Protein phosphatase 1 regulatory subunit 15 A promotes translation initiation and induces G2M phase arrest during cuproptosis in cancers.

Copper ions play a crucial role as cofactors for essential enzymes in cellular processes. However, when the intracellular concentration of copper ions exceeds the homeostatic threshold, they become toxic to cells. In our study, we demonstrated that elesclomol, as a carrier of copper ions, caused an upregulation of protein phosphatase 1 regulatory subunit 15 A (PPP1R15A), which plays a role in regulating substrate selectivity of protein phosphatase 1 during cuproptosis. Mechanistically, we investigated that PPP1R15A activated translation initiation by dephosphorylating eukaryotic translation initiation factor 2 subunit alpha at the S51 residue through protein phosphatase 1 and phosphorylating eukaryotic translation initiation factor 4E binding protein 1 at the T70 residue. In addition, PPP1R15A reduced H3K4 methylation by altering the phosphorylation of histone methyltransferases, which led to the silencing of MYC and G2M phase arrest.

CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression.

Chromatin accessibility plays important roles in revealing the regulatory networks of gene expression, while its application in bladder cancer is yet to be fully elucidated. Chloride intracellular channel 3 (CLIC3) protein has been reported to be associated with the progression of some tumors, whereas the specific mechanism of CLIC3 in tumor remains unclear. Here, we screened for key genes in bladder cancer through the identification of transcription factor binding site clustered region (TFCR) on the basis of chromatin accessibility and TF motif. CLIC3 was identified by joint profiling of chromatin accessibility data with TCGA database. Clinically, CLIC3 expression was significantly elevated in bladder cancer and was negatively correlated with patient survival. CLIC3 promoted the proliferation of bladder cancer cells by reducing p21 expression in vitro and in vivo. Mechanistically, CLIC3 interacted with NAT10 and inhibited the function of NAT10, resulting in the downregulation of ac4C modification and stability of p21 mRNA. Overall, these findings uncover an novel mechanism of mRNA ac4C modification and CLIC3 may act as a potential therapeutic target for bladder cancer.

The complete mitochondrial genome of the chicken roundworm Ascaridia galli (Nematoda: Ascaridiidae).

Ascaridia galli (Nematoda: Ascaridiidae), infecting mainly the small intestine of chickens, is one of the most common nematodes in poultry worldwide. The complete mitochondrial genome sequence of A. galli was 13,981 bp in total length with 36 coding genes, namely, 12 protein-coding genes (PCGs), two ribosomal RNAs, and 22 transfer RNAs. All PCGs were transcribed in one direction. Phylogenetic analysis of the mitogenome of A. galli would further contribute to resolving its phylogenetic position and offer novel perspectives on phylogenetic studies of A. galli.

ARID1A Inactivation Increases Expression of circ0008399 and Promotes Cisplatin Resistance in Bladder Cancer.

OBJECTIVE: Cisplatin (CDDP)-based chemotherapy is a first-line, drug regimen for muscle-invasive bladder cancer (BC) and metastatic bladder cancer. Clinically, resistance to CDDP restricts the clinical benefit of some bladder cancer patients. AT-rich interaction domain 1A (ARID1A) gene mutation occurs frequently in bladder cancer; however, the role of CDDP sensitivity in BC has not been studied. METHODS: We established ARID1A knockout BC cell lines using CRISPR/Cas9 technology. IC50 determination, flow cytometry analysis of apoptosis, and tumor xenograft assays were performed to verify changes in the CDDP sensitivity of BC cells losing ARID1A. qRT-PCR, Western blotting, RNA interference, bioinformatic analysis, and ChIP-qPCR analysis were performed to further explore the potential mechanism of ARID1A inactivation in CDDP sensitivity in BC. RESULTS: It was found that ARID1A inactivation was associated with CDDP resistance in BC cells. Mechanically, loss of ARID1A promoted the expression of eukaryotic translation initiation factor 4A3 (EIF4A3) through epigenetic regulation. Increased expression of EIF4A3 promoted the expression of hsa_circ_0008399 (circ0008399), a novel circular RNA (circRNA) identified in our previous study, which, to some extent, showed that ARID1A deletion caused CDDP resistance through the inhibitory effect of circ0008399 on the apoptosis of BC cells. Importantly, EIF4A3-IN-2 specifically inhibited the activity of EIF4A3 to reduce circ0008399 production and restored the sensitivity of ARID1A inactivated BC cells to CDDP. CONCLUSION: Our research deepens the understanding of the mechanisms of CDDP resistance in BC and elucidates a potential strategy to improve the efficacy of CDDP in BC patients with ARID1A deletion through combination therapy targeting EIF4A3.

Association between Helicobacter pylori infection and irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND: In recent years, the incidence of IBS has gradually increased, and it is considered as one of the most common functional gastrointestinal diseases. However, the etiology of IBS is still unclear, and expectations are rising for more targeted treatments. Many clinical trials have explored the link between Helicobacter pylori (H pylori) and IBS, with different conclusions. Therefore, we conducted a meta-analysis to explore whether there is an association between H pylori and IBS, which is of great significance for targeted treatment of IBS. METHODS: We performed a systematic review and meta-analysis of the association between H pylori and IBS. We searched PubMed, EMBASE, Medline and the Cochrane Library to collect related studies. OR was used to describe the ratio of the probability of the H pylori infection occurring in IBS patients versus the controls. Heterogeneity was assessed by subgroup and meta-regression analysis. RESULTS: Eight studies, including 1861 patients, assessed the association between H pylori infection and IBS. The OR of H pylori in IBS patients compared to controls was 1.32 (95% CI: 0.94-1.87; P = 0.11). Subgroup analyses showed a difference between IBS patients diagnosed with Roman III criteria and those diagnosed with non-Roman III criteria. CONCLUSIONS: Our study suggests that H pylori may have a positive effect on the development of IBS. Although the differences were not statistically significant, there were significant differences among subgroups of patients. Considering the limitations and heterogeneity, high quality studies are needed to further explore the effect of H pylori on the development of IBS.

Endoscopic ultrasound guided fine needle aspiration for the diagnosis of intra-abdominal lymphadenopathy: a systematic review and meta-analysis.

Background: It is difficult to diagnose the cause of abdominal lymphadenopathy without determining the primary lesions. With the advent of curved ultrasound endoscopy, EUS-FNA can sample lymph nodes safely, accurately and conveniently. Due to the lack of formal quantitative and comprehensive literature review to determine the diagnostic value of EUS-FNA in the diagnosis of enlarged intra-abdominal lymph nodes of unknown origin, we conducted this study to systematically evaluate the diagnostic accuracy of EUS-FNA in the enlarged intra-abdominal lymph nodes.Methods: We performed a systematic review and meta-analysis to evaluate the accuracy of EUS-FNA for the diagnosis of intra-abdominal lymphadenopathy. We searched PubMed, Embase, and Cochrane Library to collect related studies and diagnostic performance data. We used a random-effects model to estimate the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio (DOR). Heterogeneity was assessed by subgroup and meta-regression analysis.Results: Twelve eligible studies involved 774 patients were identified. The pooled sensitivity and specificity of all studies is 94% (95% CI: 91% to 96%) and 98% (95% CI: 96% to 99%), respectively. The pooled positive and negative likelihood ratios are 17.44 (95% CI, 6.50 to 46.79) and 0.09 (95% CI: 0.06 to 0.14). The pooled DOR is 277.82 (95% CI, 97.65 to 790.46).Conclusions: EUS-FNA is a safe and feasible technique with high sensitivity and specificity for the diagnosis of abdominal lymph node enlargement. Considering the limitations and heterogeneity, high-quality studies are needed to further explore the diagnostic value of EUS-FNA.