HDAC6 inhibitor ACY-1215 protects from nonalcoholic fatty liver disease via inhibiting CD14/TLR4/MyD88/MAPK/NFκB signal pathway.

Background & aims: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic steatosis, for which there is currently no effective treatment. ACY-1215 is a selective inhibitor of histone deacetylation 6, which has shown therapeutic potential in many tumors, as well as acute liver injury. However, no research about ACY-1215 on NAFLD has been published. Therefore, our study aims to explore the role and mechanism of ACY-1215 in the experimental model of NAFLD, to propose a new treatment strategy for NAFLD. Methods: We established cell and animal models of NAFLD and verified the effect of ACY-1215 on NAFLD. The mechanism of ACY-1215 on NAFLD was preliminarily explored through TMT relative quantitative proteomics, and then we verify the mechanism discovered in the experimental model of NAFLD. Results: ACY-1215 can reduce lipid aggregation, IL-1ß, and TNF α mRNA levels in liver cells in vitro. ACY-1215 can reduce the weight gain and steatosis in the liver of the NAFLD mouse model, alleviate the deterioration of liver function, and reduce IL-1ßs and TNF α mRNA levels in hepatocytes. TMT relative quantitative proteomics found that ACY-1215 decreased the expression of CD14 in hepatocytes. It was found that ACY-1215 can inhibit the activation level of CD14/TLR4/MyD88/MAPK/NFκB pathway in the NAFLD experimental model. Conclusions: ACY-1215 has a protective effect on the cellular model of NAFLD induced by fatty acids and lipopolysaccharide, as well as the C57BL/6J mouse model induced by a high-fat diet. ACY-1215 may play a protective role by inhibiting CD14/TLR4/MyD88/MAPK/NFκB signal pathway.

Risk factors for positive resection margins after endoscopic resection for gastrointestinal neuroendocrine tumors.

BACKGROUND: In recent years, the incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has remarkably increased due to the widespread use of screening gastrointestinal endoscopy. Currently, the most common treatments are surgery and endoscopic resection. Compared to surgery, endoscopic resection possesses a higher risk of resection margin residues for the treatment of GI-NETs. METHODS: A total of 315 patients who underwent surgery or endoscopic resection for GI-NETs were included. We analyzed their resection modality (surgery, ESD, EMR), margin status, Preoperative marking and Prognosis. RESULTS: Among 315 patients included, 175 cases underwent endoscopic resection and 140 cases underwent surgical treatment. A total of 43 (43/175, 24.57%) and 10 (10/140, 7.14%) patients exhibited positive resection margins after endoscopic resection and surgery, respectively. Multivariate regression analysis suggested that no preoperative marking and endoscopic treatment methods were risk factors for resection margin residues. Among the patients with positive margin residues after endoscopic resection, 5 patients underwent the radical surgical resection and 1 patient underwent additional ESD resection. The remaining 37 patients had no recurrence during a median follow-up of 36 months. CONCLUSIONS: Compared with surgery, endoscopic therapy has a higher margin residual rate. During endoscopic resection, preoperative marking may reduce the rate of lateral margin residues, and endoscopic submucosal dissection may be preferred than endoscopic mucosal resection. Periodical follow-up may be an alternative method for patients with positive margin residues after endoscopic resection.

Association between grip strength and non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background: The association between grip strength (GS) and non-alcoholic fatty liver disease (NAFLD) has been reported by recent epidemiological studies, however, the results of these studies are inconsistent. This meta-analysis was conducted to collect all available data and estimate the risk of NAFLD among people with low GS, as well as the risk of low GS among patients with NAFLD. Methods: We systematically searched several literature databases including PubMed, Web of Science, Cochrane Library, and Embase from inception to March 2022. These observational studies reported the risk of NAFLD among people with low GS and/or the risk of low GS among patients with NAFLD. Qualitative and quantitative information was extracted, statistical heterogeneity was assessed using the I 2 test, and potential for publication bias was assessed qualitatively by a visual estimate of a funnel plot and quantitatively by calculation of the Begg's test and the Egger's test. Results: Of the citations, 10 eligible studies involving 76,676 participants met inclusion criteria. The meta-analysis of seven cross-section studies (69,757 participants) showed that people with low GS had increased risk of NAFLD than those with normal GS (summary OR = 3.32, 95% CI: 1.91-5.75). In addition, the meta-analysis of four studies (14,920 participants) reported that the risk of low GS patients with NAFLD was higher than those in normal people (summary OR = 3.31, 95% CI: 2.45-4.47). Conclusion: In this meta-analysis, we demonstrated a strong relationship between low GS and NAFLD. We found an increased risk of NAFLD among people with low GS, and an increased risk of lower GS among NAFLD patients. Systematic review registration: [www.crd.york.ac.uk/prospero], identifier [CRD42022334687].

Role of Selective Histone Deacetylase 6 Inhibitor ACY-1215 in Cancer and Other Human Diseases.

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.

Corrigendum: Role of selective histone deacetylase 6 inhibitor ACY-1215 in cancer and other human diseases.

[This corrects the article DOI: 10.3389/fphar.2022.907981.].

Artificial intelligence can increase the detection rate of colorectal polyps and adenomas: a systematic review and meta-analysis.

Colonoscopy is an important method to diagnose polyps, especially adenomatous polyps. However, the rate of missed diagnoses is relatively high. In this study, we aimed to determine whether artificial intelligence (AI) improves the polyp detection rate (PDR) and adenoma detection rate (ADR) with colonoscopy. We performed a systematic search in PubMed, Cochrane Library, Embase, and Web of Science databases; the search included entries in the databases up to and including 29 February 2020. Five articles that involved a total of 4311 patients fulfilled the selection criteria. The results of these studies showed that both PDR and ADR increased with the assistance of AI compared with those in control groups {pooled odds ratio (OR) = 1.91 [95% confidence interval (CI) 1.68-2.16] and 1.75 (95% CI 1.52-2.01), respectively}. Good bowel preparation reduced the impact of AI, but significant differences were still apparent in PDR and ADR [pooled OR = 1.69 (95% CI 1.32-2.16) and 1.36 (95% CI 1.04-1.78), respectively]. The characteristics of polyps and adenomas also influenced the results. The average number of polyps and adenomas detected varied significantly by location, and small polyps and adenomas were more likely to be missed. However, the effect of the morphology of polyps and AI-assisted detection needs further studies. In conclusion, AI increases the detection rates of polyps and adenomas in colonoscopy. Without AI assistance, detection rates can be improved with better bowel preparation and training for small polyp and adenoma detection.

Retraction Note: BRD7 inhibits the Warburg effect and tumor progression through inactivation of HIF1α/LDHA axis in breast cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

BRD7 inhibits the Warburg effect and tumor progression through inactivation of HIF1α/LDHA axis in breast cancer.

The bromodomain-containing protein 7 (BRD7) was first identified as a tumor suppressor in nasopharyngeal carcinoma and has critical roles in cancer development and progression. However, the regulatory roles and mechanisms of BRD7 in cancer metabolism are still unknown. In this study, we demonstrated that BRD7 was lowly expressed in breast cancer tissues and was identified as a poor prognostic factor in breast cancer. Meanwhile, BRD7 could suppress cell proliferation, initiate cell apoptosis and reduce aerobic glycolysis, suggesting that BRD7 plays a tumor suppressive roles in breast cancer. Mechanistically, BRD7 could negatively regulate a critical glycolytic enzyme LDHA through directly interaction with its upstream transcription factor, HIF1α, facilitating degradation of HIF1α mediated by ubiquitin-proteasome pathway. Moreover, restoring the expression of LDHA in breast cancer cells could reverse the effect of BRD7 on aerobic glycolysis, cell proliferation, and tumor formation, as well as the expression of cell cycle and apopotosis related molecules such as cyclin D1, CDK4, P21, and c-PARP both in vitro and in vivo. Taken together, these results indicate that BRD7 acts as a tumor suppressor in breast cancer and represses the glycolysis and tumor progression through inactivation of HIF1α/LDHA transcription axis.