Phillyrin improves myocardial remodeling in salt-sensitive hypertensive mice by reducing endothelin1 signaling.

OBJECTIVES: Prolonged exposure to chronic hypertension places the heart under excessive strain, resulting in myocardial remodeling. Phillyrin, derived from the natural plant Forsythia suspensa, has been found to possess cardioprotective properties. The objective of this study is to investigate the role and mechanism of phillyrin in hypertension-induced myocardial remodeling in mice. METHODS: We constructed a mouse model of salt-sensitive hypertension. The mice were treated with varying doses of phillyrin, and their blood pressure, cardiac function, cardiac hypertrophy, fibrosis, inflammation, and other conditions were assessed. KEY FINDINGS: Our research findings demonstrated that phillyrin has the potential to lower blood pressure, enhance cardiac function, and mitigate cardiac hypertrophy, fibrosis, and inflammatory responses in deoxycorticosterone acetate-salt hypertension mice. In hypertensive mice, there was an elevated expression of endothelin1 (ET-1) in heart tissue, which can be reduced by phillyrin. Additionally, phillyrin effectively reduced the hypertrophy of H9c2 cells induced by ET-1 stimulation. CONCLUSIONS: Our research highlights the therapeutic capabilities of phillyrin in the treatment of myocardial remodeling through the reduction of ET-1 signaling. These results contribute to the advancement of novel applications for phillyrin and establish a solid conceptual basis for future investigations in this area.

Salidroside attenuates myocardial remodeling in DOCA-salt-induced mice by inhibiting the endothelin 1 and PI3K/AKT/NFκB signaling pathways.

Myocardial remodeling, which occurs in the final stage of cardiovascular diseases such as hypertension, can ultimately result in heart failure. However, the pathogenesis of myocardial remodeling remains incompletely understood, and there is currently a lack of safe and effective treatment options. Salidroside, which is extracted from the plant Rhodiola rosea, shows remarkable antioxidant and anti-inflammatory characteristics. The purpose of this investigation was to examine the cardioprotective effect of salidroside on myocardial remodeling, and clarify the associated mechanism. Salidroside effectively attenuated cardiac dysfunction, myocardial hypertrophy, myocardial fibrosis, and cardiac inflammation, as well as renal injury and renal fibrosis in an animal model of deoxycortone acetate (DOCA)-salt-induced myocardial remodeling. The cardioprotective effect of salidroside was mediated by inhibiting the endothelin 1 and PI3K/AKT/NFκB signaling pathways. Salidroside was shown to inhibit the expression of endothelin1 in the hearts of mice treated with DOCA-salt. Additionally, it could prevent cardiomyocyte hypertrophy induced by endothelin-1 stimulation. Furthermore, Salidroside could effectively inhibit the excessive activation of the PI3K/AKT/NFκB pathway, which was caused by DOCA-salt treatment in mouse hearts and endothelin 1 stimulation in cardiomyocytes. Our study suggests that salidroside can be used as a therapeutic agent for the treatment of myocardial remodeling.

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.

Phillyrin attenuates norepinephrine-induced cardiac hypertrophy and inflammatory response by suppressing p38/ERK1/2 MAPK and AKT/NF-kappaB pathways.

Phillyrin, a well-known natural compound from the dried fruits of Forsythia suspensa (Thunb.) Vahl., has shown anti-inflammatory, antioxidant and anti-virus activities as well as renal protective effects on diabetic nephropathy. In this study, we investigated whether phillyrin attenuated cardiac hypertrophy induced by catecholamine in vivo and in vitro, and explored the underlying mechanisms. Cardiac hypertrophy was induced in C57BL/6 mice by subcutaneous injection of norepinephrine (NE, a key catecholamine), and in rat cardiomyoblasts (H9c2) by stimulation with NE in vitro. Our results showed that administration of phillyrin (100 mg/kg, i.p. for 15 days) significantly improved cardiac function, histopathological changes, cardiac hypertrophy and decreased the upregulated hypertrophic markers (ANP, BNP, and ß-MHC). Moreover, treatment with phillyrin obviously reduced the infiltration of the CD68 positive macrophages and the mRNA expression of proinflammatory genes (IL-1ß, IL-6, and TNF-α) in left ventricular tissue. In addition, treatment with phillyrin markedly inhibited the phosphorylation of p38 MAPK, ERK1/2, AKT, and NF-κB p65 in heart tissues. Furthermore, in NE-treated H9c2 cells, pretreatment with phillyrin clearly attenuated cardiomyocyte hypertrophy, reduced ROS production and inhibited the phosphorylation of p38 MAPK, ERK1/2, AKT, and NF-κB p65 in vitro. Collectively, our results demonstrate that phillyrin effectively alleviates NE-induced cardiac hypertrophy and inflammatory response by suppressing p38 MAPK/ERK1/2 and AKT/NF-κB signaling pathways.

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.

[Predicting RNA secondary structures including pseudoknots by covariance with stacking and minimum free energy].

Prediction of RNA secondary structures including pseudoknots is a difficult topic in RNA field. Current predicting methods usually have relatively low accuracy and high complexity. Considering that the stacking of adjacent base pairs is a common feature of RNA secondary structure, here we present a method for predicting pseudoknots based on covariance with stacking and minimum free energy. A new score scheme, which combined stacked covariance with free energy, was used to assess the evaluation of base pair in our method. Based on this score scheme, we utilized an iterative procedure to compute the optimized RNA secondary structure with minimum score approximately. In each interaction, helix of high covariance and low free energy was selected until the sequences didn't form helix, so two crossing helixes which were selected from different iterations could form a pseudoknot. We test our method on data sets of ClustalW alignments and structural alignments downloaded from RNA databases. Experimental results show that our method can correctly predict the major portion of pseudoknots. Our method has both higher average sensitivity and specificity than the reference algorithms, and performs much better for structural alignments than for ClustalW alignments. Finally, we discuss the influence on the performance by the factor of covariance weight, and conclude that the best performance is achieved when lambda1 : lambda2 = 5 : 1.

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.