Background: We explored the preventive effect and mechanism of YS-10, a novel synthesized flavonoid derivative based on the structure of icariside II (ICA II), on a rat model of radiation-induced erectiledysfunction (Ri-ED).Methods: Eighteen 10-week-old male Sprague-Dawley (SD) rats were randomly divided into 3 groups. Six rats were used as the control group (Control), and the remaining 12 were given a single X-ray irradiation of 20 Gy in the prostate and then randomly divided into the radiation injury group (Ri-ED group) and YS-10 treatment group (Ri-ED+YS-10, 2.5 mg/kg/day). After 4 weeks of drug administration and a 2-week drug washout period in the YS-10 treatment group, the erectile function of the animals was evaluated, and the tissues were collected for histopathological analysis and detection of oxidative stress indicators.Results: After radiation injury, the ratio of maximum intracavernosal pressure (ICP) to mean arterial pressure (MAP), the number of neuronal nitric oxide synthase (n-NOS) positive nerve fibers in the penis cavernosa, endothelial cell content, and n-NOS and endothelial nitric oxide synthase (e-NOS) proteins in the Ri-ED group were significantly lower than those in control group. Compared with the control group, the Ri-ED group had lower superoxide dismutase (SOD) levels and higher malondialdehyde (MDA) levels.Compared with the Ri-ED group, the YS-10 group had a significant increase in the ratio of ICP/MAP in the corpus cavernosum (0.59±0.06 vs. 0.43±0.06, P<0.01), the number of n-NOS positive nerve fibers, and the content of endothelial cells. The protein content of n-NOS and e-NOS in the corpus cavernosum increased and could significantly reduce the level of MDA (2.67±0.27 vs. 3.25±0.21, P<0.05).Conclusions: As a novel ICA II derivative, YS-10 could significantly improve the erectile dysfunction and pathological damage in rats caused by radiation injury, and its mechanism may be related to the improvement of radiation-induced oxidative stress.

This work aims to investigate the therapeutic effect of ursolic acid (UA) plus insulin (In) on diabetic nephropathy (DN) in streptozotocin (STZ)-induced T1DM rats. The experimental groups and operational details are as follows: A total of thirty-two SD rats were divided into four groups: the DN model group (DN, n = 8), DN + In treatment group (DN + In, n = 8), DN + In + UA administration group (DN + In + UA, n = 8), and negative control group (control, n = 8). After 8 weeks, changes in renal function indices and pathological damage were assessed. Additionally, oxidative stress-, apoptosis-, and fibrosis-related proteins in kidney tissue were measured. Compared with the control group, the vehicle group showed higher levels of creatine, blood urea nitrogen, urinary protein, apoptosis, and lipid peroxidation; lower superoxide dismutase levels; more severe levels of pathological kidney damage and renal fibrosis; and a deepened degree of EMT and EndMT. Better outcomes were achieved with the combined treatment than with insulin-only treatment. The improvement of TGF-β1, phosphorylated p38 MAPK, FGFR1, SIRT3 and DPP-4 expression levels in renal tissues after combination therapy was greater than that after insulin-only treatment. This study shows that the combination of insulin and UA significantly improved the pathological changes in the renal tissue of T1DM rats, and the underlying mechanism may be related to improving apoptosis and oxidative stress by regulating p38 MAPK, SIRT3, DPP-4 and FGFR1 levels, thereby blocking TGF-β signaling pathway activation and inhibiting EMT and EndMT processes.

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BackgroundErectile dysfunction (ED) and weakness of the penis are processes related to hemodynamic alteration. Low‐intensity pulsed ultrasound (LIPUS), as a new mechanical modality for the treatment of ED, deserves to be explored in depth for the biomechanical mechanisms it exerts.ObjectiveThe aim of this study was to explore the role of YAP/TAZ‐mediated mechanotransduction in mechanical therapy for the treatment of neurogenic erectile dysfunction (NED).Materials and methodsForty‐two male SD rats (12 w old) were randomly divided into sham‐operated (n = 14), bilateral cavernous nerve injury (BCNI, n = 14), and LIPUS‐treated (n = 14) groups. Intracavernosal pressure/mean arterial pressure (ICP/MAP) was measured 14 and 28 days after treatment. Penile tissue specimens were collected for pathological examination, and the changes in YAP, TAZ, connective tissue growth factor (CTGF), CYR61, LATS1, and p38 mitogen‐activated protein kinase expression levels were assessed by Western blot, real‐time quantitative polymerase chain reaction (RT–qPCR) and immunological staining.ResultsCompared with BCNI, LIPUS significantly improved ICP/MAP levels and enhanced histopathological changes. The penile expression levels of YAP, TAZ, CTGF, and CYR61 were significantly downregulated in the BCNI group (p < 0.01), and LIPUS upregulated the expression levels of these proteins (p < 0.05). The expression levels of p‐LATS1 and LATS1 were not significantly different among the groups (p > 0.05). Interestingly, the expression level of p‐p38/p38 significantly increased in BCNI rats (p < 0.05), which was reversed by LIPUS treatment (p < 0.05). However, the p38 inhibitor SB203580 did not change the expression of YAP/TAZ in rat primary smooth muscle cells or mouse MOVAS cells (p > 0.05).Discussion and conclusionLIPUS can effectively improve penile erectile function in NED rats. The underlying mechanism may be related to the regulation of YAP/TAZ‐mediated mechanotransduction. However, the upstream regulatory signal may differ from the classical Hippo pathway.

Background Benign prostatic hyperplasia (BPH) most often occurs in older men，previous studies and clinical experience suggest a potential link between lifestyle habits such as sleep habits, sedentary behaviour, exercise levels and BPH, but whether they have a clear causal relationship and the direction of that causality is unclear. We aimed to investigate the causal relationship between lifestyle habits and BPH using two-sample Mendelian randomization (MR) analysis. Methods Instrumental genetic independent variables strongly associated with the selected exposure factors were filtered from published genome-wide association studies (GWAS) consisting primarily of European ancestry samples. GWAS from BPH was analysed as an MR outcome with the inverse variance weighted method (IVW), maximum likelihood, weighted median method, MR‒Egger regression, and several sensitivity analyses, including Cochran’s Q test, intercept of MR‒Egger, and MR pleiotropy residual sum and outlier test (MR-PRESSO). Results MR analysis showed a significant causal risk relationship between sleep duration and BPH, with an odds ratio (OR) of 0.42 (95% confidence interval (CI), 0.25-0.69, p=0.001) for BPH when sleep duration was increased by one standard deviation (SD), but we did not find a causal relationship between the two when we performed a reverse analysis. However, sedentary behaviour and different levels of exercise did not significantly affect the risk of BPH. Conclusions This study showed a strong causal relationship between sleep levels and BPH, with adequate sleep duration being a protective factor for BPH.