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2.
Small ; : e2006807, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33590690

RESUMO

Ionic conductive hydrogel electrolyte is considered to be an ideal electrolyte candidate for flexible supercapacitor due to its flexibility and high conductivity. However, due to the lack of effective recycling methods, a large number of ineffective flexible hydrogel supercapacitors caused by some irreversible damages and dryness of hydrogel electrolyte are abandoned, which would induce heavy economic and environmental protection problems. Herein,a smart ionic conductive hydrogel (SPMA-Zn: ZnSO4 /sodium alginate/polymethylacrylic acid) is developed for flexible hybrid supercapacitor (SPMA-ZHS). The SPMA-Zn exhibits an excellent self-healing ability and can recover its electrochemical performance after multiple mechanical damages. More importantly, it possesses an outstanding powder self-healable property, which could easily regenerate the hydrogel electrolyte after powdering, and maintain stable electrochemical performance of SPMA-ZHS. Besides, the SPMA-ZHS displays excellent electrochemical performance with a wide and stable working voltage range of 0-2.2 V, high energy density of 164.13 Wh kg-1 at the power density of 1283.44 Wh kg-1 and good stability with a capacity retention of 95.3% after 5000 charge/discharge cycles at 10 A g-1 . The strategy in this work would provide a new insight in exploring flexible hydrogel electrolyte-based supercapacitor with good sustainability and high energy density for flexible wearable electronic devices.

3.
Eye (Lond) ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33564136

RESUMO

OBJECTIVES: To evaluate choroidal arterial watershed zones (CWZ) in highly myopic patients. The relationships between CWZ location and myopic maculopathy location and classification were also examined. METHODS: This retrospective study included 102 consecutive patients who had been diagnosed with myopic maculopathy. Indocyanine green videoangiography was used to evaluate CWZ presence, location, and configuration. Maculopathy signs were used to examine the relationship between CWZ and myopic maculopathy. RESULTS: Various CWZ types were identified in 102 of 158 eyes. The CWZ patterns were classified as vertical optic nerve head (vertical-ONH) in 30 eyes, stellate in 29 eyes, vertical-ONH extending to the macula in 28 eyes, horizontal fovea in eight eyes, and vertical parafovea in seven eyes. Choroidal neovascularization occurred within CWZs in 35 of 42 eyes, and macular atrophy was located within foveal CWZs in 20 of 23 eyes. The CWZ type was significantly correlated with mCNV presence (OR = 5.652, P = 0.014). CONCLUSIONS: Variations in CWZ topography are associated with myopic maculopathy, particularly in eyes with myopic choroidal neovascularization (mCNV) and macular atrophy, and CWZ is a risk factor for mCNV. This suggests that eyes with macular CWZs are vulnerable to developing myopic maculopathy and are predisposed to mCNV because of ischaemic hypoxia.

5.
Eur J Clin Nutr ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536570

RESUMO

Gastric-tube feeding and post-pyloric feeding are the two most common forms of enteral nutrition, each with advantages and disadvantages. To explore the effects and safety of gastric-tube versus post-pyloric feeding in critical patients by comparing pulmonary aspiration- and nutrition-related outcomes, a meta-analysis was conducted. It was performed by systematically searching the following databases: PubMed, EMBASE, Cochrane library, BMJ best practice, ProQuest dissertations and theses, CINAHL, web of science, SinoMed, WANFANG, CNKI, and the platform of clinical trial registration. The databases were searched through December 31, 2019, and studies were evaluated by two independent researchers. Review Manager software was used for data analysis. We included 41 studies conducted in ten countries and involving 3248 participants. Meta-analysis showed that post-pyloric feeding had a lower incidence rate of pulmonary aspiration, gastric reflux, and pneumonia (P < 0.001, all), less incidence of gastrointestinal complications including vomiting, nausea, diarrhea, abdominal distension, high gastric residual volume, and constipation (P < 0.05, all), more optimal gastrointestinal nutrition including the percentage of total nutrition provided to the patient, the time to tolerate enteral nutrition, the time required to start feeding and the time required to reach nutritional targets (P < 0.05, all), shorter length of mechanical ventilation, stay in ICU and stay in hospital (P < 0.001, all), compared with gastric-tube feeding. No significant differences were shown in the time of gastrointestinal function recovery, mortality, or hospitalization expenses between the two feeding routes. This review provides evidence that post-pyloric feeding appears to be the safer and more effective choice, as compared to gastric-tube feeding among critical patients.

6.
J Ethnopharmacol ; 271: 113893, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33524511

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Zuojin Pill (ZJP) is a classic prescription composed of Coptis chinensis and Tetradium ruticarpum (A.Juss.) T.G.Hartley, which is often used in the treatment of digestive system diseases. AIM OF THIS STUDY: The purpose of this study was to explore the therapeutic effect and potential mechanism of ZJP on chronic atrophic gastritis (CAG) induced by MNNG. MATERIALS AND METHODS: The GES-1 and rat model of CAG was established by MNNG. Detection of cell viability, morphological changes and proliferation of GES-1 by CCK-8 and high content screening (HCS) assay. G-17, IL-8 and TNF-α in rat serum were detected by ELISA kit. The expression of related mRNA and protein on TGF-ß1/PI3K/Akt signal axis were detected by RT-PCR and Western blot. RESULTS: The results showed that ZJP could significantly improve the GES-1 damage induced by MNNG and improve the gastric histomorphology of CAG rats. The intervention of ZJP could significantly reduce the content of G-17 and inflammatory factors IL-8, TNF- α, IL-6 and IL-1ß, inhibit the expression of TGF-ß1, PI3K and their downstream signals p-Akt, p-mTOR, P70S6K, and promote the expression level of PTEN, LC3-II and Beclin-1. CONCLUSION: ZJP has a good therapeutic effect on CAG induced by MNNG, which may be closely related to the inhibition of TGF-ß1/PI3K/Akt signal pathway.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33612357

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of Editors-in-Chief and first Author. The article duplicates significant parts of a paper that had already appeared in Fish & Shellfish Immunology, Volume 93 (2019) 726-731, https://doi.org/10.1016/j.fsi.2019.06.052. One of the conditions of submission of a paper for publication is that authors declare explicitly that the paper has not been previously published and is not under consideration for publication elsewhere. As such this article represents a misuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process. The article was published without the knowledge of the co-authors.

8.
Biomed Res Int ; 2021: 6621894, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33604379

RESUMO

Objective: To evaluate the efficiency of a radiomics model in predicting the prognosis of patients with acute paraquat poisoning (APP). Materials and Methods: Chest computed tomography images and clinical data of 80 patients with APP were obtained from November 2014 to October 2017, which were randomly assigned to a primary group and a validation group by a ratio of 7 : 3, and then the radiomics features were extracted from the whole lung. Principal component analysis (PCA) and least absolute shrinkage and selection operator (LASSO) regression were used to select the features and establish the radiomics signature (Rad-score). Multivariate logistic regression analysis was used to establish a radiomics prediction model incorporating the Rad-score and clinical risk factors; the model was represented by nomogram. The performance of the nomogram was confirmed by its discrimination and calibration. Result: The area under the ROC curve of operation was 0.942 and 0.865, respectively, in the primary and validation datasets. The sensitivity and specificity were 0.864 and 0.914 and 0.778 and 0.929, and the prediction accuracy rates were 89.5% and 87%, respectively. Predictors included in the individualized predictive nomograms include the Rad-score, blood paraquat concentration, creatine kinase, and serum creatinine. The AUC of the nomogram was 0.973 and 0.944 in the primary and validation datasets, and the sensitivity and specificity were 0.943 and 0.955, respectively, in the primary dataset and 0.889 and 0.929 in the validation dataset, and the prediction accuracy was 94.7% and 91.3%, respectively. Conclusion: The radiomics nomogram incorporates the radiomics signature and hematological laboratory data, which can be conveniently used to facilitate the individualized prediction of the prognosis of APP patients.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33482359

RESUMO

Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus. Disorders in this process are tightly associated with adverse pregnancy outcomes including recurrent miscarriage (RM). However, an in-depth understanding of the systematic and decidual immune environment in RM remains largely lacking. In this study, we utilized single-cell RNA-sequencing (scRNA-seq) to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and unexplained RM pregnancies at the early stage of gestation. Integrative analysis identifies 22 distinct cell clusters in total, and a dramatic difference in leukocyte subsets and molecular properties in RM cases is revealed. Specifically, the cytotoxic properties of CD8+ effector T cells, nature killer (NK), and mucosal-associated invariant T (MAIT) cells in peripheral blood indicates apparently enhanced pro-inflammatory status, and the population proportions and ligand-receptor interactions of the decidual leukocyte subsets demonstrate preferential immune activation in RM patients. The molecular features, spatial distribution, and the developmental trajectories of five decidual NK (dNK) subsets have been elaborately illustrated. In RM patients, a dNK subset that supports embryonic growth is diminished in proportion, while the ratio of another dNK subset with cytotoxic and immune-active signature is significantly increased. Notably, a unique pro-inflammatory CD56+CD16+ dNK subset substantially accumulates in RM decidua. These findings reveal a comprehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy and provide an in-depth insight into the immune pathogenesis for early pregnancy loss.

10.
Food Chem ; 343: 128410, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33406573

RESUMO

Monascus, which is traditionally used in various Asian industries, produces several secondary metabolites during the fermentation process, including citrinin, a toxin whose impact limits the development of the Monascus industry. We have previously found that the addition of 2.0 g/L genistein to Monascus medium reduces citrinin production by approximately 80%. Here, we explored the molecular mechanisms whereby genistein affects citrinin production. We sequenced the Monascus genome and performed transcriptome analysis on genistein-treated and -untreated groups. Comparison between the two groups showed 378 downregulated and 564 upregulated genes. Among the latter, we further examined the genes related to citrinin biosynthesis and quantified them using quantitative real-time polymerase chain reaction (qRT-PCR). Genes orf5, pksCT, orf3, orf1, orf6, and ctnE were significantly downregulated, demonstrating that genistein addition indeed affects citrinin synthesis. Our results may lay the groundwork for substantial improvements in the Monascus fermentation industry.


Assuntos
Citrinina/biossíntese , Genisteína/farmacologia , Monascus/química , Transcriptoma/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Ontologia Genética , Genes Fúngicos , Monascus/genética , Monascus/metabolismo , Família Multigênica , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima/efeitos dos fármacos
11.
Proc Natl Acad Sci U S A ; 118(3)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33402432

RESUMO

During pregnancy, the appropriate allocation of nutrients between the mother and the fetus is dominated by maternal-fetal interactions, which is primarily governed by the placenta. The syncytiotrophoblast (STB) lining at the outer surface of the placental villi is directly bathed in maternal blood and controls feto-maternal exchange. The STB is the largest multinucleated cell type in the human body, and is formed through syncytialization of the mononucleated cytotrophoblast. However, the physiological advantage of forming such an extensively multinucleated cellular structure remains poorly understood. Here, we discover that the STB uniquely adapts to nutrient stress by inducing the macropinocytosis machinery through repression of mammalian target of rapamycin (mTOR) signaling. In primary human trophoblasts and in trophoblast cell lines, differentiation toward a syncytium triggers macropinocytosis, which is greatly enhanced during amino acid shortage, induced by inhibiting mTOR signaling. Moreover, inhibiting mTOR in pregnant mice markedly stimulates macropinocytosis in the syncytium. Blocking macropinocytosis worsens the phenotypes of fetal growth restriction caused by mTOR-inhibition. Consistently, placentas derived from fetal growth restriction patients display: 1) Repressed mTOR signaling, 2) increased syncytialization, and 3) enhanced macropinocytosis. Together, our findings suggest that the unique ability of STB to undergo macropinocytosis serves as an essential adaptation to the cellular nutrient status, and support fetal survival and growth under nutrient deprivation.

12.
J Reprod Dev ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33455972

RESUMO

Depletion of hepatocyte growth factor (HGF) or mesenchymal-epithelial transition factor (c-Met) in mice leads to fetal lethality and placental maldevelopment. However, the dynamic change pattern of HGF/c-Met signaling during placental development and its involvement in the early differentiation of trophoblasts remain to be elucidated. In this study, using in situ hybridization assay, we elaborately demonstrated the spatial-temporal expression of HGF and c-Met in mouse placenta from E5.5, the very early stage after embryonic implantation, to E12.5, when the placental structure is well developed. The concentration of the soluble form of c-Met (sMet) in maternal circulation peaked at E10.5. By utilizing the induced differentiation model of mouse trophoblast stem cells (mTSCs), we found that HGF significantly promoted mTSC differentiation into syncytiotrophoblasts (STBs) and invasive parietal trophoblast giant cells (PTGCs). Interestingly, sMet efficiently reversed the effect of HGF on mTSC differentiation. These findings indicate that HGF/c-Met signaling participates in regulating placental trophoblast cell fate at the early differentiation stage and that sMet acts as an endogenous antagonist in this aspect.

13.
Int Ophthalmol ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33392941

RESUMO

PURPOSE: Pars plana vitrectomy is the gold standard for the treatment of idiopathic macular hole. Several chromovitrectomy dyes have been used to improve the visualization of the internal limiting membrane (ILM), including indocyanine green, trypan blue (TB), brilliant blue G (BBG), and triamcinolone acetonide (TA). We conducted a network meta-analysis (NMA) to establish the optimum concentration of chromovitrectomy dye-assisted ILM peeling for IMH. METHODS: We searched PubMed, Embase, and Cochrane Library for relevant studies before January 2020. We performed a random-effects NMA using STATA version 15.1 to assess mean difference and odds ratios with 95% confidence intervals. RESULTS: We identified twelve retrospective trails and five randomized controlled trials (RCTs), comprising 1 492 patients of IMH on stage II-IV for ILM peeling. The results of IMH closure rate show that the effect of ILM peeling without dye was better than 0.25% ICG, the effects of ILM peeling with 0.5% ICG or TA were better than without dye, and the effects of ILM peeling with 0.05% BBG, 0.15% TB, 0.5% ICG or 0.05% ICG were better than 0.25% ICG. Ranking probability analysis shows that the rates of IMH closure after ILM peeling with 0.15% TB or 0.05% BBG were better than nine other concentrations of chromovitrectomy dyes. CONCLUSION: The 0.15% TB and 0.05% BBG were recommended as the better efficient treatment-assisted ILM peeling for IMH closure. For retina specialists who prefer to use ICG to assist ILM peeling, 0.05% ICG may be a good choice. However, high-quality large-scale RCTs are recommended to confirm the NMA results.

14.
Oral Dis ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33503275

RESUMO

BACKGROUND: Cyclin-dependent kinase 7 (CDK7) has been critically linked to human cancer. However, the roles of CDK7 in head and neck squamous cell carcinoma (HNSCC) remain incompletely known. Here, we sought to dissect the functions of CDK7 underlying HNSCC tumorigenesis and explore whether pharmacological inhibition of CDK7 could induce anti-cancer effects. METHODS: CDK7 expression was measured in a panel of HNSCC cell lines with p53 mutation and 20 pairs of HNSCC samples and adjacent non-tumor tissues. Genetic targeting and pharmacological inhibition of CDK7 were conducted to dissect the biological roles of CDK7 in p53-mutated HNSCC cells. An HNSCC xenograft model was developed to determine the therapeutic effects of THZ1 in vivo. Potential genes and pathways responsible for therapeutic effects of THZ1 were identified by genome-wide RNA-sequencing and bioinformatics interrogations. RESULTS: CDK7 expression was significantly elevated in cancerous cells and samples as compared with their adjacent non-tumor counterparts. Impaired cell proliferation, migration, and invasion as well increased apoptosis were observed in cells upon CDK7 knockdown or THZ1 exposure. THZ1 administration potently inhibited tumor overgrowth in vivo. Mechanistically, hundreds of genes enriched in cell proliferation, apoptosis, and cancer-related categories were identified to be potentially mediated the therapeutic effects of THZ1 in HNSCC. CONCLUSION: Our findings reveal that CDK7 might serve as a novel putative pro-oncogenic gene underlying HNSCC tumorigenesis and therapeutic targeting of CDK7 might be a promising strategy for p53-mutated HNSCC.

15.
Food Chem ; 348: 129128, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33516992

RESUMO

A novel colorimetric aptasensor based on unmodified gold nanoparticle (AuNPs) and single-strand DNA (ssDNA) aptamer was developed for the rapid and sensitive detection of T-2 toxin. In the absence of T-2, the AuNPs were wrapped by the aptamer to avoid the salt-induced aggregation and the solution remains red. In the presence of T-2, the aptamer was bound with T-2 and released from the surface of AuNPs, resulting in the aggregation of AuNPs under proper salt solution and the color change from red to purple-blue. The aptasensor exhibited a high sensitivity and selectivity for the detection of T-2. The range of linearity and detection limit were 0.1 ng/mL-5000 ng/mL (0.21435 nM-10717.5 nM) and 57.8 pg/mL (0.124 nM), respectively. The aptasensor developed here was applicable to assay T-2 in wheat and corn samples. These results implied that the colorimetric aptasensor was potentially useful in food detection.

16.
J Hazard Mater ; 402: 123933, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33254827

RESUMO

Microplastics, which are new types of environmental pollutants, are recently receiving widespread attention worldwide. Hydrogen sulfide (H2S) as the third endogenous gaseous mediator had protective effects in multiple physiological and pathological conditions. However, the protective role of H2S in microplastics-induced hepatotoxocity remain unclear. In this study, our data showed that H2S significantly suppressed inflammation, apoptosis and oxidative stress induced by polystyrene microplastics (mic-PS) (20 mg/kg b.w.) in the liver. Strikingly, although mic-PS exposure increased the expression of nuclear factor-E2-related factor (Nrf2), it did not influence the levels of heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQOl) in the L02 hepatocytes. Immunofluorescence assay showed that sodium hydrosulfide (NaHS) reduced micro-Ps-induced hepatic apoptosis by facilitating nuclear accumulation of Nrf2. Simultaneously, flow cytometry also showed that NaHS could prevent mic-PS-induced accumulation of reactive oxygen species (ROS) by increasing the expression of HO-1 and NQO1. Furthermore, inhibition of HO-1 could reverse the hepatic protective effects of NaHS during mic-PS exposure. Mechanistically, H2S elevating the HO-1 and NQO1 expression by facilitating nuclear accumulation of Nrf2, and consequently reducing mic-PS-induced hepatic apoptosis and inflammation. This study unveils the hepatotoxic effects of MPs and suggest NaHS have protective effects on mic-PS-induced liver damage.

17.
Heart Lung Circ ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277180

RESUMO

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a type of acute respiratory failure syndrome characterised by severe respiratory distress and stubborn hypoxaemia. Patients with ARDS have a prolonged hospital stay and high mortality rate. Over long-term follow-up, ARDS is found to be associated with a high incidence of long-term complications and decreased quality of life. Venovenous extracorporeal membrane oxygenation (vv-ECMO) has been widely used for the treatment of refractory ARDS. However, it is not the standard treatment as recommended by ARDS guidelines. AIM: The aim of this study was to compare the effects of ECMO (vv-ECMO) and conventional mechanical ventilation (CMV) on the clinical outcomes in patients with ARDS. METHOD: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, Medline, EMBASE, Web of Science, and PubMed databases up to November 2019. We selected appropriate studies according to our inclusion and exclusion criteria, and extracted and analysed the data using RevMan 5.0 software to evaluate the effectiveness of ECMO systematically. RESULTS: A total of 18 articles and 2,399 patients were included in this meta-analysis: 898 patients in the ECMO group and 1,501 patients in the CMV group. Treatment with ECMO may be associated with reduced 1-year mortality (95% confidence interval [CI], 0.27-0.83; p=0.009) and 60-day mortality (95% CI, 0.37-0.86; p=0.008), but increased Intensive Care Unit mortality (95% CI, 1.26-2.36; p=0.0007) of patients with ARDS. Extracorporeal membrane oxygenation may not be related to 30-day mortality or complications such as nosocomial pneumonia, haemorrhagic stroke, or continuous renal replacement therapy in patients with ARDS. However, some results showed heterogeneity, such as bleeding complications and in-hospital mortality. Subgroup analysis showed that ECMO treatment might increase ICU mortality (p=0.002) and nosocomial pneumonia complications (p=0.03) in patients with H1N1 ARDS. CONCLUSIONS: Compared with CMV, ECMO contributed to lower 60-day and 1-year mortality, and increased ICU mortality in patients with ARDS. However, H1N1 ARDS was independently associated with higher ICU mortality and nosocomial pneumonia. The results were not affected by removing retrospective control studies or articles published >20 years ago from the sensitivity analysis. This meta-analysis demonstrates the effectiveness of ECMO and its importance in standard treatment of patients with ARDS.

18.
Aging (Albany NY) ; 122020 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33260157

RESUMO

Retinal ischemia emerges in many ocular diseases and is a leading cause of neuronal death and dysfunction, resulting in irreversible visual impairment. We previously reported that brain-derived neurotrophic factor (BDNF)-expressing human 293T cells could steadily express BDNF and play a protective role in ARPE-19 cells, a human retinal epithelial cell line. Thus, we hypothesized that exosomes might be essential in the interaction between BDNF-expressing 293T cells and recipient cells. The study investigated whether exosomes derived from BDNF-expressing 293T cells (293T-Exo) can be internalized by ischemic retinal cells and exert neuroprotective roles. The results demonstrated that 293T-Exo significantly attenuated the loss of cell proliferation and cell death in R28 cells in response to oxygen-glucose deprivation treatment. Mechanistic studies revealed that the endocytosis of 293T-Exo by R28 cells displayed dose- and temperature-dependent patterns and may be mediated by the caveolar endocytic pathway via the integrin receptor. In the retinal ischemia rat model, the administration of 293T-Exo into the vitreous humor of ischemic eyes reduced apoptosis in the retina. Furthermore, 293T-Exo was mainly taken up by retinal neurons and retinal ganglion cells. Together, the results demonstrated that 293T-Exo has a neuroprotective effect in retinal ischemia and has therapeutic potential for retinal disorders.

19.
Biol Reprod ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33336235

RESUMO

Uterine spiral artery (SPA) remodeling is a crucial event during pregnancy to provide enough blood supply to maternal-fetal interface and meet the demands of the growing fetus. Along this process, the dynamic change and the fate of spiral artery vascular smooth muscle cells (SPA-VSMCs) have long been debatable. In the present study, we analyzed the cell features of SPA-VSMCs at different stages of vascular remodeling in human early pregnancy, and we demonstrated the progressively morphological change of SPA-VSMCs at un-remodeled (Un-Rem), remodeling, and fully remodeled (Fully-Rem) stages, indicating the extravillous trophoblast (EVT)-independent and EVT-dependent phases of SPA-VSMC dedifferentiation. In vitro experiments in VSMC cell line revealed the efficient roles of decidual stromal cells, decidual natural killer cells (dNK), decidual macrophages, and EVTs in inducing VSMCs dedifferentiation. Importantly, the potential transformation of VSMC toward CD56+ dNKs was displayed by immunofluorescence-DNA in-situ hybridization-proximity ligation and chromatin immunoprecipitation assays for H3K4dime modification in the myosin heavy chain 11 (MYH11) promoter region. The findings clearly illustrate a cascade regulation of the progressive dedifferentiation of SPA-VSMCs by multiple cell types in uterine decidual niche and provide new evidences to reveal the destination of SPA-VSMCs during vascular remodeling.

20.
Mol Ther Nucleic Acids ; 22: 542-556, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33230456

RESUMO

The study investigated the regulation of Smad2 by miR-18a and its role in preeclampsia (PE). Bioinformatics analysis showed that both Smad2 and Smad3 were the predicted targets for miR-18a. Mass spectrum analysis showed that two mature Smad2 isoforms existed in human placenta: full length, Smad2(FL), and that lacking exon3, Smad2(Δexon3). The protein level of Smad2(FL), but not Smad2(Δexon3) or Smad3, was significantly increased in severe PE (sPE) placenta, which was inversely correlated with the level of miR-18a. Elevated Smad2(FL) phosphorylation level appeared in sPE placenta, and Smad2 was colocalized with miR-18a in various subtypes of trophoblasts in human placenta. Smad2(FL) was validated as the direct target of miR-18a in HTR8/SVneo cells. miR-18a enhanced trophoblast cell invasion, which was blocked by the overexpression of Smad2(FL). Furthermore, overexpression of miR-18a repressed Smad2 activation and the inhibition of trophoblast cell invasion by transforming growth factor-ß (TGF-ß). In conclusion, our results suggest that miR-18a inhibits the expression of Smad2(FL), but not Smad2(Δexon3) or Smad3, which can reduce TGF-ß signaling, leading to the enhancement of trophoblast cell invasion. A lack of miR-18a, which results in the upregulation of Smad2(FL), contributes to the development of PE.

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