Interleukin-17A stimulation induces alterations in Microglial microRNA expression profiles.

BACKGROUND: Increased maternal interleukin (IL)-17A and activated microglia are pivotal factors contributing to the pathological phenotypes of maternal immune activation (MIA), developing neurodevelopmental disorders in offspring. This study aimed to determine whether IL-17A affects the microglial microRNA (miRNA) profiles. METHODS: The miRNA expression profiles of primary cultured microglia stimulated with recombinant IL-17A were examined comprehensively using miRNA sequencing and validated through qRT-PCR. The expressions of miRNAs target genes identified using bioinformatics, were investigated in microglia transfected with mimic miRNA. The target gene's expression was also examined in the fetal brains of the MIA mouse model induced by maternal lipopolysaccharide (LPS) administration. RESULTS: Primary cultured microglia expressed the IL-17A receptor and increased proinflammatory cytokines and nitric oxide synthase 2 upon treatment with IL-17A. Among the three miRNAs with |log2FC | >1, only mmu-miR-206-3p expression was significantly up-regulated by IL-17A. Transfection with the mmu-miR-206-3p mimic resulted in a significant decrease in the expression of Hdac4 and Igf1, target genes of mmu-miR-206-3p. Hdac4 expression also significantly decreased in the LPS-induced MIA model. CONCLUSIONS: IL-17A affected microglial miRNA profiles with upregulated mmu-miR-206-3p. These findings suggest that targeting the IL-17A/mmu-miR-206-3p pathway may be a new strategy for predicting MIA-related neurodevelopmental deficits and providing preventive interventions. IMPACT: Despite the growing evidence of interleukin (IL)-17A and microglia in the pathology of maternal immune activation (MIA), the downstream of IL-17A in microglia is not fully known. IL-17A altered microRNA profiles and upregulated the mmu-miR-206-3p expression in microglia. The mmu-miR-206-3p reduced autism spectrum disorder (ASD) related gene expressions, Hdac4 and Igf1. The Hdac4 expression was also reduced in the brain of MIA offspring. The hsa-miR-206 sequence is consistent with that of mmu-miR-206-3p. This study may provide clues to pathological mechanisms leading to predictions and interventions for ASD children born to mothers with IL-17A-related disorders.

Predicting preterm birth within 2 weeks in asymptomatic women with a short cervix: Combined effects of cervicovaginal fluid cytokine levels and fetal fibronectin test.

AIMS: To predict preterm birth (PTB) accurately, we conducted a comprehensive cytokine assay using cervicovaginal fluid (CVF) and evaluated the additive effects of cytokine levels on the fetal fibronectin (fFN) test. METHODS: A total of 645 CVF samples were collected from 256 asymptomatic pregnant women between 24 and 35 weeks gestation, exhibiting short cervix. After selection based on specific criteria, 17 cytokines in 105 CVF samples were simultaneously measured using multiplex assay. Multivariate logistic regression analysis was performed to evaluate the association between cytokine levels and impending PTB, which is defined as PTB within 2 weeks after CVF collection. Moreover, receiver operating characteristic (ROC) analysis was performed in women with positive fFN results, which was validated using another set of 65 CVF samples. RESULTS: In positive fFN women, the CCL2 level was significantly higher in the impending PTB group than the other group (p < 0.01) and a predictor of impending PTB (adjusted odds ratio 1.020, 95% confidence interval [95% CI] 1.003-1.038, p = 0.020). The cutoff value of CCL2 was 64.8 pg/mL (are under the curve 0.726, p = 0.004, 95% CI 0.593-0.859, sensitivity 45.2%, specificity 91.7%). Additionally, the reliable classification performance of proposed ROC model could be validated. However, measuring cytokine levels could not help in predicting impending PTB in women with negative fFN or normal labor onset in healthy-term women. CONCLUSION: Comprehensive analysis of CVF cytokines revealed that the CCL2 level significantly improves the prediction of impending PTB in asymptomatic fFN-positive women with a short cervix, which may contribute to better clinical management.

Risk factors for non-previa placenta accreta spectrum in pregnancies conceived through frozen embryo transfer during a hormone replacement cycle in Japan.

Purpose: Non-previa placenta accreta spectrum (PAS) is associated with assisted reproductive technology (ART), particularly frozen embryo transfer during hormone replacement therapy (HRC-FET). We especially aimed to evaluate the prevalence and risk factors for non-previa PAS in HRC-FET pregnancies. Methods: Overall, 279 women who conceived through ART at three ART facilities and delivered at a single center were included in this retrospective study. Data regarding endometrial thickness at embryo transfer, previous histories, and type of embryo transfer-HRC-FET, frozen embryo transfer during a natural ovulatory cycle (NC-FET), and fresh embryo transfer (Fresh-ET)-were collected. Univariable logistic regression analyses were conducted. Results: The prevalence of non-previa PAS was 27/192 (14.1%) in the HRC-FET group and 0 (0.0%) in both the NC-FET and Fresh-ET groups. Significantly high odds ratio [95% confidence interval] of non-previa PAS was associated with a history of artificial abortion (6.45 [1.98-21.02]), endometrial thickness <8.0 mm (6.11 [1.06-35.12]), resolved low-lying placenta (5.73 [2.13-15.41]), multiparity (2.90 [1.26-6.69]), polycystic ovarian syndrome (2.62 [1.02-6.71]), and subchorionic hematoma (2.49 [1.03-6.04]). Conclusions: A history of artificial abortion, endometrial thickness <8.0 mm, and resolved low-lying placenta may help in antenatal detection of a high-risk population of non-previa PAS in HRC-FET pregnancies.

Trend changes in age-related body mass index gain after coronavirus disease 2019 pandemic in Japan: a multicenter retrospective cohort study.

BACKGROUND: Accumulating studies suggest that strict lockdown with enforcement including segregation to control the coronavirus disease 2019 (COVID-19) pandemic is associated with excess weight gain, but the such lockdown was not practiced in Japan. We aimed to compare the age-related weight gain before and after the COVID-19 pandemic in Japan where achieved epidemic control based on individual voluntary action. METHODS: This multicenter retrospective cohort study used electronic data from annual health checkups for workers from January 2015 to December 2021 at four facilities belonging to the Central Clinic Group, Aichi, Japan. We defined pre-pandemic and post-pandemic periods as January 2015-December 2019 and January 2020-December 2021, respectively. Participants were grouped by sex, age, and body mass index (BMI) stratus as of 2015, and the pre-pandemic and post-pandemic age-related BMI changes in overall individuals and each specific group were compared using a paired t-test. RESULTS: The total number of eligible participants was 19,290. During the pre-pandemic period, the mean BMI increased linearly in every group. The mean age-related BMI changes in females' pre-pandemic and post-pandemic periods were + 0.11 and + 0.02 kg/m2/year, respectively. This significant decrease was also shown in males, + 0.11 in the pre-pandemic and - 0.02 kg/m2/year in the post-pandemic periods. The reduction was consistently observed in all age strata. Furthermore, a significant reduction was also observed in the normal-weight females of reproductive ages aged 15-44 years. CONCLUSIONS: This is the first report showing that age-related weight gain was reduced after the COVID-19 pandemic in Japan, which could affect the reproductive age of females.

Sex-specific differences in head circumference of term singletons after assisted reproductive technology: a multicentre study in Japan.

RESEARCH QUESTION: Does fertility treatment, specifically assisted reproductive technology (ART), affect head circumference in term singletons? DESIGN: A total of 32,651 women who delivered at term at 12 maternity hospitals in Japan between 2010 and 2018 were included in the analysis; of these, 1941 (5.9%) and 2984 (9.1%) women conceived through ART and non-ART fertility treatments (timed intercourse, ovulation induction or artificial insemination), respectively. The study evaluated the adjusted odds ratios of head circumference ≥90th percentile stratified by infant sex and type of ART procedure after adjusting for covariates, with natural conception as the reference group. RESULTS: ART significantly increased the risk of head circumference ≥90th percentile (adjusted odds ratio 1.56 [95% confidence interval 1.25-1.96]), whereas non-ART fertility treatment did not increase the risk (1.14 [0.92-1.42]). This increased risk of head circumference ≥90th percentile was observed exclusively in male neonates (1.73 [1.33-2.26]) and not in female neonates (1.18 [0.76-1.85]) in the ART group. Frozen embryo transfer (FET), FET in a hormone replacement cycle (HRC-FET) and blastocyst-stage embryo transfer were significantly associated with head circumference ≥90th percentile (1.60 [1.26-2.02], 1.70 [1.30-2.22] and 1.72 [1.33-2.24], respectively). CONCLUSIONS: The use of ART, particularly FET, HRC-FET or blastocyst-stage embryo transfer, was linked with a heightened risk of head circumference ≥90th percentile compared with non-ART fertility treatment or natural conception. The increased risk was observed only in male neonates.

The prognostic impact of limited-staging surgery in patients with stage IA epithelial ovarian cancer: a multi-center study with a propensity score-adjusted analysis.

OBJECTIVE: Complete-staging surgery is recommended for stage IA ovarian cancer, but may be omitted for various reasons, including the preservation of fertility and an advanced age. We herein investigated the prognostic impact of limited-staging surgery in patients with stage IA epithelial ovarian cancer. METHODS: We retrospectively collected data on 4730 patients with malignant ovarian tumors from the databases of multiple institutions and ultimately included 293 with stage IA epithelial ovarian cancer. Limited-staging surgery was defined as one that did not involve hysterectomy, systematic retroperitoneal lymphadenectomy or the collection of ascites cytology. We used an inverse probability of treatment weighting analysis with propensity scores and estimated the hazard ratios of recurrence and death with limited-staging surgery. RESULTS: In total, 176 out of 293 patients (39.9%) were assigned to the limited-staging surgery group. After propensity score adjustments, no significant differences were observed in recurrence-free survival or overall survival between the limited- and complete-staging surgery groups. Even in the subgroup analysis with age stratification, recurrence-free survival and overall survival were similar in the limited- and complete-staging surgery groups. CONCLUSIONS: The present results indicate the limited prognostic impact of limited-staging surgery for stage IA epithelial ovarian cancer.

Comparison of the efficacy between controlled-release dinoprostone delivery system (PROPESS) and Cook's double balloon catheter plus oxytocin: A retrospective single-center study in Japan.

AIMS: To compare the efficacy of the controlled-release dinoprostone delivery system (PROPESS) and Cook's double balloon catheter (DBC) plus oxytocin as induction treatment. METHODS: A total of 197 term pregnant women with unfavorable cervix were admitted for scheduled induction and enrolled retrospectively (PROPESS, 113; Cook's DBC plus oxytocin, 84). The main birth outcomes were cervical ripening at the treatment-end and 24 h after the treatment-start, and rate of vaginal birth. Logistic regression and propensity score matching analyses were performed to evaluate the association between the outcomes and clinical characteristics including which treatment was selected. RESULTS: The choice of PROPESS was associated with the success of cervical ripening at 24 h after (adjusted odds ratio (OR) 2.17, 95% confidence interval (CI) 1.11-4.26, p = 0.024) and increased the rate of vaginal birth (adjusted OR 2.03, 95% CI 1.04-3.98, p = 0.039). Similar trends in the association between PROPESS and birth outcomes were maintained after adjusting for propensity scores (p = 0.072 and p = 0.163, respectively). However, some of the women with gestational age of early 39 weeks and low Bishop scores could achieve cervical ripening at 24 h after using Cook's DBC plus oxytocin, and none by PROPESS. CONCLUSION: Our findings suggest the possibility of slight advantages of PROPESS for scheduled induction of labor. In women with early term and extremely low Bishop scores, Cook's DBC plus oxytocin may be a superior or alternative treatment to PROPESS. Therefore, the optimal choice of induction treatment should be managed on an individual basis.

Clinical significances of Bishop score and vaginal bleeding to controlled-release dinoprostone delivery system (PROPESS) efficacy for cervical ripening: A retrospective single-center study in Japan.

AIMS: To evaluate the effect of vaginal bleeding on the efficacy of controlled-release dinoprostone delivery system (PROPESS) for cervical ripening and the factors affecting the PROPESS efficacy in a Japanese clinical setting. METHODS: A total of 100 term pregnant women in whom PROPESS was used due to an unfavorable cervix (Bishop score ≤ 6) were enrolled. We retrospectively investigated which factors, including vaginal bleeding, were associated with the success of cervical ripening using logistic regression analysis. Moreover, the effect of vaginal bleeding on vaginal acidity was examined in 24 selected cases (control, 11; rupture of membrane, 4; and vaginal bleeding, 8). RESULTS: A 25 women successfully ripened the cervix (effective group), and 75 were unsuccessful (noneffective group). Bishop score at insertion (adjusted odds ratio: 1.87; 95% confidence interval: 1.23-2.86; p = 0.004), and vaginal bleeding at PROPESS insertion (adjusted odds ratio 6.63; 95% confidence interval 1.21-36.36; p = 0.029) affected cervical ripening success. The cases with vaginal bleeding showed a significantly higher vaginal pH than the control cases (median value: 6.75 and 5.0, respectively). We identified no obvious adverse outcomes, such as tachysystole, fetal heart rate abnormality, or low Apgar/pH, associated with vaginal bleeding at insertion. CONCLUSIONS: Our findings suggest that the PROPESS efficacy depends on Bishop score at insertion and that vaginal bleeding at PROPESS insertion might have a significantly positive effect on cervical ripening in term pregnant women.

Factors associated with response to compression-based physical therapy for secondary lower limb lymphedema after gynecologic cancer treatment: a multicenter retrospective study.

BACKGROUND: Lower limb lymphedema (LLL) is one of the most refractory and debilitating complications related to gynecological cancer treatment. We investigated factors associated with response to compression-based physical therapy (CPT) for secondary LLL after gynecologic cancer treatment. METHODS: We performed a multicenter retrospective study using the records of seven medical institutions from 2002 and 2014. Patients who developed LLL after gynecological cancer treatment were included. Limb volumes were calculated from the lengths of the limb circumferences at four points. All participants underwent compression-based physical therapy for LLL. Factors, including MLD, indicative of circumference reductions in LLL were determined. RESULTS: In total, 1,034 LLL met the required criteria of for the study. A multivariate linear regression analysis identified age; body mass index (BMI); endometrial cancer; radiotherapy; and initial limb circumference as significant independent prognostic factors related to improvement in LLL. In analysis of covariance for improvement in LLL adjusted by the initial limb circumference and stratified by BMI and radiotherapy, patients with BMI 28 kg/m2 or higher and receiving radiation rarely responded to CPT. CONCLUSIONS: Improvements in the lower limb circumference correlated with clinical histories and physical characteristics, which may be used as independent prognostic factors for successful CPT for LLL after gynecological cancer treatment.

Proton beam therapy for the isolated recurrence of endometrial cancer in para-aortic lymph nodes: a case report.

BACKGROUND: Proton beam therapy penetrates tumor tissues with a highly concentrated dose. It is useful when normal structures are too proximate to the treatment target and, thus, may be damaged by surgery or conventional photon beam therapy. However, proton beam therapy has only been used to treat recurrent endometrial cancer in a few cases; therefore, its effectiveness remains unclear. CASE PRESENTATION: We herein report a case of the isolated recurrence of endometrial cancer in the para-aortic lymph nodes in a 59-year-old postmenopausal woman that was completely eradicated by proton beam therapy. The patient was diagnosed with stage IIIC2 endometrial cancer and treated with 6 courses of doxorubicin (45 mg/m2) and cisplatin (50 mg/m2) in adjuvant chemotherapy. Fifteen months after the initial therapy, the isolated recurrence of endometrial cancer was detected in the para-aortic lymph nodes. The site of recurrence was just under the left renal artery. Due to the potential risks associated with left kidney resection due to the limited surgical space between the tumor and left renal artery, proton beam therapy was administered instead of surgery or conventional photon beam therapy. Following proton beam therapy, the complete resolution of the recurrent lesion was confirmed. No serious complications occurred during or after treatment. There have been no signs of recurrence more than 7 years after treatment. CONCLUSIONS: Proton beam therapy is a potentially effective modality for the treatment of recurrent endometrial cancer where the tumor site limits surgical interventions and the use of conventional photon beam therapy.

Who are the long-term survivors of recurrent ovarian carcinoma?: a retrospective analysis of a multicenter study.

BACKGROUND: The aim of the present study was to investigate the incidence and hallmarks of long-term survivors of recurrent ovarian carcinoma (LTSROC) in a large-scale retrospective cohort of patients from a multicenter study group. METHODS: We performed a regional multicenter retrospective study between January 1986 and September 2021 using clinical data collected under the central pathological review system. Patients who underwent surgery for primary OC at diagnosis and developed recurrent tumors after the initial treatment were included. We defined LTSROC as patients who survived for 5 years or longer after initial tumor recurrence and examined factors affecting the long-term survival of ROC and outcomes of LTSROC. RESULTS: We collected information on patients with malignant ovarian tumors and finally 657 of them that developed ROC were included in the study population. Sixty-eight (10.4%) patients were LTSROC while 399 (60.7%) were short-term survivors of recurrent ovarian carcinoma. In a multivariate logistic regression analysis, negative ascites cytology [odds ratio (OR) 1.865; 95% CI 1.026-3.393; p = 0.041] and a recurrence-free interval (RFI) of 1 year or longer (OR 2.896; 95% CI 1.546-5.425; p < 0.001) were identified as independent factors associated with LTSROC. Approximately 80% of LTSROC presented with solitary recurrent tumors. Furthermore, more than 50% of LTSROC underwent tumor debulking surgery for the first recurrent tumor with or without chemotherapy. CONCLUSION: RFI of 1 year or longer and negative ascites cytology in the initial surgery were identified as independent predictive factors for LTSROC.

Pro-tumoral behavior of omental adipocyte-derived fibroblasts in tumor microenvironment at the metastatic site of ovarian cancer.

Adipocyte-rich omentum offers "good soil" for disseminating ovarian cancer (OvCa), contributing to therapeutic difficulty. However, little is understood about the association between adipocytes and tumor growth at peritoneal dissemination site. Herein, we report the induction of adipocyte dedifferentiation by OvCa cells and pro-tumorigenic effects of resulted adipocyte-derived fibroblasts. We confirmed that malignant ascites promoted the dedifferentiation of the primary human adipocytes obtained from surgical omental specimen into omental adipocyte-derived fibroblast (O-ADF) that possess both mesenchymal stem cell and myofibroblast-like features. This promotion of dedifferentiation by malignant ascites was blocked by addition of Wnt signaling inhibitor. The effects of dedifferentiated adipocytes in proliferation and migration of OvCa cells were analyzed with in vitro coculturing experimental models and in vivo mice model, and we demonstrated that OvCa cell lines showed enhanced proliferative characteristics, as well as increased migratory abilities upon coculturing with O-ADF. Additionally, exogenous transforming growth factor-ß1 augmented desmoplastic morphological change of O-ADF, leading to higher proliferative ability. Our results suggest that OvCa cells promote dedifferentiation of peritoneal adipocytes by activating Wnt/ß-catenin signaling, and generated O-ADFs exhibit pro-tumoral hallmarks.

Vitamin D improves pulmonary function in a rat model for congenital diaphragmatic hernia.

A congenital diaphragmatic hernia (CDH) is an anomaly caused by defects in the diaphragm; the resulting limited thorax cavity in turn restricts lung growth (pulmonary hypoplasia). This condition is related to pulmonary hypertension. Despite advances in neonatal CDH therapy, the mortality for severe pulmonary hypoplasia remains high. Therefore, it is essential to establish prenatal therapeutic interventions. Vitamin D was reported to have beneficial effects on adult pulmonary hypertension. This study aims to evaluate the efficacy of prenatal vitamin D administration for CDH. First, serum 25-hydroxyvitamin D [25(OH)D] levels in umbilical cord blood were evaluated among CDH newborns. Second, Sprague Dawley rat CDH models were exposed to nitrofen on embryo day 9 (E9). Randomly selected rats in the nitrofen-treated group were infused with calcitriol from E9 to E21. Samples from CDH pups diagnosed after birth were used for lung weight measurements, blood gas analysis, and immunohistochemical analysis. Third, microarray analysis was performed to examine the effect of vitamin D on gene expression profiles in CDH pulmonary arterial tissues. Serum 25(OH)D levels in the umbilical cord blood of newborns who did not survive were significantly lower than those who were successfully discharged. Prenatal vitamin D showed no significant effect on CDH incidence or lung weight but attenuated alveolarization and pulmonary artery remodeling accompanied the improved blood gas parameters. Vitamin D inhibited several gene expression pathways in the pulmonary arteries of CDH rats. Our results suggest that prenatal vitamin D administration attenuates pulmonary vascular remodeling by influencing several gene pathways in CDH.

Does complete-staging lymphadenectomy improve survival outcomes in stage I endometrioid epithelial ovarian carcinoma? A multi-institutional retrospective study with propensity score-weighted analysis.

BACKGROUND: We investigated the prognostic impact of complete-staging lymphadenectomy on patients with clinically apparent Stage I endometrioid epithelial ovarian carcinoma. METHODS: We conducted a regional multi-institutional retrospective study between 1986 and 2018. Amongst 4897 patients with malignant ovarian tumours diagnosed under central pathological review, 259 women with Stage I endometrioid epithelial ovarian carcinoma were eligible. We evaluated differences in survival of patients with both pelvic and para-aortic lymphadenectomy (Group A) and those with only pelvic lymphadenectomy and/or clinical lymph node evaluation (Group B). To analyse the therapeutic effects, the baseline imbalance between patients with both pelvic and para-aortic lymphadenectomy and others was adjusted with an inverse probability of treatment weighting using propensity score involving independent clinical variables. RESULTS: In total, 145 patients (56.0%) received both pelvic and para-aortic lymphadenectomy. With propensity score-based adjustment, estimated survival was better in Group A compared with that in Group B but not significant. Pelvic and para-aortic lymphadenectomy also led to no significant improvement of overall survival in most of the subgroups. However, point estimations of the hazard ratio for lymphadenectomy in patients with an age of 45 or younger (hazard ratio, 0.304; 95% confidence interval, 0.094-0.982), a Grade 1-2 (hazard ratio, 0.441; 95% confidence interval, 0.204-0.954) and T1c2-3 tumour (hazard ratio, 0.449; 95% confidence interval, 0.164-1.231) were better compared with those with the opposite characteristics. CONCLUSIONS: Complete-staging lymphadenectomy was not a significant prognostic factor in patients with Stage I endometrioid epithelial ovarian carcinoma, where we still need to explore appropriate candidate for the procedure.

Relationship between vaginal group B streptococcus colonization in the early stage of pregnancy and preterm birth: a retrospective cohort study.

BACKGROUND: Although infection and inflammation within the genital tract during pregnancy is considered a major risk factor for spontaneous preterm birth (PTB), there are few studies on association between vaginal microorganisms in the early stage of pregnancy and PTB. The aim of this study was to investigate relationship between vaginal Group B streptococcus (GBS) colonization, a leading cause of infection during pregnancy, in the early stage of pregnancy and PTB. METHODS: This single-center, retrospective cohort study utilized data from 2009 to 2017 obtained at TOYOTA Memorial Hospital. Women with singleton pregnancies who underwent vaginal culture around 14 weeks of gestation during their routine prenatal check-up were included. Vaginal sampling for Gram staining and culture was performed regardless of symptoms. GBS colonization was defined as positive for GBS latex agglutination assay. Statistical analysis was performed to determine the factors associated with PTB. RESULTS: Overall 1079 singleton pregnancies were included. GBS (5.7%) and Candida albicans (5.5%) were the most frequently observed microorganisms. The incidence of PTB (before 34 and before 37 weeks of gestation) were significantly higher in the GBS-positive group than in the GBS-negative group (6.6% vs 0.5%, p = 0.001 and 9.8% vs 4.3%, p = 0.047). Our multivariable logistic regression analysis revealed that GBS colonization was a factor associated with PTB before 34 and before 37 weeks of gestation (Odds ratio [OR] 15.17; 95% confidence interval [CI] 3.73-61.74), and OR 2.42; 95%CI 1.01-5.91, respectively). CONCLUSIONS: The present study found that vaginal GBS colonization in the early stage of pregnancy was associated with PTB. Our study indicates that patients at a high risk for PTB can be extracted by a simple method using conventional culture method.

Prenatal Molecular Hydrogen Administration Ameliorates Several Findings in Nitrofen-Induced Congenital Diaphragmatic Hernia.

Oxidative stress plays a pathological role in pulmonary hypoplasia and pulmonary hypertension in congenital diaphragmatic hernia (CDH). This study investigated the effect of molecular hydrogen (H2), an antioxidant, on CDH pathology induced by nitrofen. Sprague-Dawley rats were divided into three groups: control, CDH, and CDH + hydrogen-rich water (HW). Pregnant dams of CDH + HW pups were orally administered HW from embryonic day 10 until parturition. Gasometric evaluation and histological, immunohistochemical, and real-time polymerase chain reaction analyses were performed. Gasometric results (pH, pO2, and pCO2 levels) were better in the CDH + HW group than in the CDH group. The CDH + HW group showed amelioration of alveolarization and pulmonary artery remodeling compared with the CDH group. Oxidative stress (8-hydroxy-2'-deoxyguanosine-positive-cell score) in the pulmonary arteries and mRNA levels of protein-containing pulmonary surfactant that protects against pulmonary collapse (surfactant protein A) were significantly attenuated in the CDH + HW group compared with the CDH group. Overall, prenatal H2 administration improved respiratory function by attenuating lung morphology and pulmonary artery thickening in CDH rat models. Thus, H2 administration in pregnant women with diagnosed fetal CDH might be a novel antenatal intervention strategy to reduce newborn mortality due to CDH.

Upregulation of ENDOU in cytotrophoblasts from placenta complicated with preeclampsia and fetal growth restriction.

Placental hypoplasia is associated with the pathophysiology of fetal growth restriction and preeclampsia. The placenta consists of differentiated trophoblasts, including cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts. Cytotrophoblasts are thought to have stem-like characteristics and the ability to differentiate into syncytiotrophoblasts and extravillous trophoblasts. However, it is poorly understood whether isolated cytotrophoblasts derived from hypoplastic placentas have specific features compared with those in normal placentas. This study aimed to determine the features of cytotrophoblasts in hypoplastic placentas. Differentially expressed proteins between isolated cytotrophoblasts from hypoplastic placenta with fetal growth restriction and those from the normal placenta were determined by liquid chromatography-tandem mass spectrometry. Among 6,802 proteins, 1,253 and 2,129 proteins were more than 2-fold upregulated and downregulated, respectively. Among them, ENDOU (endonuclease, poly(U) specific), which has high homology with the coronavirus endoribonuclease nonstructural protein 15 (Nsp15), showed a significantly increased expression in cytotrophoblasts from the placenta with fetal growth restriction related to preeclampsia compared with those in normal control placenta. These results provide insight into the pathological mechanisms of placental hypoplasia and additional information on preeclamptic symptoms in cases of SARS-CoV-2 infected placenta, although further investigation is needed.

Reasons for previous Cesarean deliveries impact a woman's independent decision of delivery mode and the success of trial of labor after Cesarean.

BACKGROUND: Cesarean delivery rates are increasing globally with almost half of them occurring due to a previous Cesarean delivery. A trial of labor after Cesarean (TOLAC) is considered a safe procedure, but most eligible women instead undergo Cesarean before 39 weeks of gestation. Lack of education about TOLAC is often associated with increased repeat Cesarean. To reveal the safety and feasibility of TOLAC, we conducted this observational, prospective study with women's independent decisions. We aimed to clarify the relationship between their chosen mode of delivery and the reason for their previous Cesarean. Additionally, we have tried to identify maternal and obstetric factors associated with failed TOLAC to improve its success rate. METHODS: This was a prospective, observational study of 1086 pregnant women with at least one previous Cesarean delivery. Of these, 735 women met our TOLAC criteria (Table 1), and then, could choose TOLAC or repeat Cesarean after receiving detailed explanations regarding the risks and benefits of both procedures. The primary outcomes were the number of successful TOLAC procedures and 5-min Apgar scores < 7 for the trial of labor after Cesarean group and elective Cesarean group. We collected the maternal and neonatal data including the reasons of previous Cesarean. RESULTS: In total, 64.1% of women chose TOLAC. The success rate was 91.3%. The uterine rupture rate was 0.6%. There were no significant differences in the rate of Apgar scores at 5 min < 7 between both groups. Histories of experience of labor in previous Cesarean delivery were observed in 30 and 50% of women who chose TOLAC and repeat Cesarean, respectively (p < 0.05). Factors related to failed TOLAC included ≥40 weeks of gestation (odds: 5.47, 95% CI: 2.55-11.70) and prelabor rupture of membranes (PROM) (odds: 4.47, 95% CI: 2.07-9.63). CONCLUSIONS: TOLAC is a favorable delivery option for both mothers and neonates when women meet criteria and choose after receiving detailed explanations. Women who experience PROM or ≥ 40 weeks of gestation, their modes of delivery should be reconsulted.

Microphthalmia-Associated Transcription Factor-Dependent Melanoma Cell Adhesion Molecule Activation Promotes Peritoneal Metastasis of Ovarian Cancer.

Ovarian cancer (OvCa) is one of the leading causes of death due to its high metastasis rate to the peritoneum. Recurrent peritoneal tumors also develop despite the use of conventional platinum-based chemotherapies. Therefore, it is still important to explore the factors associated with peritoneal metastasis, as these predict the prognosis of patients with OvCa. In this study, we investigated the function of microphthalmia-associated transcription factor (MITF), which contributes to the development of melanoma, in epithelial ovarian cancer (OvCa). High MITF expression was significantly associated with a poor prognosis in OvCa. Notably, MITF contributed to the motility and invasion of OvCa cells, and specifically with their peri-mesothelial migration. In addition, MITF-positive cells expressed the melanoma cell adhesion molecule (MCAM/CD146), which was initially identified as a marker of melanoma progression and metastasis, and MCAM expression was regulated by MITF. MCAM was also identified as a significant prognostic factor for poor progression-free survival in patients with OvCa. Collectively, our results suggest that MITF is a novel therapeutic target that potentially promotes peritoneal metastasis of OvCa.