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Prostate cancer (PCa) is one of the most common malignant tumors in the world. Thioredoxin interacting protein (TXNIP) is downregulated in a variety of human tumors and plays an important role in tumor suppression. However, the expression level and biological functions of TXNIP in PCa have not been identified yet. Therefore, this study aims to investigate the expression and biological functions of TXNIP in PCa. We reported that the expression of TXNIP was significantly decreased in PCa and associated with clinicopathological features. Overexpression of TXNIP could significantly inhibited PC‐3 cells proliferation, migration, invasion, and glucose uptake. Additionally, overexpression of TXNIP could remarkably block cell cycle in the G0/G1 phase and promoted cell apoptosis. Furthermore, TXNIP expression correlated inversely with GLUT1 expression in PCa. Taken together, our results for the first time revealed that TXNIP was decreased in PCa. Moreover, TXNIP might act as a tumor suppressor of PCa and correlated with tumor occurrence and development. Our findings cast a new light on better understanding the occurrence and development of PCa and indicated that TXNIP might be favorable for PCa molecular target therapy.

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Glucose oxidase (GOD) could benefit intestinal health and growth performance in animals. However, it is unknown whether GOD can protect piglets against bacterial challenge. This study aimed to evaluate the protective effects of GOD on growth performance, clinical symptoms, serum parameters, and intestinal health in piglets challenged by enterotoxigenic Escherichia coli (ETEC). A total of 44 male weaned piglets around 38 days old were divided into four groups (11 replicates/group): negative control (NC), positive control (PC), CS group (PC piglets +40 g/t colistin sulfate), and GOD group (PC piglets +200 g/t GOD). All piglets except those in NC were challenged with ETEC (E. coli K88) on the 11th day of the experiment. Parameter analysis was performed on the 21st day of the experiment. The results showed that the ETEC challenge elevated (p < 0.05) the rectal temperature and fecal score of piglets at certain time-points post-challenge, reduced (p < 0.05) serum glucose and IgG levels but increased (p < 0.05) serum alanine aminotransferase activity, as well as caused (p < 0.05) intestinal morphology impairment and inflammation. Supplemental GOD could replace CS to reverse (p < 0.05) the above changes and tended to increase (p = 0.099) average daily gain during the ETEC challenge. Besides, GOD addition reversed ETEC-induced losses (p < 0.05) in several beneficial bacteria (e.g., Lactobacillus salivarius) along with increases (p < 0.05) in certain harmful bacteria (e.g., Enterobacteriaceae and Escherichia/Shigella). Functional prediction of gut microbiota revealed that ETEC-induced upregulations (p < 0.05) of certain pathogenicity-related pathways (e.g., bacterial invasion of epithelial cells and shigellosis) were blocked by GOD addition, which also normalized the observed downregulations (p < 0.05) of bacterial pathways related to the metabolism of sugars, functional amino acids, nucleobases, and bile acids in challenged piglets. Collectively, GOD could be used as a potential antibiotic alternative to improve growth and serum parameters, as well as attenuate clinical symptoms and intestinal disruption in ETEC-challenged piglets, which could be associated with its ability to mitigate gut microbiota dysbiosis. Our findings provided evidence for the usage of GOD as an approach to restrict ETEC infection in pigs.

Introduction: The role of pyroptosis and its effects on tumor-infiltrating cells (TICs) in the pathogenesis and treatment outcomes of patients with bladder urothelial carcinoma (BLCA) remains unclear.Methods: We conducted a bioinformatics analysis on the pyroptosis-related genes (PRGs) and TICs using data from public domains, and evaluated their impact on the pathogenesis and clinical outcomes of BLCA patients. A risk score based on PRGs and a prognostic risk model that incorporated patient demographics, tumor characteristics, and differentially expressed genes (DEGs) were developed.Results: Twenty-three DEGs of 52 PRGs were identified in BLCA and normal samples from the TCGA database. Missense mutations and single nucleotide polymorphisms in PRGs are the most common genetic abnormalities. Patients with high PRG risk scores showed an inferior survival compared to those with low risk scores. The prognostic risk model based on patient demographics, tumor characteristics, and DEGs showed good predictive values for patient survival at 1, 3, and 5 years in BLCA patients. Caspase-8 (CASP8) was the only intersection gene of the prognostic genes, DEGs, and different genes expressed in tissue. Patients with a high CASP8 expression had improved survival, and an increased CASP8 expression level was observed in activated CD4 memory T cells, follicular T helper cells, resting NK cells, M0 macrophages, and activated dendritic cells. CASP8 expression also showed a positive correlation with the IL7R expression—a key cell marker of CD4 memory T cells. CASP8 expression also showed correlations with immune checkpoints (PDCD1, CD274, and CTLA4) and response to immune checkpoint inhibitors.Conclusion: Our data suggest that PRGs, especially CASP8, showed strong associations with patient outcomes and TICs in BLCA. If validated, these results could potentially aid in the prognostication and guide treatment in BLCA patients.

Chromatin regulators (CRs) are essential upstream regulatory factors of epigenetic modification. The role of CRs in the pathogenesis of renal ischemia-reperfusion injury (IRI) remains unclear. We analyzed a bioinformatic analysis on the differentially expressed chromatin regulator genes in renal IRI patients using data from public domains. The hub CRs identified were used to develop a risk prediction model for renal IRI, and their expressions were also validated using Western blot, qRT-PCR, and immunohistochemistry in a murine renal IRI model. We also examined the relationships between hub CRs and infiltrating immune cells in renal IRI and used network analysis to explore drugs that target hub CRs and their relevant downstream microRNAs. The results of machine learning methods showed that five genes (DUSP1, GADD45A, GADD45B, GADD45G, HSPA1A) were upregulated in renal IRI, with key roles in the cell cycle, p38 MAPK signaling pathway, p53 signaling pathway, FoxO signaling pathway, and NF-κB signaling pathway. Two genes from the network, GADD45A and GADD45B (growth arrest and DNA damage-inducible protein 45 alpha and beta), were chosen for the renal IRI risk prediction model. They all showed good performance in the testing and validation cohorts. Mice with renal IRI showed significantly upregulated GADD45A and GADD45B expression within kidneys compared to sham-operated mice. GADD45A and GADD45B showed correlations with plasmacytoid dendritic cells (pDCs) in infiltrating immune cell analysis and enrichment in the MAPK pathway based on the weighted gene co-expression network analysis (WGCNA) method. Candidate drugs that target GADD45A and GADD45B include beta-escin, sertraline, primaquine, pimozide, and azacyclonol. The dysregulation of GADD45A and GADD45B is related to renal IRI and the infiltration of pDCs, and drugs that target GADD45A and GADD45B may have therapeutic potential for renal IRI.

Background and Aims Patients with systemic lupus erythematosus (SLE) are at an increased risk of developing lupus nephritis (LN), which results in high morbidity and mortality. There is preliminary data showing the efficacy of low dose of Arsenic Trioxide (ATO) in reducing renal flares amongst LN patients, but the underlying mechanism for such benefit remains unclear. Method We performed bioinformatic analysis and network pharmacology to elucidate the potential targets from differentially expressed genes (DEGs) of human SLE and LN peripheral blood mononuclear cells (PBMCs) datasets and pharmacological databases. The relationship between the potential targets and immune cells was further analyzed. Results Twelve intersection genes of DEGs in SLE, predicting targets of ATO and immune related genes were identified. KEGG pathway analysis suggested that the mechanisms of ATO in SLE were associated with IL-17 signalling pathway (p = 1.67E-18), TNF signalling pathway (p = 5.77E-11) and NOD-like receptor signalling pathway (p = 1.93E-09). Ten types of immune cells showed significant difference with intersection genes expression in SLE using ssGSEA approach. MMP9 was the most significantly associated with immune cells and showed positive correlations with macrophages and neutrophils. A significant TF-MMP9-miRNA regulatory network was constructed using cytoscape software. Pilot data from our in vitro studies suggested that ATO might downregulate MMP9 expression in PBMCs obtained from LN patients during disease remission (n = 3). Conclusion ATO interacts with immune cells in LN patients via different inflammatory pathways and may downregulate MMP9 expression in PBMCs.

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