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Background: N1-methyladenosine (m1A), among the most common internal modifications on RNAs, has a crucial role to play in cancer development. The purpose of this study were systematically investigate the modification characteristics of m1A in hepatocellular carcinoma (HCC) to unveil its potential as an anticancer target and to develop a model related to m1A modification characteristics with biological functions. This model could predict the prognosis for patients with HCC. Methods: An integrated analysis of the TCGA-LIHC database was performed to explore the gene signatures and clinical relevance of 10 m1A regulators. Furthermore, the biological pathways regulated by m1A modification patterns were investigated. The risk model was established using the genes that showed differential expression (DEGs) between various m1A modification patterns and autophagy clusters. These in vitro experiments were subsequently designed to validate the role of m1A in HCC cell growth and autophagy. Immunohistochemistry was employed to assess m1A levels and the expression of DEGs from the risk model in HCC tissues and paracancer tissues using tissue microarray. Results: The risk model, constructed from five DEGs (CDK5R2, TRIM36, DCAF8L, CYP26B, and PAGE1), exhibited significant prognostic value in predicting survival rates among individuals with HCC. Moreover, HCC tissues showed decreased levels of m1A compared to paracancer tissues. Furthermore, the low m1A level group indicated a poorer clinical outcome for patients with HCC. Additionally, m1A modification may positively influence autophagy regulation, thereby inhibiting HCC cells proliferation under nutrient deficiency conditions. Conclusions: The risk model, comprising m1A regulators correlated with autophagy and constructed from five DEGs, could be instrumental in predicting HCC prognosis. The reduced level of m1A may represent a potential target for anti-HCC strategies. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to describe the changes in the gut microbiome of patients with cirrhosis and hepatic encephalopathy (HE), as well as quantify the variations in short-chain fatty acid (SCFA) and tryptophan metabolite levels in serum and faeces. Methods: Fresh faeces and serum were collected from 20 healthy volunteers (NC group), 30 cirrhosis patients (Cir group), and 30 HE patients (HE group). Then, 16S rRNA sequencing and metabolite measurements were performed using the faeces. Gas chromatography‒mass spectrometry and ultrahigh-performance liquid chromatography-tandem mass spectrometry were used to measure SCFA and tryptophan levels, respectively. The results were analysed by SIMCA16.0.2 software. Differences in species were identified using MetaStat and t tests. The correlations among the levels of gut microbes and metabolites and clinical parameters were determined using Spearman correlation analysis. Results: Patients with cirrhosis and HE had lower microbial species richness and diversity in faeces than healthy volunteers; these patients also had altered β-diversity. Serum valeric acid levels were significantly higher in the HE group than in the Cir group. Serum SCFA levels did not differ between the Cir and NC groups. Serum melatonin and 5-HTOL levels were significantly higher in the HE group than in the Cir group. The Cir and NC groups had significant differences in the levels of eight serum tryptophan metabolites. Furthermore, the levels of faecal SCFAs did not differ between the HE and Cir groups. Faecal IAA-Ala levels were significantly lower in the HE group than in the Cir group. There were significant differences in the levels of 6 faecal SCFAs and 7 faecal tryptophan metabolites between the Cir and NC groups. Certain gut microbes were associated with serum and faecal metabolites, and some metabolites were associated with certain clinical parameters. Conclusion: Reduced microbial species richness and diversity were observed in patients with HE and cirrhosis. In both serum and faeces, the levels of different SCFAs and tryptophan metabolites showed varying patterns of change. In HE patients, the levels of some serum tryptophan metabolites, and not SCFAs, were correlated with liver function and systemic inflammation. Systemic inflammation in patients with cirrhosis was correlated with faecal acetic acid levels. In summary, this study identified metabolites important for HE and cirrhosis. [ABSTRACT FROM AUTHOR]

Background: Thoracic aortic dissection (TAD) is the most common life-threatening disorder, and MMP-2 is involved in TAD pathogenesis. Our purpose is to systematically evaluate the association of the MMP-2 gene with TAD risk in Chinese Han population.Methods: In our case-control study, we recruited 755 unrelated participants: 315 case participants with TAD and 440 controls. Twenty-two tag SNPs were selected from MMP-2 gene and were genotyped. Genotype data were analyzed by logistic regression.Results: Although we did not find any significant association for MMP-2 SNPs using single-marker analysis, we identified many windows with haplotype frequencies significantly different between case participants and control participants using a variable-sized sliding-window strategy. In particular, the most significant association was shown by a 2-SNP window consisting of rs2241145 and rs9928731 (omnibus test: asymptotic Pasym = 7.48 × 10 (-5) and empirical Pemp = 0.001867). There were two protective haplotypes: CT (Pasym = 0.00303; odds ratio [OR], 0.403) and GC (Pasym = 0.000976; OR, 0.448).Conclusions: MMP-2 haplotypes are associated with genetic susceptibility to thoracic aortic dissection in Chinese Han population. [ABSTRACT FROM AUTHOR]

Background: Thoracic aortic dissection (TAD) is the most common life-threatening disorder, and MMP-2 is involved in TAD pathogenesis. Our purpose is to systematically evaluate the association of the MMP-2 gene with TAD risk in Chinese Han population., Methods: In our case-control study, we recruited 755 unrelated participants: 315 case participants with TAD and 440 controls. Twenty-two tag SNPs were selected from MMP-2 gene and were genotyped. Genotype data were analyzed by logistic regression., Results: Although we did not find any significant association for MMP-2 SNPs using single-marker analysis, we identified many windows with haplotype frequencies significantly different between case participants and control participants using a variable-sized sliding-window strategy. In particular, the most significant association was shown by a 2-SNP window consisting of rs2241145 and rs9928731 (omnibus test: asymptotic Pasym = 7.48 × 10 (-5) and empirical Pemp = 0.001867). There were two protective haplotypes: CT (Pasym = 0.00303; odds ratio [OR], 0.403) and GC (Pasym = 0.000976; OR, 0.448)., Conclusions: MMP-2 haplotypes are associated with genetic susceptibility to thoracic aortic dissection in Chinese Han population.