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1.
Nucleic Acids Res ; 49(15): 8961-8973, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34365506

RESUMO

Histone recognition constitutes a key epigenetic mechanism in gene regulation and cell fate decision. PHF14 is a conserved multi-PHD finger protein that has been implicated in organ development, tissue homeostasis, and tumorigenesis. Here we show that PHF14 reads unmodified histone H3(1-34) through an integrated PHD1-ZnK-PHD2 cassette (PHF14PZP). Our binding, structural and HDX-MS analyses revealed a feature of bipartite recognition, in which PHF14PZP utilizes two distinct surfaces for concurrent yet separable engagement of segments H3-Nter (e.g. 1-15) and H3-middle (e.g. 14-34) of H3(1-34). Structural studies revealed a novel histone H3 binding mode by PHD1 of PHF14PZP, in which a PHF14-unique insertion loop but not the core ß-strands of a PHD finger dominates H3K4 readout. Binding studies showed that H3-PHF14PZP engagement is sensitive to modifications occurring to H3 R2, T3, K4, R8 and K23 but not K9 and K27, suggesting multiple layers of modification switch. Collectively, our work calls attention to PHF14 as a 'ground' state (unmodified) H3(1-34) reader that can be negatively regulated by active marks, thus providing molecular insights into a repressive function of PHF14 and its derepression.


Assuntos
Histonas/química , Histonas/metabolismo , Proteínas de Peixe-Zebra/química , Proteínas de Peixe-Zebra/metabolismo , Regulação Alostérica , Animais , Cristalografia por Raios X , Humanos , Modelos Moleculares , Mutagênese , Proteínas Nucleares/química , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Fatores de Transcrição/química , Proteínas de Peixe-Zebra/genética
2.
Neuroimage Clin ; 31: 102765, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34339947

RESUMO

Artificial intelligence has recently gained popularity across different medical fields to aid in the detection of diseases based on pathology samples or medical imaging findings. Brain magnetic resonance imaging (MRI) is a key assessment tool for patients with temporal lobe epilepsy (TLE). The role of machine learning and artificial intelligence to increase detection of brain abnormalities in TLE remains inconclusive. We used support vector machine (SV) and deep learning (DL) models based on region of interest (ROI-based) structural (n = 336) and diffusion (n = 863) brain MRI data from patients with TLE with ("lesional") and without ("non-lesional") radiographic features suggestive of underlying hippocampal sclerosis from the multinational (multi-center) ENIGMA-Epilepsy consortium. Our data showed that models to identify TLE performed better or similar (68-75%) compared to models to lateralize the side of TLE (56-73%, except structural-based) based on diffusion data with the opposite pattern seen for structural data (67-75% to diagnose vs. 83% to lateralize). In other aspects, structural and diffusion-based models showed similar classification accuracies. Our classification models for patients with hippocampal sclerosis were more accurate (68-76%) than models that stratified non-lesional patients (53-62%). Overall, SV and DL models performed similarly with several instances in which SV mildly outperformed DL. We discuss the relative performance of these models with ROI-level data and the implications for future applications of machine learning and artificial intelligence in epilepsy care.


Assuntos
Epilepsia do Lobo Temporal , Inteligência Artificial , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Esclerose/patologia , Máquina de Vetores de Suporte
3.
Artigo em Inglês | MEDLINE | ID: mdl-34232884

RESUMO

Closed-loop deep brain stimulation (DBS) paradigm is gaining tremendous favor due to its potential capability of further and more efficient improvements in neurological diseases. Preclinical validation of closed-loop controller is quite necessary in order to minimize injury risks of clinical trials to patients, which can greatly benefit from real-time computational models and thus potentially reduce research and development costs and time. Here we developed an embedded multi-core real-time simulation platform (EMC-RTP) for a biological-faithful computational network model of basal ganglia (BG). The single neuron model is implemented in a highly real-time manner using a reasonable simplification. A modular mapping architecture with hierarchical routing organization was constructed to mimic the pathological neural activities of BG observed in parkinsonian conditions. A closed-loop simulation testbed for DBS validation was then set up using a host computer as the DBS controller. The availability of EMC-RTP and the testbed system was validated by comparing the performance of open-loop and proportional-integral (PI) controllers. Our experimental results showed that the proposed EMC-RTP reproduces abnormal beta bursts of BG in parkinsonian conditions while meets requirements of both real-time and computational accuracy as well. Closed-loop DBS experiments using the EMC-RTP suggested that the platform could perform reasonable output under different kinds of DBS strategies, indicating the usability of the platform.


Assuntos
Estimulação Encefálica Profunda , Gânglios da Base , Simulação por Computador , Humanos , Modelos Neurológicos , Neurônios
4.
Ophthalmic Genet ; : 1-5, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34251978

RESUMO

PURPOSE: Genetic factors have been studied to be associated with diabetic retinopathy (DR). This study aimed to investigate the association between the polymorphisms in the osteoproterin (OPG) gene and DR in a Han Chinese population. METHODS: There were 475 patients with diabetic retinopathy (DR), 478 type 2 diabetes mellitus without retinopathy (DNR) and 469 healthy controls collected in this study. OPG single-nucleotide polymorphisms (SNPs) rs2073618 and rs3134069 were genotyped by Mass ARRAY MALDI-TOF system. The genotype and allele frequencies were evaluated using the χ2 tests. Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated for the risk of genotype and allele. RESULTS: There was a statistically significant difference for OPG SNP rs3134069 between DR cases and healthy controls in the allelic model (P = .036, OR = 1.33, 95% CI = 1.02-1.73). The C allele frequency of this polymorphism was 0.154 in the DR cases, whereas it was 0.120 in healthy controls, suggesting a risk effect for DR. SNP rs3134069 had a significant association with DR in the dominant model (P = .038, OR = 1.37, 95% CI = 1.02-1.84), indicating that the CC/AC genotype was more likely to suffer from DR. For rs2073618, no significant difference was identified in the allelic model (P = .632, OR = 0.95, 95% CI = 0.78-1.16) and the four genetic models. CONCLUSIONS: This study showed that OPG SNP rs3134069 was associated with DR in the dominant model, suggesting that the OPG gene variant may be involved in the development of DR.

5.
Nat Cell Biol ; 23(7): 782-795, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34183801

RESUMO

Endosome fission is essential for cargo sorting and targeting in the endosomal system. However, whether organelles other than the endoplasmic reticulum (ER) participate in endosome fission through membrane contacts is unknown. Here, we characterize a Golgi-derived vesicle, the SEC14L2 compartment, that plays a unique role in facilitating endosome fission through ternary contacts with endosomes and the ER. Localized to the ER-mediated endosome fission site, the phosphatidylinositol transfer protein SEC14L2 promotes phosphatidylinositol 4-phosphate (PtdIns4P) to phosphatidylinositol 3-phosphate (PtdIns3P) conversion before endosome fission. In the absence of SEC14L2, endosome fission is attenuated and more enlarged endosomes arise due to endosomal accumulation of PtdIns4P and reduction in PtdIns3P. Collectively, our data suggest roles of the Golgi network in ER-associated endosome fission and a mechanism involving ER-endosome contacts in the regulation of endosomal phosphoinositide conversion.


Assuntos
Proteínas de Transporte/metabolismo , Retículo Endoplasmático/metabolismo , Endossomos/metabolismo , Complexo de Golgi/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Células COS , Proteínas de Transporte/genética , Chlorocebus aethiops , Classe III de Fosfatidilinositol 3-Quinases/genética , Classe III de Fosfatidilinositol 3-Quinases/metabolismo , Retículo Endoplasmático/genética , Endossomos/genética , Complexo de Golgi/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transporte Proteico , Proteínas de Peixe-Zebra/genética
6.
Environ Res ; 200: 111434, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34087194

RESUMO

BACKGROUND: Urban greenness may protect against obesity, but very few studies have assessed 'street view' (SV) greenness metrics, which may better capture people's actual exposure to greenness compared to commonly-used satellite-derived metrics. We aimed to investigate these associations further in a Chinese adult study. METHODS: Our analysis included 24,845 adults in the 33 Chinese Community Health Study in 2009. SV images from Tencent Map, segmented by machine learning algorithms, were used to determine the average proportion of green vegetation in SV images at community level in 800m road network buffer. Sensitivity analyses were performed with an alternative buffer size. Overall greenness was assessed as normalized difference vegetation index (NDVI) in 800 m buffer. We used predicted PM2.5 and monitored NO2 as proxies of air pollution. Body mass index (BMI), waist circumference (WC) and hip circumference (HC) were regressed on SV greenness by generalized linear mixed models, with adjustment for covariates. Mediation analyses were performed to assess the mediation effects of air pollution. RESULTS: Each interquartile range (IQR = 3.6%) increase in street view greenness was associated with a 0.15 kg/m2 (95% CI: -0.22, -0.09) decrease in BMI and 0.23 cm (95% CI: -0.35, -0.11) reduction in HC, and was associated with 7% lower odds of overweight (OR = 0.93, 95% CI:0.90, 0.96) and 18% lower odds of obesity (OR = 0.82, 95% CI:0.76, 0.89). Similar effect estimation was observed compared with commonly-used NDVI measures. PM2.5 and NO2 mediated 15.5% and 6.1% of the effects of SV greenness with BMI, respectively. CONCLUSIONS: Our findings suggest beneficial associations between community-level SV greenness and lower body weight in Chinese adults. The effects were observed in women but not in men. Air pollution may partially mediate the association. These findings may have implications to support efforts to promote greening in urban areas.


Assuntos
Poluição do Ar , Saúde Pública , Adulto , Poluição do Ar/análise , Índice de Massa Corporal , China/epidemiologia , Feminino , Humanos , Masculino , Obesidade/epidemiologia
7.
Br J Ophthalmol ; 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039561

RESUMO

AIMS: To identify single-nucleotide polymorphisms (SNPs) associated with central serous chorioretinopathy (CSCR) by a systematic review and meta-analysis, and to compare the association profiles between CSCR, neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: We searched the EMBASE, PubMed and Web of Science for genetic studies of CSCR from the starting dates of the databases to 12 September 2020. We then performed meta-analyses on all SNPs reported by more than two studies and calculated the pooled OR and 95% CIs. We also conducted sensitivity analysis and adopted the funnel plot to assess potential publication bias. RESULTS: Totally 415 publications were reviewed, among them 10 were eligible for meta-analysis. We found 10 SNPs that have been reported at least twice. Meta-analysis and sensitivity analysis confirmed significant associations between CSCR and six SNPs in three genes, namely age-related maculopathy susceptibility 2 (ARMS2) (rs10490924, OR=1.37; p=0.00064), complement factor H (CFH) (rs800292, OR=1.44; p=7.80×10-5; rs1061170, OR=1.34; p=0.0028; rs1329428, OR=1.40; p=0.012; and rs2284664, OR=1.36; p=0.0089) and tumour necrosis factor receptor superfamily, member 10a (TNFRSF10A) (rs13278062, OR=1.34; p=1.44×10-15). Among them, only TNFRSF10A rs13278062 showed the same trend of effect on CSCR, nAMD and PCV, while the SNPs in ARMS2 and CFH showed opposite trends in the SNP associations. CONCLUSIONS: This study confirmed the associations of ARMS2, CFH and TNFRSF10A with CSCR, and revealed that ARMS2, CFH and TNFRSF10A may affect different phenotypic expressions of CSCR, nAMD and PCV.

8.
JAMA Netw Open ; 4(5): e2110931, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-34014325

RESUMO

Importance: Few studies have investigated the association between the exposure window (prenatal, early postnatal, and current period) of secondhand smoke (SHS) and attention-deficit/hyperactivity disorder (ADHD) symptoms and subtypes in children. Objective: To evaluate the associations of prenatal, early postnatal, or current SHS exposure with ADHD symptoms and subtypes among school-aged children. Design, Setting, and Participants: In this cross-sectional study, 48 612 children aged 6 to 18 years from elementary and middle schools in Liaoning province, China, between April 2012 and January 2013 were eligible for participation. Data on SHS exposure and ADHD symptoms and subtypes for each child were collected via questionnaires administered to parents or guardians by school teachers. Data were analyzed from September 14 to December 2, 2020. Main Outcomes and Measures: The ADHD symptoms and subtypes (inattention, hyperactivity-impulsivity, and combined) were measured based on a validated tool developed from the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Generalized linear mixed models were evaluated to estimate the association of SHS exposure with ADHD symptoms and subtypes. Results: A total of 45 562 participants completed the questionnaires and were included in this study (22 905 girls [50.3%]; mean [SD] age, 11.0 [2.6] years; 2170 [4.8%] with ADHD symptoms). Compared with their unexposed counterparts, children who were ever exposed (odds ratio [OR], 1.50; 95% CI, 1.36-1.66) or always exposed to SHS (OR, 2.88; 95% CI, 2.55-3.25) from pregnancy to childhood had higher odds of having ADHD symptoms and subtypes (ORs ranged from 1.46 [95% CI, 1.31-1.62] to 2.94 [95% CI, 2.09-4.13]). Compared with their unexposed counterparts, children with SHS exposure had higher odds of having ADHD symptoms when exposed in the prenatal period (OR, 2.28; 95% CI, 2.07-2.51), early postnatal period (OR, 1.47; 95% CI, 1.29-1.68), or current period (OR, 1.20; 95% CI, 1.09-1.31). Compared with their unexposed counterparts, children whose fathers smoked 10 or more cigarettes/d on both weekdays and weekends had higher odds of having ADHD symptoms and subtypes (ORs ranged from 1.48 [95% CI, 1.28-1.70] to 2.25 [95% CI, 1.29-3.93]). Conclusions and Relevance: Being exposed to SHS from pregnancy to childhood was associated with higher odds of having ADHD symptoms and subtypes among school-aged children, and the associations were somewhat stronger for SHS exposure during prenatal and early postnatal periods. Our findings highlight the important public health implications of reducing SHS exposure, which may decrease the health and economic burdens of individuals with ADHD.

9.
Food Funct ; 12(9): 4060-4071, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33977982

RESUMO

A germination treatment was explored in this study as a green strategy to reduce the in vitro starch digestibility of cooked quinoa. The alterations of chemical compositions, starch chain-length distributions (CLDs) and rheological characteristics of quinoa flours after the germination treatment were characterized. Results showed that a significant alteration of amylose CLDs and the starch digestibility was observed for cooked quinoa flours after different germination times. By fitting starch digestograms to the logarithm of slop (LOS) plot and the combination of parallel and sequential kinetics model (CPS), two starch digestible fractions with distinct rate constants were identified. Pearson correlation analysis further found that the observed starch digestive characteristics could be largely explained by the alterations of amylose CLDs caused by the germination treatment. More specifically, the rapidly digestible starch fraction mainly consisted of amorphous amylopectin molecules and amylose intermolecular crystallites. On the other hand, the slowly digestible starch fraction was largely formed by intramolecular interactions among amylose short chains (degree of polymerization (DP) < 500). These results suggest that germination may be a promising way to develop cereal products with slower starch digestibility.


Assuntos
Chenopodium quinoa/química , Chenopodium quinoa/crescimento & desenvolvimento , Digestão , Germinação , Amido/química , Amilopectina/química , Amilose/química , Culinária , Hidrogéis , Técnicas In Vitro , Reologia , Viscosidade
10.
Theranostics ; 11(11): 5539-5552, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859762

RESUMO

Rationale: We developed a cocktail of soluble molecules mimicking the in vivo milieu supporting liver regeneration that could convert mature hepatocytes to expandable liver progenitor-like cells in vitro. This study aimed to induce endogenous liver progenitor cells by the administration of the soluble molecules to provide an alternative approach for the resolution of liver fibrosis. Methods: In vitro cultured hepatocyte-derived liver progenitor-like cells (HepLPCs) were transplanted into CCL4-treated mice to investigate the therapeutic effect against liver fibrosis. Next, we used HGF in combination with a cocktail of small molecules (Y-27632, A-83-01, and CHIR99021 (HACY)) to induce endogenous CD24+ liver progenitor cells and to inhibit the activation of hepatic stellate cells (HSCs) during CCL4-induced hepatic injury. RNA sequencing was performed to further clarify the features of HACY-induced CD24+ cells compared with CCL4-induced CD24+ cells and in vitro derived HepLPCs. Finally, we evaluated the expansion of HACY-induced CD24+ cells in human hepatocyte-spheroids from fibrotic liver tissues. Results: HepLPCs exhibited the capacity to alleviate liver fibrosis after transplantation into CCL4-treated mice. The in vivo administration of HACY not only induced the conversion of mature hepatocytes (MHs) to CD24+ progenitor cells but prevented the activation of HSCs, thus leading to enhanced improvement of liver fibrosis in CCL4-treated mice. Compared to CD24+ cells induced by CCL4 alone, HACY-induced CD24+ cells retained an enhanced level of hepatic function and could promote the restoration of liver function that exhibited comparable gene expression profiles with HepLPCs. CD24+ cells were also observed in human liver fibrotic tissues and were expanded in three-dimensional (3D) hepatic spheroids in the presence of HACY in vitro. Conclusions: Hepatocyte-derived liver progenitor-like cells are crucial for liver regeneration during chronic hepatic injuries. The administration of HACY, which allowed the induction of endogenous CD24+ progenitor cells and the inactivation of HSCs, exerts beneficial effects in the treatment of liver fibrosis by re-establishing a balance favoring liver regeneration while preventing fibrotic responses.


Assuntos
Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Fígado/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Células-Tronco/efeitos dos fármacos , Amidas/farmacologia , Animais , Antígeno CD24/metabolismo , Tetracloreto de Carbono/farmacologia , Células Cultivadas , Expressão Gênica/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Fígado/metabolismo , Cirrose Hepática/metabolismo , Regeneração Hepática/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piridinas/farmacologia , Pirimidinas/farmacologia , Células-Tronco/metabolismo
11.
Eur J Obstet Gynecol Reprod Biol ; 259: 146-152, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33676123

RESUMO

OBJECTIVE: During the past three decades, applying IVF for infertility treatment PCOS women has increased significantly, and the landscape of treatment strategies has changed dramatically. However, early review of IVF on PCOS have insufficiently accounted for efficacy and safety of the technic. With abundant studies in recent years, there is a need to reconcile these new data. MATERIAL AND METHODS: To compare reproductive and obstetric outcomes of IVF between women with and without PCOS, a meta-analysis of 95 studies involving more than 21289 PCOS patients and 43036 controls was performed. RESULTS: Despite longer stimulation duration (WMD = 0.34 day, 95 % CI: 0.09, 0.59) and lower dose of Gn required (WMD = -361.3 IU, 95 % CI: -442.3, -280.4), more oocytes (WMD = 3.67, 95 % CI: 3.14-4.21) and matured oocytes (WMD = 2.16, 95 % CI: 1.52-2.80) per cycle were obtained from PCOS women. There were no statistically significant differences for cleavage, high-grade embryo and implantation rate. Although similar pregnancy and live birth rates per cycle were achieved in PCOS and non-PCOS women after IVF, women with PCOS still suffered from significantly increased risks of miscarriage (OR = 1.44, 95 % CI: 1.20-1.72), biochemical pregnancy loss (OR = 1.89, 95 % CI: 1.48-2.41), and OHSS (OR = 3.58, 95 % CI: 2.86-4.48), in addition to lower fertilization rate (OR = 0.79, 95 % CI: 0.71-0.88). Adverse obstetric outcomes including ectopics pregnancy and multiple pregnancies are comparable between two groups. The overall cycle cancellation rate was significantly higher among PCOS women with OR of 2.55 (95 % CI: 1.67-3.89), and concern over OHSS or hyper-response constitute the main cause. Similar results were also observed after stratified analysis. CONCLUSIONS: Our results support the effectiveness of IVF for infertility treatment among PCOS patients. However, options to minimize adverse outcomes regarding to lower fertilization, miscarriage, biochemical pregnancy loss and OHSS are required. Further studies elucidating detailed mechanism underlying these adverse outcomes could be of great importance to improve the experience of IVF treatment.


Assuntos
Infertilidade Feminina , Síndrome de Hiperestimulação Ovariana , Síndrome do Ovário Policístico , Coeficiente de Natalidade , Feminino , Fertilização In Vitro , Humanos , Infertilidade Feminina/etiologia , Infertilidade Feminina/terapia , Indução da Ovulação , Síndrome do Ovário Policístico/complicações , Gravidez , Taxa de Gravidez
12.
Food Chem ; 353: 129467, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33740510

RESUMO

Starch lamellar and crystalline structures are important controller of its physicochemical and digestion properties. Here, starch lamellar/crystalline structures of 16 different rice starches were investigated and correlated with their chain-length distributions (CLDs) and molecular size distributions. Results showed that the thickness of amorphous lamellae was mainly correlated with the amount of amylose short and medium chains. Thickness of both amorphous and crystalline lamellae was negatively correlated with the amount of amylopectin medium chains and relative length of amylopectin short chains. The degree of crystallinity was negatively correlated with the amount of amylose short and long chains. The lamellar ordering, fractal nature and thickness polydispersity were also related to the starch CLDs. Whereas, starch molecular size distributions were shown to be lack of correlations with the starch lamellar/crystalline structures. This study helps a better understanding of the molecular nature of starch semi-crystalline lamellae.


Assuntos
Oryza/química , Amido/química , Amilopectina/química , Amilose/química , Espalhamento a Baixo Ângulo , Difração de Raios X
13.
Signal Transduct Target Ther ; 6(1): 110, 2021 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-33677468

RESUMO

The 2019 coronavirus disease (COVID-19) outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency. However, the virus' pathogenesis remains unclear, and there is no cure for the disease. We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5' gene expression, T cell receptor (TCR), and B cell receptors (BCR) V(D)J transcriptome analysis at a single-cell resolution. We obtained single-cell mRNA sequencing (scRNA-seq) data of 341,420 peripheral blood mononuclear cells (PBMCs) and 185,430 clonotypic T cells and 28,802 clonotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies. In addition, we used three control samples. We found expansion of dendritic cells (DCs), CD14+ monocytes, and megakaryocytes progenitor cells (MP)/platelets and a reduction of naïve CD4+ T lymphocytes in patients with COVID-19, along with a significant decrease of CD8+ T lymphocytes, and natural killer cells (NKs) in patients in critical condition. The type I interferon (IFN-I), mitogen-activated protein kinase (MAPK), and ferroptosis pathways were activated while the disease was active, and recovered gradually after patient conditions improved. Consistent with this finding, the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls. The concentration of interferon-α (IFN-α) in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls, further suggesting the important role of the IFN-I pathway in the immune response of COVID-19. TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens. Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection, providing clues for therapeutic potentials in treating COVID-19.


Assuntos
COVID-19/imunologia , Leucócitos/imunologia , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , SARS-CoV-2/imunologia , Análise de Célula Única , Adulto , COVID-19/genética , Feminino , Ferroptose/genética , Ferroptose/imunologia , Humanos , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/imunologia , Masculino , Pessoa de Meia-Idade , RNA-Seq , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos T/genética , SARS-CoV-2/genética
14.
J Med Virol ; 93(5): 3165-3175, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33590923

RESUMO

The disease spectrum of coronavirus disease 2019 (COVID-19) varies from asymptomatic infection to critical illness and death. Identification of prognostic markers is vital for predicting progression and clinical practice. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, known as RNAemia, has been detected in the blood. However, the potential clinical value of SARS-CoV-2 RNAemia remains unknown. We, therefore, conducted a meta-analysis using a random-effects model to estimate the pooled prevalence of SARS-CoV-2 RNAemia as well as summary strength of RNAemia in association with disease severity and unfavorable clinical outcomes. A total of 21 studies involving 2181 patients were included. SARS-CoV-2 RNAemia in COVID-19 patients varied from 9.4% to 74.1%, with a pooled estimate of 34% (95% confidene interval [CI]: 26%-43%). Overall, SARS-CoV-2 RNAemia was associated with COVID-19 severity with odds ratio (OR) of 5.43 (95% CI: 3.46-8.53). In addition, SARS-CoV-2 RNAemia was a significant risk factor for unfavorable clinical outcomes (OR = 6.54, 95% CI: 3.82-11.21). The summary OR was 4.28 (95% CI: 2.20-8.33) for intensive care unit (ICU) admission, 11.07 (95% CI: 5.60-21.88) for mortality. Furthermore, RNAemia was also a significant risk factor for invasive mechanical ventilation and multiple organ failure. SARS-CoV-2 RNAemia is associated with disease severity, ICU admission, death in COVID-19, and may serve as a clinical predictor. More prospective trials in evaluating the potential of SARS-CoV-2 RNAemia as a prognostic indicator are necessary.


Assuntos
COVID-19/diagnóstico , RNA Viral/sangue , SARS-CoV-2/genética , Índice de Gravidade de Doença , COVID-19/mortalidade , COVID-19/terapia , Bases de Dados Factuais , Hospitalização , Humanos , Razão de Chances , Prognóstico , RNA Viral/isolamento & purificação , Respiração Artificial , Fatores de Risco , Carga Viral
15.
J Assist Reprod Genet ; 38(4): 931-939, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33496916

RESUMO

PURPOSE: Obesity, measured by body mass index (BMI), is implicated in adverse pregnancy outcomes for women seeking in vitro fertilization (IVF) care. However, the shape of the dose-response relationship between BMI and IVF outcomes remains unclear. METHODS: We therefore conducted a dose-response meta-analysis using a random effects model to estimate summary relative risk (RR) for clinical pregnancy (CPR), live birth (LBR), and miscarriage risk (MR) after IVF. RESULTS: A total of 18 cohort-based studies involving 975,889 cycles were included. For each 5-unit increase in BMI, the summary RR was 0.95 (95% CI: 0.94-0.97) for CPR, 0.93 (95% CI: 0.92-0.95) for LBR, and 1.09 (95% CI: 1.05-1.12) for MR. There was evidence of a non-linear association between BMI and CPR (Pnon-linearity < 10-5) with CPR decreasing sharply among obese women (BMI > 30). Non-linear dose-response meta-analysis showed a relatively flat curve over a broad range of BMI from 16 to 30 for LBR (Pnon-linearity = 0.0009). In addition, we observed a J-shaped association between BMI and MR (Pnon-linearity = 0.006) with the lowest miscarriage risk observed with a BMI of 22-25. CONCLUSIONS: In conclusion, obesity contributed to increased risk of adverse IVF outcomes in a non-linear dose-response manner. More prospective trials in evaluating the effect of body weight control are necessary.


Assuntos
Aborto Espontâneo/epidemiologia , Índice de Massa Corporal , Nascido Vivo/epidemiologia , Obesidade/epidemiologia , Aborto Espontâneo/patologia , Aborto Espontâneo/fisiopatologia , Adulto , Transferência Embrionária , Feminino , Fertilização In Vitro/métodos , Humanos , Obesidade/complicações , Obesidade/fisiopatologia , Gravidez , Resultado da Gravidez/epidemiologia , Taxa de Gravidez
16.
Food Funct ; 12(2): 682-695, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33410441

RESUMO

Native rice starch is a source of slowly digestible starch in e.g. low-moisture baked products, while the molecular and lamellar/crystalline structure giving rise to this low-digestibility property is still largely unknown. In this study, the in vitro digestion kinetics of 11 rice starches with a wide range of amylose content were investigated. Applying the logarithm of slope (LOS) plot to the starch digestograms suggested that only a single first-order kinetics phase existed. More importantly, results for the first time showed that rice starches with shorter amylopectin short chains (DP 10-26) had more perfectly aligned crystalline lamellae and much slower digestion rates than the other starches. Interestingly, no correlations were found between the starch lamellar thicknesses with its digestion rate. It suggests that lamellar perfection plays a dominant role in the determination of native starch digestibility. Furthermore, starches with relatively shorter amylose short and medium chains showed a significantly higher amount of V-type amylose-lipid complex, and smaller maximum digestion extent. These results could help the rice industry develop a new generation of rice products with slower starch digestion rate and more desirable nutritional values.


Assuntos
Oryza/química , Amido/química , Configuração de Carboidratos , Digestão
17.
Carbohydr Polym ; 254: 117275, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357853

RESUMO

In current study, the effects of starch fine molecular structures on its in vitro digestibility at fully gelatinized stage were investigated. The digestion kinetics of 15 fully gelatinized rice starches were obtained and correlated with starch chain-length distributions and molecular size distributions. Both logarithm of slopes and parallel first-order kinetic model were applied to fit the digestion curves to a few kinetics-based parameters. Result showed there were two simultaneous digestion fractions (fast versus slow) for fully gelatinized rice starches. The rate constants of slowly-digestible fraction significantly correlated with starch molecular sizes, especially with that of amylopectin molecules. Hydrodynamically larger amylopectin molecules tend to contain more shorter branches but less long chains. This slows down the starch hydrolysis by α-amylase while the action of AMG is less antagonistically hindered, increasing overall digestion rate. This study provides important information for rice breeders and manufacturers to develop rice products with reduced starch digestibility.


Assuntos
Oryza/química , Amido/química , Amilopectina/química , Amilopectina/farmacocinética , Digestão , Gelatina/química , Humanos , Técnicas In Vitro , Cinética , Modelos Biológicos , Estrutura Molecular , Peso Molecular , Amido/farmacocinética
18.
Cell Signal ; 79: 109882, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33316386

RESUMO

Identifying biomarkers for the early diagnosis of glioma and elucidating the molecular mechanisms underlying the development of this cancer are of considerable clinical importance. Recently, studies performing microarray profiling of genes to identify distinct gene signatures reported specific subtypes with predictive and prognostic relevance. Thus, we performed deep sequencing on a total of 26 glioma tissue samples to identify the frequently mutated of oncogenes and tumor suppressors in gliomas. A total of 2306 single-nucleotide polymorphisms (SNPs) and 2010 insertion and deletion sites (indels) were found by aligning sequencing information from 26 glioma samples with sequences from the normal human gene database (GRCh37/hg19). GSEA results suggest that an underexpressed gene, calmodulin binding transcription activator 1 (CAMTA1), participates in the cell proliferation and cell cycle regulation of glioma cells. Moreover, overexpression of CAMTA1 in glioma cells notably inhibited cell growth, migration, invasion and cell cycle and enhanced temozolomide (TMZ)-induced cell apoptosis in glioma cells, while CAMTA1 overexpression decreased the ITGA5, ITGB1, p-AKT, p-FAK, and Myc protein levels, suggesting that the signaling pathways of these proteins might be involved in the cellular functions of CAMTA1 in glioma. Moreover, overexpression of CAMTA1 attenuated the growth and tumorigenesis of glioma in vivo. In summary, we identified high-frequency mutant genes in glioma and provided an experimental basis for a novel mechanism by which CAMTA1 may serve as a tumor suppressor in glioma.

19.
Environ Pollut ; 270: 116211, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33348139

RESUMO

Evidence concerning effects of ambient air pollution on homocysteine (HCY) metabolism is scarce. We aimed to explore the associations between ambient particulate matter (PM) exposure and the HCY metabolism markers and to evaluate effect modifications by folate, vitamin B12, and methylenetetrahyfrofolate reductase (MTHFR) C677T gene polymorphism. Between December 1, 2017 and January 5, 2018, we conducted a panel study in 88 young college students in Guangzhou, China, and received 5 rounds of health examinations. Real-time concentrations of PMs with aerodynamic diameter ≤2.5 (PM2.5), ≤1.0 (PM1.0), and ≤0.1 (PM0.1) were monitored, and the serum HCY metabolism markers (i.e., HCY, S-Adenosylhomocysteine [SAH], and S-Adenosylmethionine [SAM]) were repeatedly measured. We applied linear mixed effect models combined with a distributed lag model to evaluate the associations of PMs with the HCY metabolism markers. We also explored effect modifications of folate, vitamin B12, and the MTHFR C677T polymorphism on the associations. We observed that higher concentrations of PM2.5 and PM1.0 were associated with higher serum levels of HCY, SAH, SAM, and SAM/SAH ratio (e.g., a 10 µg/m3 increase in PM2.5 during lag 0 day and lag 5 day was significantly associated with 1.3-19.4%, 1.3-28.2%, 6.2-64.4%, and 4.8-28.2% increase in HCY, SAH, SAM, and SAM/SAH ratio, respectively). In addition, we observed that the associations of PM2.5 with the HCY metabolism markers were stronger in participants with lower B vitamins levels. This study demonstrated that short-term exposure to PM2.5 and PM1.0 was deleteriously associated with the HCY metabolism markers, especially in people with lower B vitamins levels.


Assuntos
Complexo Vitamínico B , China , Homocisteína , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Oxirredutases , Material Particulado , Polimorfismo Genético
20.
Aging (Albany NY) ; 12(20): 20285-20307, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33085646

RESUMO

Glioma is one of the most commonly diagnosed brain malignancies with a high cancer-related death rate in humans. The prognosis of glioma patients is still unsatisfactory. In the present study, we attempted to identify lncRNAs and miRNAs that might be related to NF-κB-mediated epithelial-mesenchymal transition in glioma cells based on online microarray expression profiles, and investigate the specific effects of lncRNA-miRNA-mRNA axes on glioma cell phenotypes. Herein, we identified lncRNA DGCR5 as a downregulated lncRNA in glioma that was negatively regulated by NF-κB1 in an NF-κB1 RE-dependent manner. LncRNA DGCR5 overexpression significantly inhibited the capacity of glioma cells to proliferate, migrate, and invade, whereas promoted the apoptosis of glioma cells. Moreover, lncRNA DGCR5 overexpression upregulated the epithelial marker E-cadherin while downregulating the mesenchymal marker VIM, as well as Snai2 and TWIST. Regarding the underlying molecular mechanisms, lncRNA DGCR5 could inhibit miR-21 and miR-23a expression, and miR-21 or miR-23a overexpression significantly reversed the tumor-suppressive effects of lncRNA DGCR5 overexpression. LncRNA DGCR5 exerted its tumor-suppressive effects through the DGCR5/miR-21/Smad7 and DGCR5/miR-23a/PTEN axes. In conclusion, lncRNA DGCR5 suppresses the capacity of glioma cells to migrate and invade via miR-21/Smad7, whereas it inhibits the proliferation and enhances the apoptosis of glioma cells through miR-23a/PTEN.


Assuntos
Neoplasias Encefálicas/enzimologia , Transição Epitelial-Mesenquimal , Glioma/enzimologia , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , RNA Longo não Codificante/metabolismo , Proteína Smad7/metabolismo , Animais , Apoptose , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/patologia , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Subunidade p50 de NF-kappa B/genética , Subunidade p50 de NF-kappa B/metabolismo , Invasividade Neoplásica , RNA Longo não Codificante/genética , Transdução de Sinais , Carga Tumoral
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