Cervical incompetence occurs when the cervix fails to maintain its normal morphology and function during second-trimester, leading to recurrent second-trimester miscarriages or preterm births. To standardize and guide the clinical diagnosis and treatment of cervical insufficiency in China, the Perinatal Medicine Branch of the Chinese Medical Association and the Obstetrics Group of the Chinese Society of Obstetrics and Gynecology developed this consensus by referencing related research evidence and so on. This consensus provides evidence-based analysis and recommendations on key clinical issues including the diagnosis of cervical incompetence, indications for cervical cerclage, surgical techniques, timing of intervention, perioperative management, and adjunctive therapies, offering evidence-based guidance for obstetric clinical practice.Practice guideline registration:International Practice Guidelines Registry and Transparency Platform (PREPARE-2024CN1155)

Background Acute chlorine inhalation is well established as a cause of respiratory injury, but few studies have examined the effects of long-term occupational exposure to low chlorine concentrations. We therefore evaluated the association between cumulative occupational chlorine exposure and lung function. Methods In this retrospective cohort, occupational health examination records were linked to enterprise- and job-specific monitoring data collected in Wuhan, China, during 2021–2025. Cumulative exposure was defined as the long-term mean chlorine concentration multiplied by exposure duration. Lung function was assessed by spirometry; abnormalities were determined by qualified occupational health physicians, and FEV₁, FVC, and FEV₁/FVC z-scores were calculated using Global Lung Function Initiative equations. Low FEV₁ and low FVC were defined as the corresponding z-scores < − 1.645. Associations were estimated using generalized estimating equations with an exchangeable correlation structure and robust standard errors, accounting for repeated examinations and adjusting for sex, age, body mass index, smoking, and alcohol consumption. Restricted cubic splines were used to characterize exposure-response relationships. Results Among 7,231 examinations, 430 (5.9%) were classified as having clinically abnormal lung function. The median workplace mean chlorine concentration was 0.047 mg/m³. For each one-unit increase in log₂-transformed cumulative exposure, higher odds were observed for clinically abnormal lung function (OR, 1.06; 95% CI, 1.02–1.10), low FEV₁ (OR, 1.03; 95% CI, 1.01–1.05), and low FVC (OR, 1.03; 95% CI, 1.01–1.05). Exposure–response curves generally showed increasing odds of these outcomes with increasing exposure, accompanied by decreasing FEV₁ and FVC z-scores. No clear exposure-related pattern was observed for FEV₁/FVC-related outcomes. Conclusions Despite a median workplace chlorine concentration far below the current Chinese maximum allowable concentration (MAC), greater cumulative exposure was associated with higher odds of abnormal lung function and lower FEV₁ and FVC, while FEV₁/FVC remained largely unchanged. These findings raise concern that repeated low-level exposure may carry respiratory risks not fully captured by ceiling-based monitoring and underscore the importance of cumulative exposure assessment and longitudinal lung-function surveillance.

BACKGROUND:Bronchopulmonary dysplasia (BPD) is a common complication in premature infants, particularly those born extremely preterm, and is a significant risk factor for neurodevelopmental impairment. Rehabilitation therapy has been shown to improve both pulmonary and neurological functions in infants with BPD. However, in China, there is no consensus on the optimal timing, type, frequency or follow-up of rehabilitation exercises for these infants. Understanding the current clinical practices, challenges and areas for improvement is essential to enhancing outcomes. AIM:To investigate current clinical rehabilitation practices for BPD in the Neonatal Intensive Care Unit (NICU). STUDY DESIGN:Qualitative descriptive study. RESULTS:A total of 12 informants participated in this study. Four major themes were identified: (1) Non-standardized rehabilitation practices: Inconsistent frequency and intensity of rehabilitation therapy, delayed initiation and lack of follow-up. (2) Lack of consensus and collaboration: Absence of expert consensus on rehabilitation practices and insufficient interdisciplinary communication. (3) Limited parental involvement in rehabilitation: Minimal kangaroo care, low engagement in caregiver training and limited support for family participation in rehabilitation. (4) Nurses' involvement in rehabilitation therapy is limited, with issues including unstandardized positioning management, minimal participation in rehabilitation coordination and a lack of proactive feedback on BPD infants' rehabilitation tolerance. (5) Inadequate rehabilitation environment: Constraints such as limited space, lack of family-centred wards, insufficient equipment and environmental issues with noise and lighting. CONCLUSIONS:Rehabilitation practices for BPD in the NICU are inconsistent, with limited interdisciplinary collaboration and suboptimal parental involvement. The study underscores the need for establishing a multidisciplinary team and developing evidence-based, culturally tailored rehabilitation protocols. Improving parental participation, creating appropriate rehabilitation spaces, managing environmental factors like noise and lighting, nurses should participate in training on positioning management and assist with rehabilitation therapy, actively providing feedback to the medical team on the tolerance of BPD infants and enhancing equipment availability will contribute to the early recovery of infants with BPD. RELEVANCE TO CLINICAL PRACTICE:This study highlights critical gaps in current rehabilitation practices for BPD in NICUs, suggesting that a standardized, evidence-based approach is needed to optimize care. Clinicians should focus on fostering multidisciplinary collaboration, enhancing parental involvement and improving the physical environment of NICUs to support the rehabilitation process for premature infants with BPD. Nurses in the NICU play a pivotal role in the rehabilitation of children with BPD. Their key responsibilities include assessing the infants' condition to determine their ability to tolerate rehabilitation and providing hands-on support throughout the treatment process.

Pre-eclampsia (PE) is a serious pregnancy disorder linked to genetic factors, particularly the ACVR2A gene, which encodes a receptor involved in the activin signaling pathway and plays a critical role in reproductive processes. Transcriptomic data analysis and experimental verification confirmed a downregulation of ACVR2A expression in placental tissues from PE patients. In this study, CRISPR/Cas9 technology was employed to investigate the effect of ACVR2A gene deletion on trophoblast cells using the HTR8/SVneo and JAR cell lines. Deletion of ACVR2A inhibits trophoblastic migration, proliferation, and invasion, underscoring its pivotal role in cellular function. RNA-seq data analysis unveiled an intricate regulatory network influenced by ACVR2A gene knockout, especially in the TCF7/c-JUN pathway. By employing RT-PCR and immunohistochemical analysis, a potential association between ACVR2A and the TCF7/c-JUN pathway was hypothesized and confirmed. The complexity of PE onset and the significance of genetic factors were emphasized, particularly the role of the ACVR2A gene identified in genome-wide association study. This study established a robust foundation for delving deeper into the intricate mechanisms of PE, paving the way for focused early intervention, personalized treatment, and enhanced obstetric healthcare.

BACKGROUND:Mothers with chronic hepatitis B and advanced fibrosis may require antiviral therapy throughout pregnancy. Current guidelines recommend tenofovir disoproxil fumarate (TDF), which is unsuitable for mothers at risk of renal dysfunction or decreased bone mineral density. AIMS:This study aimed to evaluate the safety of tenofovir alafenamide (TAF) therapy during pregnancy. METHODS:Mothers with chronic hepatitis B treated with TAF or no therapy were retrospectively enrolled and categorised into three groups: (A) TAF-first trimester, (B) TAF-late trimester and (C) no treatment. Propensity score matching was applied to create comparable groups. Primary assessments included serious adverse events up to postpartum week 28, while secondary assessments examined predictors of such events and vertical transmission rates. RESULTS:Among 284 mothers, 160 were selected. No significant differences were observed in foetal loss, low birth weight, preterm delivery or congenital abnormalities between groups A and B, or between groups A and C. Other adverse events were similar across groups, except for a higher incidence of gestational diabetes in the TAF-first trimester group. In vitro fertilisation was identified as the sole predictor of serious events. No infants were reported with hepatitis B virus infection at 28 weeks postpartum. CONCLUSIONS:This study suggests that TAF treatment throughout pregnancy is safe for mothers with chronic hepatitis B and their infants. TAF therapy represents a viable treatment option for these mothers.

Preeclampsia (PE) is a multisystem progressive disease unique to pregnancy, the pathogenesis of PE is thought to be linked to inadequate trophoblast invasion. Annexin a2 (ANXA2) has been found to be closely related to tumor metastasis and it may be involved in trophoblast invasion. Evidence from translational oncology research indicates that ANXA2 overexpression drives metastatic progression in malignancies via canonical Wnt/β-catenin pathway activation, particularly through stabilization of cytoplasmic β-catenin and subsequent nuclear translocation. The Wnt/β-catenin signaling pathway is an important pathway in placental implantation and embryonic development. This study aims to elucidate the role of ANXA2 in the progression of PE. ANXA2 expression in PE placentas was analyzed using Western blotting and immunohistochemistry. The cell proliferation, invasion, and migration were assessed using MTT assay, transwell, and wound healing assays. Our findings indicate a significant reduction in ANXA2 expression in the placentas of PE patients compared to controls. ANXA2 knockdown in HTR-8/SVneo cells resulted in decreased cell proliferation, invasion, and migration. Conversely, overexpression of ANXA2 enhanced these cellular functions. Furthermore, knockdown of ANXA2 led to suppression of the β-catenin signaling pathway through the modulation of GSK-3β expression. The downregulation of ANXA2 contributes significantly to the pathogenesis of PE by impairing trophoblast invasion and migration via inhibition of the β-catenin signaling pathway. These findings highlight the critical role of ANXA2 in the development of PE and suggest that targeting ANXA2-related pathways may offer novel therapeutic avenues for the management of this disorder.

OBJECTIVE:To evaluate the association between previous non-cesarean uterine surgery and placenta accreta spectrum (PAS) in subsequent pregnancies. DATA SOURCES:PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov , CNKI (China National Knowledge Infrastructure), and Wan-fang Database were searched from inception to April 2024, supplemented by manual searches. METHODS OF STUDY SELECTION:Studies included prospective, retrospective cohort, case-control, and cross-sectional studies involving pregnant women diagnosed with PAS and reporting at least one risk factor associated with previous uterine surgery. TABULATION, INTEGRATION, AND RESULTS:Two authors independently screened potentially eligible studies and extracted data. The quality of the studies was assessed with the Newcastle-Ottawa Scale. The pooled odds ratios (ORs), adjusted ORs, and their 95% CIs were estimated with fixed- or random-effects models if the heterogeneity ( I2 ) was high. Sensitivity analyses were conducted to account for potential study bias. The main measures were myomectomy, uterine artery embolization, dilatation and curettage, hysteroscopic adhesiolysis, abortion, endometrial ablation, and operative hysteroscopy. A total of 38 studies involving 7,353,177 participants were included in the systematic review, with an overall prevalence of PAS of 0.16%, and 31 studies were included in the meta-analysis. Prior non-cesarean uterine surgeries were associated with PAS in subsequent pregnancy (pooled OR 2.29, 95% CI, 1.43-3.68). Distinct associations between specific uterine surgery and PAS included myomectomy (OR 2.29, 95% CI, 1.77-2.97), uterine artery embolization (OR 43.16, 95% CI, 20.50-90.88), dilatation and curettage (OR 2.28, 95% CI, 1.78-2.93), hysteroscopic adhesiolysis (OR 7.72, 95% CI, 4.10-14.53), abortion (OR 1.65, 95% CI, 1.43-1.92), endometrial ablation (OR 20.26, 95% CI, 17.15-23.93), and operative hysteroscopy (OR 3.10, 95% CI, 1.86-5.18). CONCLUSION:Prior non-cesarean uterine surgery is associated with a significantly increased odds for development of PAS in subsequent pregnancy, and the risk varies depending on the types of uterine surgery. SYSTEMATIC REVIEW REGISTRATION:PROSPERO: CRD42024552210.

BACKGROUND:Listeria monocytogenes is one of the major bacteria responsible for meningitis. Controversy exists regarding the neuropathological effect of human pegivirus-1 (HPgV-1). Whether HPgV-1 interacts with L. monocytogenes is unknown. Herein, we describe a multiple myeloma patient with disseminated L. monocytogenes and HPgV-1 coinfection. CASE PRESENTATION:The case of a 57-year-old patient with fever accompanied by headache, dizziness, nausea, vomiting of stomach contents, and urinary and faecal incontinence is presented. Through metagenomic next-generation sequencing and the detection of L. monocytogenes and HPgV-1 in cerebrospinal fluid, along with blood culture of L. monocytogenes and PCR of HPgV-1 in the blood, a diagnosis of HPgV-1 and L. monocytogenes meningitis, HPgV-1 viremia, and L. monocytogenes sepsis was made, enabling timely and proper treatment with meropenem. After treatment, the patient recovered and was discharged from the hospital. CONCLUSIONS:To our knowledge, this is the first reported case of disseminated L. monocytogenes and HPgV-1 coinfection. Determining whether HPgV-1 was responsible for meningitis will require further research, including histopathological analysis.

Chronic inflammation is a key element in the progression of essential hypertension (EH). Calcium plays a key role in inflammation, so its receptor, the calcium-sensing receptor (CaSR), is an essential mediator of the inflammatory process. Compelling evidence suggests that CaSR mediates inflammation in tissues and immune cells, where it mediates their activity and chemotaxis. Macrophages (Mφs) play a major role in the inflammatory response process. This study provided convincing evidence that R568, a positive regulator of CaSR, was effective in lowering blood pressure in spontaneously hypertensive rats (SHRs), improving cardiac function by alleviating cardiac hypertrophy and fibrosis. R568 can increase the content of CaSR and M2 macrophages (M2Mφs, exert an anti-inflammatory effect) in myocardial tissue, reduce M1 macrophages (M1Mφs), which have a pro-inflammatory effect in this process. In contrast, NPS2143, a negative state regulator of CaSR, exerted the opposite effect in all of the above experiments. Following this study, R568 increased CaSR content in SHR myocardial tissue, lowered blood pressure, promoted macrophages to M2Mφs and improved myocardial fibrosis, but interestingly, both M1Mφs and M2Mφs were increased in the peritoneal cavity of SHRs, the number of M2Mφs remained lower than M1Mφs. In vitro, R568 increased CaSR content in RAW264.7 cells (a macrophage cell line), regulating intracellular Ca2+ ([Ca2+]i) inhibited NOD-like receptor family protein 3 (NLRP3) inflammasome activation and ultimately prevented its conversion to M1Mφs. The results showed that a decrease in CaSR in hypertensive rats causes further development of hypertension and cardiac damage. EH myocardial remodeling can be improved by CaSR overexpression by suppressing NLRP3 inflammasome activation and macrophage polarization toward M1Mφs and increasing M2Mφs.

The cardiac inflammatory response, characterized by immune cell infiltration, is involved in developing myocardial fibrosis during hypertension. Although calcium-sensitive receptor (CaSR) regulates inflammatory response, the specific mechanism remains unclear. To determine the role of CaSR in regulating hypertensive macrophage polarization, CaSR agonists/inhibitors were intraperitoneally injected into16-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, followed by examining the macrophage polarization markers and cardiac collagen deposition in the rat hearts. The study used the RAW264.7 macrophage cell line and the mouse myocardial fibroblast cell line to investigate the signaling pathway of CaSR regulating macrophage polarization and the effect of macrophage polarization on myocardial fibroblasts. We also detected the changes in macrophage polarization markers and Ca /cAMP/NF-κB/NLRP3 inflammasome signaling molecules, myocardial fibroblast proliferation, and transdifferentiation markers with the intervention of related drugs. CaSR reduces M1-type polarization and enhances M2-type polarization of SHR myocardial tissue macrophages by reducing NLRP3 inflammasome activation, alleviating hypertensive myocardial fibrosis. In isolated macrophages, CaSR activates NLRP3 inflammasome via the PLC/Ca and cAMP/NF-κB signaling pathways, which subsequently promotes M1-type polarization, reduces M2-type polarization in macrophages, and promotes activation of cardiac fibroblasts via paracrine effects.

Biomass exposure is a significant environmental risk factor for COPD, but the underlying mechanisms have not yet been fully elucidated. Inflammatory microenvironment has been shown to drive the development of many chronic diseases. Pollution exposure can cause increased levels of inflammatory factors in the lungs, leading to an inflammatory microenvironment which is prevalent in COPD. Our findings revealed that IL-17F was elevated in COPD, while exposure to biomass led to increased expression of IL-17F in both alveolar epithelial and macrophage cells in mice. Blocking IL-17F could alleviate the lung inflammation induced by seven days of biomass exposure in mice. We employed a transwell co-culture system to simulate the microenvironment and investigate the interactions between MLE-12 and MH-S cells. We demonstrated that anti-IL-17F antibody attenuated the inflammatory responses induced by BRPM2.5 in MLE-12 and MH-S co-cultured with BRPM2.5-MLE-12, which reduced inflammatory changes in microenvironment. We found that IL-17RC, an important receptor for IL-17F, played a key role in the interactions. Knockout of IL-17RC in MH-S resulted in inhibited IL-17F signaling and attenuated inflammatory response after MH-S co-culture with BRPM2.5-MLE-12. Our investigation suggests that BRPM2.5 induces lung epithelial-macrophage interactions via IL-17F/IL-17RC axis regulating the inflammatory response. These results may provide a novel strategy for effective prevention and treatment of biomass-related COPD.

Rare gene variants have been found to play a role in complex disorders. Preeclampsia, and especially early-onset preeclampsia, has a strong genetic link. However, the role of rare variants in the offspring of mothers with preeclampsia remains unclear. In this study, whole-exome sequencing (WES) was used to identify rare pathogenic variants in two families with early-onset preeclampsia. Two heterozygous rare variants in CCDC7, c.625C>T (p.R209C) and c.1015C>T (p.R339X), were detected in two families and were cosegregated in the offspring of preeclamptic pregnancies. We examined the spatiotemporal expression pattern of CCDC7 in human placental villi and the effects of CCDC7 on migration and invasion of trophoblast cells JEG-3. The quantitative real-time PCR and Western blot results showed that the expression of CCDC7 in placental villi was the lowest during the first trimester and increased as the pregnancy progressed. The CCDC7 p.R339X variant showed a decrease in mRNA and protein expressions. Loss-of-function assays showed that knockdown of CCDC7 suppressed the migration and invasion of JEG-3 cells. In conclusion, CCDC7 is a potential susceptibility gene for preeclampsia, which is key for the migration and invasion of trophoblast cells. Rare variants of preeclampsia in offspring may play a crucial role in the pathogenesis of preeclampsia and require further research.

BackgroundCHKB mutations have been described in 49 patients with megaconial congenital muscular dystrophy, which is a rare autosomal recessive disorder, of which 40 patients showed homozygosity. MethodsPeripheral blood genomic DNA samples were extracted from patients and their parents and were tested by whole exome sequencing. Quantitative PCR was performed to detect deletion. Single nucleotide polymorphism analysis was performed to identify uniparental disomy. Quantitative PCR and western blot were used to measure the expression level of CHKB in patient 1-derived immortalized lymphocytes. Mitochondria were observed in lymphocytes by electron microscopy. ResultsTwo unrelated cases born to non-consanguineous parents were diagnosed with megaconial congenital muscular dystrophy due to apparently homozygous mutations (patient 1: c.225-2A>T; patient 2: c.701C>T) in the CHKB gene using whole exome sequencing. Quantitative PCR revealed that patient 1 had a large deletion encompassing the CHKB gene, inherited from the mother. Single nucleotide polymorphism analysis revealed patient 2 had paternal uniparental isodisomy containing the CHKB gene. In the immortalized lymphocytes from patient 1, decreased expression of CHKB was revealed by quantitative PCR and western blot, and giant mitochondria were observed using electron microscopy. ConclusionWe provide a possibility to detect giant mitochondria in other cells when muscle was not available. Moreover, clinicians should be aware that homozygous variants can be masqueraded by uniparental disomy or large deletions in offspring of non-consanguineous parents, and excessive homozygosity may be misdiagnosed.

In brief Placenta accreta spectrum (PAS) has an urgent need for reliable prenatal biomarkers. This study profiled the circular RNAs (circRNAs) in PAS placenta and maternal blood and identified two circRNAs can regulate trophoblast cells invasion and serve as noninvasive prenatal biomarkers for PAS prediction. Abstract PAS is one of the most alarming obstetric diseases with high mortality rates. The regulating mechanism underlying PAS remains to be investigated, and reliable blood biomarkers for PAS have not emerged. Circular RNAs (circRNAs) have become important regulators and biomarkers for disparate human diseases. However, the circRNA profiles of PAS were not reported, and the regulatory role and predictive value of circRNAs in PAS were unknown. Here, we comprehensively profiled the circRNAs in the placenta of PAS by transcriptome sequencing and analysis and uncovered 217 abnormally expressed circRNAs. Through competing endogenous RNA network analysis, we found that the target genes of upregulated circRNAs in PAS were enriched in placenta development-related pathways and further uncovered two circRNAs, circPHACTR4 and circZMYM4, that could regulate trophoblast cells invasion and migration in vitro. Finally, we verified that circPHACTR4 and circZMYM4 were also upregulated in the maternal peripheral blood of PAS women before delivery using transcriptome sequencing and RT-qPCR and evaluated their predictive value by ROC curves. We found that circPHACTR4 and circZMYM4 could serve as effective predicting biomarkers for PAS (area under the curve (AUC): 0.86 and 0.85) and propose an improved model for PAS prenatal prediction by combining the conventional ultrasound diagnosis with the new circRNA predictive factors (AUC: 0.91, specificity: 0.89, sensitivity: 0.82).Altogether, this work provides new resources for deciphering the biological roles of circRNAs in PAS, identified two circRNAs that could regulate trophoblast cells invasion during placentation, and revealed two noninvasive diagnostic markers for PAS.

Background Placenta accreta spectrum (PAS) disorder is a major cause of postpartum hemorrhage-associated maternal and fetal death, and novel methods for PAS screening are urgently needed for clinical application. Methods The purpose of this study was to develop new methods for PAS screening using serum biomarkers and clinical indicators. A total of 95 PAS cases and 137 controls were enrolled in a case–control study as cohort one, and 44 PAS cases and 35 controls in a prospective nested case–control study were enrolled as cohort two. All subjects were pregnant women of Chinese Han population. Biomarkers for PAS from maternal blood samples were screened based on high-throughput immunoassay and were further validated in three phases of cohort one. Screening models for PAS were generated using maternal serum biomarkers and clinical indicators, and were validated in two cohorts. The expression levels of biomarkers were analyzed using histopathological and immunohistochemical (IHC) techniques, and gene expression was examined by QPCR in the human placenta. Binary logistic regression models were built, and the area under the curve (AUC), sensitivity, specificity, and Youden index were calculated. Statistical analyses and model building were performed in SPSS and graphs were generated in GraphPad Prism. The independent-sample t test was used to compare numerical data between two groups. For nonparametric variables, a Mann–Whitney U test or a X 2 test was used. Results The results demonstrated that the serum levels of matrix metalloproteinase-1 (MMP-1), epidermal growth factor (EGF), and vascular endothelial growth factor-A (VEGF-A) were consistently higher, while the level of tissue-type plasminogen activator (tPA) was significantly lower in PAS patients compared with normal term controls and patients with pre-eclampsia (PE) and placenta previa (PP). IHC and QPCR analysis confirmed that the expression of the identified biomarkers significantly changed during the third trimester in human placenta. The generated screening model combining serum biomarkers and clinical indicators detected 87% of PAS cases with AUC of 0.94. Conclusions Serum biomarkers can be used for PAS screening with low expense and high clinical performance; therefore, it may help to develop a practicable method for clinical prenatal PAS screening.

Our previous study demonstrated in vivo that mouse cytomegalovirus (MCMV) infection promoted vascular remodeling after downregulation of miR-1929-3p. This study aimed to investigate the role of miR-1929-3p/ETAR/NLRP3 pathway in mouse vascular smooth muscle cells (MOVAS) after MCMV infection. First, PCR was used to detect the success of the infection. Second, MOVAS were transfected with the miR-1929-3p mimic, inhibitor, and ETAR overexpressed adenovirus vector. Cell proliferation was detected using EdU, whereas apoptosis was detected using flow cytometry. The expression of miR-1929-3p and ETAR were detected using qRT-PCR. Western blot detected proteins of cell proliferation, apoptosis, and the NLRP3 inflammasome. Interleukin-1 beta and interleukin-18 were determined using ELISA. The results revealed that after 48 h, MCMV infection promoted the proliferation of MOVAS when the MOI was 0.01. MCMV infection increased ETAR by downregulating miR-1929-3p. The miR-1929-3p mimic reversed the proliferation and apoptosis, whereas the miR-1929-3p inhibitor promoted this effect. ETAR overexpression further promoted MCMV infection by downregulating miR-1929-3p-mediated proliferation and apoptosis. MCMV infection mediates the downregulation of miR-1929-3p and the upregulation of ETAR, which activates NLRP3 inflammasome. In conclusion, MCMV infection promoted the proliferation of MOVAS, possibly by downregulating miR-1929-3p, promoting the upregulation of the target gene ETAR and activating NLRP3 inflammasome.

Downstream of the primary cause of fetal growth restriction are placental insufficiency and fetal malnutrition. Gut microbiota and metabolites appear to play an important role in the progression of gestation, while dysbiosis induces maternal and fetal complications.

MicroRNAs are crucial in the development of myocardial remodeling in hypertension. Low miR-1929-3p expression induced by murine cytomegalovirus ( MCMV) infection is closely related to hypertensive myocardial remodeling. This study investigated the molecular mechanism of miR-1929-3p-induced myocardial remodeling after MCMV infection. We modeled MCMV-infected mouse cardiac fibroblasts (MMCFs) as the primary cell model. First, MCMV infection reduced the expression of miR-1929-3p and increased the mRNA and protein expression of its target gene endothelin receptor type A (ETAR) in mouse cardiac fibroblasts (MCFs), which demonstrated an internal relationship with myocardial fibrosis (MF) based on high proliferation, phenotypic transformation (alpha-SMA), and collagen expression in MMCFs. The transfection of the miR1929-3p mimic downregulated the high expression of ETAR and alleviated these adverse effects in MMCFs. Inversely, these effects were exacerbated by the miR-1929-3p inhibitor. Second, the transfection of endothelin receptor type A over-expressed adenovirus (adETAR) reversed these positive effects of the miR-1929-3p mimic on MF improvement. Third, the transfection of adETAR exhibited a strong inflammatory response in MMCFs with increased expression of NOD-like receptors pyrin domain containing 3 (NLRP3) and increased secretion of interleukin-18. However, we found that the ETAR antagonist BQ123 and the selected NLRP3 inflammasome inhibitor MCC950 effectively eliminated the inflammatory response induced by both MCMV infection and miR-1929-3p inhibitor. Moreover, the MCF supernatant was related to cardiomyocyte hypertrophy. Our findings suggest that MCMV infection promotes MF by inducing the downregulation of miR-1929-3p and the high expression of ETAR, which activates NLRP3 inflammasomes in MCFs.