Downregulation of m6A Reader YTHDC2 Promotes the Proliferation and Migration of Malignant Lung Cells via CYLD/NF-κB Pathway

Lung cancer is one of the most common types of carcinoma worldwide. Cigarette smoking is considered the leading cause of lung cancer. Aberrant expression of several YT521-B homology (YTH) family proteins has been reported to be closely associated with multiple cancer types. The present study aims to evaluate the function and regulatory mechanisms of the N6-methyladenosine (m⁶A) reader protein YTH domain containing 2 (YTHDC2) by in vitro, in vivo and bioinformatics analyses. The results revealed that YTHDC2 was reduced in lung cancer and cigarette smoke-exposed cells. Notably, bioinformatics and tissue arrays analysis demonstrated that decreased YTHDC2 was highly associated with smoking history, pathological stage, invasion depth, lymph node metastasis and poor outcomes. The in vivo and in vitro studies revealed that YTHDC2 overexpression inhibited the proliferation and migration of lung cancer cells as well as tumor growth in nude mice. Furthermore, YTHDC2 decreased expression was modulated by copy number deletion in lung cancer. Importantly, the cylindromatosis (CYLD)/NF-κB pathways were confirmed as the downstream signaling of YTHDC2, and this axis was mediated by m⁶A modification. The present results indicated that smoking-related downregulation of YTHDC2 was associated with enhanced proliferation and migration in lung cancer cells, and appeared to be regulated by DNA copy number variation. Importantly, YTHDC2 functions as a tumor suppressor through the CYLD/NF-κB signaling pathway, which is mediated by m⁶A modification.     

Serum amyloid A facilitates expansion of CD4+ T cell and CD19+ B cell subsets implicated in the severity of myasthenia gravis patients

Serum amyloid A (SAA) is a clinically useful inflammatory marker involved in the pathogenesis of autoimmune diseases. This study aimed to explore the SAA levels in a cohort of patients with myasthenia gravis (MG) in relation to disease-related clinical parameters and myasthenic crisis (MC) and elucidate the effects of SAA on immune response. A total of 82 MG patients including 50 new-onset MG patients and 32 MC patients were enrolled in this study. Baseline data and laboratory parameters of all enrolled MG patients were routinely recorded through electronic medical systems. SAA levels were measured by enzyme-linked immunosorbent assay (ELISA) kit. CD4⁺ T and CD19⁺ B cell subsets were analyzed by flow cytometry. In vitro, human recombinant SAA (Apo-SAA) was applied to stimulate peripheral blood mononuclear cells (PBMCs) from MG patients to observe the effect on T and B cell differentiation. Our results indicated that SAA levels in new-onset MG patients were higher than those in controls and were positively correlated with QMG score, MGFA classification, plasmablast cells, IL-6, and IL-17 levels. Subgroup analysis revealed that SAA levels were increased in generalized MG (GMG) patients than in ocular MG (OMG), as well as elevated in late-onset MG (LOMG) than in early-onset MG (EOMG) and higher in MGFA III/IV compared with MGFA I/II. The ROC curve demonstrated that SAA showed good diagnostic value for MC, especially when combined with NLR. In vitro, Apo-SAA promoted the Th1 cells, Th17 cells, plasmablast cells, and plasma cells differentiation in MG PBMCs. The present findings suggested that SAA was increased in MG patients and promoted expansion of CD4⁺ T cell and CD19⁺ B cell subsets, which implicated in the severity of MG patients.

     

Effects of Heat Stress on Gut Microbiome in Rats

Gut microbiome, as the largest and most important micro-ecosystem, plays a critical role in health. The purpose of this study was to evaluate whether heat stress modulates the composition and diversity of the gut microbiome in rats. The heat stress model was prepared in rats with the heating temperature maintained at 35–38°C. Cecum contents were collected after heat stress for 3 h and days 1, 3 and 7. Total DNA was extracted for 16 S rRNA sequencing and analysis of intestinal microbiome composition and diversity. The study showed that the composition of the intestinal microbiome of heat stress group was changed. And the heat stress modulated key phylotypes of gut microbiota at the level of phylum and genus. In particular, the genus of Lactobacillus and Bacteroides were significantly reduced, whereas the Oscillospira and Clostridium were increased by heat stress. Meanwhile, the rats under the heat stress encountered the change in carbohydrate metabolism, amino acid metabolism, and membrane transport to defense against stress. Taken together, the composition and structure of gut microbiome were affected by heat stress and some key phylotypes were also significantly altered. We conclude that the heat stress could impact multiple biological functions, via altering the gut microbiome.     

人胰腺α-淀粉酶抑制剂高通量筛选模型的建立及其应用

【目的】针对人胰腺α-淀粉酶这个糖代谢途径中重要的靶蛋白,建立α-淀粉酶抑制剂高通量筛选模型。【方法】采用毕赤酵母表达系统克隆和表达人胰腺α-淀粉酶;利用酶的催化特性建立α-淀粉酶抑制剂筛选模型;应用该模型对放线菌发酵液冻干物进行高通量筛选;通过构建16S rRNA系统发育树分析阳性菌株的分类地位。【结果】成功克隆、表达了具催化活性的人胰腺α-淀粉酶;建立了α-淀粉酶抑制剂的筛选模型;对近2000株放线菌的发酵液冻干物进行高通量筛选,最终得到14株α-淀粉酶抑制剂产生菌株,且在分类学上具有丰富的菌种多样性。【结论】本研究建立的α-淀粉酶抑制剂高通量筛选模型具有很强的实用价值,可用于新型淀粉酶抑制剂类降糖药物的开发。