Bile Acid Metabolic Profiles and Their Correlation with Intestinal Epithelial Cell Proliferation and Barrier Integrity in Suckling Piglets.

Bile acids (BAs) are crucial for maintaining intestinal epithelial homeostasis. However, the metabolic changes in BAs and the communication between intestinal epithelial cells (IECs) in infants after birth remain unclear. This study aims to elucidate the BA profiles of newborn piglets (NPs) and suckling piglets (SPs), and to investigate their regulatory effects on IEC proliferation and barrier integrity, as well as the potential underlying mechanisms. In this study, compared with NPs, there were significant increases in serum triglycerides, total cholesterol, glucose, and albumin levels for SPs. The total serum BA content in SPs exhibited an obvious increase. Moreover, the expression of BA synthase cytochrome P450 27A1 (CYP27A1) was increased, and the ileal BA receptor Takeda G-coupled protein receptor 5 (TGR5) and proliferation marker Ki-67 were upregulated and showed a strong positive correlation through a Spearman correlation analysis, whereas the expression of farnesoid X receptor (FXR) and occludin was markedly downregulated in SPs and also revealed a strong positive correlation. These findings indicate that the increased synthesis and metabolism of BAs may upregulate TGR5 and downregulate FXR to promote IEC proliferation and influence barrier function; this offers a fresh perspective and evidence for the role of BAs and BA receptors in regulating intestinal development in neonatal pigs.

Oleanolic acid alleviate intestinal inflammation by inhibiting Takeda G-coupled protein receptor (TGR) 5 mediated cell apoptosis.

Oleanolic acid (OA) is a bioactive compound present in plant-based foods known for its beneficial impact on gastrointestinal health, specifically in alleviating diarrhea. Nonetheless, the underlying mechanisms by which OA mitigates gut epithelial damage have yet to be elucidated. In this study, OA significantly markedly ameliorated adverse effects induced by Dextran Sulfate Sodium (DSS), including weight loss and epithelial morphological damage in a murine model. Remarkably, compared to normal mice, standalone administration of OA had no discernible impact on the animals. Concurrently, we identified a significant up-regulation in the expression levels of TGR5 and BAX in the intestines of DSS-exposed mice, coupled with a decline in Bcl2 expression. Correlation analyses revealed a robust association between TGR5 and BAX expression. Oral administration of OA efficaciously counteracted these alterations. To probe the role of TGR5 in cellular apoptosis, further, a lentivirus transfection approach was utilized to induce TGR5 overexpression in intestinal epithelial cells (IPEC-J2). RNA sequencing indicated that TGR5 overexpression significantly influenced biological processes, particularly in modulating cellular activation and intercellular adhesion, in contrast to the control group cells. Functional assays substantiated that TGR5 overexpression compromised cell viability and accelerated apoptosis. Notably, OA treatment in TGR5-overexpressed cells restored cell viability, suppressed TGR5 and BAX expression, and augmented Bcl2 expression. In sum, our data suggest that OA mitigates intestinal epithelial apoptosis and bolsters cellular proliferation by downregulating TGR5. This research provides valuable insights into the prospective utility of OA as a functional food supplement or adjunctive therapeutic agent for enhancing gastrointestinal health.

Caenorhabditis elegans LIN-24, a homolog of bacterial pore-forming toxin, protects the host from microbial infection.

Aerolysin-like pore-forming protein (af-PFP) superfamily members are double-edge swords that assist the bacterial infection but shied bacteria from the host by various mechanisms in some species including the toad Bombina maxima and zebrafish. While members of this family are widely expressed in all kingdoms, especially non-bacteria species, it remains unclear whether their anti-bacterial function is conserved. LIN-24 is an af-PFP that is constitutively expressed throughout the Caenorhabditis elegans lifespan. Here, we observed that LIN-24 knockdown reduced the maximum lifespan of worms. RNA-seq analysis identified 323 differentially expressed genes (DEGs) post-LIN-24 knockdown that were enriched in "immune response" and "lysosome pathway," suggesting a possible role for LIN-24 in resisting microbial infection. In line with this, we found that Pseudomonas aeruginosa 14 (PA14) infection induced LIN-24 expression, and that survival after PA14 infection was significantly reduced by LIN-24 knockdown. In contrast, LIN-24 overexpression (LIN-24-OE) conferred protection against PA14 infection, with worms showing longer survival time and reduced bacterial load. Weighted gene co-expression network analysis of LIN-24-OE worms showed that the highest correlation module was enriched in factors related to immunity and the defense response. Finally, by predicting transcription factors from RNA-seq data and knocking down candidate transcription factors in LIN-24-OE worms, we revealed that LIN-24 may protect worms against bacterial infection by stimulating DAF-16-mediated immune responses. These findings agree with our previous studies showing an anti-microbial role for the amphibian-derived af-PFP complex ßγ-CAT, suggesting that af-PFPs may play a conserved role in combatting microbial infections. Further research is needed to determine the roles this protein family plays in other physio-pathological processes, such as metabolism, longevity, and aging.

Handelin extends lifespan and healthspan of Caenorhabditis elegans by reducing ROS generation and improving motor function.

Aging and aging-related disorders contribute to formidable socioeconomic and healthcare challenges. Several promising small molecules have been identified to target conserved genetic pathways delaying aging to extend lifespan and healthspan in many organisms. We previously found that extract from an edible and medicinal plant Chrysanthemum indicum L. (C. indicum L.) protect skin from UVB-induced photoaging, partially by reducing reactive oxygen species (ROS) generation. Thus, we hypothesized that C. indicum L. and its biological active compound may extend lifespan and health span in vivo. We find that both water and ethanol extracts from C. indicum L. extended lifespan of Caenorhabditis elegans, with better biological effect on life extending for ethanol extracts. As one of the major biological active compounds, handelin extended lifespan of C. elegans too. RNA-seq analysis revealed overall gene expression change of C. elegans post stimulation of handelin focus on several antioxidative proteins. Handelin significantly reduced ROS level and maintained the number and morphology of mitochondria. Moreover, handelin improveed many C. elegans behaviors related to healthspan, including increased pharyngeal pumping and body movement. Muscle fiber imaging analyses revealed that handelin maintains muscle architecture by stabilizing myofilaments. In conclusion, our present study finds a novel compound handelin, from C. indicum L., which bring about biologically beneficial effects by mild stress response, termed as hormetin, that can extend both lifespan and healthspan in vivo on C. elegans. Further study on mammal animal model of natural aging or sarcopenia will verify the potential clinical value of handelin.

Application of the Caprini risk assessment model for deep vein thrombosis among patients undergoing laparoscopic surgery for colorectal cancer.

ABSTRACT: Application of the Caprini risk assessment model was explored in patients with deep vein thrombosis (DVT) after laparoscopic colorectal cancer surgery.This study was a prospective study. The risk factors for DVT were assessed with a survey at baseline and on the morning of surgery, first day after surgery and sixth day by using repeated blood vessels on color Doppler ultrasound of the lower limbs, and the intraoperative and postoperative conditions were recorded.Among 148 surgical patients, 24.3% had asymptomatic DVT. According to the risk stratification, the incidence of DVT was related to the Caprini score (P < .001). The area under the curve of the Caprini model was 0.701 ±â€Š0.047 (95% CI: 0.609-0.793, P<.001). The Youden index was 0.368, while the critical point was 10.5 in the Caprini model, corresponding to a sensitivity of 0.806 and a specificity of 0.563. Age, cardiovascular disease, intraoperative blood loss, postoperative fever, preoperative preparation, and hospital stay were higher in DVT patients than in patients without DVT. Moreover, the incidence of DVT in patients with a lithotomy position was higher than that in patients with a scissors position. In binary logistic regression analysis, the independent risk factors for DVT development were age, intraoperative blood loss, and preoperative preparation time.The Caprini model can be used for the prediction of venous thromboembolism in laparoscopic colorectal cancer surgery patients. The thrombosis risk assessment model must be established in line with patients undergoing endoscopic malignant tumor surgery.