Erectile dysfunction (ED) is an adverse side effect of pelvic surgery with no effective treatment. In this study, it is explored whether melatonin could improve the therapeutic effects of small extracellular vesicles (sEVs), derived from mesenchymal stem cells (MSCs), on cavernous nerve injury (CNI) ED, and the underlying mechanisms are investigated. The sEVs from melatonin‐pretreated MSCs (MT‐EVs) and MSCs (NC‐EVs) are isolated and applied to CNI ED. Transplantation of MT‐EVs remarkably increases erectile function and reduces phenotypic modulation in CNI ED rats. The therapeutic effects of MT‐EVs are superior to those of NC‐EVs. Sequencing implies that miR‐10a‐3p is enriched in MT‐EVs, and directly targets the protein kinase inhibitor α (PKIA). After the suppression of miR‐10a‐3p, the therapeutic actions of MT‐EVs are abolished, but are rescued by PKIA. Similarly, RhoA/ROCK is inhibited by MT‐EVs, but this action is reversed by suppressing miR‐10a‐3p, accompanied by corresponding changes in PKIA. In conclusion, transplantation of MT‐EVs could significantly alleviate CNI ED. MT‐EVs may relieve the phenotypic modulation of the corpora cavernosum smooth muscle cells via the miR‐10a‐3p/PKIA/RhoA/ROCK signaling axis. These nanovesicles should be potential therapeutic vectors or bioactive materials for CNI ED.
Neurogenic erectile dysfunction (NED) is a common and serious complication after pelvic surgery. The clinical translation of adipose-derived mesenchymal stem cell (ADSC) therapies in NED remains a major challenge due to their low survival rate and limited therapeutic effect. Peroxiredoxin 2 (PRDX2) is a member of the peroxidase family that exerts its therapeutic effects by inhibiting oxidative stress (OS) and ferroptosis, and PRDX2 is expected to enhance the therapeutic effect of ADSCs in treating NED. The purpose of this study was to investigate whether PRDX2 could improve the survival of ADSCs and determine whether overexpression of PRDX2 in ADSCs (PRDX2-ADSCs) could enhance the therapeutic effect of NED. This study investigated the potential role of PRDX2-ADSCs through a NED model induced by bilateral cavernous nerve injury (BCNI) and three in vitro models established by H2O2-stimulated ADSCs, H2O2-stimulated corpus cavernosum smooth muscle cells (CCSMCs), and RSL3-stimulated CCSMCs. We found that PRDX2 could significantly improve the viability of ADSCs by suppressing apoptosis and OS in H2O2-stimulated ADSCs. We also found that BCNI triggered ferroptosis of the corpus cavernosum, which was manifested by increased reactive oxygen species (ROS), total iron content, and MDA as well as decreased SOD and GSH. Our results further demonstrated changes in the expression of key proteins (GPX4 and ACSL4) in the ferroptosis pathway, whereas PRDX2-ADSCs ameliorated BCNI-induced erectile dysfunction and ferroptosis of the corpus cavernosum in NED rats. Consistently, PRDX2-ADSCs attenuated OS in H2O2-stimulated CCSMCs and inhibited ferroptosis in RSL3-stimulated CCSMCs, as evidenced by the decrease in ROS, total iron content, and MDA and the increase in SOD and GSH together with changes in ferroptosis-related protein (GPX4 and ACSL4) expression. In conclusion, overexpression of PRDX2 in ADSCs enhanced the therapeutic effect in a rat model of neurogenic erectile dysfunction by inhibiting ferroptosis via regulation of the GPX4/ACSL4 axis.
Aim: Rectal stenosis is a relatively rare complication after transanal endoscopic microsurgery (TEM). This study aims to identify the predictive parameters for stenosis and the application of TEM in the treatment. Method:The clinical data of patients who underwent TEM for rectal adenoma and early cancer from 2008 to 2019 were retrospectively reviewed. We compared the clinicopathological characteristics of patients with stenosis and those without stenosis and analysed the risk factors for stenosis. Treatment outcomes of stenosis with TEM were evaluated.Results: A total of 230 patients were enrolled in this study. Overall, the postoperative complication rate was 11.7% (27/230), including eight (3.5%) patients with stenosis.Patients with stenosis exhibited a higher rate of tumour showing a laterally spreading morphology (P = 0.048), a wider circumferential extent of mucosal defect (P < 0.001), a shorter distance of the tumour from the anal verge (P = 0.001) and a wider longitudinal extent of mucosal defect (P = 0.027). A circumferential extent of mucosal defect >3/4 (OR 94.945, 95% CI 3.611-2496.41, P = 0.006) was identified as the only independent risk factor for stenosis. The four patients with both stenosis and clinical symptoms were treated by incising the stenosis ring using the TEM platform; the stenosis was cured, and symptoms disappeared after one to four courses of treatment.Conclusions: Circumferential extent of mucosal defect ≥3/4 was an independent risk factor for stenosis in treating rectal adenoma and early cancer with TEM. Incision of the stenosis ring using the TEM platform is an effective strategy for treating stenosis.
Purpose Erectile dysfunction (ED) is a common postoperative complication of pelvic surgery for which there is currently no effective treatment. This study investigated the therapeutic effects and potential mechanisms of adipose derived mesenchymal stem cells-derived mitochondria (ADSCs-mito) transplantation in a rat model of bilateral cavernous nerve injury (CNI) ED. Materials and Methods We isolated mitochondria from ADSCs and tested their quality. In vivo , twenty male Sprague Dawley rats were randomly divided into four groups: sham operation group and CNI groups that received intracavernous injection of either phosphate buffer solution, ADSCs-mito or ADSCs. Two weeks after therapy, the erectile function of the rats was evaluated and the penile tissues were harvested for histologic analysis and western blotting. In vitro , the apoptosis rate, reactive oxygen species (ROS), mitochondria derived active oxygen (mtROS) and adenosine triphosphate (ATP) levels were detected in corpus cavernosum smooth muscle cells (CCSMCs) after the incubation with ADSCs-mito. In addition, intercellular mitochondrial transfer was visualized by co-culture of ADSCs and CCSMCs. Results The ADSCs, ADSCs-mito and CCSMCs were isolated and identified successfully. ADSCs-mito transplantation notably restored the erectile function and smooth muscle content of CNI ED rats. Moreover, the levels of ROS, mtROS and cleaved-caspase 3 were reduced and the levels of superoxide dismutase and ATP were increased after ADSCs-mito transplantation. In CNI ED rats, the mitochondrial structure of cells in penile tissues was destroyed. ADSCs could transfer its own mitochondria to CCSMCs. Pre-treatment with ADSCs-mito could significantly decrease apoptosis rate, ROS levels and mtROS levels as well as restore the ATP level in CCSMCs. Conclusions ADSCs-mito transplantation significantly ameliorated ED induced by CNI, with similar potency to ADSCs treatment. The ADSCs-mito might exert their effects via anti-oxidative stress, anti-apoptosis and modulating energy metabolism of CCSMCs. Mitochondrial transplantation should be a promising therapeutic method for treating CNI ED in the future.
Background Anastomotic leakage remains one of the most common serious complications after rectal cancer surgery. How to predict its occurrence and prevent it remains largely elusive. Objective This study aimed to identify the risk factors of anastomotic leakage and construct a nomogram for predicting postoperative anastomotic leakage in patients with rectal cancer. Methods The data of 406 patients with rectal cancer after gastrointestinal surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2011 to May 2020 were collected (243 in the training set and 163 in the testing set). Logistic regression was applied to determine the risk factors of postoperative anastomotic leakage of rectal cancer, and a nomogram prediction model was thus established. Predictive performance of the nomogram was evaluated by C-index and area under the receiver-operating characteristic (ROC) curve. Results Logistic regression analysis showed that preoperative bowel obstruction (odds ratio [OR] = 12.846, 95% confidence interval CI [1.441–114.54], p = 0.022) and early first defecation after surgery (OR = 0.501, 95% CI [0.31–0.812], p = 0.005) were independent risk factors, which could be used to develop a nomogram to predict the occurrence of anastomotic leakage accurately. The evaluation of the prediction model shows that the C-index value of the model was 0.955, the area under the ROC curve (AUC) of the training set was 0.820, and the testing set was 0.747, whereas the optimal cut-off point based on the nomogram score was 174.6. Conclusion This nomogram had a good prediction ability for postoperative anastomotic leakage in patients with rectal cancer. It can provide a reference for perioperative treatment and the selection of surgical methods to promote individualized and accurate treatment.
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