Linggui Zhugan Decoction activates the SIRT1-AMPK-PGC1α signaling pathway to improve mitochondrial and oxidative damage in rats with chronic heart failure caused by myocardial infarction.

Objective: To investigate the effects of Linggui Zhugan Decoction on mitochondrial and oxidative damage in rats with chronic heart failure after myocardial infarction and the related mechanisms. Methods: Chronic heart failure after myocardial infarction was established by coronary artery ligation. Heart failure rats were randomly divided into three groups: Model group (n = 11), Linggui Zhugan Decoction group (n = 12), and captopril group (n = 11). Rats whose coronary arteries were only threaded and not ligated were sham group (n = 11). Cardiac function, superoxide dismutase (SOD), malondialdehyde (MDA) contents, soluble growth-stimulating expression factor (ST2), and N-terminal B-type brain natriuretic peptide precursor (NTproBNP) levels were analyzed after treatment. Moreover, the level of mitochondrial membrane potential was detected by JC-1 staining, the ultrastructural of myocardial mitochondria were observed by transmission electron microscopy. The related signal pathway of silent information regulator factor 2-related enzyme 1 (SIRT1), adenylate activated protein kinase (AMPK), phosphorylated adenylate activated protein kinase (p-AMPK), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is an important pathway to regulate mitochondrial energy metabolism, and to initiate mitochondrial biogenesis. The expression level was detected by Western blot and reverse transcription to explore the mechanism of the decoction. Results: Compared with the model rats, Linggui Zhugan Decoction significantly improved cardiac function (p < 0.05), reduced MDA production (p < 0.01), increased SOD activity (p < 0.05), reduced ST-2(p < 0.01), and NT-proBNP(p < 0.05) levels, increased mitochondrial membrane potential, and improved mitochondria function. In addition, Linggui Zhugan Decoction upregulated the expression of SIRT1, p-AMPK, PGC-1α protein, and mRNA in cardiac myocytes. Conclusion: Linggui Zhugan Decoction can improve the cardiac function of heart failure rats by enhancing myocardial antioxidant capacity and protecting the mitochondrial function, the mechanism is related to activating SIRT1/AMPK/PGC-1α signaling pathway.

Research Progress on the Cardiovascular Protective Effect of Glucagon-Like Peptide-1 Receptor Agonists.

The risk of cardiovascular diseases is closely related to diabetes. Macrovascular disease is the main cause of death and disability in patients with type 2 diabetes. In recent years, the glucagon-like peptide-1 receptor agonist (GLP-1RA), a new type of hypoglycemic drug, has been shown to regulate blood sugar levels, improve myocardial ischemia, regulate lipid metabolism, improve endothelial function, and exert a protective role in the cardiovascular system. This study reviewed the protective effects of GLP-1RA on the cardiovascular system.

Virtual Reality Fitness (VRF) for Behavior Management During the COVID-19 Pandemic: A Mediation Analysis Approach.

BACKGROUND: During the COVID-19 pandemic, cellphone health apps and virtual reality fitness for treating neurological disorders such as Parkinson's were beneficial. Virtual reality has been used to treat PTSD, depression, anxieties, dementia, ADHD, dyslexia, and pain control in various settings. Virtual reality exercise has been studied for its effects on biological, mental, rehabilitation, behavior, and attitude management. PURPOSE: This research aimed to find out the role of virtual reality fitness (VRF) for behavior management during the COVID-19 pandemic concerning the demographic characteristics of the study participants and the use of fitness and health apps. METHODS: The population for the current study was Chinese residents across China who were in home isolation during the early pandemic in China. According to the study objective, a convenience sampling method was used to collect the primary data through an online survey. SPSS-25 statistical software was used to analyze the demographic information and clean and prepare the data to test all proposed hypotheses. The proposed research framework was examined using the structural equation modeling (SEM) approach through SmartPLS 3.0 software. RESULTS: The structural equation model analysis shows that all the proposed hypotheses (H1: ß = 0.137, t = 10.454, p = <0.000; H2: ß = 0.256, t = 16.824, p = <0.000; H3: ß = 0.418, t = 27.827, p = <0.000; H4: ß = 0.133, t = 8.913, p = <0.000; H5: ß = 0.076, t = 4.717, p = <0.000; H6: ß = 0.162, t = 10.532, p = <0.000; H7: ß = 0.384, t = 26.645, p = <0.000) are confirmed. CONCLUSION: Fitness and health apps with virtual reality fitness play a substantial role in improving the overall quality of life and positively influencing behavior and attitude.

[Soluble hepatitis C virus E2 glycoprotein inhibits the secretion of proinflammatory cytokines in activated human CD4+ T cells].

Objective To explore the immunoregulatory effect of soluble hepatitis C virus E2 glycoprotein on activated human CD4+ T cells. Methods HEK293T cells were transfected with eukaryotic expression plasmid pcDNA3.1-HCV sE2, and soluble HCV E2 protein was purified by Ni-NTA resin affinity chromatography. CD4+ T cells from peripheral blood of healthy donors were sorted by flow cytometry, and cultured with 1.0 ug/mL mouse anti-human CD3 monoclonal antibody and 1.0 ug/mL mouse anti-human CD28 monoclonal antibody in vitro for 48 hours. The stimulated CD4+ T cells were divided into a blank control group, 2, 5, 10 µg/mL HCV E2 protein groups. Thirty-six hours after HCV E2 glycoprotein treatment, the expression of CD4+ T cell programmed death protein 1 (PD-1) was detected by flow cytometry, and the tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in cell culture supernatant were detected by ELISA. Results Compared with the blank control group, the expression of PD-1 on CD4+ T cells in the HCV E2 protein group decreased slightly, but the difference was not statistically significant. Compared with the blank control group, the secretion of TNF-α by CD4+ T cells in the soluble E2 protein group significantly decreased, which showed a dose-dependent effect. Compared with the blank control group, the level of IFN-γ secreted by CD4+ T cells in the soluble E2 protein group was significantly reduced, but there was no significant difference between the high and low dose groups. Conclusion Soluble HCV E2 glycoprotein can inhibit the secretion of antiviral proinflammatory cytokines in activated human CD4+ T cells.

Interleukin-6 Gene Polymorphism and the Risk of Systemic Inflammatory Response Syndrome Caused by Wasp Sting Injury.

Previous studies have shown that serum levels of interleukin-6 (IL-6), which plays an important role in the development of systemic inflammatory response syndrome (SIRS), is significantly increased in wasp sting patients. However, the association between IL-6 gene variants and the risk of SIRS development in these patients is not clearly understood. In this study, we investigated the association between IL-6 gene polymorphism in the promoter region and the risk of SIRS in wasp sting patients. A total of 160 patients were divided into SIRS group and non-SIRS group (control), and evaluated for polymorphisms in IL-6 (-174G/C, -572G/C, -597G/A, and -634C/G), using DNA sequencing. The IL-6 serum levels were assessed using an enzyme-linked immunosorbent assay. Risk factors were analyzed by logistic regression analysis. We found that the IL-6 serum level was significantly higher in the SIRS group than in the control group (p < 0.001). A significant association was observed in the genotypic distribution of the IL-6 - 572G allele in the SIRS group, when compared with the control group [OR = 3.909 (1.906-8.019), p < 0.001], and SIRS is more likely to occur in wasp sting patients with more than 10 stings. Thus, the IL-6 - 572G allele and more than 10 stings can be used as predictors of risk of SIRS development in wasp sting patients.

A protease-activated receptor 1 antagonist protects against global cerebral ischemia/reperfusion injury after asphyxial cardiac arrest in rabbits.

Cerebral ischemia/reperfusion injury is partially mediated by thrombin, which causes brain damage through protease-activated receptor 1 (PAR1). However, the role and mechanisms underlying the effects of PAR1 activation require further elucidation. Therefore, the present study investigated the effects of the PAR1 antagonist SCH79797 in a rabbit model of global cerebral ischemia induced by cardiac arrest. SCH79797 was intravenously administered 10 minutes after the model was established. Forty-eight hours later, compared with those administered saline, rabbits receiving SCH79797 showed markedly decreased neuronal damage as assessed by serum neuron specific enolase levels and less neurological dysfunction as determined using cerebral performance category scores. Additionally, in the hippocampus, cell apoptosis, polymorphonuclear cell infiltration, and c-Jun levels were decreased, whereas extracellular signal-regulated kinase phosphorylation levels were increased. All of these changes were inhibited by the intravenous administration of the phosphoinositide 3-kinase/Akt pathway inhibitor LY29004 (3 mg/kg) 10 minutes before the SCH79797 intervention. These findings suggest that SCH79797 mitigates brain injury via anti-inflammatory and anti-apoptotic effects, possibly by modulating the extracellular signal-regulated kinase, c-Jun N-terminal kinase/c-Jun and phosphoinositide 3-kinase/Akt pathways.

[Dachengqi decoction reduces the serum levels of mast cell tryptase and inflammatory cytokines in rabbits with post-cardiac arrest syndrome].

OBJECTIVE: To observe the effects of Dachengqi decoction on serum levels of mast cell tryptase, monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in rabbits with post-cardiac arrest syndrome (PCAS). METHODS: Thirty healthy male Japanese rabbits were randomly divided into three groups: sham-operation group, PCAS model group and Dachengqi decoction treatment group. The model of PCAS was established by asphyxia-induced cardiac arrest. Fifteen minutes after return of spontaneous circulation, Dachengqi decoction [15 g/(kg.d), bid] was given by intra-gastric administration in Dachengqi decoction treatment group. The indicators of organ function were evaluated 24, 48 and 72 hours after cardiac arrest. The serum levels of mast cell tryptase, MCP-1 and IL-8 were determined by ELISA. RESULTS: Dachengqi decoction alleviated the dysfunction significantly in heart, brain, liver and kidney. Compared with the sham group, the serum levels of mast cell tryptase, MCP-1 and IL-8 increased significantly in PCAS group (P<0.01). Compared with the PCAS group, the serum levels of mast cell tryptase (at 6 hours), MCP-1 (at 6, 24 and 48 hours) and IL-8 (at 6 and 24 hours) decreased significantly in Dachengqi decoction treatment group (P<0.05 or P<0.01). CONCLUSION: Dachengqi decoction can reduce the serum levels of mast cell tryptase, MCP-1 and IL-8 in rabbits with post-cardiac arrest syndrome.

[In vitro refolding and functional study of soluble HLA-G1-peptide complex].

AIM: To form soluble HLA-G1-peptide complex by refolding in vitro, and to study its immune function. METHODS: The heavy chain and beta(2m) of sHLA-G1 were expressed as insoluble aggregates in E. coli, and then the two subunits were refolded to form HLA-G1-peptide complex by dilution method in the presence of specific peptide. The refolded product was purified through Sephadex G-75 gel filtration. The purified product was identified by Western blot with mAb W6/32. The function of soluble HLA-G1 was explored from following three aspects, namely, the influences on cytotoxicity of NK cells, on proliferation of T cells in mixed lymphocyte culture and apoptosis of activated T cells. RESULTS: The refolded complex was recognized by mAb W6/32. It effectively inhibited cytotoxicity of NK cells and proliferation of T cells, and induced apoptosis of activated T cells. CONCLUSION: The refolding of soluble HLA-G1-peptide complex has been successfully realized in vitro. The complex can inhibit the functions of NK cells and T cells.

[In vitro induction and expansion of dendritic cells from rat bone marrow and their characterization].

AIM: To induce and expand dendritic cells (DC) from rat bone marrow in vitro and identify their biological characterization. METHODS: The rat bone marrow cells were collected and cultured for 48 hours and the floating cells were removed. Then IL-4 and GM-CSF were added into the fresh medium. After 2 weeks, the morphological character of the cultured DCs was observed under light microscope and transmission electron microscope. Expressions of MHC class II molecule, B7-1 and B7-2 were detected by flow cytometry. The cultured DCs were co-cultured with allogenic T cells derived from rat spleen. T cell proliferation was measured by MTT colorimetry. RESULTS: The cultured DCs had the typical morphological characterization of DC, and the expression rates of MHC class II molecule, B7-1 and B7-2 were 74.2%, 81% and 76% respectively. The cultured DCs could notably stimulate the proliferation of allogeneic T cells. CONCLUSION: The adherent culture of rat bone marrow cells, and co-culture with IL-4 and GM-CSF can obtain a number of high purity of DCs, which lay the foundation for study on DC's function.