Senkyunolide H Affects Cerebral Ischemic Injury through Regulation on Autophagy of Neuronal Cells via P13K/AKT/mTOR Signaling Pathway.

Cerebral ischemia (CI) is associated with high global incidence and risk; therefore, its rapid and reliable therapeutic management is essential for protecting patients' lives and improving health. Senkyunolide H (SH) is remarkably effective against phlebosclerosis, oxidation, and apoptosis. Blood-brain barrier is the main obstacle impeding the delivery of drugs and xenobiotics to brain areas. Drugs' loading in nanoparticles can overcome the blood-brain barrier obstacle and thus directly and completely act on brain tissue, and such a loading can also change the half-life of drugs in vivo and lower the dosage requirement of drugs. In this study, we loaded the SH in lipid nanoparticles to improve its delivery to the brain for the therapy of CI. Thus, this study preliminarily analyzed the mechanism of SH-loaded nanoparticles in CI. The SH-loaded lipid nanoparticles were prepared and characterized with electron microscopy and PS potentiometery. The SH-loaded nanoparticles were intraperitoneally administered to CI-induced rats and brain tissue water content, and neuronal apoptosis and autophagy-associated proteins were determined. Our assays revealed SH-loaded nanoparticle's ability to reduce nerve injury and brain tissue water content in rats with CI and inhibit the apoptosis and autophagy of their neuronal cells (NCs). Additionally, under intervention with SH-loaded nanoparticles, P13K/AKT/mTOR pathway-associated proteins in brain tissue of rats decreased. As the assay results showed, SH-loaded nanoparticles can suppress the autophagy of NCs through medicating P13K/AKT/mTOR pathway and lower apoptosis, thus delivering the effect of treating CI. Results of this study indicate SH-loaded nanoparticles as promising strategy for delivery SH to brain areas for treating CI.

Effect of miR-495 on lower extremity deep vein thrombosis through the TLR4 signaling pathway by regulation of IL1R1.

Lower extremity deep vein thrombosis (LEDVT), a common peripheral vascular disease caused by a blood clot in a deep vein is usually accompanied by swelling of the lower limbs. MicroRNAs (miRs) have been reported to play roles in LEDVT. We aimed to investigate the effect of miR-495 on LEDVT via toll-like receptor 4 (TLR4) signaling pathway through interleukin 1 receptor type 1 (IL1R1). LEDVT mouse model was established, and the femoral vein (FV) tissues were collected to detect expressions of miR-495, IL1R1, and TLR4 signaling-related genes. The expressions of both CD31 and CD34 (markers for endothelial progenitor cells) in the FV endothelial cells as well as the proportion of CD31+/CD34+ cells in peripheral blood were measured in order to evaluate thrombosis. The effect of miR-495 on cell viability, cell cycle, and apoptosis was analyzed. IL1R1 was confirmed as the target gene of miR-495. Besides, inhibiting the miR-495 expression could increase IL1R1 expression along with activating the TLR4 signaling pathway. The total number of the leukocytes along with the ratio of weight to length of thrombus in the FV tissue showed an increase. The overexpression of miR-495 could promote FV endothelial cell viability. By injecting agomiR-495 and antagomiR-495 in vivo, the number of leukocytes in the FV tissues and the ratio of weight to length of thrombus were significantly decreased in the mice injected with the overexpressed miR-495, and the IL1R1/TLR4 signaling pathway was inhibited. Collectively, overexpressed miR-495 directly promotes proliferation while simultaneously inhibiting apoptosis of FV endothelial cells, alleviating FV thrombosis by inhibiting IL1R1 via suppression of TLR4 signaling pathway.

Prognostic factors for chronic severe hepatitis and construction of a prognostic model.

BACKGROUND: Chronic severe hepatitis is a serious illness with a high mortality rate. Discussion of prognostic judgment criteria for chronic severe hepatitis is of great value in clinical guidance. This study was designed to investigate the clinical and laboratory indices affecting the prognosis of chronic severe hepatitis and construct a prognostic model. METHODS: The clinical and laboratory indices of 213 patients with chronic severe hepatitis within 24 hours after diagnosis were analyzed retrospectively. Death or survival was limited to within 3 months after diagnosis. RESULTS: The mortality of all patients was 47.42%. Compared with the survival group, the age, basis of hepatocirrhosis, infection, degree of hepatic encephalopathy (HE) and the levels of total bilirubin (TBil), total cholesterol (CHO), cholinesterase (CHE), blood urea nitrogen (BUN), blood creatinine (Cr), blood sodium ion (Na), peripheral blood leukocytes (WBC), alpha-fetoprotein (AFP), international normalized ratio (INR) of blood coagulation and prothrombin time (PT) were significantly different in the group who died, but the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB) and hemoglobin (HGB) were not different between the two groups. At the same time, a regression model, Logit (P) =1.573XAge+1.338XHE-1.608XCHO+0.011XCr-0.109XNa+1.298XINR+11.057, was constructed by logistic regression analysis and the prognostic value of the model was higher than that of the MELD score. CONCLUSIONS: Multivariate analysis excels univariate analysis in the prognosis of chronic severe hepatitis, and the regression model is of significant value in the prognosis of this disease.

[Clinical observation on treatment of SARS with combination of chaihu droplet pill and huoxiang zhengqi droplet pill].

OBJECTIVE: To observe the effect of combination treatment with Chaihu Droplet pill (CHDP) and Huoxiang Zhengqi Droplet pill (HZDP) in treating severe acute respiratory syndrome (SARS) in early stage. METHODS: Twenty-two patients of SARS were randomly selected and paired according to such controlling factors as age, sex and profession into 11 couples. To them all symptomatic treatment was applied, combined CHDP and HZDP (CH-HZ) was given additionally to one of each couple randomly. The treatment was lasted for 13 days to investigate the changes of the clinical indexes such as creatine kinase (CK), lactate dehydogenase (LDH) and serum sodium levels. RESULTS: Early applying of CH-HZ treatment showed good effects in improving CK, LDH, oxygenation index and absolute value of neutrophils, and could reduce the daily maximal dosage of glucocorticoid needed for SARS patients. CONCLUSION: Early application of CH-HZ treatment in treating SARS could alleviate the injury in lung of SARS patients and the neutrophil dependent inflammatory reaction, and reduce the dosage of glucocorticoid used.