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2.
Neuron ; 112(13): 2177-2196.e6, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38653248

RESUMO

White matter injury (WMI) causes oligodendrocyte precursor cell (OPC) differentiation arrest and functional deficits, with no effective therapies to date. Here, we report increased expression of growth hormone (GH) in the hypoxic neonatal mouse brain, a model of WMI. GH treatment during or post hypoxic exposure rescues hypoxia-induced hypomyelination and promotes functional recovery in adolescent mice. Single-cell sequencing reveals that Ghr mRNA expression is highly enriched in vascular cells. Cell-lineage labeling and tracing identify the GHR-expressing vascular cells as a subpopulation of pericytes. These cells display tip-cell-like morphology with kinetic polarized filopodia revealed by two-photon live imaging and seemingly direct blood vessel branching and bridging. Gain-of-function and loss-of-function experiments indicate that GHR signaling in pericytes is sufficient to modulate angiogenesis in neonatal brains, which enhances OPC differentiation and myelination indirectly. These findings demonstrate that targeting GHR and/or downstream effectors may represent a promising therapeutic strategy for WMI.


Assuntos
Bainha de Mielina , Neovascularização Fisiológica , Pericitos , Animais , Pericitos/metabolismo , Pericitos/efeitos dos fármacos , Camundongos , Bainha de Mielina/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/fisiologia , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento/farmacologia , Animais Recém-Nascidos , Hipóxia/metabolismo , Diferenciação Celular/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Células Precursoras de Oligodendrócitos/metabolismo , Células Precursoras de Oligodendrócitos/efeitos dos fármacos , Receptores da Somatotropina/metabolismo , Receptores da Somatotropina/genética , Angiogênese
3.
J Imaging Inform Med ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491235

RESUMO

Radiofrequency ablation (RFA) is the treatment of choice for atrial fibrillation (AF). Additionally, the utilization of 3D printing for cardiac models offers an in-depth insight into cardiac anatomy and cardiovascular diseases. The study aims to evaluate the clinical utility and outcomes of RFA following in vitro visualization of the left atrium (LA) and pulmonary vein (PV) structures via 3D printing (3DP). Between November 2017 and April 2021, patients who underwent RFA at the First Affiliated Hospital of Xinxiang Medical University were consecutively enrolled and randomly allocated into two groups: the 3DP group and the control group, in a 1:1 ratio. Computed tomography angiography (CTA) was employed to capture the morphology and diameter of the LA and PV, which facilitated the construction of a 3D entity model. Additionally, surgical procedures were simulated using the 3D model. Parameters such as the duration of the procedure, complications, and rates of RFA recurrence were meticulously documented. Statistical analysis was performed using the t-test or Mann-Whitney U test to evaluate the differences between the groups, with a P-value of less than 0.05 considered statistically significant. In this study, a total of 122 patients were included, with 53 allocated to the 3DP group and 69 to the control group. The analysis of the morphological measurements of the LA and PV taken from the workstation or direct entity measurement showed no significant difference between the two groups (P > 0.05). However, patients in the 3DP group experienced significantly shorter RFA times (97.03 ± 28.39 compared to 120.51 ± 44.76 min, t = 3.05, P = 0.003), reduced duration of radiation exposure (2.55 [interquartile range 2.01, 3.24] versus 3.20 [2.28, 3.91] min, Z = 3.23, P < 0.001), and shorter modeling times (7.68 ± 1.03 compared to 8.89 ± 1.45 min, t = 5.38, P < 0.001). 3DP technology has the potential to enhance standard RFA practices by reducing the time required for intraoperative interventions and exposure to radiation.

4.
BMC Med Imaging ; 24(1): 57, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443826

RESUMO

BACKGROUND: The morphological information of the pulmonary vein (PV) and left atrium (LA) is of immense clinical importance for effective atrial fibrillation ablation. The aim of this study is to examine the consistency in different LA diameter measurement techniques. METHODS: Retrospective imaging data from 87 patients diagnosed with PV computed tomography angiography were included. The patients consisted of 50 males and 37 females, with an average age of (60.74 ± 8.70) years. Two physicians independently measured the anteroposterior diameter, long diameter, and transverse diameter of the LA using six different methods. Additionally, we recorded the post-processing time of the images. Physician 1 conducted measurements twice with a one-month interval between the measurements to assess intra-rater reliability. Using the intraclass correlation coefficient (ICC), the consistency of each LA diameter measurement by the two physicians was evaluated. We compared the differences in the LA diameter and the time consumed for measurements using different methods. This was done by employing the rank sum test of a randomized block design (Friedman M test) and the q test for pairwise comparisons among multiple relevant samples. RESULTS: (1) The consistency of the measured LA diameter by the two physicians was strong or very strong. (2) There were statistical differences in the anteroposterior diameter, long diameter, and transverse diameter of LA assessed using different methods (χ2 = 222.28, 32.74, 293.83, P < 0.001). (3) Different methods for measuring the diameters of LA required different amounts of time (χ2 = 333.10, P < 0.001). CONCLUSION: The results of left atrium (LA) diameter measurements conducted by different physicians were found to be reliable. However, the LA diameters obtained through various techniques exhibited variations. It was observed that measuring LA long diameters using only the VR (volume rendering) picture was the most clinically applicable method.


Assuntos
Fibrilação Atrial , Átrios do Coração , Feminino , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Reprodutibilidade dos Testes , Estudos Retrospectivos , Átrios do Coração/diagnóstico por imagem , Fibrilação Atrial/diagnóstico por imagem , Angiografia
5.
ACS Chem Neurosci ; 15(2): 382-393, 2024 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-38155530

RESUMO

Major facilitator superfamily domain-containing 2a (Mfsd2a) is a sodium-dependent lysophosphatidylcholine cotransporter that plays an important role in maintaining the integrity of the blood-brain barrier and neurological function. Abnormal degradation of Mfsd2a often leads to dysfunction of the blood-brain barrier, while upregulation of Mfsd2a can retrieve neurological damage. It has been reported that Mfsd2a can be specifically recognized and ubiquitinated by neural precursor cell-expressed developmentally downregulated gene 4 type 2 (NEDD4-2) ubiquitin ligase and finally degraded through the proteasome pathway. However, the structural basis for the specific binding of Mfsd2a to NEDD4-2 is unclear. In this work, we combined deep learning and molecular dynamics simulations to obtain a Mfsd2a structure with high quality and a stable Mfsd2a/NEDD4-2-WW3 interaction model. Moreover, molecular mechanics generalized Born surface area (MM-GBSA) methods coupled with per-residue energy decomposition studies were carried out to analyze the key residues that dominate the binding interaction. Based on these results, we designed three peptides containing the key residues by truncating the Mfsd2a sequences. One of them was found to significantly inhibit Mfsd2a ubiquitination, which was further validated in an oxygen-glucose deprivation (OGD) model in a human microvascular endothelial cell line. This work provides some new insights into the understanding of Mfsd2a and NEDD4-2 interaction and might promote further development of drugs targeting Mfsd2a ubiquitination.


Assuntos
Barreira Hematoencefálica , Simulação de Dinâmica Molecular , Humanos , Transporte Biológico , Barreira Hematoencefálica/metabolismo , Linhagem Celular , Ubiquitinação
6.
Nutrients ; 15(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37447266

RESUMO

Colorectal cancer (CRC) risk is influenced by dietary patterns and gut microbiota enterotypes. However, the interaction between these factors remains unclear. This study examines this relationship, hypothesizing that different diets may affect colorectal tumor risk in individuals with varied gut microbiota enterotypes. We conducted a case-control study involving 410 Han Chinese individuals, using exploratory structural equation modeling to identify two dietary patterns, and a Dirichlet multinomial mixture model to classify 250 colorectal neoplasm cases into three gut microbiota enterotypes. We assessed the association between dietary patterns and the risk of each tumor subtype using logistic regression analysis. We found that a healthy diet, rich in vegetables, fruits, milk, and yogurt, lowers CRC risk, particularly in individuals with type I (dominated by Bacteroides and Lachnoclostridium) and type II (dominated by Bacteroides and Faecalibacterium) gut microbiota enterotypes, with adjusted odds ratios (ORs) of 0.66 (95% confidence interval [CI] = 0.48-0.89) and 0.42 (95% CI = 0.29-0.62), respectively. Fruit consumption was the main contributor to this protective effect. No association was found between a healthy dietary pattern and colorectal adenoma risk or between a high-fat diet and colorectal neoplasm risk. Different CRC subtypes associated with gut microbiota enterotypes displayed unique microbial compositions and functions. Our study suggests that specific gut microbiota enterotypes can modulate the effects of diet on CRC risk, offering new perspectives on the relationship between diet, gut microbiota, and colorectal neoplasm risk.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Humanos , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Dieta Hiperlipídica , População do Leste Asiático , Dieta Saudável
7.
Sci Total Environ ; 894: 164948, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37336414

RESUMO

Brucellosis is a highly contagious zoonotic and systemic infectious disease caused by Brucella, which seriously affects public health and socioeconomic development worldwide. Particularly, in China accumulating eco-environmental changes and agricultural intensification have increased the expansion of human brucellosis (HB) infection. As a traditional animal husbandry area adjacent to Inner Mongolia, Datong City in northwestern China is characterized by a high HB incidence, demonstrating obvious variations in the risk pattern of HB infection in recent years. In this study, we built Bayesian spatiotemporal models to detect the transfer of high-risk clusters of HB occurrence in Datong from 2005 to 2020. Geographically and Temporally Weighted Regression and GeoDetector were employed to investigate the synergistic driving effects of multiple potential risk factors. Results confirmed an evident dynamic expansion of HB from the east to the west and south in Datong. The distribution of HB showed a negative correlation with urbanization level, economic development, population density, temperature, precipitation, and wind speed, while a positive correlation with the normalized difference vegetation index, and grassland/cropland cover areas. Especially, the local animal husbandry and related industries imposed a large influence on the spatiotemporal distribution of HB. This work strengthens the understanding of how HB spatial heterogeneity is driven by environmental factors, through which helpful insights can be provided for decision-makers to formulate and implement disease control strategies and policies for preventing the further spread of HB.


Assuntos
Brucelose , Humanos , Animais , Teorema de Bayes , Brucelose/epidemiologia , Brucelose/veterinária , Fatores de Risco , China/epidemiologia , Criação de Animais Domésticos
8.
Front Pharmacol ; 14: 1091616, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36814490

RESUMO

Cerebral ischemia, resulting from compromised blood flow, is one of the leading causes of death worldwide with limited therapeutic options. Potential deleterious injuries resulting from reperfusion therapies remain a clinical challenge for physicians. This study aimed to explore the metabolomic alterations during ischemia-reperfusion injury by employing metabolomic analysis coupled with gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and ultraperformance liquid chromatography quadrupole (UPLC/Q)-TOF-MS. Metabolomic data from mice subjected to middle cerebral artery occlusion (MCAO) followed by reperfusion (MCAO/R) were compared to those of the sham and MCAO groups. A total of 82 simultaneously differentially expressed metabolites were identified among each group. The top three major classifications of these differentially expressed metabolites were organic acids, lipids, and organooxygen compounds. Metabolomics pathway analysis was conducted to identify the underlying pathways implicated in MCAO/R. Based on impactor scores, the most significant pathways involved in the response to the reperfusion after cerebral ischemia were glycerophospholipid metabolism, linoleic acid metabolism, pyrimidine metabolism, and galactose metabolism. 17 of those 82 metabolites were greatly elevated in the MCAO/Reperfusion group, when compared to those in the sham and MCAO groups. Among those metabolites, glucose-6-phosphate 1, fructose-6-phosphate, cellobiose 2, o-phosphonothreonine 1, and salicin were the top five elevated metabolites in MCAO/R group, compared with the MCAO group. Glycolysis, the pentose phosphate pathway, starch and sucrose metabolism, and fructose and mannose degradation were the top four ranked pathways according to metabolite set enrichment analysis (MSEA). The present study not only advances our understanding of metabolomic changes among animals in the sham and cerebral ischemia groups with or without reperfusion via metabolomic profiling, but also paves the way to explore potential molecular mechanisms underlying metabolic alteration induced by cerebral ischemia-reperfusion.

9.
Ther Adv Chronic Dis ; 14: 20406223221142670, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36699111

RESUMO

Background: Thrombosis and inflammation are crucial elements in the pathogenesis of cardiovascular disease. Hematological parameters elucidate information involving the inflammatory and blood coagulation processes. Objectives: The current study explored the association of hematological parameters with EOCAD to identify specific risk factors. Design: A single-center retrospective case-control study was conducted with 1693 coronary artery disease patients and 1693 controls. Methods: Hematological parameters were examined through an automated analyzer. Results: The basophil percentage was significantly reduced in EOCAD (0.43 ± 0.26, p < 0.001) and MI (0.33 ± 0.24, p < 0.001) groups compared with controls (0.54 ± 0.28). The eosinophil percentage was also significantly lower in EOCAD (2.21 ± 1.71, p < 0.001) and MI (1.71 ± 2.44, p < 0.001) groups compared with controls (2.41 ± 1.75). The lymphocyte percentage in patients of EOCAD and MI and controls was 31.65 ± 7.93, 25.48 ± 9.43, and 34.82 ± 7.28, respectively. A significant difference was observed among the groups (p < 0.001). Except for the mean corpuscular hemoglobin (MCH), other red blood cell (RBC) parameters significantly differed between EOCAD patients and controls. The red blood cell distribution width (RDW), hematocrit (HCT), RBC count, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), and hemoglobin level were associated with EOCAD prevalence after adjusting for baseline differences. Platelet volume distribution width (PDW) also correlated with EOCAD prevalence (ORadjust = 1.087, 95% CI: 1.044-1.131). Conclusions: Hematological parameters are closely associated with EOCAD. Moreover, leukocyte parameters correlated with the presence and severity of the disease. In addition, erythrocyte parameters were associated with the disease presence but not with the disease severity. Among the platelet parameters, only PDW was related to the disease presence.

10.
Am J Trop Med Hyg ; 108(3): 599-608, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36689943

RESUMO

Malaria is a parasitic disease caused by Plasmodium, and Anopheles sinensis is a vector of malaria. Although malaria is no longer indigenous to China, a high risk remains for local transmission of imported malaria. This study aimed to identify the risk distribution of vector An. sinensis and malaria transmission. Using data collected from routine monitoring in Shanghai from 2010 to 2020, online databases for An. sinensis and malaria, and environmental variables including climate, geography, vegetation, and hosts, we constructed 10 algorithms and developed ensemble models. The ensemble models combining multiple algorithms (An. sinensis: area under the curve [AUC] = 0.981, kappa = 0.920; malaria: AUC = 0.959, kappa = 0.800), with the best out-of-sample performance, were used to identify important environmental predictors for the risk distributions of An. sinensis and malaria transmission. For An. sinensis, the most important predictor in the ensemble model was moisture index, which reflected degree of wetness; the risk of An. sinensis decreased with higher degrees of wetness. For malaria transmission, the most important predictor in the ensemble model was the normalized differential vegetation index, which reflected vegetation cover; the risk of malaria transmission decreased with more vegetation cover. Risk levels for An. sinensis and malaria transmission for each district of Shanghai were presented; however, there was a mismatch between the risk classification maps of An. sinensis and malaria transmission. Facing the challenge of malaria transmission in Shanghai, in addition to precise An. sinensis monitoring in risk areas of malaria transmission, malaria surveillance should occur even in low-risk areas for An. sinensis.


Assuntos
Anopheles , Malária , Plasmodium , Animais , Humanos , Anopheles/parasitologia , Mosquitos Vetores/parasitologia , China/epidemiologia , Malária/epidemiologia
11.
Chinese Journal of Epidemiology ; (12): 1092-1098, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-985638

RESUMO

Objective: To analyze the relationship between sedentary behavior and the force expiratory volume in 1 second (FEV1) reduction in middle-aged and elderly people in communities. Methods: The participants aged ≥40 years were randomly selected from a natural population cohort in Songjiang District, Shanghai, for pulmonary function tests and survey by using international physical activity questionnaire, a generalized additive model was used to analyze the association between sedentary behavior and FEV1 reduction in the study population and different sex-age subgroups. Results: A total of 3 121 study subjects aged ≥40 years were included. The prevalence of FEV1 reduction was 14.8%, which was higher in men than in women. There were 24.8% participants were completely sedentary. The prevalence of FEV1 reduction in women aged <60 years in complete sedentary group was 2.04 (95%CI: 1.11-3.72) times higher than that in non-complete sedentary group. In men aged <60 years, the prevalence of FEV1 reduction increased with daily sedentary time (OR=1.16, 95%CI: 1.04-1.29), and the prevalence of FEV1 reduction was also higher in those with sedentary time >5 hours/day than those with sedentary time ≤5 hours/day (OR=3.02, 95%CI: 1.28-7.16). The sensitivity analysis also found such associations. Conclusions: FEV1 reduction rate in age group <60 years was associated with sedentary behavior. Complete sedentary behavior or absence of moderate to vigorous physical activity played important roles in FEV1 reduction in women, while men were more likely to be affected by increased sedentary time, which had no association with physical activity. Reducing sedentary time to avoid complete sedentary behavior, along with increased physical activity, should be encouraged in middle-aged and elderly adults in communities to improve their pulmonary function.


Assuntos
Masculino , Idoso , Pessoa de Meia-Idade , Humanos , Adulto , Feminino , Lactente , Comportamento Sedentário , China/epidemiologia , Exercício Físico , Inquéritos e Questionários , Prevalência
12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-985451

RESUMO

In 2021, a total of 151 pregnant women were selected from the suburb of Shanghai. A questionnaire survey was conducted to obtain data about maternal age, gestational week, total annual household income, education level and passive smoking among pregnant women and one spot urine was collected. The concentrations of eight neonicotinoid pesticides and four metabolites in urine were measured by ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry. The differences in detection frequencies and concentrations of neonicotinoid pesticides and their metabolites among pregnant women with different characteristics were compared, and the influencing factors of the detection of neonicotinoid pesticides in urine were analyzed. The results showed that at least one neonicotinoid pesticide was detected in 93.4% (141 samples) of urine samples. The detection frequencies of N-desmethyl-acetamiprid, clothianidin, thiamethoxam, and N-desmethyl-clothianidin were high, about 78.1% (118 samples), 75.5% (114 samples), 68.9% (104 samples), and 44.4% (67 samples), respectively. The median concentration of the sum of all neonicotinoid pesticides was 2.66 μg/g. N-desmethyl-acetamiprid had the highest detection concentration with a median concentration of 1.04 μg/g. A lower urinary detection frequency of imidacloprid and its metabolites was seen in pregnant women aged 30-44 years [OR (95%CI): 0.23 (0.07-0.77)]. A higher detection frequency of clothianidin and its metabolites was seen in pregnant women with per capita annual household income≥100 000 yuan [OR (95%CI): 6.15 (1.56-24.28)]. There was widespread exposure to neonicotinoid pesticides and their metabolites in pregnant women from the suburb of Shanghai, which might pose potential health risks to pregnant women, and maternal age and household income were potential influencing factors of the exposure to neonicotinoid pesticides.


Assuntos
Humanos , Feminino , Gravidez , Praguicidas/análise , Gestantes , China , Neonicotinoides/análise , Inseticidas
14.
Transl Cancer Res ; 11(9): 3315-3321, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36237246

RESUMO

Background: Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent B cell lymphoma. Its occurrence in the pleura is rare, with atypical clinical manifestations. MALT of the pleura is easily misdiagnosed. This is the first case report of pleural MALT lymphoma in China. Case Description: We report the case of a 54-year-old Chinese man with no notable medical history who complained of cough, sputum, and shortness of breath for 3 months. He had a positive purified protein derivative (PPD) test. An initial misdiagnosis of pleural tuberculosis was corrected, after 3 thoracoscopic biopsies and tests, to primary pleural MALT lymphoma. He received treatments of R-CHOP (rituximab, cyclophosphamide, epirubicin, vindesine and prednisolone) and traditional Chinese medicine. The patient was followed for 3 years until June 2022, with no obvious respiratory symptoms. Pleural MALT lymphoma is extremely rare, with only a few cases reported. This article describes our case, and includes an overview of 15 previously reported cases to summarize the characteristics, treatments, and prognosis of primary pleural MALT lymphoma. Conclusions: Pleural MALT lymphoma is rare, and a correct diagnosis depends on tissue biopsy, immunohistochemical staining, and detection of gene rearrangement. Thoracoscopy is important to diagnose this disease. Multiple thoracoscopic biopsies may be necessary.

15.
Front Neurosci ; 16: 639656, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35495024

RESUMO

The contribution of histone mark redistribution to the age-induced decline of endogenous neuroprotection remains unclear. In this study, we used an intracerebral hemorrhage (ICH)-induced acute brain injury rat model to study the transcriptional and chromatin responses in 13- and 22-month-old rats. Transcriptome analysis (RNA-seq) revealed that the expression of neuroinflammation-associated genes was systematically upregulated in ICH rat brains, irrespective of age. Further, we found that interferon-γ (IFN-γ) response genes were activated in both 13- and 22-month-old rats. Anti-IFN-γ treatment markedly reduced ICH-induced acute brain injury in 22-month-old rats. At the chromatin level, ICH induced the redistribution of histone modifications in the promoter regions, especially H3K4me3 and H3K27me3, in neuroinflammation-associated genes in 13- and 22-month-old rats, respectively. Moreover, ICH-induced histone mark redistribution and gene expression were found to be correlated. Collectively, these findings demonstrate that histone modifications related to gene expression are extensively regulated in 13- and 22-month-old rats and that anti-IFN-γ is effective for ICH treatment, highlighting the potential of developing therapies targeting histone modifications to cure age-related diseases, including brain injury and neuroinflammation.

16.
Trends Endocrinol Metab ; 33(6): 390-400, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35396164

RESUMO

Reactive astrocytes undergo morphological, molecular, metabolic, and functional remodeling in response to central nervous system (CNS) damage. However, we still know very little about how the metabolic switching of astrocytes influences, or is influenced by, reactive astrocytes in response to neurological diseases. In this review, we initially cover a brief introduction into reactive astrocyte function under pathological conditions. Subsequently, we summarize the emerging roles of glucose and lipid metabolism in reactive astrocytes in the context of CNS injury to provide a new insight into metabolic mechanisms of reactive astrocyte-mediated neuroprotection or damage. Finally, we propose that deciphering the mechanistic link between astrocyte heterogeneity metabolism and improved methods is an emerging frontier for the therapeutic investigation of CNS injury and disease.


Assuntos
Astrócitos , Sistema Nervoso Central , Astrócitos/metabolismo , Astrócitos/patologia , Sistema Nervoso Central/metabolismo , Glucose/metabolismo , Humanos
18.
Cell Mol Neurobiol ; 42(6): 1897-1908, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33712886

RESUMO

Neurons in the penumbra (the area surrounding ischemic tissue that consists of still viable tissue but with reduced blood flow and oxygen transport) may be rescued following stroke if adequate perfusion is restored in time. It has been speculated that post-stroke angiogenesis in the penumbra can reduce damage caused by ischemia. However, the mechanism for neovasculature formation in the brain remains unclear and vascular-targeted therapies for brain ischemia remain suboptimal. Here, we show that VEGFR1 was highly upregulated in pericytes after stroke. Knockdown of VEGFR1 in pericytes led to increased infarct area and compromised post-ischemia vessel formation. Furthermore, in vitro studies confirmed a critical role for pericyte-derived VEGFR1 in both endothelial tube formation and pericyte migration. Interestingly, our results show that pericyte-derived VEGFR1 has opposite effects on Akt activity in endothelial cells and pericytes. Collectively, these results indicate that pericyte-specific expression of VEGFR1 modulates ischemia-induced vessel formation and vascular integrity in the brain.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Circulação Cerebrovascular/fisiologia , Células Endoteliais/metabolismo , Humanos , Isquemia/metabolismo , Perfusão , Pericitos , Acidente Vascular Cerebral/metabolismo
19.
Chinese Journal of Epidemiology ; (12): 387-391, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-935400

RESUMO

Objective: To estimate the incidence of metabolic syndrome and explore possible risk factors for metabolic syndrome in adults of rural communities in Yuhuan county, Zhejiang province, China. Methods: During June-December, 2018, a follow-up survey was conducted in participants without metabolic syndrome at baseline survey in 2012 to obtain the information collected in questionnaire survey, anthropometric data and laboratory data. The incidence of metabolic syndrome in the participants was estimated, and Logistic regression model was used to explore the risk factors, adjusted risk ratio (aRR) and 95%CI. Results: Among 3 162 participants, 522 new metabolic syndrome cases were identified. The 6-year cumulative incidence rate of metabolic syndrome was 16.5%, and the cumulative incidence rate was higher in women (20.6%) than that in men (12.3%, P<0.001). Those incidence rates were higher in those in jobless, smoking or drinking groups. Being women (aRR=1.96, 95%CI: 1.50-2.58) and family history of hypertension (aRR=1.31, 95%CI: 1.04-1.63) were independent risk factors for metabolic syndrome. Conclusion: The follow up indicated that the incidence of metabolic syndrome was relatively high in rural adults on islands in Zhejiang, and women or those with family history of hypertension were more likely to have metabolic syndrome.


Assuntos
Adulto , Feminino , Humanos , Masculino , Incidência , Ilhas , Síndrome Metabólica/epidemiologia , Fatores de Risco , População Rural
20.
Chinese Journal of Epidemiology ; (12): 260-268, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-935380

RESUMO

Objective: To analyze the diversity differences of gut microbiota between school-aged obese children and normal-weight children and identify the characteristic flora in obese children to provide some evidence for the subsequent study of the following study-related mechanisms and the prevention and treatment of obesity in school-aged children. Methods: This study was based on a cohort established in a primary school in Jiading district, Shanghai, 2016. Sixty-three children, including 43 boys and 20 girls, who were obese during the three years from 2016 to 2018, were enrolled in the obesity group. Among children who were average weight for three years, a total of 63 were selected as the control group, with matching with the obese ones in a 1 to 1 way according to age, sex and class. The primary characteristics, diet status, breastfeeding, and other information of children were collected by questionnaire. Fecal samples of participants in both groups were collected, and 16S rDNA sequencing was performed. Operable taxon units clustering according to 97% similarity and species annotation were based on the quality-optimized sequences. The difference in the diversity and genius of gut microbiota among children in the obesity and control groups were analyzed. The α diversity indices, including Ace, Chao1, Shannon, and Simpson index, were calculated. The β diversity was presented based on unweighted Unifrac distance and weighted Unifrac space by principal coordinate analysis. The differences in β diversity between the two groups were compared by similarity analysis (ANOSIM).The differences in genus distribution between the two groups were selected by STAMP software. The association of obesity with the α diversity and genus with significant differences were analyzed by the generalized linear model (GLM). Results: The Ace and Chao1 index in the obesity group was significantly lower than those in the control group (The P values were 0.026 and 0.039, respectively). There was no significant difference in Shannon and Simpson index between the two groups (The P values were 0.879 and 0.922, respectively). The results of ANOSIM showed differences in gut microbiota between the two groups (R>0), but the group contribution was not significant (unweighted Unifrac distance: R=0.006, P=0.223; weighted Unifrac distance: R=0.010, P=0.134). Among the obese group, the relative abundance of Prevotella and Sarcina was highest in the endemic genus. The STAMP results showed that the relative lots of 15 genera were significantly different between the two groups (P<0.05). The results of GLM showed that, compared with the control group, the obesity group had a lower level of the relative abundance in Akkermansia muciniphila, while a higher level in Coprococcus_3, Ruminococcus, Agathobacter and Collinsella. After stratification by sex, the Chao1 index was also lower in the obese boys than that in the normal-weight boys. However, the obese girls only had a higher level in Coprococcus_3 than the ordinary weight girls. Conclusions: Compared with children with average weight, obese children had lower α diversity of gut microbiota and lower relative abundance of dominant probiotics but had a higher relative lot of genus associated with metabolic disorders, inflammation promotion, and metabolism rate reduction.


Assuntos
Criança , Feminino , Humanos , Masculino , China/epidemiologia , Estudos de Coortes , Fezes , Microbioma Gastrointestinal/genética , Obesidade Infantil/epidemiologia
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