Inflammatory bowel diseases (IBD), mainly comprising ulcerative colitis (UC) and Crohn's Disease, are most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. Strategies that target the microbiota have emerged as potential therapies and, of these, probiotics have gained the greatest attention. Herein, we isolated a strain of Lactobacillus paracasei R3 (L.p R3) with strong biofilm formation ability from infant feces. Interestingly, we also found L.p R3 strain can ameliorate the general symptoms of murine colitis, alleviate inflammatory cell infiltration and inhibit Th17 while promote Treg function in murine dextran sulfate sodium (DSS)-induced colitis. Overall, this study suggested that L.p R3 strain significantly improves the symptoms and the pathological damage of mice with colitis and influences the immune function by regulating Th17/Treg cell balance in DSS-induced colitis in mice.

Inflammatory bowel diseases (IBDs) represent a group of chronic inflammatory disorders of the gastrointestinal (GI) tract including ulcerative colitis (UC), Crohn’s disease (CD), and unclassified IBDs. The pathogenesis of IBDs is related to genetic susceptibility, environmental factors, and dysbiosis that can lead to the dysfunction of immune responses and dysregulated homeostasis of local mucosal tissues characterized by severe inflammatory responses and tissue damage in GI tract. To date, extensive studies have indicated that IBDs cannot be completely cured and easy to relapse, thus prompting researchers to find novel and more effective therapeutics for this disease. Due to their potent multipotent differentiation and immunomodulatory capabilities, mesenchymal stem/stromal cells (MSCs) not only play an important role in regulating immune and tissue homeostasis but also display potent therapeutic effects on various inflammatory diseases, including IBDs, in both preclinical and clinical studies. In this review, we present a comprehensive overview on the pathological mechanisms, the currently available therapeutics, particularly, the potential application of MSCs-based regenerative therapy for IBDs.

Endometrial carcinoma (EC) is the most common malignant tumors in female derived from the endometrial epithelium. Several previous studies have described estrogen receptors (ER), progesterone Receptor (PR) and phosphatase and tensin homolog (PTEN) are associated with clinicopathological factors and prognosis in EC patients. However, during EC patients follow-up, we found that some EC patients with down-regulation of PTEN, but up-regulation of ER or PR , and some EC patients with down-regulation of ER or PR, but up-regulation of PTEN also had a poor prognosis. Therefore, to reveal the prognosis of EC patients with different phenotypes based on PTEN, ER and PR expression, 120 cases formalin-fixed paraffin-embedded EC tissues and 543 cases uterine corpus endometrial carcinoma (UCEC) patients from the cancer genome atlas (TCGA) UCEC datasets were analyzed. Results showed that EC tissues can be classified to PTEN^LER^LPR^L, PTEN^HER^LPR^L, PTEN^HER^HPR^H, PTEN^LER^HPR^H, PTEN^HER^HPR^L, PTEN^HER^LPR^H, and PTEN^LER^HPR^L phenotypes basing on IHC analysis. Additionally, EC patients with PTEN^LER^LPR^L showed high malignancy, while patients with PTEN^HER^HPR^H showed low malignancy. Therefore, combined detection of PTEN, ER, PR may help identify a small subset of EC with more aggressive behavior and may aid in risk stratification.

Dysregulation of cellular metabolism is a key marker of cancer, and it is suggested that metabolism should be considered as a targeted weakness of colorectal cancer. Increased polyamine metabolism is a common metabolic change in tumors. Thus, targeting polyamine metabolism for anticancer therapy, particularly polyamine blockade therapy, has gradually become a hot topic. Quercetin-3-methyl ether is a natural compound existed in various plants with diverse biological activities like antioxidant and antiaging. Here, we reported that Quercetin-3-methyl ether inhibits colorectal cancer cell viability, and promotes apoptosis in a dose-dependent and time-dependent manner. Intriguingly, the polyamine levels, including spermidine and spermine, in colorectal cancer cells were reduced upon treatment of Quercetin-3-methyl ether. This is likely resulted from the downregulation of SMOX, a key enzyme in polyamine metabolism that catalyzes the oxidation of spermine to spermidine. These findings suggest Quercetin-3-methyl ether decreases cellular polyamine level by suppressing SMOX expression, thereby inducing colorectal cancer cell apoptosis. Our results also reveal a correlation between the anti-tumor activity of Quercetin-3-methyl ether and the polyamine metabolism modulation, which may provide new insights into a better understanding of the pharmacological activity of Quercetin-3-methyl ether and how it reprograms cellular polyamine metabolism.

Hyperlipidemia, a chronic disorder caused by abnormal lipid metabolism, increases risks of atherosclerosis and cardiovascular diseases. Current single-target drugs have limited efficacy and side effects, prompting interest in probiotics such as Lactobacillus rhamnosus, though their mechanisms remain unclear. A novel Lactobacillus rhamnosus strain from healthy human feces was identified via API 50CH and ANI analysis. Integrated genomic and proteomic analyses were performed on the novel Lactobacillus rhamnosus B16 (L. rB16) strain to characterize its lipid metabolism-related traits. A cholesterol degradation assay, gastrointestinal fluid tolerance test, and biofilm formation assay were used to evaluate the functional properties of L. rB16, while foam cell models were employed to assess its cholesterol-lowering effects. Western blotting was used to determine the expression levels of key lipid metabolism-associated proteins (LXRα, ABCA1, ABCG1, HMGCR, and SREBP1) in foam cells treated with heat-inactivated L. rB16 (HI-L. rB16). For in vivo validation, a high-fat diet (HFD)-induced hyperlipidemic mouse model was established, and analyses including serum lipid profiling, histological examination, and immunohistochemical staining were conducted. Metabolomic and short-chain fatty acids (SCFAs) analyses identified key metabolites, validated by sodium acetate treatment. We identified a novel strain of L. rB16 from healthy human feces, which had cholesterol-lowering ability in a cholesterol-enriched MRS broth. Moreover, we found that HI-L. rB16 could reduce foam cell cholesterol levels through the Liver X receptor alpha (LXRα) signaling pathway and regulate hepatic lipid metabolism balance by regulating the expression of key lipid proteins. Metabolomics showed the acetic acid produced by HI-L. rB16 was the main metabolite that exerted the cholesterol-lowering effect. HI-L. rB16 alleviates HFD-induced hyperlipidemia in mice by reducing cholesterol through acetate-mediated LXRα signaling, demonstrating its therapeutic potential as a probiotic for lipid metabolism disorders. Novel L. rB16 isolated from healthy human feces exhibits gastrointestinal tolerance, biofilm formation, and in vitro cholesterol degradation. HI-L. rB16 reduces cholesterol in foam cells via LXRα signaling and alleviates hyperlipidemia in HFD mice. L. rB16 reduces cholesterol through acetate production, demonstrating therapeutic potential against hyperlipidemia in mice.