Archives of Physiology and Biochemistry最新文献

Keratinocyte and fibroblast dysfunctions contribute to delayed healing of diabetic wounds. Small extracellular vesicles (sEV) are key mediators of intercellular communication and are involved in the pathogenesis of several diseases. Recent findings suggest that sEV derived from high-glucose-treated keratinocyte (HaCaT-HG-sEV) can transport LINC01435 to inhibit tube formation and migration of HUVECs, thereby delaying wound healing. This study aimed to elucidate sEV-related communication mechanisms between keratinocytes and fibroblasts during diabetic wound healing. HaCaT-HG-sEV treatment and LINC01435 overexpression significantly decreased fibroblast collagen level and migration ability but significantly increased fibroblast autophagy. However, treatment with an autophagy inhibitor suppressed LINC01435 overexpression-induced decrease in collagen levels in fibroblasts. In diabetic mice, HaCaT-HG-sEV treatment decreased collagen levels and increased the expression of the autophagy-related proteins Beclin-1 and LC3 at the wound site, thereby delaying wound healing. Conclusively, LINC01435 in keratinocyte-derived sEV activates fibroblast autophagy and reduces fibroblast collagen synthesis, leading to impaired diabetic wound healing.

Objective: To investigate the comprehensive effects of daily chronic asprosin administration on various pubertal and reproductive parameters in female rats. This study aims to elucidate the role of asprosin in regulating the onset of puberty and its influence on hormonal profiles and ovarian histology.

Methods: Asprosin was administered intraperitoneally (i.p.) at a dose of 500 ng/kg daily for eight weeks. Hormonal assays and histological analyses were performed to evaluate the effects of asprosin on the onset of puberty and reproductive function.

Results: Daily chronic administration of asprosin accelerated the onset of the first oestrus. Hormonal assays revealed significant elevations in serum levels of Follicle-Stimulating Hormone (FSH) and Oestradiol (E2), while Inhibin B levels decreased. Histological evaluations demonstrated an increased number of primary and secondary follicles in ovarian tissue, without affecting primordial follicle counts or reproductive organ weights.

Conclusions: Role of adipokines in regulating puberty and reproductive function has increasingly gained recognition. This study aimed to provide the first comprehensive examination of the effects of daily chronic asprosin administration on pubertal and reproductive parameters in female rats. Utilising hormonal assays and histological analyses, asprosin was administered intraperitoneally (i.p.) at a dose of 500 ng/kg, daily, for eight weeks. Our findings revealed that daily chronic administration of asprosin accelerated the onset of the first oestrus. Hormonal assays showed significant elevations in serum levels of Follicle-Stimulating Hormone (FSH) and Oestradiol (E2), while Inhibin B levels decreased. Histological evaluations demonstrated an increased number of primary and secondary follicles in ovarian tissue, without affecting primordial follicle counts or reproductive organ weights. These results provide new insights into asprosin's role in advancing the age of first oestrus and modulating hormonal profiles, thereby offering potential benefits to the female reproductive system.

Type 2 Diabetes mellitus (T2DM) has the potential to impair cardiac function and cause heart failure. We aimed to study the cardioprotective influence of Galactin-3 (Gal-3) inhibitor; modified citrus pectin (MCP) in isoprenaline induced myocardial infarction (MI) in T2DM rats. Forty rats were allocated into 4 groups; groups I and II served as control. T2DM was provoked in groups III and IV by serving them high fat diet followed by a single low dose of Streptozotocin (STZ), then group IV were administered MCP in drinking water for 6 weeks. Groups III and IV were then subcutaneously injected isoprenaline hydrochloride once daily on the last 2 successive days to induce MI. MCP restored echocardiographic parameters with significant decline in Gal-3 area % in cardiac tissue alongside protection against cardiac remodelling. our data showed that there is a protective potential for Gal-3 inhibitor (MCP) against cardiac injury in isoprenaline induced MI in T2DM.

The aim of this study was to investigate the protective effects of Mangiferin (MG) on glucolipotoxicity-induced pancreatic beta-cell injury. In vivo administration of MG significantly reduced the level of blood glucose in high-fat diet (HFD)-fed mice. MG treatment inhibited beta-cell apoptosis in HFD-treated mice. In vitro, MG protected INS-1 cells against apoptosis and impairment of insulin secretion following High glucose/Palmitic acid (HG/PA) treatment. MG treatment enhanced autophagy flux which was blocked by HG/PA treatment. Inhibition of autophagosome formation by 3-Methyladenine or blockade of autolysosome by Chloroquine reversed the protective effects of MG on INS-1 cells. MG treatment increased AMPK phosphorylation and reduced mTOR activation in INS-1 cells. Administration of the AMPK blocker abrogated MG-induced autophagy, and similar results were observed in INS-1 cells after cotreatment with MG and mTOR activator. In conclusion, MG ameliorated pancreatic beta-cell injury induced by glucolipotoxicity through modulation of autophagy via the AMPK-mTOR pathway.

Diabetic retinopathy (DR) is a complication of diabetes and a leading cause of blindness in adults. Studies have shown that glucagon-like peptide-1 (GLP-1) exerts a protective effect on patients with DR. Here, we investigated the protective effects of Exendin-4, a GLP-1 analogue, on DR. We established a high-glucose-induced HREC cell model and an STZ-induced rat DR Model to study the effect of Exendin-4 in DR in vitro and in vivo. The qRT-PCR, CCK-8, TUNEL, western blotting, tube formation assays, and ELISA were performed. In addition, we overexpressed TGFB2 to observe whether the protective effect of Exendin-4 was reversed. Our results showed that Exendin-4 inhibited the progression of DR. Furthermore, the protective effect of Exendin-4 was suppressed in cells overexpressing TGFB2. Our findings suggest that Exendin-4 may be involved in the regulation of TGFB2 expression levels to inhibit DR. These results indicate that Exendin-4 could be an effective therapy for DR.

Objective: Chronic inflammation contributes to myocardial complications in diabetes, marked by tissue fibrosis, necrosis, and apoptosis. Zingiber officinale, Allium sativum, and Moringa oleifera have individually demonstrated efficacy in diabetes management. In this study, it is hypothesised that a combination of these herbs in a polyherbal formulation would protect against diabetic cardiomyopathy.

Materials and methods: Diabetes was induced in male Sprague Dawley rats using strepetozotocin at a single dose of (55 mg/kg of body weight, i.p) in citrate buffer. Polyherbal formulation was administred as a treatment for 8 weeks.

Rats receiving treatment with polyherbal formulation showed decreased blood glucose, plasma creatinine, Blood Urea Nitrogen, Creatine kinase- myocardial band, lactate dehydrogenase, aspartate aminotransferase, Troponin-I, NADPH oxidase 4, and Ras-related C3 botulinum toxin substrate-1. In contrast, Superoxide dismutase, catalase, and glutathione enzyme activities were increased.

Conclusion: Thus, a polyherbal formulation containing herbs was able to attenuate the progression of diabetes mellitus and diabetic cardiomyopathy.

Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) plays a crucial role in regulation of metabolic homeostasis. To understand the role of the catalytic α2 subunit of AMPK in skeletal muscle energy metabolism, myotube cultures were established from AMPKα2^+/+ and AMPKα2^-/- mice. Myotubes from AMPKα2^-/- mice had lower basal oleic acid and glucose oxidation compared to myotubes from AMPKα2^+/+ mice. However, the relative response to mitochondrial uncoupling was increased for oleic acid oxidation. Incorporation of acetate into lipids was also lower in myotubes from AMPKα2^-/- mice. Proteomics analysis revealed that AMPKα2^-/- myotubes had upregulated pathways related to mitochondrial function and fatty acid oxidation, and decreased pathways related to fatty acid biosynthesis. In conclusion, ablation of AMPKα2 catalytic subunit in skeletal muscle cells resulted in reduced basal oxidation of glucose and fatty acids, however upregulated pathways related to mitochondrial function and fatty acid oxidation and reduced lipid formation.

Background: Lipid metabolism, one of the three major metabolic processes, plays a crucial role in male fertility, particularly when lipid homeostasis is disrupted. Lipid droplets (LDs), cellular organelles that store lipids primarily in the form of triglycerides and cholesterol esters, serve as central hubs in lipid metabolism.The degradation of LDs is regulated by lipases and lipophagy.

Objective:: This review explores the various forms of lipophagy, its molecular mechanisms, and its critical role in male fertility. Specifically, it examines the association between lipophagy and male infertility, sexual dysfunction, and reproductive cancers.

Methods:: This review synthesizes current research on the molecular pathways regulating lipophagy, focusing on its impact on male reproductive health.

Results:: Lipophagy is essential for maintaining lipid homeostasis in male reproductive tissues. Dysfunction of lipophagy is associated with impaired sperm function, infertility, sexual dysfunction, and an increased risk of reproductive cancers in men.

Conclusion:: Lipophagy plays a pivotal role in regulating lipid metabolism and maintaining male fertility. It may serve as a potential therapeutic target for treating male reproductive disorders.

Objective: This research assesses renoprotective effects of saracatinib (Src) in diabetic nephropathy (DN) and the potential underlying processes.

Materials and methods: Rats were divided into: control, DN, DN + Met + Los, DN + Met + Src, and DN + Met + Los + Src. Rats' ABP, urinary albumin, urinary nephrin, and creatinine clearance were assessed. Blood samples were collected for measuring glycaemic state parameters, renal functions, oxidative stress markers, inflammatory mediators, aldosterone, and lipid profile. Kidneys were extracted for KIM-1 and nephrin gene expression, H&E, Masson's trichrome staining, and immunohistochemical assessment.

Results: Significant increases in ABP, urinary albumin and nephrin, glycaemic measurements, urea, creatinine, aldosterone, inflammatory cytokines, MDA, lipids, renal fibrosis, H scores of VEGF and TGF-β, and renal KIM-1 expression were related to DN. However, there was a significant decrease in creatinine clearance, GSH, and nephrin expression in DN group compared with control group.

Discussion and conclusion: The combination of metformin (Met), losartan (Los), and Src repaired DN alterations. Adding Src to Met and Los is superior to using them alone.