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.

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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: Hematologic diseases have seriously threatened human health. Although hematopoietic stem cell transplantation (HSCT) is an effective curative option, the complications, especially graft-versus-host disease (GVHD), are a big problem. Methods: TNF-α pretreatment of hematopoietic stem cells. Apoptosis was detected by flow cytometry, Transwell, and wound healing assays were used to assess cell migration and invasion, E-selectin expression was observed by fluorescence imaging, the levels of NO were measured by a kit, the expression of E-cadherin, MMP2, and MMP9 was detected in cells by qRT-PCR, and western blot was used to analyze the expression of E-cadherin, CXCL12, MCP-1, MCP-3, MMP2, and MMP9. Results: TNF-α induces a high apoptosis rate of CD3, CD19, and CD133 and a low apoptosis rate of CD34. The level of Fas and TNF-R1 was significantly high than that of TNF-R2. HSCs treated with TNF-α declined the invasion and migration of HUVECs. E-selectin, MMP2 and MMP9 mRNA levels of HUVECs and MMP2, CXCL12, MCP-1, and MCP-3 were decreased after HSCs-TNF-α treatment, while the E-cadherin mRNA and protein level of HUVECs was enhanced with HSCs-TNF-α treatment. Conclusion: TNF-α pretreated HSCs can lead to reduced levels of migration, adhesion, and chemokines of HUVECs, thereby declining the inflammatory response and GVHD.