Study on the mechanism of inhibition of Escherichia coli by Polygonum capitatum based on network pharmacology and molecular docking technology: A review.

This study aims to analyze the effective components of Polygonum capitatum (PC) inhibiting Escherichia coli based on network pharmacology methods and predict its molecular mechanism of action. PC compounds and targets were collected from the TCMSP database, Swiss Target Prediction, and the literature. E coli targets were searched using the GeneCards database. The targets of E coli and the targets of the active ingredients of PC were taken as intersections to obtain the intersecting targets. The resulting overlapping targets were uploaded to the STRING database to construct the protein interaction network diagram of E coli target inhibition. The key targets for the inhibitory effect of PC on E coli were obtained. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed by uploading key targets into the DAVID database. The results showed that there were 50 targets for PC to inhibit E coli. Among them, there are 5 core targets, mainly including AKT1, TNF, EGFR, JUN, and ESR1. A total of 196 gene ontology functional analysis results and 126 Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis results were obtained. These include cellular response to cadmium-ion, cellular response to reactive oxygen species, pathways in cancer, prostate cancer, and PI3K-Akt signaling pathway. Molecular docking results indicate that Lutedin, Hirsutin, Flazin, and Ellagic acid in PC have high affinity for the target genes AKT1, TNF, MAPK3 and EGFR. PC exerts its inhibitory effect on E coli through multi-targets and multi-pathways, which provides a new basis for the new use of PC as an old medicine.

The relationship between the expression of Stathmin and tumor immune cell infiltration in primary cervical carcinoma and its prognostic diagnostic value.

To analyse the relationship between the Stathmin expression and the tumor immune cell infiltration in primary cervical carcinoma (CC), and its prognostic diagnostic value. Cervical tissue samples from 128 patients admitted to our hospital from February 2021 to February 2022 who underwent hysterectomy or cervical biopsy were selected as the observation objects, and then divided into control group (normal cervical tissue specimen, n = 30), cervical intraepithelial neoplasia (CIN) group (CIN neoplasia cervical tissue specimen, n = 30), and cervical cancer group (cervical tissue specimen of cervical cancer lesion, n = 68) according to pathological results. The expression of Stathmin was detected by Immunohistochemistry (IHC). The numbers of infiltrated neutrophils (TINs) were measured by the specific esterase staining. The pathological data of CC patients were collected, and the protein expression of Stathmin was compared with different pathological data. According to the protein expression of Stathmin, the samples were divided into Stathmin positive group and negative group. The infiltration numbers, the levels of CD3+T, CD4+T and CD8+T of TINs were compared in each group, and CD4+/CD8+ were calculated. Kaplan-Meier survival curve was used for the analysis of the relationship between the Stathmin expression and the clinical prognosis in CC. COX analysis was used to determine the factors affecting the prognosis of patients with CC. The proportion of positive expression of cervical tissue Stathmin in CIN group and cervical cancer group was significantly higher than that in the control group, and the proportion of positive expression of cervical tissue Stathmin in cervical cancer group was significantly higher than that in CIN group (P < 0.001). The ratio of the clinical stage II + III, tissue grade low and medium differentiation, and lymph node metastasis in Stathmin positive group was significantly higher than that in the Stathmin negative group (P < 0.05). Compared with the Stathmin negative group, the numbers of TINs infiltration and the level of CD4+/CD8+ were visibly higher, and the content of CD3+T, CD4+T and CD8+T were sharply lower in the Stathmin positive group (P < 0.001). Compared with the Stathmin negative group, the numbers of TINs infiltration were higher, but the content of CD4+T and CD8+T were lower in Stathmin-positive group (P < 0.001). The 68 CC patients were followed up, with a median follow-up time of 25 months (5-60 months) and an overall survival rate of 66.18 % (45/68). The results of Kaplan-Meier survival curve showed that the median survival time of patients with the Stathmin positive expression was 30 months, which was significantly lower than that of 46 months (P < 0.05) in patients with the Stathmin negative expression. Multivariate analysis of COX proportional regression risk model showed that the Stathmin positive expression, TINs infiltration numbers≥55, CD3+<5.5 %, CD4+<4.5 %, CD8+<3 %, CD4+/CD8+≥1.3 were independent factors affecting the prognosis of CC patients (P < 0.05). Stathmin in the primary tissue of CC had a significantly high expression state, which was involved in the occurrence and development of CC, thus affecting the immune microenvironment balance damaged by tumor immune cell infiltration. Detecting its expression level might help the diagnosis and prognosis assessment of CC, and Stathmin might become a new target of CC immunotherapy.

Chronic Fluoride Exposure Induces Ovarian Dysfunction and Potential Association with Premature Ovarian Failure in Female Rats.

Chronic fluorosis has been widely investigated for its adverse effects on skeletal and neurological health; however, its impact on reproductive health, especially in females, remains underexplored. In this study, female Sprague-Dawley rats were exposed to different fluoride concentrations (0.75, 50, and 100 mg/L) in their drinking water for six months. Dental fluorosis and increased urinary fluoride content were observed in fluoride-exposed rats, reflecting fluoride accumulation and exposure levels. Chronic fluorosis resulted in reduced ovary organ coefficient, indicating harmful effects on ovarian tissue. Additionally, the number of ovarian primordial and primary/secondary follicles decreased, while the number of atresia follicles increased. Furthermore, chronic fluorosis led to disrupted estrous cycles. Hormonal analysis revealed altered secretion of estrogen, progesterone, anti-Müllerian hormone, luteinizing hormone, follicular stimulating hormone, and inhibin B in response to fluoride exposure. Ultrastructural observation of ovarian granulosa cells showed evidence of apoptosis, which was further confirmed by flow cytometry. Caspase-3 activity was increased, and ATP levels were decreased, suggesting mitochondrial impairment and apoptosis induction. The mRNA and protein expression of BMP15 and GDF9, essential regulators of ovarian function, significantly decreased with increasing fluoride concentration. Furthermore, gene expression analysis identified a panel of premature ovarian failure-related genes that were downregulated in fluoride-exposed rat ovaries. These findings suggest that chronic fluoride exposure may contribute to ovarian dysfunction and possibly the pathogenesis of premature ovarian failure. Understanding the toxicological effects of chronic fluoride exposure on ovarian function is essential for identifying potential environmental risk factors affecting female reproductive health.

Oxidized high-density lipoprotein enhances endocrine disorders and ovarian damage in rats.

Previous findings have highlighted the association between oxidized high-density lipoprotein (ox-HDL) and polycystic ovary syndrome (PCOS) development; however, the underlying mechanism remains unclear. Under such context, the present study aimed to investigate the mechanism underlying the involvement of ox-HDL in PCOS in relation to the p65/micro-RNA-34a (miR-34a)/FOS axis. PCOS rat models were established with the injection of dehydroepiandrosterone (6 mg/100 g body weight). Both PCOS-modelled rats and granulosa cells (GCs) were received treatment with ox-HDL in order to identify its role in PCOS. Next, apoptosis and viability of GCs were detected with the application of TdT-mediated dUTP Nick-End Labeling and flow cytometry and Cell counting kit-8, respectively. A series of assays were performed to determine the interaction among ox-HDL, p65, miR-34a, FOS and nuclear factor-κB (NF-κB). The results revealed high expression of ox-HDL in PCOS, and enhanced endocrine disorders and ovarian damage in rats. ox-HDL promoted apoptosis of GCs and decreased its viability. ox-HDL activated NF-κB pathway and induced p65 phosphorylation to promote miR-34a expression. miR-34a targeted and inhibited FOS expression. In conclusion, our findings suggested that ox-HDL promoted the activation of p65 and transcription of miR-34a, which stimulated apoptosis of GCs and inhibited expression of FOS, resulting in the overall acceleration of PCOS development.