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1.
J Immunol ; 207(8): 2118-2128, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34507947

RESUMO

Sepsis is a life-threatening organ dysfunction caused by a dysfunctional host response to infection. Neutrophils play a protective role by releasing antibacterial proteins or by phagocytizing bacteria. However, excess neutrophils can induce tissue damage. Recently, a novel intercellular communication pathway involving extracellular vesicles (EVs) has garnered considerable attention. However, whether EVs secreted by macrophages mediate neutrophil recruitment to infected sites has yet to be studied. In this study, we assessed the chemotactic effect of EVs isolated from mouse Raw264.7 macrophages on mouse neutrophils and found that CXCL2 was highly expressed in these EVs. By regulating CXCL2 in Raw264.7 macrophages, we found that CXCL2 on macrophage EVs recruited neutrophils in vitro and in vivo. The CXCL2 EVs activated the CXCR2/PKC/NOX4 pathway and induced tissue damage. This study provides information regarding the mechanisms underlying neutrophil recruitment to tissues and proposes innovative strategies and targets for the treatment of sepsis.

2.
Front Microbiol ; 12: 673969, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489882

RESUMO

Accumulated evidence shows that complex microbial communities resides in the healthy human urinary tract and can change in urological disorders. However, there lacks a comprehensive profiling of the genitourinary microbiota in healthy cohort. Here, we performed 16S rRNA gene sequencing of midstream urine specimens from 1,172 middle-aged and elderly healthy individuals. The core microbiota included 6 dominant genera (mean relative abundance >5%), including Prevotella, Streptococcus, Lactobacillus, Gardnerella, Escherichia-Shigella, and Veillonella, and 131 low-abundance genera (0.01-5%), displaying a distinct microbiome profiles to that of host-matched gut microbiota. The composition and diversity of genitourinary microbiome (GM) were distinct between genders and may fluctuate with ages. Several urotypes were identified by the stratification of microbiome profiles, which were mainly dominated by the six most predominant genera. The prevalence of urotypes was disparate between genders, and the male sample additionally harbored other urotypes dominated by Acinetobacter, Corynebacterium, Staphylococcus, or Sphingomonas. Peptoniphilus, Ezakiella, and Porphyromonas were co-occurred and co-abundant, and they may play crucial roles as keystone genera and be associated with increased microbial diversity. Our results delineated the microbial structure and diversity landscape of the GM in healthy middle-aged and elderly adults and provided insights into the influence of gender and age to it.

3.
Clin Psychol Psychother ; 28(5): 1146-1159, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33592682

RESUMO

The aim of current study was to investigate risk perception of COVID-19 pandemic, sleep quality and time change of leisure activity and their correlations with posttraumatic stress disorder (PTSD) in healthcare workers (HCWs) from four designated hospitals in China. Medical staffs (n = 317) from three designated hospitals in Guangdong Province and one designated hospital in Guangxi Province were surveyed on their demographic information, sleep quality and time change of leisure activity, risk perception of pandemic and PTSD symptoms (by using PTSD checklist for DSM-5 (PCL-5)). Hierarchical regression and structural equation model (SEM) were used to examine the correlated factors of PTSD. The prevalence of high level of PTSD symptoms (PCL-5 > =33, a probable diagnosis of PTSD) was 10.7%. Regression analysis found that risk perception (dread: ß = 0.142, p < 0.01; familiarity: ß = 0.203, p < 0.01), sleep quality (ß = 0.250, p < 0.001), time change of leisure activity (ß = -0.179, p < 0.01), were independently correlated with PTSD severity, which was further confirmed by SEM. Locations of COVID-19-related hazards were significant different in cognitive map of risk perception between groups with high and low levels of PTSD symptoms. Risk perception of COVID-19 pandemic influenced PTSD symptoms in HCWs. Adequate time for leisure activity and good sleep quality protected some HCWs against PTSD symptoms under the influence of pandemic. More researches were warranted to understand the path from pre-factors of risk perception to its psychological consequences among HCWs.

4.
BMC Endocr Disord ; 21(1): 2, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407364

RESUMO

BACKGROUND: Noonan syndrome is an inherited disease involving multiple systems. More than 15 related genes have been discovered, among which LZTR1 was discovered recently. However, the pathogenesis and inheritance pattern of LZTR1 in Noonan syndrome have not yet been elucidated. CASE PRESENTATION: We herein describe a family with LZTR1-related Noonan syndrome. In our study, the proband, sister, mother, maternal aunt and grandmother and female cousin showed the typical or atypical features of Noonan syndrome. Only 3 patients underwent the whole-exome sequencing analysis and results showed that the proband as well as her sister inherited the same heterozygous LZTR1 variant (c.1149 + 1G > T) from their affected mother. Moreover, the proband accompanied by growth hormone deficiency without other associated variants. CONCLUSION: In a Chinese family with Noonan syndrome, we find that the c.1149 + 1G > T variant in LZTR1 gene shows a different autosomal dominant inheritance from previous reports, which changes our understanding of its inheritance and improves our understanding of Noonan syndrome.


Assuntos
Heterozigoto , Mutação , Síndrome de Noonan/patologia , Fenótipo , Fatores de Transcrição/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Síndrome de Noonan/etiologia , Síndrome de Noonan/metabolismo , Linhagem , Prognóstico
5.
Front Genet ; 11: 741, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765589

RESUMO

Familial chylomicronemia syndrome (FCS) is a rare monogenic autosomal recessive disease caused by loss-of-function mutations in genes involved in chylomicron breakdown through hydrolysis of triglycerides into free fatty acids. Patients are often diagnosed in early childhood with extremely high triglyceride levels and symptoms including abdominal pain, eruptive cutaneous xanthomata, hepatosplenomegaly, and significant cognitive, psychological, and social impairment. The most serious medical condition suffered by FCS patients is recurrent acute pancreatitis. Lipoprotein lipase (LPL) gene mutation accounts for majority of the known pathogenic mutations. Early diagnosis and strict low-fat diet are critical for successful management of the triglyceride concentration to lower the risk of pancreatitis. The true prevalence of FCS in China is unknown and here we report a Chinese female preterm neonate presented with an extremely high triglyceride level of 22.11 mmol/L on day 13 after birth. Clinical and laboratory workup including whole-exome sequencing revealed two novel compound heterozygous LPL mutations (c.406G > C and c.829G > C) that are co-segregated with her non-consanguineous parents, consistent with autosomal recessive inheritance. A diagnosis of FCS based on clinical, biochemical, and genetic ground was made to guide her management.

6.
Molecules ; 25(11)2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32521705

RESUMO

Research on the composition and structure of coal is the most important and complex basic research in the coal chemistry field. Various methods have been used to study the structure of coal from different perspectives. However, due to the complexity of coal and the limitations of research methods, research on the macromolecular structure of coal still lacks systematicness. Huainan coalfield is located in eastern China and is the largest coal production and processing base in the region. In this study, conventional proximate analysis and ultimate analysis, as well as advanced instrumental analysis methods, such as Fourier transform infrared spectroscopy (FITR), X-ray diffraction (XRD), 13C-CP/MAS NMR, and other methods (SEM and AFM), were used to analyze the molecular structure of Huainan coal (HNC) and the distribution characteristics of oxygen in different oxygen-containing functional groups (OCFGs) in an in-depth manner. On the basis of SEM observation, it could be concluded that the high-resolution morphology of HNC's surface contains pores and fractures of different sizes. The loose arrangement pattern of HNC's molecular structure could be seen from 3D AFM images. The XRD patterns show that the condensation degree of HNC's aromatic ring is low, and the orientation degree of carbon network lamellae is poor. The calculated ratio of the diameter of aromatic ring lamellae to their stacking height (La/Lc = 1.05) and the effective stacking number of aromatic nuclei (Nave = 7.3) show that the molecular space structure of HNC is a cube formed of seven stacked aromatic lamellae. The FTIR spectra fitting results reveal that the aliphatic chains in HNC's molecular structure are mainly methyne and methylene. Oxygen is mainly -O-, followed by -C=O, and contains a small amount of -OH, the ratio of which is about 8:1:2. The molar fraction of binding elements has the approximate molecular structure C100H76O9N of organic matter in HNC. The results of the 13C NMR experiments show that the form of aromatic carbon atoms in HNC's structure (the average structural size X_b of aromatic nucleus = 0.16) is mainly naphthalene with a condensation degree of 2, and the rest are aromatic rings composed of benzene rings and heteroatoms. In addition, HNC is relatively rich in ≡CH and -CH2- structures.


Assuntos
Espectroscopia de Ressonância Magnética Nuclear de Carbono-13/métodos , Carvão Mineral/análise , Microscopia de Força Atômica/métodos , Microscopia Eletrônica de Varredura/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodos , Estrutura Molecular
7.
Diagn Pathol ; 15(1): 49, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393293

RESUMO

BACKGROUND: The objective of this study was to investigate genetic variations and the relationships between these genetic variations and clinicopathological features of high-recurrence risk papillary thyroid carcinoma in a southern Chinese population. METHODS: One hundred sixty-eight patients of high-recurrence risk papillary thyroid carcinoma were recruited for this study from 2017 to 2018. Formalin-fixed paraffin-embedded tissue and the data of clinicopathological characteristics were all collected and analyzed from these patients. We used next-generation sequencing technology to investigate the targeted gene mutations and gene fusions of the pathology specimens. RESULTS: The frequency of candidate tumor driver gene mutation was 85.1% in 143 patients, including BRAF V600E mutation in 119 patients(70.8%), RET fusion in 13 patients(7.7%), TERT promoter mutations in 11 patients(6.5%), RAS (HRAS, NRAS, KRAS) gene mutations in 10 patients(6.0%), and other mutations involving TP53, PIK3CA, AKT1, PTEN and NTRK1. Concomitant presence of more than two genetic aberrations was seen in 27 patients (16.1%). Our study showed that BRAF V600E mutation is highly correlated with conventional PTC (p < 0.001), BRAF V600E and TERT promoter mutation duet was associated with older patient age (> 45, p = 0.003) and higher disease stage of III or IV (p = 0.002). RAS gene and BRAF V600E co-mutations were only seen in multifocal PTC (p = 0.015). CONCLUSION: In our high-recurrence risk PTC cohort, most patients had more than one driver gene aberration. Coexistence of BRAF V600E with TERT promoter mutations or with RAS mutations were significantly correlated with worse clinicopathological characteristics.


Assuntos
Recidiva Local de Neoplasia/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Telomerase/genética , Proteínas ras/genética
8.
Bioinformatics ; 36(12): 3913-3915, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32186699

RESUMO

MOTIVATION: Liquid chromatography-mass spectrometry-based non-targeted metabolomics is routinely performed to qualitatively and quantitatively analyze a tremendous amount of metabolite signals in complex biological samples. However, false-positive peaks in the datasets are commonly detected as metabolite signals by using many popular software, resulting in non-reliable measurement. RESULTS: To reduce false-positive calling, we developed an interactive web tool, termed CPVA, for visualization and accurate annotation of the detected peaks in non-targeted metabolomics data. We used a chromatogram-centric strategy to unfold the characteristics of chromatographic peaks through visualization of peak morphology metrics, with additional functions to annotate adducts, isotopes and contaminants. CPVA is a free, user-friendly tool to help users to identify peak background noises and contaminants, resulting in decrease of false-positive or redundant peak calling, thereby improving the data quality of non-targeted metabolomics studies. AVAILABILITY AND IMPLEMENTATION: The CPVA is freely available at http://cpva.eastus.cloudapp.azure.com. Source code and installation instructions are available on GitHub: https://github.com/13479776/cpva. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Metabolômica , Software , Cromatografia Líquida , Internet , Espectrometria de Massas
9.
Materials (Basel) ; 13(6)2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32192167

RESUMO

This paper aimed to perform systematical study on the distribution of landslide thrust in pile-anchor support system, which has been a widely applicable treatment method in landslide control with safety, highly efficiency and adaptation. The advantage of photoelastic technique is visualization of strain and stress fields, therefore photoelastic model tests are conducted to show the distribution of landslide thrust in pile-anchor structure before failure in landslide. The effects of different materials and pile lengths are investigated by 6 photoelastic test cases under different loading conditions. It can be found from quantitative analysis of experimental results that load proportion of anchor would increase gradually with the decrease of pile embedded depth or the increase of landslide thrust force. Meanwhile, landslide thrust distribution in pile-anchor structure is directly affected by the stiffness of piles. The pile-anchor structure is significantly better at reducing bending moment value and optimizing bending moment distribution of pile. Finally, some theoretical analysis and design suggestions are proposed based on the experimental study.

10.
Reprod Biol Endocrinol ; 18(1): 15, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32113484

RESUMO

BACKGROUND: The study is aimed to provide prediction for fertility risk in the setting of assisted reproduction for a woman with complex chromosomal rearrangements (CCRs). METHODS: We implemented a robust approach, which combined whole-genome low-coverage mate-pair sequencing (WGL-MPS), junction-spanning PCR and preimplantation genetic testing for aneuploidy (PGT-A) method to provide accurate chromosome breakpoint junctional sequences in the embryo selection process in the setting of assisted reproduction for a couple with recurrent abortions due to CCRs. RESULT: WGL-MPS was applied to a female carrying CCRs which consisted of 9 breakpoints and 1 cryptic deletion related to fertility risks. Sequencing data provided crucial information for designing junction-spanning PCR and PGT-A process, which was performed on the 11 embryos cultivated. One embryo was considered qualified for transplanting, which carried the exact same CCRs as the female carrier, whose phenotype was normal. The amniotic fluid was also investigated by WGL-MPS and karyotyping at 19 weeks' gestation, which verified the results that the baby carried the same CCRs. A healthy baby was born at 39 weeks' gestation by vaginal delivery. CONCLUSION(S): Our study illustrates the WGL-MPS approach combining with junction-spanning PCR and PGT-A is a powerful and practical method in the setting of assisted reproduction for couples with recurrent miscarriage due to chromosomal abnormalities, especially CCRs carriers.


Assuntos
Aborto Habitual/genética , Aberrações Cromossômicas , Diagnóstico Pré-Implantação/métodos , Diagnóstico Pré-Natal/métodos , Adulto , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 4/genética , Cromossomos Humanos Par 5/genética , Transferência Embrionária/métodos , Feminino , Testes Genéticos/métodos , Humanos , Recém-Nascido , Masculino , Gravidez , Técnicas de Reprodução Assistida
11.
Phys Rev Lett ; 124(5): 057201, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32083901

RESUMO

Magnets with chiral crystal structures and helical spin structures have recently attracted much attention as potential spin-electronics materials, but their relatively low magnetic-ordering temperatures are a disadvantage. While cobalt has long been recognized as an element that promotes high-temperature magnetic ordering, most Co-rich alloys are achiral and exhibit collinear rather than helimagnetic order. Crystallographically, the B20-ordered compound CoSi is an exception due to its chiral structure, but it does not exhibit any kind of magnetic order. Here, we use nonequilibrium processing to produce B20-ordered Co_{1+x}Si_{1-x} with a maximum Co solubility of x=0.043. Above a critical excess-Co content (x_{c}=0.028), the alloys are magnetically ordered, and for x=0.043, a critical temperature T_{c}=328 K is obtained, the highest among all B20-type magnets. The crystal structure of the alloy supports spin spirals caused by Dzyaloshinskii-Moriya interactions, and from magnetic measurements we estimate that the spirals have a periodicity of about 17 nm. Our density-functional calculations explain the combination of high magnetic-ordering temperature and short periodicity in terms of a quantum phase transition where excess-cobalt spins are coupled through the host matrix.

12.
J Assist Reprod Genet ; 36(12): 2525-2531, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31720905

RESUMO

PURPOSE: To establish a single-nucleotide polymorphism-based analysis (SBA) method to identify triploidy in the miscarriage tissue by using low-coverage whole-genome sequencing (LC-WGS). METHODS: The method was established by fitting a quadratic curve model by counting the distribution of three heterozygous mutation content intervals. The triploid test result was mainly determined by the opening direction and the axis of symmetry of the quadratic curve, and Z test between the same batch samples was also used for auxiliary judgment. RESULTS: Two hundred thirteen diploid samples and 8 triploid samples were used for establishment of the analytical method and 203 unknown samples were used for blind testing. In the blind testing, we found 2 cases positive for triploidy. After chromosome microarray analysis (CMA) and mass spectrometry verification, we found that both samples were true positives. We randomly selected 5 samples from the negative samples for mass spectrometry verification, and the results showed that these samples were all true negatives. CONCLUSIONS: Our method achieved accurate detection of triploidy in the miscarriage tissue and has the potential to detect more chromosomal abnormality types such as uniparental disomy (UPD) using a single LC-WGS approach.


Assuntos
Aborto Espontâneo/genética , Transtornos Cromossômicos/genética , Triploidia , Sequenciamento Completo do Genoma , Aborto Espontâneo/diagnóstico , Aborto Espontâneo/patologia , Adulto , Aberrações Cromossômicas , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/patologia , Feminino , Humanos , Análise em Microsséries , Mutação , Polimorfismo de Nucleotídeo Único/genética , Gravidez
13.
Biochem Biophys Res Commun ; 514(2): 386-392, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31047638

RESUMO

Acute liver injury seriously endangers human health. Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, has antioxidative effects in addition to being widely used in the treatment of type 2 diabetes and was reported to ameliorate liver diseases. The aim of this study was to evaluate the hepatoprotective effects of liraglutide on carbon tetrachloride (CCl4)-induced acute liver injury in mice and to investigate the mechanisms involved in this protective effect. Male BALB/c mice were pre-treated with liraglutide (200 µg/kg/day) by hypodermic injection for 3 days before a 0.1% (v/v) CCl4 (10 ml/kg, dissolved in olive oil) intraperitoneal injection, or post-treated with liraglutide once immediately after a CCl4 intraperitoneal injection. The experimental data showed that liraglutide treatment significantly decreased the serum ALT and AST levels and ameliorated the liver histopathological changes induced by CCl4. In addition, liraglutide pre-treatment dramatically increased the number of proliferating cell nuclear antigen (PCNA)-positive hepatocytes and significantly reduced hepatocyte apoptosis after CCl4 treatment. As a consequence, liraglutide pre-treatment significantly prevented CCl4-induced malondialdehyde (MDA) production and increased the activity of the antioxidant superoxide dismutase (SOD) enzyme. In addition, liraglutide pre-treatment significantly ameliorated mitochondrial respiratory functions and ultrastructural features. Furthermore, liraglutide pre-treatment enhances the activation of the NRF2/HO-1 signaling pathway. In summary, liraglutide protects against CCl4-induced acute liver injury by protecting mitochondrial functions and inhibiting oxidative stress, which may partly involve the activation of NRF2/HO-1 signaling pathway.


Assuntos
Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Liraglutida/farmacologia , Substâncias Protetoras/farmacologia , Animais , Apoptose/efeitos dos fármacos , Respiração Celular/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo
14.
Pharmacol Res ; 139: 412-421, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30508676

RESUMO

Myocarditis can be caused by several infectious and noninfectious causes. Treatment for myocarditis is still a difficult task in clinical practice. The gut microbiota is related to cardiovascular diseases such as atherosclerosis and hypertension. However, little is known about the role of the gut microbiota in myocarditis. In our study, we tested the hypothesis that gut dysbiosis is associated with myocarditis. We focused on whether fecal microbiota transplantation (FMT) can be used as an effective treatment for myocarditis. We used an experimental autoimmune myocarditis (EAM) mouse model. Fecal samples were isolated from the control and EAM groups for bacterial genome analysis. We observed an increase in microbial richness and diversity in the myocarditis mice. These changes were accompanied by an increased Firmicutes/Bacteroidetes ratio. We also evaluated the efficacy of FMT for the treatment of myocarditis. EAM mouse guts were repopulated with fecal contents from an untreated male mouse donor. We found that myocardial injury was improved by diminished inflammatory infiltration, showing that IFN-γ gene expression in the heart tissue and CD4+IFN-γ+ cells in the spleen were decreased after FMT in EAM mice. We also found that FMT was able to rebalance the gut microbiota by restoring the Bacteroidetes population and reshaping the microbiota composition. Myocarditis is associated with gut microbiota dysbiosis and characterized by an increased F/B ratio. FMT treatment can rebalance the gut microbiota and attenuate myocarditis. Thus, FMT may be a potential therapeutic strategy for the treatment of myocarditis.


Assuntos
Disbiose/terapia , Transplante de Microbiota Fecal , Miocardite/terapia , Animais , Disbiose/microbiologia , Disbiose/patologia , Masculino , Camundongos Endogâmicos BALB C , Microbiota , Miocardite/microbiologia , Miocardite/patologia , Miocárdio/patologia
15.
Angew Chem Int Ed Engl ; 57(50): 16370-16374, 2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30320428

RESUMO

Sodium-ion batteries (SIBs) are a promising alternative for the large-scale energy storage owing to the natural abundance of sodium. However, the practical application of SIBs is still hindered by the low working voltage, poor rate performance, and insufficient cycling stability. A sodium-ion based full battery using a multi-ion design is now presented. The optimized full batteries delivered a high working voltage of about 4.0 V, which is the best result of reported sodium-ion full batteries. Moreover, this multi-ion battery exhibited good rate performance up to 30 C and a high capacity retention of 95 % over 500 cycles at 5 C. Although the electrochemical performance of this multi-ion battery may be further enhanced via optimizing electrolyte and electrode materials for example, the results presented clearly indicate the feasibility of this multi-ion strategy to improve the electrochemical performance of SIBs for possible energy storage applications.

16.
Mol Med Rep ; 18(6): 5579-5593, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30365077

RESUMO

The present study aimed to identify a long non­coding (lnc) RNAs­based signature for prognosis assessment in gastric cancer (GC) patients. By integrating gene expression data of GC and normal samples from the National Center for Biotechnology Information Gene Expression Omnibus, the EBI ArrayExpress and The Cancer Genome Atlas (TCGA) repositories, the common RNAs in Genomic Spatial Event (GSE) 65801, GSE29998, E­MTAB­1338, and TCGA set were screened and used to construct a weighted correlation network analysis (WGCNA) network for mining GC­related modules. Consensus differentially expressed RNAs (DERs) between GC and normal samples in the four datasets were screened using the MetaDE method. From the overlapped lncRNAs shared by preserved WGCNA modules and the consensus DERs, an lncRNAs signature was obtained using L1­penalized (lasso) Cox­proportional hazard (PH) model. LncRNA­mRNA networks were constructed for these signature lncRNAs, followed by functional annotation. A total of 14,824 common mRNAs and 2,869 common lncRNAs were identified in the 4 sets and 5 GC­associated WGCNA modules were preserved across all sets. MetaDE method identified 1,121 consensus DERs. A total of 50 lncRNAs were shared by preserved WGCNA modules and the consensus DERs. Subsequently, an 11­lncRNA signature was identified by LASSO­based Cox­PH model. The lncRNAs signature­based risk score could divide patients into 2 risk groups with significantly different overall survival and recurrence­free survival times. The predictive capability of this signature was verified in an independent set. These signature lncRNAs were implicated in several biological processes and pathways associated with the immune response, the inflammatory response and cell cycle control. The present study identified an 11­lncRNA signature that could predict the survival rate for GC.


Assuntos
Perfilação da Expressão Gênica , RNA Longo não Codificante/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Transcriptoma , Idoso , Biologia Computacional/métodos , Feminino , Ontologia Genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , RNA Mensageiro , Reprodutibilidade dos Testes , Neoplasias Gástricas/patologia
17.
Mol Cytogenet ; 11: 24, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29636822

RESUMO

Background: 1q43-q44 deletion syndrome is a well-defined chromosomal disorder which is characterized by moderate to severe mental retardation, and variable but characteristic facial features determined by the size of the segment and the number of genes involved. However, patients with 1q43-q44 duplication with a clinical phenotype comparable to that of 1q43-q44 deletion are rarely reported. Moreover, pure 1q43-q44 deletions and duplications derived from balanced insertional translocation within the same family with precisely identified breakpoints have not been reported. Case presentation: The proband is a 6-year-old girl with profound developmental delay, mental retardation, microcephaly, epilepsy, agenesis of the corpus callosum and hearing impairment. Her younger brother is a 3-month-old boy with macrocephaly and mild developmental delay in gross motor functions. G-banding analysis of the subjects at the 400-band level did not reveal any subtle structural changes in their karyotypes. However, single-nucleotide polymorphism (SNP) array analysis showed a deletion and a duplication of approximately 6.0 Mb at 1q43-q44 in the proband and her younger brother, respectively. The Levicare analysis pipeline of whole-genome sequencing (WGS) further demonstrated that a segment of 1q43-q44 was inserted at 14q23.1 in the unaffected mother, which indicated that the mother was a carrier of a 46,XX,ins(14;1)(q23.1;q43q44) insertional translocation. Moreover, Sanger sequencing was used to assist the mapping of the breakpoints and the final validation of those breakpoints. The breakpoint on chromosome 1 disrupted the EFCAB2 gene in the first intron, and the breakpoint on chromosome 14 disrupted the PRKCH gene within the 12th intron. In addition, fluorescence in situ hybridization (FISH) further confirmed that the unaffected older sister of the proband carried the same karyotype as the mother. Conclusion: Here, we describe a rare family exhibiting pure 1q43-q44 deletion and duplication in two siblings caused by a maternal balanced insertional translocation. Our study demonstrates that WGS with a carefully designed analysis pipeline is a powerful tool for identifying cryptic genomic balanced translocations and mapping the breakpoints at the nucleotide level and could be an effective method for explaining the relationship between karyotype and phenotype.

18.
Dis Markers ; 2017: 7909407, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29259350

RESUMO

Regulatory T cells (Tregs) play an essential role in acute coronary syndrome (ACS). However, there is debate about which Treg subsets are truly critical to ACS. Helios, a transcription factor, was recently reported to be a bona fide marker for natural Tregs or activated Tregs with a suppression function, but little is known about its role in ACS. We therefore examined Helios+ Tregs in patients with ACS, patients with stable angina, and control subjects. 73 patients with ACS, 30 patients with stable angina, and 48 control subjects were enrolled. The frequencies and estimated absolute numbers of different Treg subsets in peripheral blood were measured by flow cytometry. Plasma cytokine level was measured by ELISA. The mRNA expression of Foxp3 and Helios in purified CD4+ T cells was determined by RT-PCR. Helios+ Tregs was decreased significantly in patients with ACS. The frequency and estimated absolute numbers of CD4+Foxp3+Helios+ Tregs were negatively correlated with IL-6 and positively correlated with circulating level of TGF-beta1 and HDL-C. The mRNA expression of Foxp3 and Helios was decreased in CD4+ T cells from patients with ACS. In summary, Helios+ Tregs was downregulated in patients with ACS and may play a role in ACS.


Assuntos
Síndrome Coronariana Aguda/sangue , Angina Estável/sangue , Fator de Transcrição Ikaros/sangue , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/metabolismo , Angina Estável/genética , Angina Estável/metabolismo , Biomarcadores/sangue , Linfócitos T CD4-Positivos/metabolismo , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Humanos , Fator de Transcrição Ikaros/genética , Fator de Transcrição Ikaros/metabolismo , Masculino , Pessoa de Meia-Idade
19.
Cardiovasc Res ; 113(5): 475-487, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28339742

RESUMO

Aims: Monocytes/macrophages response plays a key role in post-infarction inflammation that contributes greatly to post-infarction ventricular remodelling and cardiac rupture. Therapeutic targeting of the GABAA receptor, which is enriched in monocytes/macrophages but not expressed in the myocardium, may be possible after myocardial infarction (MI). Methods and results: After MI was induced by ligation of the coronary artery, C57BL/6 mice were intraperitoneally administered with one specific agonist or antagonist of the GABAA receptor (topiramate or bicuculline), in the setting of presence or depletion of monocytes/macrophages. Our data showed that within the first 2 weeks after MI, when monocytes/macrophages dominated, in contrast with bicuculline, topiramate treatment significantly reduced Ly-6Chigh monocyte numbers by regulating splenic monocytopoiesis and promoted foetal derived macrophages preservation and conversion of M1 to M2 or Ly-6Chigh to Ly-6Clow macrophage phenotype in the infarcted heart, though GABAAergic drugs failed to affect M1/M2 or Ly-6Chigh/Ly-6Clow macrophage polarization directly. Accordingly, pro-inflammatory activities mediated by M1 or Ly-6Chigh macrophages were decreased and reparative processes mediated by M2 or Ly-6Clow macrophages were augmented. As a result, post-infarction ventricular remodelling was attenuated, as reflected by reduced infarct size and increased collagen density within infarcts. Echocardiographic indices, mortality and rupture rates were reduced. After depletion of monocytes/macrophages by clodronate liposomes, GABAAergic drugs exhibited no effect on cardiac dysfunction and surrogate clinical outcomes. Conclusion: Control of the GABAA receptor activity in monocytes/macrophages can potently modulate post-infarction inflammation. Topiramate emerges as a promising drug, which may be feasible to translate for MI therapy in the future.


Assuntos
Anti-Inflamatórios/farmacologia , Frutose/análogos & derivados , Agonistas GABAérgicos/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Miocardite/prevenção & controle , Receptores de GABA/efeitos dos fármacos , Animais , Antígenos Ly/metabolismo , Colágeno/metabolismo , Modelos Animais de Doenças , Fibrose , Frutose/farmacologia , Ruptura Cardíaca Pós-Infarto/metabolismo , Ruptura Cardíaca Pós-Infarto/fisiopatologia , Ruptura Cardíaca Pós-Infarto/prevenção & controle , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Monócitos/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocardite/metabolismo , Miocardite/patologia , Miocardite/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Fenótipo , Receptores de GABA/metabolismo , Receptores de GABA-A/efeitos dos fármacos , Receptores de GABA-A/metabolismo , Fatores de Tempo , Topiramato , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/prevenção & controle , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
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