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1.
Appl Biochem Biotechnol ; 196(1): 573-587, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37160564

RESUMO

Molecular-targeted therapies for lung squamous cell carcinoma (LSCC) are limited mainly because targetable oncogenic aberrations are absent in LSCC. Recent genomic analyses have revealed that the fibroblast growth factor (FGF) signaling pathway plays a fundamental role in LSCC progression via cancer cell proliferation and angiogenesis. In the present study, we designed, expressed, and purified a fibroblast growth factor receptor fragment (FGFR1-Fc) fusion protein using NS/0 cells. In FGF2-FGFR1 overexpressed NCI-H1703 cells, the FGFR1-Fc fusion protein effectively inhibited proliferation and invasion and arrested the cell cycle at the G0-G1 phase. In NCI-H1703 cells treated with the FGFR1-Fc fusion protein, the phosphorylation levels of FGFR1, FRS2, ERK, and AKT were significantly reduced. Using an siRNA assay, we demonstrated that FGF2-FGFR1 is the major anti-tumor target of FGFR1-Fc fusion the FGFR1-Fc fusion protein, which also significantly inhibited proliferation and invasion by NCI-H1703 cells via the FGF2-FGFR1 signaling pathway. In addition, the FGFR1-Fc fusion protein significantly inhibited angiogenesis in an embryonic chorioallantoic membrane model. The FGFR1-Fc fusion protein may be an effective therapeutic candidate for LSCC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Imunoglobulina G , Neoplasias Pulmonares , Proteínas Recombinantes de Fusão , Humanos , Fator 2 de Crescimento de Fibroblastos , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Proliferação de Células , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/tratamento farmacológico , Pulmão/metabolismo , Linhagem Celular Tumoral
2.
Zhongguo Zhong Yao Za Zhi ; 48(19): 5345-5355, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-38114124

RESUMO

The study investigated the effect of Buyang Huanwu Decoction(BYHWD) on endogenous biomarkers in the urine of rats with chronic inflammation induced by lipopolysaccharide(LPS) using ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS), aiming to elucidate the molecular mechanism underlying the therapeutic effect of BYHWD on chronic inflammation from a metabolomics perspective. Male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose BYHWD groups(7.5, 15, and 30 g·kg~(-1)). The model group and BYHWD groups received tail intravenous injection of LPS(200 µg·kg~(-1)) on the first day of each week, followed by oral administration of BYHWD once a day for four consecutive weeks. Urine samples were collected at the end of the administration period, and UPLC-Q-TOF-MS was used to analyze the metabolic profiles of the rat urine in each group. Multivariate statistical analysis methods such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the effect of BYHWD on endogenous metabolites. One-way ANOVA and variable importance for the projection(VIP) were used to screen for potential biomarkers related to chronic inflammation. The identified biomarkers were subjected to pathway and enrichment analysis using MetaboAnalyst 5.0. A total of 25 potential biomarkers were screened and identified in the rat urine in this experiment. Compared with the normal group, the model group showed significant increases in the levels of 14 substances(P<0.05) and significant decreases in the levels of 11 substances(P<0.05). BYHWD was able to effectively reverse the trend of most endogenous biomarkers. Compared with the model group, BYHWD significantly down-regulated 13 biomarkers(P<0.05) and up-regulated 10 biomarkers(P<0.05). The metabolic products were mainly related to the biosynthesis of pantothenic acid and coenzyme A, tryptophan metabolism, retinol metabolism, and propionate metabolism. BYHWD has therapeutic effect on chronic inflammation induced by LPS, which may be related to its ability to improve the levels of endogenous metabolites, enhance the body's anti-inflammatory and antioxidant capabilities, and restore normal metabolic activity.


Assuntos
Lipopolissacarídeos , Metabolômica , Ratos , Masculino , Animais , Cromatografia Líquida de Alta Pressão/métodos , Ratos Sprague-Dawley , Metabolômica/métodos , Inflamação/tratamento farmacológico , Biomarcadores/urina
3.
Digit Health ; 9: 20552076231205269, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37808241

RESUMO

Background: In this study, our aim was to quantify eHealth literacy and determine a cut-off value for eHEALS scores that signifies adequate eHealth literacy among rural residents in Gansu, China. Methods: This cross-sectional investigation encompassed 18 rural areas across three cities-Lanzhou, Wuwei, and Dingxi-in Gansu. A total of 451 residents were recruited and underwent evaluations for both eHealth literacy and eHealth skills, utilizing the eHEALS and self-constructed tasks, respectively. A receiving operator characteristic curve was plotted with eHealth skills as the dependent variable and eHealth literacy levels as the independent variable, aiming to determine a cut-off value for eHEALS indicating adequate eHealth literacy and evaluate its predictive capacity. Results: Among the 451 respondents, 10.9% did not possess a personal electronic device with Internet access, while 6.4% owned but had never used them. Within the remaining 373 residents, the mean eHealth literacy score was 25.85 (SD:10.93), item scores ranged from 3.12 (SD:1.45) to 3.42 (SD:1.60). Completion rates for three eHealth skills varied from 39.1% to 59.8%. The cut-off value was 29.5 determined by the Youden index. The area under the receiver operating curve was 0.829, with a sensitivity of 86.7%, and a specificity of 66.8%. Conclusions: Our findings emphasized that eHealth literacy among rural residents remains at a low level. Moreover, we identified a cut-off value of 29.5 for eHEALS scores that signifies adequate eHealth literacy within this demographic.

4.
Front Pharmacol ; 14: 1176136, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37288111

RESUMO

Introduction: Recombinant human fibroblast growth factor 21 (FGF-21) is a potential therapeutic agent for multiple metabolic diseases. However, little is known about the toxicokinetic characteristics of FGF-21. Methods: In the present study, we investigated the toxicokinetics of FGF-21 delivered via subcutaneous injection in vivo. Twenty cynomolgus monkeys were injected subcutaneously with different doses of FGF-21 for 86 days. Serum samples were collected at eight different time points (0, 0.5, 1.5, 3, 5, 8, 12, and 24 h) on day 1, 37 and 86 for toxicokinetic analysis. The serum concentrations of FGF-21 were measured using a double sandwich Enzyme-linked immunosorbent assay. Blood samples were collected on day 0, 30, 65, and 87 for blood and blood biochemical tests. Necropsy and pathological analysis were performed on d87 and d116 (after recovery for 29 days). Results: The average AUC(0-24h) values of low-dose FGF-21 on d1, d37, and d86 were 5253, 25268, and 60445 µg h/L, and the average AUC(0-24h) values of high-dose FGF-21 on d1, d37, and d86 were 19964, 78999, and 1952821 µg h/L, respectively. Analysis of the blood and blood biochemical indexes showed that prothrombin time and AST content in the high-dose FGF-21 group increased. However, no significant changes in other blood and blood biochemical indexes were observed. The anatomical and pathological results showed that continuous subcutaneous injection of FGF-21 for 86 days did not affect organ weight, the organ coefficient, and histopathology in cynomolgus monkeys. Discussion: Our results have guiding significance for the preclinical research and clinical use of FGF-21.

5.
Front Oncol ; 12: 1038135, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465362

RESUMO

Purpose: To determine whether gross tumor volume (GTV) of adenocarcinoma of esophagogastric junction (AEG) corresponding to cT and cN stages measured on CT could help quantitatively determine resectability. Materials and methods: 343 consecutive patients with AEG, including 279 and 64 randomly enrolled in training cohort (TC) and validation cohort (VC), respectively, underwent preoperative contrast-enhanced CT. Univariate and multivariate analyses for TC were performed to determine factors associated with resectability. Receiver operating characteristic (ROC) analyses were to determine if GTV corresponding to cT and cN stages could help determine resectability. For VC, Cohen's Kappa tests were to assess performances of the ROC models. Results: cT stage, cN stage and GTV were independently associated with resectability of AEG with odds ratios of 4.715, 4.534 and 1.107, respectively. For differentiating resectable and unresectable AEG, ROC analyses showed that cutoff GTV of 32.77 cm3 in stage cT1-4N0-3 with an area under the ROC curve (AUC) of 0.901. Particularly, cutoffs of 27.67 and 32.77 cm3 in stages cT3 and cT4 obtained AUC values of 0.860 and 0.890, respectively; and cutoffs of 27.09, 33.32 and 37.39 cm3 in stages cN1, cN2 and cN3 obtained AUC values of 0.852, 0.821 and 0.902, respectively. In VC, Cohen's Kappa tests verified that the ROC models had good performance in distinguishing between resectable and unresectable AEG (all Cohen's K values > 0.72). Conclusions: GTV, cT and cN stages could be independent determinants of resectability of AEG. And GTV corresponding to cT and cN stages can help quantitatively determine resectability.

6.
PLoS One ; 17(12): e0279290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36548282

RESUMO

OBJECTIVE: This study examined the reliability and validity of a Shame and Stigma Scale (SSS) and assessed shame and stigma among patients with facial disfigurement from nasopharyngeal carcinoma (NPC). METHODS: Data were collected from 218 patients with NPC through a cross-sectional survey between January 14, 2020, and December 1, 2020. The original SSS is a 20-item scale with four dimensions (i.e., shame with appearance, sense of stigma, regret, and social/speech concern). We used Cronbach's alpha and McDonald's omega to assess reliability and exploratory factor analysis (EFA) to assess the factor structure. We also used Pearson correlation analysis to examine the relationship between each item and total score of scale items and convergent validity. RESULTS: The final 18-item SSS had a Cronbach's alpha coefficient of .89. The EFA revealed that the SSS has a four-factor structure: sense of stigma, social/speech concern, shame with appearance, and regret. These factors showed satisfactory reliability, with McDonald's omega coefficients of .87, .77, .86, and .79, respectively. The scale showed significant relationship between each item and total score of scale items with respect to item-total correlations, item-subscale correlations, and item-other-subscale correlations. Convergent validity was supported by the significant positively correlated with the total scores for depression and anxiety. CONCLUSION: The SSS is valid and reliable in assessing shame and stigma and monitoring treatment compliance among patients with NPC.


Assuntos
Neoplasias Nasofaríngeas , Estigma Social , Humanos , Reprodutibilidade dos Testes , Carcinoma Nasofaríngeo , Estudos Transversais , População do Leste Asiático , Vergonha , Inquéritos e Questionários , Psicometria
7.
AIDS Behav ; 26(5): 1477-1488, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34697704

RESUMO

Given the recent evidence on "Undetectable = Untransmittable" (U=U) and pre-exposure prophylaxis (PrEP), the present study aimed to investigate HIV disclosure behaviors and their associations with sexual risk behaviors and U=U and PrEP awareness among men who have sex with men (MSM) in China. A cross-sectional survey was conducted among 689 MSM recruited through a gay-friendly non-governmental organization located in Chengdu, China in 2018-2019. Information was collected by a structured self-administrated questionnaire. The enrolled sample included 554 (80.4%) participants who were HIV-negative and 135 (19.6%) participants with an unknown HIV status. In terms of disclosure, 41.4% of participants informed all partners about their HIV status all the time (informing behavior), while 30.4% asked all partners about their HIV status all the time (asking behavior). Only one-fifth knew about U=U, but this was not statistically associated with either informing or asking behavior. Half (50.5%) had heard of PrEP but this was not statistically associated with either informing or asking behavior. Common barriers to informing and asking behaviors were lower risk perception of HIV infection, a history of sexually transmitted infections, engagement in receptive sex, and a history of sex with casual partners. We found that both U=U and PrEP awareness and HIV serostatus disclosure were infrequent and not associated in this study of Chinese MSM. These data indicate huge information gaps among MSM in China.


Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , China/epidemiologia , Estudos Transversais , Revelação , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Comportamento Sexual , Parceiros Sexuais
8.
BMC Public Health ; 21(1): 2243, 2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893061

RESUMO

BACKGROUND: This study aimed to determine whether the disclosure of same-sex behavior to health care providers (HCPs) is associated with higher rates of prior human immunodeficiency virus (HIV) testing experience and greater awareness of immediate antiretroviral therapy (ART), Undetectable = Untransmittable (U=U), and pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM). METHODS: We conducted a cross-sectional survey among 689 adult males in Chengdu, China who self-reported having had anal intercourse with at least one man in the past 6 months. We measured same-sex behavior disclosure to three types of HCPs (hospital clinicians, community-based organization peer educators, and Center for Disease Control and Prevention public health specialists), and the awareness of immediate ART, U=U, and PrEP. RESULTS: Of the 689 enrolled participants, 31.4% had disclosed their same-sex behavior to some or all of the clinicians, 83.9% had done so to the peer educators, and 56.8% had done so to the public health specialists. Approximately four in five (82.1%) of the participants had ever been tested for HIV. The awareness rate was 84.8% for immediate ART, 20.2% for U=U, and 50.7% for PrEP. After controlling for significant background variables, same-sex behavior disclosure to clinicians was associated with greater awareness of PrEP (adjusted odds ratio [AOR] = 1.64; 95% confidence interval [CI]: 1.08-2.48), but similar findings were not reported regarding disclosure to peer educators or public health specialist. Same-sex behavior disclosure to any types of HCPs was not associated with HIV testing experience, and awareness of immediate ART or U=U. CONCLUSIONS: The rates of same-sex behavior disclosure varied with different types of HCPs. Disclosure to clinicians was associated with greater awareness of PrEP, but not awareness of immediate ART or U=U.


Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Adulto , Estudos Transversais , Revelação , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Homossexualidade Masculina , Humanos , Masculino , Comportamento Sexual
9.
BMC Infect Dis ; 21(1): 895, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470607

RESUMO

BACKGROUND: In China, men who have sex with men (MSM) face a high risk of HIV infection. Intimate partner violence (IPV) is common in this population and leads to various adverse consequences, including risky sexual behaviors, substance abuse, and poor mental health, which pose huge challenges to HIV prevention and control. METHODS: An anonymous cross-sectional study was conducted to investigate the lifetime prevalence of IPV and prevalence of risky sexual behaviors during the previous 6 months in a convenience sample of 578 MSM from 15 cities covering seven geographical divisions in mainland China. The associations between IPV and risky sexual behaviors and the moderating effect of self-efficacy on these associations were explored through univariate and multivariate regression analyses. RESULTS: The prevalence rates of IPV perpetration and victimization were 32.5% and 32.7%, respectively. The proportions of participants who reported inconsistent condom use with regular or casual partners and multiple regular or casual sexual partners were 25.8%, 8.3%, 22.2%, and 37.4%, respectively. Multiple IPV experiences were positively associated with risky sexual behaviors; for example, any IPV victimization was positively associated with multiple regular partners, adjusted odds ratio (ORa) = 1.54, 95% CI [1.02,2.32], and multiple casual partners, ORa = 1.93, 95% CI [1.33, 2.80]. Any IPV perpetration was positively associated with inconsistent condom use with regular partners, ORa = 1.58, 95% CI [1.04, 2.40], and multiple casual partners, ORa = 2.11, 95% CI [1.45, 3.06]. Self-efficacy was identified as a significant moderator of the association between multiple casual sexual partnership and emotional IPV. CONCLUSIONS: In conclusion, given the high prevalence of both IPV and risky sexual behaviors among Chinese MSM in this study, the inclusion of self-efficacy in interventions targeting IPV and risky sexual behaviors should be considered.


Assuntos
Infecções por HIV , Violência por Parceiro Íntimo , Minorias Sexuais e de Gênero , China/epidemiologia , Estudos Transversais , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Prevalência , Fatores de Risco , Autoeficácia , Parceiros Sexuais
10.
BMJ Open ; 11(8): e048449, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433597

RESUMO

INTRODUCTION: In the past three decades, China has made great strides in the prevention and treatment of tuberculosis (TB). However, the TB burden remains high. In 2019, China accounted for 8.4% of global incident cases of TB, the third highest in the world, with a higher prevalence in rural areas. The Healthy China 2030 highlights the gate-keeping role of primary healthcare (PHC). However, the impact of PHC reforms on the future TB burden is unclear. We propose to use mathematical models to project and evaluate the impacts of different gate-keeping policies. METHODS AND ANALYSIS: We will develop a deterministic, population-level, compartmental model to capture the dynamics of TB transmission within adult rural population. The model will incorporate seven main TB statuses, and each compartment will be subdivided by service providers. The parameters involving preference for healthcare seeking will be collected using discrete choice experiment (DCE) method. We will solve the deterministic model numerically over a 20-year (2021-2040) timeframe and predict the TB prevalence, incidence and cumulative new infections under the status quo or various policy scenarios. We will also conduct an analysis following standard protocols to calculate the average cost-effectiveness for each policy scenario relative to the status quo. A numerical calibration analysis against the available published TB prevalence data will be performed using a Bayesian approach. ETHICS AND DISSEMINATION: Most of the data or parameters in the model will be obtained based on secondary data (eg, published literature and an open-access data set). The DCE survey has been reviewed and approved by the Ethics Committee of the School of Public Health, Sun Yat-sen University. The approval number is SYSU [2019]140. Results of the study will be disseminated through peer-reviewed journals, media and conference presentations.


Assuntos
Tuberculose , Adulto , Teorema de Bayes , China/epidemiologia , Reforma dos Serviços de Saúde , Humanos , Modelos Teóricos , Atenção Primária à Saúde , Tuberculose/epidemiologia , Tuberculose/prevenção & controle
11.
BMC Public Health ; 21(1): 802, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902499

RESUMO

BACKGROUND: The prevalence of HIV among men who have sex with men (MSM) in southwest China is still increasing. This study aimed to investigate the trend in HIV incidence and its associated risk factors among MSM in Chengdu, China. METHOD: Incidence data were collected from the largest local non-governmental organization (NGO) serving MSM in Chengdu between 2012 and 2018, while information on sexual behaviors was collected from 2014. All MSM who received voluntary counseling and testing services (VCT) in the collaborating NGO at least twice during the study period were included. We calculated the HIV incidence density among MSM every 2 years and the overall incidence rate. A Cox proportional hazards regression model was employed to identify risk factors for HIV infection. RESULT: A total of 4578 HIV-negative participants were included in the cohort. The total incidence density was 5.95 (95% CI: 5.37-6.56)/100 person-years (PYs) between 2012 and 2018. The segmented incidence density was 9.02 (95% CI: 7.46-10.78), 5.85 (95% CI: 4.86-6.97), 5.43 (95% CI: 4.53-6.46), and 3.09 (95% CI: 2.07-4.41)/100 PYs in 2012-2013, 2014-2015, 2016-2017, and 2018, respectively. After adjusting for sociodemographic characteristics, compared to participants without sexual partners within 6 months, MSM with one fixed partner (Adjusted Hazard Ratio, AHR = 1.18, 95% CI: 0.44-3.19) and more than five partners (AHR = 2.24, 95% CI: 0.81-6.20) had increased risk of HIV infection. MSM who used condom inconsistently had a higher risk of HIV infection (AHR = 1.87, 95% CI: 1.46-2.38) compared to consistent condom users. CONCLUSION: The decreased HIV incidence density among MSM was potentially related to the successful comprehensive HIV prevention strategies in Chengdu. Multiple male sexual partnerships and inconsistent condom use during anal intercourse were risk factors associated with HIV occurrence.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , China/epidemiologia , Estudos de Coortes , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Risco , Comportamento Sexual , Parceiros Sexuais
12.
Front Pharmacol ; 10: 151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30890932

RESUMO

Pulmonary fibrosis is common in a variety of inflammatory lung diseases, there is currently no effective clinical drug treatment. It has been reported that the ethanol extract of Eclipta prostrata L. can improve the lung collagen deposition and fibrosis pathology induced by bleomycin (BLM) in mice. In the present study, we studied whether wedelolactone (WEL), a major coumarin ingredient of E. prostrata, provided protection against BLM-induced pulmonary fibrosis. ICR or C57/BL6 strain mice were treated with BLM to establish lung fibrosis model. WEL (2 or 10 mg/kg) was given daily via intragastric administration for 2 weeks starting at 7-day after intratracheal instillation. WEL at 10 mg/kg significantly reduced BLM-induced inflammatory cells infiltration, pro-inflammatory factors expression, and collagen deposition in lung tissues. Additionally, treatment with WEL also impaired BLM-induced increases in fibrotic marker expression (collagen I and α-SMA) and decrease in an anti-fibrotic marker (E-cadherin). Treatment with WEL significantly prevented BLM-induced increase in TGF-ß1 and Smad2/3 phosphorylation in the lungs. WEL administration (10 mg/kg) also significantly promoted AMPK activation compared to model group in BLM-treated mice. Further investigation indicated that activation of AMPK by WEL can suppressed the transdifferentiation of primary lung fibroblasts and the epithelial mesenchymal transition (EMT) of alveolar epithelial cells, the inhibitive effects of WEL was significantly blocked by an AMPK inhibitor (compound C) in vitro. Together, these results suggest that activation of AMPK by WEL followed by reduction in TGFß1/Raf-MAPK signaling pathways may have a therapeutic potential in pulmonary fibrosis.

13.
BMJ Open ; 9(1): e024080, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30782725

RESUMO

OBJECTIVES: This study aimed to examine the urban-rural disparity in health-related quality of life (HRQoL) of the Chinese elderly and to explore the mediating roles of socioeconomic status (SES) and frequency of contact with children in the relationship between urban/rural areas and HRQoL. METHODS: This cross-sectional study used data from China Health and Retirement Longitudinal Study for 2015-2016, involving 12 369 Chinese aged 45 years and over. HRQoL of respondents was measured by three-level EuroQol five dimensions (EQ-5D-3L). SES, based on principal components analysis, was combined by the individual possessions of durable consumer goods and houses. Frequency of contact with children was derived from the responses to whether they live with children and how often they contact with them. Mediation analyses were performed to examine the mediating effects of SES and frequency of contact in the relationship between urban/rural areas and HRQoL. RESULTS: Urban respondents had higher scores of HRQoL than rural respondents (p<0.05). As SES and frequency of contact with children increased, the scores of HRQoL of the elderly went up as well. Mediation analyses proved the possible mediating effects of SES and frequency of contact in the relationship between urban/rural areas and HRQoL (0.0713 and 0.0064). The indirect effects induced by SES and frequency of contact were 65.45% and 5.90%, respectively. CONCLUSIONS: There was a significant difference in HRQoL between urban and rural middle-aged and elderly participants, which was partially mediated by urban-rural disparities in SES and frequency of contact with children. Higher SES and frequency of contact with children contributed to higher health status in the Chinese elderly.


Assuntos
Relações Pais-Filho , Qualidade de Vida , População Rural , Classe Social , População Urbana , Idoso , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Sci Rep ; 7: 45025, 2017 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-28322352

RESUMO

Lean body mass (LBM) is a complex trait for human health. To identify genomic loci underlying LBM, we performed a gene-based genome-wide association study of lean mass index (LMI) in 1000 unrelated Caucasian subjects, and replicated in 2283 unrelated Caucasians subjects. Gene-based association analyses highlighted the significant associations of three genes UQCR, TCF3 and MBD3 in one single locus 19p13.3 (discovery p = 6.10 × 10-5, 1.65 × 10-4 and 1.10 × 10-4; replication p = 2.21 × 10-3, 1.84 × 10-3 and 6.95 × 10-3; combined p = 2.26 × 10-6, 4.86 × 10-6 and 1.15 × 10-5, respectively). These results, together with the known functional relevance of the three genes to LMI, suggested that the 19p13.3 region containing UQCR, TCF3 and MBD3 genes was a novel locus underlying lean mass variation.


Assuntos
Composição Corporal/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 19 , Estudo de Associação Genômica Ampla , Magreza/genética , Adulto , Idoso , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único
15.
Obesity (Silver Spring) ; 25(4): 757-764, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28224759

RESUMO

OBJECTIVE: Body fat mass (BFM) is more homogeneous and accurate than body total mass in measuring obesity but has rarely been studied. Aiming to uncover the genetic basis of fat-induced obesity, a genome-wide association meta-analysis of BFM, after adjustment by body lean mass, was performed in the European population. METHODS: Three samples of European ancestry were included in the meta-analysis: the Framingham Heart Study (N = 6,004), the Kansas City osteoporosis study (N = 2,207), and the Omaha osteoporosis study (N = 968). RESULTS: At the genome-wide significance level (α = 5.0×10-8 ), a cluster of 10 single-nucleotide polymorphisms (SNPs) at chromosomal region 20p11 that were associated with BFM (lead SNP rs2069126, P = 1.82×10-9 , closest gene SLC24A3) was identified in 9,179 subjects. One of the top SNPs, rs6046308 (P = 3.74×10-8 ), was found to be nominally significant for body fat percentage in another independent study (P = 0.03, N = 75,888) and was reported to transregulate the expression of the MPZ gene at 1q23.3 (unadjusted P = 9.78×10-6 , N = 1,490). Differential gene expression analysis demonstrated that SLC24A3 and CFAP61 at the identified locus were differentially expressed in tissues of people with versus without obesity (P = 3.40×10-5 and 8.72×10-4 , N = 126 and 70), implying their potential role in fat development. CONCLUSIONS: These results may provide new insights into the biological mechanism that underlies fat-induced obesity pathology.


Assuntos
Tecido Adiposo , Cromossomos Humanos Par 20 , Obesidade/genética , Polimorfismo de Nucleotídeo Único , População Branca/genética , Adulto , Idoso , Índice de Massa Corporal , Feminino , Estudo de Associação Genômica Ampla , Genômica , Humanos , Masculino , Pessoa de Meia-Idade
16.
J Ethnopharmacol ; 175: 172-80, 2015 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-26385580

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ecliptae Herba, a nourishing traditional Chinese medicine, is also a folk medicine for the treatment of lung diseases. AIM OF THE STUDY: To investigate the anti-fibrosis effects and the underlying mechanism of the extract of Ecliptae Herba and its potential active components. MATERIALS AND METHODS: The resulting extract (EXT) was prepared from the 80% ethanol extract of Ecliptae Herba. After intratracheally administrated with bleomycin (BLM, 5mg/kg), mice were orally treated with EXT at 2.5, 1.25, 0.625 g/kg and eclipta saponin A (ESA) at 80 mg/kg once daily for 28 day. The bodyweight, survival rate, pathological changes of lung and levels of hydroxyproline (HYP) were used to evaluate the anti-fibrotic effects. The malonaldehyde (MDA), superoxidae dismutase (SOD) activity, and the protein expressions of matrix metalloproteinase (MMP)-2, 9, tissue inhibitor of metalloproteinase-1 (TIMP-1), cyclooxygenase-2 (COX-2), α-smooth muscle actin (α-SMA) and transforming growth factor-ß1 (TGF-ß1) in lung tissue were analyzed by kits or western blot. RESULTS: Compared with BLM group, EXT administration could significantly ameliorated the pathological changes of lung, decreased the HYP content, enhanced the SOD activity, and reduced the MDA content of lung tissues. In mechanism, EXT significantly alleviated the levels of COX-2, TGF-ß1, MMP-2 and α-SMA, as well as elevated the ratio value of MMP-9/TIMP-1. Additionally, the anti-fibrosis effects of ESA, a large amount of saponins isolated from Eclipta prostrata , was also evaluated by the BLM-induced model. The results showed that ESA could block BLM-induced histological changes of lung tissue and decrease the high levels of TGF-ß1 and α-SMA. CONCLUSIONS: Ecliptae Herba has protective effects against the pulmonary fibrosis induced by BLM via reducing the oxidative stress, lung tissue inflammation, and the subsequent epithelial-mesenchymal transition. The active chemical constituents may be involved with triterpenoid saponins, such as ESA.


Assuntos
Eclipta , Extratos Vegetais/uso terapêutico , Fibrose Pulmonar/tratamento farmacológico , Saponinas/uso terapêutico , Actinas/metabolismo , Animais , Bleomicina , Ciclo-Oxigenase 2/metabolismo , Hidroxiprolina/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Malondialdeído/metabolismo , Metaloproteinases da Matriz/metabolismo , Camundongos Endogâmicos ICR , Componentes Aéreos da Planta , Extratos Vegetais/farmacologia , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Saponinas/farmacologia , Superóxido Dismutase/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
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