Retrospective Analysis of Azithromycin-Resistant Ureaplasma urealyticum and Mycoplasma hominis Cervical Infection Among Pregnant Women.

Purpose: Ureaplasma urealyticum and Mycoplasma hominis began to show resistance to azithromycin, a macrolide antibiotic commonly used in pregnancy. Unfortunately, there are few effective and safe drugs in the clinic for genital mycoplasmas in pregnant women. In the present study, we investigated the prevalence of azithromycin-resistant U. urealyticum and M. hominis infections in pregnant women. The secondary research objects were possible influencing factors and consequences of insensitive Mycoplasma infection. Patients and methods: A retrospective analysis was carried out in pregnant women who underwent cervical Mycoplasma culture between October 2020 and October 2021 at a large general hospital in eastern China. The sociological characteristics and clinical information of these women were collected and analyzed. Results: A total of 375 pregnant women were enrolled, and 402 cultured mycoplasma specimens were collected. Overall, 186 (49.60%) patients tested positive cervical Mycoplasma infection, and 37 (9.87%) had infections caused by azithromycin-resistant Mycoplasma. In total, 39 mycoplasma samples were insensitive to azithromycin in vitro, also showing extremely high resistance to erythromycin, roxithromycin, and clarithromycin. Azithromycin was the only antibiotic used in women with Mycoplasma cervical infection, regardless of azithromycin resistance in vitro. Statistical results showed that azithromycin-resistant cervical Mycoplasma infection in pregnant women was unrelated to age, body mass index (BMI), gestational age, number of embryos, and assisted reproductive technology (ART) use, but led to a significantly increased incidence of adverse pregnancy outcomes (spontaneous abortion (SA), preterm birth (PTB), preterm prelabor rupture of membranes (PPROM), and stillbirth). Conclusion: Azithromycin-resistant U. urealyticum and M. hominis cervical infections are relatively common during pregnancy, and can increase the risk of adverse pregnancy outcomes; however, there is currently a lack of safe and effective drug treatments. Herein, we show that azithromycin-resistant mycoplasma infection requires timely intervention.

Investigation of the potential theranostic role of KDM5B/miR-29c signaling axis in paclitaxel resistant endometrial carcinoma.

OBJECTIVE: Endometrial cancer (EC) is one of the most common female reproductive system tumors. In this study, we explored the clinical significance of Histone demethylase KDM5B gene and its effects on paclitaxel (PTX) sensitivity in EC. METHOD: First, we found that KDM5B expression significantly higher in EC tissues and cell lines. The elevated KDM5B expression was associated with high pathological grade and low PTX sensitivity. The functional role of KDM5B in PTX-resistant Ishikawa-R and HEC1A-R cells were examined by gene silencing experiments. RESULTS: Knockdown of KDM5B resulted in the re-sensitization towards paclitaxel in both resistant cell lines. In addition, we also identified that microRNA-29c-3p (a tumor suppressor) was significantly lower in the EC cells and linked to the low PTX sensitivity of EC. The up-regulation of miR-29c-3p using exogenous mimic molecules markedly increased PTX sensitivity in both cell lines and reduced expression of KDM5B while the inhibitor of miR-29-3p resulted in the opposite effects. Notably, we also demonstrated that the level of miR-29c-3p was inversely correlated to the invasive, colony-forming abilities and PTX resistance in both cell lines. We also identified that miR-29c-3p has a binding site in the 3'UTR of the KDM5B gene, establishing a link of this signaling axis. In conclusion, high-expression of KDM5B is associated with the poor response to PTX in EC patients. Silencing of KDM5B led to the reversal of PTX resistance through miR-29c-3p/KDM5B pathway in EC. CONCLUSION: Our findings provide new insights into the mechanism by which EC cells acquire paclitaxel resistance and potential this signaling as a theronostic marker for this malignancy.

TRPV1 agonism inhibits endothelial cell inflammation via activation of eNOS/NO pathway.

BACKGROUND AND AIMS: Transient receptor potential vanilloid type 1 channel (TRPV1) is found to be expressed in endothelial cells (ECs) and activate endothelial nitric oxide synthase (eNOS). Recent studies implicate TRPV1 in attenuating inflammatory responses. However, the mechanisms underlying the beneficial effects remain unclear. In this study, we investigated whether TRPV1 suppresses inflammatory responses of ECs via eNOS/NO pathway. METHODS: Human umbilical vein endothelial cells (HUVECs) and renal microvascular endothelial cells (MVECs) isolated from deoxycorticosterone (DOCA)-salt hypertensive mice were cultured in the presence of capsaicin (CAP, a specific TRPV1 agonist) with or without the specific inhibitor of TRPV1, NOS, or Ca2+-dependent phosphatidylinositol 3-kinase (PI3K)/Akt pathway, before lipopolysaccharide (LPS) stimulation. NO metabolites, protein expression, and inflammatory molecules were evaluated by Griess assay and immune assay-based multiplex analysis, respectively. Monocyte adhesion was determined by measuring the fluorescently labeled human monocytes attached to LPS-stimulated ECs. RESULTS: In HUVECs, treatment with CAP increased NO production, and CAP-induced NO production was accompanied by increased eNOSser1177 phosphorylation. Additionally, CAP attenuated LPS-induced cytokine and chemokine production, adhesion molecule expression, activation of NF-κB, and monocyte adhesion in HUVECs, and these effects were abrogated by the inhibition of TRPV1, NOS, or Ca2+-dependent PI3K/Akt pathway. Moreover, these protective actions of TRPV1 were also observed in renal MVECs isolated from DOCA-salt hypertensive mice. CONCLUSIONS: Our results indicate that TRPV1 activation suppresses the inflammatory response of ECs via the activation of Ca2+/PI3K/Akt/eNOS/NO pathway, the protective effects are also documented in ECs derived from salt-sensitive hypertensive mice.