OBJECTIVETo investigate the role played by γδ T cells in acute liver injury using the concanavalin A (ConA)-induced liver injury mouse model.

METHODSAcute liver injury was induced by intravenous injection of 10 mug/g of ConA into male C57BL/6J mice with wild-type or T cell receptor-γ knockout (TCR δ-/-) genetic backgrounds. Mice injected with PBS alone served as negative controls. The degree of liver damage was assessed by measuring serum levels of transaminase and cytokines at post-injection hours 3, 6, 12, 24, 48, and 72. The percentage of γδ T cells and proportions of different subsets in liver lymphocytes were measured by flow cytometry.

RESULTSThe TCR δ-/- mice showed significantly higher levels of the inflammatory cytokines IFN-γ, TNFα and IL-4 than the wild-type mice at post-injection hour 3. The percentage of liver γδ T cells increased with increased injury degree, and the extent of increase was significantly higher in the TCR δ-/- mice than the wild-type mice (post-injection hour 6: 6302.61+/-592.06 vs. 1319.26+/-355.48, 12: 6569.44+/-1060.98 vs. 3415.53+/-343.90, 24: 6514.29+/-757.26 vs. 2062.73+/-365.67, 48: 1262.61+/-558.07 vs. 113.66+/-113.26, and 72: 226.54+/-98.20 vs. 42.35+/-21.51 U/L; all P less than 0.05). In addition, compared to the negative control mice, the ConA-induced mice showed a higher proportions of Vγ4 γδ T cells to total γδ T cells (17.78+/-2.95 vs. 25.26+/-2.43) and to total liver lymphocytes (0.47+/-0.07 vs. 0.66+/-0.05). Similarly, compared to the negative control mice, the ConA-induced mice showed a higher proportion of Vγ1 γδ T cells to total γδ T cells (38.37+/-6.10 vs. 50.19+/-5.52) but the proportion to total liver lymphocytes was not significantly different among the groups (0.76+/-0.18 vs. 0.78+/-0.25). Reinfusion of Vγ4 γδ T lymphocytes into TCR δ-/- mice led to lower serum ALT levels than reinfusion of Vγ1 γδ T lymphocytes (5054.10+/-1748.51 vs. 12333.56+/-663.535 U/L).

CONCLUSIONγδ T cells play a protective role in ConA-induced liver injury and this effect maybe mediated by the Vγ4 γδ T cell subset.

Animals ; Chemical and Drug Induced Liver Injury ; immunology ; pathology ; Concanavalin A ; toxicity ; Interferon-gamma ; immunology ; Interleukin-4 ; immunology ; Liver ; drug effects ; immunology ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, Antigen, T-Cell, gamma-delta ; metabolism ; T-Lymphocyte Subsets ; immunology ; Tumor Necrosis Factor-alpha ; immunology

OBJECTIVETo study the effect of total saponins from Entada phaseoloides (TSEP) on islet morphology and skeletal muscle PI3K pathway-related protein expression of type 2 diabetic rats.

METHODType 2 diabetic rats were induced by high-fat diet and low-dose streptozotocin and then randomly divided into 5 groups, i.e. the normal control, the model group, the positive control drug (200 mg x kg(-1) metformin), the low-dose TSEP (25 mg x kg(-1)) group and the high-dose TSEP (50 mg x kg(-1)). Three weeks later, the islet morphology of rat pancreas were observed by HE staining, and protein expressions of insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), protein tyrosine phosphatase-1B (PTP-1 B) and glucose transporter 4 (GLUT4) in rat skeletal muscle were detected by Western blot.

RESULTCompared with the modal group, TSEP administration groups showed relatively normal structures, clear pancreatic cells and intact capsula structures in pancreatic tissue pathological sections, with the number of pancreatic islets close to the normal control group. Meanwhile, above TSEP administration groups showed increased IRS-1, PI3K and GLUT4 protein expressions in their skeletal muscle tissues and decreased PTP-1B protein expression compared with the model group.

CONCLUSIONTSEP has an effect on protecting pancreatic tissues of type 2 diabetic rats and intervening in abnormal expression of proteins in skeletal muscle tissues.

Animals ; Diabetes Mellitus, Type 2 ; drug therapy ; Fabaceae ; chemistry ; Glucose Transporter Type 4 ; analysis ; Islets of Langerhans ; drug effects ; pathology ; Male ; Muscle, Skeletal ; drug effects ; pathology ; Phosphatidylinositol 3-Kinases ; analysis ; Rats ; Rats, Sprague-Dawley ; Saponins ; therapeutic use

OBJECTIVETo study in vitro anti-tumor activity of phaseoloideside E (PE) with human hepatoma HepG2 cells as the objective.

METHODMTT assay was adopted to detect the cytotoxic effect of PE of different concentrations on HepG2 cells after being processed for 48 h. Changes in morphology of PE-processed cells were observed under an optical microscope and fluorescence microscope. DNA agrose gel electrophoresis was used to detect the DNA ladder, an important characteristic of cell apoptosis. The expression levels of Bax and Bcl-2 were determined by western blot assay.

RESULTPE dramatically repressed the viability of HepG2 cells. Typical morphological changes of apoptosis had been detected by both direct microscopic observation and Hoechst 33,258 staining. Typical DNA Ladder was also observed by agarose gel electrophoresis in the administration group, but it did not exist in the control group. Western blot showed that the expression of Bax was up-regulated and Bcl-2 was down-regulated.

CONCLUSIONAbove data demonstrates that PE can induce apoptosis in human hepatoma HepG2 cells, and indicate that PE-induced expression level changes of Bax and Bcl2 may be related to the apoptosis-induction effect.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Hep G2 Cells ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Saponins ; pharmacology ; Triterpenes ; pharmacology ; bcl-2-Associated X Protein ; analysis

Aortic stenosis (AS) is the most common primary valve lesion requiring surgery or transcatheter intervention in modern era. Its prevalence is rising rapidly as a consequence of the aging population. Transcatheter aortic valve replacement (TAVR) as a therapy option for older high-risk symptomatic severe AS patients has emerged and is currently extending its indications towards surgery intermediate- and low-risk subjects. Considering the common characteristics of frailty and high comorbidity among AS patients, cardiac rehabilitation (CR) has been proven to improve not only survival but also quality of life in previous reports. CR as a classⅠ recommendation in guidelines for the prevention and treatment of cardiovascular disease has been widely used in clinical practice. The purpose of this article is to sort out the current CR programs for TAVR patients in global medical management, and explore the CR optimization program fit for China medical model in post COVID-19 pandemic era.

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.