BCL2L1 is regulated by the lncRNA MIR4435-2HG-miR-513a-5p-BCL2L1 ceRNA axis and serves as a biomarker for pancreatic adenocarcinoma treatment and prognosis.

Pancreatic adenocarcinoma (PAAD) is one of the most malignant cancers. After escaping death, cancer cells are made more metastatic, aggressive, and also drug-resistant through anoikis resistance. The aim of this study is to explore the molecular mechanisms of anoikis-related genes in PAAD and to identify potential key biomarkers. We integrated information about PAAD from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases and identified anoikis-related gene BCL2L1 by survival analysis, univariate Cox regression analysis, and multifactorial Cox regression analysis. Various bioinformatics approaches showed that BCL2L1 was a valuable prognostic marker that might be involved in PAAD development and progression through different mechanisms, including cancer intervention, genomic heterogeneity, and RNA modifications. Our analysis showed that BCL2L1 expression also closely correlates with the expression of various immune checkpoint inhibitors. In particular, we found that long non-coding RNA MIR4435-2HG acted as ceRNA sponging miR-513a-5p to promote the expression of BCL2L1, thereby promoting pancreatic cancer cells proliferation. In conclusion, BCL2L1 expression regulated by the MIR4435-2HG-miR-513a-5p-BCL2L1 ceRNA axis might be used as a biomarker for cancer prognosis, treatment selection, and follow-up in PAAD patients.

Machine learning reveals PANoptosis as a potential reporter and prognostic revealer of tumour microenvironment in lung adenocarcinoma.

Lung adenocarcinoma (LUAD), a prominent lung cancer subtype, has an underexplored relationship with PANoptosis, a recently discovered mode of tumour cell death. This study incorporated iron death, copper death, scorch death, necrotizing apoptosis and bisulfide death into a pan-death gene set (PANoptosis) and conducted single-cell analysis of scRNA-seq data from 11 LUAD samples. Differentially expressed genes were identified, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. Univariate COX regression and least absolute shrinkage and selection operator (LASSO) regression were used to screen PANoptosis key genes for constructing an LUAD risk model. The model's prognostic performance was evaluated using survival curves, risk scores and validation in the Gene Expression Omnibus database. The study also explored the correlation between risk scores, tumour biological function, immunotherapy, drug sensitivity and immune infiltration. The SMS gene in the PANoptosis model was silenced in two LUAD cell lines for cellular validation. Single-cell analysis revealed eight major cell types and several PANoptosis genes significantly associated with LUAD survival. The risk model demonstrated strong prognostic performance and association with immune infiltration, suggesting PANoptosis involvement in LUAD tumour immunity. Cellular validation further supported these findings. The PANoptosis key risk genes are believed to be closely related to the tumour microenvironment and immune regulation of LUAD, potentially providing valuable insights for early diagnosis and clinical treatment, and broader applications in other tumours and complex diseases.

[T follicular helper cells and their related molecules in rheumatoid arthritis: A review].

Abnormal T follicular helper (Tfh) cells in patients with rheumatoid arthritis (RA) is related to the occurrence and development of RA. At present, the mechanism of Tfh cells regulating RA is still unclear. In addition, Tfh cell surface molecules C-X-C motif chemokine receptor 5 (CXCR5), inducible costimulatory molecule (ICOS) and programmed death factor 1 (PD-1) and its secreted interleukin 21 (IL-21), B-cell lymphoma 6 (BCL6) have been shown to be involved in the development of RA. We mainly reviewied the mechanism of RA regulation from the perspective of Tfh cell surface molecules and their secreted factors, analyzed the effects of various molecules related to Tfh cells on RA, and explored the significance of each molecule in the clinical diagnosis of RA and the potential ways of treating RA with each molecule as a target.

[IgG4-related diseases: A comprehensive review].

IgG4-related disease (IgG4-RD) is an inflammatory disorder with slow progression in multiple organs, characterized by abundant infiltration of IgG4-positive plasmacytes and fibrosis in the involved organs. The precise pathogenic mechanism of IgG4-RD still remains unclear. Currently, the abnormal regulation of acquired immunity and adaptive immunity is considered as the main pathogenesis of IgG4-RD, and its clinical manifestations are diverse. IgG4-RD can affect any tissue and organ. Inflammatory pseudotumor and diffuse enlargement are the common manifestations, which are easily misdiagnosed as tumor or inflammation. The treatment of glucocorticoid-based drugs is effective. However, the symptoms of IgG4-RD are variable and the prognosis is poor. We mainly summarized the research progress in the pathogenesis, clinical features, diagnosis and treatment of IgG4-RD.

[The Study of Protective Effect of Paeoniflorin on Lung Injury in MRL/lpr Mice].

OBJECTIVE: To investigate the protective effects of paeoniflorin on the lung injury in systemic lupus erythematosus with mouse model. METHODS: Ten wild type mice and 40 MRL/lpr mice were used in this study. MRL/lpr mice were randomly assigned to MRL/lpr group,MRL/lpr + dexamethasone (1.5 mg/kg) group,MRL/lpr + paeoniflorin (20 mg/kg) group,and MRL/lpr + paeoniflorin (40 mg/kg). The levels of malondialdehyde (MDA) , superoxide dismutase (SOD) ,catalase (CAT) ,glutathione peroxidase (GSH-Px) in serum were detected. The serum levesl of inflammatory cytokines were measured. Lung pathological changes were determined by HE staining. The protein level of phospho-phosphatidylinositol-3 kinase (P-PI3K),phospho-serine-threonine kinase B(P-Akt) ,phospho-nuclear factor kappa B (P-NF-κB),phospho-inhibitor of nuclear factor kappa Bα (P-IκBα) were detected by Western blot. RESULTS: Paeoniflorin decreased serum level of MDA and increased the levels of SOD,CAT,GSH-PX,and decreased the levels of inflammatory cytokines. Paeoniflorin improved lung pathological changes and inhibited the protein levels of P-PI3K,P-Akt,P-NF-κBp65,and P-IκBα in the lung tissue of MRL/lpr mice. CONCLUSION: Paeoniflorin may be beneficial for the prevention of lung injury in systemic lupus erythematosus.

[Paeoniflorin ameliorates liver injury of MRL/lpr mice through inhibition of NF-κB pathway].

Objective To investigate the effects of paeoniflorin (PF) on liver injury of MRL/lpr mice and its underlying mechanisms. Methods The research included 10 normal control C57BL/6 mice and 40 MRL/lpr mice. MRL/lpr mice were randomly assigned equally to a blank control group, a dexamethasone (1.5 mg/kg) group, and two PF (20, 40 mg/kg) groups. The serum levels of alanine transaminase (ALT) and aspartate transaminase (AST) were tested with microplate assay. Inflammatory cytokines in the serum and liver were also detected using ELISA. Liver pathological changes were observed using HE staining. The protein levels of receptor interacting protein140 (RIP140), Toll-like receptor 4 (TLR4), p-NF-κBp65, NF-κBp65, p-IκBα and IκBα in the liver were detected by Western blot analysis. Results PF significantly decreased the serum levels of AST and ALT, obviously decreased the expressions of the inflammatory cytokines IL-1ß, IL-6 and TNF-α in the serum and liver, alleviated liver pathological changes and inhibited the expressions of RIP140, TLR4, p-NF-κBp65, p-IκBα proteins in the MRL/lpr mice. Conclusion PF has protective effects against liver injury in MRL/lpr mice by inhibiting NF-κB pathway.