Li Cui

Cardiac surgery induces systemic stress responses that may compromise intestinal homeostasis in animal patients, yet the underlying mechanisms remain poorly understood. This study investigated postoperative intestinal pathophysiology in a porcine model, focusing on the activation of the NF-κB pathway and its impact on intestinal stem cell function. Thirty-two large white pigs (40–50 kg) were randomized into control and model groups; the model group underwent simulated cardiac procedures involving aortotomy and left ventricular outflow tract exposure under standardized anesthesia. Our findings revealed significant NF-κB pathway activation and upregulation of matrix metalloproteinases (MMPs) in the intestine following surgery. Intestinal stem cells isolated from crypts showed downregulated expression of key barrier proteins. Notably, organoids derived from the model group exhibited impaired early proliferative capacity and delayed morphogenesis, despite preserved differentiation potential upon extended culture. This suggests a stress-induced state that favors the maintenance of stemness over commitment to differentiation. These results delineate an NF-κB/MMP-mediated mechanism linking surgical stress to intestinal barrier dysfunction and stem cell dysregulation in this large animal model. Crucially, the study provides insights that may help improve perioperative care and reduce gastrointestinal complications in animal patients undergoing major surgeries, thereby enhancing animal welfare. The identified pathways offer potential targets for developing supportive therapies in veterinary practice.

The human microbiota-associated (HMA) pig model provides a physiologically relevant platform that bridges preclinical and translational research. However, its use remains limited, with existing studies showing considerable variation in establishment methods. This scoping review systematically evaluates methodological frameworks, engraftment outcomes, and research applications of HMA pig models. Additionally, it highlights their strengths, limitations, and implications for future studies. We conducted a comprehensive literature search in PubMed, Web of Science, Scopus, and Directory of Open Access Journals, following PRISMA guidelines for Scoping Reviews. The review examines the methodological foundations of HMA pig model generation and proposes a minimal reporting framework to promote standardization. It synthesizes studies on human microbiota engraftment in pigs, identifying factors that influence colonization efficiency. Finally, it summarizes current applications, discusses persistent limitations and translational challenges, and outlines opportunities for future research. Overall, these integrated insights aim to foster standardized, reproducible protocols for HMA pig model preparation and guide advancements in the field.

Introduction: Ulcerative colitis (UC) is a chronic disease that requires pharmacological therapy to achieve remission. This study aimed to evaluate the effect of glucosamine selenium (GASe) on chronic colitis and reveal the underlying regulatory mechanisms. Methods: We evaluated the cumulative toxicity of GASe by gavage in mice for 40 days. Dextran sulfate sodium (DSS; 2.5%) was added to drinking water to induce chronic colitis, and GASe was administered to mice with chronic DSS colitis. 16S rRNA sequencing was performed to investigate the influence of GASe on gut microbiota, followed by diversity and LDA Effect Size (LEfSe) analyses. Differentially expressed genes (DEGs) associated with chronic DSS colitis were identified based on the expression profiling from the Gene Expression Omnibus (GEO) database and were subjected to functional enrichment analysis. Next, the effects of GASe on pyroptosis and chemokine signaling pathways were studied in vitro and in vivo. Results: GASe had no significant toxicity in mice, and administration of low-GASe and high-GASe increased the length of the colon, inhibited the expression of IL-12, IL-6, and TNF-α, and improved colonic tissue structure. Low-GASe improved the diversity of the gut microbiota and mainly affected the Burkholderiaceae family, Paenalcaligenes genus, and Erysipelatoclostridium genus. Low-GASe and high-GASe suppressed the pyroptosis-related proteins NLRP3, GSDMD, and caspase-1. Furthermore, we identified 114 DEGs from the GSE87466 and GSE53306 datasets and these DEGs were mainly enriched in the chemokine signaling pathway and some inflammatory pathways. Further experiments showed that administration of GASe inhibited the chemokine signaling pathway in chronic DSS colitis mice and NCM460 cells. Discussion: This study reveals abnormalities in the gut microbiota, pyroptosis, and chemokine signaling pathways involved in chronic colitis and may provide GASe as an alternative supplement for chronic colitis management.

Background: Kidney renal papillary cell carcinoma (KIRP), kidney chromophobe (KICH), and kidney renal clear cell carcinoma (KIRC) are three most common subtypes of renal cell carcinomas (RCC), and its development is a multifaceted process that intricately involves the interplay of numerous genes. Despite recent advances in research on renal cell carcinoma, the prognosis of KIRC patients remains dismal. Therefore, there is an urgent need to explore new prognostic biomarkers and treatment strategies to help clinicians choose more effective treatment methods and accurately predict long-term efficacy. Our study aimed to systematically evaluate the gene expression profiles of three RCC subtypes, especially KIRC, and to identify survival-related biomarker. Methods: In our present study, we systematically evaluate the genes expression profile difference among three subtypes of RCC, and identify the survival-related key genes signature based on GEPIA2. GeneMANIA was used to identify the functionality-related differentially expressed genes (DEGs). Furthermore, focusing on KIRC, we intersected functionality-related and survival-related DEGs based on two datasets. Results: We ascertained five DEGs (ANK3, FREM2, KIF13B, MPP7 and SOX6) as key survival-related genes in KIRC. High levels of these five DEGs expressions were strongly associated with favorable prognosis, but not correlated to metastasis. Downregulation of these five DEGs expressions was closely associated with immunomodulators, chemokines, and infiltrating levels of different immune cells, which indicated that these five DEGs were key immune-related novel prognostic biomarkers for KIRC. Conclusions: The five identified DEGs serve as potential novel prognostic biomarkers for KIRC. However, the crucial factors that lead to the downregulation and functional inactivation of these five key genes need to be explored in future studies.

Schizophrenia (SCZ), as a neurodevelopmental disorder and devastating disease, affects approximately 1% of the world population. Although numerous studies have attempted to elucidate the causes of SCZ occurrence, it is not clearly understood. Recently, the emerging roles of the gut microbiota in a range of brain disorders, including SCZ, have attracted much attention. While the molecular mechanism of gut microbiota in regulating the pathogenesis of SCZ is still lacking. Here, we first confirmed the difference of gut microbiome between SCZ patients and healthy controls, and then, we performed fecal microbiota transplantation (FMT) to clarify the roles of SCZ patients-derived microbiota in a specific pathogen free (SPF) mice model. 16 S rDNA sequencing confirmed that a significant difference of gut microbiome was present between two groups of FMT mice, which has a similar trend with the above human gut microbiome. Furthermore, we found that transplantation of fecal microbiota from SCZ patients into SPF mice was sufficient to induce schizophrenia-like (SCZ-like) symptoms, such as deficits in sociability and hyperactivity. Furthermore, the brains of mice colonized with SCZ microbiota displayed dysregulated transcript response and alternative splicing of SCZ-relevant genes. Moreover, 10 key genes were identified to be correlated with SCZ by an integrative transcriptome data analysis. Finally, 4 key genes were identified to be correlated with the 12 differential genera between two groups of FMT mice. Our results thus demonstrated that the gut microbiome might modify the transcriptomic profile in the brain, thereby modulating social behavior, and our present study can help better understand the link between gut microbiota and SCZ pathogenesis through the gut-brain axis.

Background: Although diabetes mellitus (DM) is regarded as a risk factor of colorectal cancer (CRC), the impacts of pre‐existing DM on CRC without drug intervention remain unknown. The purpose of this study was to investigate and analyze the effects of diabetes mellitus (DM) on colorectal cancer (CRC). And, to further explore the influencing factors and the mechanisms of DM affects CRC progression.Methods: In this study, we investigated the effects of DM on CRC progression in a streptozotocin‐induced DM mice model. Furthermore, we evaluated the change of T cells levels using flow cytometry and indirect immunofluorescence. We assessed the alternation of gut microbiome and the transcriptional response using 16s rRNA sequencing and RNA‐seq.Results: Results showed that the mice survival time was significantly decreased in CRC complicated with DM group (DM‐CRC), compared with only tumor bearing mice (CRC group). Furthermore, we found that DM could affect the immune response by changing the infiltration of CD4⁺ T cells, CD8⁺ T cells and mucosal‐associated invariant T cell (MAIT) in the CRC progression. In addition, DM could induce gut microbiome dysbiosis and change the transcriptional response in CRC complicated with DM.Conclusion: For the first time, the effects of DM on CRC were systematically characterized in a mice model. Our findings highlight the effects of pre‐existing DM on CRC, and these findings should facilitate further studies in exploring and developing potentially targeted therapy for CRC in diabetic patients. Our results suggest that the effects induced by DM should be considered in the treatment for CRC complicated with DM patients.

To explore whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) is expressed in fungal keratitis in mice and investigate its role in this disease. NOX2 expression was detected in C57BL/6 mice. After testing the inhibitory effect of diphenyleneiodonium chloride (DPI) on NOX2, its impact on clinical performance, myeloperoxidase levels, the number of colonies forming units, the level of H3, the generation of reactive oxygen species (ROS) and the release of cytokines [NF-κB, interleukin-17A (IL-17A), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), Nrf2, IL-10, and TGF-β] were compared. A one-way ANOVA and an unpaired, two-tailed Student's t-test was used to determine the statistical significance. NOX2 expression was significantly increased after Aspergillus fumigatus injection in corneas and that this increase could be reduced by treatment with DPI. DPI treatment produced more severe inflammation and resulted in higher clinical scores, more neutrophils infiltration, a weakened ability to clear fungi, the release of fewer ROS and the formation of neutrophil extracellular traps. Treatment with DPI increased the expression of the proinflammatory cytokines NF-κB, IL-17A, IL-6, and TNF-α and decreased the expression of the anti-inflammatory cytokines Nrf2, IL-10 and TGF-β compared to their expression levels without DPI treatment. NOX2 plays an important role against Aspergillus fumigatus in the mouse cornea through killing fungi and limiting the degree of inflammation.

Breast cancer complicated with diabetes mellitus (DM) is a common disease. To evaluate the effect of preexisting DM on breast cancer progression without drug interference, we used a streptozotocin (STZ)-induced type 2 diabetes mellitus BALB/c mouse model. We found that 4T1 breast cancer complicated with DM decreased the mouse survival time compared with 4T1-bearing mice. The diversity of gut microbiome was affected by DM. The infiltration of mucosal-associated invariant T cell (MAIT), CD8+ T cell, and CD4+ T cell in the tumor was significantly decreased in the DM-4T1 group compared with the 4T1 group. The transcriptome data of tumor tissues indicated that the expressions of inflammatory C–C chemokine- and metabolism-related genes were greatly changed. The abnormal expression of these genes may be related with the decreased T-cell infiltration in DM-4T1. In conclusion, the gut microbiome and tumor microenvironment of diabetic breast cancer patients have unique features. The effect of diabetes on breast cancer should be considered in the treatment for diabetic breast cancer patients.

Wang S, et al. J Vet Sci. 2021 Apr;22(3):e37. https://doi.org/10.4142/jvs.2021.22.e37