Autophagy enhances the differentiation of insulin-producing cells from Wharton's jelly-derived mesenchymal stem cells.

Autophagy disruption suppresses insulin production and induces diabetes. The role of autophagy in the differentiation of Wharton's jelly (WJ)-derived mesenchymal stem cells (WJSCs) into insulin-producing cells (IPCs) was investigated in this experimental study. The WJSCs were incubated in a differentiation medium (DM) with or without an autophagy inhibitor (3-methyladenine: 3MA). The differentiation of IPCs was confirmed by flow cytometry analysis of PDX-1 and insulin-positive cells, insulin secretion, and the high expression of ß cell-specific genes, Glucose transporter 2 (GLUT-2), and INSULIN. Autophagy has been assessed by calculating the percentage of Acridine orange (AO)-positive cells, expression of autophagy-related genes, and the LC3B/LC3A ratio. ß cell-specific genes were up-regulated in the DM group, and 3MA decreased their expression. In the DM+3MA-treated cells, the expression of GLUT-2 and INSULIN genes and insulin secretion decreased compared to the DM group. In cells treated with 3MA, there was a significant decrease in the percentage of PDX-1 and insulin-positive cells compared to 3MA-untreated cells. Additionally, in the group receiving both DM and 3MA treatment, the expression of autophagy-related genes, the LC3B/LC3A protein ratio, and the percentage of AO-stained cells were significantly reduced compared to the group receiving only DM treatment. These findings suggest autophagy is essential for ß cell differentiation and insulin secretion.

Effects of sodium hydrosulfide (NaHS) on cisplatin-induced hepatic and cardiac toxicity.

In recent years, the cardiotoxicity and hepatotoxicity induced by chemotherapeutic drugs such as cisplatin (CP) have become significant issues. The current research looks into the effects of sodium hydrosulfide (NaHS) on CP-induced hepatotoxicity and cardiotoxicity in rats. A total of 32 male Sprague Dawley rats were separated into four different groups: (1) control group, received only normal saline; (2) NaHS group, was intraperitoneally injected with NaHS (200 µg/kg/d, dissolved in saline) for 15 days; (3) CP group, was intraperitoneally injected only one dose of CP (5 mg/kg) and (4) CP plus NaHS group, received CP along with NaHS. Blood and tissues samples were harvested for biochemical, histopathological, and immunohistochemical investigations. To determine the data's statistical significance, a one-way analysis of variance was used. CP injection significantly increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), Creatine phospho kinase (CK-MB), cholesterol, low-density lipoprotein (LDL), triglyceride (TG), and lipid peroxidation levels, while high-density lipoprotein (HDL), albumin, glutathione peroxidase, superoxide dismutase, and catalase (CAT) levels were significantly reduced with pathological alterations in liver and heart tissues. Co-treatment NaHS with CP ameliorates the biochemical and histological parameters. Also, Treatment solely with CP resulted in increased tissue expression of interleukin-1ß (IL-1ß) in liver and heart but co-treatment NaHS with CP reduced the expression of this inflammatory factor. We conclude that NaHS operates in the liver and heart as an anti-inflammatory and powerful free radicals' scavenger to inhibit the toxic effects of CP, both at the biochemical and histopathological levels.

NaHS protects the liver and heart against Cisplatin-induced toxicity.

A high-efficient antibacterial and biocompatible polyurethane film with Ag@rGO nanostructures prepared by microwave-assisted method: Physicochemical and dermal wound healing evaluation.

Wound infections are a significant issue that can hinder the wound healing process. One way to address this problem is by enhancing the antibacterial activity of wound dressings. Accordingly, this work focuses on developing a castor-oil-based antibacterial polyurethane nanocomposite film impregnated with silver nanoparticles (AgNPs) decorated on the surface of reduced graphene oxide (rGO) nanostructures (Ag@rGO). To this aim, rGOs act as a platform to stabilize AgNPs and improve their bioavailability and dispersion quality within the PU film. The microwave-assisted synthesis of Ag@rGO nanohybrids was proved by FTIR, XRD, TGA, FE-SEM, EDS, and TEM analyses. Compared to PU/GO, the effect of Ag@rGO nanohybrids on thermo-mechanical features, morphology, antibacterial activity, cytocompatibility, and in vivo wound healing was assessed. SEM photomicrographs revealed the enhanced dispersion of Ag@rGO nanohybrids compared to GO nanosheets. Besides, according to XRD results, PU/Ag@rGO nanocomposite film demonstrated higher microphase mixing, which could be due to the finely dispersed Ag@rGO nanostructures interrupting the hydrogen bonding interactions in the hard segments. Moreover, PU/Ag@rGO nanocomposite showed excellent antibacterial behavior with completely killing E. coli and S. aureus bacteria. In vitro and in vivo wound healing studies displayed PU/Ag@rGO film effectively stimulated fibroblast cells proliferation, migration and re-epithelialization. However, the prepared antibacterial PU/Ag@rGO nanocomposite film has the potential to be used as a biomaterial for dermal wound healing applications.

Decellularized Wharton's jelly scaffold enhances differentiation of mesenchymal stem cells to insulin-secreting cells.

Diabetes is caused by the destruction of beta-cells in the pancreatic islets. This study was designed to fabricate a favorable bio-scaffold to improve the differentiation of Wharton's jelly (WJ) mesenchymal stem cells (WMJSCs) to the insulin-secreted cells (ISCs). In this study, a decellularized-WJ scaffold (DWJS) was established and characterized by histological assessments, scanning electron microscopy, determination of residual DNA, and examination of the mechanical tensile property. The WJMSCs were seeded on DWJS and exposed to ISC-differentiation media. The functional maturity of ISCs was examined using Ditizone (DTZ) staining, insulin and C-Peptide secretion, and mRNA expression of insulin-related genes. The main components of the WJ such as collagens, proteoglycans, and glycosaminoglycans remained after decellularization. Very low residual DNA, good mechanical behavior, and appropriate porosity of the DWJS provided an ideal extracellular microenvironment for the ISCs. The insulin secretion of DWJS-seeded ISCs in response to glucose stimulation was significantly more than that in the 2D-culture system. DWJS significantly increased the number of DTZ-positive cells compared to the 2D-culture system. In addition, it enhanced the expression of the PDX-1, GLUT-2, and INS genes in the ISCs. These results collectively provided solid evidence that DWJS is a suitable scaffold for stabilizing the artificial pancreatic island.

Assessment of the effect of sodium hydrogen sulfide (hydrogen sulfide donor) on cisplatin-induced testicular toxicity in rats.

Cisplatin (CIS) is an antineoplastic drug able to produce free radicals that are capable to induce various side effects in different tissues. Hydrogen sulfide (H2S) has notable antioxidant, anti-apoptotic, and anti-inflammatory effects in different systems but its role in male reproductive system is not fully understood. In the present research, the effect of sodium hydrosulfide (NaHS) on cisplatin-induced testicular toxicity in male rats was studied. Thirty-two Sprague-Dawley rats were equally divided into 4 groups. The control group was treated with normal saline by intraperitoneal injection. The NaHS group received NaHS (200 µg/kg/day) intraperitoneally for 15 days. The CIS group received single dose of cisplatin (5 mg/kg) intraperitoneally, while the combination of CIS and NaHS was given to the CIS+ NaHS group. At the end of the study, body and testicular weights, plasma testosterone level, histological and morphometrical alterations, inflammation via IL-1ß protein, lipid peroxidation, and activity of antioxidant enzymes (including glutathione peroxidase, superoxide dismutase, and catalase) of testicular tissue were evaluated. CIS injection revealed a significant decrease (p < 0.01) in body and testis weights, plasma testosterone concentration, diameter of seminiferous tubules, germinal epithelium thickness, the number of Sertoli cells, spermatogonia and spermatocyte, Johnsen's testicular score, and testicular antioxidant enzymes, whereas it caused a significant increase (p < 0.01) in lumen diameter of the seminiferous tubules, level of lipid peroxidation, and IL-1ß protein expression when compared with the control group. NaHS administration to CIS-treated rats provided marked improvement (p < 0.05) in all biochemical, histological, and morphometrical changes induced by CIS. The beneficial effects of NaHS were mediated, at least partly, by its antioxidant and anti-inflammatory properties.