Nomogram to predict gas-related complications during transoral endoscopic resection of upper gastrointestinal submucosal lesions: Clinical significance.

Transoral endoscopic resections in treating upper gastrointestinal submucosal lesions have the advantages of maintaining the integrity of the gastrointestinal lumen, avoiding perforation and reducing gastrointestinal fistulae. They are becoming more widely used in clinical practice, but, they may also present a variety of complications. Gas-related complications are one of the most common, which can be left untreated if the symptoms are mild, but in severe cases, they can lead to rapid changes in the respiratory and circulatory systems in a short period, which can be life-threatening. Therefore, it is important to predict the occurrence of gas-related complications early and take preventive measures actively. Based on the authors' results in the prepublication of the article "Nomogram to predict gas-related complications during transoral endoscopic resection of upper gastrointestinal submucosal lesions," and in conjunction with our evaluation and additions to the relevant content, radiographs may help screen patients at high risk for gas-related complications. Controlling blood glucose levels, shortening the duration of surgery, and choosing the most appropriate surgical resection may positively impact the prognosis of patients at high risk for gas-related complications during transoral endoscopic resection of upper gastrointestinal submucosal lesions.

Insulin reverses impaired alveolar fluid clearance in ARDS by inhibiting LPS-induced autophagy and inflammatory.

Until now, acute respiratory distress syndrome (ARDS) has been a difficult clinical condition with a high mortality and morbidity rate, and is characterized by a build-up of alveolar fluid and impaired clearance. The underlying mechanism is not yet fully understood and no effective medications available. Autophagy activation is associated with ARDS caused by different pathogenic factors. It represents a new direction of prevention and treatment of ARDS to restrain autophagy to a reasonable level through pharmacological and molecular genetic methods. Na, K-ATPase is the main gradient driver of pulmonary water clearance in ARDS and could be degraded by the autophagy-lysosome pathway to affect its abundance and enzyme activity. As a normal growth hormone in human body, insulin has been widely used in clinical for a long time. To investigate the association of insulin with Na, K-ATPase, autophagy and inflammatory markers in LPS-treated C57BL/6 mice by survival assessment, proteomic analysis, histologic examination, inflammatory cell counting, myeloperoxidase, TNF-α and IL-1ß activity analysis etc. This was also verified on mouse alveolar epithelial type II (AT II) and A549 cells by transmission electron microscopy. We found that insulin restored the expression of Na, K-ATPase, inhibited the activation of autophagy and reduced the release of inflammatory factors caused by alveolar epithelial damage. The regulation mechanism of insulin on Na, K-ATPase by inhibiting autophagy function may provide new drug targets for the treatment of ARDS.

Identification of different proteins binding to Na, K-ATPase α1 in LPS-induced ARDS cell model by proteomic analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by refractory hypoxemia caused by accumulation of pulmonary fluid, which is related to inflammatory cell infiltration, impaired tight junction of pulmonary epithelium and impaired Na, K-ATPase function, especially Na, K-ATPase α1 subunit. Up until now, the pathogenic mechanism at the level of protein during lipopolysaccharide- (LPS-) induced ARDS remains unclear. METHODS: Using an unbiased, discovery and quantitative proteomic approach, we discovered the differentially expressed proteins binding to Na, K-ATPase α1 between LPS-A549 cells and Control-A549 cells. These Na, K-ATPase α1 interacting proteins were screened by co-immunoprecipitation (Co-IP) technology. Among them, some of the differentially expressed proteins with significant performance were identified and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Data are available via ProteomeXchange with identifier PXD032209. The protein interaction network was constructed by the related Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Several differentially expressed proteins were validated by Western blot. RESULTS: Of identified 1598 proteins, 89 were differentially expressed proteins between LPS-A549 cells and Control-A549 cells. Intriguingly, protein-protein interaction network showed that there were 244 significantly enriched co-expression among 60 proteins in the group control-A549. while the group LPS-A549 showed 43 significant enriched interactions among 29 proteins. The related GO and KEGG analysis found evident phenomena of ubiquitination and deubiquitination, as well as the pathways related to autophagy. Among proteins with rich abundance, there were several intriguing ones, including the deubiquitinase (OTUB1), the tight junction protein zonula occludens-1 (ZO-1), the scaffold protein in CUL4B-RING ubiquitin ligase (CRL4B) complexes (CUL4B) and the autophagy-related protein sequestosome-1 (SQSTM1). CONCLUSIONS: In conclusion, our proteomic approach revealed targets related to the occurrence and development of ARDS, being the first study to investigate significant differences in Na, K-ATPase α1 interacting proteins between LPS-induced ARDS cell model and control-A549 cell. These proteins may help the clinical diagnosis and facilitate the personalized treatment of ARDS.

Autophagy in glaucoma pathogenesis: Therapeutic potential and future perspectives.

Glaucoma is a common blinding eye disease characterized by progressive loss of retinal ganglion cells (RGCs) and their axons, progressive loss of visual field, and optic nerve atrophy. Autophagy plays a pivotal role in the pathophysiology of glaucoma and is closely related to its pathogenesis. Targeting autophagy and blocking the apoptosis of RGCs provides emerging guidance for the treatment of glaucoma. Here, we provide a systematic review of the mechanisms and targets of interventions related to autophagy in glaucoma and discuss the outlook of emerging ideas, techniques, and multidisciplinary combinations to provide a new basis for further research and the prevention of glaucomatous visual impairment.

Regulatory effect of insulin on the structure, function and metabolism of Na+/K+-ATPase (Review).

Na+/K+-ATPase is an ancient enzyme, the role of which is to maintain Na+ and K+ gradients across cell membranes, thus preserving intracellular ion homeostasis. The regulation of Na+/K+-ATPase is affected by several regulatory factors through a number of pathways, with hormones serving important short-term and long-term regulatory functions. Na+/K+-ATPase can also be degraded through activation of the ubiquitin proteasome and autophagy-lysosomal pathways, thereby affecting its abundance and enzymatic activity. As regards the regulatory effect of insulin, it has been found to upregulate the relative abundance of Na+/K+-ATPase and restore the transport efficiency in multiple in vitro and in vivo experiments. Therefore, elucidating the role of insulin in the regulation Na+/K+-ATPase may help uncover new drug targets for the treatment of related diseases. The aim of the present study was to review the structure and function of Na+/K+-ATPase and to discuss the possible mechanisms through which it may be regulated by insulin, in order to investigate the possibility of designing new therapies for related diseases.

Non-targeted proteomics of acute respiratory distress syndrome: clinical and research applications.

Acute respiratory distress syndrome (ARDS) is characterized by refractory hypoxemia caused by accumulation of pulmonary fluid with a high mortality rate, but the underlying mechanism is not yet fully understood, causing absent specific therapeutic drugs to treat with ARDS. In recent years, more and more studies have applied proteomics to ARDS. Non-targeted studies of proteomics in ARDS are just beginning and have the potential to identify novel drug targets and key pathways in this disease. This paper will provide a brief review of the recent advances in the application of non-targeted proteomics to ARDS.