Overexpression of SESN1 improves mitochondrial damage and mitophagy, a potential therapeutic strategy for cognitive dysfunction after anaesthesia.

Postoperative cognitive dysfunction (POCD) is a prevalent central nervous system complication predominantly observed in elderly patients. Sevoflurane, a general anaesthetic agent, has been implicated in the development of POCD, yet the underlying regulatory mechanisms potentially involving Sestrin1 (SESN1), a stress-responsive protein that plays a critical role in cellular homeostasis and protection against stress-induced damage, including oxidative stress and DNA damage, remain elusive. This study endeavoured to elucidate the impact of SESN1 on sevoflurane-induced cognitive impairment in rats. Employing a model in which SESN1 was transfected into SD male rats and cognitive dysfunction was induced by sevoflurane. The Morris Water Maze test was used for behavioural evaluation, Enzyme-Linked Immunosorbent Assay, Western blotting and immunofluorescence were applied to assess the influence of SESN1 on the inflammatory response and mitophagy in the rat hippocampus. The study further aimed to uncover the putative mechanism by which SESN1, through SIRT1, might modulate cognitive function. Concurrently, levels of malondialdehyde, superoxide dismutase and mitochondrially produced ATP within the rat hippocampus were quantified. Experimental outcomes suggested that SESN1 overexpression significantly mitigated the deleterious effects of sevoflurane anaesthesia, ameliorated neuroinflammation and inflammasome activation, modified mitochondrial function and facilitated mitophagy. Additionally, SESN1, via the activation of SIRT1, may suppress inflammasome activation and mitochondrial dysfunction. Collectively, these findings underscore SESN1's integral role in counteracting sevoflurane-induced cognitive impairment, impeding inflammasome activation, enhancing mitochondrial function and fostering mitophagy, which appear to be intricately linked to SESN1-mediated SIRT1 activation. SESN1 is a novel therapeutic target for POCD, potentially advancing neuroprotective strategies in clinical settings.

SESN2 attenuates sevoflurane-induced cognitive impairment and neuroinflammation in rats.

Long-term use of sevoflurane, an inhalation anesthetic, could negatively impact cognitive function. Current studies have suggested that cognitive impairment induced by sevoflurane may be associated with neuroinflammation. Sestrin2 (SESN2), which belongs to a family of stress-inducible genes, has been reported to exert neuroprotective effects against brain injury. However, its role and underlying mechanisms in sevoflurane-induced cognitive dysfunction in aged rats remain unknown. A sevoflurane-induced aging rat injury model with or without SESN2 overexpression was constructed. The learning and memory abilities of rats were evaluated by the MWM test. ELISA assay and qRT-PCR were conducted to analyze the level of pro-inflammatory factors in the hippocampus. Levels of oxidative stress markers were measured by DHE staining or kit methods. Neuronal apoptosis in the hippocampus was detected using TUNEL assay. Expression of proteins were analyzed by western blot. Sevoflurane exposure caused elevated protein level of SESN2 in hippocampus and cognitive impairment of aged rats. Importantly, overexpression of SESN2 alleviated sevoflurane-induced cognitive dysfunction and inhibited the production of pro-inflammatory factors, oxidative stress, and neuronal apoptosis in the hippocampus. Furthermore, SESN2 overexpression suppressed NLRP3 inflammasome activation induced by sevoflurane. These findings suggested that SESN2 could exert neuroprotective against sevoflurane-induced nerve injury of aged rats through anti-oxidant and anti-inflammatory effects.

The aesthetic repair of complete traumatic cleft earlobe with a three-flap method.

BACKGROUND: The aesthetic repair of complete traumatic cleft earlobe is a common procedure for the plastic surgeon. In this article, a new surgical technique for the repair of complete traumatic cleft earlobe using a 3-flap method was introduced. METHODS OR DESIGN: We shared the experience of treating patients with complete traumatic cleft earlobe by using the 3-flap method in this article. The patients were followed up for >3 months. The reconstructed earlobes were aesthetically pleasing and retained a smooth margin in all cases without prospective complications. CONCLUSIONS: This method not only increases the longitudinal length of the cleft in the earlobe, but also regulates the tissue quantity of the reconstructed earlobe and avoids extension of suture line.

[Study on effect of PluronicF-127 and vascular endothelial growth factor composite delivery system for improving the survival of grafted fat].

To explore the effect of PluronicF-127 and Vascular endthelial growth factor(VEGF) delivery system on the survival of the grafted fat, we divided fat harvest under the same condition into 4 groups. One group served as blank control; the other 3 groups served for experiments with respective to DMEM containing 20 ng/ml VEGF; DMEM containing 30% Pluronic F-127; DMEM containing 20 ng/ml VEGF and 30% Pluronic F-127, and then we transplanted the 4 groups of fat, subcutaneously, on the back of 3 groups of BALB/c nude mice (8 mice per group; injecting 4 points per mouse; 0.2 ml per point). At 3 weeks, 6 weeks and 12 weeks, we dissected the fat grafts, measured their weight retention, and put them in histopathologic examination with the use of HE and CD34 staining. And we compared the weight retention and microvessel density (MVD) of each experiment group versus those of control group. The relation between adipose cell and PluronicF-127 was observed through electron microscope. The results reveal that the MVD and weight of pluronicF-127 and VEGF of the experiment groups are significantly greater than those of other groups. The PluronicF-127 and VEGF composite delivery system can significantly improve the blood circulation for fat transplantation, and increase the survival rate of grafted fat.

Role of Nectin-1/c-Src Signaling in the Analgesic Effect of GDNF on a Rat Model of Chronic Constrictive Injury.

Neuropathic pain results from nerve injury and is one of the most refractory disorders. Recently, many studies reported that glial cell-derived neurotrophic factor (GDNF) exhibited potent analgesic effects, but the underlying mechanisms still remain unknown. In addition to the classical GDNF-GFRα1-Ret pathway, GDNF can bind to adhesion proteins such as E-cadherin and NCAM via GFRα1 in a Ret-independent way. In this study, we aimed to examine whether the adhesion protein nectin-1 and its downstream protein c-Src are involved in neuropathic pain. We found that nectin-1 was expressed in the superficial dorsal horn of the spinal cord and that it was increased after chronic constrictive injury (CCI). Intrathecal administration of nectin-1 siRNA attenuated neuropathic pain induced by CCI via interference of the expression of nectin-1. Furthermore, we found that GDNF can downregulate the phosphorylation level of nectin-1-associated c-Src without changing the expression level of nectin-1. In summary, these data suggest that nectin-1 is involved in neuropathic pain, and that GDNF exerts analgesic effects by directly or indirectly regulating nectin-1/c-Src signaling. These findings may lead to a new target for the treatment of neuropathic pain.

Complications after polyacrylamide hydrogel injection for facial soft-tissue augmentation in China: twenty-four cases and their surgical management.

BACKGROUND: Polyacrylamide hydrogel has been used for soft-tissue augmentation for more than 10 years. Although it is considered a nontoxic, nonimmunogenic material, complications after polyacrylamide hydrogel injections during facial soft-tissue augmentation have been reported. METHODS: Between 2003 and 2009, 24 patients underwent surgical management of complications after facial soft-tissue augmentation. Histories, preoperative imaging, and photographs of operations were recorded. RESULTS: Complications included hematomas, infection, nodule formation, and migration. Ultimately, 23 of 24 cases underwent surgery to remove the gel; the remaining case underwent surgical drainage to remove it. CONCLUSIONS: As more complications have been reported, especially ones that are difficult to treat, the safety of polyacrylamide hydrogel needs to be reconsidered. The authors' experiences provide methods to remove polyacrylamide hydrogel if complications occur. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.