General physiology and biophysics最新文献

This study aimed to elucidate the mechanism of Wenzheng Jiedu Powder Modified Formula (WJPMF) in treating neuropathic pain (NP). Network pharmacology and experimental verification were integrated to explore the therapeutic effects and key targets of WJPMF. Active components, corresponding target genes, and absorption, distribution, metabolism, and excretion (ADME) genes of WJPMF against NP were screened from public databases. Network analysis and molecular docking were conducted to identify key targets and verify binding abilities. In vivo experiments were performed on spared nerve injury (SNI) rats to assess the analgesic effects and regulatory mechanisms of WJPMF. WJPMF significantly improved pain behaviors in SNI rats by regulating ATP-binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor alpha (PPARA), peroxisome proliferator-activated receptor gamma (PPARG), and superoxide dismutase 2 (SOD2) expression, which were key targets involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. WJPMF shows promising therapeutic potential for NP through the modulation of specific targets, offering a novel therapeutic strategy for managing NP.

The aim of this study was to investigate the molecular mechanism by which miR-497-5p regulates neuronal injury after ischemic stroke through the BDNF/TrkB/Akt signaling pathway. PC12 cells were used to construct a stroke injury model by oxygen-glucose deprivation/reoxygenation (OGD/R). The expression level of miR-497-5p was measured by RT-qPCR. CCK-8 kit was used to detect cell viability. Cell apoptosis and reactive oxygen species (ROS) were detected by flow cytometry. MDA and SOD detection kits were used to detect MDA content and SOD activity. A double luciferase reporter system was used to verify the targeting relationship between miR-497-5p and BDNF. The expression of BDNF, TrkB, p-TrkB, Akt and p-Akt was detected by Western blot. We have found that miR-497-5p expression was inhibited after treatment with OGD/R. Simultaneously, cell apoptosis, MDA content and ROS were upregulated, while cell viability and SOD were significantly decreased in PC12 cells. The effects of OGD/R on PC12 cells were reversed with the downregulation of miR-497-5p. A double luciferase reporter assay demonstrated that miR-497-5p negatively targets BDNF. BDNF inhibited cell apoptosis and oxidative stress injury in PC12 cells. These findings suggest that miR-497-5p aggravates neuronal injury in experimental model of ischemic stroke by inhibiting the BDNF/TrkB/PI3K/Akt signaling pathway.

I previously reported chromosomal damage in human peripheral blood lymphocytes (HPBLs) induced by: a) mobile telephony (MT) electromagnetic fields (EMFs)/electromagnetic radiation (EMR), b) a high caffeine dose, and c) the combination of the two stressors. HPBLs from the same subjects exposed to gamma radiation at doses 0.1, 0.3, or 0.5 Gy, displayed more aberrations than those exposed to MT EMFs or the high caffeine dose in a dose-dependent manner. When the cells exposed to these gamma radiation doses were pre-exposed to a single 15-min MT EMF exposure, the number of aberrations increased significantly more than the sum number of aberrations induced by the individual stressors in all subjects. Thus, MT EMF exposure at a power density ~136 times below the latest International Commission on Non- Ionizing Radiation Protection (ICNIRP) exposure limit, apart from the fact that it is genotoxic by itself, significantly enhanced the genotoxic action of gamma radiation. Since gamma radiation at similar doses is applied for diagnostic and therapeutic purposes, people should be aware of the increased risk during treatment periods. Comparison of the genotoxic action between MT EMF and gamma radiation shows that the ICNIRP limits are, at least, ~4.5×10⁴ times less stringent than the limits for gamma radiation.

Immune cells in the immune microenvironment of lung adenocarcinoma (LUAD) are involved in tumour progression. The aim of this study was to investigate the molecular mechanisms of immune infiltration-related genes in LUAD. The GEO, GeneCards, BioGPS and Genehopper databases were utilized to screen for immune infiltration-related differentially expressed genes (DEGs) in LUAD. Protein-protein interaction (PPI) network construction and survival analysis were performed in the Kaplan-Meier database to identify hub genes. The TIMER 2.0 database was used to analyse the correlations between hub gene expression and immune infiltration level. Co-culture of LUAD cells with macrophages and plasmid transfection to overexpress ANGPT1 were performed to investigate the function of the hub genes in LUAD using RT-qPCR, Western blot, CCK-8 assays, cell wound healing assays and transwell assays. A total of 88 immune infiltration-related DEGs were screened. The hub genes ANGPT1, CDH5 and CLDN5 were reduced in LUAD, while COL3A1 was overexpressed. ANGPT1 was significantly correlated with OS, FP and PPS, and ANGPT1 promoted the polarization of M1 macrophages. Further experiments revealed that ANGPT1 inhibited the proliferation, migration and invasion of LUAD cells by inhibiting the TGF-β signalling pathway. ANGPT1 promotes polarization of M1 macrophages and reduces the progression of LUAD by inhibiting the TGF-β signalling pathway. Thus, ANGPT1 could be employed as a predictive biomarker and immunotherapy target for lung cancer.

Hepatic steatosis and dyslipidaemia are associated with excessive fructose consumption. We investigated the effect of quercetin intake during the early pre-weaning period on metabolic dysfunction caused by a high fructose diet. Sprague Dawley rats, 21-day-old, were weaned onto standard rat chow and randomly allocated to four groups which either water or 20% fructose solution to drink with or without quercetin (100 mg/kg body mass). Quercetin was administered for two weeks. Thereafter, rats continued on their respective diets for six weeks without quercetin. Terminally, serum triglyceride concentrations were not significantly different (p > 0.05) between males across groups. However, females receiving quercetin alone had lower serum triglyceride levels than those receiving fructose (p < 0.01). Quercetin increased the incidence of hepatic steatosis in female rats. Quercetin intake in the immediate post-weaning period may prevent hypertriglyceridemia. However, female rats receiving quercetin alone are predisposed to hepatic steatosis associated with a high fructose diet.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent and fatal disease worldwide. The function of club cells, which are considered progenitor/stem cells of the bronchial epithelium, and their secreted protein CC16, have been proposed as potential targets for COPD treatment. This study aimed to investigate the role of the TGF-β1/ALK5 signaling pathway in club cell function and COPD progression. C57BL/6J mice were divided into Normal group (exposed to fresh air) and COPD group (exposed to incremental cigarette smoke extract for 12 weeks). The COPD mice were further divided into COPD group, DMSO group, and LY2109761 group (injected with 150 mg/kg LY2109761, a TGF-β1 inhibitor). Tissue staining was used to assess lung damage, and the expression of CC16 was measured. The levels of inflammatory factors and DNA damage-related indicators were also measured. The involvement of the MEK/ERK signaling pathway was determined. COPD mice exhibited severe lung damage and impaired club cell function. Activation of the TGF-β1/ALK5 and MEK/ERK pathways were observed in COPD mice. However, administration of LY2109761 in COPD mice inactivated the TGF-β1/ALK5 and MEK/ERK pathways. Administration of LY2109761 also alleviated pulmonary fibrosis, downregulated the levels cleaved caspase-3, IL-4, IL-5, IL-13, IL-12, and IFN-γ, and limited the phosphorylation of Chk1. Moreover, LY2109761 enhanced CC16 expression and decreased lung cell apoptosis. Inactivation of the TGF-β1/ALK5 axis inhibits the MEK/ERK signaling pathway, enhances club cell function, and alleviates lung tissue damage. These findings suggest that TGF-β1 is a potential therapeutic target for COPD.

To investigate the potential functions and regulatory mechanism of circRSU1 on septic acute lung injury (sepsis-ALI) progression. We used lipopolysaccharide (LPS)-stimulated human pulmonary microvascular endothelial cells (HPMECs) to establish the cell model of sepsis-ALI in vitro. qRT-PCR and Western blotting were used for the detection of genes and proteins. The migration and tubulogenesis of HPMECs were assessed by transwell, wound healing, and tube formation assays. Inflammatory factors were detected by ELISA analysis. Cell permeability (PA) was determined by transendothelial resistance (TEER) and fluorescein isothiocyanate (FITC) with transwell assay. The interaction between miR-1224-5p and circRSU1 or ITGA5 (Integrin Subunit Alpha 5) was studied by dual-luciferase reporter and RNA pull-down assays. CircRSU1 expression was decreased after LPS treatment in HPMECs. Functionally, re-expression of circRSU1 in HPMECs could alleviate LPS-induced inflammatory response, the inhibition of cell migration and tube formation and enhancement of cell permeability. Mechanistically, circRSU1 acted as a sponge for miR-1224-5p. LPS treatment enhanced miR-1224-5p expression, and inhibition of miR-1224-5p reversed LPS-evoked HPMEC dysfunction mentioned above. Moreover, miR-1224-5p could abolish the protective effects of circRSU1 on HPMECs. In addition, miR-1224-5p directly targeted ITGA5, and circRSU1 was able to regulate ITGA5 expression via interacting with miR-1224-5p. CircRSU1 could alleviate LPS-induced HPMEC injury by miR-1224-5p/ITGA5 axis, indicating the potential molecular contribution of circRSU1 in sepsis-ALI.

The most prevalent cause of lung cancer is smoking tobacco, but exposure to second hand smoke, air pollution, and certain chemicals and substances at work can also raise the risk of disease. In this study, we scrutinized the chemoprotective effect of the metformin and atorvastatin combination against benzo[a]pyrene (BaP)-induced lung cancer in mice of Swiss albino. BaP (50 mg/kg) was used for induction of lung cancer and mice were treated with metformin, atorvastatin or their combination. Metformin + atorvastatin combination significantly (p< 0.001) improved the body weight, liver weight, suppressed the lung weight and tumor incidence and altered the levels of immunocompetent cells, polyamines, lung tumor markers, lung parameters and antioxidant parameters, respectively. Metformin + atorvastatin combination also suppressed cytokines levels, inflammatory parameters and caspase parameters. On the basis of the results, we can conclude that metformin + atorvastatin combination remarkably suppressed lung cancer via the inflammatory pathway.

The objective of this article is to describe and classify usual interstitial pneumonia (UIP) changes according to their relevance in the pathology of the idiopathic pulmonary fibrosis (IPF) process. In a cohort of 50 patients (25♀, 25♂) with UIP findings, the percentage ratio between fibrotic and preserved parts of the lungs was quantified. Three quantitative stages of fibrotic involvement of the lung parenchyma and concomitant changes were defined. These are initial (≤20%), advanced (21-40%), and diffuse (≥41%) fibrosis of the lungs. Histologically, temporal heterogeneity is predominant with thickened alveolar septa, interstitial fibrosis, and the presence of fibroblastic foci up to mature diffuse fibrosis with honeycomb changes. The finding is accompanied by variably mature lymphocytic inflammation, presence of macrophages, emphysema, bronchioloectasia of the alveoli, bronchiectasis, bronchial muscle wall hypertrophy, hypertrophy of the vessel walls, alveolar mucosa, focal haemorrhage, and hyalinization of the lungs. Pneumocyte hyperplasia, occasionally atypical in appearance with hobnail changes, as well as squamous metaplasia are observed. In the methodically quantified stages of fibrous involvement, 14 subjects were classified (6♀, 8♂) into the stage of initial fibrosis, 21 subjects (11♀; 10♂) into the stage of advanced fibrosis, and 15 subjects (8♀; 7♂) into the stage of diffuse fibrosis.

This study investigated whether microbubbles activated by low-frequency ultrasound enhanced the anti-tumor effects of curcumin in glioma cells. CCK8 proliferation assay, scratch migration assay, and transwell invasion assay were performed to estimate the proliferation, migration, and invasion rates of the glioma cells in blank control and different treatment groups, respectively. Quantitative RT-PCR (qRT-PCR) analysis was performed to determine the relative expression levels of VEGF and NCAM mRNAs in the various experimental groups. Western blotting was performed to determine the activity status of the TGF-β1/Smad signaling pathway in various groups of glioma cells by estimating the expression levels of p-SMAD2/3, VEGF, and NCAM proteins. Combined treatment (Cur-Us-MBs) with microbubbles activated by low-frequency ultrasound and curcumin significantly reduced the in vitro proliferation, migration, and invasiveness of glioma cells compared to the control and other treatment groups. Furthermore, Cur-Us-MBs significantly reduced the expression levels of VEGF and NCAM mRNAs and proteins and p-Smad2/3 proteins , including those cells stimulated with rhTGF-β. These suggested that microbubbles activated by low-frequency ultrasound enhanced the inhibition of TGF-β1/Smad/VEGF/NCAM signaling pathway by curcumin，and enhanced the antitumor effects of curcumin by significantly reducing in vitro proliferation, migration, and invasiveness of glioma cells through this pathway.