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Diabetes is one of the most prevalent metabolic diseases. Irisin (FNDC5 protein) is involved in the new strategy of combating type 2 diabetes. In the liver, the antidiabetic mechanism of silymarin at the molecular level is unknown. This study investigated the effects of silymarin on irisin and the related gene expression and oxidative stress status in the liver of type 2 diabetic rats. Thirty-six rats were divided into 6 groups (n=6 each) by simple randomization: control, control+silymarin (60 mg/kg daily in normal saline orally for 60 days), control+silymarin (120 mg/kg daily in normal saline orally for 60 days), diabetic, diabetic+silymarin (60 mg/kg daily for 60 days), and diabetic+silymarin (120 mg/kg daily for 60 days). Biochemical parameters were measured by spectrophotometric and immunoassay methods, and quantitative polymerase chain reaction was used to evaluate gene expression. The data were analyzed by one-way ANOVA, followed by the Tukey test, using SPSS software, version 16.0. The results were considered statistically significant at a P value less than 0.05. In the diabetic rats treated with silymarin (60 and 120 mg/kg), by comparison with the diabetic group, body weight (P=0.04 and P=0.02), insulin (P<0.001), expression of PGC-1α (P=0.04 and P=0.02), expression of FNDC5 (P=0.03 and P=0.01), and concentration of irisin in the liver (P=0.02 and P=0.01) and serum (P<0.001) were significantly increased, whereas the levels of glucose (P<0.001), HOMA-IR (P=0.03 and P=0.01), and liver injury markers (P<0.001) were significantly reduced. Oxidative stress status and histopathological changes were improved in the treated groups. These results suggest that silymarin because of its ability to upregulate irisin and antioxidant effects can be considered an antidiabetic agent.

Tamoxifen (TMX) is used to treat hormone-receptor-positive breast cancers at early stages. This research aimed to assess the potential of NPs in targeted delivery of TMX against MCF7 and TMX-resistant MCF7 breast cancer cell lines. For this purpose, a targeted delivery system including chitosan NPs coated with hyaluronic acid (HA-CS NPs) was created and examined in vitro. Chitosan NPs were first fabricated and loaded with TMX using the ionic-gelation method to prepare a drug-delivery system. Then, TMX-loaded CS NPs were coated by crosslinking the amino groups of chitosan to the carboxylic group of hyaluronic acid. The developed TMX delivery system was then optimized and characterized for particle fabrication, drug release, and targeting against cancer cells. The HA-CS particle size was 210 nm and its zeta potential was +25 mv. The encapsulation efficiency of TMX in NPs was 55%. TMX released from the NPs in acidic pH (5–6) was higher than the physiological pH (7.4). The cytotoxic effect of TMX-loaded HA-CS NPs on MCF7 and TMX-resistant MCF7 cells was significantly higher than TMX-loaded CS NPs and free drug. The findings confirmed the significant suppressive impact of TMX-loaded HA-CS NPs on MCF7 and TMX-resistant MCF7 cancer cells compared to the TMX-loaded CS NPs and free TMX.

Background: Hyperglycemia damages various tissues such as the testes through oxidative stress and inflammation, which can eventually lead to infertility. Objective: Garlic extract effects on the testicular tissue of diabetic rats were investigated. Materials and Methods: In this experimental study, 36 male Wistar rats (8-wk old, weighing 230-300 gr) were randomly divided into 6 groups (n = 6/each) including; C: control rats, G: received 0.4 gr of garlic extract/100 gr body weight, D1: Streptozotocin-induced-diabetic rats or type 1, D1+G: D1 rats that were treated with garlic, D2: Streptozotocin + nicotinamide-induced-diabetic rats or type 2, D2+G: D2 rats treated with garlic. At the end of the study, serum testosterone was assayed by ELISA. Also, sperm quality and quantity were evaluated. For determination of oxidative stress status, total antioxidant capacity, total oxidative status, lipid peroxidation, and thiol groups were assayed in the testis tissues of the rats by colorimetric methods. Also, inducible nitric oxide synthase (iNOS) gene expression and the protein level of interleukin-1-1β (IL-1β) were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Results: In diabetic rats, glucose, total oxidative status and lipid peroxidation, iNOS gene expression, and IL-1β were higher than in non-diabetic rats, whereas testosterone, total antioxidant capacity and thiol groups, and sperm quality were significantly lower compared with control rats. These alterations were normalized by garlic intervention. Conclusion: In diabetic rats, garlic was associated with reduced glucose, oxidative stress, IL-1β, and iNOS gene expression and increased testosterone and sperm quality. So, the results suggest that garlic can reduce the severity of damage in testicular tissues of diabetic rats through its hypoglycemic, antioxidant, and anti-inflammatory properties. Key words: Diabetes mellitus, Garlic, Oxidative stress, Inflammation, Testis.

MoS₂ nanoflakes are emerging as a promising material for photothermal therapy due to their high absorption in the NIR region, large specific surface area, biocompatibility, efficient photothermal conversion, and ability to be functionalized for targeted therapy. In this paper, MoS₂ nanoflakes were incorporated to Fe 3 O 4 nanoparticles, gold nanorod (GNR), and copper sulfide (CuS) (MCG nanocomposite) to investigate chemo-photothermal therapy in this nanocomposite. The structural and optical properties of the MCG nanocomposite were characterized by X-ray diffraction (XRD), Transmission electron microscopy (TEM), Zeta potential, Dynamic Light Scattering (DLS), Fourier transform infrared (FTIR), and Ultraviolet-visible (UV-Vis) spectroscopies. The photothermal results of samples indicated that MCG nanocomposite produced higher photothermal heat than each individual sample alone (808 nm NIR laser irradiation at a power density of 1 W/cm 2 after 10 min). Under NIR laser irradiation, the release of DOX was greatly accelerated at pH = 5.5 as compared to pH = 7.4. So, this nanocomposite can be used as dual responsive systems, with DOX release controllable through pH and NIR irradiation. Finally, MTT assays experiment showed that, using NIR irradiation, the relative viabilities of HeLa cells decreased when the concentration of drug increased. Hence MCG nanocomposite could be a potent system for targeted drug delivery and synergistic chemo-photothermal cancer therapy.

This study investigates the effects of 4-farnesyloxycoumarin (4-FOC)-conjugated NCC/CTAB/CS nanoparticles (NPs) on PANC-1 pancreatic cancer cells, highlighting their cytotoxicity and antioxidant properties. Dynamic light scattering (DLS) analysis revealed a Z-average particle size of 275.68 nm, with a polydispersity index of 0.3020. The mean intensity diameter was 334.68 nm, and the mean volume diameter was 380.97 nm. The zeta potential was recorded at 28.88 ± 12.64 mV, confirming good stability due to electrostatic repulsion. Field emission scanning electron microscopy (FESEM) confirmed the successful conjugation of 4-FOC to the NPs, and Fourier-transform infrared (FTIR) spectroscopy validated the incorporation of functional groups. In contrast, the encapsulation efficiency of 4-FOC was measured at 88.49%. Cytotoxicity assays indicated a significant reduction in PANC-1 cell viability, with an IC50 value of 61.23 µg/mL; in contrast, human dermal fibroblast (HDF) cells exhibited greater resilience, maintaining 92.61 ± 2.33% viability at 100 µg/mL. Apoptotic assays revealed a dose-dependent increase in early and late apoptotic cells, with late apoptosis rising to 54.1% at 81 µg/mL. Gene expression analysis showed significant upregulation of caspase 3 (2.25 ± 0.33), p21 (1.70 ± 0.05), and p53 (2.71 ± 0.29 at 61 µg/mL), underscoring the NPs’ role in apoptosis and cell cycle regulation. Additionally, the antioxidant capacity of the NPs was confirmed through ABTS and DPPH radical scavenging assays, achieving 38.82% and 68.25% scavenging activity at the highest concentrations, respectively. These findings suggest that 4-FOC-conjugated NCC/CTAB/CS NPs hold promise as a therapeutic strategy for treating pancreatic cancer.

Entrapping phytochemical bioactive compounds into nano-structured biocompatible polymers has been successfully utilized for improving cancer treatment efficiency. Silibinin is a potent compound that shows promising anticancer properties. In the present study, the Zein-β-cyclodextrin complex was used to encapsulate silibinin and evaluate the induced cell death type and cytotoxic impacts on human cancer cells. The silibinin-loaded Zein-β cyclodextrin nano-carriers (SZBC-NCs) were synthesized utilizing a gradual ultrasound-mediated homogenization technique and characterized by Zeta potential, DLS, FESEM, and FTIR analysis. The SZBC-NCs’ antioxidant activity was studied by conducting ABTS and DPPH radical scavenging assays. Finally, the SZBC-NCs selective toxicity and cellular death induction mechanism were studied on the HT-29 and AGS cancer cells by measuring the cell survival and apoptotic gene (Caspase 3, 9), respectively, which were verified by conducting the DAPI staining analysis. The negatively charged (− 27.47 mV) nanoparticles (286.55 nm) showed significant ABTS and DPPH radical scavenging activity. Moreover, the remarkable decrease in the IC50 concentrations of the SZBC-NCs among the HT-29 and AGS cancer cell lines exhibited their selective cytotoxic potential. Also, the overexpressed apoptotic (Caspases 3 and 9) and down-regulated necrotic (NFKB) gene expressions following the SZBC-NCs treatment doses indicated the apoptotic activity of SZBC-NCs, which were verified by the increased apoptotic morphology of the DAPI-stained HT-29 cancer cells. The antioxidant and colon cancer cell-related apoptotic activity of the SZBC-NCs make it an appropriate anti-colon cancer nano delivery system. Therefore, they can potentially be used as a safe efficient colon cancer treatment strategy. However, further in vivo experiments including animal cancer models have to be studied.

The objective of the present study was to develop a novel molybdenum disulfide/iron oxide/gold nanorods (MoS 2 /Fe 3 O 4 /GNR) nanocomposite (MFG) with different concentrations of AgNO 3 solution (MFG1, MFG2, and MFG3) for topical doxorubicin (DOX) drug delivery. Then, these nanocomposites were synthesized and characterized by Fourier transform infrared (FTIR), Transmission electron microscopy (TEM), Dynamic light scattering (DLS), and Ultraviolet-visible (UV–Vis) spectroscopies to confirm their structural and optical properties. Cytotoxicity of samples on Hela cell was determined using MTT assay. Results indicated that nanocomposites possess little cytotoxicity without NIR laser irradiation. Also, the relative viabilities of Hela cells decreased when the concentration of AgNO 3 solution increased in this nanocomposite. Using NIR irradiation, the relative viabilities of Hela cells decreased when the concentration of samples increased. Acridine orange/propidium iodide (PI) staining, flow cytometry were recruited to evaluate the effect of these nanocomposites on apoptosis of Hela cells. Finally, results revealed when DOX loading increased in nanocomposite, then cell viability was decreased in it. Therefore, these properties make MFG3 nanocomposite a good candidate for photothermal therapy and drug loading. Graphical Abstract

Background Growing body of evidence suggest the association between SNP − 11377 C > G and SNP + 276 G > T polymorphisms of adiponectin gene with type 2 diabetes (T2D). However, these findings have not been conclusive and consistent. The present study quantitatively evaluates the data on the association between DIPOQ − 11377C/G, and + 276G/T polymorphisms and risk of T2D through a meta-analysis. Methods A systematic search was performed in the PubMed, Web of science, Scopus and Cochrane library databases to extract published studies according to the inclusion criteria. Among the 741 studies, 391 of them were screened as full text and 31 studies were finally included in the meta-analysis. Analysis of data was performed using random-effects model. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to analyze the strength of association. Subgroup and meta-regression analyses were performed to identify the potential source of heterogeneity. Results The pooled analysis showed that there was no statistically significant association between genotypes of CC (OR = 0.76, 95% CI: 0.53–1.09, P  = 0.14), CG (OR = 0.93, 95% CI: 0.72–1.20, P = 0.58) and GG (OR = 1, 95% CI: 0.80–1.26, P = 0.94) ADIPO − 11377 polymorphism with increased risk of T2D. In addition, the results revealed a trend toward an increased risk of T2D for the SNP + 276 TT genotype (OR = 0.87, 95% CI: 0.77–0.98, P = 0.026) as compared with the GT and GG genotypes. Subgroup analysis by ethnicity indicated significant association between the TT genotype of the SNP + 276 and increased risk of T2D among Europeans. Met-regression demonstrated significant association between the GT genotype of + 276 polymorphism with risk of T2D in male individuals (slope: 0.0006; 95% CI: 0.0002–0.0009; P < 0.001). Conclusions Collectively, our findings demonstrated a positive association between ADIPOQ + 276 G > T polymorphism with increased risk of T2D in male individuals with European ethnicity. Graphical Abstract Highlights Adiponectin (ADIPOQ) plays an important role in the development of type 2 diabetes and previous studies regarding the association between ADIPOQ polymorphisms and T2D risk reported conflicting results. We performed a meta-analysis to assess the association between two ADIPOQ polymorphisms [− 11377C/G (rs266729), and +276G/T (rs1501299)] and risk for T2D. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were pooled to assess the association between four aforementioned polymorphisms and susceptibility to T2D. Overall, there was an association between ADIPOQ +276 G > T with increased T2D risk. Subgroup by ethnicity suggested significant association between +276G/T polymorphism and T2D risk among European ethnicities. Our findings evidence a positive association between ADIPOQ +276 G > T polymorphism with increased risk of T2D in male individuals with European ethnicity.

This study aimed to assess the efficacy of ezetimibe in combination with metformin versus metformin alone in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and type 2 diabetes mellitus. Patients were randomly divided into two groups: one receiving ezetimibe and metformin (Met + EZY) and the other receiving metformin alone (Met group) for six months. Parameters were measured at baseline (T1), after three months (T2), and after six months (T3). The findings indicated that insulin levels and HOMA-IR exhibited a significant decrease from T1 to T2 in the Met + EZY group ( p  < 0.05). Malondialdehyde (MDA) and triglycerides levels also demonstrated significant decreases from T1 to T2 in the Met + EZY group ( p  < 0.05). The expression of peroxisome proliferator-activated receptor gamma ( PPAR-γ ) and adiponectin ( ADIPO ) showed a significant increase from T1 to T2 in the Met + EZY group ( p  < 0.01). Additionally, ADIPO expression showed a significant increase from T1 to T3 ( p  < 0.001) in both groups. When comparing the two treatment groups, PPAR-γ and ADIPO expression were significantly higher in the Met + EZY group during T2 and T3 compared to the Met group ( p  < 0.001). Combination therapy appears to be more effective than metformin treatment alone and should be used cautiously.

Differentiation process of mesenchymal stem cells (MSCs) into adipocyte is involved in obesity. Multiple factors such as Ca2+ play important roles in different stages of this process. Because of the complicated roles of Ca2+ in adipogenesis, the aim of present investigation was to study the influx and efflux of Ca2+ into and out of the cells during adipogenesis. Adipose-derived MSCs were used to differentiate into adipocytes. MSCs were exposed to 2.5 mM Ca2+ or 1.8 mM Ca2+ plus calcium ionophore, A23187, for 3 days. Lipid staining, triglycerides (TG) content, and glyceraldehyde phosphate dehydrogenase (GAPDH) activity were evaluated to confirm the efficiency of the differentiation. Gene expression of GLUT4, PPARγ2, RAR-α, and calreticulin, as well as the protein levels of GLUT4 and PPARγ2 were determined. Ca2+ and in particular Ca2+ plus A23187 significantly lowered the efficiency of differentiation accompanied by decrease in intracellular TG deposits, GAPDH activity and alleviation of gene, and protein levels of GLUT4 and PPARγ2. While calreticulin and RAR-α were remarkably upregulated in A23187 group. This study showed the inhibitory effects of calcium in adipogenesis. Additionally, it indicated the greater inhibitory effect of calreticulin and RAR-α in controlling adipogenesis by higher levels of calcium.