Search

Ulcerative colitis (UC), characterized by disrupted intestinal barrier integrity and chronic inflammation, was modeled in mice via dextran sulfate sodium (DSS) induction. This study explored the therapeutic potential of berberine-evodiamine (BBR-EVO), bioactive components of the traditional Chinese medicine Yulian decoction, in DSS colitis. BBR-EVO intervention ameliorated weight loss, diarrhea, colonic shortening, and histopathological damage in colitic mice. The substance increased antioxidant activity while reducing high levels of pro-inflammatory cytokines in the colon, including as TNF-α, IL-1β, and IL-6. BBR-EVO inhibited the DSS-induced decrease in the tight junction proteins ZO-1 and occludin, according to immunohistochemistry. 16S rRNA sequencing demonstrated BBR-EVO partially attenuated DSS-elicited intestinal dysbiosis, reducing opportunistic pathogens and restoring diminished beneficial taxa. Critically, BBR-EVO alleviated secondary hepatic injury in colitic mice, mitigating immune cell infiltration, oxidative stress, cytokine production, and ultrastructural damage, likely by beneficially modulating gut-liver crosstalk. This study reveals BBR-EVO, derived from a traditional Chinese medicine, confers multi-target protective effects in experimental colitis and associated hepatic pathology, warranting further evaluation as a potential therapy for inflammatory bowel diseases like UC. The mechanisms may involve simultaneous augmentation of intestinal barrier integrity, inhibition of inflammation, microbiota regulation, and gut-liver axis optimization.

Human papillomavirus (HPV)-mediated cervical carcinogenesis is a multistep progressing from persistent infection, precancerous lesion to cervical cancer (CCa). Although molecular alterations driven by viral oncoproteins are necessary in cervical carcinogenesis, the key regulators behind the multistep process remain not well understood. It is pivotal to identify the key genes involved in the process for early diagnosis and treatment of this disease. Here we analyzed the mRNA expression profiles in cervical samples including normal, cervical intraepithelial neoplasia (CIN), and CCa. A co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) to reveal the crucial modules in the dynamic process from HPV infection to CCa development. Furthermore, the differentially expressed genes (DEGs) that could distinguish all stages of progression of CCa were screened. The key genes involved in HPV-CCa were identified. It was found that the genes involved in DNA replication/repair and cell cycle were upregulated in CIN compared with normal control, and sustained in CCa, accompanied by substantial metabolic shifts. We found that upregulated fibronectin type III domain-containing 3B (FNDC3B) and downregulated bisphosphoglycerate mutase (BPGM) could differentiate all stages of CCa progression. In patients with CCa, a higher expression of FNDC3B or lower expression of BPGM was closely correlated with a shorter overall survival (OS) and disease-free survival (DFS). A receiver operating characteristic (ROC) analysis of CIN and CCa showed that FNDC3B had the highest sensitivity and specificity for predicting CCa development. Taken together, the current data showed that FNDC3B and BPGM were key genes involved in HPV-mediated transformation from normal epithelium to precancerous lesions and CCa.

As a member of the POU (Pit-Oct-Unc) transcription factor family, OCT4 (Octamer-binding transcription factor 4) is associated with the cellular proliferative. However, the roles of OCT4 in regulating the transition from preantral follicle to early antral follicle are still remains unclear. To evaluate the effect of OCT4 on cellular development in ovary, mice were injected with eCG in vivo or granulosa cells were co-cultured with FSH in vitro. The results showed that eCG up-regulated ovarian OCT4 expression. Meanwhile, OCT4 expression in granulosa cells was also up-regulated by FSH, and knockdown of OCT4 by siRNA significantly decreased FSH-induced cellular viability. Moreover, gonadotropin increased p-GSK3β (Glycogen synthase kinase 3-beta) level, β-catenin expression and its translocation to nuclear in ovarian cells. In addition, the inhibition of GSK3β activity by CT99021 significantly increased the expression of β-catenin and OCT4 in granulosa cells. And knockdown β-catenin by siRNA dramatically abolished FSH-induced OCT4 expression and cellular development. Furthermore, FSH-induced the phosphorylation of GSK3β, expression of β-catenin and OCT4, and translocation of β-catenin were mediated by the PI3K/Akt pathway. Taken together, the present study demonstrates that FSH regulated OCT4 expression via GSK3β/β-catenin pathway, which was mediated by the PI3K/Akt pathway. And these regulations are involved in ovarian cell development.