Crosstalk between hypoxia-inducible factor-1α and short-chain fatty acids in inflammatory bowel disease: key clues toward unraveling the mystery.

The human intestinal tract constitutes a complex ecosystem, made up of countless gut microbiota, metabolites, and immune cells, with hypoxia being a fundamental environmental characteristic of this ecology. Under normal physiological conditions, a delicate balance exists among these complex "residents", with disruptions potentially leading to inflammatory bowel disease (IBD). The core pathology of IBD features a disrupted intestinal epithelial barrier, alongside evident immune and microecological disturbances. Central to these interconnected networks is hypoxia-inducible factor-1α (HIF-1α), which is a key regulator in gut cells for adapting to hypoxic conditions and maintaining gut homeostasis. Short-chain fatty acids (SCFAs), as pivotal gut metabolites, serve as vital mediators between the host and microbiota, and significantly influence intestinal ecosystem. Recent years have seen a surge in research on the roles and therapeutic potential of HIF-1α and SCFAs in IBD independently, yet reviews on HIF-1α-mediated SCFAs regulation of IBD under hypoxic conditions are scarce. This article summarizes evidence of the interplay and regulatory relationship between SCFAs and HIF-1α in IBD, pivotal for elucidating the disease's pathogenesis and offering promising therapeutic strategies.

Circular RNA FOXO3 regulates endometrial carcinoma progression through the microRNA-29a-3p/HDAC4 axis.

Previous studies determined that circular RNA FOXO3 (circ_FOXO3) plays a critical role in tumorigenesis. The definite molecular mechanism of cir_FOXO3 in endometrial carcinoma (EC), nevertheless, had not been fully explored. Circ_FOXO3 expression was determined using quantitative real-time polymerase chain reaction in human EC tissues and cell lines, whereas small interfering RNAs were used to specifically silence circ_FOXO3 expression in cultured EC cells. The cell counting kit-8 assay was employed to determine the effect of ectopic circ_FOXO3 expression on cell viability. Cell proliferation and apoptosis were evaluated by flow cytometry. Further, migration and invasion of EC cells were characterized using the Transwell assay. The interaction between microRNA (miR)-29a-3p and circ_FOXO3/histone deacetylase 4 (HDAC4) was validated using dual luciferase reporter assay. Additionally, qRT-PCR and WB were employed to determine HDAC4 levels. We found that circ_FOXO3 was highly expressed in EC cells and tissues. Moreover, suppressing circ_FOXO3 expression abrogated EC by regulating cell proliferation, apoptosis, migration, and invasion. Furthermore, circ_FOXO3 could act as a sponge for miR-29a-3p, and inhibition of miR-29a-3p expression reversed the effects of circ_FOXO3 suppression on EC progression. Overexpression of miR-29a-3p inhibited EC cell growth, migration, and invasion through the regulation of HDAC4, as it is a target of miR-29a-3p. In conclusion, circ_FOXO3 promotes EC progression by sponging miR-29a-3p and upregulating HDAC4, making it a promising therapeutic target in EC.

The Clearance of High-Risk Human Papillomavirus is Sooner After Thin Loop Electrosurgical Excision Procedure (t-LEEP).

Purpose/aim of the study: To investigate high-risk human papillomavirus (HPV) infection clearance following thin loop electrosurgical excision procedure (t-LEEP) among patients with cervical benign lesion. Materials and Methods: This retrospective study analyzed clinical data from patients with cervical benign lesion and HPV infection, who had undergone t-LEEP (T-Group), compared with patients with HPV infection undergone no treatment (NT-Group). Both groups attended regular follow-up between January 2008 and January 2012. Kaplan-Meier analysis was used to compare the HPV clearance time. Results: The average clearance time was 7.7 months (M) (95% confidence interval [CI]: 6.5-8.9 M) in T-Group, and 10.4 M (95%CI: 9.4-11.3 M) in NT-Group, with significant difference between groups (p = 0.003). Among patients with low viral load, the HPV clearance times were 7.6 M (95%CI: 6.3-9.0 M) in T-Group and 9.7 M (95%CI: 8.6-10.8 M) in NT-Group (p = 0.042). Among patients with high viral load, the HPV clearance times were 8.0 M (95%CI: 5.3-10.6 M) in T-Group and 11.4 M (95%CI: 9.7-13.1 M) in NT-Group (p = 0.041). The average time of HPV clearance in T-Group was shorter than NT-Group in all age groups, with significant differences in ≤29Y-group (p = 0.008) and 30-39Y-group (p = 0.005). The accumulated clearance rate of HPV infection at sixth month and 12th month were 24.5% and 67.9% in T-Group, 7.8% and 43.1% in NT-Group, with significant differences (p = 0.001 at 6th month, p = 0.032 at 12th month). Conclusions: T-LEEP accelerates the clearance of high-risk HPV infection and make the HPV infection rates dropped rapidly in the first year.

[Spontaneous clearance of high risk human papillomavirus infection].

OBJECTIVE: To study the clearance of high risk human papillomavirus (HPV) infection among the women with normal cervical pathologic diagnosis. METHODS: One hundred and seventy-two HPV-positive cases with normal cervical pathologic diagnosis were enrolled in the study. The infection status of HPV was monitored during follow-up from Aug 2006 to Aug 2008. The time of HPV infection spontaneous clearance, as well as effect factors, were analyzed. RESULTS: During follow-up, there were 62.2% (107 cases, 107/172) of the HPV infection cleared. The medium clearance time was 11.3 months (95%CI: 10.6 - 16.6 months). The medium clearance time of aged < 30 years, 30 - 39 years, 40 - 49 years and > 49 years were 11.3, 12.0, 10.9 and 8.5 months, respectively. There were not significant difference among aged intervals (P = 0.384). The virus copies of HPV-clearance cases and persistent-infection were 22.6 and 95.0, respectively. There was not significant difference between groups (P = 0.061). CONCLUSIONS: Most of the high risk HPV infection with normal cervical pathologic diagnosis would spontaneously cleared. Age and HPV copies may play little role in the HPV clearance.