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1.
Alzheimers Dement ; 20(4): 2329-2339, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38284799

RESUMO

INTRODUCTION: Various associations between social factors and motoric cognitive risk syndrome (MCR) have been reported. However, whether social frailty (integrated from multiple social factors) is associated with MCR is still unclear. METHODS: We included 4657 individuals without MCR at Round 1 of the NHATS as the discovery sample, and 3075 newly recruited individuals from Round 5 of the NHATS as the independent validation sample. Social frailty was assessed by five social items. MCR was defined as the presence of both subjective cognitive complaints and slow gait speed in individuals without dementia or mobility disability. RESULTS: Compared with normal individuals, those with social frailty had higher risk of incident MCR (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.34-1.84). Each additional unfavorable social item was associated with an increased risk of MCR (HR: 1.32, 95% CI: 1.22-1.43). DISCUSSION: Social frailty was associated with an increased risk of incident MCR in older adults. HIGHLIGHTS: Various associations between social factors and motoric cognitive risk syndrome (MCR) have been reported. Social frailty that integrated from multiple social factors was associated with an increased risk of incident MCR. Social frailty should be included in the early screening of individuals to identify those at higher risk of MCR.


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Fragilidade , Humanos , Idoso , Transtornos Cognitivos/epidemiologia , Incidência , Fragilidade/epidemiologia , Fragilidade/complicações , Fatores de Risco , Cognição , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/complicações
2.
Acta Pharmacol Sin ; 44(12): 2347-2357, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37532784

RESUMO

SARS-CoV-2 infection causes injuries of not only the lungs but also the heart and endothelial cells in vasculature of multiple organs, and induces systemic inflammation and immune over-reactions, which makes COVID-19 a disease phenome that simultaneously affects multiple systems. Cardiovascular diseases (CVD) are intrinsic risk and causative factors for severe COVID-19 comorbidities and death. The wide-spread infection and reinfection of SARS-CoV-2 variants and the long-COVID may become a new common threat to human health and propose unprecedented impact on the risk factors, pathophysiology, and pharmacology of many diseases including CVD for a long time. COVID-19 has highlighted the urgent demand for precision medicine which needs new knowledge network to innovate disease taxonomy for more precise diagnosis, therapy, and prevention of disease. A deeper understanding of CVD in the setting of COVID-19 phenome requires a paradigm shift from the current phenotypic study that focuses on the virus or individual symptoms to phenomics of COVID-19 that addresses the inter-connectedness of clinical phenotypes, i.e., clinical phenome. Here, we summarize the CVD manifestations in the full clinical spectrum of COVID-19, and the phenome-wide association study of CVD interrelated to COVID-19. We discuss the underlying biology for CVD in the COVID-19 phenome and the concept of precision medicine with new phenomic taxonomy that addresses the overall pathophysiological responses of the body to the SARS-CoV-2 infection. We also briefly discuss the unique taxonomy of disease as Zheng-hou patterns in traditional Chinese medicine, and their potential implications in precision medicine of CVD in the post-COVID-19 era.


Assuntos
COVID-19 , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/genética , Fenômica , Medicina de Precisão , SARS-CoV-2/genética , Síndrome de COVID-19 Pós-Aguda , Células Endoteliais
3.
BMC Pulm Med ; 22(1): 306, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35945553

RESUMO

BACKGROUND: Acute exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) contributes significantly to mortality among patients with COPD in Intensive care unit (ICU). This study aimed to develop a nomogram to predict 30-day mortality among AECOPD patients in ICU. METHODS: In this retrospective cohort study, we extracted AECOPD patients from Medical Information Mart for Intensive Care III (MIMIC-III) database. Multivariate logistic regression based on Akaike information criterion (AIC) was used to establish the nomogram. Internal validation was performed by a bootstrap resampling approach with 1000 replications. The discrimination and calibration of the nomogram were evaluated by Harrell's concordance index (C-index) and Hosmer-Lemeshow (HL) goodness-of-fit test. Decision curve analysis (DCA) was performed to evaluate its clinical application. RESULTS: A total of 494 patients were finally included in the study with a mean age of 70.8 years old. 417 (84.4%) patients were in the survivor group and 77 (15.6%) patients were in the non-survivor group. Multivariate logistic regression analysis based on AIC included age, pO2, neutrophil-to-lymphocyte ratio (NLR), prognostic nutritional index (PNI), invasive mechanical ventilation and vasopressor use to construct the nomogram. The adjusted C-index was 0.745 (0.712, 0.778) with good calibration (HL test, P = 0.147). The Kaplan-Meier survival curves revealed a significantly lower survival probability in the high-risk group than that in the low-risk group (P < 0.001). DCA showed that nomogram was clinically useful. CONCLUSION: The nomogram developed in this study could help clinicians to stratify AECOPD patients and provide appropriate care in clinical setting.


Assuntos
Nomogramas , Doença Pulmonar Obstrutiva Crônica , Idoso , Humanos , Unidades de Terapia Intensiva , Prognóstico , Estudos Retrospectivos
4.
Eur J Neurol ; 28(8): 2680-2687, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33905575

RESUMO

BACKGROUND AND PURPOSE: Motoric cognitive risk syndrome (MCR) is characterized by slow walking speed and subjective memory complaints (SMCs). This study investigated the prevalence and potential risk factors of MCR and its association with falls in Chinese community-dwelling older adults. METHODS: The analysis was based on data from the Rugao Longevity and Aging Study (RuLAS). MCR was defined as the presence of both SMCs and slow walking speed in participants free of major neurocognitive disorders. SMCs were determined according to a positive answer to the question 'Do you feel you have more problems with memory than most?' in the 15-item Geriatric Depression Scale. Slow walking speed was defined as one standard deviation or more below the mean value for patients' age and sex. Data on falls were derived from a standardized questionnaire. RESULTS: The prevalence of SMCs, slow walking speed and MCR in the RuLAS cohort (N = 1592) was 51.9%, 15.6% and 8.3%, respectively. After adjusting for other covariates, an occupation of farming (odds ratio [OR] 2.358, 95% confidence interval [CI] 1.007-5.521, p = 0.048), history of cerebrovascular disease (OR 2.215, 95% CI 1.032-4.752, p = 0.041) and hospitalization (OR 2.008, 95% CI 1.120-3.602, p = 0.019) were risk factors for MCR. Binary logistic regression analysis indicated that the risk of falls was increased by MCR (OR 1.547, 95% CI 1.009-2.371), SMC (OR 1.308, 95% CI 1.003-1.707) and slow walking speed (OR 1.442, 95% CI 1.030-2.017). CONCLUSIONS: Early identification of potential risk factors of MCR can prevent the occurrence of adverse health events such as falls in the elderly.


Assuntos
Cognição , Idoso , China/epidemiologia , Estudos Transversais , Humanos , Prevalência , Fatores de Risco
5.
Mol Med ; 26(1): 70, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32640974

RESUMO

BACKGROUND: Ovarian cancer is one of the most common gynecologic cancers and has high mortality rate due to the lack of early diagnosis method and efficient therapeutic agents. circCELSR1 is up-regulated in ovarian cancer, but its role and mechanisms in ovarian cancer are unclear. METHODS: Gene expression of circCELSR1, miR-598 and BRD4 in ovarian cells was examined by qRT-PCR. Protein level was determined by Western blotting. Bioinformatic analysis and luciferase assay determined the molecular binding among circCELSR1, miR-598 and BRD4 3' UTR. Cell proliferation, migration, invasion and apoptosis were determined by colony formation, wound healing assay, transwell assay and flow cytometry analysis, respectively. An abdominal cavity metastasis nude mice model was used to determine the in vivo function of circCELSR1. RESULTS: circCELSR1 and BRD4 were promoted, but miR-598 was suppressed in various ovarian cancer cells. circCELSR1 bound to miR-598 and promoted expression of its downstream target BRD4. Knockdown of circCELSR1 suppressed proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), but promoted apoptosis in ovarian cancer cells, and these effects were reversed by miR-598 inhibition or BRD4 overexpression. circCELSR1 inhibition decreased the expression of BRD4 and its downstream proliferation/migration related genes by targeting miR-598. Furthermore, knockdown of circCELSR1 suppressed ovarian cancer growth and metastasis in nude mice. CONCLUSION: Knockdown of circCELSR1 inhibited BRD4-mediated proliferation/migration related signaling via sponging miR-598, thereby repressing ovarian cancer progression. This study provides a new regulatory mechanism of ovarian cancer may facilitate the development of therapeutic agents for ovarian cancer.


Assuntos
Caderinas/genética , Proteínas de Ciclo Celular/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , RNA Circular , Transdução de Sinais , Fatores de Transcrição/metabolismo , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Modelos Animais de Doenças , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Neoplasias Ovarianas/patologia , Interferência de RNA
6.
BMC Geriatr ; 20(1): 9, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906855

RESUMO

BACKGROUND: Previous studies suggest that poor sleep quality or abnormal sleep duration may be associated with frailty. Here we test the associations of sleep disturbances with both frailty and pre-frailty in an elderly population. METHODS: Participants included 1726 community-dwelling elders aged 70-87 years. Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep disturbances. Frailty was defined using phenotype criteria. Logistic regression models were used to estimate odds ratio of the associations. RESULTS: The average PSQI score was 5.4 (SD, 3.1). Overall 43.6% of the participants had poor sleep quality (PSQI> 5), 8.2% had night sleep time ≤ 5 h, and 27.8% had night sleep time ≥ 9 h. The prevalence of frailty and pre-frailty was 9.2 and 52.8%, respectively. The proportions of PSQI> 5 increased with the severity of frailty status (robust: pre-frail: frail, 34.5%: 48%: 56.1%, P < 0.001). After adjustment for multiple potential confounders, poor sleep quality (PSQI> 5) was associated with higher odds of frailty (OR = 1.78, 95% CI 1.19-2.66) and pre-frailty (OR = 1.51, 95% CI 1.20-1.90). Sleep latency, sleep disturbance, and daytime dysfunction components of PSQI measurements were also associated with frailty and pre-frailty. In addition, sleep time 9 h/night was associated with higher odds of frailty and pre-frailty. CONCLUSIONS: We provided preliminary evidences that poor sleep quality and prolonged sleep duration were associated with being frailty and pre-frailty in an elderly population aged 70-87 years. The associations need to be validated in other elderly populations.


Assuntos
Envelhecimento , Fragilidade , Transtornos do Sono-Vigília , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Humanos , Longevidade , Masculino , Sono , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/epidemiologia
7.
Aging Clin Exp Res ; 32(2): 305-311, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31004283

RESUMO

BACKGROUND AND AIMS: To explore whether frailty, defined by frailty index (FI), is associated with the risk of elevated B-type natriuretic peptide (BNP), a surrogate endpoint of cardiovascular events. METHODS: Data of 1382 community-dwelling elders who had no documented cardiovascular diseases aged 70-84 years from the ageing arm of the Rugao Longevity and Ageing Study was used. Traditional risk factor index (TI) was constructed using eight established cardiovascular-related risk factors. FI was constructed using 36 health deficits. Elevated BNP was defined as BNP ≥ 100pg/mL. Cardiovascular events include incident major cardiovascular events and cardiovascular death. RESULTS: During a 3-year follow-up period, 97 participants had cardiovascular events. TI was not associated with the risk of elevated BNP, but was associated with cardiovascular events (HR = 1.16, 95% CI 1.01-1.34). Frailty index was not only associated with cardiovascular events (HR = 1.32, 95% CI 1.06-1.64), but also associated with elevated BNP with an OR of 1.22 (95% CI 1.02-1.47) for each 0.1 increment. Further, both frailty (OR = 1.93, 95% CI 1.67-3.17) and pre-frailty (OR = 1.54, 95% CI 1.06-2.25) were associated with increased risk of elevated BNP. CONCLUSION: FI is associated with increased risks of both cardiovascular events and surrogated endpoint of cardiovascular disease-elevated BNP. Frailty may be a non-traditional risk factor of cardiovascular diseases and frailty index may be a measurement for early identifying high risk elderly individuals of cardiovascular abnormities.


Assuntos
Doenças Cardiovasculares , Fragilidade , Peptídeo Natriurético Encefálico/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Doenças Cardiovasculares/diagnóstico , Feminino , Humanos , Vida Independente , Longevidade , Masculino , Fatores de Risco
8.
Aging Clin Exp Res ; 32(11): 2297-2302, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31786744

RESUMO

BACKGROUND AND AIMS: This study aimed at investigating whether depression symptoms are associated with prevalent and incident physical frailty in Chinese older population. METHODS: We analyzed data of 1168 older Chinese adults aged 70 and above in the aging arm of the Rugao Longevity and Aging Study (RuLAS). Depressive symptoms (Geriatric Depression Scale ≥ 6) were assessed by the Geriatric Depression Scale. Frailty was defined using Fried phenotype criteria at baseline and 3-year survey. RESULTS: At baseline, 8.9% of the participants had depression symptoms. The prevalence of pre-frailty and frailty were 34.5% and 5.9%, respectively. The percentages of depressive symptoms increase from robust (5.3%) to pre-frail (11.2%), and then to frail (31.9%) groups. After adjustments of multiple covariates, depressive symptoms were associated with both prevalent pre-frailty (OR = 1.75, 95% CI 1.08-2.84) and prevalent frailty (OR = 5.64, 95% CI 2.85-11.14) at baseline. At 3-year survey, 9.3% participants reported the development of frailty. After multiple adjustments, depressive symptoms were associated with a 2.79-fold (95% CI 1.09-7.10) increased risk of 3-year incident frailty. CONCLUSION: Depressive symptoms are associated with prevalent and incident frailty in Chinese older population. Together with the observations of the European populations, depressive symptoms may be a candidate risk factor of frailty.


Assuntos
Depressão , Fragilidade , Idoso , Envelhecimento , Povo Asiático , Estudos Transversais , Depressão/epidemiologia , Idoso Fragilizado , Fragilidade/epidemiologia , Avaliação Geriátrica , Humanos , Longevidade , Pessoa de Meia-Idade
9.
Psychogeriatrics ; 20(5): 691-698, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32558008

RESUMO

BACKGROUND: To explore the cross-sectional and longitudinal associations between frailty and incident depressive symptoms in a Chinese elderly sample. METHODS: We analysed data of 1264 older Chinese elders aged 70-87 years in the Rugao Longevity and Ageing Study. The frailty phenotype was assessed using the Fried criteria and depression symptoms was measured by the Geriatric Depression Scale. RESULTS: At baseline, 10.6% of participants had depressive symptoms and 9.0% had frailty. In cross-sectional analysis, both pre-frailty (odds ratio (OR) = 2.18, 95% CI 1.35-3.51) and frailty (OR = 4.64, 95% CI 2.49-8.66) were associated with depressive symptoms. In longitudinal analyses, frailty (OR = 2.12, 95% CI 1.17-3.83), instead of pre-frailty, was associated with 1.5-year incident depressive symptoms in a full-adjusted model among participants free of baseline depressive symptoms. In the components of frailty, lower grip strength was associated with increased risk of depressive symptoms onset (OR = 1.56, 95% CI 1.06-2.29). CONCLUSIONS: Frailty and lower grip strength were associated with incident depressive symptoms in a Chinese elderly sample. Interventions designed to prevent depressive symptoms may be useful by utilising physical aspects of the elderly population.


Assuntos
Envelhecimento , Depressão , Fragilidade , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , China/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Avaliação Geriátrica , Humanos , Longevidade
10.
Age Ageing ; 47(3): 416-422, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29447359

RESUMO

Objective: To examine the associations of the actinin alpha 3 gene (ACTN3) R577X polymorphism with physical performance and frailty in an older Chinese population. Methods: Data from 1,463 individuals (57.8% female) aged 70-87 years from the Rugao Longevity and Ageing Study were used. The associations between R577X and timed 5-m walk, grip strength, timed Up and Go test, and frailty index (FI) based on deficits of 23 laboratory tests (FI-Lab) were examined. Analysis of variance and linear regression models were used to evaluate the genetic effects of ACTN3 R577X on physical performance and FI-Lab. Results: The XX and RX genotypes of the ACTN3 R557X polymorphism accounted for 17.1 and 46.9%, respectively. Multivariate regression analysis revealed that in men aged 70-79 years, the ACTN3 577X allele was significantly associated with physical performance (5-m walk time, regression coefficient (ß) = 0.258, P = 0.006; grip strength, ß = -1.062, P = 0.012; Up and Go test time ß = 0.368, P = 0.019). In women aged 70-79 years, a significant association between the ACTN3 577X allele and the FI-Lab score was observed, with a regression coefficient of ß = 0.019 (P = 0.003). These findings suggest an age- and gender-specific X-additive model of R577X for 5-m walk time, grip strength, Up and Go Test time, and FI-Lab score. Conclusion: The ACTN3 577X allele is associated with an age- and sex-specific decrease in physical performance and an increase in frailty in an older population.


Assuntos
Actinina/genética , Fragilidade/genética , Longevidade/genética , Polimorfismo Genético , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , China/epidemiologia , Feminino , Fragilidade/diagnóstico , Fragilidade/etnologia , Fragilidade/fisiopatologia , Frequência do Gene , Predisposição Genética para Doença , Avaliação Geriátrica/métodos , Força da Mão , Humanos , Masculino , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real , Medição de Risco , Fatores de Risco , Fatores Sexuais , Teste de Caminhada
11.
Molecules ; 23(4)2018 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-29561787

RESUMO

Coal is a major contributor to the global emission of nitrogen oxides (NOx). The NOx formation during coal utilization typically derives from the thermal decomposition of N-containing compounds (e.g., pyrrolic groups). NH3 and HCN are common precursors of NOx from the decomposition of N-containing compounds. The existence of H2O has significant influences on the pyrrole decomposition and NOx formation. In this study, the effects of H2O on pyrrole pyrolysis to form NOx precursors HCN and NH3 are investigated using the density functional theory (DFT) method. The calculation results indicate that the presence of H2O can lead to the formation of both NH3 and HCN during pyrrole pyrolysis, while only HCN is formed in the absence of H2O. The initial interaction between pyrrole and H2O determines the N products. NH3 will be formed when H2O attacks the C2 position of pyrrole with its hydroxyl group. On the contrary, HCN will be generated instead of NH3 when H2O attacks the C3 position of pyrrole with its hydroxyl group. In addition, the DFT calculations clearly indicate that the formation of NH3 will be promoted by H2O, whereas the formation of HCN is inhibited.


Assuntos
Amônia/química , Temperatura Alta , Cianeto de Hidrogênio/química , Modelos Moleculares , Pirróis/química , Água/química , Conformação Molecular
12.
Hum Genet ; 136(10): 1353-1362, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28799012

RESUMO

Considerable attention has been focused on the effect of deleterious mutations caused by the recent relaxation of selective constraints on human health, including the prevalence of obesity, which might represent an adaptive response of energy-conserving metabolism under the conditions of modern society. Mitochondrial DNA (mtDNA) encoding 13 core subunits of oxidative phosphorylation plays an important role in metabolism. Therefore, we hypothesized that a relaxation of selection constraints on mtDNA and an increase in the proportion of deleterious mutations have played a role in obesity prevalence. In this study, we collected and sequenced the mtDNA genomes of 722 Uyghurs, a typical population with a high prevalence of obesity. We identified the variants that occurred in the Uyghur population for each sample and found that the number of nonsynonymous mutations carried by Uyghur individuals declined with elevation of their BMI (P = 0.015). We further calculated the nonsynonymous and synonymous ratio (N/S) of the high-BMI and low-BMI haplogroups, and the results showed that a significantly higher N/S occurred in the whole mtDNA genomes of the low-BMI haplogroups (0.64) than in that of the high-BMI haplogroups (0.35, P = 0.030) and ancestor haplotypes (0.41, P = 0.032); these findings indicated that low-BMI individuals showed a recent relaxation of selective constraints. In addition, we investigated six clinical characteristics and found that fasting plasma glucose might be correlated with the N/S and selective pressures. We hypothesized that a higher proportion of deleterious mutations led to mild mitochondrial dysfunction, which helps to drive glucose consumption and thereby prevents obesity. Our results provide new insights into the relationship between obesity predisposition and mitochondrial genome evolution.


Assuntos
Povo Asiático/genética , Densidade Óssea/genética , DNA Mitocondrial/genética , Genoma Mitocondrial , Haplótipos , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/etnologia , China/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/etnologia , Obesidade/genética
13.
Biochem Biophys Res Commun ; 491(2): 537-544, 2017 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-28385530

RESUMO

Metastatic hepatocellular carcinoma (HCC) remains a mostly incurable disease. The fact that the identity of the mechanisms that regulate metastasis in HCC is known hampers the development of anti-metastatic therapies. Currently, there is no effective treatment for HCC once it is progressed to metastatic stage. Therefore, further study to elucidate the molecular mechanism underlying the metastasis of HCC is urgently required for the improvement of HCC treatment. Here, we describes actin gamma smooth muscle 2 (ACTG2) over-express in HCC and demonstrates high-expression of ACTG2 as a promising therapeutic target in HCC metastasis. The use of shRNA to knock-down ACTG2 impaired cells migration and invasion in vitro. Moreover, silencing of ACTG2 causes almost complete inhibition of metastasis in vivo. In contrast, overexpression ACTG2 significantly enforces HCC cells migration and metastasis. Finally, ACTG2 boosts the metastatic potential of HCC cells in a Notch homolog 1 (Notch1) dependent manner. Collectively, our study reveals a critical role of ACTG2 in HCC tumor metastasis, and renders it a novel target for the treatment of HCC.


Assuntos
Actinas/genética , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Receptor Notch1/genética , Actinas/antagonistas & inibidores , Actinas/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Movimento Celular , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Nus , Invasividade Neoplásica , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptor Notch1/metabolismo , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Acta Pharmacol Sin ; 38(7): 1048-1058, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28344324

RESUMO

Diallyl trisulfide (DATS), a garlic organosulfide, has shown excellent chemopreventive potential. Cisplatin (DDP) is widely used to treat solid malignant tumors, but causing serious side effects. In the current study, we attempted to elucidate the chemopreventive mechanisms of DATS in human gastric cancer BGC-823 cells in vitro, and to investigate whether DATS could enhance the anti-tumor efficacy of DDP and improve quality of life in BGC-823 xenograft mice in vivo. Treatment with DATS (25-400 µmol/L) dose-dependently inhibited the viability of BGC-823 cells in vitro with an IC50 of 115.2±4.3 µmol/L after 24 h drug exposure. DATS (50-200 µmol/L) induced cell cycle arrest at G2/M phase in BGC-823 cells, which correlated with significant accumulation of cyclin A2 and B1. DATS also induced BGC-823 cell apoptosis, which was accompanied by the modulation of Bcl-2 family members and caspase cascade activation. In BGC-823 xenograft mice, administration of DATS (20-40 mg·kg-1·d-1, ip) dose-dependently inhibited tumor growth and markedly reduced the number of Ki-67 positive cells in tumors. Interestingly, combined administration of DATS (30 mg·kg-1·d-1, ip) with DDP (5 mg/kg, every 5 d, ip) exhibited enhanced anti-tumor activity with fewer side effects. We showed that treatment of BGC-823 cells with DATS in vitro and in vivo significantly activated kinases such as p38 and JNK/MAPK and attenuated the Nrf2/Akt pathway. This study provides evidence that DATS exerts anticancer effects and enhances the antitumor efficacy of DDP, making it a novel candidate for adjuvant therapy for gastric cancer.


Assuntos
Compostos Alílicos/farmacologia , Antineoplásicos/farmacologia , Cisplatino/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Sulfetos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Proteína Oncogênica v-akt/antagonistas & inibidores , Proteína Oncogênica v-akt/metabolismo , Neoplasias Gástricas/patologia , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Zhongguo Zhong Yao Za Zhi ; 42(8): 1603-1608, 2017 Apr.
Artigo em Zh | MEDLINE | ID: mdl-29071869

RESUMO

Under the traditional processing theory "wine processing could promote the efficacy", Rhubarb after wine processing could treat the upper energizer diseases such as red swelling, and breath sores. Processing changes the medicinal properties of rhubarb, and thus results in different focuses in clinical application. In this study, a sensitive and specific method was developed for the determination of aloe-emodin, rhein and emodin in rats tissue. Rhubarb raw materials and its wine processed decoction were given to SD rats respectively by gavage administration, and then the contents of aloe-emodin, rhein and emodin in the tissues (heart, lung, brain, liver, kidney) were determined by HPLC-MS to explore the effect of wine processing on free anthraquinones in rat tissues. Experimental results showed that wine processing can significantly change the distribution of aloe emodin, rhein and emodin in rats in vivo, and the distribution of these components was increased in heart and lung tissues.There was no significant change of distribution in the liver and the kidney as compared with raw product group, and these three ingredients were not detected in the brain, indicating that aloe-emodin, rhein, emodin can not pass through the blood brain barrier.Therefore, wine processing had greater effect on distribution of free anthraquinones in rat tissues.This also verified the theory of traditional Chinese medicine, providing experimental basis for rhubarb processing mechanism.


Assuntos
Antraquinonas/farmacocinética , Emodina/farmacocinética , Rheum/química , Animais , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual , Vinho
16.
Appl Microbiol Biotechnol ; 100(5): 2417-27, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26549238

RESUMO

The feasibility of the anaerobic ammonium oxidation (anammox) process to treat synthetic swine wastewater containing antibiotics and heavy metals was studied in this work. Nitrogen removal performance and granule characteristics were tracked by continuous-flow monitoring to evaluate the long-term joint effects of Cu and Zn and of Cu and oxytetracycline (OTC). Cu and Zn with a joint loading rate (JLR) of 0.04 kg m(-3) day(-1) did not affect the performance, while a JLR of 0.12 kg m(-3) day(-1) caused a rapid collapse in performance. Cu and OTC addition with a JLR of 0.04 kg m(-3) day(-1) for approximately 2 weeks induced significant nitrite accumulation. Granule characteristic analysis elucidated the disparate inhibition mechanisms of heavy metals and antibiotics: the internalization of heavy metals caused metabolic disorders, whereas OTC functioned as a growth retarder. However, anammox reactors could adapt to a JLR of 0.04 kg m(-3) day(-1) via self-regulation during the acclimatization to subinhibitory concentrations, which had a stable nitrogen removal rate (>8.5 kg m(-3) day(-1)) and removal rate efficiency (>75 %) for reactors with Cu-OTC addition. Therefore, this study supports the great potential of using anammox granules to treat swine wastewater.


Assuntos
Amônia/metabolismo , Antibacterianos/metabolismo , Metais Pesados/metabolismo , Consórcios Microbianos/efeitos dos fármacos , Águas Residuárias/microbiologia , Anaerobiose , Animais , Oxirredução , Suínos , Tempo , Purificação da Água
17.
Appl Microbiol Biotechnol ; 100(10): 4637-49, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26780355

RESUMO

Preserving active anaerobic ammonium oxidation (anammox) biomass is a potential method for securing sufficient seeding biomass for the rapid start-up of full-scale anammox processes. In this study, anammox granules were cultured in an upflow anaerobic sludge blanket (UASB) reactor (R0), and then the enriched anammox granules were preserved at 35, 20, 4, and -30 °C. The subsequent reactivation characteristics of the granules were evaluated in four UASB reactors (denoted R1, R2, R3, and R4, respectively) to investigate the effect of preservation temperature on the characteristics of anammox granules and their reactivation performance. The results demonstrated that 4 °C was the optimal preservation temperature for maintaining the biomass, activity, settleability, and integrity of the anammox granules and their cellular structures. During the preservation period, a first-order exponential decay model may be used to simulate the decay of anammox biomass and activity. The protein-to-polysaccharide ratio in the extracellular polymeric substances and the heme c content could not effectively indicate the changes in settleability and activity of the anammox granules, respectively, and a loss of bioactivity was positively associated with the degree of anaerobic ammonium-oxidizing bacteria cell lysis. After 42 days of storage, the anammox granules preserved at 4 °C (R3) exhibited a better recovery performance than those preserved at 20 °C (R2), -30 °C (R4), and 35 °C (R1). The comprehensive comparison indicated that 4 °C is the optimal storage temperature for anammox granular sludge because it promotes improved maintenance and recovery performance properties.


Assuntos
Compostos de Amônio/química , Bactérias Anaeróbias/metabolismo , Esgotos/microbiologia , Temperatura , Anaerobiose , Biodegradação Ambiental , Biomassa , Reatores Biológicos , Microbiologia Industrial , Modelos Teóricos
18.
Endocr Res ; 39(1): 34-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23772656

RESUMO

UNLABELLED: Abstract Introduction: To test whether genetic variants of osteoprotegerin gene (TNFRSF11B) affect metabolic traits (body mass index [BMI], glucose, triglyceride, total cholesterol) and bone mass traits. METHODS: We conducted a population based association study to investigate associations of eight tagging single nucleotide polymorphisms (tSNPs) of the TNFRSF11B gene with the aforementioned traits in a Chinese Han population and an ethnic group admixed with Caucasians and Asians - Uyghur. The associations between the tSNPs and bone mass density (BMD) were also tested in Han population. RESULTS: We found that SNP rs3102727, located in the first intron of the TNFRSF11B gene, was significantly associated with triglyceride levels in Uyghur population and Han population simultaneously. T allele of the rs3102727 variant was associated with a 0.10 mmol/L and 0.09 mmol/L lower level of triglyceride than C allele in Uyghur (p = 0.019) and Han subjects (p = 0.037), respectively. In addition, the T allele is also associated with a lower level of hip BMD (p = 0.025) and total BMD (p = 0.048). Further, we found significant associations between SNP rs11573869 and BMI in Uyghur subjects and SNP rs3134062 with hip BMD in Han sbujects. Rs11573869-T allele was associated with a 0.81 kg/m(2) lower level of BMI than C allele (p = 0.002) and the hip BMD decreases with the copy of rs3134062-T allele increases (p = 0.002). CONCLUSION: We detected novel associations between TNFRSF11B polymorphisms and metabolic traits in Uyghur and Han populations. In addition, we found associations between TNFRSF11B polymorphisms and bone mass traits in Han population.


Assuntos
Povo Asiático/genética , Glicemia/genética , Densidade Óssea/genética , Metabolismo Energético/genética , Osteoprotegerina/genética , Polimorfismo de Nucleotídeo Único , Alelos , Índice de Massa Corporal , China , Frequência do Gene , Estudos de Associação Genética , Humanos , Triglicerídeos/sangue
19.
World J Gastrointest Surg ; 16(2): 628-634, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38463361

RESUMO

BACKGROUND: Collision tumors involving the small intestine, specifically the combination of a hamartomatous tumor and a lipoma, are extremely rare. To our knowledge, no previous case report has described a collision tumor composed of two benign tumors of different origins in the small intestine. CASE SUMMARY: Here, we present the case of an 82-year-old woman who presented with hemorrhagic shock and was found to have a mass measuring approximately 50 mm × 32 mm × 30 mm in the terminal ileum. Based on computed tomography scan findings, the mass was initially suspected to be a lipoma. A subsequent colonoscopy revealed a pedunculated submucosal elevation consisting of two distinct parts with a visible demarcation line. A biopsy of the upper portion suggested a juvenile polyp (JP). Owing to the patient's advanced age, multiple comorbidities, and poor surgical tolerance, a modified endoscopic submucosal dissection was performed. Histopathological examination of the excised mucosal mass revealed a lipoma at the base and a JP at the top, demonstrating evidence of rupture and associated bleeding. The patient's overall health remained satisfactory, with no recurrence of hematochezia during the six-month follow-up period. CONCLUSION: This case report provides new evidence for the understanding of gastrointestinal collision tumors, emphasizing their diverse clinical presentations and histopathological characteristics. It also offers diagnostic and therapeutic insights as well as an approach for managing benign collision tumors.

20.
Opt Express ; 21(24): 30030-8, 2013 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-24514553

RESUMO

The plasmonic resonance effect on metasurfaces generates an abrupt phase change. We employ this phase modulation mechanism to design the longitudinal field distribution of an ultrathin terahertz (THz) lens for achieving the axial long-focal-depth (LFD) property. Phase distributions of the designed lens are obtained by the Yang-Gu iterative amplitude-phase retrieval algorithm. By depositing a 100 nm gold film on a 500 µm silicon substrate and etching arrayed V-shaped air holes through the gold film, the designed ultrathin THz lens is fabricated by the micro photolithography technology. Experimental measurements have demonstrated its LFD property, which basically agree with the theoretical simulations. In addition, the designed THz lens possesses a good LFD property with a bandwidth of 200 GHz. It is expected that the designed ultrathin LFD THz lens should have wide potential applications in broadband THz imaging and THz communication systems.


Assuntos
Lentes , Membranas Artificiais , Nanotecnologia/instrumentação , Radiação Terahertz , Desenho de Equipamento , Análise de Falha de Equipamento
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