Effect of allisartan on blood pressure and left ventricular hypertrophy through Kv1.5 channels in hypertensive rats.

BACKGROUND: The objective of the present work was to study the anti-hypertensive effect of allisartan on blood pressure (BP) and in facilitating left ventricular remodeling through voltage-gated potassium channels (Kv) 1.5 channels. METHODS: A total of 30 SD rats were randomly divided into sham operation group, hypertension control group, and allisartan treatment group. Hypertension was induced by renal artery stenosis. The animals of treatment group were administered with allisartan once a day at a dose of 30 mg/kg body weight through an oral gavage for 4 weeks. The heart function of animals post 4 weeks of treatment was evaluated by echocardiography, and the degree of ventricular hypertrophy and cardiomyocyte hypertrophy were evaluated by histomorphology. The expression of Kv1.5 is detected by real-time quantitative polymerase chain reaction while Western blotting was used to detect the protein expression. RESULTS: Four weeks after renal artery stenosis, a significant difference was observed in the whole heart ratio, left heart ratio, and cardiomyocyte area between allisartan treatment group and the hypertension control group (P< .01). A significant decrease in BP of allisartan treatment group compared to hypertension control group (P< .01) was observed. The expression of Kv1.5 mRNA was increased significantly (P< .01) in allisartan treatment group compared to hypertension control group. Western blot analysis also confirmed the increased expression of Kv1.5 channel. CONCLUSION: The results showed that allisartan lowers BP and improves left ventricular remodeling through increased expression of Kv1.5 mRNA.

Development of a prognostic signature for immune-associated genes in bladder cancer and exploring potential drug findings.

BACKGROUND: Bladder cancer, predominantly affecting men, is a prevalent malignancy of the urinary system. Although platinum-based chemotherapy has demonstrated certain enhancements in overall survival when compared to surgery alone, the efficacy of treatments is impeded by the unfavorable side effects of conventional chemotherapy medications. Nonetheless, immunotherapy exhibits potential in the treatment of bladder cancer. METHODS: To create an immune-associated prognostic signature for bladder cancer, bioinformatics analyses were performed utilizing The Cancer Genome Atlas (TCGA) database in this study. By identifying differential gene expressions between the high-risk and low-risk groups, a potential therapeutic drug was predicted using the Connectivity Map database. Subsequently, the impact of this drug on the growth of T24 cells was validated through MTT assay and 3D cell culture techniques. RESULTS: The signature included 1 immune-associated LncRNA (NR2F1-AS1) and 16 immune-associated mRNAs (DEFB133, RBP7, PDGFRA, CGB3, PDGFD, SCG2, ADCYAP1R1, OPRL1, PGR, PSMD1, TANK, PRDX1, ADIPOR2, S100A8, AHNAK, EGFR). Based on the assessment of risk scores, the patients were classified into cohorts of low-risk and high-risk individuals. The cohort with low risk demonstrated a considerably higher likelihood of survival in comparison to the group with high risk. Furthermore, variations in immune infiltration were noted among the two categories. Cephaeline, a possible medication, was discovered by analyzing variations in gene expression. It exhibited promise in suppressing the viability and growth of T24 bladder cancer cells. CONCLUSION: The novel predictive pattern allows for efficient categorization of patients with bladder cancer, enabling focused and rigorous treatment for those expected to have a worse prognosis. The discovery of a possible curative medication establishes a basis for forthcoming immunotherapy trials in bladder cancer.

SOX4 as a potential therapeutic target for pathological cardiac hypertrophy.

Pathological cardiac hypertrophy can lead to heart failure, making its prevention crucial. SOX4, a SOX transcription factor, regulates tissue growth and development, although its role in pathological cardiac hypertrophy is unclear. We found that the SOX4 expression was elevated in hypertrophic hearts and angiotensin II (Ang II)-treated neonatal rat cardiomyocytes (NRCMs), and knocking down the SOX4 expression in NRCMs and mouse hearts significantly reduced the hypertrophic response. Mechanistically, SOX4 can bind to the SIRT3 promoter, inhibit SIRT3 transcription and expression, and thus affect downstream MnSOD acetylation levels, leading to abnormal increases in ROS and oxidative stress levels and promoting the occurrence of cardiac hypertrophy. In conclusion, this study identified a new role for SOX4 in regulating cardiac hypertrophy, and decreasing SOX4 expression may be a potential treatment for pathological cardiac hypertrophy.