Periodontitis, a chronic infectious disease caused by pathogenic bacteria, characterized by a severe host immune response. Combined antimicrobial and anti-inflammatory strategies can enhance therapeutic efficacy, and a critical factor for the therapeutic efficacy of anti-inflammatory drugs is the maintenance of a localized antimicrobial microenvironment. Therefore, the release profiles of antimicrobial and anti-inflammatory drugs directly affect the treatment outcomes of periodontitis. In this study, a double-cross-linked injectable hydrogel with temperature-responsive and dynamic covalent cross-linking properties is developed as a codelivery carrier for antimicrobial and anti-inflammatory drugs, enabling sequential drug release for synergistic periodontitis therapy. This system adapts to the irregular geometry of the periodontal pocket upon injection and subsequently self-reinforces to resist salivary flow. Notably, the antimicrobial drug metronidazole is sustainedly released over the first 7 days to establish an antimicrobial microenvironment. After 12 h, the anti-inflammatory drug metformin is continuously released over 14 days to suppress the inflammatory response and promote periodontal tissue regeneration. The synergistic antibacterial, anti-inflammatory, and regenerative capabilities of the hydrogel are further validated in a rat model of periodontitis. This injectable and self-reinforcing system for locally sequential drug release demonstrates significant potential for the clinical management of periodontitis.

AI-based prediction and validation in zebrafish model elucidates potential bioactivity of novel thiazolone derivative

Chronic hyperglycemia accelerates immune aging and contributes to diabetic complications, yet the mitochondrial mechanisms responsible for macrophage senescence remain unclear. In this study, both cultured and primary macrophages were treated with high glucose to model hyperglycemic conditions. High glucose significantly increased markers of macrophage senescence, including SA-β-Gal staining, expression of p16 and p21, and secretion of pro-inflammatory cytokines. Mitochondrial dysfunction was evident, as shown by loss of mitochondrial membrane potential (ΔΨm) and elevated mitochondrial reactive oxygen species (mtROS). In addition, mitophagy was impaired, with PINK1 accumulation and reduced Parkin recruitment. Rescue experiments demonstrated that treatment with the mitochondria-targeted antioxidant MitoTempo, the general antioxidant N-acetylcysteine, or the anti-diabetic drug metformin effectively restored mitochondrial function and alleviated senescence. These findings indicate that mitochondrial dysfunction and impaired mitophagy are central to high glucose-induced macrophage senescence, and that targeting mitochondrial oxidative stress with antioxidants or metformin may offer a promising strategy to mitigate immune aging and inflammation associated with metabolic disorders.

Obesity and type 2 diabetes mellitus are serious issues in modern healthcare, making the implementation of treatment methods highly relevant. These diseases are closely interrelated: approximately 80% of patients with type 2 diabetes mellitus are obese, which is a key pathophysiological factor in the development and progression of diabetes. Classic approaches to treating type 2 diabetes mellitus, such as prescribing standard antihyperglycemic drugs (metformin, sulfonylureas, insulin), are insufficiently effective in achieving sustainable glycemic control and weight loss. Modern medications, such as glucagon-like peptide-1 receptor agonists (glutides), are utilized to treat obesity and type 2 diabetes. This class of drugs addresses several issues: weight loss, blood sugar control, and cardioprotective and renal effects.

Erectile dysfunction is a prevalent and distressing complication of diabetes mellitus that markedly affects quality of life in male patients. Although the role of diabetes in erectile dysfunction is well-established, potential drug-induced sexual dysfunction associated with commonly prescribed antidiabetic medications remains underrecognized. The objective of this study was to investigate whether commonly prescribed antidiabetic medications, including glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, metformin, and sodium-glucose cotransporter-2 inhibitors, are associated with an increased reporting of erectile dysfunction in real-world clinical practice. This retrospective pharmacovigilance study was conducted using the FDA Adverse Event Reporting System. A disproportionality analysis was performed to evaluate the reporting frequency of erectile dysfunction associated with commonly prescribed antidiabetic medications. The reporting odds ratio served as the primary metric for evaluating disproportionality in adverse event reporting. In addition, time-to-onset and Weibull shape parameter analyses were performed to assess temporal trends in adverse event occurrence. We identified 49 semaglutide-, 54 sitagliptin-, and 42 dapagliflozin-associated erectile dysfunction reports. All three drugs demonstrated significant disproportionality signals: semaglutide (reporting odds ratio: 1.53, 95% confidence interval: 1.16-2.03; information component025=0.19), sitagliptin (reporting odds ratio: 1.52, 95% confidence interval: 1.16-1.98; information component025=0.20), and dapagliflozin (reporting odds ratio: 1.51, 95% confidence interval: 1.11-2.04; information component025=0.13). Time-to-onset analysis indicated a random failure-type distribution for all three drugs (semaglutide, sitagliptin, and dapagliflozin), suggesting that the occurrence of erectile dysfunction appears relatively random over the course of treatment rather than concentrated shortly after initiation and underscoring the need for continuous monitoring throughout therapy. Other agents in the same drug classes, including dulaglutide, linagliptin, and metformin, did not show significant signals. This FDA Adverse Event Reporting System-based pharmacovigilance analysis identified potential safety signals linking erectile dysfunction to semaglutide, sitagliptin, and dapagliflozin. These findings do not establish causality and should be regarded as preliminary and hypothesis-generating. Further mechanistic and prospective clinical studies are needed to determine whether these signals reflect true drug-related risks. Clinicians should be aware that erectile dysfunction has been reported in some users of these agents and may consider incorporating sexual health into routine discussions and shared decision-making with male patients.

Abstract Glioblastoma (GBM) is a highly aggressive brain tumor sustained by glioblastoma stem cells (GSCs), whose metabolic plasticity contributes to tumor progression and therapeutic resistance. Targeting tumor-specific membrane proteins that support this plasticity represents a promising strategy. Chloride Intracellular Channel 1 (CLIC1), particularly its transmembrane form (tmCLIC1), is selectively enriched on GSC membranes and largely absent in healthy cells, making it an attractive therapeutic target. Notably, tmCLIC1 is inhibited by the antidiabetic drug metformin, although the molecular basis of this interaction and its clinical relevance remain unclear due to the high drug concentrations required. Here, we investigated the structural and functional determinants of metformin binding to tmCLIC1 and explored strategies to enhance its therapeutic potential in GBM. Molecular dynamics simulations identified arginine 29 (R29) as a critical residue stabilizing a negatively charged binding pocket involving aspartate 76 (D76) and glutamate 81 (E81). Electrophysiological analyses in GSCs expressing CLIC1 mutants demonstrated that metformin fully inhibits wild-type tmCLIC1 activity, whereas R29 mutations abolish drug sensitivity, and D76A or E81A mutations partially reduce it. An R29M substitution confirmed that the positive charge at R29 is essential for metformin binding. Structural studies are underway, with crystals of the CLIC1–metformin complex and the R29A mutant successfully obtained for X-ray analysis. Functional assays revealed that metformin binding induces tmCLIC1 internalization and promotes intracellular and mitochondrial accumulation of the drug, as demonstrated by immunofluorescence and NanoSIMS imaging. Short-term exposure to metformin resulted in sustained reductions in GSC proliferation and mitochondrial activity, while prolonged low-dose treatment effectively inhibited tmCLIC1 currents and cell proliferation, recapitulating the effects of acute high-dose exposure. Together, these findings define R29 as a key molecular determinant of metformin–tmCLIC1 interaction and reveal a mechanism by which tmCLIC1 mediates metformin uptake and antitumor activity in GSCs. Importantly, they support continuous low-dose metformin administration as a feasible therapeutic strategy, opening new avenues for tmCLIC1-targeted, low-toxicity treatments for glioblastoma. Citation Format: Guido Rey, Francesca Cianci, Francesco Emanuele. Caridi, Sara Torabi, Michele Mazzanti. tmCLIC1 as a Key to Metformin’s Action: Connecting Molecular Insights to Glioblastoma Therapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr B026.

Enzalutamide Plus Metformin Versus Enzalutamide Alone in Metastatic Castration-resistant Prostate Cancer: A Randomized Phase 2 Trial (SAKK 08/14).

Given the multifactorial nature of diabetes and limitations of conventional monotherapies, combination therapies involving natural bioactive compounds offer a complementary strategy for more effective management. This study investigated the antidiabetic potential of chlorogenic acid (CGA) and gallic acid (GA), individually and in combination, using in silico, in vitro and in vivo approaches. Pharmacokinetic and molecular docking analyses were conducted to assess drug-likeness and target interactions. Antioxidant activity and α-amylase inhibition were evaluated in vitro, while therapeutic efficacy was assessed in streptozotocin-nicotinamide-induced (STZ-NA) diabetic mice. In silico analysis revealed favorable ADMET profiles and strong binding affinities of CGA and GA to key diabetic targets, including α-amylase, DPP4, PPARγ, TNF-α and IL-6, surpassing metformin. The combination showed enhanced antioxidant and α-amylase enzyme inhibitory activity compared to individual compounds. In vivo findings using an STZ-NA-induced type II diabetic mouse model demonstrated a significant reduction in blood glucose (p < 0.0001) and improvement in lipid profile upon oral supplementation. Both compounds showed a decline in gene expression of TNF-α, TGF-β and IL-6 while enhancing the level of PPARγ. Additionally, hepatic markers (ALT, AST and ALP) were significantly reduced (p < 0.05), suggesting hepatoprotective effects. Histological analysis revealed restoration of pancreatic and liver tissues. Notably, the combination of both compounds exhibited a greater antidiabetic effect than the individual compounds and the standard antidiabetic drug (metformin). Given their favorable pharmacokinetic profile, affinity for multiple antidiabetic targets and synergistic antidiabetic activities both in vitro and in vivo, CGA-GA combination may offer a safer alternative to current therapies. These findings warrant further investigation of this combination strategy for more effective diabetes management.

&amp;lt;i&amp;gt;Introduction:&amp;lt;/i&amp;gt; Metabolic syndrome is associated with hepatic and renal dysfunction driven by hyperglycaemia, hyperlipidaemia, oxidative stress, and electrolyte imbalance. &amp;lt;i&amp;gt;Terminalia catappa&amp;lt;/i&amp;gt; nuts (TCN) are rich in lipophilic bioactive compounds with reported antioxidant and anti-inflammatory properties. This study investigated the effects of the &amp;lt;i&amp;gt;n&amp;lt;/i&amp;gt;-hexane extract of TCN on serum biochemical markers of hepatic and renal function in Wistar rats with metabolic syndrome. &amp;lt;i&amp;gt;Methods&amp;lt;/i&amp;gt;&amp;lt;i&amp;gt;:&amp;lt;/i&amp;gt; Forty-eight male Wistar rats were divided into six groups (&amp;lt;i&amp;gt;n&amp;lt;/i&amp;gt; = 8): negative control, metabolic syndrome control, standard drug (metformin + atorvastatin), and TCN-treated group (200, 400, and 800 mg/kg/day). Metabolic syndrome was induced using a high-fat and high-sugar diet. Serum liver enzymes, serum proteins, total bilirubin, creatinine, urea, and electrolytes were analysed. Data were evaluated using one-way ANOVA with Tukey&amp;apos;s post-hoc test (&amp;lt;i&amp;gt;p&amp;lt;/i&amp;gt; &amp;lt; 0.05). &amp;lt;i&amp;gt;Results&amp;lt;/i&amp;gt;&amp;lt;i&amp;gt;:&amp;lt;/i&amp;gt; The metabolic syndrome control group exhibited significant increases in ALP (148±0.98 U/L), ALT (23.4±0.25 U/L), AST (22.0±0.01 U/L), urea (5.2±0.49 mmol/L), creatinine (92.8±1.22 μmol/L), and bilirubin (10.4±0.25 μmol/L), alongside reduced total protein (65.0±0.01 g/L) and albumin (31.0±0.01 g/L). TCN treatment ameliorated these alterations. At 200 mg/kg, ALP, ALT, and AST levels decreased to 138±1.22 U/L, 20.6±0.98 U/L, and 17.8±0.49 U/L, respectively, with urea and creatinine reducing to 4.8±0.49 mmol/L and 86.2±0.74 μmol/L. The 400 mg/kg dose further improved these markers (ALP: 134±1.71 U/L; ALT: 17.0±0.01 U/L; urea: 4.2±0.74 mmol/L; creatinine: 81.4±0.74 μmol/L). At 800 mg/kg, maximum efficacy was observed, with ALP (127±1.22 U/L), ALT (12.6±0.98 U/L), urea (3.6±0.49 mmol/L), and creatinine (73.0±1.22 μmol/L) approaching baseline levels. TCN restored electrolyte balance across all doses, improved protein synthesis (TP: 68.2±0.49 g/L, ALB: 37.8±0.74 g/L), and reduced bilirubin to 6.8±0.49 μmol/L at the highest dose. &amp;lt;i&amp;gt;Conclusion&amp;lt;/i&amp;gt;&amp;lt;i&amp;gt;:&amp;lt;/i&amp;gt; The &amp;lt;i&amp;gt;n&amp;lt;/i&amp;gt;-hexane extract of TCN demonstrates dose-dependent hepatoprotective and nephroprotective effects, as evidenced by improvements in serum biochemical and electrolyte markers in metabolic syndrome-induced Wistar rats.

The presence of micropollutants, such as pharmaceuticals, in aquatic environments is a major concern due to the risks they pose to living organisms. Given the often inadequate management of wastewater, it is crucial to develop reliable and effective methods to eliminate these contaminants, thus ensuring our safety and protecting the ecosystem. This study aims to test the ability of a polyvinyl chloride/graphene oxide (PVC/GO) composite membrane to adsorb metformin (Met) in an aqueous solution. The graphene oxide was synthesized using the Hummers method from recycled graphite obtained from drilling molds, thereby adding an ecological dimension to this research. This graphene oxide was then used to prepare PVC/GO. The resulting materials were characterized using Fourier-transform infrared spectroscopy, thermogravimetric analysis and Brunauer–Emmett–Teller analysis. The following adsorption parameters were investigated: pH (2–8), temperature (25–40 °C), time (5–30 min), GO content in PVC/GO (0–15%) and initial concentration (4, 6, 8, and 10 mg/L). Adsorption experiments revealed that 75% removal of Met was achieved within 15 min at an optimum concentration of 4 mg/L. Maximum adsorption efficiency of Met was obtained at 40 °C in an acidic medium (pH 2); however, adsorption decreased as the pH increased. Thermodynamic studies indicated that Met adsorption was spontaneous (∆ G ° &lt; 0) and exothermic (∆ H ° &lt; 0) at 25, 30, and 35 °C. However, the process was endothermic and non-spontaneous at 40 °C. Based on the obtained results, PVC/GO 5% was found to be an efficient and promising adsorbent for Met.

The antidiabetic drug metformin has potential as an anticancer agent, particularly due to its observed efficacy in breast cancer. Metformin exerts its cytotoxic effects in the induction of endoplasmic reticulum (ER) stress, which can trigger apoptotic cell death pathways. Therefore, the present study aimed to investigate the dose-dependent effects of metformin on ER stress and apoptosis in HER2-positive breast cancer SKBR3 cells. For this purpose, SKBR3 cells were treated with 5, 10 and 20 mM metformin. Cell proliferation was assessed using real-time cell analysis, while expression levels of ER stress-associated genes [glucose-regulated protein 78 kDa (GRP78), PRKR-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6) and CHOP)] were measured by revese transcription-quantitative PCR. Apoptosis was analyzed by Annexin V-FITC/PI flow cytometry in cells treated with 10 and 20 mM metformin. Findings revealed that metformin (5, 10 and 20 mM) dose-dependently inhibited cell proliferation and activated ER stress pathways. Significant increases were observed in gene expression following treatment with 5, 10 and 20 mM metformin, respectively, including GRP78 (3.70-, 5.06- and 7.33-fold; all P<0.0001) PERK (2.48-, 4.36- and 9.11-fold; all P<0.0001), IRE1 (2.15-fold, P=0.001; 2.90-fold, P<0.001; 5.55-fold, P<0.0001), ATF6 (2.43-2.44- and 3.63-fold; all P<0.0001) and particularly in pro-apoptotic CHOP (3.31-, 27.47- and 49.85-fold; all P<0.0001). Flow cytometry revealed that 10 and 20 mM metformin significantly increased early apoptosis to 6.05% (P<0.001) and 7.28% (P<0.001) and late apoptosis to 13.24% (P<0.001) and 20.59% (P<0.001), respectively, compared with controls (early apoptosis, 0.02%; late apoptosis, 0.05%). The present findings demonstrated that metformin activates ER stress response and induces apoptosis in HER2-positive breast cancer cells in a dose-dependent manner. This supports the potential of metformin as an adjuvant therapy, though further in vivo studies are needed to evaluate its clinical applicability.

This review evaluates the available pharmacokinetic data on the plasma-to-breastmilk transfer of first- and second-line T2DM drugs against available clinical guideline recommendations. A list of drug therapies for treating T2DM was generated from national and international clinical guidelines. A systematic search of research articles reporting human plasma and breastmilk drug concentrations was conducted in Scopus, PubMed, Google Scholar, and LactMed® in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies evaluating breastmilk drug transfer in T2DM, with fully accessible abstract and main text reported in English, were included. Study quality was evaluated using the ClinPK checklist. Authors evaluated clinical guideline recommendations on the use of T2DM drugs in lactation and the basis upon which such recommendations were made. Only 5 out of 20 drugs (metformin, glyburide, glipizide, tolbutamide, and semaglutide) have clinical data on plasma-to-breastmilk transfer. Metformin and tolbutamide were detectable in maternal plasma and breastmilk. Half (51.7%) of guideline recommendations provide explicit guidance. Only 4.4% of recommendations were based on clinical evidence. Over half (57.8%) of recommendations were accessible online, and most guideline recommendations (78%) were against the use of antiglycemic agents while breastfeeding. The scarce clinical evidence to guide T2DM drug therapy during breastfeeding available has several design and methodological limitations. Published recommendations remain largely inconsistent, thus perpetuating uncertainty in the use of T2DM drug therapies in lactation. Addressing knowledge gaps is critical in developing clinical consensus to optimize T2DM drug therapy among breastfeeding mothers.

Telomere length serves as a critical biomarker of ageing, and diabetes is associated with shorter telomeres. This study aims to investigate the association and underlying molecular mechanism between telomere attrition rate in healthy individuals and patients with type 2 diabetes who consume the anti-diabetic drug metformin. Leukocyte telomere length was measured using the telomere restriction fragment assay in 111 healthy individuals and in 73 individuals with type 2 diabetes who were consuming metformin. Telomere length-regulating mRNA and protein expression studies were performed. The BJ fibroblast cell line was treated with different concentrations of metformin, and telomere length analysis, gene expression and chromatin immunoprecipitation (ChIP) were performed. Compared to healthy volunteers, telomere attrition was markedly reduced in diabetic patients who were on metformin. Diabetic females, in particular, showed an increase in telomere length, while males showed a reduction in the telomere attrition rate. In the BJ fibroblasts, metformin slowed telomere attrition in a dose-dependent manner. Molecular studies revealed that metformin treatment resulted in increased expression of telomeric protein RAP1 via enhanced PGC1α-dependent Foxo3a recruitment to the RAP1 promoter. Metformin is associated with decreased telomere attrition and increased telomeric protein RAP1 expression in both diabetic patients and in the fibroblast model. The effect is particularly significant in females. To our knowledge, this is the first study to identify a PGC-1α-FOXO3a-RAP1 signaling axis linking metformin exposure to telomere protection in human diabetic cohorts and to mechanistically validate this pathway using a fibroblast model.

Ligands of the antidiabetic drug metformin and the natural flavonoid chrysin were used to synthesize Cu-(II) and Zn-(II) heteroleptic complexes. Metal complexation was used to repurpose metformin against the breast cancer cell line MCF-7. Structural information on the metal complexes was acquired using UV-vis absorption spectroscopy, FTIR, HRMS, TGA/DTA, XRD, SEM-EDX, molar conductance analysis, and time-dependent density functional theory (TDDFT). Accordingly, we proposed that the structure of complex 1 was [Cu-(C4H11N5)-(C15H9O4)-(C2H3O2)], with a square pyramidal geometry, while complex 2 was [Zn-(C4H11N5)-(C15H9O4)]-C2H3O2 and exhibited a tetrahedral geometry. The IC50 values were 18.93 and 43.31 μM for complexes 1 and 2, respectively, compared to the positive control cisplatin (IC50 = 18.62 μM). The cancer cells' morphology changed from epithelial to a round shape, and the cell density decreased upon treatment, confirming the potential of the metal complexes to induce apoptosis. Computationally, the biological significance of the metal complexes was inferred from quantum chemical descriptors and molecular docking analysis. The band gap energies of the metal complexes were 2.964 and 3.648 eV for complexes 1 and 2, respectively, compared to those of metformin (5.988 eV) and chrysin (4.403 eV). Moreover, molecular docking simulations against estrogen receptor alpha (ERα; PDB: 5GS4) revealed a binding energy of -5.69 kcal mol-1 and an inhibition constant (K i) of 51.37 μM for complex 1, and -6.12 kcal mol-1 and 30.12 μM, respectively, for complex 2. This work demonstrates the therapeutic switching capability of metformin via metal complexation.

PACAP: A promising disease-modifying target for Alzheimer's disease.

Type II diabetes mellites (TIIDM) characterized by hyperglycemia, insulin resistance, insensitivity, and pancreatic β-cell atrophy has gained concern due to high rise in such cases globally. This study highlighted the therapeutic potency of a novel polyherbal formulation (PHF) of Phyllanthus urinaria and Adhatoda vasica Nees mice by in vitro, in vivo, and in silico analysis in high-fat diet (HFD)-streptozotocin (STZ)-induced Swiss albino. The findings showed significant inhibition of α-amylase and α-glucosidase activity of the PHF along with decreased blood glucose level, increased glycogen and serum insulin level, elevated mRNA expression of GIPR and GLP1R, GLUT2, GLUT4, INSR, INS1, INS2, TCF7L2, and Pdx1 in both low and high dose of PHF-treated mice as compared to HFD-STZ-induced diabetic mice. Western blot results also demonstrated augmented insulin protein level in both PHF-treated groups. Okanin and vomicine, identified from LCMS analysis as potent antidiabetic bioactive compounds bind to dipeptidyl peptidase 4 (DPP4) with a binding energy of -8.04 and -7.81kcal/mol, respectively, as compared to standard drug metformin (-5.33kcal/mol). Inhibition of DDP-4 by bioactives of PHF aids in enhanced secretion of incretion hormones leading to insulin secretion thereby established itself as a complementary and alternative therapeutics in the management of diet-induced TIIDM.

Background/ObjectiveThis study evaluated the antidiabetic and antihypercholesterolemic potential of the botanical metabolite troxerutin (TRX) and compared it with that of metformin in high-fat diet-fed streptozotocin-induced diabetic male Wistar rats.MethodsThe rats (n = 48) were divided into six groups. Diabetes was induced in the treatment groups, and different doses of troxerutin (TRX)—25 mg/kg/day (TRX25-D), 50 mg/kg/day (TRX50-D), and 75 mg/kg/day (TRX75-D)—or the standard drug (10 mg/kg/day; MET10-D) were administered for a period of 7 weeks, compared to the negative (non-diabetic control, NDC) and positive (diabetic control, DC) control groups. At the end of the trial period, serum was collected to determine the lipid profile (high-density lipoprotein, low-density lipoprotein, and very-low-density lipoprotein (VLDL)) and the concentrations of hepatic (aspartate aminotransferase and alanine aminotransferase), renal (urea and creatinine), and oxidative stress (catalase and malondialdehyde) markers. Adipose tissue, skeletal muscle, and liver tissue samples were collected to determine mRNA expression, of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] and genes involved in lipid metabolism [peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and sterol regulatory element-binding protein-1c (SREBP-1c)].ResultsThe results showed a significant decrease (p < 0.05) in total cholesterol (TC), triglycerides (TGs), VLDL, and LDL levels, along with hepatic, renal, and stress markers, in the rats treated with a higher concentration of troxerutin (TRX75-D) compared to diabetic control rats. Moreover, troxerutin significantly (p < 0.05) upregulated the expression of PPARα and PPARγ, while the expression of FAS, SREBP-1c, TNF-α, and IL-6 genes were significantly (p < 0.05) downregulated simultaneously in the adipose tissue, skeletal muscles, and liver in a dose-dependent manner, compared to diabetic ct control rats.ConclusionTroxerutin has considerable antidiabetic and antihypercholesterolemic potential and thus could be safely used as an alternative therapeutic compound to the standard antidiabetic drug metformin.

Chidamide and Anlotinib act synergistically in Jurkat cells by inhibiting the Hippo signaling pathway

Development of a densitometric method for the simultaneous estimation of antidiabetic drugs metformin and evogliptin

Background: Recombinant human arginase (rhArg) has been proven to exhibit an anticancer effect via arginine starvation. To further improve the efficacy of rhArg, we examined the feasibility of a combination strategy with Bcl-2 inhibitors (ABT263 and ABT199) or an antidiabetic drug (metformin) and investigated the mechanistic basis for these strategies. Methods: The combination effects were evaluated in a panel of human cancer cell lines modeling pancreatic ductal carcinoma (PDAC), triple-negative breast cancer (TNBC), colorectal cancer (CRC) and glioblastoma (GBM). Western blot analysis was used to evaluate the expression of apoptotic and cell cycle markers. MTT assay was used to evaluate the combination efficacy. Flow cytometric assays were used to investigate the apoptotic and cell cycle effects. Results: The combination of rhArg with sublethal doses of ABT263 significantly induced dose-dependent apoptosis, with elevated expression of apoptotic markers and a CI of 0.47 in U251. The combination inhibited CDK2 and cyclin A expression, indicating that the observed synergy also resulted from cell cycle arrest. We also found that rhArg + metformin was synergistic in a time-dependent manner. Compared to other amino acid depletion agents, rhArg + ABT263 was the most favorable combination pair. Conclusions: The combination of rhArg and ABT263 enhanced apoptosis and cell cycle arrest, demonstrating a potential broad-spectrum antitumor strategy.