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1.
Clinics (Sao Paulo) ; 75: e1277, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31939557

RESUMO

The gut microbiota is a group of over 38 trillion bacterial cells in the human microbiota that plays an important role in the regulation of human metabolism through its symbiotic relationship with the host. Changes in the gut microbial ecosystem are associated with increased susceptibility to metabolic disease in humans. However, the composition of the gut microbiota in those with type 2 diabetes mellitus and in the pathogenesis of metabolic diseases is not well understood. This article reviews the relationship between environmental factors and the gut microbiota in individuals with type 2 diabetes mellitus. Finally, we discuss the goal of treating type 2 diabetes mellitus by modifying the gut microbiota and the challenges that remain in this area.

2.
Clin Chim Acta ; 501: 147-153, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31678272

RESUMO

Diabetic retinopathy (DR) is the leading cause of vision loss among older adults. The goal of this case-control study was to identify circulating miRNAs for the diagnosis of DR. The miRNeasy Serum/Plasma Kit was used to extract serum miRNAs. The µParaflo™ MicroRNA microarray was used to detect the expression levels of the miRNAs. The miRWalk algorithm was applied to predict the target genes of the miRNAs, which were further confirmed by the dual luciferase reporter gene system in HEK293T cells. A microarray was performed between 5 DR cases and 5 age-, sex-, body mass index-, and duration of diabetes-matched type 2 diabetic (T2DM) controls. The quantitative reverse transcription polymerase chain reaction technique was used to validate the differentially expressed circulating miRNAs in 45 DR cases and 45 well-matched controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the circulating miRNAs as diagnostic biomarkers for DR. Our microarray analysis screened out miR-2116-5p and miR-3197 as significantly up-regulated in DR cases compared with the controls. Furthermore, two miRNAs were validated in the 45 DR cases and 45 controls. The ROC analysis suggested that both miR-3197 and miR-2116-5p distinguished DR cases from controls. An additional dual-luciferase reporter gene assay confirmed that notch homolog 2 (NOTCH2) was the target gene of miR-2116-5p. Both miR-3197 and miR-2116-5p were identified as promising diagnostic biomarkers for DR. Future research is still needed to explore the molecular mechanisms of miR-3197 and miR-2116-5p in the pathogenesis of DR.

3.
Emerg Microbes Infect ; 8(1): 367-376, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31851879

RESUMO

The dimorphic fungus Talaromyces marneffei (TM) is a common cause of HIV-associated opportunistic infections in Southeast Asia. Cotrimoxazole (CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi and has been used to prevent several opportunistic infections among HIV/AIDS patients. We question whether CTX is effective in preventing TM infection. To investigate this question, we conducted an 11-year (2005-2016) retrospective observational cohort study of all patients on the Chinese national antiretroviral therapy (ART) programme in Guangxi, a province with high HIV and TM burden in China. Survival analysis was conducted to investigate TM cumulative incidence, and Cox regression and propensity score matching (PSM) were used to evaluate the effect of CTX on TM incidence. Of the 3359 eligible individuals contributing 10,504.66 person-years of follow-up, 81.81% received CTX within 6 months after ART initiation, and 4.73% developed TM infection, contributing 15.14/1,000 person-year TM incidence rate. CTX patients had a significantly lower incidence of TM infection than non-CTX patients (4.11% vs. 7.53%; adjusted hazard ratio (aHR) = 0.50, 95% CI 0.35-0.73). CTX reduced TM incidence in all CD4+ cell subgroups (<50 cells/µL, 50-99 cells/µL, 100-199 cells/µL), with the highest reduction observed in patients with a baseline CD4+ cell count <50 cells/µL in both Cox regression and the PSM analyses. In conclusion, in addition to preventing other HIV-associated opportunistic infections, CTX prophylaxis has the potential to prevent TM infection in HIV/AIDS patients receiving ART.

4.
Sci Rep ; 9(1): 7816, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31127157

RESUMO

Previous studies investigating HIV-infected patients suggested a direct link between underweight and the mortality rate of AIDS. However, there was a lack of evidence showing the optimal range of initial body mass index (BMI) patients maintain during antiretroviral therapy (ART). We aimed to evaluate associations of the BMI values pre-ART and during the entire ART duration with mortality among HIV-positive individuals. In total, 5101 HIV/AIDS patients, including 1439 (28.2%) underweight, 3047 (59.7%) normal-weight, 548 (10.7%) overweight and 67 (1.3%) obese patients, were included in this cohort. The cumulative mortality of underweight, normal-weight, and overweight were 2.4/100 person-years (95% CI 1.9-2.9), 1.1/100 person-years (95% CI 0.9-1.3), and 0.5/100 person-years (95% CI 0.1-0.9), respectively. Cumulative mortality was lower in both the normal-weight and overweight populations than in the underweight population, with an adjusted hazard ratio (AHR) of 0.5 (95% CI 0.4-0.7, p < 0.001) and 0.3 (95% CI 0.1-0.6, p = 0.002), respectively. Additionally, in the 1176 patients with available viral load data, there was significant difference between the underweight and normal-weight groups after adjustment for all factors, including viral load (p = 0.031). This result suggests that HIV-infected patients in Guangxi maintaining a BMI of 19-28 kg/m2, especially 24-28 kg/m2, have a reduced risk of death.

5.
J Immunother ; 41(9): 406-410, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30198955

RESUMO

Cytokine release syndrome (CRS) remains to be a major adverse effect of chimeric antigen receptor T (CAR-T) cell therapy in B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma. It was urgent to explore novel strategy for managing severe CRS. We conducted a clinical trial to assess the safety and efficacy of CD19-targeting CAR-T-cells in the treatment of relapsed and chemotherapy-refractory B-ALL and lymphoma. A 10-year-old boy with B-ALL who never achieved minimal residual disease (MRD) negative status after 5 courses of chemotherapy was enrolled into our study and received a total of 3.19×10/kg autologous CD19 CAR-T-cells. Before CAR-T-cell infusion, naive lymphocytes made up 41.8% of bone marrow cells, which were reduced to 1% at the 14th day after transfusion, with MRD<10. However, this patient developed grade 4 CRS, multiple organ failure, hemophagocytic syndrome, neurotoxicity, and severe pulmonary infection after CAR-T-cell therapy. Tocilizumab and glucocorticoids treatment were ineffective for controlling the adverse effects and in contrast, hemofiltration immediately ameliorated the severe CRS and prevented the exacerbation of multiple organ dysfunction, pneumonia, and hydrosarca caused by CAR-T-cell therapy. All side effects disappeared within days following hemofiltration. Hemofiltration helped quickly clear cytokines, speeded up patient recover, and successfully resolved the severe CRS crisis. This was the first report, reporting the successful use of hemofiltration to eliminate adverse reactions of CAR-T-cell therapy.


Assuntos
Citocinas/imunologia , Hemofiltração , Imunoterapia Adotiva/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Antígenos CD19 , Criança , Humanos , Masculino , Receptores de Antígenos Quiméricos/imunologia , Síndrome
6.
Yi Chuan ; 40(3): 250-256, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29576548

RESUMO

With the implementation of the "Education and Training Program for Outstanding Agricultural and Forestry Talents" in our country, our university established the "Outstanding Class" for students majoring in the animal science. We also carried out a series of educational management and curriculum reforms to cultivate students' systematic model of thinking and the ability of technology innovation. In this paper, we designed a comprehensive experiment that focused on analyzing early and late feather genetic traits of chicken. The students initially observed the phenotype of chickens and gradually were led into genetics analysis. We introduced the breeding practice, and guided the students to use genetic theories to breed chick strains of early and late feather traits. The experiment is not only based on the sex-linkage theory and sex determination mechanism, but also molecular genetics technologies, such as genomic DNA extraction, amplification, enzyme digestion and electrophoresis. Conducting this experiment can enhance students' comprehensive analysis ability and professional skills, as well as be beneficial to cultivate their scientific research interests and curiosity on animal sciences. Thus, we integrated the genetics theories into animal breeding practice that meet the requirement of comprehensive applied talents of animal science specialty. The teaching ideas and methods described in this paper can be applied to other biological experiment teaching practice.


Assuntos
Galinhas/genética , Plumas/crescimento & desenvolvimento , Genética/educação , Animais , Galinhas/crescimento & desenvolvimento , Plumas/metabolismo , Feminino , Genética/instrumentação , Humanos , Masculino , Fenótipo , Estudantes , Ensino
7.
Biochem Biophys Res Commun ; 497(2): 726-733, 2018 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-29462615

RESUMO

Ubiquitination modification has been shown to play a key role in autophagy. Increasing studies reported the involvement of de-ubiquitinating enzymes (DUBs) in autophagy pathway. To systematically search how DUBs manipulate autophagy, we utilized a double fluorescence tagged LC3 stable HeLa cell line, and did a genome wide screen of 55 human DUBs which is about 60% coverage of the DUB family. We found a bunch of DUBs have impact on autophagy by either changing the LC3 puncta formation or the autophagy flux. One of them, Ubiquitin C-Terminal Hydrolase L1 (UCHL1) correlated to Parkinson's disease, strongly affects autophagy by inhibiting autophagosome formation. We found UCHL1 overexpression inhibits LC3 puncta formation and is dependent on its DUB activity. Knockdown of UCHL1 significantly promotes LC3 puncta formation. Further study revealed that UCHL1 may affect autophagy by interacting with LC3 but not other autophagy related proteins. Interestingly, a Parkinson's disease related mutant UCHL1 I93 M defects its DUB activity and can no longer inhibit autophagosome formation. We further screened 22 commercially available DUB inhibitors and found two potent UCHL1 inhibitors LDN-57444 (LDN) and NSC632839 (NSC), when treating cells, both strongly induce LC3 puncta formation. Taken together, our results indicated a new insight into the manner in which DUB regulates autophagy and provided potential drugs for the Parkinson's disease.


Assuntos
Autofagossomos/metabolismo , Autofagia , Ubiquitina Tiolesterase/metabolismo , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Ubiquitina/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitinação
8.
Biol Trace Elem Res ; 183(2): 296-304, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28856574

RESUMO

The aim of this experiment is to explore the effects of aluminum chloride (AlCl3) on the ATPase enzymes and gonadotropin receptors in the testes. Eighty male Wistar rats were orally exposed to 0 mg/kg body weight (BW) (control group, CG), 64 mg/kg BW (low-dose group, LG), 128 mg/kg BW (mid-dose group, MG), or 256 mg/kg BW (high-dose group, HG) for 120 days. The microstructure and ultrastructure of testes; the activities of Na+-K+-ATPase, Mg2+-ATPase, and Ca2+-ATPase; and the mRNA and protein expressions of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptors (LHR) in the testes were examined. The results showed that the testes histological structure were damaged; the activities of Na+-K+-ATPase, Mg2+-ATPase, and Ca2+-ATPase, the mRNA and protein expressions of FSHR and LHR in the testes were all decreased in the rats with AlCl3 exposure. It indicates that AlCl3 causes the dysfunction of testes in rats.


Assuntos
Compostos de Alumínio/toxicidade , ATPase de Ca(2+) e Mg(2+)/metabolismo , ATPases Transportadoras de Cálcio/metabolismo , Cloretos/toxicidade , Receptores da Gonadotropina/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Cloreto de Alumínio , Animais , Masculino , Ratos , Ratos Wistar , Receptores do FSH/metabolismo
9.
Glob Public Health ; 13(5): 612-625, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-27756194

RESUMO

Although the HIV epidemic continues to spread among older adults over 50 years old in China, little empirical research has investigated the interrelationships among ageism, adaptability, family support, and quality of life among older people living with HIV/AIDS (PLWHAs). In this cross-sectional study, among 197 older PLWHAs over 50 years old, path analytic modelling was used to assess the interrelationships among ageism, resilience, coping, family support, and quality of life. Compared with female PLWHAs, male PLWHAs had a higher level of resilience and coping. There were no significant differences in the scores of quality of life, ageism, family support, HIV knowledge, and duration since HIV diagnosis between males and females. The following relationships were statistically significant in the path analysis: (1) family support → resilience [ß (standardised coefficient) = 0.18], (2) resilience → ageism (ß = -0.29), (3) resilience → coping (ß = 0.48), and (4) coping → quality of life (ß = 0.24). In addition, male PLWHAs were more resilient than female PLWHAs (ß = 0.16). The findings indicate that older PLWHAs do not only negatively accept adversity, but build their adaptability to positively manage the challenges. Family-based interventions need take this adaptability to adversity into consideration.


Assuntos
Adaptação Psicológica , Ageismo/psicologia , Família/psicologia , Infecções por HIV/psicologia , Qualidade de Vida , Resiliência Psicológica , Apoio Social , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade
10.
Exp Ther Med ; 14(4): 2976-2982, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29042909

RESUMO

The present study aimed to investigate the contribution of DNA methylation of the protein tyrosine phosphatase, non-receptor type 1 (PTPN1) gene to the susceptibility to type 2 diabetes (T2D). Peripheral blood mononuclear cells (PBMCs) were collected from 97 patients with T2D and 97 age- and gender-matched controls. DNA methylation of the PTPN1 gene promoter was evaluated by bisulfite pyrosequencing. Independent sample t-tests were used to compare the differences in the PTPN1 promoter and other phenotypes between the patients with T2D and the controls. The results indicated a significant correlation between PTPN1 promoter methylation and the risk of T2D. Additionally, a breakdown analysis by gender revealed that PTPN1 methylation was associated with an increased risk of T2D in females. Furthermore, low-density lipoprotein (r=-0.183, P=0.046) and total cholesterol (r=-0.310, P=0.001) were inversely associated with PTPN1 methylation in females. In conclusion, the results indicate that elevated PTPN1 promoter methylation is a risk factor for T2D in the female Chinese population.

11.
Sci Rep ; 7(1): 3657, 2017 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-28623361

RESUMO

This study evaluated the prevalence and factors associated with sleep disturbance in a large cohort of HIV-infected patients across China. A cross-sectional study was conducted among HIV-infected patients on antiretroviral therapy at 20 AIDS clinics. The Pittsburgh Sleep Quality Index was self-administered by subjects. Socio-demographic characteristics, medical history and HIV-related clinical data were collected. 4103 patients had complete data for analysis. Sleep disturbances were observed in 43.1% of patients. Associated factors in multivariable analysis included psychological factors: anxiety (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.44-4.00; P < 0.001), depression (OR, 2.09; 95% CI, 1.70-2.57; P < 0.001), and both anxiety and depression (OR, 5.90; 95% CI, 4.86-7.16; P < 0.001); sociodemographic factors: MSM (OR, 1.26; 95% CI, 1.04-1.52; P = 0.018), being single (OR, 1.45; 95%CI 1.21-1.74; P < 0.001), higher education (OR, 1.25; 95% CI, 1.03-1.53; P = 0.025); and clinical factors: suboptimal adherence (OR,1.51; 95% CI,1.23-1.85; P < 0.001), regimen-switching (OR, 1.94; 95% CI, 1.12-3.35; P = 0.018), and antidepressant use (OR, 1.98; 95% CI, 1.47-2.67; P = 0.044). Prevalence of sleep disturbance is high in this large Chinese cohort. Associated factors appear related to psychological and social-demographic factors. Health workers may consider routinely assessing sleep disturbances among HIV-infected patients, especially in the first three months after HIV diagnosis, and referring for mental health services, which may positively impact adherence to treatment.


Assuntos
Efeitos Psicossociais da Doença , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia , Adulto , Terapia Antirretroviral de Alta Atividade , Ansiedade , China/epidemiologia , Estudos Transversais , Depressão , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de Risco , Transtornos do Sono-Vigília/diagnóstico
12.
J Inorg Biochem ; 174: 55-62, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28605655

RESUMO

Aluminum (Al) is known to exert hepatotoxicity. However, the mechanisms mostly are unclear. Liver is a metabolism organ that maintains the energy level and structural stability of body, mitochondria are the main sites of energy metabolism, thus, we hypothesized that mitochondrial energy metabolism disorder contributes to liver dysfunction in aluminum chloride (AlCl3) treatment rat. To verify the hypothesis, forty male Wistar rats were randomly allocated and orally exposed to 0, 64mg/kg, 128mg/kg and 256mg/kg body weight AlCl3 in drinking water for 120days, respectively. We found that AlCl3 exposure reduced the electron transport chain complexes I-V activities and adenosine triphosphate (ATP) level, as well as disturbed mitochondrial DNA transcript, presenting as the inhibited mRNA expressions of NADH dehydrogenase 1, NADH dehydrogenase 2, cytochrome b, cytochrome c oxidase subunit 1, cytochrome c oxidase subunit 3 and ATP synthase 6, indicating that AlCl3 exposure disturbs the mitochondrial energy metabolism, and it caused an increase in liver enzymes (Aspartate aminotransferase and Alanine aminotransferase) and histopathological lesions. Additionally, we found that reactive oxygen species accumulation and decreased superoxide dismutase activity in mitochondria, and increased 8-Hydroxydeoxyguanosine levels in mitochondrial DNA, demonstrating AlCl3 exposure promotes mitochondrial oxidative stress, which may be a contributing factor to mitochondrial energy metabolism disorder and liver dysfunction. The study displayed that mitochondria are the potential target of liver damage induced by AlCl3, providing considerable direction for the prevention and clinical intervention of liver diseases.


Assuntos
Compostos de Alumínio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Cloretos/toxicidade , Metabolismo Energético/efeitos dos fármacos , Fígado/metabolismo , Mitocôndrias Hepáticas/metabolismo , Cloreto de Alumínio , Animais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fígado/patologia , Masculino , Mitocôndrias Hepáticas/patologia , Ratos , Ratos Wistar
13.
Clinics (Sao Paulo) ; 72(2): 111-115, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28273235

RESUMO

OBJECTIVES:: The aim of this study was to compare the expression levels of serum miRNAs in diabetic retinopathy and type 2 diabetes mellitus. METHODS:: Serum miRNA expression profiles from diabetic retinopathy cases (type 2 diabetes mellitus patients with diabetic retinopathy) and type 2 diabetes mellitus controls (type 2 diabetes mellitus patients without diabetic retinopathy) were examined by miRNA-specific microarray analysis. Quantitative real-time polymerase chain reaction was used to validate the significantly differentially expressed serum miRNAs from the microarray analysis of 45 diabetic retinopathy cases and 45 age-, sex-, body mass index- and duration-of-diabetes-matched type 2 diabetes mellitus controls. The relative changes in serum miRNA expression levels were analyzed using the 2-ΔΔCt method. RESULTS:: A total of 5 diabetic retinopathy cases and 5 type 2 diabetes mellitus controls were included in the miRNA-specific microarray analysis. The serum levels of miR-3939 and miR-1910-3p differed significantly between the two groups in the screening stage; however, quantitative real-time polymerase chain reaction did not reveal significant differences in miRNA expression for 45 diabetic retinopathy cases and their matched type 2 diabetes mellitus controls. CONCLUSION:: Our findings indicate that miR-3939 and miR-1910-3p may not play important roles in the development of diabetic retinopathy; however, studies with a larger sample size are needed to confirm our findings.


Assuntos
Diabetes Mellitus Tipo 2/genética , Retinopatia Diabética/genética , MicroRNAs/sangue , Idoso , Animais , Diabetes Mellitus Tipo 2/sangue , Retinopatia Diabética/sangue , Perfilação da Expressão Gênica , Humanos , Reação em Cadeia da Polimerase em Tempo Real
14.
Clinics ; 72(2): 111-115, Feb. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-840040

RESUMO

OBJECTIVES: The aim of this study was to compare the expression levels of serum miRNAs in diabetic retinopathy and type 2 diabetes mellitus. METHODS: Serum miRNA expression profiles from diabetic retinopathy cases (type 2 diabetes mellitus patients with diabetic retinopathy) and type 2 diabetes mellitus controls (type 2 diabetes mellitus patients without diabetic retinopathy) were examined by miRNA-specific microarray analysis. Quantitative real-time polymerase chain reaction was used to validate the significantly differentially expressed serum miRNAs from the microarray analysis of 45 diabetic retinopathy cases and 45 age-, sex-, body mass index- and duration-of-diabetes-matched type 2 diabetes mellitus controls. The relative changes in serum miRNA expression levels were analyzed using the 2-ΔΔCt method. RESULTS: A total of 5 diabetic retinopathy cases and 5 type 2 diabetes mellitus controls were included in the miRNA-specific microarray analysis. The serum levels of miR-3939 and miR-1910-3p differed significantly between the two groups in the screening stage; however, quantitative real-time polymerase chain reaction did not reveal significant differences in miRNA expression for 45 diabetic retinopathy cases and their matched type 2 diabetes mellitus controls. CONCLUSION: Our findings indicate that miR-3939 and miR-1910-3p may not play important roles in the development of diabetic retinopathy; however, studies with a larger sample size are needed to confirm our findings.


Assuntos
Humanos , Animais , Idoso , Diabetes Mellitus Tipo 2/genética , Retinopatia Diabética/genética , MicroRNAs/sangue , Diabetes Mellitus Tipo 2/sangue , Retinopatia Diabética/sangue , Perfilação da Expressão Gênica , Reação em Cadeia da Polimerase em Tempo Real
15.
Clin Nutr ; 36(5): 1215-1230, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-27908565

RESUMO

AIMS: Hyperhomocysteinemia (HHcy) is known to increase the risk of many diseases. Factors influencing HHcy in healthy and hypertensive subjects remain under-researched. METHODS: A large population-based study was conducted in 60 communities from Shenzhen, China. Responses to standardized questions on lifestyle factors and blood samples were collected from all participants after a 12-h overnight fast. Multiple linear and multivariate logistic regressions were used to explore risk factors for HHcy. Results were then compared to those from a systematic review of English-language articles listed in Pubmed, EBSCOhost, Web of Science, Embase and Cochrane libraries that investigated HHcy risk factors in healthy and hypertensive subjects. RESULTS: A total of 1586 healthy (Male/Female = 642/944) and 5935 hypertensive subjects (Male/Female = 2928/3007) participated in our population-based study. In logistic regression analyses, age, BMI and creatinine (Cr) were risk factors, while being female, fruit intake and physical activity were protective factors for HHcy in healthy subjects. In hypertensive subjects, seven [age, smoking, salt intake, systolic blood pressure (SBP), uric acid, triglycerides (TG), and Cr] and four [female, fruit intake, total cholesterol (TC), and glucose] factors were associated with higher and lower HHcy respectively. The review of 71 studies revealed that potential risk factors for Hcy included nutritional, physiologic, lifestyle habits, ethnicity, genetics, interactions between gene-environment, gene-gene, gene-nutritional, environment-environment, nutritional-nutritional. CONCLUSION: Our study indicates the potential importance of increasing folic acid and vitamin B supplementation, daily fruit and vegetable intake, regular exercise and refraining from tobacco smoking and alcohol consumption as preventive strategies for Hcy.


Assuntos
Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/epidemiologia , Hipertensão/epidemiologia , Pressão Sanguínea , Índice de Massa Corporal , China , Creatinina/sangue , Suplementos Nutricionais , Exercício , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/sangue , Frutas , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/sangue , Hipertensão/sangue , Estilo de Vida , Masculino , Fatores de Risco , Triglicerídeos/sangue , Ácido Úrico/sangue , Verduras , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/sangue
16.
J Biol Chem ; 291(35): 18252-62, 2016 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-27387505

RESUMO

The endoplasmic reticulum (ER) network comprises sheets and tubules that are connected by dynamic three-way junctions. Lunapark (Lnp) localizes to and stabilizes ER three-way junctions by antagonizing the small GTPase Atlastin, but how Lnp shapes the ER network is unclear. Here, we used an affinity purification approach and mass spectrometry to identify Lnp as an interacting partner of the ER protein quality control ubiquitin ligase gp78. Accordingly, Lnp purified from mammalian cells has a ubiquitin ligase activity in vitro Intriguingly, biochemical analyses show that this activity can be attributed not only to associated ubiquitin ligase, but also to an intrinsic ubiquitin ligase activity borne by Lnp itself. This activity is contained in the N-terminal 45 amino acids of Lnp although this segment does not share homology to any known ubiquitin ligase motifs. Despite its interaction with gp78, Lnp does not seem to have a broad function in degradation of misfolded ER proteins. On the other hand, the N-terminal ubiquitin ligase-bearing motif is required for the ER three-way junction localization of Lnp. Our study identifies a new type of ubiquitin ligase and reveals a potential link between ubiquitin and ER morphology regulation.


Assuntos
Retículo Endoplasmático/metabolismo , Proteínas de Homeodomínio/metabolismo , Receptores do Fator Autócrino de Motilidade/metabolismo , Motivos de Aminoácidos , Animais , Células COS , Retículo Endoplasmático/genética , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Células HeLa , Proteínas de Homeodomínio/genética , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Transporte Proteico , Receptores do Fator Autócrino de Motilidade/genética
17.
Brief Funct Genomics ; 15(6): 460-469, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27142121

RESUMO

Hypertension is a multifactorial disease influenced by an interaction of environmental and genetic factors. The exact molecular mechanism of hypertension remains unknown. Aberrant DNA methylation is the most well-defined epigenetic modification that regulates gene transcription. However, studies on the association between DNA methylation and hypertension are still in their infancy. This review summarizes the latest evidence and challenges regarding the role of DNA methylation on hypertension.


Assuntos
Metilação de DNA , Epigênese Genética , Regulação da Expressão Gênica , Hipertensão/genética , Animais , Humanos
18.
Chin Med J (Engl) ; 129(3): 304-8, 2016 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-26831232

RESUMO

BACKGROUND: The prevalence of hepatitis B virus (HBV) infection is high among individuals infected with human immunodeficiency virus (HIV) in China. Both HIV and HBV can be treated with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC), so we evaluated the safety and efficacy of combination antiretroviral therapy (ART) that included TDF, 3TC, and efavirenz (EFV) among ART-naive individuals who were co-infected with HIV and HBV. METHODS: One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen of TDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed. RESULTS: Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels (71%) and/or HIV RNA levels (90%). Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline (109 ml·min-1·1.73 m-2) to week 12 (104 ml·min-1·1.73 m-2) but was almost back to baseline at week 48 (111 ml·min-1·1.73 m-2). CONCLUSION: This combination ART regimen is safe and effective for patients with HIV/HBV co-infection. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01751555; https://clinicaltrials.gov/ct2/show/NCT01751555.


Assuntos
Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Tenofovir/uso terapêutico , Adulto , Alanina Transaminase/metabolismo , Fármacos Anti-HIV/uso terapêutico , Aspartato Aminotransferases/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Coinfecção/tratamento farmacológico , Feminino , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/patogenicidade , Humanos , Masculino
19.
Mol Biol Cell ; 26(24): 4438-50, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26424800

RESUMO

Eukaryotic cells eliminate misfolded proteins from the endoplasmic reticulum (ER) via a conserved process termed ER-associated degradation (ERAD). Central regulators of the ERAD system are membrane-bound ubiquitin ligases, which are thought to channel misfolded proteins through the ER membrane during retrotranslocation. Hrd1 and gp78 are mammalian ubiquitin ligases homologous to Hrd1p, an ubiquitin ligase essential for ERAD in Saccharomyces cerevisiae. However, the functional relevance of these proteins to Hrd1p is unclear. In this paper, we characterize the gp78-containing ubiquitin ligase complex and define its functional interplay with Hrd1 using biochemical and recently developed CRISPR-based genetic tools. Our data show that transient inactivation of the gp78 complex by short hairpin RNA-mediated gene silencing causes significant stabilization of both luminal and membrane ERAD substrates, but unlike Hrd1, which plays an essential role in retrotranslocation and ubiquitination of these ERAD substrates, knockdown of gp78 does not affect either of these processes. Instead, gp78 appears to act downstream of Hrd1 to promote ERAD via cooperation with the BAG6 chaperone complex. We conclude that the Hrd1 complex forms an essential retrotranslocation module that is evolutionarily conserved, but the mammalian ERAD system uses additional ubiquitin ligases to assist Hrd1 during retrotranslocation.


Assuntos
Retículo Endoplasmático/metabolismo , Receptores do Fator Autócrino de Motilidade/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Degradação Associada com o Retículo Endoplasmático , Células HEK293 , Humanos , Chaperonas Moleculares/metabolismo , Ligação Proteica , Dobramento de Proteína , Proteólise , Ubiquitina/metabolismo , Ubiquitinação
20.
Asian Pac J Cancer Prev ; 16(15): 6569-73, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26434876

RESUMO

OBJECTIVE: To evaluate the application value of serum CA19-9, CEA, CA125 and CA242 in diagnosis and prognosis of pancreatic cancer cases treated with concurrent chemotherapy. MATERIALS AND METHODS: 52 patients with pancreatic cancer, 40 with benign pancreatic diseases and 40 healthy people were selected. The electrochemiluminescence immunoassay method was used for detecting levels of CA19-9, CEA and CA125, and a CanAg CA242 enzyme linked immunoassay kit for assessing the level of CA242. The Kaplan-Meier method was used for analyzing the prognostic factors of patients with pancreatic cancer. The Cox proportional hazard model was applied for analyzing the hazard ratio (HR) and 95% confidential interval (CI) for survival time of patients with pancreatic cancer. RESULTS: The levels of serum CA19-9, CEA, CA125 and CA242 in patients with pancreatic cancer were significantly higher than those in patients with benign pancreatic diseases and healthy people (P<0.001). The sensitivity of CA19-9 was the highest among these, followed by CA242, CA125 and CEA. The specificity of CA242 is the highest, followed by CA125, CEA and CA19-9. The sensitivity and specificity of joint detection of serum CA19-9, CEA, CA125and CA242 were 90.4% and 93.8%, obviously higher than single detection of those markers in diagnosis of pancreatic cancer. The median survival time of 52 patients with pancreatic cancer was 10 months (95% CI7.389~12.611).. Patients with the increasing level of serum CA19-9, CEA, CA125, CA242 had shorter survival times (P=0.047. 0.043, 0.0041, 0.029). COX regression analysis showed that CA19-9 was an independent prognostic factor for patients with pancreatic cancer (P=0.001, 95%CI 2.591~38.243). CONCLUSIONS: The detection of serum tumor markers (CA19.9, CEA, CA125 and CA242) is conducive to the early diagnosis of pancreatic cancer and joint detection of tumor markers helps improve the diagnostic efficiency. Moreover, CA19-9 is an independent prognostic factor for patients with pancreatic cancer.


Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Antígeno Ca-125/sangue , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Neoplasias Pancreáticas/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , Quimiorradioterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cisto Pancreático/sangue , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Pancreatite/sangue , Valor Preditivo dos Testes , Prognóstico , Taxa de Sobrevida
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