Endoscopic submucosal dissection (ESD) has been widely applied as a less invasive and more effective method for treating early esophageal cancers such as squamous cell carcinoma and dysplasia of Barrett's esophagus. However, post-ESD esophageal stricture often occurs if patients suffer circumferential mucosal defects of more than three-quarters of the circumference of the esophagus, which makes it difficult for patients to swallow and greatly reduces their quality of life. Moreover, there is currently no standard method to treat post-ESD esophageal stricture, even though it is extraordinarily important to prevent its formation. In recent years, several strategies to prevent esophageal stricture have emerged. These strategies can be classified into pharmacological, mechanical, tissue engineering, and other novel strategies, with each strategy having its own strengths and weaknesses. Although the pharmacological prophylaxis and mechanical strategies are relatively mature, they still have their drawbacks like high time-consumption, the occurrence of re-stricture, and significant side effects. Tissue engineering strategies and other novel strategies have shown promising preliminary results, but more clinical trials are needed. In this review, we discuss these strategies, with a particular focus on tissue engineering strategies and other novel strategies. It is hoped that this discussion will aid in finding more effective and safer strategies to prevent esophageal stricture.

Purpose Sharp-pointed FBs with both sides embedded in the duodenal wall are rare. Compared with smooth edged FBs, sharp objects are more likely to be associated with significant adverse events, when penetrating the wall of the digestive tract. The clinical features of patients who experienced sharp-pointed FBs embedded in both sides of the duodenum were retrospectively analyzed, as were the efficacy and safety of endoscopic removal of these FBs. Patients and Methods This retrospective study included 21 adults with both sides of sharp-pointed FBs embedded into the duodenal wall who were admitted to the Second Xiangya Hospital in China between January 1, 1996, and May 31, 2021. Data associated with the endoscopic removal of these FBs were collected from the electronic medical record system (EMRS) of the hospital. Results The incidence rate of duodenal total FBs and FBs embedded in both sides was 8.87% and 1.03%, respectively. The success rate of endoscopic treatment was 100.00% in 124 patients without embedded duodenal FBs and 97.14% in 35 patients with one side embedded duodenal FBs. Of the 21 patients with FBs embedded in both sides of the duodenal wall, endoscopic removal was successful in 85.71% of patients, whereas 14.29% required surgery. FBs removed from these patients included toothpicks in 12; needles in 3; jujube pits in 2; and a chopstick, dentures, fish bones, and chicken bones in one each. Most of these 21 FBs were located in the bulb and descending duodenum, followed by the third part of duodenum. Conclusion Sharp-edged FBs with both sides embedded in the duodenal wall are rare. Endoscopic removal may be considered as a feasible, safe, and effective method of removing sharp-pointed FBs with both sides embedded in the duodenal wall. And if endoscopic removal is unsuccessful, surgical management can be a secondary option.

DNA damage-regulated autophagy modulator protein 1 (DRAM1), a multi-pass membrane lysosomal protein, is reportedly a tumor protein p53 (TP53) target gene involved in autophagy. During cerebral ischemia/reperfusion (I/R) injury, DRAM1 protein expression is increased, and autophagy is activated. However, the functional significance of DRAM1 and the relationship between DRAM1 and autophagy in brain I/R remains uncertain. The aim of this study is to investigate whether DRAM1 mediates autophagy activation in cerebral I/R injury and to explore its possible effects and mechanisms. We adopt the oxygen-glucose deprivation and reperfusion (OGD/R) Neuro-2a cell model to mimic cerebral I/R conditions in vitro, and RNA interference is used to knock down DRAM1 expression in this model. Cell viability assay is performed using the LIVE/DEAD viability/cytotoxicity kit. Cell phenotypic changes are analyzed through Western blot assays. Autophagy flux is monitored through the tandem red fluorescent protein–Green fluorescent protein–microtubule associated protein 1 light chain 3 (RFP–GFP–LC3) construct. The expression levels of DRAM1 and microtubule associated protein 1 light chain 3II/I (LC3II/I) are strongly up-regulated in Neuro-2a cells after OGD/R treatment and peaked at the 12 h reperfusion time point. The autophagy-specific inhibitor 3-Methyladenine (3-MA) inhibits the expression of DRAM1 and LC3II/I and exacerbates OGD/R-induced cell injury. Furthermore, DRAM1 knockdown aggravates OGD/R-induced cell injury and significantly blocks autophagy through decreasing autophagosome-lysosome fusion. In conclusion, our data demonstrate that DRAM1 knockdown in Neuro-2a cells inhibits autophagy by blocking autophagosome-lysosome fusion and exacerbated OGD/R-induced cell injury. Thus, DRAM1 might constitute a new therapeutic target for I/R diseases.

Alterations in vascular smooth muscle cells (SMCs) contribute to the pathogenesis of intracranial aneurysms (IAs), but the genetic mechanisms underlying these alterations are unclear. We used microarray analysis to compare tissue small noncoding RNA and messenger RNA expression profiles in vessel wall samples from patients with late-stage IAs. We identified myocardin (MYOCD), a key contractility regulator of vascular SMCs, as a critical factor in IA progression. Using a multifaceted computational and experimental approach, we determined that depletion of competitive endogenous RNAs (ARHGEF12, FGF12, and ADCY5) enhanced factors that downregulate MYOCD, which induces the conversion of SMCs from differentiated contractile states into dedifferentiated phenotypes that exhibit enhanced proliferation, synthesis of new extracellular matrix, and organization of mural thrombi. These effects may lead to the repair and maintenance of IAs. This study presents guidelines for the prediction and validation of the IA regulator MYOCD in competitive endogenous RNA networks and facilitates the development of novel therapeutic and diagnostic tools for IAs.

The deacetylation process regulated by histone deacetylases (HDACs) plays an important role in human health and diseases. HDAC6 belongs to the Class IIb of HDACs family, which mainly modifies non-histone proteins located in the cytoplasm. HDAC6 plays a key role in tumors, neurological diseases, and inflammatory diseases. Therefore, targeting HDAC6 has become a promising treatment strategy in recent years. ACY-1215 is the first orally available highly selective HDAC6 inhibitor, and its efficacy and therapeutic effects are being continuously verified. This review summarizes the research progress of ACY-1215 in cancer and other human diseases, as well as the underlying mechanism, in order to guide the future clinical trials of ACY-1215 and more in-depth mechanism researches.

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MicroRNA (miR)-361-5p has been studied to suppress gliomas development. Based on that, an insight into the regulatory mechanism of miR-361-5p in gliomas was supplemented from ubiquitin protein ligase E3 component N-recognin 5 (UBR5)-mediated ubiquitination of ataxia-telangiectasia mutated interactor (ATMIN). miR-361-5p, ATMIN, and UBR5 levels were clinically analyzed in gliomas tissues, which were further validated in gliomas cell lines. Loss/gain-of-function method was applied to determine the roles of miR-361-5p and UBR5 in gliomas, as to cell viability, migration, invasion, colony formation ability, and apoptosis in vitro and tumorigenesis in vivo. The relationship between miR-361-5p and UBR5 was verified and the interaction between UBR5 and ATMIN was explored. It was detected that reduced miR-361-5p and ATMIN and enhanced UBR5 levels showed in gliomas. Elevating miR-361-5p was repressive in gliomas progression. UBR5 was directly targeted by miR-361-5p. UBR5 can ubiquitinate ATMIN. miR-361-5p suppressed gliomas by regulating UBR5-mediated ubiquitination of ATMIN. Downregulating UBR5 impeded gliomas tumor growth in vivo. Upregulating miR-361-5p targets UBR5 to promote ATMIN protein expression, thus to recline the malignant phenotype of gliomas cells.

Endoplasm reticulum stress and inflammation response have been found to be linked to cerebral ischemia-reperfusion (IR) injury. Sphingosine kinase 1 (SPHK1) has been reported to be a novel endoplasm reticulum regulator. The aim of our study is to figure out the role of SPHK1 in cerebral IR injury and verify whether it has an ability to regulate inflammation and endoplasm reticulum stress. Hydrogen peroxide was used to induce cerebral IR injury. Enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, western blots, and immunofluorescence were used to measure the alterations of cell viability, inflammation response, and endoplasm reticulum stress. The results demonstrated that after exposure to hydrogen peroxide, cell viability was reduced whereas SPHK1 expression was significantly elevated.Knockdown of SPHK1 attenuated hydrogen peroxide-mediated cell death and reversed cell viability. Our data also demonstrated that SPHK1 deletion reduced endoplasm reticulum stress and alleviated inflammation response in hydrogen peroxide-treated cells. In addition, we also found that SHPK1 modulated endoplasm reticulum stress and inflammation response to through the NF-κB signaling pathway.Inhibition of NF-κB signaling pathway has similar results when compared with the cells with SPHK1 deletion. Altogether, our results demonstrated that SPHK1 upregulation, induced by hydrogen peroxide, is responsible for cerebral IR injury through inducing endoplasm reticulum stress and inflammation response in a manner working through the NF-κB signaling pathway. This finding provides new insight into the molecular mechanism to explain the neuron death induced by cerebral IR injury.