Calycosin (CAL) is the main active component present in Astragalus and reportedly possesses diverse pharmacological properties. However, the cardioprotective effect and underlying mechanism of CAL against doxorubicin- (DOX-) induced cardiotoxicity need to be comprehensively examined. Herein, we aimed to investigate whether the cardioprotective effects of CAL are related to its antipyroptotic effect. A cardiatoxicity model was established by stimulating H9c2 cells and C57BL/6J mice using DOX. In vitro, CAL increased H9c2 cell viability and decreased DOX-induced pyroptosis via NLRP3, caspase-1, and gasdermin D signaling pathways in a dose-dependent manner. In vivo, CAL-DOX cotreatment effectively suppressed DOX-induced cytotoxicity as well as inflammatory and cardiomyocyte pyroptosis via the same molecular mechanism. Next, we used nigericin (Nig) and NLRP3 forced overexpression to determine whether CAL imparts antipyroptotic effects by inhibiting the NLRP3 inflammasome in vitro. Furthermore, CAL suppressed DOX-induced mitochondrial oxidative stress injury in H9c2 cells by decreasing the generation of reactive oxygen species and increasing mitochondrial membrane potential and adenosine triphosphate. Likewise, CAL attenuated the DOX-induced increase in malondialdehyde content and decreased superoxide dismutase and glutathione peroxidase activities in H9c2 cells. In vivo, CAL afforded a protective effect against DOX-induced cardiac injury by improving myocardial function, inhibiting brain natriuretic peptide, and improving the changes of the histological morphology of DOX-treated mice. Collectively, our findings confirmed that CAL alleviates DOX-induced cardiotoxicity and pyroptosis by inhibiting NLRP3 inflammasome activation in vivo and in vitro.
Direct measurements of dynamic loads acting on engineering structures such as a ship during operation can be challenging. Consequently, dynamic load identification as a technique is being used to predict dynamic loads acting on structures from the measured structural responses. In this paper, a cantilever beam as a simple continuous system subjected to a time-dependent force is analyzed analytically to extract structural stress dynamics characteristics in global matrix form, then by using the concept of continuous-time state-space model, the Green's Kernel Function (GKF) is determined. Due to the ill-posed nature of the GKF matrix, a convex optimization is employed to convert the ill-posed problem into well-posed one, but in this paper by estimating the exact time step, the dynamic load associated with the kernel function matrix can be reliably determined without the need for any further regularization method. Numerical simulations are utilized to validate the proposed method, and the applicability of the function is analyzed.
Multi-potent adult progenitor cells (MAPCs) differentiate into endothelial cells (ECs) in the presence of vascular endothelial growth factor (VEGF). The mechanism(s) of VEGF-induced differentiation of MAPCs to ECs are not yet known. We, therefore, examined the role of mitogen-activated protein kinase/extracellular signal-regulated kinase (p42/44-MAPK/ERK1/2) signalling in endothelial differentiation from bone marrow stem cells. We observed that VEGF stimulation of MAPCs for 14 days results in a significant expression of endothelial-specific gene and/or proteins including von Willebrand factor (vWF), vascular endothelial-cadherin (VE-cadherin), VEGF receptor-2 (VEGFR2), and CD31. Up-regulation of EC-specific markers was accompanied by a cobblestone morphology, expression of endothelial nitric oxide synthase (eNOS), and Dil-Ac-LDL uptake, typical for EC morphology and function. VEGF induced a sustained activation of p42 MAPK/ERK, but not that of p44 MAPK/ERK during the course of MAPCs differentiation in a time-dependent manner up to 14 days. VEGF-induced activation of p42 MAPK/ERK also led to the nuclear translocation of MAPK/ERK1/2. Incubation of MAPCs with MAPK/ERK1/2 phosphorylation inhibitor PD98059 blocked the sustained VEGF-induced MAPK/ERK1/2 phosphorylation as well as its nuclear translocation in the differentiating MAPCs. Inhibition of MAPK/ERK1/2 phosphorylation by PD98059 also blocked the expression of EC-specific genes in these cells and their differentiation to ECs. These data suggest that VEGF induces MAPC differentiation into EC via a. MAPK/ERK1/2 signalling pathway-mediated mechanism in vitro.
To investigate the chemical components and the activity of anti-endometrial cancer cells of the petroleum ether extract in Scutellariae barbatae and Hedyotis diffusa and the herb pair.Main composition analysis and identification were determined by the GC-MS technology combined with Kovats retention index( KI). Activity of anti-endometrial cancer cells was researched by MTT assay.Unsaturated fatty acid,esters,sterol and other compounds in Scutellariae barbatae,Hedyotis diffusa and the herb pair were identified by GC-MS. Hedyotis diffusa and the herb pair contained more anthraquinones which distinguished from Scutellariae barbatae. The IC50 values for HEC-1A cells of petroleum ether extract in Scutellariae barbatae and Hedyotis diffusa and the herb pair were 275. 204 μg / m L,105. 826 μg / m L,148. 645 μg / m L. The IC50 values for Ishikawa cells of petroleum ether extract in Scutellariae barbatae and Hedyotis diffusa and the herb pair are 189. 114 μg / m L,77. 974 μg / m L,137. 999 μg / m L.Petroleum ether extract in Scutellariac barbatae and Hedyotis diffusa and the herb pair has inhibition effect on the proliferation of HEC-1A and Ishikawa cells,the Hedyotis diffusa has the strongest activity of anti-endometrial cancer. It is speculated that the strongest activity could be related to the higher content of anthraquinones.
To observe the effect of Pi transportation, dampness resolving and phlegm expelling herbs (PTDRPEH) on the obesity degree, fat hormones, and leptin resistance in diet-induced obesity (DIO) rats.Among the 120 Wister rats, 10 were recruited as the blank control group (fed with basal forage), and the remaining 110 were administered with high-fat high-nutrition forage for 17 weeks. According to weight, we obtained 40 DIO rats and 10 diet-induced obesity resistance (DIO-R) rats. DIO rats were further divided into four groups, i.e., the DIO model group (normal saline, at the daily dose of 2 mL), the sibutramine group (at the daily dose of 1.6 mg/kg), the dampness resolving and phlegm expelling group (DRPE, at the daily dose of 3.2 g/kg), and the Pi transportation group (PT, at the daily dose of 3.2 g/kg). All were given by gastrogavage. Normal saline (2 mL) was given by gastrogavage to rats in the blank control group and the DIO-R group. The basal forage was administered to rats in the blank control group, while high fat forage was continually given to rats in the remaining five groups. Their body weights and body lengths were measured after 16 weeks of gastrogavage. All intra-abdominal fat was taken out to measure the degree of obesity and fat contents. Insulin resistance index (IRI), blood glucose, triglycerides, cholesterol, leptin, neuropeptide Y (NPY), tumor necrosis factor alpha (TNF-alpha), and adiponectin were detected after blood withdrawing. Leptin, TNF-alpha, adiponectin, suppressors of cytokine signaling-3 (SOCS-3), and other relevant adipose hormones and inflammatory cytokines were examined in the fat homogenate.Compared with the blank control group, DIO model rats' body weight, body mass index (BMI), fat factor, IRI, serum leptin, TNF-alpha, and SOCS-3 significantly increased (P < 0.05, P < 0.01); serum NPY, serum leptin, and adiponectin decreased (P < 0.05). Leptin increased and NPY decreased in DIO-R model rats. Compared with the DIO group, DIO-R model rats' body weight, BMI, fat factor, IRI, serum NPY, TNF-alpha, and SOCS-3 all decreased (P < 0.05, P < 0.01); leptin and adiponectin in serum and the fat homogenate all increased (P < 0.05, P < 0.01). After intervention with Sibutramine, rats' body weight, BMI, fat factor, and TNF-alpha in the fat homogenate obviously decreased (P < 0.05, P < 0.01). Serum TNF-alpha decreased, leptin and adiponectin increased in rats of the DRPE group (P < 0.05, P < 0.01). BMI, fat factor, IRI, leptin, and SOCS-3 showed a decreasing tendency, but with no statistical difference (P > 0.05). The body weight, BMI, fat factor, IRI, TNF-alpha, and SOCS-3 all decreased in the PT group (P < 0.05, P < 0.01); leptin and adiponectin in the serum and the fat homogenate increased (P < 0.05, P < 0.01).Sibutramine could reduce body weight and TNF-alpha in the adipose tissue. Herbs of PT could inhibit fat diet-induced obesity and insulin resistance (IR), with superior effect to herbs of DRPE. Its mechanism might be closely related to promoting leptin and adiponectin secreted by fat, reducing leptin resistance, and elevating serum levels of leptin and adiponectin.
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