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Concurrent changing precipitation regimes and atmospheric nitrogen (N) deposition can have profound influences on soil carbon (C) cycling. However, how N enrichment regulates the responses of soil C fluxes to increasing variability of precipitation remains elusive. As part of a field precipitation gradient experiment with nine levels of precipitation amounts (-60 %, -45 %, -30 %, -15 %, ambient precipitation, +15 %, +30 %, +45 %, and +60 %) and two levels of N addition (0 and 10 g N m-2 yr-1) in a semi-arid temperate steppe on the Mongolian Plateau, this work was conducted to investigate the responses of soil respiration to decreased and increased precipitation (DP and IP), N addition, and their possible interactions. Averaged over the three years from 2019 to 2021, DP suppressed soil respiration by 16.1 %, whereas IP stimulated it by 27.4 %. Nitrogen addition decreased soil respiration by 7.1 % primarily via reducing microbial biomass C. Soil respiration showed symmetric responses to DP and IP within all the four precipitation variabilities (i.e., 15 %, 30 %, 45 %, and 60 %) under ambient N. Nevertheless, N addition did not alter the symmetric responses of soil respiration to changing precipitation due to the comparable sensitivities of microbial biomass and root growth to DP and IP under the N addition treatment. These findings indicate that intensified precipitation variability does not change but N addition could alleviate soil C releases. The unchanged symmetric responses of soil respiration to precipitation variability under N addition imply that N deposition may not change the response pattern of soil C releases to predicted increases in precipitation variability in grasslands, facilitating the robust projections of ecosystem C cycling under future global change scenarios.
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Ecossistema , Pradaria , Nitrogênio/análise , Solo , Microbiologia do Solo , CarbonoRESUMO
The O- GlcNAc transferase OGT interacts robustly with all three mammalian TET methylcytosine dioxygenases. We show here that deletion of the Ogt gene in mouse embryonic stem cells (mESC) results in a widespread increase in the TET product 5-hydroxymethylcytosine (5hmC) in both euchromatic and heterochromatic compartments, with concomitant reduction of the TET substrate 5-methylcytosine (5mC) at the same genomic regions. mESC engineered to abolish the TET1-OGT interaction likewise displayed a genome-wide decrease of 5mC. DNA hypomethylation in OGT-deficient cells was accompanied by de-repression of transposable elements (TEs) predominantly located in heterochromatin, and this increase in TE expression was sometimes accompanied by increased cis -expression of genes and exons located 3' of the expressed TE. Thus, the TET-OGT interaction prevents DNA demethylation and TE expression in heterochromatin by restraining TET activity genome-wide. We suggest that OGT protects the genome against DNA hypomethylation and impaired heterochromatin integrity, preventing the aberrant increase in TE expression observed in cancer, autoimmune-inflammatory diseases, cellular senescence and ageing.
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Preeclampsia (PE) is a multisystem disorder with high maternal morbidity and mortality rates. Currently, no practical therapeutic approach is available to prevent PE progression, except for early delivery. Gut dysbiosis is associated with PE development. Previous data showed that the abundance of Akkermansia muciniphila (Am) was lower in patients with PE than in normotensive pregnant women. Here, in this study, decreased abundance of Am was observed in a PE mouse model. Also, we found that administration with Am could significantly attenuate systolic blood pressure, promote foetal growth and improve the placental pathology in mice with PE. Moreover, Am-derived extracellular vesicles (AmEVs) were transferred from the gastrointestinal (GI) tract to the placenta and mitigated pre-eclamptic symptoms in PE mice. These beneficial effects of AmEVs were mediated by enhanced trophoblast invasion of the spiral artery (SpA) and SpA remodelling through activation of the epidermal growth factor receptor (EGFR)-phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT) signalling pathway. Collectively, our findings revealed the potential benefit of using AmEVs for PE treatment and highlighted important host-microbiota interactions.
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Vesículas Extracelulares , Pré-Eclâmpsia , Gravidez , Feminino , Camundongos , Humanos , Animais , Placentação , Placenta/metabolismo , Placenta/patologia , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/prevenção & controle , Vesículas Extracelulares/metabolismoRESUMO
BACKGROUND: This study evaluated vitamin A (VA), copper (Cu), and zinc (Zn) levels in the population with autism spectrum disorder (ASD) in Jilin Province, China. Furthermore, we examined their links to core symptoms and neurodevelopment, as well as gastrointestinal (GI) comorbidities and sleep disorders. METHODS: This study included 181 children with autism and 205 typically developing (TD) children. The participants had not taken vitamin/mineral supplements in the prior three months. High-performance liquid chromatography was used to measure serum VA levels. By using inductively coupled plasma-mass spectrometry, Zn and Cu concentrations in plasma were determined. Importantly, the Childhood Autism Rating Scale, the Social Responsiveness Scale, and the Autism Behavior Checklist were used to measure core ASD symptoms. However, the Griffith Mental Development Scales-Chinese were used to measure neurodevelopment. GI comorbidities and sleep abnormalities were assessed with the 6 Item-Gastrointestinal Severity Index and Children's Sleep Habits Questionnaire, respectively. Children with ASD with GI issues were grouped according to severity (low GI severity and high GI severity groups). RESULTS: (i) The difference in VA, Zn, Cu levels and the Zn/Cu ratio between ASD and TD children is small. But children with ASD had lower VA levels and Zn/Cu ratio, higher Cu levels than TD children. Cu levels in children with ASD were associated with the severity of core symptoms. (ii) Children with ASD were much more likely than their TD counterparts to suffer from GI comorbidities or sleep problems. Furthermore, it was observed that high GI severity was associated with lower levels of VA, whereas low GI severity was associated with higher levels of VA. (iii) The children with ASD who had both lower VA and lower Zn/Cu ratio had more severe scores on the Autism Behavior Checklist, but not on other measures. CONCLUSION: Children with ASD had lower VA and Zn/Cu ratio, and higher Cu levels. Cu levels in children with ASD were weakly correlated with one subscale on social or self-help. ASD children with lower VA levels may face more serious GI comorbidities. Children with ASD combined VA-Zn/Cu lower had more severe core symptoms. TRIAL REGISTRATION: Registration number: ChiCTR-OPC-17013502. Date of registration: 2017-11-23.
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Transtorno do Espectro Autista , Humanos , Criança , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/complicações , Vitamina A , Cobre , Zinco , VitaminasRESUMO
O-GlcNAc transferase (OGT) modifies serine and threonine residues on nuclear and cytosolic proteins with O-linked N-acetylglucosamine (GlcNAc). OGT is essential for mammalian cell viability, but the underlying mechanisms are still enigmatic. We performed a genome-wide CRISPR-Cas9 screen in mouse embryonic stem cells (mESCs) to identify candidates whose depletion rescued the block in cell proliferation induced by OGT deficiency. We show that the block in cell proliferation in OGT-deficient cells stems from mitochondrial dysfunction secondary to mTOR (mechanistic target of rapamycin) hyperactivation. In normal cells, OGT maintains low mTOR activity and mitochondrial fitness through suppression of proteasome activity; in the absence of OGT, increased proteasome activity results in increased steady-state amino acid levels, which in turn promote mTOR lysosomal translocation and activation, and increased oxidative phosphorylation. mTOR activation in OGT-deficient mESCs was confirmed by an independent phospho-proteomic screen. Our study highlights a unique series of events whereby OGT regulates the proteasome/ mTOR/ mitochondrial axis in a manner that maintains homeostasis of intracellular amino acid levels, mitochondrial fitness, and cell viability. A similar mechanism operates in CD8+ T cells, indicating its generality across mammalian cell types. Manipulating OGT activity may have therapeutic potential in diseases in which this signaling pathway is impaired.
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Linfócitos T CD8-Positivos , Complexo de Endopeptidases do Proteassoma , Animais , Camundongos , Acetilglucosamina/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Sobrevivência Celular , Mitocôndrias/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteômica , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Pre-eclampsia (PE) is a serious pregnancy complication, and gut dysbiosis is an important cause of it. Puerariae lobatae Radix (PLR) is a medicine and food homologous species; however, its effect on PE is unclear. This study aimed to investigate the efficacy of PLR in alleviating PE and its mechanisms. We used an NG-nitro-L-arginine methyl ester (L-NAME)-induced PE mouse model to examine the efficacy of preventive and therapeutic PLR supplementation. The results showed that both PLR interventions alleviated hypertension and proteinuria, increased fetal and placental weights, and elevated the levels of VEGF and PlGF. Moreover, PLR protected the placenta from oxidative stress via activating the Nrf2/HO-1/NQO1 pathway and mitigated placental damage by increasing intestinal barrier markers (ZO-1, Occludin, and Claudin-1) expression and reducing lipopolysaccharide leakage. Notably, preventive PLR administration corrected gut dysbiosis in PE mice, as evidenced by the increased abundance and positive interactions of beneficial bacteria including Bifidobacterium, Blautia, and Turicibacter. Fecal microbiota transplantation confirmed that the gut microbiota partially mediated the beneficial effects of PLR on PE. Our findings revealed that modulating the gut microbiota is an effective strategy for the treatment of PE and highlighted that PLR might be used as an intestinal nutrient supplement in PE patients.
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Microbioma Gastrointestinal , Pré-Eclâmpsia , Humanos , Animais , Feminino , Camundongos , Gravidez , Pré-Eclâmpsia/metabolismo , Placenta/metabolismo , Disbiose/metabolismo , ProteinúriaRESUMO
Hyperglycaemia is known to be associated with unfavourable outcomes in subarachnoid haemorrhage (SAH), but the pathogenic mechanism is unclear, and there is also a lack of effective therapeutic drugs in clinical practice. Phosphorylation of GSK3ß at serine 9 can inhibit its activity to further worsen SAH. The aim of the present study was to evaluate the protective effect and the potential mechanism of the GSK3ß inhibitor TDZD8 on brain injury in a hyperglycaemic SAH rat model. Hyperglycaemia was induced by intraperitoneal injection of streptozocin for 3 days. The SAH model was established by injecting fresh autologous femoral artery blood into the prechiasmatic cistern. p-GSK3ß (Ser9) expression was induced by intraperitoneal injection of TDZD8 (30 min post-SAH). The expression levels of GSK3ß, p-GSK3ß, SOD1/2, caspase 3, Bax and Bcl-2 were detected by western blot analysis. Terminal deoxynucleotidyl transferase dUTP nick end-labelling (TUNEL) staining was used to detect neuronal apoptosis of basal temporal lobe. Neurological scores were calculated to determine behavioural recovery. Neuronal survival was detected by Nissl staining. Hyperglycaemia significantly decreased p-GSK3ß expression, further exacerbated neurobehavioural deficits and increased oxidative stress and neuronal apoptosis in the brain after SAH compared to normal glycaemic SAH rats and hyperglycaemic rats. In addition, hyperglycaemic SAH rats had obvious oxidative stress and apoptosis. However, TDZD8 effectively decreased cleaved caspase 3 expression and TUNEL-positive cells and increased the Bcl2/Bax ratio, expression of SOD1/2 and activity of superoxide dismutase (SOD) enzyme compared with hyperglycaemic SAH rats. The GSK3ß inhibitor TDZD8 has therapeutic potential for hyperglycaemic SAH. The neuroprotective effect of TDZD8 appears to be mediated through its antioxidative and antiapoptotic activity.
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Lesões Encefálicas , Hiperglicemia , Hemorragia Subaracnóidea , Animais , Ratos , Hemorragia Subaracnóidea/complicações , Caspase 3/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Espécies Reativas de Oxigênio , Proteína X Associada a bcl-2/metabolismo , Hiperglicemia/patologia , Superóxido Dismutase-1/metabolismo , Superóxido Dismutase-1/farmacologia , Superóxido Dismutase-1/uso terapêutico , Ratos Sprague-Dawley , Lesões Encefálicas/tratamento farmacológico , Apoptose , Encéfalo/metabolismoRESUMO
In this cross-sectional study, 84 children with autism spectrum disorder (ASD) and 77 healthy subjects showing typical development (TD) were reviewed. Parents reviewed the age of introduction of complementary foods (CFs), completed a demographic, diet behavior questionnaire and the Autism Behavior Checklist (ABC). The results showed that the age of introduction of CFs was later in children with ASD than their TD counterparts. The age of introduction of CFs in ASD group was positively correlated with feeding problem. While the correlation was not observed in TD group. Children in the ASD group had higher total scores of the diet behavior questionnaire and all four subdomains (poor eating ability, mealtime eating behavior, food selectivity, and parental feeding behavior). ASD symptoms were clearly associated with feeding problems. The sensory subdomain score in ABC was positively correlated with poor eating ability, mealtime behavior and total score of the diet behavior questionnaire. The social self-care subdomain score was positively correlated with food selectivity. The interaction subdomain score was negative correlated with parental feeding behavior and total score of the diet behavior questionnaire. Further studies are required to establish the utility of delayed CFs introduction and/or early feeding problems as potential indicators of ASD.
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Vitamin D (VD) deficiency during pregnancy and early brain development is an important environmental risk factor for autism spectrum disorder (ASD). Its specific mechanism of action is still unclear. However, one study on the correlation between metabolomics and VD levels in children with ASD has found that the whole-blood arginine (Arg) levels of children with ASD are significantly negatively correlated with serum VD levels, suggesting that the effect of VD on ASD may be related to the signaling pathway involving Arg. Arg is a precursor of nitric oxide (NO), and changes in its levels most directly affect NO levels and signal transduction pathways. NO, a biologically active free radical, is both a neurotransmitter and a neuromodulator in the central nervous system and is related to the pathogeneses of various neurological diseases. The NO signaling pathway is not only affected by VD levels but also closely related to ASD through a series of mechanisms, such as neurotransmitter imbalance, immune disorders, and oxidative stress. Therefore, the effect of VD on ASD may be achieved via regulation of the NO signaling pathway. The current review discusses the relationship among VD, NO, and ASD as suggested by a large body of evidence in the literature in an effort to provide clues for researchers on the pathogenesis of ASD and the mechanism of VD's impact on ASD.
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INTRODUCTION: Preeclampsia (PE) is associated with abnormal placental vascular structure. However, the volume density of fetoplacental vessels in PE remains unclear. Additionally, manually annotated CT angiography, which is widely used to analyze placental vessels, has issues regarding inaccuracy. Thus, computer-aided CT angiography for analyzing the volume density of fetoplacental vessels would facilitate the understanding of PE pathogenesis. METHODS: We performed computer-aided CT angiography to compare differences in placentas among 17 women with PE and 34 normotensive women. The contrast ratio in CT angiography was significantly enhanced using a three-dimensional (3-D) Hessian matrix algorithm. The PE-like mouse model was established by administration of 125 mg/kg/day NG-nitro-l-arginine methyl ester (l-NAME) for 10 days. The presence of endothelial marker CD31 was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The expression of angiogenic factors (PlGF, VEGFA, and sFlt1) in placentas was detected using qRT-PCR and western blotting. RESULTS: The volume density in fetoplacental vessels and CD31 expression were significantly reduced in women with PE and l-NAME-induced mice. Additionally, the downregulation of angiogenic factors (PlGF/VEGFA) and upregulation of an anti-angiogenic factor (sFlt1) were determined in a mouse model. DISCUSSION: Contrast-enhanced CT angiography with the aid of a 3-D Hessian matrix algorithm was performed. PE significantly affects the formation of vascular vessels, resulting in a lower volume density of fetoplacental vessels in humans and mice. This may be explained by the abnormal release of angiogenic factors during PE.
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Pré-Eclâmpsia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Indutores da Angiogênese/metabolismo , Animais , China , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , NG-Nitroarginina Metil Éster/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Placenta/metabolismo , Fator de Crescimento Placentário/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
The decreased expression of tumour suppressor candidate 3 (TUSC3) is associated with proliferation in several types of cancer, leading to an unfavourable prognosis. The present study aimed to assess the cellular and molecular function of TUSC3 in patients with cervical squamous cell carcinoma (CSCC). Levels of mRNA expressions of TUSC3 were analysed in CSCC tissues and six cell lines using qRT-PCR. Immunohistochemistry(IHC) was used to evaluate the protein expression level of TUSC3 in four paired specimens, 220 paraffin-embedded CSCC specimens and 60 cases of normal cervical tissues(NCTs), respectively. Short hairpin RNA interference was employed for TUSC3 knockdown. Cell proliferation, migration and invasion were evaluated using growth curve, MTT assay, wound healing, transwell assay and xenograft tumour model, respectively. The results demonstrated that TUSC3 mRNA and protein expression levels were downregulated in CSCC samples. Multivariate and univariate analyses indicated that TUSC3 was an independent prognostic factor for patients with CSCC. Decreased TUSC3 expression levels were significantly associated with proliferation and an aggressive phenotype of cervical cancer cells both in vitro and in vivo. Moreover, the knockdown of TUSC3 promoted migration and invasion of cancer cells, while the increased expression of TUSC3 exhibited the opposite effects. The downregulation of TUSC3 facilitated proliferation and invasion of CSCC cells through the activation of the AKT signalling pathway. Our data demonstrated that the downregulation of TUSC3 promoted CSCC cell metastasis via the AKT signalling pathway. Therefore, TUSC3 may serve as a novel prognostic marker and potential target for CSCC.
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Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Feminino , Humanos , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , Proteínas Supressoras de Tumor , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: The prevalence of autism spectrum disorder (ASD) has increased rapidly in recent years. Environmental factors may play an important role in the pathogenesis of ASD. These factors may include socioeconomic factors, nutritional factors, heavy metal exposure, air pollution, etc. Our aim is to analyze possible environmental factors associated with the severity of ASD. METHODS: All participating children were divided into two groups (mild and moderate/severe) according to the severity of their symptoms, as determined by their Childhood Autism Rating Scale (CARS) scores. The socioeconomic, demographic factors and the nutritional factors that may affect the severity of ASD were included in the logistic regression to analyze whether they were predictors that affected the severity of ASD. RESULTS: Logistic regression showed that caregivers(P = 0.042), maternal education (P = 0.030), gastrointestinal problems (P = 0.041) and a high serum concentration of lead (P = 0.003) were statistically significantly associated with ASD severity. CONCLUSION: Many environmental factors affect the severity of ASD. We concluded that non-parental caregivers, low maternal education, gastrointestinal problems and high blood lead level maybe predictors that affected the severity of ASD in northeast China.
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Transtorno do Espectro Autista , Gastroenteropatias , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/etiologia , Cuidadores , Estudos de Casos e Controles , Criança , Gastroenteropatias/complicações , Humanos , ChumboRESUMO
Objective: The vitamin K family has a wide range of effects in the body, including the central nervous system. Menaquinone-4 (MK-4), a form of vitamin K2, is converted from phylloquinone (PK), which is the main source of dietary vitamin K and is the main form of vitamin K in the brain. We conducted this study to investigate the serum concentration of MK-4 and the correlations between MK-4 and developmental quotients in children with autism spectrum disorder (ASD). Methods: We selected 731 children with ASD who were diagnosed for the first time. During the same period, 332 neurotypical children who underwent regular physical examinations in our outpatient department were selected as the TD group. We investigated the general situation of children, including gender and age. Children in ASD group were assessed for autistic symptoms and development quotients, including Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), ADOS-2, and Griffiths Development Scales-Chinese Language Edition (GDS-C). Both groups of children were tested for serum menaquinone-4. We compared serum menaquinone-4 levels of ASD group and TD group. We then conducted a correlation analysis between the level of menaquinone-4 and the developmental quotient of children with ASD. Results: The results of this study indicate that the serum concentration of MK-4 in children with ASD is lower than that in children with typical development (t = -2.702, P = 0.007). The serum concentration of MK-4 is related to the developmental quotients of several subscales in ASD children, and this correlation is more obvious in males. Conclusion: we conclude that MK-4 is present in lower concentrations in children with ASD, which may affect cognition and developmental quotients. The role of MK-4 in ASD needs to be further explored.
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Preeclampsia is a common obstetric disorder affecting 2-8% of pregnancy worldwide. Fibrosis is an important histological change occurring in preeclamptic placenta, and might depend on the excess deposition of collagen I. However, the role of fibrotic placenta and collagen I in the pathogenesis of preeclampsia remains unclear. Therefore, we analyzed the collagen deposition and the expression of Collagen I in human placenta by Masson staining, Sirius red staining and western blotting. Further, the role of collagen I in preeclampsia pathogenesis was studied in C57BL/6 mice. HTR-8/SVneo cells were used to investigate the mechanisms underlying the effects of collagen I in trophoblasts by transcriptome sequencing and pharmacological agonists. Human preeclamptic placenta exhibited a significantly higher degree of fibrosis in stem villi and terminal villi than normal placenta, and was characterized by collagen I deposition. In vivo, a single injection of collagen I on gestational day 0.5 led to an increase in systolic pressure of pregnant mice from gestational days 4.5-17.5, to a decrease in weight and number of embryos, and to enhanced placental collagen I expression and degree of fibrosis compared with control mice. In vitro, collagen I attenuated the proliferation and invasion of HTR-8SV/neo cells. This effect could be reversed by treatment with agonists of ERK and ß-catenin. Moreover, transcriptome sequencing demonstrated that signaling pathways related to cell proliferation and invasion were significantly downregulated in HTR-8SV/neo cells. Thus, we propose that collagen I induced preeclampsia-like symptoms by suppressing the proliferation and invasion of trophoblasts through inhibition of the ERK phosphorylation and WNT/ß-catenin signaling pathways. Our findings could pave the way to the discovery of small-molecule inhibitors for preeclampsia treatment and future studies with larger sample size are required.
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Colágeno Tipo I/efeitos adversos , Placenta/patologia , Pré-Eclâmpsia/patologia , Transcriptoma , Trofoblastos/patologia , Animais , Movimento Celular , Proliferação de Células , Colágeno Tipo I/metabolismo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/metabolismo , Gravidez , Trofoblastos/metabolismo , Via de Sinalização WntRESUMO
TET methylcytosine dioxygenases are essential for the stability and function of regulatory T cells (Treg cells), which maintain immune homeostasis and self-tolerance and express the lineage-determining transcription factor Foxp3. Here, we use whole-genome analyses to show that the transcriptional program and epigenetic features (DNA modification, chromatin accessibility) of Treg cells are attenuated in the absence of Tet2 and Tet3. Conversely, the addition of the TET activator vitamin C during TGFß-induced iTreg cell differentiation in vitro potentiates the expression of Treg signature genes and alters the epigenetic landscape to better resemble that of Treg cells generated in vivo. Vitamin C enhances IL-2 responsiveness in iTreg cells by increasing IL2Rα expression, STAT5 phosphorylation, and STAT5 binding, mimicking the IL-2/STAT5 dependence of Treg cells generated in vivo. In summary, TET proteins play essential roles in maintaining Treg molecular features and promoting their dependence on IL-2. TET activity during endogenous Treg development and potentiation of TET activity by vitamin C during iTreg differentiation are necessary to maintain the transcriptional and epigenetic features of Treg cells.
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Dioxigenases , Linfócitos T Reguladores , Diferenciação Celular/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta/metabolismoAssuntos
Afibrinogenemia/genética , Fibrinogênio/genética , Mutação de Sentido Incorreto , Adulto , Idoso , Povo Asiático/genética , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Linhagem , GravidezRESUMO
OBJECTIVE: This research aimed to explore the predictive value of levels of vitamin A and E in pre-eclampsia and postpartum kidney injury. METHODS: A total of 106 pregnant women with severe pre-eclampsia diagnosed in our hospital from May 2015 to December 2018 were selected as the research subjects. There from, 75 pregnant women with severe pre-eclampsia were enrolled into the severe PE group (SPE) and 31 with acute kidney injury were divided into the severe PE and AKI group (SPE and AKI). Serum vitamin A and E content was determined by high-performance liquid chromatography (HPLC), and the correlation between vitamins A and E and disease was analyzed. The expression levels of kidney injury markers in both groups were detected, and the correlation between markers and vitamin A and E levels was analyzed. RESULTS: The expression level of vitamins A and E decreased in the pre-eclampsia and postpartum kidney injury, and it was negatively correlated with disease severity. The expression of the two decreased further in the severe pre-eclampsia patients with kidney injury. In addition, the expression of kidney injury markers in the severe pre-eclampsia patients with postpartum kidney injury was higher than that in severe pre-eclampsia patients, and it was negatively correlated with vitamin A and E levels. CONCLUSION: Vitamins A and E are expressed in low levels in pre-eclampsia and postpartum kidney injury, and the latter has a higher sensitivity and specificity than the former. It is negatively correlated with kidney injury markers KIM-1, NGAL, UA and Scr, which can be used as a physical and chemical indexes for clinical prediction.
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Preeclampsia (PE) is a life-threatening disease of pregnant women associated with severe hypertension, proteinuria, or multi-organ injuries. Mitochondrial-mediated placental oxidative stress plays a key role in the pathogenesis of PE. However, the underlying mechanism remains to be revealed. Here, we identify Rnd3, a small Rho GTPase, regulating placental mitochondrial reactive oxygen species (ROS). We showed that Rnd3 is down-regulated in primary trophoblasts isolated from PE patients. Loss of Rnd3 in trophoblasts resulted in excessive ROS generation, cell apoptosis, mitochondrial injury, and proton leakage from the respiratory chain. Moreover, Rnd3 overexpression partially rescues the mitochondrial defects and oxidative stress in human PE primary trophoblasts. Rnd3 physically interacts with the peroxisome proliferators-activated receptor γ (PPARγ) and promotes the PPARγ-mitochondrial uncoupling protein 2 (UCP2) cascade. Forced expression of PPARγ rescues deficiency of Rnd3-mediated mitochondrial dysfunction. We conclude that Rnd3 acts as a novel protective factor in placental mitochondria through PPARγ-UCP2 signaling and highlight that downregulation of Rnd3 is a potential factor involved in PE pathogenesis.
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Mitocôndrias/patologia , PPAR gama/metabolismo , Placenta/patologia , Pré-Eclâmpsia/patologia , Trofoblastos/patologia , Proteína Desacopladora 2/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Feminino , Humanos , Mitocôndrias/metabolismo , Estresse Oxidativo , PPAR gama/genética , Placenta/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Gravidez , Trofoblastos/metabolismo , Proteína Desacopladora 2/genética , Proteínas rho de Ligação ao GTP/genéticaRESUMO
Background: Electronic screen media play an increasingly vital role in children's entertainment; however, excessive screen time may negatively influence child development. The purpose of this study was to investigate the relationship between the screen time of children with autism spectrum disorder (ASD) and their autistic symptoms and development quotients (DQs). Methods: We compared the screen time of 101 children with ASD and 57 typically developing (TD) children. Then, we performed a correlation analysis to determine the correlations between the screen time and the ASD-related scale scores and developmental quotients of the Gesell Developmental Schedules (GDS) of ASD children. We further divided the ASD group into subgroups according to the screen time and age and then separately conducted the above correlation analyses by subgroup. Result: The results showed that the screen time of the children with ASD was longer than that of the TD children (3.34 ± 2.64 h vs. 0.91 ± 0.93 h). The screen time of the children with ASD was positively correlated with the Childhood Autism Rating Scale (CARS) score (r = 0.242, P = 0.021) and "taste, smell and touch" item of CARS(r = 0.304, P = 0.005), and negatively correlated with the language DQ of the GDS (r = -0.236, P = 0.047). The subgroup analysis showed that in the longer screen time subgroup of ASD children, the screen time was positively correlated with the CARS score (r = 0.355, P = 0.026) and negatively correlated with the DQs of all domains of the GDS (P < 0.05). In addition, in the younger age group of ASD children, the screen time was positively correlated with the CARS score (r = 0.314, P = 0.021) and negatively correlated with the DQs of all domains of the GDS, except for the personal-social behavior domain (P < 0.05). Conclusion: Compared with TD children, children with ASD have a longer screen time. The screen time is related to autism-like symptoms and the DQs of children with ASD. The longer the screen time, the more severe the symptoms of ASD (especially sensory symptoms), and the more obvious the developmental delay, especially in ASD children with a longer screen time and younger age, particularly in the language domain.
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To study the changes in porosity-permeability and the characteristics of the pore structure of shale under stress and high temperature, the Lower Silurian Longmaxi Formation shale in the southern Sichuan Basin, China, was investigated under conditions of continuous pressurization and heating. In addition, the pore compression coefficients and permeability stress sensitivity coefficients were analyzed and quantified. The mineral composition of these black shales was analyzed using scanning electron microscopy (SEM) and nuclear magnetic resonance (NMR). Our results reveal that the porosity and permeability of the shales exponentially decreases with increasing stress, reflecting that microfracture development during increasing stress causes the pores in these shale samples to enlarge. However, the pore compressibility and stress sensitivity coefficient vary for each sample, and the quantitative results indicate an overall decrease with increasing stress, suggesting that the shale deformation is nonlinear during stress release. Based on the mineral composition analyses and SEM measurements, we conclude that the nonuniform changes during stress release are related to the complexity of the shale mineral compositions and the different intercrystalline/ interlaminar pores of the different minerals, which are affected in different ways by pressure. The NMR measurements reveal that the mesopores are most developed in the shale samples, the pore volumes of the micro- and macropores are small, and the nanoscale pores are mainly from 1-60 nm in diameter. The different types of pore sizes decrease with increasing stress, indicating that the porosities measured experimentally reflect the synergistic effects of the different pore sizes on porosity. As the temperature increases, the permeability of the shale decreases significantly, which is primarily caused by the thermal expansion effect. The high clay mineral content of the shales also causes their permeabilities to be sensitive to temperature.