Graphical abstract

Introduction: Endoplasmic reticulum (ER) stress induced the mobilization of two protein breakdown routes, the proteasomal- and autophagy-associated degradation. During ERassociated degradation, unfolded ER proteins are translocated to the cytosol where they are cleaved by the proteasome. When the accumulation of misfolded or unfolded proteins excels the ER capacity, autophagy can be activated in order to undertake the degradative machinery and to attenuate the ER stress. Autophagy is a mechanism by which macromolecules and defective organelles are included in autophagosomes and delivered to lysosomes for degradation and recycling of bioenergetics substrate. Materials and Methods: Autophagy upon ER stress serves initially as a protective mechanism, however when the stress is more pronounced the autophagic response will trigger cell death. Because autophagy could function as a double edged sword in cell viability, we examined the effects autophagy modulation on ER stress-induced cell death in HT22 murine hippocampal neuronal cells. We investigated the effects of both autophagy-inhibition by 3-methyladenine (3-MA) and autophagy-activation by trehalose on ER-stress induced damage in hippocampal HT22 neurons. We evaluated the expression of ER stress- and autophagy-sensors as well as the neuronal viability. Results and Conclusion: Based on our findings, we conclude that under ER-stress conditions, inhibition of autophagy exacerbates cell damage and induction of autophagy by trehalose failed to be neuroprotective.

ObjectiveOur study aimed to compare surgical success rate (SR) and oral morbidity of augmentation urethroplasty for anterior urethral strictures using autologous tissue‐engineered oral mucosa graft (TEOMG) named MukoCell® versus native oral mucosa graft (NOMG).MethodsWe conducted a single‐institution observational study on patients undergoing TEOMG and NOMG urethroplasty for anterior urethral strictures >2 cm in length from January 2016 to July 2020. SR, oral morbidity, and potential risk factors of recurrence were compared between groups were analyzed. A decrease of maximum uroflow rate < 15 mL/s or further instrumentation was considered a failure.ResultsOverall, TEOMG (n = 77) and NOMG (n = 76) groups had comparable SR (68.8% vs. 78.9%, p = 0.155) after a median follow‐up of 52 (interquartile range [IQR] 45–60) months for TEOMG and 53.5 (IQR 43–58) months for NOMG. Subgroup analysis revealed comparable SR according to surgical technique, stricture localization, and length. Only following repetitive urethral dilatations, TEOMG achieved lower SR (31.3% vs. 81.3%, p = 0.003). Surgical time was significantly shorter by TEOMG use (median 104 vs. 182 min, p < 0.001). Oral morbidity and the associated “burden” in patients' quality of life were significantly less at 3 weeks following the biopsy required for TEOMG manufacture, compared to NOMG harvesting and totally absent at 6 and 12 months postoperatively.ConclusionsThe SR of TEOMG urethroplasty appeared to be comparable to NOMG at a mid‐term follow‐up but taking into account the uneven distribution of stricture site and the surgical techniques used in both groups. Surgical time was significantly shortened, since no intraoperative mucosa harvesting was required, and oral complications were diminished through the preoperative biopsy for MukoCell® manufacture.

Staged urethroplasty is performed to treat long-segment obliterating anterior urethral strictures. The technique is particularly challenging when the penobulbar junction is involved, as it requires the transection of the scrotum and the formation of lateral testicular fans. To date, there is no established surgical protocol for this ancillary technique in large volume scrotums with excess skin. We report a case of staged urethroplasty with the necessity of performing T-scrotoplasty due to bulky scrotum. After six months, the Tplasty was successfully resolved, and a new scrotum was formed from the two hemiscrota. In conclusion, scrotoplasty using a bilateral T-plasty is an excellent technique to overcome the necessity of splitting the scrotum by externalizing the urethra to allow for excellent buccal mucosal graft healing over a period of six months. The two separate testicular fans can be reapproximated along the raphe after re-tubularizing the urethra in the 2nd stage, shaping a new scrotum with satisfactory cosmetic results.