Deciphering the molecular nexus of BTG2 in periodontitis and diabetic kidney disease.

OBJECTIVE: To investigate the role of BTG2 in periodontitis and diabetic kidney disease (DKD) and its potential underlying mechanism. METHODS: Gene expression data for periodontitis and DKD were acquired from the Gene Expression Omnibus (GEO) database. Differential expression analysis identified co-expressed genes between these conditions. The Nephroseq V5 online nephropathy database validated the role of these genes in DKD. Pearson correlation analysis identified genes associated with our target gene. We employed Gene Set Enrichment Analysis (GSEA) and Protein-Protein Interaction (PPI) networks to elucidate potential mechanisms. Expression levels of BTG2 mRNA were examined using quantitative polymerase Chain Reaction (qPCR) and immunofluorescence assays. Western blotting quantified proteins involved in epithelial-to-mesenchymal transition (EMT), apoptosis, mTORC1 signaling, and autophagy. Additionally, wound healing and flow cytometric apoptosis assays evaluated podocyte migration and apoptosis, respectively. RESULTS: Analysis of GEO database data revealed BTG2 as a commonly differentially expressed gene in both DKD and periodontitis. BTG2 expression was reduced in DKD compared to normal conditions and correlated with proteinuria. GSEA indicated enrichment of BTG2 in the EMT and mTORC1 signaling pathways. The PPI network highlighted BTG2's relevance to S100A9, S100A12, and FPR1. Immunofluorescence assays demonstrated significantly lower BTG2 expression in podocytes under high glucose (HG) conditions. Reduced BTG2 expression in HG-treated podocytes led to increased levels of EMT markers (α-SMA, vimentin) and the apoptotic protein Bim, alongside a decrease in nephrin. Lower BTG2 levels were associated with increased podocyte mobility and apoptosis, as well as elevated RPS6KB1 and mTOR levels, but reduced autophagy marker LC3. CONCLUSION: Our findings suggest that BTG2 is a crucial intermediary gene linking DKD and periodontitis. Modulating autophagy via inhibition of the mTORC1 signaling pathway, and consequently suppressing EMT, may be pivotal in the interplay between periodontitis and DKD.

Genome-Wide Identification of R2R3-MYB Transcription Factor and Expression Analysis under Abiotic Stress in Rice.

The myeloblastosis (MYB) family comprises a large group of transcription factors (TFs) that has a variety of functions. Among them, the R2R3-MYB type of proteins are the largest group in plants, which are involved in controlling various biological processes such as plant growth and development, physiological metabolism, defense, and responses to abiotic and biotic stresses. In this study, bioinformatics was adopted to conduct genome-wide identification of the R2R3-MYB TFs in rice. We identified 190 MYB TFs (99 R2R3-MYBs), which are unevenly distributed on the 12 chromosomes of rice. Based on the phylogenetic clustering and protein sequence characteristics, OsMYBs were classified into five subgroups, and 59.6% of the Os2R_MYB genes contained two introns. Analysis of cis-acting elements in the 2000 bp upstream region of Os2R_MYB genes showed that all Os2R_MYB genes contained plant hormones-related or stress-responsive elements since 91.9%, 79.8%, 79.8%, and 58.6% of Os2R_MYB genes contain ABRE, TGACG, CGTCA, and MBS motifs, respectively. Protein-protein network analysis showed that the Os2R_MYBs were involved in metabolic process, biosynthetic process, and tissue development. In addition, some genes showed a tissue-specific or developmental-stage-specific expression pattern. Moreover, the transcription levels of 20 Os2R_MYB genes under polyethylene glycol (PEG) and cadmium chloride (CdCl2) stress inducers were dissected by qRT-PCR. The results indicated genes with an altered expression upon PEG or CdCl2 stress induction. These results potentially supply a basis for further research on the role that Os2R_MYB genes play in plant development and stress responses.

Neoantigen-reactive T cells exhibit effective anti-tumor activity against colorectal cancer.

Neoantigens play a crucial role in cancer immunotherapy. However, the effectiveness and safety of neoantigen-based immunotherapies in patients with colorectal cancer (CRC), particularly in the Chinese population, have not been well studied. This study explored the feasibility and effectiveness of neoantigens in the treatment of CRC. Whole-exome sequencing (WES) and transcriptome sequencing were used to identify somatic mutations, RNA expression, and human leukocyte antigen (HLA) alleles. Neoantigen candidates were predicted, and immunogenicity was assessed. The neoantigens TSHZ3-L523P, RARA-R83H, TP53-R248W, EYA2-V333I, and NRAS-G12D from Patient 4 (PW4); TASP1-P161L, RAP1GAP-S215R, MOSPD1-V63I, and NAV2-D1973N from Patient 10 (PW10); and HAVCR2-F39V, SEC11A-R11L, SMPDL3B-T452M, LRFN3-R118Q, and ULK1-S248L from Patient 11 (HLA-A0201+PW11) induced a heightened neoantigen-reactive T cell (NRT) response as compared with the controls in peripheral blood lymphocytes (PBLs) isolated from patients with CRC. In addition, we identified neoantigen-containing peptides SEC11A-R11L and ULK1-S248L from HLA-A0201+PW11, which more effectively elicited specific CTL responses than the corresponding native peptides in PBLs isolated from HLA-A0201+PW11 as well as in HLA-A2.1/Kb transgenic mice. Importantly, adoptive transfer of NRTs induced by vaccination with two mutant peptides could effectively inhibit tumor growth in tumor-bearing mouse models. These data indicate that neoantigen-containing peptides with high immunogenicity represent promising candidates for peptide-mediated personalized therapy.Abbreviations: CRC: colorectal cancer; DCs: dendritic cells; ELISPOT: enzyme-linked immunosorbent spot; E:T: effector:target; HLA: human leukocyte antigen; MHC: major histocompatibility complex; Mut: mutant type; NGS: next-generation sequencing; NRTs: neoantigen-reactive T cells; PBMCs: peripheral blood mononuclear cells; STR: short tandem repeat; PBLs: peripheral blood lymphocytes; PBS: phosphate-buffered saline; PD-1: programmed cell death protein 1; TILs: tumor-infiltrating lymphocytes; RNA-seq: RNA sequencing; Tg: transgenic; TMGs: tandem minigenes; WES: whole-exome sequencing; WT: wild-type.

IncRNA LUCAT1 acts as a Potential Biomarker and Demonstrates Malignant Biological Behaviors in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) remains the fourth-leading malignancy worldwide and has a high mortality rate. Accumulating evidence reveals that long noncoding RNAs (lncRNAs) play essential roles in tumorigenesis and metastasis and can be used as potential biomarkers for diagnosis and prognosis. METHODS: We downloaded gene expression profiles from the National Center of Biotechnology Information Gene Expression Omnibus (GEO), screened lncRNAs differentially expressed in gastric cancer tissues and adjacent tissues, and then constructed a lncRNA-miRNA-mRNA network. Seventy patients with gastric cancer were divided into two groups according to different clinical characteristics. The expression of lncRNA LUCAT1 in gastric cancer was detected by reverse transcription polymerase chain reaction (RT-PCR). The AGS and SGC-7901 cell lines were used in CCK8 assay, apoptosis, cell cycle test, transwell assay, and wound healing assay. RESULTS: The expression level of LUCAT1 was associated with tumor diameter (p < 0.001), tissue differentiation grade (p = 0.026), and LNM status (p = 0.020) in GC. The results showed that the lncRNA LUCAT1 could promote the proliferation, invasion, and migration of GC cells, inhibit the apoptosis of GC cells, and affect the process of cell cycles. CONCLUSIONS: The lncRNA LUCAT1 may be used as a potential biomarker for early signs of LNM in GC and may play a crucial role in the development of GC.

Therapeutic Effect of Tanshinone IIA on Liver Fibrosis and the Possible Mechanism: A Preclinical Meta-Analysis.

BACKGROUND: Liver fibrosis is a serious human health problem, and there is a need for specific antifibrosis drugs in the clinic. Tanshinone IIA has recently been reported to have a role in the treatment of liver fibrosis. However, the evidence supporting its antifibrotic effect is not sufficient, and the underlying mechanism is not clear. We thus performed this meta-analysis of animal research to assess the therapeutic effect of tanshinone IIA on liver fibrosis and analyzed the possible associated mechanism to provide a reference for further clinical drug preparation and clinical research. METHODS: We collect related articles from the databases PubMed, Web of Science, Embase, Wanfang, VIP, and CNKI. The quality of the included studies was evaluated according to the SYRCLE risk of bias tool for animal studies. Data were analyzed using RavMan 5.3 and Stata 12.0 software. RESULTS: A total of 404 articles were retrieved from the databases. After screening, 11 articles were included in the analysis. The included studies' methodological quality was generally low, and an obvious publication bias was found. The results showed that tanshinone IIA significantly improved liver function in experimental animals and reduced the level of liver fibrosis by reducing inflammation and inhibiting immunity, antiapoptotic processes, and HSC activation. CONCLUSION: Tanshinone IIA can effectively improve liver fibrosis and liver function in animal models and is worthy of future higher quality animal studies and clinical drug trials.