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关键词： Aescin   Alcoholic liver disease   Inflammation   Oxidative stress   p38 MAPK   TNF-alpha  

摘要： Alcoholic liver disease (ALD) is a commonly known liver disease mediated by prolonged alcohol consumption. Aescin is a triterpene saponin that can manage several conditions, including brain trauma, arthritis, venous congestion, stroke, and thrombophlebitis. Even so, studies illustrating the aescin role in ALD are scarce. Our study explored the potential effect of aescin in ALD in mice. In the current experiment, forty mice were utilized and sorted randomly into four groups: the control group received only vehicles, the alcohol group was given 5% alcohol in drinking water for four weeks, and the aescin-treated groups were given 5% alcohol in drinking water and aescin (10 and 20 mg/kg/day) for four weeks, then two doses of 60% alcohol (3g/kg) were given in the 29th and 30th day of the experiment. Our study revealed that aescin ameliorated alcohol-mediated liver damage, including reducing inflammatory cell infiltration and vascular dilatation. The serum concentrations of liver enzymes (ALT and AST) decreased in the aescin-treated groups. The apoptosis and oxidative stress also decreased, and the antioxidant enzyme activities were restored by aescin in alcohol-treated mice. Additionally, aescin decreased ethanol-induced inflammation by downregulating p38 MAPK and tumor necrosis factor-alpha (TNF alpha), suggesting that aescin positively reduces alcohol-caused inflammation and oxidative stress. Consequently, aescin could ameliorate alcohol-induced hepatic damage by targeting the p38 MAPK/TNF-alpha signalling and could be developed as a novel health product that potentially ameliorates ALD.

关键词： DEHP   Testes   Integrative transcriptome and metabolome analysis   TNF-alpha   Apoptosis  

摘要： Di-(2-ethylhexyl) phthalate (DEHP) exposure has been associated with male reproductive damage, but the mechanisms involved remain incompletely defined. This study aims to investigate the effects of DEHP exposure on the testes of prepubertal rats through an integrative analysis of metabolomics and transcriptomics, combined with molecular experiments. DEHP exposure resulted in decreased testis weight and increased oxidative stress level in the testis tissues of prepubertal male rats. Moreover, our findings showed a disordered testis structure, reduced spermatogenic and Sertoli cells as well as destruction of mitochondria structure in the testis tissues of DEHP-treated prepubertal male rats. Transcriptome function analysis together with metabolome function analysis indicated that spermatogenesis, apoptosis, inflammatory, lipid metabolism as well as DNA repair signaling pathway were enriched in the testis of DEHP-treated prepubertal male rats. The integrative omics analysis further suggested that TNF-alpha induced apoptosis played a crucial role in mediating the detrimental effects of DEHP exposure on the testis of prepubertal rats, which was validated by ELISA, Western blotting and Tunel assays. Validation experiments conducted in vitro using GC-2 cells corroborated these findings, demonstrating that mono-(2-ethylhexyl) phthalate (MEHP), the main active metabolite of DEHP, significantly inhibits cell proliferation and increases apoptosis via activating the TNF-alpha apoptosis pathway. Overall, these findings provided a novel mechanism of dysregulated spermatogenesis of DEHP exposure on the testes of prepubertal rats.

关键词： HLA   HLA-DQA1   nanotype sequencing   novel allele   sequencing-based typing  

摘要： The novel allele HLA-DQA1*05:89 differs from HLA-DQA1*05:05:01:01 by one non-synonymous nucleotide substitution in exon 2.

关键词： HLA   HLA-B*58:01:50   novel allele   sequence-based typing   Taiwanese  

摘要： Nucleotide substitution in codon 164 of HLA-B*58:01:01:01 results in the novel allele, HLA-B*58:01:50.

关键词： HLA-C*03:689   novel allele   sequence-based typing  

摘要： The novel HLA-C*03:689 allele differs from HLA-C*03:03:01:01 by two nucleotide substitutions in codons 81 and 82 in exon 2.

关键词： Kimura disease   Nocardiosis   Primary immune deficiency  

摘要： A 12-year-old boy who had been diagnosed with Kimura disease was brought with a history suggestive of acute pyelonephritis. There was a family history of a first-degree relative with a diagnosis of Mendelian Susceptibility to Mycobacterial disease. Investigations revealed a left renal abscess. Aspirate culture grew Nocardia otitidiscaviarum. Targeted gene sequencing revealed a novel mutation in the IL12RB1 gene. Based on the above information a diagnosis of an underlying primary immune deficiency disorder was made. He was managed with appropriate antibiotics, showing steady improvement and eventually a complete recovery.

关键词： Crohn's disease   Pediatrics   Anti-TNF therapy   Steroid-free remission   Biomarkers  

关键词： HLA   HLA-C*15:02:01:69Q   NGS   novel allele   questionable expression  

摘要： HLA-C*15:02:01:69Q differs from HLA-C*15:02:01:01 by a single substitution at the genomic nucleotide position 2727 in intron 7.

关键词： Immune checkpoints   Colorectal cancer   B7family   TNF family  

摘要： Soluble immune checkpoints (sIC) are crucial factors in the immune system. They regulate immune responses by transforming intercellular signals via binding to their membrane-bound receptor or ligand. Moreover, soluble ICs are vital in immune regulation, cancer development, and prognosis. They can be identified and measured in various tumor microenvironments. Recently, sICs have become increasingly important in clinically assessing malignancies like colorectal cancer (CRC) patients. This review explores the evolving role of the soluble B7 family and soluble tumor necrosis factor (TNF) superfamily members in predicting disease progression, treatment response, and overall patient outcomes in CRC. We comprehensively analyze the diagnostic and prognostic potential of soluble immune checkpoints in CRC. Understanding the role of these soluble immune checkpoints in CRC management and their potential as targets for precision medicine approaches can be critical for improving outcomes for patients with colorectal cancer.