Eplerenone improves hyperglycemia and sympathetic excitation in chronic renocardiac syndrome in rats.

We aimed to assess the efficacy of eplerenone, a steroidal mineralocorticoid receptor antagonist known to reduce blood pressure and mitigate cardiovascular disease (CVD) progression, in retarding the progression of chronic kidney disease (CKD) and CVD in a rat model of type 4 cardiorenal syndrome (CRS). We grouped rats into four experimental categories: sham surgery, sham treatment with eplerenone, nephrectomy without eplerenone (Nx), and nephrectomy with eplerenone (Nx + EP). For the Nx + EP group, rats received five-sixths nephrectomy, inducing CKD and CVD conditions such as renal hypertension and hyperglycemia, and were then treated with eplerenone (100 mg/kg/day, orally) over 4 weeks after an initial 4-week observation period. Heart rate, blood pressure, blood sugar levels, and sympathetic nerve excitation were monitored biweekly. In addition, assessments of renal and cardiac tissues, including evaluation of renal tubulointerstitial injury, glomerular injury, and cardiomyocyte hypertrophy, were conducted at week 8. Eplerenone administration mitigated CKD and CVD progression in the Nx + EP group, evident by improved blood pressure (217.3 ± 5.4 versus 175.3 ± 5.6), blood sugar (121.8 ± 1.3 versus 145.6 ± 6.0) level, reduced sympathetic nerve excitation, and cardiomyocyte hypertrophy compared to the Nx group. However, renal tubulointerstitial injury, glomerular injury, and cardiovascular dysfunction, which were increased in rats with type 4 CRS, did not show significant changes with eplerenone treatment. Our study demonstrated that eplerenone treatment did not exacerbate type 4 CRS but improved blood pressure, blood sugar levels, sympathetic nerve excitation, and cardiomyocyte hypertrophy in this model.

Paricalcitol improved cardiac hypertrophy and fibrosis through upregulation of fibroblast growth factor-23 and downregulation of transforming growth factor-beta in a rat model of isoproterenol-induced cardiomyopathy.

Acute cardiomyopathy is a significant global health concern and one of the leading causes of death in developed countries. Prior studies have shown an association between acute cardiomyopathy and low vitamin D levels. Although paricalcitol, a vitamin D receptor (VDR) activator, has demonstrated clinical benefits in patients with advanced kidney disease, its effect on cardiac remodeling in cardiomyopathy is unknown. This study aimed to investigate the relative effects of paricalcitol on cardiomyopathy in rats. Wistar-Kyoto rats were administered vehicle (sham control group) or isoproterenol to induce cardiomyopathy. Rats administered isoproterenol were subsequently treated with paricalcitol (experimental group) or vehicle (isoproterenol group). Picrosirius red and immunofluorescence staining were used to analyze cardiac fibrosis and hypertrophy. Immunohistochemistry staining was used to confirm the molecular mechanisms involved in isoproterenol-induced cardiomyopathy in rats. Injection of paricalcitol could reduce collagen and transforming growth factor-beta 1 (TGF-ß1) levels while activating fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor-23 (FGF23) without the help of Klotho, thereby reducing myocardial hypertrophy and fibrosis. As a VDR activator, paricalcitol reduces isoproterenol-induced cardiac fibrosis and hypertrophy by reducing the expression of TGF-ß1 and enhancing the expression of VDR, FGFR1, and FGF23.

Prospective Exploratory Study of the Effects of Postoperative Endocrine Medication on the Endometrium in Breast Cancer Patients.

Objective: This study aimed to investigate the pathological effects of long-term postoperative endocrine medication on the endometrium in breast cancer patients. Methods: Data of 99 patients with primary breast cancer who underwent hysteroscopy and obtained endometrial biopsy from 1 June 2018 to 31 December 2021 at the Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital were prospectively collected. Results: Hysteroscopy was performed followed by endometrial histopathological examination in 99 breast cancer patients, including 44 taking tamoxifen (TAM), 26 taking other endocrine drugs, and 29 not taking endocrine drugs. The endometrial thickness in the TAM group was significantly higher than that in the other endocrine drug groups and the group not taking endocrine drugs (p=0.017). The receiver operating characteristic curves for the abnormal premenopausal endometrial thickening were plotted in this study; an endometrial thickness of 15.5 mm seen on ultrasound could be used as the most accurate ultrasound diagnostic threshold for the diagnosis of abnormal premenopausal endometrial hyperplasia, with an area under the curve of 0.888 (95% CI: 0.716, 1.000), a sensitivity of 100%, and a specificity of 75%, which was consistent with the results of our previous retrospective study. An endometrial thickness of ≥5 mm in postmenopausal women with breast cancer taking TAM was still used as the cut-off value for routine ultrasound diagnosis of abnormal postmenopausal endometrial hyperplasia. Conclusion: An ultrasound endometrial thickness (proliferative phase) of >15 mm in premenopausal patients can be used as the most accurate ultrasound diagnostic threshold for the diagnosis of abnormal endometrial hyperplasia. After menopause, an ultrasound endometrial thickness of ≥5 mm is still used as the criterion for diagnosing abnormal endometrial hyperplasia. Older patients should be monitored for signs of vaginal bleeding and fluid discharge, and hysteroscopy should be performed if necessary to ascertain the endometrial condition.

SGK1 Target Genes Involved in Heart and Blood Vessel Functions in PC12 Cells.

Serum and glucocorticoid-regulated kinase 1 (SGK1) is expressed in neuronal cells and involved in the pathogenesis of hypertension and metabolic syndrome, regulation of neuronal function, and depression in the brain. This study aims to identify the cellular mechanisms and signaling pathways of SGK1 in neuronal cells. In this study, the SGK1 inhibitor GSK650394 is used to suppress SGK1 expression in PC12 cells using an in vitro neuroscience research platform. Comparative transcriptomic analysis was performed to investigate the effects of SGK1 inhibition in nervous cells using mRNA sequencing (RNA-seq), differentially expressed genes (DEGs), and gene enrichment analysis. In total, 12,627 genes were identified, including 675 and 2152 DEGs at 48 and 72 h after treatment with GSK650394 in PC12 cells, respectively. Gene enrichment analysis data indicated that SGK1 inhibition-induced DEGs were enriched in 94 and 173 genes associated with vascular development and functional regulation and were validated using real-time PCR, Western blotting, and GEPIA2. Therefore, this study uses RNA-seq, DEG analysis, and GEPIA2 correlation analysis to identify positive candidate genes and signaling pathways regulated by SGK1 in rat nervous cells, which will enable further exploration of the underlying molecular signaling mechanisms of SGK1 and provide new insights into neuromodulation in cardiovascular diseases.

Systematic review and meta-analysis: Tai Chi for preventing falls in older adults.

OBJECTIVE: It remains unclear whether Tai Chi is effective for preventing falls in older adults. We undertook this systematic review to evaluate the preventive effect of Tai Chi by updating the latest trial evidence. DESIGN: Systematic review and meta-analysis. METHODS: The Cochrane Library, MEDLINE and EMBASE were searched up to February 2016 to identify randomised trials evaluating Tai Chi for preventing falls in older adults. We evaluated the risk of bias of included trials using the Cochrane Collaboration's tool. Results were combined using random effects meta-analysis. OUTCOME MEASURES: Number of fallers and rate of falls. RESULTS: 18 trials with 3824 participants were included. The Tai Chi group was associated with significantly lower chance of falling at least once (risk ratio (RR) 0.80, 95% CI 0.72 to 0.88) and rate of falls (incidence rate ratio (IRR) 0.69, 95% CI 0.60 to 0.80) than the control group. Subgroup analyses suggested that the preventive effect was likely to increase with exercise frequency (number of fallers: p=0.001; rate of falls: p=0.007) and Yang style Tai Chi was likely to be more effective than Sun style Tai Chi (number of fallers: p=0.01; rate of falls: p=0.001). The results might be influenced by publication bias as the funnel plots showed asymmetry. Sensitivity analyses by sample size, risk of bias and comorbidity showed no major influence on the primary results. CONCLUSIONS: Tai Chi is effective for preventing falls in older adults. The preventive effect is likely to increase with exercise frequency and Yang style Tai Chi seems to be more effective than Sun style Tai Chi.