factors in shaping their prevalence, progression, and management. This review synthesizes findings from recent studies to elucidate how SDH create disparities in chronic disease outcomes, particularly among marginalized populations. We examine mechanisms linking SDH to chronic disease, including biopsychosocial and behavioral pathways, and discuss implications for public health interventions and policy-making. Addressing these social determinants through comprehensive public health strategies could help reduce the burden of chronic diseases, improve health equity, and support healthier communities.

Trimetazidine restores autophagy via lncRNA H19/AMPK in diabetic heart: Implications for its therapeutic value against diabetic cardiomyopathy.

Previous studies have shown that trimetazidine (TMZ) alleviates diabetes-induced cardiac dysfunction. However, the underlying mechanism for its protective effects on cardiac function remains incompletely understood. Diminished autophagy was found in diabetic hearts, and restoration of autophagy generates cardioprotective effect. This study aims to investigate whether and how TMZ produces protective effect through increasing autophagic activity in the diabetic heart. A high-fat diet and low-dose streptozotocin were applied to induce type 2 diabetes mellitus (T2DM) in male C57BL/6 mice, followed by treatment with TMZ for 14 weeks before cardiac function was evaluated. To mimic the diabetic condition, the neonatal rat cardiomyocytes (NRCMs) were exposed to high glucose/palmitic acid (HP) in the presence or absence of TMZ. We found that TMZ treatment promotes autophagic flux in cardiomyocytes, which is impaired in diabetes. We further found that the AMPK and lncRNA H19 played critical roles in mediating TMZ-induced enhancement of autophagy in cardiomyocyte. We showed that TMZ treatment restored the level of H19 and phosphorylated AMPK (p-AMPK T172) in diabetic heart and NRCMs exposed to HP. Of note, the effect of TMZ on autophagy and p-AMPK was abolished by knockdown of H19. These findings indicated that TMZ is able to recover the cardiac autophagic activity which is impaired by T2DM, and the underlying mechanism accounted for this ability is mostly likely attributed to the restored expression of H19 and AMPK activity.

Chronic hyperglycemia induces hepatocyte pyroptosis via Gα12/Gα13-associated endoplasmic reticulum stress: Effect of pharmacological intervention

AimsHyperglycemia induces pathophysiological changes. Endoplasmic reticulum (ER) stress with Gα12 overexpression may promote hepatocyte death. This study investigated whether sustained hyperglycemia triggers ER stress-associated pyroptosis and fibrosis in the liver alongside an overexpression of Gα12, and examined the potential link with VEGF-A levels. Main methodsMice were subjected to a high-fat diet (60 kcal% fat) with streptozotocin (50 mg/kg body weight, three consecutive times, between 12‐13th weeks). AZ2 (a functional Gα12 inhibitor) was treated at 10 mg/kg body weight (5 times/week, 3 weeks). Immunoblotting and immunohistochemistry analyses were performed. Key findingsHepatic Gα12/Gα13 were overexpressed in the diabetic mice. The following proteins downstream from the Gα12 axis were upregulated: PGC1α, PPARα, and SIRT1. Sustained hyperglycemia promoted ER stress marker levels. Histopathological and biochemical assays showed large-sized lipid droplet accumulation, hepatocyte degeneration, and damage as blood transaminase activities increased. Moreover, the diabetic condition increased IL-1β, caspase-1, and NLRP3 levels, which were supportive of pyroptosis. Consistently, the intensities of Masson's trichrome, collagen-1A1, α-SMA, vimentin, and fibronectin all increased. VEGF-A and VEGFR2 levels also increased in the liver and/or sera. The levels of hepatic pigment epithelial-derived factor (PEDF), a physiological antagonist of VEGF-A, decreased with its reciprocal increase in serum. These events were reversed by AZ2 treatment, supporting the role of Gα12 in hyperglycemic stress in the liver. SignificanceChronic hyperglycemia causes hepatic pyroptosis and fibrosis related to ER stress with Gα12/Gα13 and VEGF overexpression, which may be overcome by AZ2 treatments.

Tiliroside protects against diabetic nephropathy in streptozotocin-induced diabetes rats by attenuating oxidative stress and inflammation.

Diabetic nephropathy (DN), affecting half of diabetic patients and contributing significantly to end-stage kidney disease, poses a substantial medical challenge requiring dialysis or transplantation. The nuanced onset and clinical progression of kidney disease in diabetes involve consistent renal function decline and persistent albuminuria. To investigate Tiliroside's (Til) protective effect against diabetic nephropathy (DN) in rats under diabetic conditions. Five groups of six rats each were included in this study: Rats treated with DMSO by intraperitoneal injection as controls, those treated with STZ by intraperitoneal injection, those treated with STZ + Til (25 mg/kg body weight [bwt]) or Til (50 mg/kg bwt), and those treated with anti-diabetic medication glibenclamide (600 μg/kg bwt). Biochemical markers, fasting blood glucose, food intake, kidney weight, antioxidant enzymes, inflammatory and fibrotic markers, and renal injury were monitored in different groups. Molecular docking analysis was performed to identify the interactions between Til and its targeted biomarkers. Til significantly reduced biochemical markers, fasting blood glucose, food intake, and kidney weight and elevated antioxidant enzymes in diabetic rats. It also mitigated inflammatory and fibrotic markers, lessened renal injury, and displayed inhibitory potential against crucial markers associated with DN as demonstrated by molecular docking analysis. These findings suggest Til's potential as a therapeutic agent for DN treatment, highlighting its promise for future drug development.

Investigating DNA damage caused by COVID-19 and influenza in post COVID-19.

The SARS-CoV-2 virus (termed COVID-19) was responsible for over 34 million global deaths. Although the COVID-19 pandemic has subsided, infection by emerging mutant variants of SARS-CoV-2 poses a continuing threat to public health. COVID-19 infection has been associated with the development of cytokine storm syndrome, hypercoagulability, immunological dysregulation and direct viral invasion of organs, and the long-term consequences for the health of COVID-19 survivors are currently unknown. Our research focuses on the possible mutagenic aspects of infection by COVID-19 and measures their harmful effects on DNA composition. DNA damage was investigated, using the comet assay method, during two periods: in the epidemic peak of COVID-19 and during the post-COVID-19 period, both in patients infected with COVID-19 and in those with influenza. During the epidemic peak, the levels of DNA damage ranged from the highest to the lowest levels in the following groups, respectively: intubated-ICU, non-intubated-ICU, non-ICU, and influenza, with a discernible increase in DNA damage in ICU-treated patients. The levels of DNA damage in the post-COVID-19 period were significantly lower compared to those in the epidemic peak period but there was still a discernible increase in DNA damage in the ICU group. Our results indicate that levels of DNA damage may be an effective indicator in prognostic decision-making and may therefore help to reduce mortality. Given that DNA damage and impaired repair processes can contribute to chronic diseases like diabetes, cancer, and neurodegenerative conditions, it will be crucial to investigate potential similar effects in patients with COVID-19.