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1.
Mol Psychiatry ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33005028

RESUMO

Converging evidence increasingly implicates shared etiologic and pathophysiological characteristics among major psychiatric disorders (MPDs), such as schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Examining the neurobiology of the psychotic-affective spectrum may greatly advance biological determination of psychiatric diagnosis, which is critical for the development of more effective treatments. In this study, ensemble clustering was developed to identify subtypes within a trans-diagnostic sample of MPDs. Whole brain amplitude of low-frequency fluctuations (ALFF) was used to extract the low-dimensional features for clustering in a total of 944 participants: 581 psychiatric patients (193 with SZ, 171 with BD, and 217 with MDD) and 363 healthy controls (HC). We identified two subtypes with differentiating patterns of functional imbalance between frontal and posterior brain regions, as compared to HC: (1) Archetypal MPDs (60% of MPDs) had increased frontal and decreased posterior ALFF, and decreased cortical thickness and white matter integrity in multiple brain regions that were associated with increased polygenic risk scores and enriched risk gene expression in brain tissues; (2) Atypical MPDs (40% of MPDs) had decreased frontal and increased posterior ALFF with no associated alterations in validity measures. Medicated Archetypal MPDs had lower symptom severity than their unmedicated counterparts; whereas medicated and unmedicated Atypical MPDs had no differences in symptom scores. Our findings suggest that frontal versus posterior functional imbalance as measured by ALFF is a novel putative trans-diagnostic biomarker differentiating subtypes of MPDs that could have implications for precision medicine.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33016859

RESUMO

A novel Gram-stain-negative, strictly aerobic, rod-shaped, brick red-pigmented bacterium, designated R-22-1 c-1T, was isolated from water from Baiyang Lake, Hebei Province, PR China. The strain was able to grow at 20-30 °C (optimum, 30 °C) and pH 6-7 (optimum, pH 6) in Reasoner's 2A medium. 16S rRNA gene sequence and phylogenetic analyses of R-22-1 c-1T revealed closest relationships to Rufibacter immobilis MCC P1T (97.8 %), Rufibacter sediminis H-1T (97.9 %) and Rufibacter glacialis MDT1-10-3T (97.0 %), with other species of the genus Rufibacter showing less than 97.0 % sequence similarity. The predominant polar lipids were phosphatidylethanolamine, two unidentified aminophospholipids and three unidentified lipids. The major cellular fatty acids were iso-C15 : 0, C15 : 1 ω6c, C17 : 1 ω6c, anteiso-C15 : 0, summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1 ω7c and/or C16 : 1 ω6c) and summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B). The respiratory quinone was MK-7. The draft genome of R-22-1 c-1T was 5.6 Mbp in size, with a G+C content of 50.2 mol%. The average nucleotide identity and digital DNA-DNA hybridization relatedness values between strain R-22-1 c-1T and related type strains were R. immobilis MCC P1T (77.2 and 21.8 %), R. sediminis H-1T (81.6 and 21.4 %) and R. tibetensis 1351T (78.5 and 22.9 %). Based on these phylogenetic, chemotaxonomic and genotypic results, strain R-22-1 c-1T represents a novel species in the genus Rufibacter, for which the name Rufibacter latericius sp. nov. is proposed. The type strain is R-22-1 c-1T (=CGMCC 1.13570T=KCTC 62781T).

3.
Carbohydr Polym ; 250: 116906, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33049882

RESUMO

Recently, molecular dynamic simulation technique has been proved to be a powerful tool providing structural insights for better understanding the functionality of carbohydrates. Here, by using molecular dynamic simulation method we investigated the detailed conformational properties of the single-stranded curdlan with 12 glucose units. The results showed that the right-handed 6/1 helix structure was thermodynamically the most stable conformation in solution. The formation of the helix conformation was determined by many factors such as the glycosidic linkage, explicit water solvation and hydrogen bonds. When temperature was increased, the representative helix conformation was found becoming unstable giving rise to metastable conformations because when water mobility was accelerated with temperature, the hydrogen bonding strength between the curdlan chain and water went down, breaking the continuity of the hydrogen bonding network of water and hydroxyl groups. When the number of repeating glucose units varied from 6 to 24, the major helix conformation remained, but the conformational properties of longer chains were more apparently aff ;ected by chain flexibility.

4.
Gastroenterology ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33039464

RESUMO

BACKGROUND & AIMS: Preclinical identification of compounds at risk of causing drug induced liver injury (DILI) remains a significant challenge in drug development, highlighting a need for a predictive human system to study complicated DILI mechanism and susceptibility to individual drug. Here, we established a human liver organoid (HLO) based screening model for analyzing DILI pathology at organoid resolution. METHODS: We first developed a reproducible method to generate HLO from storable foregut progenitors from pluripotent stem cell (PSC) lines with reproducible bile transport function. The qRT-PCR and single cell RNA-seq determined hepatocyte transcriptomic state in cells of HLO relative to primary hepatocytes. Histological and ultrastructural analyses were performed to evaluate micro-anatomical architecture. HLO based drug-induced liver injury assays were transformed into a 384 well based high-speed live imaging platform. RESULTS: HLO, generated from 10-different pluripotent stem cell lines, contain polarized immature hepatocytes with bile canaliculi-like architecture, establishing the unidirectional bile acid transport pathway. Single cell RNA-seq profiling identified diverse and zonal hepatocytic populations that in part emulate primary adult hepatocytes. The accumulation of fluorescent bile acid into organoid was impaired by CRISPR-Cas9 based gene editing and transporter inhibitor treatment of BSEP. Furthermore, we successfully developed an organoid based assay with multiplexed readouts measuring viability, cholestatic and/or mitochondrial toxicity with high predictive values for 238 marketed drugs at 4 different concentrations (Sensitivity: 88.7%, Specificity: 88.9%). LoT positively predicts genomic predisposition (CYP2C9*2) for Bosentan-induced cholestasis. CONCLUSIONS: Liver organoid-based Toxicity screen (LoT) is a potential assay system for liver toxicology studies, facilitating compound optimization, mechanistic study, and precision medicine as well as drug screening applications.

5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1552-1555, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018288

RESUMO

The introduction of deep learning techniques for the computer-aided detection scheme has shed a light for real incorporation into the clinical workflow. In this work, we focus on the effect of attention in deep neural networks on the classification of tuberculosis x-ray images. We propose a Convolutional Block Attention Module (CBAM), a simple but effective attention module for feed-forward convolutional neural networks. Given an intermediate feature map, our module infers attention maps and multiplied it to the input feature map for adaptive feature refinement. It achieves high precision and recalls while localizing objects with its attention. We validate the performance of our approach on a standard-compliant data set, including a dataset of 4990 x-ray chest radiographs from three hospitals and show that our performance is better than the models used in previous work.


Assuntos
Redes Neurais de Computação , Radiografia Torácica , Tuberculose , Humanos , Tuberculose/diagnóstico por imagem
6.
Radiology ; : 202944, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32969761

RESUMO

Background Radiologists are proficient in differentiating between chest x-ray radiographs (CXRs) with and without symptoms of pneumonia, but have found it more challenging to differentiate CXRs with COVID-19 pneumonia symptoms from those without. Purpose To develop an artificial intelligence algorithm to differentiate COVID-19 pneumonia from other causes of CXR abnormalities. Materials and Methods In this retrospective study, a deep neural network, CV19-Net, was trained, validated, and tested on CXRs from patients with and without COVID-19 pneumonia. For the COVID-19 positive CXRs, patients with reverse transcriptase polymerase chain reaction positive results for severe acute respiratory syndrome coronavirus 2 with positive pneumonia findings between February 1, 2020 and May 30, 2020 were included. For the non-COVID-19 CXRs, patients with pneumonia who underwent CXR between October 1, 2019 and December 31, 2019 were included. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated to characterize diagnostic performance. To benchmark the performance of CV19-Net, a randomly sampled test dataset containing 500 CXRs from 500 patients was evaluated by both the CV19-Net and three experienced thoracic radiologists. Results A total of 2060 patients (5806 CXRs; mean age 62 ± 16, 1059 men) with COVID-19 pneumonia and 3148 patients (5300 CXRs; mean age 64 ± 18, 1578 men) with non-COVID-19 pneumonia were included and split into training + validation and test datasets. For the test set, CV19-Net achieved an AUC of 0.92 (95% confidence interval [CI]: 0.91, 0.93) corresponding to a sensitivity of 88% (95% CI: 87%, 89%) and a specificity of 79% (95% CI: 77%, 80%) using a high sensitivity operating threshold, or a sensitivity of 78% (95% CI: 77%, 79%) and a specificity of 89% (95% CI: 88%, 90%) using a high specificity operating threshold. For the 500 sampled CXRs, CV19-Net achieved an AUC of 0.94 (95% CI: 0.93, 0.96) compared to a 0.85 AUC (95% CI: 0.81, 0.88) of radiologists. Conclusion CV19-Net was able to differentiate COVID-19 related pneumonia from other types of pneumonia with performance exceeding that of experienced thoracic radiologists.

7.
Ageing Res Rev ; : 101165, 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32898718

RESUMO

The process of ageing includes molecular changes within cells and interactions between cells, eventually resulting in age-related diseases. Although various cells (immune cells, parenchymal cells, fibroblasts and endothelial cells) in tissues secrete proinflammatory signals in age-related diseases, immune cells are the major contributors to inflammation. Many studies have emphasized the role of metabolic dysregulation in parenchymal cells in age-related inflammatory diseases. However, few studies have discussed metabolic modifications in immune cells during ageing. In this review, we introduce the metabolic dysregulation of major nutrients (glucose, lipids, and amino acids) within immune cells during ageing, which leads to dysfunctional NAD + metabolism that increases immune cell senescence and leads to the acquisition of the corresponding senescence-associated secretory phenotype (SASP). We then focus on senescent immune cell interactions with parenchymal cells and the extracellular matrix and their involvement in angiogenesis, which lead to proinflammatory microenvironments in tissues and inflammatory diseases at the systemic level. Elucidating the roles of metabolic modifications in immune cells during ageing will provide new insights into the mechanisms of ageing and therapeutic directions for age-related inflammatory diseases.

9.
J Voice ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32917458

RESUMO

OBJECTIVE: To explore the factors affecting the therapeutic efficacy of laryngeal contact granuloma. METHODS: The clinical data of 534 patients with laryngeal contact granuloma treated in our hospital from April 2014 to December 2019 were studied. The multivariable logistic regression was performed to find the risk factors influencing the treatment efficacy. RESULTS: Multivariable logistic regression showed that factors related to therapeutic efficacy were granuloma size (P = 0.0006) and gender (P = 0.0299) in conservative treatment group; laryngopharyngeal reflux (P = 0.0115), cough (P = 0.0124), and previous surgical history (P < 0.001) in combined treatment group. The surgical treatment had the worst therapeutic efficacy compared with combined treatment and conservative treatment. In the larger granuloma size subgroup, combined treatment showed better results than conservative treatment. CONCLUSION: Granuloma size and gender affect the therapeutic efficacy of conservative treatment. Previous surgical history, laryngopharyngeal reflux, and cough affect the therapeutic efficacy of combined treatment. Combined treatment is better than conservative treatment alone and surgical treatment shows the worst efficacy.

10.
J Immunol Res ; 2020: 4904217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908939

RESUMO

Acute coronary syndrome (ACS) is a major cause of acute death worldwide. Both innate and adaptive immunity regulate atherosclerosis progression, plaque stability, and thrombus formation. Immune and inflammation dysfunction have been indicated in the pathogenesis of ACS. The imbalance in the proatherogenic and antiatherogenic immune networks promotes the transition of plaques from a stable to unstable state and results in the occurrence of acute coronary events. The residual inflammatory risk (RIR) has received increasing attention in recent years, and lowering RIR has been expected to improve the outcomes of ACS patients. The CANTOS, COLCOT, and LoDoCo trials verified the benefits of reducing cardiovascular events using anti-inflammation therapies; however, most of the other studies focusing on lowering RIR produced negative or contradicting results. Therefore, restoring the balance in autoimmune regulation is essential because proatherogenic and antiatherogenic immunomodulatory effects are equally important in the complex human immune network. In this review, we summarized the recent evidence of the roles of proatherogenic and antiatherogenic immune networks in the pathogenesis of ACS and discussed how immune and inflammation contribute to atherosclerosis progression, plaque instability, and adverse cardiovascular events. We also provide a "from bench to bedside" perspective of a novel and promising personalized strategy in RIR intervention and therapeutic approaches for the treatment of ACS.

11.
Mol Psychiatry ; 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32792660

RESUMO

Amyloid-ß peptide (Aß) accumulation in the brain is a hallmark of Alzheimer's Disease. An important mechanism of Aß clearance in the brain is uptake and degradation by microglia. Presenilin 1 (PS1) is the catalytic subunit of γ-secretase, an enzyme complex responsible for the maturation of multiple substrates, such as Aß. Although PS1 has been extensively studied in neurons, the role of PS1 in microglia is incompletely understood. Here we report that microglia containing phospho-deficient mutant PS1 display a slower kinetic response to micro injury in the brain in vivo and the inability to degrade Aß oligomers due to a phagolysosome dysfunction. An Alzheimer's mouse model containing phospho-deficient PS1 show severe Aß accumulation in microglia as well as the postsynaptic protein PSD95. Our results demonstrate a novel mechanism by which PS1 modulates microglial function and contributes to Alzheimer's -associated phenotypes.

12.
Cancer Manag Res ; 12: 5831-5843, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765086

RESUMO

Background: Programmed death-ligand 1 (PD-L1) is a negative costimulatory molecule, and its main function is widely considered to be in the regulation of T cells. Tumor-associated macrophages (TAMs) are an important part of the tumor microenvironment, and they also play an important role in immunosuppression. However, the relationship between the expression of PD-L1 and TAMs in cervical carcinoma (CC) remains unclear. We detected the expression of PD-L1 and TAMs in tumor tissue to study the correlation between them. Methods: Immunohistochemical staining of PD-L1, CD68 (pan-macrophage), and CD163 (M2-like macrophage) was performed in 120 cases of cervical squamous cell carcinoma. Logistic regression analysis was used to evaluate the predictors related to positive PD-L1 expression. We also apply the Kaplan-Meier method to study the recurrence-free and overall survival rate of CC patients. Results: The increase in PD-L1 expression in tumor cells (TC) was significantly correlated with the increase in CD163 density (r=0.8550, p<0.0001), while PD-L1 in the stroma was also significantly associated with the intratumoral density of CD68- or CD163-positive cells (CD68 p<0.0001; CD163 p=0.0009). The mean infiltration rates of CD68- and CD163-positive cells in PD-L1-positive TC were significantly higher than in PD-L1-negative TC (CD68 p=0.0095; CD163 p<0.0001). In multivariate logistic regression analyses, only the density of CD163-positive cells was correlated with the expression of PD-L1 in TC cells (OR 1.52; p=0.032). In prognostic analysis, PD-L1 more than 10% was significantly correlated with short RFS (HR=2.66; p=0.028). For CD163+ macrophage evaluation, the density above the median was also significantly correlated with RFS (HR=2.48; p=0.021). Conclusion: CD163+ M2-like macrophage infiltration is highly associated with PD-L1 expression in CC, suggesting that macrophage infiltration can serve as a potential therapeutic target.

13.
Molecules ; 25(16)2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32784972

RESUMO

The synthesis of cyclic carbonates from carbon dioxide (CO2) and epoxides is a 100% atom economical reaction and an attractive pathway for CO2 utilisation. Because CO2 is a thermodynamically stable molecule, the use of catalysts is mandatory in reducing the activation energy of the CO2 conversion. Considering environmental compatibility and the high-efficiency catalytic conversion of CO2, there is the strong need to develop green catalysts. Biomass-based catalysts, a type of renewable resource, have attracted considerable attention due to their unique properties-non-toxic, low-cost, pollution-free, etc. In this review, recent advances in the development of biomass-based catalysts for the synthesis of cyclic carbonates by CO2 and epoxides coupling are summarized and discussed in detail. The effect of biomass-based catalysts, functional groups, reaction conditions, and co-catalysts on the catalytic efficiency and selectivity of synthesizing cyclic carbonates process is discussed. We intend to provide a comprehensive understanding of recent experimental and theoretical progress of CO2 and epoxides coupling reaction and pave the way for both CO2 conversion and biomass unitization.

14.
J Colloid Interface Sci ; 582(Pt A): 236-245, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32823125

RESUMO

To obtain MOFs materials with good electrochemical performance in both lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs), a kind of hollow urchins Co-MOF with doping fluorine (F) was in-situ assembled on reduced graphene oxide (rGO) using a simple solvothermal reaction. According to XRD, XPS and EDS mapping analysis, the molecular structure should be Co2[Fx(OH)1-x]2(C8O4H4) (denoted as F-Co-MOF). When the composite material is used as active material to assemble LIBs, it not only presents the outstanding reversible capacity (1202.0 mA h g-1 at 0.1 A g-1), but also gives the excellent rate performance and cycle performance (771.5 mA h g-1 at 2 A g-1 after 550 repeated cycles). The remarkable lithium storage capacity of F-Co-MOF/rGO is also reflected in the full cell, where it can still maintain a high capacity of 165.2 mA h g-1 after 300 cycles at 0.2 A g-1. It benefits from the synergistic effect of F-Co-MOF and high conductive rGO networks, so that the reversibility of lithium and sodium storage can be improved. This kind of F doped solvothermal synthesis of MOFs is of great significance for the exploration of high performance materials.

15.
Artigo em Chinês | MEDLINE | ID: mdl-32791597

RESUMO

Objective:To investigate the relationship between laryngopharyngeal reflux and arytenoid cartilage calcification in male idiopathic laryngeal contact granuloma. Method:The clinical data of 92 male patients with idiopathic laryngeal contact granuloma who had the thin laryngeal CT scan images and laryngeal reflux symptom index(RSI) scale data before treatment were analyzed retrospectively. The effect of laryngopharyngeal reflux on the calcification of arytenoid cartilage in laryngeal contact granuloma patients was analyzed by Chi-square statistics with SPSS 16.0 software. Result:Among the 92 patients, 44 patients with RSI>13(47.83%) and 48 patients with RSI≤13(52.17%). Unilateral granuloma was found in 87 cases(94.57%) and bilateral granuloma in 5 cases(5.43%). A total of 97 sides of the diseased side, there were 87 sides of arytenoid cartilage with calcification(89.69%) and 10 sides without calcification(10.31%). Among the patients with RSI>13, there were 45 sides of arytenoid cartilage with calcification(45/46, 97.83%) and one side without calcification(1/46, 2.17%), and in the patients with RSI≤13, there were 42 sides of arytenoid cartilage with calcification(42/51, 82.35%) and 9 sides without calcification(9/51, 17.65%). The calcification rate of arytenoid cartilage in patients with RSI>13 group was significantly higher than that in RSI≤13 group(χ²=4.701, P=0.030). Conclusion:The calcification rate of arytenoid cartilage in male idiopathic laryngeal contact granuloma patients with laryngopharyngeal reflux is higher than that in patients without laryngopharyngeal reflux. Laryngopharyngeal reflux may aggravate or promote the inflammatory reaction of granuloma and accelerate the calcification of arytenoid cartilage.


Assuntos
Granuloma Laríngeo , Refluxo Laringofaríngeo , Cartilagem Aritenoide , Granuloma , Humanos , Masculino , Estudos Retrospectivos
16.
Artigo em Chinês | MEDLINE | ID: mdl-32842234

RESUMO

Objective:To investigate the clinical characteristics, diagnosis and treatment of female laryngeal contact granuloma. Method:The clinical data of 46 female patients with laryngeal contact granuloma diagnosed and treated by our clinical team from March 2011 to October 2018 were retrospectively analyzed. Result:The age of the 46 patients ranged from 5 to 58 years old, with an average age of 36.76 years old. The causes of the contact granulomas historically may be the result of intubation in 33 cases, laryngopharyngeal reflux in 8 cases, chronic cough in 2 cases, laryngopharyngeal reflux combined with chronic cough in 2 cases, and voice abuse and excessive clearing of the throat in one case. All patients were followed up for at least half a year, and all of them were cured. Among the 6 patients with large lesions who underwent surgical treatment, 3 relapsed within 3 months, PPI treatment was performed for 2 to 6 months after recurrence, and no recurrence was observed during follow-up, with an average course of treatment of (1.67±2.34) months. All the 11 patients who received corticosteroid injections recovered after 1 to 7 injections, with a median of 3 injections, and an average course of treatment of (2.64±1.69) months. All the 13 patients with oral PPI were cured, with an average course of treatment of (4.15±2.76 )months; No recurrence was found in the follow-up of 16 patients with conservative treatment under regular observation, with an average course of treatment of (5.88±3.76) months. The difference in cure time between the intervention group (30 cases) and the observation group (16 cases) was statistically significant, and the cure time of the intervention group was shorter than that of the observation group (H=11.902, P=0.008). Conclusion:Female patients with laryngeal contact granuloma are common after intubation, and various treatments or conservative observation can achieve good results, and treatment intervention may shorten the cure time.


Assuntos
Granuloma Laríngeo , Refluxo Laringofaríngeo , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Granuloma , Humanos , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Adulto Jovem
17.
DNA Cell Biol ; 39(9): 1606-1620, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32749870

RESUMO

The sugars will eventually be exported transporters (SWEET) gene family is a glycoprotein gene family that can regulate the transport of sugar in plants and plays an important role in plant growth and development, as well as in response to environmental stress. In this study, Kentucky bluegrass (cv. Baron) seedlings were grown in various treatments, including heavy metal cadmium, salt, drought, cold, and heat stress for 6 h, 24 h, 48 h, and 7 day. The relative expression of the identified PpSWEET genes in Kentucky bluegrass was measured. The results showed there were a total of 13 SWEET genes, which could be divided into four clades by phylogenetic analysis. Most PpSWEET genes are alkali proteins with seven transmembrane helices. Moreover, almost all PpSWEET proteins possess similar conserved motifs and active sites. In addition, an analysis of the relative expression of PpSWEET genes under various stress treatments indicated that PpSWEET12 and PpSWEET15 had very high expression under the five types of stress, meaning they can be used as important candidate genes for studying responses to environmental stresses of turfgrass. Furthermore, certain genes only showed changes in expression under one or two specific stress treatments. This study provides important insight into the SWEET gene family in Kentucky bluegrass and its functional roles in responses to various environmental stresses.


Assuntos
Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Plantas/genética , Poa/genética , Estresse Fisiológico , Sequência Conservada , Regulação da Expressão Gênica de Plantas , Proteínas de Transporte de Monossacarídeos/química , Proteínas de Transporte de Monossacarídeos/metabolismo , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Poa/classificação , Poa/metabolismo , Domínios Proteicos
18.
PLoS One ; 15(8): e0237773, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822378

RESUMO

Microglial cells play a key role in brain homeostasis from development to adulthood. Here we show the involvement of a site-specific phosphorylation of Presenilin 1 (PS1) in microglial development. Profiles of microglia-specific transcripts in different temporal stages of development, combined with multiple systematic transcriptomic analysis and quantitative determination of microglia progenitors, indicate that the phosphorylation of PS1 at serine 367 is involved in the temporal dynamics of microglial development, specifically in the developing brain rudiment during embryonic microgliogenesis. We constructed a developing brain-specific microglial network to identify transcription factors linked to PS1 during development. Our data showed that PS1 functional connections appear through interaction hubs at Pu.1, Irf8 and Rela-p65 transcription factors. Finally, we showed that the total number of microglia progenitors was markedly reduced in the developing brain rudiment of embryos lacking PS1 phosphorylation compared to WT. Our work identifies a novel role for PS1 in microglial development.


Assuntos
Redes Reguladoras de Genes , Microglia/fisiologia , Presenilina-1/metabolismo , Células-Tronco/metabolismo , Animais , Encéfalo/embriologia , Encéfalo/metabolismo , Feminino , Masculino , Camundongos Endogâmicos C57BL , Fosforilação , Presenilina-1/genética , Células-Tronco/citologia , Transcriptoma
19.
Schizophr Res ; 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32684357

RESUMO

BACKGROUND: Alterations of white matter (WM) integrity have been observed in both schizophrenia (SZ) and individuals at genetic high risk for SZ (GHR-SZ); however, the molecular mechanisms underlying WM disruption remain unclear. Cytokines are chemical messengers of the immune system that are closely related to inflammation and neurogenesis in the brain. This study aimed to identify abnormalities in WM integrity, cytokine levels, and their association in SZ and GHR-SZ. METHODS: A total of 355 participants (126 with SZ, 99 GHR-SZ, and 130 healthy controls [HCs]) were recruited. All participants underwent diffusion tensor imaging and blood samples were obtained from 113 participants within 24 h of imaging. RESULTS: In SZ, there was decreased fractional anisotropy(FA) in the genu and body of the corpus callosum (GCC/BCC), anterior corona radiata, anterior and posterior limbs of the internal capsule (ALIC/PLIC), superior fronto-occipital fasciculus, external capsule, and fornix, and elevated IL-6 levels. In both SZ and GHR-SZ, decreased FA in the splenium of the corpus callosum (SCC), posterior corona radiate (PCR), and posterior thalamic radiation (PTR) was observed, and elevated leptin levels were present. Additionally, the IL-6 levels were negatively correlated with FA in the GCC and ALIC in SZ, and leptin levels were negatively correlated with the SCC, PCR, and PTR in SZ and GHR-SZ. CONCLUSIONS: Abnormal WM integrity in SZ may reflect the state of disease and is associated with increased IL-6 levels. In addition, these leptin-associated WM integrity abnormalities in both SZ and GHR-SZ may reflect a genetic vulnerability to SZ.

20.
Anticancer Res ; 40(8): 4755-4762, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727802

RESUMO

BACKGROUND: Developmental disorders are associated with microglial dysfunction. Oral administration of lipopolysaccharide derived from Pantoea agglomerans bacteria (LPSp) leads to normalization of phagocytic activity of microglia and suppression of inflammation in mice. In this article, we report on a successful trial in which we achieved a significant improvement of symptoms in patients with developmental disorders. PATIENTS AND METHODS: Five pediatric patients diagnosed with autism spectrum disorders (ASD)/attention deficit hyperactivity disorder (ADHD) who visited our clinic received either 0.75 or 1 mg/day LPSp for 6 months or more, in addition to our usual therapy regimens (detoxification therapy, nutritional therapy, and vibration therapy). A survey questionnaire was completed by the patients' parents and evaluated using the Numerical Rating Scale. RESULTS: Behavior, verbal ability, and communication disabilities associated with ASD/ADHD improved in all patients. CONCLUSION: Oral administration of LPSp may represent a new treatment option in the area of developmental disorders where there is currently no treatment available.


Assuntos
Deficiências do Desenvolvimento/tratamento farmacológico , Lipopolissacarídeos/administração & dosagem , Pantoea/química , Administração Oral , Criança , Pré-Escolar , Citocinas/metabolismo , Deficiências do Desenvolvimento/metabolismo , Feminino , Humanos , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fagocitose/efeitos dos fármacos
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