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Liping Meng Hui Lin Xingxiao Huang Jingfan Weng Fang Peng Shengjie Wu 《Cell death & disease》2022,13(1)
N6-methyladenosine (m6A) is one of the most important epigenetic regulation of RNAs, such as lncRNAs. However, the underlying regulatory mechanism of m6A in diabetic cardiomyopathy (DCM) is very limited. In this study, we sought to define the role of METTL14-mediated m6A modification in pyroptosis and DCM progression. DCM rat model was established and qRT-PCR, western blot, and immunohistochemistry (IHC) were used to detect the expression of METTL14 and TINCR. Gain-and-loss functional experiments were performed to define the role of METTL14-TINCR-NLRP3 axis in pyroptosis and DCM. RNA pulldown and RNA immunoprecipitation (RIP) assays were carried out to verify the underlying interaction. Our results showed that pyroptosis was tightly involved in DCM progression. METTL14 was downregulated in cardiomyocytes and hear tissues of DCM rat tissues. Functionally, METTL14 suppressed pyroptosis and DCM via downregulating lncRNA TINCR, which further decreased the expression of key pyroptosis-related protein, NLRP3. Mechanistically, METTL14 increased m6A methylation level of TINCR gene, resulting in its downregulation. Moreover, the m6A reader protein YTHDF2 was essential for m6A methylation and mediated the degradation of TINCR. Finally, TINCR positively regulated NLRP3 by increasing its mRNA stability. To conclude, our work revealed the novel role of METTL14-mediated m6A methylation and lncRNA regulation in pyroptosis and DCM, which could help extend our understanding the epigenetic regulation of pyroptosis in DCM progression.Subject terms: Cardiomyopathies, Endocrine system and metabolic diseases 相似文献
94.
Xiaoying Yang Xuhao Liu Fengcheng Song Hao Wei Fuli Gao Haolin Zhang Yingying Han Qiang Weng Zhengrong Yuan 《European journal of histochemistry : EJH》2022,66(1)
G-protein-coupled receptor 41 (GPR41) and G-protein-coupled receptor 43 (GPR43) are important short-chain fatty acids (SCFAs) receptors. Previous studies indicated that GPR41 and GPR43 are involved in the secretion of gastrointestinal peptides, and glucose and lipid metabolism, and are closely related to obesity and type II diabetes, and other diseases. The purpose of the study was to explore the relationship of the GPR41 and GPR43 with seasonal breeding, and provide new prospects for further exploring the nutritional needs of breeding. We identified the localization and expression levels of GPR41 and GPR43 in the colon of the wild ground squirrels (Spermophilus dauricus) both in the breeding season and non-breeding season. The histological results revealed that the lumen diameter of the colon had obvious seasonal changes, and the diameter of the colonic lumen in the non-breeding season was larger than that in the breeding season. Immunohistochemical staining suggested that GPR41 and GPR43 are expressed in the simple layer columnar epithelium. In addition, compared with the breeding season, the mRNA and protein expression levels of GPR41 and GPR43 in the colon were higher during the non-breeding season. In general, these results indicated that GPR41 and GPR43 might play a certain role in regulating seasonal breeding.Key words: GPR41, GPR43, colon, wild ground squirrel, seasonal breeding 相似文献
95.
In order to meet the requirements for miniaturization detection of oil shale pyrolysis process and solve the problem of low sensitivity of oil and gas detection... 相似文献
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Yanan Ma Shanshan Wang Yongle Wu Bihan Liu Lei Li Wenjing Wang Honglei Weng Huiguo Ding 《Cell death & disease》2022,13(3)
Hepatic stellate cells (HSC) and hydrogen sulfide (H2S) both play important roles in the development of hepatocellar carcinoma (HCC). Whereas, in the microenvironment of HCC, whether HSC participate in regulating the biological process of HCC cells by releasing H2S remains elusive. In vitro, Flow cytometry (FCM), CCK-8, RNA-sequencing, Western blotting, RT-qPCR, immunofluorescence and ChIP assays were carried out in the HCC cells to investigate the effect of H2S on biological functions and JNK/JunB-TNFSF14 signaling pathway. Specimens from HCC patients were analyzed by RT-qPCR and Western blotting assays for evaluating the expression of TNFSF14 and CSE. Statistical analysis was used to analyze the correlation between TNFSF14 expression and clinical data of HCC patients. Based on the FCM and CCK-8 results, we found the LX-2 cells were able to induce HCC cells apoptosis through releasing H2S. RNA-sequencing, RT-qPCR, and Western blotting results showed that TNFSF14 gene was upregulated in both LX-2 and NaHS group. NaHS treated in HCC cells led to JNK/JunB signaling pathway activating and greater binding of p-JunB to its responsive elements on TNFSF14 promoter. Impairment of TNFSF14 induction alleviated LX-2 and NaHS induced apoptosis of HepG2 and PLC/PRF/5 cells. Furthermore, TNFSF14 expression in HCC tissues was lower than the adjacent tissue. HCC patients with low expression of TNFSF14 had higher malignant degree and poor prognosis. In summary, demonstration of the involvement of HSC-derived H2S in JNK/JunB mediated expression of TNFSF14 gene strongly indicates H2S palys an important role in the regulation of HCC apoptosis.Subject terms: Apoptosis, Liver cancer 相似文献
98.
The crystal structure of praseodymium chloride.alpha-D-ribopyranose pentahydrate, PrCl3-C5H10O5-5 H2O, M(r)=487.47, a=9.1989(8), b=8.8214(7), c=9.8233(9) A, beta=94.060(3) degrees, V=795.2(1) A(3), Z=2, mu=0.71073 A and R=0.0418 for 1923 observed reflections and 172 parameters has been determined. The sugar provides three hydroxyl groups, ax-eq-ax for coordination. The Pr(3+) ion is nine-coordinated with five Pr-O bonds from water molecules, three from hydroxyl groups and one from chloride. The OH, CO stretching vibrations and COH bending vibrations are shifted in the complex IR spectrum and the hydroxyl groups, water molecules, chloride ions form an extensive hydrogen-bond network. 相似文献
99.
The pathogenicity of human immunodeficiency virus (HIV) type 1 Nef in CD4C/HIV transgenic mice is abolished by mutation of its SH3-binding domain, and disease development is delayed in the absence of Hck
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The human immunodeficiency virus type 1 (HIV-1) Nef protein is an important determinant of AIDS pathogenesis. We have previously reported that HIV-1 Nef is responsible for the induction of a severe AIDS-like disease in CD4C/HIV transgenic (Tg) mice. To understand the molecular mechanisms of this Nef-induced disease, we generated Tg mice expressing a mutated Nef protein in which the SH3 ligand-binding domain (P(72)XXP(75)XXP(78)) was mutated to A(72)XXA(75)XXQ(78). This mutation completely abolished the pathogenic potential of Nef, although a partial downregulation of the CD4 cell surface expression was still observed in these Tg mice. We also studied whether Hck, one of the effectors previously found to bind to this PXXP motif of Nef, was involved in disease development. Breeding of Tg mice expressing wild-type Nef on an hck(-/-) (knockout) background did not abolish any of the pathological phenotypes. However, the latency of disease development was prolonged. These data indicate that an intact PXXP domain is essential for inducing an AIDS-like disease in CD4C/HIV Tg mice and suggest that interaction of a cellular effector(s) with this domain is required for the induction of this multiorgan disease. Our findings indicate that Hck is an important, but not an essential, effector of Nef and suggest that another factor(s), yet to be identified, may be more critical for disease development. 相似文献
100.
Hwang PP Lee TH Weng CF Fang MJ Cho GY 《Physiological and biochemical zoology : PBZ》1999,72(2):138-144
The purpose of this study is to provide biochemical evidence for the functions of the mitochondria-rich cell (MR cell) in the yolk-sac epithelium of the developing larvae of tilapia Oreochromis mossambicus. Western blotting with the antibody (6F) raised against avian Na-K-ATPase alpha1 subunit demonstrated the presence of Na-K-ATPase in yolk-sac epithelium of tilapia larvae and about 1. 46-fold more of the enzyme in seawater larvae than in freshwater ones. The yolk-sac MR cells were immunoreacted to the antibody (alpha5) against the alpha subunit of avian Na-K-ATPase and were double-labeled with anthroylouabain and dimethylaminostyrylethyl-pyridiniumiodine, suggesting the existence and activity of Na-K-ATPase in these cells. Binding of 3H-ouabain in the yolk sac of seawater larvae was much higher than in that of freshwater larvae (4.183+/-0.143 pmol/mg protein versus 1.610+/-0. 060 pmol/mg protein or 0.0508+/-0.0053 pmol/yolk sac versus 0. 0188+/-0.0073 pmol/yolk sac). These biochemical results are further evidence that yolk-sac MR cells are responsible for a major role in the osmoregulatory mechanism of early developmental stages before the function of gills is fully developed. 相似文献