Explore the vast range of titles available.

Primary biliary cholangitis (PBC) is an autoimmune liver disease with a strong hereditary component. Here, we report a genome-wide association study that included 1,122 PBC cases and 4,036 controls of Han Chinese descent, with subsequent replication in a separate cohort of 907 PBC cases and 2,127 controls. Our results show genome-wide association of 14 PBC risk loci including previously identified 6p21 ( HLA-DRA and DPB1 ), 17q12 ( ORMDL3 ), 3q13.33 ( CD80 ), 2q32.3 ( STAT1 / STAT4 ), 3q25.33 ( IL12A ), 4q24 ( NF-κB ) and 22q13.1 ( RPL3 / SYNGR1 ). We also identified variants in IL21 , IL21R , CD28/CTLA4/ICOS , CD58 , ARID3A and IL16 as novel PBC risk loci. These new findings and histochemical studies showing enhanced expression of IL21 and IL21R in PBC livers (particularly in the hepatic portal tracks) support a disease mechanism in which the deregulation of the IL21 signalling pathway, in addition to CD4 T-cell activation and T-cell co-stimulation are critical components in the development of PBC. Primary biliary cholangitis is an autoimmune liver disease. Here, the authors show that variants in interleukin genes which potentially deregulate their expression are associated with this condition, and suggest that the IL21 signalling pathway may have a role in disease aetiology.

Lung cancer (LC) is a serious threat to mankind. The survival of LC patients is still poor despite the enormous efforts that have been made to develop novel treatments. A copper-dependent cell death termed cuproptosis is distinct from known programmed cell death (PCD). Cuproptosis is induced by the disruption of the binding of copper to lipoylated tricarboxylic acid (TCA) cycle proteins of mitochondrial respiratory chains. Potential approaches for treating LC are inducing cell cuproptosis and targeting cell copper death mechanisms. Thus, in this review, we summarize the systemic and cellular metabolic processes of copper. We highlight the possible therapeutic options of employing copper ionophores and chelators for inducing cuproptosis. Moreover, we summarize the prognostic models based on cuproptosis-related genes (CRGs) to identify promising biomarkers for tumor diagnosis and therapy. This review aims to provide a comprehensive summary of CRGs-based prognostic models and promising therapeutic options for cuproptosis induction in LC.

Susceptibility to primary biliary cholangitis (PBC) is in part genetically determined. In our previous PBC genome-wide association study (GWAS) in 1118 Han Chinese PBC and 4036 controls, we noted that multiple SNPs in the runt-related transcription factor 3 (RUNX3) regions showed a nominally significant association. The tag SNP rs7529070 was genotyped using a TaqMan assay in a separately collected 1435 PBC and 3205 controls. A meta-analysis with a combined 2553 PBC and 7241 controls showed that rs7529070 is still nominally associated with PBC (p = 1.7 × 10–4, odds ratio (OR) = 1.18, 95% confidence interval (CI) = 1.08–1.28). Further analysis indicated that the risk allele of rs7529070 (G allele) is in complete linkage disequilibrium (LD) (r2 = 1) with the G allele of rs4648889, which is known to be associated with increased RUNX3 expression. Bioinformatic analysis with existing expression data showed that the expression of RUNX3 is significantly increased in PBC patients (p = 0.001) and the expression level is correlated with disease severity. Consistently, we also found significantly increased RUNX3 expression (p < 0.01) in the livers of dnTGFβRII mice (a PBC mouse model). This study suggests that the RUNX3 locus may associate with PBC in Han Chinese.

Lung cancer (LC) is the leading cause of cancer-related deaths and the second most commonly diagnosed malignancy worldwide. Lung adenocarcinoma (LUAD) and lung squamous cell LC (LUSCC) are the most common subtypes of non-small cell LC (NSCLC). Early diagnosis of LC can be challenging due to a lack of biomarkers. The overall survival (OS) of patients with NSCLC is still poor despite the enormous efforts that have been made to develop novel treatments. Understanding fundamental molecular and genetic mechanisms is necessary to develop new therapeutic approaches for NSCLC. A recently identified type of programmed cell death known as ferroptosis is one potential approach. Ferroptosis causes oxidative damage and the death of cancerous cells by peroxidizing unsaturated phospholipids and accumulating reactive oxygen species (ROS) in an iron-dependent manner. Ferroptosis-related gene (FRG) signatures have recently been evaluated for their ability to predict patient OS and prognosis. These analyses show FRGs are involved in cancer progression, and may serve as promising biomarkers for tumor diagnosis and therapy. Moreover, we summarize the current pharmaceutical options of ferroptosis induction and their underlying molecular mechanism in LC. Therefore, this review aims to provide a comprehensive summary of FRG-based prognostic models, their associated metabolic and signaling pathways, and promising therapeutic options for ferroptosis induction in NSCLC.

Multiple genome-wide association studies of primary biliary cirrhosis (PBC) in both European and Japanese ancestries have shown significant associations of many genetic loci contributing to the susceptibility to PBC. Major differences in susceptibility loci between these two population groups were observed. In this study, we examined whether the most significant loci observed in either European and/or Japanese cohorts are associated with PBC in a Han Chinese population. In 1070 PBC patients and 1198 controls, we observed highly significant associations at CD80 (rs2293370, P  = 2.67 × 10 −8 ) and TNFSF15 (rs4979462, P  = 3.86 × 10 −8 ) and significant associations at 17q12-21 (rs9303277), PDGFB (rs715505), NF-κB1 (rs7665090), IL12RB2 (rs11209050), and STAT4 (rs7574865; all corrected P values <0.01). However, no association was observed for POU2AF1 (rs4938534), IL12A (rs485499 and rs2366408), IL7R (rs6897932), CXCR5 (rs715412), SOCS1 (rs725613), and TNFRSF1A (rs1800693). STAT4 (rs7574865) was strongly associated after additional control samples were analyzed. Our study is the first large-scale genetic analysis in a Han Chinese PBC cohort. These results do not only reflect that Han Chinese PBC patients share common genetic susceptibility genes with both their Japanese and European counterparts but also suggest a distinctly different genetic susceptibility profile.