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Introduction: Progestin, commonly used in oral contraception and preventing preterm birth, elicits various off-target side effects on brain and gastrointestinal (GI) functions, yet the precise mechanisms remain elusive. This study aims to probe progestin's impact on GI function and anxiety-like behaviors in female mice. Methods: Colon stem cells were utilized to explore the mechanism underlying progestin 17-hydroxyprogesterone caproate (17-OHPC)-mediated suppression of claudin-1 (CLDN1), crucial for epithelial integrity. Chromatin immunoprecipitation and luciferase assays identified potential progestin-response elements on the CLDN1 promoter, with subsequent assessment of oxidative stress and pro-inflammatory cytokine release. Manipulation of vitamin D receptor (VDR) or estrogen receptor β (ERβ) expression elucidated their roles in 17-OHPC-mediated effects. Intestine-specific VDR deficient mice were generated to evaluate 17-OHPC's impact on GI dysfunction and anxiety-like behaviors in female mice. Additionally, gene expression was analyzed in various brain regions, including the amygdala, hypothalamus, and hippocampus. Results: Exposure to 17-OHPC suppressed CLDN1 expression via epigenetic modifications and VDR dissociation from the CLDN1 promoter. Furthermore, 17-OHPC intensified oxidative stress and pro-inflammatory cytokine release. VDR knockdown partly mimicked, while overexpression of either VDR or ERβ partly restored 17-OHPC-mediated effects. Intestinal VDR deficiency partly mirrored 17-OHPC-induced GI dysfunction, with minimal impact on 17-OHPC-mediated anxiety-like behaviors. Conclusions: 17-OHPC suppresses CLDN1 expression through VDR, contributing to GI dysfunction in female mice, distinct from 17-OHPC-induced anxiety-like behaviors. This study reveals a new mechanism and potential negative impact of progestin exposure on the GI tract, alongside inducing anxiety-like behaviors in female mice. Plain Language Summary: Progestin is commonly used in oral contraceptives and for preventing preterm birth, but it exhibits various off-target side effects on brain and gastrointestinal (GI) function, the full extent of which remains largely unclear. In this study, we investigate the potential impact of progestin on the GI function in female mice with anxiety-like behaviors. Our findings reveal that exposure to the progestin 17-hydroxyprogesterone caproate (17-OHPC) suppresses the expression of claudin-1 (CLDN1) through epigenetic modifications and the dissociation of the vitamin D receptor (VDR) from the CLDN1 promoter. Additionally, 17-OHPC exposure exacerbates oxidative stress and the release of pro-inflammatory cytokines. Partial VDR deficiency in the intestine partly replicates the enhanced intestinal permeability and altered gut microbiota induced by 17-OHPC, though it has minimal effect on the anxiety-like behaviors triggered by 17-OHPC in female mice. In summary, progestin 17-OHPC suppresses CLDN1 expression via epigenetic alterations, contributing to GI dysfunction, distinct from progestin-induced anxiety-like behaviors. This sheds light on a novel mechanism and potential side effect of progestin exposure on GI system, alongside eliciting anxiety-like behaviors in female mice. [ABSTRACT FROM AUTHOR]

We performed a meta‐analysis to evaluate the effect of minimally invasive surgery and laparotomy on wound infection and postoperative and intraoperative complications in the management of cervical cancer. A systematic literature search up to July 2022 was performed and 10 231 subjects with cervical cancer at the baseline of the studies; 4307 of them were using the minimally invasive surgery, and 5924 were using laparotomy. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of minimally invasive surgery and laparotomy on wound infection and postoperative and intraoperative complications in the management of cervical cancer using the dichotomous methods with a random or fixed‐effect model. The minimally invasive surgery had significantly lower wound infection (OR, 0.20; 95% CI, 0.13–0.30, P <.001), and postoperative complications (OR, 0.48; 95% CI, 0.37–0.64, P <.001) in subjects with cervical cancer compared laparotomy. However, minimally invasive surgery compared with laparotomy in subjects with cervical cancer had no significant difference in intraoperative complications (OR, 1.04; 95% CI, 0.80–1.36, P = 0.76). The minimally invasive surgery had significantly lower wound infection, and postoperative complications however, had no significant difference in intraoperative complications in subjects with cervical cancer compared with laparotomy. The analysis of outcomes should be with caution because of the low sample size of 22 out of 41 studies in the meta‐analysis and a low number of studies in certain comparisons. [ABSTRACT FROM AUTHOR]

Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) leads to dysfunctions of human trophoblast cells and further induces miscarriage. In our previous study, we have found that lnc-HZ03 and miR-hz03 are upregulated in BPDE-exposed human trophoblast cells and in recurrent miscarriage tissues; and the upregulated miR-hz03 caused by lnc-HZ03 further promotes the apoptosis of human trophoblast cells and induces miscarriage. However, how lnc-HZ03 upregulates miR-hz03 is completely unknown. In this study, we find that lnc-HZ03 upregulates the expression level of a transcription factor TFIID (a TATA-binding protein) and promotes TFIID-mediated transactivation response element RNA-binding protein (TRBP) transcription. Subsequently, the upregulated TRBP promotes the maturation of miR-hz03 by splicing its precursor pre-miR-hz03 in human trophoblast cells. In BPDE-exposed trophoblast cells or in recurrent miscarriage tissues, lnc-HZ03 was upregulated, which accelerates the TFIID-mediated TRBP transcription and thus promotes TRBP-mediated miR-HZ03 maturation. Subsequently, the upregulated miR-hz03 further promotes the apoptosis of human trophoblast cells and induces miscarriage. This work provides new insights into the regulation of miRNA expression levels by lncRNAs in BPDE-exposed human trophoblast cells. [ABSTRACT FROM AUTHOR]

Sugars and amino acids are major classes of organic components in atmospheric fine particles and play important roles in atmospheric processes. However, the identification of their sources in different regions is explored little. To characterize local primary sources (biomass burning, plant, and soil sources) and evaluate their contributions to the total sugar compound and amino acid (AA) pool in different regions, fine particulate matter samples were collected from the urban, rural, and forest areas in Nanchang, China. The concentrations and compositions of sugar compounds (anhydrosugars, primary sugars, and sugar alcohols), free amino acids (FAAs), and combined amino acids (CAAs) were analysed by gas chromatography–mass spectrometry (GC-MS) after silylation derivatization. Urban areas had significantly higher average Σ sugar concentration (317±139 ng m -3) than that of the rural (181±72 ng m -3) and forest (275±154 ng m -3) areas (p<0.05). Overall, the distribution pattern of sugar compounds and CAAs in PM 2.5 was generally similar in three areas. Levoglucosan accounted for 24.4 %, 22.0 %, and 21.7 %, respectively, of the total sugar pool in the urban, rural, and forest areas. This suggests that plant and soil sources, as well as biomass burning (BB), provide important contributions to aerosol sugars and CAAs in three areas. In the urban area, the concentrations of anhydrosugars showed a positive correlation with combined Gly concentrations, but no correlation was found between these two compounds in the rural and forest areas, indicating that the urban area is mainly affected by local combustion sources. This conclusion was also supported by the positive correlation between levoglucosan and non-sea-salt potassium, only observed in the urban area (Lev=0.07 K ++37.7,r=0.6,p<0.05). In addition, the average levoglucosan / mannosan (L/M) ratio in the urban area (59.9) was much higher than in the rural (6.9) and forest areas (7.2), implying BB aerosols collected in the urban area originated from lignite burning, while the type of biofuels used in the rural and forest areas is mainly softwood. The concentrations of sugar alcohols in the rural and forest areas were positively correlated with that of CAAs, which are abundant in the topsoil (r=0.53∼0.62,p<0.05), suggesting that the contribution of local topsoil sources is large in these two areas. In the rural and forest areas, the concentrations of primary sugars were positively correlated with those of combined CAA species abundant in local dominant vegetation. Our findings suggest that combining specific sugar tracers and chemical profiles of CAAs in local emission sources can provide insight into primary source characteristics, including the types of biofuels burned, the contribution of topsoil sources, and local vegetation types. [ABSTRACT FROM AUTHOR]