General physiology and biophysics最新文献

Physical inactivity has evidently been a hazard factor for many diseases, including cardiovascular disease, diabetes, cancer, etc. Rising evidence indicates that RNA, as competitive endogenous RNA (ceRNA), plays an important role in adaptive changes in skeletal muscle in response to exercise training. Although the effects of exercise-induced fitness on skeletal muscle have been well established, the mechanisms underlying are not fully understood. The purpose of this study is to construct a novel ceRNA network in skeletal muscle in response to exercise training. Skeletal muscle gene expression profiles were downloaded from the GEO database. Then, we identified differentially expressed lncRNAs, miRNAs, and mRNAs between the pre-exercise and post-exercise samples. Subsequently, we constructed lncRNA-miRNA-mRNA regulatory networks based on the ceRNA theory. 1153 mRNAs (687 upregulated and 466 downregulated), 7 miRNAs (3 upregulated and 4 downregulated), and 5 lncRNAs (3 upregulated and 2 downregulated) were identified as differentially expressed genes. 3 lncRNAs, 5 miRNAs and 227 mRNAs were obtained to build miRNA-mediated ceRNA networks. We constructed a novel ceRNA regulatory network in muscle in response to exercise training, which provides insights into molecular mechanisms underlying the health benefits brought by physical activity.

This study investigated whether chronic isoproterenol administration could induce kidney alterations and whether ivabradine, a heart rate (HR)-reducing substance exerting cardiovascular protection, is able to attenuate potential kidney damage. Twenty-eight Wistar rats were divided into non-diseased controls, rats treated with ivabradine, rats treated with isoproterenol, and rats treated with isoproterenol plus ivabradine. Six weeks of isoproterenol administration was associated with decreased systolic blood pressure (SBP) (by 25%) and glomerular, tubulointerstitial and vascular/perivascular fibrosis due to enhanced type I collagen volume (7-, 8-, and 4-fold, respectively). Ivabradine reduced HR (by 15%), partly prevented SBP decline (by 10%) and site-specifically mitigated kidney fibrosis by decreasing type I collagen volume in all three sites investigated (by 69, 58, and 67%, respectively) and the ratio of type I collagen-to-type III collagen in glomerular and vascular/perivascular sites (by 79 and 73%, respectively). We conclude that ivabradine exerts protection against kidney remodelling in isoproterenol-induced kidney damage.

Toxic doses of paracetamol are also known to be close to therapeutic doses. This study aimed to biochemically investigate the protective effect of ATP against paracetamol-induced oxidative liver injury in rats and to examine the tissues histopathologically. We divided the animals into the paracetamol alone (PCT), ATP + paracetamol (PATP), and healthy control (HG) groups. Liver tissues were examined biochemically and histopathologically. Malondialdehyde level, AST and ALT activity in the PCT group were significantly higher than those in the HG and PATP groups (p < 0.001). The glutathione (tGSH) level, superoxide dismutase (SOD) and catalase (CAT) activity in the PCT group was significantly lower than that in the HG and PATP groups (p < 0.001), while animal SOD activity was significantly different between the PATP and HG groups (p < 0.001). The activity of CAT was almost the same. In the group treated with paracetamol alone, lipid deposition, necrosis, fibrosis, and grade 3 hydropic degeneration were observed. No histopathological damage was observed of the ATP-treated group, except for grade 2 edema. We discovered that ATP reduces the oxidative stress caused by paracetamol ingestion and protects against paracetamol-induced liver injury at the macroscopic and histological levels.

This study aimed to explore the possible cytoprotective effects of exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the testicles of diabetic rats. Exenatide has numerous advantageous properties in addition to its hypoglycemic effect. However, its impact on testicular tissue in diabetes needs more clarification. Therefore, rats were divided into control, exenatide-treated, diabetic and exenatide-treated diabetic groups. Blood glucose and serum levels of insulin, testosterone, pituitary gonadotropins and kisspeptin-1 were measured. Real-time PCR for beclin-1, p62, mammalian target of rapamycin (mTOR), and AMP-activated protein kinase (AMPK), were estimated in testicular tissue in addition to markers of oxidative stress, inflammation, and endoplasmic reticulum stress. Also, immuno-expression of protein P53, nuclear erythroid factor2 (Nrf2) and vimentin was conducted. Exenatide was able to attenuate diabetic toxic changes and enhance autophagy in testicular tissue. These results indicate the protective effect of exenatide against diabetic testicular dysfunction.

Circular RNAs (circRNAs) have important regulation in in sepsis-related acute lung injury (ALI). Circ_0001498 was significantly overexpressed in sepsis-induced acute respiratory distress syndrome. The aims of this study were to explore role and mechanism of circ_0001498 in lipopolysaccharide (LPS)-treated WI-38 cells. Human samples were collected from 56 sepsis patients and 46 healthy volunteers at Liyang People's Hospital. Circ_0001498, microRNA-574-5p (miR-574-5p) or sex-determining region Y-related high-mobility-group box 6 (SOX6) levels were detected via reverse transcription-quantitative polymerase chain reaction assay. Cell viability was determined through Cell Counting Kit-8 assay. Apoptosis rate was examined by flow cytometry. Western blot was used for measurement of proteins. Inflammatory cytokines were detected via enzyme-linked immunosorbent assay. Target relation was analyzed via dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Circ_0001498 was overexpressed in sepsisrelated ALI patients and LPS-treated WI-38 cells. Silencing circ_0001498 reduced LPS-induced cell apoptosis and inflammation. Circ_0001498 interacted with miR-574-5p. The regulation of circ_0001498 knockdown was abolished by miR-574-5p inhibitor. Furthermore, miR-574-5p directly targeted SOX6 and circ_0001498 upregulated SOX6 via targeting miR-574-5p. Overexpression of miR-574-5p alleviated LPS-induced cell injury by downregulating SOX6. This research identified that circ_0001498 facilitated sepsis-related ALI progression by targeting miR-574-5p to upregulate SOX6.

Guillain-Barré syndrome (GBS) is an acute immune-mediated paralytic neuropathy with variable disease course and outcome. In this study, we aimed to investigate the therapeutic effects of celastrol on GBS and uncover its underlying mechanisms. Experimental autoimmune neuritis (EAN) is a typical animal model for GBS, and thus an EAN rat model was established with the injection of celastrol or/and LPS. We assessed the body weights and EAN clinical scores of rats. HE staining, flow cytometry, RT-qPCR, and Western blotting were respectively employed to measure pathological damage, proportions of cells (Th1, Th17, and Treg), Th1/Th17 cell differentiation-related mRNAs (IFN-γ, TBX21, IL-18, RORγT, IL-17, and IL-23) and TLR4/NF-κB/STAT3 pathway-related proteins (TLR4, NF-κB, p-NF-κB, STAT3, and p-STAT3). We found that celastrol attenuated clinical symptoms and pathological damage of GBS in EAN rats. Moreover, celastrol down-regulated Th1 and Th17 cell proportions, and the levels of IFN-γ, TBX21, IL-18, RORγT, IL-17, and IL-23 in EAN rats. Meanwhile, the levels of TLR4, p-NF-κB, and p-STAT3 were decreased by celastrol. Taken together, celastrol could restrain Th1/Th17 cell differentiation through inhibition of the TLR4/NF-κB/STAT3 pathway in EAN rats. Our findings suggest that celastrol may exert therapeutic effects on GBS by suppressing TLR4/NF-κB/STAT3 pathway-mediated Th1/Th17 cell differentiation.

The primary sources of reactive oxygen species (ROS) that cause ischemia-reperfusion (I/R) injuries are enzymes xanthine oxidase (XO) and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) in the literature, whereby one of the main ROS producing cells via NOX activity are polymophonuclear leukocytes (PNL). Sugammadex, the effect of which we plan to research against gastric I/R damage, is a modified gamma-cyclodextrin that antagonizes the action of steroidal neuromuscular blocking drugs. Previous studies have reported that sugammadex inhibits PNL infiltration. However, it is unknown whether an inhibitory effect on XO is present. We aimed to biochemically and histopathologically investigate the effects of sugammadex on I/R-induced stomach damage in rats. The animals were divided into groups that underwent gastric ischemia-reperfusion (GIR), 4 mg/kg sugammadex + gastric ischemia-reperfusion (SGIR), and a sham operation group (SG). The effect of sugammadex was evaluated by measuring oxidant-antioxidant and PNL parameters. There was no significant difference in XO levels between the SGIR and GIR groups. In the SGIR group, sugammadex inhibited the increase in myeloperoxidase (MPO) and malondialdehyde (MDA) levels (p < 0.001). The amount of MDA and MPO in the SGIR group was similar as in the SG group. Sugammadex significantly suppressed the decrease in tGSH levels in the SGIR group (p < 0.001). The difference between tGSH levels in the SG and SGIR groups was slight. In the SGIR group, sugammadex significantly suppressed the increase in tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL1-β) levels compared to the GIR group (p < 0.001). Additionally, sugammadex corrected histopathological modifications as much as sham group. In conclusion, sugammadex may be beneficial in preventing oxidative stress.