Identification and investigation of protein-related molecules in patients with hyperlipidemia using label-free combined with bioinformatics analysis.

This study aimed to identify proteins associated with high-fat diet patients and investigate their relationship with this dietary pattern. Five hyperlipidemia female patients and five normal individuals were included as the experiment and control groups, respectively. Blood samples were collected from both groups, and bioinformatics tools were employed for gene ontology annotation, KEGG pathway annotation, GO enrichment analysis, pathway enrichment analysis, and protein clustering to pinpoint genes, proteins, and pathways relevant to high-fat diet patients. Mass spectrometry analysis was subsequently used to confirm these proteins. The results indicated that bioinformatics analysis identified several proteins (P09871, P01019, P48740, P02654, P02649) potentially involved in the high-fat diet process by regulating downstream pathways. Label-free analysis revealed 3915 peptides in both groups, with 16 protein expression levels up-regulated in the experiment group, 13 of which showed significant differences. In contrast, 12 protein expression levels were down-regulated in the experiment group, with two showing significant differences. Notably, the proteins highlighted by bioinformatics analysis aligned with those identified through mass spectrometry. In conclusion, label-free analysis combined with bioinformatics can effectively identify proteins linked to high-fat diet patients. This research provides a fresh perspective on addressing high-fat diet-related issues using this approach.

The influence of perceived stress of Chinese healthcare workers after the opening of COVID-19: the bidirectional mediation between mental health and job burnout.

Objective: To explore the current status and interaction of perceived stress, job burnout and mental health among healthcare workers after the opening of COVID-19 which occurred in December 2022. Methods: A cross-sectional study of 792 healthcare workers from three tertiary hospitals in Wuxi was conducted from January 2023 to February 2023. Sociodemographic questionnaire, Perceived Stress Scale, Burnout Scale and Mental Health Self-Assessment Questionnaire were used for investigation. SPSS 26.0 was used to conduct data analysis. The significance of mediation was determined by the PROCESS macro using a bootstrap method. Results: The results showed that (1) The average scores of the participants for perceived stress, mental health and job burnout were 22.65 (7.67), 3.85 (4.21) and 1.88 (1.03), respectively. (2) The perceived stress score, mental health score and job burnout score of healthcare workers were positively correlated (r = 0.543-0.699, p < 0.05). (3) Mental health partially mediated the relationship between perceived stress and job burnout with a mediating effect of 17.17% of the total effect. Job burnout partially mediated the correlation between perceived stress and mental health with a mediating effect of 31.73% of the total effect. Conclusion: The results of this study suggested that perceived stress had an impact on job burnout and mental health, either directly or indirectly. Healthcare managers should intervene to reduce perceived stress to protect healthcare workers' mental health, thereby alleviating burnout under the opening COVID-19 pandemic environment.

Mass Tuberculosis Screening Among the Elderly: A Population-Based Study in a Well-Confined, Rural County in Eastern China.

BACKGROUND: Mass tuberculosis (TB) screening has been recommended in certain high-risk populations. However, population-based screening interventions have rarely been implemented. Whether mass screening improves health equity is unknown. METHODS: We implemented a mass TB screening intervention among elderly persons (>60 years old) in Lanxi County, China. Standardized questionnaires, physical examinations, and chest radiographs (CXRs) were administered to all participants. Systematic testing with computed tomography, smear, culture, or Xpert was performed among persons with an abnormal CXR. We assessed TB prevalence per 100 000 persons and constructed multivariable regression models among subgroups that were and were not screened. Medical insurance was categorized as participation in either a basic program with limited coverage or a more comprehensive coverage program. RESULTS: In total, 49 339 individuals (32% of the elderly population in Lanxi) participated in the screening. One hundred fifteen screened persons were diagnosed with TB (233 cases per 100 000 persons), significantly higher than persons not screened (168 cases among 103 979 person-years; prevalence-to-case notification ratio, 1.44 [95% confidence interval {CI}, 1.14-1.83]). This increase was largely driven by diagnosis of asymptomatic disease during mass screening (n = 57 [50% of participants with TB]). Participants with basic medical insurance were much more likely to be diagnosed through mass screening than by passive detection (adjusted odds ratio, 4.52 [95% CI, 1.35-21.28]). CONCLUSIONS: In a population-based, mass TB screening intervention encompassing >30% of the elderly population in a county in rural China, case finding was 44% higher than background detection, driven by diagnosis of TB without recognized symptoms. Importantly, mass screening identified TB in people with limited healthcare options who were less likely to be found through background case detection.

Hyperglycemia-induced endothelial exosomes trigger trophoblast dysregulation and abnormal placentation through PUM2-mediated repression of SOX2.

BACKGROUND: Hyperglycemia is closely related to adverse pregnancy outcomes including pre-eclampsia (PE), a life-threatening complication with a substantial morbidity and mortality. However, the pathogenesis of abnormal placentation in gestational diabetes mellitus (GDM)-associated PE remains elusive. METHOD: Here we isolated exosomes from the human umbilical vein endothelial cells (HUVECs) treated with normal level of glucose (NG) and high levels of glucose (HG). The exosomes were added to HTR-8a/SVneo cells, a trophoblast cell line. High-throughput RNA-sequencing was performed to analyzed the changed RNAs in the exosomes and exosome-treated HTR-8a/SVneo cells. HTR-8a/SVneo cell phenotypes were evaluated from the aspects of cell proliferation, cell invasion and DNA damage. RESULTS: After treatment with HG, the changed RNAs in exosomes was enriched in RNA stabilization and oxidative stress. The altered RNAs in the HTR-8a/SVneo cells treated with exosomes from HG-induced HUVECs were enriched in pathways related to cell adhesion, migration, DNA damage response and angiogenesis. The HG-induced exosomes impaired the proliferation and invasion of HTR-8a cells and caused the DNA damage. HG up-regulated PUM2 in the exosomes and exosome-treated HTR-8a/SVneo cells. PUM2 interacted with SOX2 mRNA, resulting in the mRNA degradation. Overexpression of SOX2 prevented the damage to HTR-8a/SVneo cells caused by the exosomes from HG-induced HUVECs. CONCLUSIONS: We demonstrate that high glucose-induced endothelial exosomes mediate abnormal phenotypes of trophoblasts through PUM2-mediated repression of SOX2. Our results reveal a novel regulatory mechanism of hyperglycemia in development of abnormal placentation and provide potential targets for preventing adverse pregnancy outcomes.

Pathogenicity and transmissibility of current H3N2 swine influenza virus in Southern China: A zoonotic potential.

Swine are considered as 'mixing vessels' of influenza A viruses and play an important role in the generation of novel influenza pandemics. In this study, we described that the H3N2 swine influenza (swH3N2) viruses currently circulating in pigs in Guangdong province carried six internal genes from 2009 pandemic H1N1 virus (pmd09), and their antigenicity was obviously different from that of current human H3N2 influenza viruses or recommended vaccine strains (A/Guangdong/1194/2019, A/Hong Kong/4801/2014). These swH3N2 viruses preferentially bonded to the human-like receptors, and efficiently replicated in human, canine and swine cells. In addition, the virus replicated in turbinate and trachea of guinea pigs, and efficiently transmitted among guinea pigs, and virus shedding last for 6 days post-infection (dpi). The virus replicated in the respiratory tract of pigs, effectively transmitted among pigs, and virus shedding last until 9 dpi. Taken together, these current swH3N2 viruses might have the zoonotic potential. Strengthening surveillance and monitoring the pathogenicity of such swH3N2 viruses are urgently needed.

MiR-186-5p Dysregulation Leads to Depression-like Behavior by De-repressing SERPINF1 in Hippocampus.

Diagnosis of major depressive disorder (MDD) is perplexing due to its multifactorial etiologies. Here, we isolated exosomes from the peripheral blood of MDD patients and healthy control subjects for mass spectrometry-based label-free quantitative proteomics. We identified that SERPINF1 is significantly diminished in the peripheral blood-derived exosomes of MDD patients compared to the healthy control subjects. Through RNA immunoprecipitation and luciferase reporter assays, we validated that SERPINF1 is a target of miR-186-5p that is upregulated in MDD patients' blood. In vivo studies in the chronic unpredictable mild stress (CUMS) mice further demonstrated that SERPINF1 in hippocampus is suppressed by miR-186-5p. Inhibiting the microRNA significantly restores the hippocampal SERPINF1 mRNA and protein expression, and ameliorates the depressive-like behaviors including sucrose preference and extended immobility time in the forced swim test. Instead, overexpressing miR-186-5p through tail intravenous injection of the mimics molecularly and behaviorally phenocopies the CUMS mice in wild-type mice. Our results indicate that the exosomal SERPINF1 in peripheral blood could serve as a reliable biomarker indicating MDD development, and miR-186-5p is a potential therapeutic target for the disease.

Willingness to receive SARS-CoV-2 vaccine among healthcare workers in public institutions of Zhejiang Province, China.

This study aims to investigate healthcare workers' (HCWs) willingness to receive SARS-CoV-2 vaccine in Zhejiang and to discover the related influential factors. The survey was conducted in six regions of Zhejiang Province, China, and 13 hospitals and 12 Centers for Disease Control and Prevention (CDC) were incorporated into the survey research. Participants were healthcare workers and a total of 3726 questionnaires were collected online, of which 3634 (97.53%) were analyzed. The relationships between the factors and the willingness to get vaccinated against COVID-19 were computed as odds ratios (ORs) by means of multi-factor non-conditional logistic regression analysis. Of the 3634 participants, 2874 (79.09%) HCWs expressed their willingness to get vaccinated if the SARS-CoV-2 vaccine becomes available. Respondents who were younger than 50 years (OR = 1.502, 95% CI: 1.047-2.154), those who believed that they were somewhat likely (OR = 1.658, 95% CI: 1.297-2.120) or likely (OR = 1.893, 95% CI: 1.334-2.684) to get infected by SARS-COV-2 and those with a positive attitude toward the SARS-CoV-2 vaccine were more willing to get vaccinated. Furthermore, compared to doctors, nurses were more reluctant to get vaccinated. In addition, it was found that higher the education level, lower the willingness to get vaccinated. This study revealed that HCWs in Zhejiang Province had a high willingness to get vaccinated. Awareness about the vaccine's effectiveness and safety and the disease severity should be promoted among HCWs over 50 years of age and nurses to increase the willingness to get vaccinated.

Identification of Differentially Expressed Proteins in Serum of Obese Patients by Isobaric Tags for Relative and Absolute Quantification (iTRAQ)-Coupled 2D LC-MS.

BACKGROUND The aim of this study was to identify the differentially expressed proteins of obese patients compared with normal participants and to provide a potential target for future investigation of obesity. MATERIAL AND METHODS We enrolled 10 obese male adults and 10 matched normal subjects. Serum samples were collected to get total protein extraction, denaturation, deoxidation, and enzymatic hydrolysis. Differentially expressed proteins were distinguished with mass spectrometry after samples were labeled with iTRAQ. RESULTS A total of 9622 differentially expressed peptides were identified, corresponding to 733 proteins; 118 proteins of these showed significant differential expression, with 15 upregulated and 103 downregulated. CONCLUSIONS iTRAQ is an effective technique to identify differentially expressed proteins in obese patients. The development of obesity is correlated with a series of complex elements and mutual effects. The proteins identified in this study may provide novel directions and targets for future pathological studies of obesity.

Association of serum IL-21 and vitamin D concentrations in Chinese children with autoimmune thyroid disease.

BACKGROUND: The etiology of Autoimmune thyroid disease (AITD) in pediatric age is multifactorial and mainly implicated with immune disorder. Previous studies have reported that interleukin-21 (IL-21) and vitamin D play crucial roles in autoimmune diseases. We investigated the correlation between IL and 21 and 25(OH)D and their potential role in the pathogenesis of AITD. METHODS: Total of 54 primary Graves disease (GD) patients, 36 Hashimato's thyroditis (HT) cases and 30 healthy subjects from The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University from September through November 2017 to 2019. The serum concentrations of IL-21, 25(OH)D, thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), antibodies against receptor for TSH (TRAb) and thyroglobulin antibody (TGAb) were determined. RESULTS: The serum concentration of 25(OH)D was lower while IL-21 was higher in the GD patients and HT patients than in the control patients. Serum 25(OH)D concentration was negatively correlated with TPOAb and TGAb while serum IL-21 concentration was positively correlated with TPOAb, TGAb and TRAb in the HT group. Moreover, the serum concentration of 25(OH)D had a significant negative correlation with serum IL-21 concentration in the HT and GD children before or after treatment. Therefore, we studied the correlation between IL and 21 and 25(OH)D, and infer that they play a role in AITD. Moreover, adding Vitamin D could inhibit the expression concentrations of TPOAb, TGAb and IL-21. CONCLUSION: IL-21 and Vitamin D may be involved in the occurrence and development of AITD. Targeting IL-21 and Vitamin D may be a promising therapeutic approach for AITD in the future.

Status and influential factors of vitamin D among children aged 0 to 6 years in a Chinese population.

BACKGROUND: Vitamin D insufficiency and deficiency in childhood are common. However, the status and influential factors of vitamin D during different ages are not clear. This study aimed to survey vitamin D concentrations in children aged 0 to 6 years and explore its influential factors. METHODS: A total of 6953 children were recruited in Wuxi City of East China from January to December in 2016. Enzyme-linked immunosorbent assay was used to determine the serum concentrations of 25-hydroxyvitamin D [25(OH)D]. RESULTS: The median vitamin D concentrations in the infant group (0-1 years of age) was 69.40 nmol/L, which were higher than that in both the toddlerhood group (1-3 years of age; 62.30 nmol/L) and the preschool group (3-6 years of age; 50.85 nmol/L). In addition, the median vitamin D concentrations were 71.70 nmol/L in summer, which was higher than that in spring (64.25 nmol/L), autumn (62.95 nmol/L) and winter (64.10 nmol/L). However, no difference was observed between genders (P = 0.974). Furthermore, the prevalence of vitamin D deficiency (< 50 nmol/L) was 48.1% in the preschool group (3-6 years of age), which was higher than the 21.2% vitamin D deficiency in the toddlerhood group (1-3 years of age) and the 17.9% vitamin D deficiency in the infant group (0-1 years of age). Interestingly, a nonlinear association between 25(OH) D and air temperature was observed. CONCLUSIONS: A high prevalence of vitamin D deficiency was common in a Chinese population of children 0-6 years old, especially in the preschool-aged children. Therefore, we suggested that we should pay more attention to vitamin D supplementation in Chinese young children.

miR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia.

Oxidative stress is a major cause of adverse outcomes in preeclampsia (PE). Ferroptosis, i.e. programmed cell death from iron-dependent lipid peroxidation, likely mediates PE pathogenesis. We evaluated specific markers for ferroptosis in normal and PE placental tissues, using in vitro (trophoblasts) and in vivo (rat) models. Increase in malondialdehyde content and total Fe2+ along with reduced the glutathione content and glutathione peroxidase activity was observed in PE placenta. While the trophoblasts experienced death under hypoxia, inhibitors of ferroptosis, apoptosis, autophagy, and necrosis increased the cell viability. Microarrays, bioinformatic analysis, and luciferase reporter assay revealed that upregulation of miR-30b-5p in PE models plays a pivotal role in ferroptosis, by downregulating Cys2/glutamate antiporter and PAX3 and decreasing ferroportin 1 (an iron exporter) expression, resulting in decreased GSH and increased labile Fe2+. Inhibition of miR-30b-5p expression and supplementation with ferroptosis inhibitors attenuated the PE symptoms in rat models, making miR-30b-5p a potential therapeutic target for PE.

Variation and Molecular Basis for Enhancement of Receptor Binding of H9N2 Avian Influenza Viruses in China Isolates.

Currently, H9N2 avian influenza viruses (H9N2 AIVs) globally circulate in poultry and have acquired some adaptation to mammals. However, it is not clear what the molecular basis is for the variation in receptor-binding features of the H9N2 AIVs. The receptor-binding features of 92 H9N2 AIVs prevalent in China during 1994-2017 were characterized through solid-phase ELISA assay and reverse genetics. H9N2 AIVs that circulated in this period mostly belonged to clade h9.4.2. Two increasing incidents occurred in the ability of H9N2 AIVs to bind to avian-like receptors in 2002-2005 and 2011-2014. Two increasing incidents occurred in the strength of H9N2 AIVs to bind to human-like receptors in 2002-2005 and 2011-2017. We found that Q227M, D145G/N, S119R, and R246K mutations can significantly increase H9N2 AIVs to bind to both avian- and human-like receptors. A160D/N, Q156R, T205A, Q226L, V245I, V216L, D208E, T212I, R172Q, and S175N mutations can significantly enhance the strength of H9N2 AIVs to bind to human-like receptors. Our study also identified mutations T205A, D208E, V216L, Q226L, and V245I as the key sites leading to enhanced receptor binding of H9N2 AIVs during 2002-2005 and mutations S119R, D145G, Q156R, A160D, T212I, Q227M, and R246K as the key sites leading to enhanced receptor binding of H9N2 AIVs during 2011-2017. These findings further illustrate the receptor-binding characteristics of avian influenza viruses, which can be a potential threat to public health.

A metabolomic study on the gender-dependent effects of maternal exposure to fenvalerate on neurodevelopment in offspring mice.

BACKGROUND: The general population is widely exposed to fenvalerate. However, the effects of maternal exposure to fenvalerate on neurodevelopment in offspring and the underlying metabolic mechanism are largely unknown. METHODS: Pregnant mice were exposed to fenvalerate for 11 consecutive days. The forced swimming test (FST) was performed in 35 day-old offspring to investigate the effects of fenvalerate on neurobehavioral responses. Blood serum free T4 and free T3 concentrations were measured using commercial ELISA. Blood and thyroid samples were used for metabolomic analyses with UPLC Q-Exactive. The expression levels of neurotransmitter metaolite receptors were determined in the frontal cortex of offspring using real-time PCR. RESULTS: The immobility time, free T4 and free T3, and expression levels of Htr1a and Htr2a were statistically changed in offspring male mice. Metabolomic analysis revealed that the pentose phosphate pathway, starch and sucrose metabolism, glutamic acid metabolism were the key changed pathways in the blood, and thiamine metabolism was the key changed pathway in the thyroid. CONCLUSION: Prenatal exposure to fenvalerate affected neurodevelopment in male offspring mice both via the changed abundances of metabolites involved in glycolysis related metabolism and medium-chain fatty acid metabolism, and the changes in 5-HT receptor expression.

Genetic, Molecular, and Pathogenic Characterization of the H9N2 Avian Influenza Viruses Currently Circulating in South China.

The prevalence and variation of the H9N2 avian influenza virus (AIV) pose a threat to public health. A total of eight viruses isolated from farmed poultry in South China during 2017-2018 were selected as representative strains for further systematic study. Phylogenetic analyses indicated that these prevalent viruses belong to the Y280-like lineage and that the internal genes are highly similar to those of recently circulating human H7N9 viruses. The receptor-binding assay showed that most of the H9N2 isolates preferentially bound to the human-like receptor, increasing the risk of them crossing the species barrier and causing human infection. Our in vitro, multi-step growth curve results indicate these viruses can effectively replicate in mammalian cells. Infection in mice showed that three viruses effectively replicated in the lung of mice. Infection in swine revealed that the viruses readily replicated in the upper respiratory tract of pig and effectively induced viral shedding. Our findings suggested that the H9N2 AIVs circulating in poultry recently acquired an enhanced ability to transmit from avian to mammalians, including humans. Based on our findings, we propose that it is essential to strengthen the efforts to surveil and test the pathogenicity of H9N2 AIVs.

HOXD8/DIAPH2-AS1 epigenetically regulates PAX3 and impairs HTR-8/SVneo cell function under hypoxia.

The present study aimed to unravel the molecular basis underlying PAX3 down-regulation, known to be involved in pre-eclampsia (PE) occurrence and development. Data obtained from databases suggested that Pax3 methylation levels in the promoter region are high in the placentas of PE patients. However, the expression of methylation-adjusting enzymes, including DNMT1, LSD1, and EZH2, did not change. Since lncRNAs enhance the function of methylation-related enzymes independently of expression, we selected three lncRNAs, RP11-269F21.2, DIAPH2-AS1, and RP11-445K13.2, predicted to interact with methylation-adjusting enzymes. Two transcription factors, HOXD8 and Lhx3, predicted to regulate the expression of lncRNAs, were also selected. Using RNA interference technology, HOXD8 and Lhx3 were found to positively regulate DIAPH2-AS1 and RP11-445K13.2 in HTR-8/SVneo cells. Chromatin immunoprecipitation assays determined that DIAPH2-AS1 recruited LSD1 to histone 3, increasing DNMT1 stability at H3. The HOXD8/DIAPH2-AS1 network regulated HTR-8/SVneo cell function under hypoxia by epigenetically regulating PAX3. This regulatory network may thus be responsible for PAX3 down-regulation in the placentas of PE patients.

Associations between Maternal AFP and ß-HCG and Preterm Birth.

OBJECTIVE: Preterm birth (PTB) is a significant public health problem. We aimed to explore whether alpha fetal protein (AFP) or ß-human gonadotropin (ß-HCG) levels during pregnancy were associated with PTB in Chinese population. STUDY DESIGN: The clinical data collected Nanjing Medical University Affiliated Suzhou Hospital and Wuxi Maternity and Child Health Care Hospital between January 2006 and December 2011 were analyzed retrospectively. A total of 64,999 pregnant women were registered. In addition, 13,828 pregnant women were collected serum from the second trimester. The maternal serum AFP and ß-HCG were measured by enzyme immunoassay. RESULTS: In our study, the rate of PTB is 6.23%. With each unit increase of maternal AFP concentration, the adjusted odds of PTB was increased by 69.3% (odds ratio = 1.693, 95% confidence interval: 1.434-1.999, p = 0.00). We set AFP concentrations as high, medium, and low levels. When comparing with low concentration of AFP, high concentration of AFP (≥1.179 M) was positively associated with PTB with adjustment for potential confounders (p < 0.05). Nevertheless, no statistically significant associations were observed between maternal ß-HCG and PTB. CONCLUSION: In this study, maternal AFP concentration was associated with increased risk of PTB.

Application of iTRAQ proteomics in identification of the differentially expressed proteins of placenta of pregnancy with preeclampsia.

OBJECTIVE: To explore the differential protein profile of preeclampsia and identify its potential biomarker. METHODS: Around 20 pregnant women with preeclampsia (preeclampsia group) and 20 normal-term pregnancy (normal group) were collected from 2017 to 2018 in the study. Total protein of placenta tissues was extracted, denaturized, deoxidized, and enzymolyzed. The sample was labeled with isobaric tags for relative and absolute quantitation (iTRAQ) and analyzed with mass spectrum to identify differentially expressed proteins. RESULTS: There were 37 proteins, which were differentially expressed with significance (P < 0.05). Among them, 17 proteins were upregulated and 20 proteins were downregulated with significance in the placenta of preeclampsia group compared with control group, those proteins may have an induction or protection function during the development of preeclampsia. CONCLUSION: iTRAQ technology can effectively screen the differentially expressed proteins in the placenta, which can effectively diagnose the preeclampsia during pregnancy.

miR-362-3p regulates cell proliferation, migration and invasion of trophoblastic cells under hypoxia through targeting Pax3.

Preeclampsia (PE), a common obstetrical disorder, is one of the leading causes of pregnancy associated death. PE is closely linked with impaired migration and invasion ability of trophoblastic cells. miR-362-3p recently received our particular attention due not only to its aberrant expression in the placentas of patients with PE, but also to its important roles in regulating migration and invasion of various cells. This study was thus conducted to investigate the roles of miR-362-3p in PE and the related mechanism. The expression of miR-362-3p and Pax3 was examined in placentas of patients with PE and in normal placentas. HTR8/SVneo cells were cultured under hypoxia and transfected with miR-362-3p mimics, miR-362-3p inhibitors or Pax3 over-expression vectors. Results showed up-regulation of miR-362-3p but down-regulation of Pax3 in placentas of preeclamptic pregnancies. Luciferase report assay confirmed that Pax3 is a direct target of miR-362-3p. Although Pax3 was predicted to be targeted by miR-30a-3p and miR-181a-5p as well, their expression either had no difference between placentas of PE patients and normal placentas or showed less increment in placentas of PE patients than miR-362-3p. Exposure to hypoxia inhibited cell viability, migration and invasion of HTR8/SVneo cells. Increasing miR-362-3p by the mimics conferred improved effects on the inhibition. However, deletion of miR-362-3p or overexpression of Pax3 abolished the inhibiton. These results suggest that miR-362-3p/Pax3 axis regulates cell viability, migration and invasion of HTR8/SVneo cells under hypoxia. The present study adds to the further understanding of the pathogenesis of PE.

Fasudil attenuates soluble fms-like tyrosine kinase-1 (sFlt-1)-induced hypertension in pregnant mice through RhoA/ROCK pathway.

Preeclampsia (PE) has become the leading cause of maternal and fetal morbidity and mortality in the world, which is characterized by a systemic maternal inflammatory response associated with endothelial dysfunction, hypertension, and proteinuria. The development of PE is still barely predictable and thus challenging to prevent and manage clinically. Fasudil (FSD), the first-generation Rho/ROCK inhibitor, has been studied widely and applied in clinical practice with high safety and efficacy in treating hypertension and other cardiovascular diseases. However, few studies have focused on the effect of fasudil on preeclampsia in vivo and in vitro. Therefore, the aim of this study is to investigate the effects of fasudil on hypoxia/reoxygenation injury in vitro and its role on preeclamptic animal model. Here, we found that RhoA/ROCK pathway was significantly activated in H/R-challenged endothelial cells and in placenta and umbilical vessel of PE mice. And fasudil pre-treatment can protect vascular endothelial cells from H/R-induced apoptosis. In addition, inhibition of RhoA/ROCK pathway with fasudil can reduce the high blood pressure and urine protein levels as well as the concentration of s-Flt in peripheral and umbilical blood in a dose-dependent manner, thus resulting in prevention of the development of PE. Thus, Fasudil attenuates soluble fms-like tyrosine kinase-1 (sFlt-1)-induced hypertension in pregnant mice through RhoA/ROCK pathway, which would become a potential strategy for PE therapy.