Search Results (7,069)

Background/Objectives: Diabetes mellitus is a common endocrine disorder characterized by hyperglycemia, which is increasing steadily all over the world. Current medications are limited due to lower efficacy and side effects; therefore, the introduction of novel compounds is crucial to improve therapeutic outcomes for diabetic patients. The objective of this study was to synthesize and evaluate 2-phenyl-3H-quinazolin-4-one and its derivatives for the glucose uptake across the yeast cell membranes, alpha-amylase inhibition, and alpha-glucosidase inhibition in silico and in vitro. Methods: The synthesis of 2-phenyl-3H-quinazolin-4-one and its derivatives was carried out by oxidative cyclocondensation of 2-aminobenzamide (anthranilamide) with various benzaldehydes in the presence of aqueous iron (III) chloride. The synthesized compounds were characterized by melting point determination and spectroscopic techniques, including FTIR, NMR and HRMS. Results: In the glucose uptake by yeast assay, compound 3f had a lower 50% glucose uptake value of 24.02 ± 0.96 mM, compared with the standard drug metformin (25.99 ± 2.41 mM). The alpha-amylase inhibition bioassay showed that compound 3e exhibited very potent inhibition, with an IC₅₀ of 0.43 ± 0.05 mM, compared with the standard drug acarbose (0.53 ± 0.21 mM). Compound 3l exhibited strong alpha-glucosidase inhibition, with an IC₅₀ of 0.42 ± 0.10 mM, compared with the standard drug acarbose (0.29 ± 0.50 mM). Coclusions: These findings suggest the potential of synthesized 2-phenyl-3H-quinazolin-4-one derivatives, 3a–o, as promising candidates for managing diabetes mellitus. However, further studies are required to validate their efficacy and determine their mechanisms of action. Full article

Polycystic ovary syndrome (PCOS) is a common hormonal disorder in women of reproductive age and is characterized by ovarian hyperandrogenism and irregular ovulation. This often leads to infertility. Beyond reproduction, PCOS causes widespread metabolic issues such as insulin resistance (IR), increasing long-term risks for diabetes, obesity, and heart disease. In a vicious cycle, IR acts as a core driver of both clinical symptoms and associated obesity, whereas compensatory hyperinsulinemia stimulates ovarian androgen production, causing ovulatory dysfunction and worsening weight gain, with immune imbalances exacerbating systemic chronic low-grade inflammation (CLGI). Berberine is a natural plant alkaloid that, owing to its multifaceted metabolic effects—including activation of 5′ adenosine monophosphate (AMP)-activated protein kinase (AMPK) and improvement of insulin sensitivity—effectively supports the restoration of homeostasis in women with PCOS. The aim of this narrative review is to comprehensively analyze the metabolic and anti-inflammatory actions of berberine, which, in combination with the known pathomechanisms of PCOS, may constitute a rationale for its therapeutic application. Attention was given to the necessity of actions aimed at increasing the bioavailability of berberine and to the consequences of the fact that berberine, unlike metformin, which is commonly used and has similar properties, is a dietary supplement and not a Food and Drug Administration (FDA)-approved prescription drug. Full article

(1) Background: Impaired diabetic wound healing stems from systemic dysregulation of the wound-healing cascade under hyperglycemic conditions, producing a disordered microenvironment marked by sustained inflammation, defective angiogenesis, and aberrant extracellular matrix remodeling, multifactorial, multistage pathological interactions demanding multi-target intervention. (2) Methods: We constructed a multifunctional nanocomposite hydrogel dressing (PGAs@CDV) based on a “drug-carrier integration” strategy, targeting the dysregulated hemostasis, inflammation, and proliferation phases of diabetic wound healing. An amphiphilic micelle carrier (PNO-GA) was synthesized by covalently conjugating Panax notoginseng oligosaccharide with gallic acid, loaded with Anemoside B4 to yield drug-loaded nanomicelles (PGAs), embedded into a carboxymethyl chitosan-dopamine-vanillin hydrogel (CDV) matrix to form PGAs@CDV. We then examined how PGAs@CDV affected diabetic wound healing. (3) Results: In vitro, PGAs@CDV enhanced cell migration and angiogenic capacity, exhibited potent antioxidant activity, and promoted M1-to-M2 macrophage polarization. We tested PGAs@CDV in a streptozotocin-induced diabetic mouse wound model. Wounds treated with PGAs@CDV closed faster than those treated with the control, CDV, PNO@CDV, and AB4@CDV. Four readouts tracked this difference: hemostasis was quicker, inflammation was lower, more blood vessels formed, and collagen deposition was higher. At the pathway level, PGAs@CDV suppressed NF-κB signaling and activated PI3K/AKT/HIF-1α. These two arms map onto the anti-inflammatory and pro-angiogenic effects observed above. (4) Conclusions: This nanocomposite hydrogel integrates a bioactive carrier with a therapeutic payload to enable coordinated intervention across multiple phases of diabetic wound repair. By combining structural support with sustained pharmacological activity, it offers a promising strategy for the treatment of chronic diabetic wounds. Full article

Astragalus species have long been recognized for their pharmacological relevance, yet the antidiabetic properties of Astragalus cruciatus Link (Ac) remain poorly explored. This study aimed to investigate the antidiabetic potential of A. cruciatus Link and to elucidate possible underlying mechanisms. The ethanolic extract of Ac (AcEE) was prepared and analyzed for phenolic and flavonoid content. Antioxidant activity was assessed through a series of in vitro assays. The in vitro inhibition of α-amylase and α-glucosidase was assessed, followed by molecular docking to probe ligand-enzyme interactions. LC-ESI-MS analysis revealed a polyphenol-rich profile, with rutin (953.54 µg/g extract) and quinic acid (797.18 µg/g of extract) identified as main compounds. The AcEE showed significant inhibitory activity against both α-amylase and α-glucosidase (IC₅₀ = 239.30 ± 7.40 and 192.60 ± 15.51 μg/mL, respectively). Moreover, low cytotoxic effects were observed in hepatic cell lines. Computational analysis revealed stable interactions between rutin and both enzymes (−12.935 and −8.073 Kcal/mol, respectively). Network pharmacology revealed that AcEE may modulate key targets, including IL-6, TNF-α, IL-1β, Akt-1, STAT3, EGFR, and INSR as well as pathways related to insulin resistance, AGE-RAGE, and inflammation. These findings suggest that AcEE exerts significant antidiabetic effects through multitarget modulation, highlighting its potential as a natural therapeutic agent for T2DM. Full article

Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it has shown potential therapeutic benefits in the management of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ochratoxin A (OTA), a common contaminant found in foods such as cereals, coffee, and raisins, is also present in traditional Chinese medicinal materials, including Astragalus and liquorice. T2DM and NAFLD share intertwined pathophysiological pathways, including insulin resistance, dyslipidaemia, chronic low-grade inflammation and oxidative stress, with insulin resistance serving as the common pathological hub for both conditions. Consequently, they frequently co-occur and exacerbate each other. OTA exerts dual-targeted toxicity to the pancreas and liver, which may synergistically drive the development of the comorbidity of T2DM and NAFLD. These two processes are mutually causal and together constitute the pathological basis of metabolic comorbidity. Methods: Network toxicology employs toxicological data, gene expression, and protein–protein interaction (PPI) networks to predict the targets of toxins, while network pharmacology, based on systems biology principles, reveals how drugs exert regulatory effects through multiple targets and pathways. In this study, we employed an integrated network toxicology and network pharmacology approach to jointly decipher the potential mechanisms by which CA intervenes in OTA-induced comorbid T2DM-NAFLD. First, a network toxicology approach was employed to preliminarily screen for core toxicological targets responsible for OTA’s pathogenicity. Subsequently, network pharmacology was used to identify potential targets of CA-mediated intervention in the disease. Finally, the common overlap among the CA intervention targets, OTA toxicity targets, and disease targets was defined as the final set of potential targets for CA-mediated intervention in OTA-induced T2DM-NAFLD comorbidity. A PPI network was constructed using the STRING database, and topological analysis was performed with Cytoscape. Core targets were selected using the median values of six parameters—betweenness centrality, closeness centrality, degree centrality, eigenvector centrality, LAC (local average connectivity) score, and network centrality—as cut-off thresholds, and the top 10 key genes were further identified using the cytoHubba plugin. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database, and the results were visualized on the CNSknowall platform. Lastly, molecular docking of the core targets was performed using the CB-DOCK2 platform to validate binding affinity. Results: Based on an integrated analysis of network toxicology, network pharmacology, and molecular docking, 10 key targets were systematically identified. These may serve as potential mediators of cinnamaldehyde in the treatment of OTA-induced T2DM-NAFLD comorbidity. Among these, six targets—albumin (ALB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-6 (IL-6), tumor necrosis factor (TNF), actin beta (ACTB), and estrogen receptor 1 (ESR1)—possess crystal structures amenable to molecular docking. KEGG enrichment analysis revealed that CA and OTA jointly participate in key pathological processes such as the cancer pathway, the lipid and atherosclerosis pathway, the advanced glycation end-products–receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway, the TNF signaling pathway, and the interleukin-17 (IL-17) signaling pathway. OTA exacerbates inflammatory responses, impairs insulin signaling, promotes hepatic steatosis, and disrupts systemic metabolic homeostasis, ultimately contributing to T2DM-NAFLD comorbidity. Conversely, cinnamaldehyde counteracts these pathological processes through multiple mechanisms, including antioxidant and anti-inflammatory effects as well as regulation of glucose and lipid metabolism, thereby restoring metabolic homeostasis. Conclusions: This study has preliminarily identified the toxicological targets of OTA and the potential intervention targets of CA, offering new avenues for preventing and intervening in OTA-induced metabolic toxicity. Furthermore, it provides a theoretical basis for CA as a potential multi-target therapeutic agent and presents novel insights worthy of further investigation into the prevention of T2DM-NAFLD comorbidity. Full article

Background/Objectives: Interactions between botanical supplements and standard antidiabetic therapies remain poorly understood. This study investigated the efficacy and mechanistic properties of a bitter melon blood-sugar-modulating protein (BMP) in relation to concurrent metformin use for improving glucose and lipid metabolism. Methods: A translational approach combined mechanistic evaluation in db/db mice with an exploratory, real-world observational cohort study of 119 individuals with prediabetes or diabetes. BMP was characterized by liquid chromatography-electrospray ionization-tandem mass spectrometry. In the retrospective self-controlled clinical arm, participants receiving daily BMP supplementation were stratified by metformin use and dosage to evaluate changes in glycated hemoglobin (HbA1c) and lipid profiles over 3 months. Results: In db/db mice, BMP significantly reduced fasting blood glucose and HbA1c, with greater glucose-lowering efficacy observed when combined with metformin compared to metformin alone (approximately 300 mg/dL vs. 200 mg/dL reduction; p < 0.05). Skeletal muscle transcriptomic analysis identified coordinated regulation of 27 shared pathways involved in glucose and lipid metabolism. In the clinical cohort, BMP supplementation was associated with reductions in HbA1c (−0.23%, p = 0.0028), total cholesterol (−7.5 mg/dL), and low-density lipoprotein cholesterol (−6.1 mg/dL) among metformin users, whereas no significant changes were observed in non-users. The greatest observed HbA1c reduction (−0.32%, p < 0.0001) occurred in participants receiving 1000 mg/day of metformin. Conclusions: Preclinical data demonstrate coordinated pathway remodeling in skeletal muscle and improved glycemic control when BMP is combined with metformin. In the clinical cohort, BMP supplementation was associated with modest reductions in HbA1c and lipid parameters, primarily among participants using concurrent metformin. Given the retrospective, self-controlled design and baseline clinical differences between treatment groups, these clinical findings reflect observational associations rather than causal effects. Overall, this study is the first to demonstrate that BMP, a major protein component of bitter melon, exhibits complementary metabolic effects when combined with first-line antidiabetic therapy in animal models. Furthermore, by revealing a corresponding observational association in human clinical settings, this work establishes an important foundation for nutritional protein research. Full article

Crinum amoenum Roxb. ex Ker Gawl. (C. amoenum) is traditionally used in Nepal, but its antidiabetic potential remains insufficiently validated. This study characterized the 80% (v/v) ethanol bulb extract of C. amoenum and evaluated its antioxidant, α-amylase inhibitory, hypoglycemic, molecular docking, molecular dynamics (MD) simulation, and ADMET profiles. The ethanolic bulb extract was evaluated through phytochemical screening, thin-layer chromatography, total phenolic content (TPC), total flavonoid content (TFC) estimation, LC-MS analysis, antioxidant assays, α-amylase inhibition assays, acute toxicity testing, and hypoglycemic/oral glucose tolerance test (OGTT) studies in Wistar rats. Lycorine, pratorinine, and palmatine were docked against α-amylase (PDB ID: 5U3A) and GLP-1R (PDB ID: 6GB1), followed by 200 ns MD simulations and ADMET prediction. Qualitative analysis of the extract was positive for flavonoids, phenolic compounds, tannins, saponins, alkaloids, and carbohydrates, and a positive Salkowski reaction indicated the presence of constituents occurring in glycosidic form. The TPC was 173.38 ± 1.22 mg GAE/g, and the TFC was 314.58 ± 0.09 mg QE/g. LC-MS tentatively annotated lycorine, pratorinine, and palmatine based on retention time, m/z values in positive-mode electrospray ionization, and comparison with previously reported spectral information. The extract showed DPPH scavenging activity (IC₅₀: 90.98 μg/mL) and strong α-amylase inhibition (IC₅₀: 49.31 μg/mL) compared with acarbose (IC₅₀: 51.51 μg/mL). No deaths were observed following oral administration at 5000 mg/kg to rats. The 500 mg/kg dose produced the greatest hypoglycemic response, reducing blood glucose by 35.78% at 120 min in non-diabetic Wistar rats and by 19.21% at 60 min in glucose-loaded rats. Among all the compounds tested, pratorinine demonstrated the highest docking affinity with α-amylase (−8.2 kcal/mol; ASP300) and GLP-1R (−7.0 kcal/mol; GLY132). MD simulation supported greater stability of the α-amylase complex, and ADMET prediction identified pratorinine as a comparatively favorable predicted lead candidate (LD₅₀: 1000 mg/kg; Class 4 toxicity category). Pratorinine was identified as the most promising in silico antidiabetic candidate from the C. amoenum extract, primarily due to stable α-amylase interactions and favorable ADMET properties. Full article

Kaempferol is a natural flavonol compound widely present in various single-herb remedies and compound formulations used for the treatment of ocular diseases. Despite its inherent pharmaceutical limitations, accumulating evidence indicates that kaempferol exerts broad protective effects against diverse ocular disorders through multiple biological pathways, highlighting its potential as a multi-target therapeutic candidate in ophthalmology. However, current evidence regarding kaempferol-based ophthalmic applications remains fragmented across different ocular diseases and mechanistic investigations, and a comprehensive evaluation of its therapeutic potential, translational challenges, and existing limitations is still lacking. This review systematically summarizes the research progress on kaempferol in the treatment of eye diseases, encompassing its source distribution, structural characteristics, ocular delivery strategies, disease spectrum coverage, molecular mechanisms, and safety profile. By critically evaluating currently available evidence, this review further identifies unresolved issues and translational barriers that hinder the clinical application of kaempferol in ophthalmology. Regarding delivery strategies, carriers such as gelatin nanoparticles, porous bovine serum albumin membranes, platelet-derived extracellular vesicles, and polyvinylpyrrolidone-based nanocomposites have preliminarily improved ocular surface retention and corneal permeability of kaempferol in models of corneal neovascularization and alkali burns. In terms of therapeutic indications, kaempferol has demonstrated protective effects in diverse experimental models, including age-related macular degeneration (AMD), diabetic retinopathy, diabetic cataract, dry eye disease, fungal keratitis, corneal transplant rejection, acute glaucoma, and retinoblastoma. At the mechanistic level, kaempferol exerts comprehensive pharmacological actions—anti-inflammatory, antioxidant, metabolic regulation, anti-angiogenic, and immunomodulatory—by modulating multiple signaling pathways, including MAPK, NF-κB, STAT1/IRF7, Nrf2/HO-1, VEGF/PI3K/Src/Akt/ERK, aldose reductase, estrogen-related receptor alpha (ERRα), and the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome. Available safety assessments suggest that kaempferol exhibits a generally favorable safety profile across ocular, cellular, systemic, and genetic evaluations. Despite these advances, the clinical translation of kaempferol in ophthalmology remains limited by insufficient clinical and pharmacokinetic evidence, underdeveloped targeted delivery strategies, and a lack of integrated understanding of its molecular basis in ocular protection. By systematically integrating evidence from ocular disease models, molecular mechanisms, delivery strategies, and safety evaluations, this review bridges fragmented knowledge regarding kaempferol-based ophthalmic applications and provides an integrated framework for understanding its therapeutic potential and translational prospects. Overall, this review highlights kaempferol as a promising multi-target therapeutic candidate for ocular diseases and provides insights into its future translational development. Full article

Solanum elaeagnifolium has been utilized for its analgesic, anti-inflammatory, and antioxidant properties to treat a range of conditions, including pain and inflammation. It possesses antibacterial, insecticidal, and molluscicidal properties as well. To investigate the pharmacological potential of the S. elaeagnifolium extract, in vitro, in vivo, and in silico studies were used. Albumin denaturation, heat-induced anti-haemolytic action, and lipooxygenase inhibition were the three techniques used to test anti-inflammatory effectiveness. The phenolic chemicals utilized were identified through the use of high-performance liquid chromatography (HPLC). The effectiveness of the extract in lowering problems connected to diabetes was further evaluated by evaluating fructosamines, carbonyl groups, and β-amyloid formations in albumin glycation. Regarding in vivo studies, the Writhing test and the tail flick test were the two techniques used to evaluate analgesic activity. For docking analysis, we used the following identifiers: cyclooxygenase (PDB ID: 6COX), lipooxygenase (PDB ID: 3V99) and VC1 domain of the receptor for advanced glycation products (PDB ID: 7LMW). The most prevalent phenolic chemicals, according to HPLC analysis, were 3,4-dihydroxybenzoic acid (4.78%), caffeic acid (1.28%), gallic acid (8.18%), ursolic acid (2.6%), syringic acid (1.78%), quercetin (24.09%), catechin (6.67%), and p-coumaric acid (20.49%). Significant suppression of albumin glycation and fructosamine production was demonstrated by the extract, indicating that it may help lessen difficulties associated with diabetes. Furthermore, the extract demonstrated a strong anti-inflammatory impact, with an IC₅₀ of 146 ± 1.17 μg/mL for lipooxygenase inhibition, 87.64 ± 5.35 μg/mL for anti-haemolytic action, and 86.94 ± 1.63 μg/mL for albumin denaturation inhibition. A similar analgesic effect to those of analgesic medications was also demonstrated by SEFE extract. Reinforcing the relevance of the observed effects, the in silico study of the tested activities validated these findings. These findings indicate significant pharmacological promise in the management of diabetes consequences, including inflammation and protein glycation, as well as an analgesic. Full article

Perirenal adipose tissue (PRAT) has emerged as a clinically relevant endocrine organ connecting obesity to cardiovascular disease (CVD), chronic kidney disease, and certain malignancies. Its unique anatomical location, surrounding the kidneys, accounts for PRAT’s role in altering intrarenal haemodynamics and hydrostatic pressure. Accordingly, PRAT’s expansion is associated with the activation of the renin–angiotensin–aldosterone system (RAAS), further increasing blood pressure. Adipokine dysregulation, together with overexpression of miR-24-3p, miR-155, miR-146a, and miR-21 in PRAT, modulates inflammation and oxidative stress, leading to endothelial dysfunction and increased risk of atherosclerosis and hypertension in obesity. Imaging assessment of PRAT thickness through computed tomography, magnetic resonance, or ultrasound has also emerged as a complementary measure for the evaluation of CVD risk. Potential therapeutic strategies targeting PRAT include lifestyle interventions, antidiabetic agents, RAAS inhibitors, adipose tissue browning agents, NOD-like receptor protein 3 (NLRP3) inflammasome inhibitors, peroxisome proliferator-activated receptor gamma (PPARγ) agonists, and surgery. Currently, novel therapeutic interventions targeting PRAT activity in CVD, such as senotherapeutic strategies, bioengineering approaches aimed at enhancing adipose-derived mesenchymal stem cell (ADMSC) function, gut microbiota modulation, and colchicine and bone morphogenetic protein 4 (BMP4) administration, are also being explored. In light of these findings, PRAT’s clinical relevance extends beyond its energy storage role, highlighting it as a metabolically active fat depot. Its assessment and therapeutic modulation may complement existing cardiovascular prevention strategies, particularly in patients with obesity. Full article

Background/Objectives: Chronic hyperglycemia drives gingival fibroblast dysfunction, disrupting extracellular matrix homeostasis and the migratory capacity required for wound healing, which contributes to increased periodontal susceptibility in diabetes. Ferulic acid (FA), a dietary phenolic compound with antioxidant and anti-inflammatory properties, has demonstrated wound-healing activity in various tissues; however, its effects on human gingival fibroblasts (HGFs) under hyperglycemic conditions remain unclear. This study investigated the effects of FA on HGF viability, wound closure, and the secreted concentrations of matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and interleukin-6 (IL-6) under normoglycemic and hyperglycemic conditions. Methods: Cultured HGFs (HGF-1 cell line) were pre-conditioned for 72 h under normal glucose (5.5 mM) or high glucose (25 mM), with an iso-osmolar mannitol control to distinguish glucose-specific effects from osmotic changes. Viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and wound closure by scratch assay following FA treatment, while MMP-1, TIMP-1, and IL-6 concentrations in conditioned medium were quantified by enzyme-linked immunosorbent assay (ELISA). Results: FA was non-cytotoxic at all tested concentrations, whereas 50 µM transiently increased viability. FA significantly enhanced wound closure under both conditions, independent of osmotic effects. High glucose increased IL-6 concentration in the conditioned medium (significant at 48 h) and MMP-1 levels. FA partially attenuated MMP-1 levels at specific time points, modestly reduced IL-6 levels, and markedly increased TIMP-1 concentration under both glucose conditions. Conclusions: FA enhanced wound closure in scratch assay and shifted the secreted MMP-1/TIMP-1 concentration ratio toward a more favorable, matrix-protective profile at the protein level, without cytotoxicity, supporting further investigation of its potential role in periodontal tissue repair under high glucose conditions. Full article

Background/Objectives: People living with HIV (PLWH) who undergo prolonged antiretroviral therapy (ART) may experience weight gain as a potential side effect. Many of these individuals are prescribed glucagon-like peptide 1 (GLP-1) receptor agonists (RAs), or dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) RAs, which are known for their weight-reducing effects and positive impact on metabolic health. However, studies investigating their effects on PLWH are limited. Methods: We conducted a retrospective study at a public hospital in the Bronx, New York, among PLWH with obesity and/or type 2 diabetes mellitus (T2DM) prescribed GLP-1 or dual GLP-1/GIP RAs between August 2020 to March 2024. We collected baseline measurements of weight, body mass index (BMI), glycated hemoglobin (HbA1c), and lipid panel, before and after initiation of treatment, to assess the potential metabolic changes associated with the therapy. Logistic regression was used to analyze the factors associated with reductions in HbA1c and weight. Results: A total of 202 patients were included in the final study, with a mean duration of 24.2 months of GLP-1 or GLP-1/GIP RA therapy. A mean HbA1c reduction of 1.0% (p < 0.001), a mean BMI reduction of 0.7 kg/m² (p < 0.001), and an average mean weight loss of 3.55% were observed. In the univariate analysis, the duration of GLP-1 or GLP-1/GIP RA use was the only factor independently associated with HbA1c reduction greater than 1% (p = 0.027). However, no correlation was found between the duration of their use and the percentage of weight loss (p = 0.126). Insulin use was associated with less weight loss (p = 0.048), while younger age was associated with greater weight loss (p = 0.048). No significant differences in weight loss were observed when the population was stratified by sex, race, comorbidities, type of GLP-1 RA therapy, or other antidiabetic or ART regimens. Conclusions: Use of GLP-1 RAs among PLWH with obesity and/or T2DM is associated with reductions in HbA1c and BMI. In this diverse cohort, which predominantly consists of Black and Hispanic individuals, longer duration of treatment was associated with reductions in HbA1c greater than 1%. These findings encourage GLP-1 RA-related treatment for PLWH with obesity and/or T2DM. Further prospective studies with larger cohorts are needed to confirm these benefits and better define their effects on long-term metabolic health. Full article

Background: The most appropriate management of glucose-lowering therapies in patients exposed to iodinated contrast media (ICM) is still debated. The recent development of antidiabetic drugs that improve cardiovascular and renal outcomes leads to questions regarding their impact on the risk of contrast-associated acute kidney injury (CA-AKI). The present study aimed to assess the effect of different glucose-lowering therapies on the rate of CA-AKI among patients undergoing coronary angiography and/or angioplasty. Methods: Diabetic patients exposed to ICM for coronary procedures were retrospectively identified and divided according to the strategy for the management of diabetes mellitus. The use of a new antidiabetic drug (NAD) was defined for patients treated with SGLT2-I, DDP4-I or GLP-1 receptor agonists on admission. The primary endpoint was the occurrence of CA-AKI within 72 h after contrast medium exposure. Results: We included 462 patients with diabetes mellitus, 51.5% treated with insulin, 44.4% treated with metformin and 50.9% receiving NAD. Among them, 48 (10.4%) experienced CA-AKI. Patients experiencing acute renal injury were more often treated with calcium channel blockers (p = 0.04) and diuretics (p = 0.004), and less often P2Y12 inhibitors (p = 0.04), and presented lower levels of hemoglobin (p = 0.02). Patients receiving NADs displayed a significantly lower occurrence of CA-AKI (33.3% vs. 53.6%, p = 0.009), mainly for those treated with SGLT2-I. On the contrary, patients treated with sulfonylureas and meglitinides displayed a significant increase in the rate of CA-AKI (10.4% vs. 3.9%, p = 0.05). The results were confirmed via multivariable analysis, with NADs and diuretics emerging as the only independent predictors of CA-AKI (NAD: adjusted OR = 0.42 [0.21–0.81], p = 0.01; diuretics: adjusted OR = 2.22 [1.14–4.35], p = 0.02). The independent predictors of CA-AKI were the use of NADs (adjusted OR = 0.45 [0.24–0.86], p = 0.02) and diuretics (adjusted OR = 2.57 [1.33–4.97], p = 0.005). Conclusions: Among patients with diabetes mellitus undergoing coronary angiographic procedures, the use of diuretics, sulfonylureas and meglitinides is associated with an increased occurrence of CA-AKI, whereas the rate of events was significantly lower among users of new antidiabetic drugs and especially SGLT2-I. Full article

Ficus deltoidea Jack (Moraceae), locally known as Mas Cotek, is a medicinal plant traditionally used throughout Southeast Asia for the management of diabetes mellitus. This review summarises the available evidence on the antidiabetic properties of F. deltoidea based on eleven in vitro, nine in vivo and one clinical study identified through a structured literature search. In vitro investigations show that F. deltoidea inhibits α-glucosidase and α-amylase, stimulates insulin secretion in pancreatic β-cells via both K⁺-ATP channel-dependent and -independent pathways, enhances glucose uptake in hepatocytes and adipocytes, promotes adiponectin secretion and inhibits protein tyrosine phosphatase 1B (PTP1B). Vitexin and isovitexin, the predominant C-glycosyl flavonoids in F. deltoidea leaves, appear to be the main bioactive compounds responsible for these effects. Meanwhile, in vivo studies in streptozotocin-induced diabetic rodents report dose-dependent reductions in fasting blood glucose, improved glucose tolerance, restoration of pancreatic islet architecture, modulation of hepatic gluconeogenic and glucose-metabolic genes, and protection against diabetic nephropathy and bone loss. Inter-varietal differences in chemical composition and biological activity were observed, with var. trengganuensis and var. intermedia reported as the most active. The only available clinical trial in adults with prediabetes (1000 mg/day for 8 weeks) showed a reduction in LDL and total cholesterol but no significant change in fasting blood glucose or insulin. The discrepancy between preclinical and clinical findings highlights the need for standardised extracts, pharmacokinetic studies and adequately powered clinical trials in patients with established type 2 diabetes mellitus. Full article

Efficient treatment of diabetic wounds (DW) remains a major clinical challenge worldwide owing to vascular insufficiency, multiple bacterial infections, and overactivation of pro-inflammatory M1 macrophages caused by hyperglycemia. The development of novel pharmaceutical agents with multiple biological functions is urgently needed. Coptis chinensis Franch. (CC) has been used to treat diabetes for thousands of years in China, but the curative effects and underlying mechanisms of CC in DW remain uncertain. Herein, a homogeneous heteropolysaccharide component, namely CCP, was isolated and purified from CC, which exhibited a molecular weight of 39,697 Da and was primarily composed of Glc, GalA, Ara, Gal, and Xyl. CCP has a light yellowish color and is distributed in a block shape with small surface granulations. In vitro experiments revealed that CCP dose-dependently mitigated high glucose-induced suppression of viability, migration, and tube formation in HUVECs. Meanwhile, CCP promotes the polarization of M1 macrophages toward the M2 phenotype to exert anti-inflammatory effects, while possessing certain antibacterial properties. In addition, a composite hydrogel system was successfully constructed by introducing sodium carboxymethyl cellulose and carbomer 940 for CCP delivery. The obtained hydrogels exhibited reasonable moisturizing, swelling, and drug release capacities, along with favorable rheological behaviors and certain antibacterial activity. More importantly, the in vivo wound healing model evaluation in diabetic rats demonstrated that CCP hydrogel dressings could effectively promote wound healing by reducing inflammation, accelerating collagen deposition, upregulating the expression of VEGF and key angiogenesis-related factors. In addition, composite hydrogels demonstrated excellent cytocompatibility and hemocompatibility, which holds great promise for clinical application in DW treatment. Full article