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1.
J Endocrinol Invest ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568373

RESUMO

BACKGROUND AND PURPOSE: Asprosin was discovered as a new endocrine hormone originating from fibrillin-1 cleavage that plays a crucial role in various metabolic-related diseases, such as obesity, nonalcoholic fatty liver disease (NAFLD), diabetes, polycystic ovary syndrome (PCOS), and cardiovascular diseases. The purpose of this review is to describe the recent advancements of asprosin. METHOD: Narrative review. RESULT: This comprehensive review explores its tissue-specific functions, focusing on white adipose tissue, liver, hypothalamus, testis, ovary, heart, pancreas, skeletal muscle, and kidney. CONCLUSION: Asprosin is a multifaceted protein with tissue-specific roles in various physiological and pathological processes. Further research is needed to fully understand the mechanisms and potential of asprosin as a therapeutic target. These insights could provide new directions for treatments targeting metabolic-related diseases.

2.
Clin Radiol ; 78(11): e847-e855, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37607844

RESUMO

AIM: To explore the value of radiomics analysis in preoperatively predicting visceral pleural invasion (VPI) of lung adenocarcinoma (LAC) with ≤3 cm maximum diameter and to compare the performance of two-dimensional (2D) and three-dimensional (3D) computed tomography (CT) radiomics models. MATERIALS AND METHODS: A total of 391 LAC patients were enrolled retrospectively, of whom 142 were VPI (+) and 249 were VPI (-). Radiomics features were extracted from 2D and 3D regions of interest (ROIs) of tumours in CT images. 2D and 3D radiomics models were developed combining the optimal radiomics features by using the logistic regression machine-learning method and radiomics scores (rad-scores) were calculated. Nomograms were constructed by integrating independent risk factors and rad-scores. The performance of each model was evaluated by using the receiver operator characteristic (ROC) curve, decision curve analysis (DCA), clinical impact curve (CIC), and calculating the area under the curve (AUC). RESULTS: There was no difference in the VPI prediction between 2D and 3D radiomics models (training group: 2D AUC=0.835, 3D AUC=0.836, p=0.896; validation group: 2D AUC=0.803, 3D AUC=0.794, p=0.567). The 2D and 3D nomograms performed similarly regarding discrimination (training group: 2D AUC=0.867, 3D AUC=0.862, p=0.409, validation group: 2D AUC=0.835, 3D AUC=0.827, p=0.558), and outperformed their corresponding radiomics models and the clinical model. DCA and CIC revealed that the 2D nomogram had slightly better clinical utility. CONCLUSION: The 2D radiomics model has a similar discrimination capability compared with the 3D radiomics model. The 2D nomogram performs slightly better for individual VPI prediction in LAC.

3.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(5): 583-589, 2022 May 06.
Artigo em Chinês | MEDLINE | ID: mdl-35644971

RESUMO

Objective: To explore the role of parental reproductive age on the risk of overweight and obesity in offspring. Methods: The participants were derived from physical examination data of students aged 6-18 years in seven provinces in China, and questionnaire survey was used to collect demographic characteristics and lifestyle information of the students and their parents. A total of 41 567 children with complete data were included. According to the restricted cubic spline curve, maternal reproductive age was divided into three categories, 14-23, 24-28, and 29-38 years, and paternal reproductive age was divided into 14-23, 24-30, and 31-42 years. Multivariate logistic regression model was used to analyze the association between parental reproductive age and parental nutritional status and the risk of overweight and obesity in offspring. Results: The mean age of 41 567 children was (10.6±3.2) years, and the mean paternal and maternal age were (27.9±4.4) years and (25.8±4.0) years, respectively. The detection rate of overweight and obesity was 23.4%. After adjusting factors of children diet and behaviors, the OR(95%CI)of offspring overweight and obesity in groups of fathers aged 24-30 years and mothers aged 24-28 years was 1.11 (1.04-1.18) and 1.16 (1.08-1.24), respectively. When none parents were overweight and obese, the difference of obesity risk was not statistically significant. When both parents were overweight and obese, the OR(95%CI)of offspring overweight and obesity in groups of fathers aged 24-30 years and mothers aged 14-28 years old was 1.27 (1.00-1.62) and 1.33 (1.07-1.65) respectively. Conclusion: Parental reproductive age and parental overweight and obesity status may both increase the risk of overweight and obesity in offspring, with a significant interaction effect.


Assuntos
Obesidade , Sobrepeso , Adolescente , Adulto , Criança , Pai , Feminino , Humanos , Masculino , Mães , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Fatores de Risco , Adulto Jovem
4.
Zhonghua Xin Xue Guan Bing Za Zhi ; 49(9): 873-879, 2021 Sep 24.
Artigo em Chinês | MEDLINE | ID: mdl-34530594

RESUMO

Objective: This analysis was performed to evaluate the efficacy and the safety of rivaroxaban-aspirin combination therapy in secondary prevention of major adverse cardiovascular events in Chinese patients enrolled in the COMPASS trial. Methods: COMPASS was a prospective, international multi-center and randomized controlled trial. From September 2014 to February 2017, 1 086 patients with stable coronary artery disease and peripheral artery diseases were recruited from 31 centers in China. Patients were randomly assigned to separately receive the therapy of rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day,) group (n=366), rivaroxaban (5 mg twice a day) alone group (n=365), and aspirin (100 mg once a day) alone group (n=355). Baseline information such as age, sex, etc. of all three groups was collected. Finally, 1 081 patients were followed up successfully, with the follow-up rate 99.5% and the average follow-up time was 19 months. The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction and stroke. The primary safety endpoint was major bleeding evaluated by modified International Society on Thrombosis and Haemostasis criteria. Results: Age of patients was (64.2±8.3) years and there were 293 male in rivaroxaban plus aspirin group. Age of patients was (63.8±9.0) years, and there were 301 male patients in rivaroxaban alone group. Age of patients was (63.6±8.8) years, and there were 282 male patients in the aspirin alone group. The incidences of primary efficacy endpoint occurred in 9 cases (1.5%) in rivaroxaban with aspirin group, 21 cases (3.7%) in rivaroxaban alone group and 14 cases (2.5%) in aspirin alone group. Meanwhile, the incidences of primary safety endpoint occurred in 6 cases (1.0%) in rivaroxaban with aspirin group, 9 cases (1.6%) in rivaroxaban alone group and 7 cases (1.2%) in aspirin alone group. The net clinical benefit events were 10 cases (1.7%) in rivaroxaban with aspirin group, 22 cases (3.9%) in rivaroxaban alone group and 15 cases (2.7%) in aspirin alone group (P>0.5%). Conclusions: The combination of rivaroxaban with aspirin can be safe and effectively used for the secondary prevention in Chinese patients with stable coronary artery disease and peripheral artery diseases.


Assuntos
Doenças Cardiovasculares , Rivaroxabana , Idoso , Aspirina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , China , Quimioterapia Combinada , Inibidores do Fator Xa/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Prospectivos , Rivaroxabana/uso terapêutico , Prevenção Secundária
5.
Infect Dis Poverty ; 10(1): 30, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731226

RESUMO

The ongoing coronavirus disease 2019 (COVID-19) pandemic has put a strain on health systems globally. Although Africa is the least affected region to date, it has the weakest health systems and an exponential rise in cases as has been observed in other regions, is bound to overwhelm its health systems. Early detection and isolation of suspected and confirmed COVID-19 cases are pivotal to the prevention and control of the pandemic. The World Health Organization (WHO) recommends that all laboratory-confirmed cases should be isolated and treated in a health care facility; however, where this is not possible due to the health system capacity, patients can be isolated in re-purposed facilities or at home. An already very apparent future challenge for Africa is facility-based isolation of COVID-19 cases, given the already limited health infrastructure and health workforce, and the risk of nosocomial transmission. Use of repurposed facilities requires additional resources, including health workers. Home isolation, on the other hand, would be a challenge given the poor housing, overcrowding, inadequate access to water and sanitation, and stigma related to infectious disease that is prevalent in many African societies. Conflict settings on the continent pose an additional challenge to the prevention and control of COVID-19 with the resultant population displacements in overcrowded camps where access to social services is limited. These unique cultural, social, economic and developmental differences on the continent, call for a tailored approach to COVID-19 case management strategies. This article proposes three broad case management strategies based on the transmission scenarios defined by WHO, and the criteria and package of care for each option, for consideration by policy makers and governments in African countries. Moving forward, African countries should generate local evidence to guide the development of realistic home-grown strategies, protocol and equipment for the management of COVID-19 cases on the continent .


Assuntos
COVID-19/epidemiologia , COVID-19/virologia , Administração de Caso , SARS-CoV-2 , África/epidemiologia , América/epidemiologia , Ásia/epidemiologia , COVID-19/diagnóstico , COVID-19/terapia , Atenção à Saúde , Gerenciamento Clínico , Europa (Continente)/epidemiologia , Pesquisas sobre Atenção à Saúde , Humanos
6.
J Endocrinol Invest ; 44(8): 1753-1765, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33423221

RESUMO

PURPOSE: Evidence is accumulating that lipocalin2 (LCN2) is implicated in insulin resistance and glucose homeostasis, but the underlying possible mechanisms remain unclear. This study is to investigate the possible linkage between LCN2 and AMP-activated protein kinase (AMPK) or forkhead transcription factor O1 (FoxO1), which influences insulin sensitivity and gluconeogenesis in liver. METHODS: LCN2 knockout (LCN2KO) mice and wild-type littermates were used to evaluate the effect of LCN2 on insulin sensitivity and hepatic gluconeogenesis through pyruvate tolerance test (PTT), glucose tolerance test (ipGTT), insulin tolerance test (ITT), and hyperinsulinemic-euglycemic clamps, respectively. LCN2KO mice and WT mice in vivo, and in vitro HepG2 cells were co-transfected with adenoviral FoxO1-siRNA (Ad-FoxO1-siRNA) or adenovirus expressing constitutively active form of AMPK (Ad-CA-AMPK), or dominant negative adenovirus AMPK (Ad-DN-AMPK), the relative mRNA and protein levels of two key gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6P) were measured. RESULTS: Improved insulin sensitivity and inhibited gluconeogenesis in the LCN2KO mice were confirmed by pyruvate tolerance tests and hyperinsulinemic-euglycemic clamps. Nuclear FoxO1 and its downstream genes PEECK and G6P were decreased in the livers of the LCN2KO mice, and AMPK activity was stimulated and directly phosphorylated FoxO1. In vitro, AMPK activity was inhibited in HepG2 cells overexpressing LCN2 leading to a decrease in phosphorylated FoxO1 and an increase in nuclear FoxO1. CONCLUSION: The present study demonstrates that LCN2 regulates insulin sensitivity and glucose metabolism through inhibiting AMPK activity, and regulating FoxO1 and its downstream genes PEPCK/G6P, which regulate hepatic gluconeogenesis.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Proteína Forkhead Box O1/metabolismo , Gluconeogênese/fisiologia , Lipocalina-2/genética , Fígado/metabolismo , Animais , Glucose/metabolismo , Células Hep G2 , Humanos , Resistência à Insulina , Lipocalina-2/metabolismo , Camundongos , Camundongos Knockout , Fosforilação
7.
Braz. j. biol ; 80(4): 790-797, Oct.-Dec. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1142527

RESUMO

Abstract Ginkgo biloba is a traditional Chinese herbal medicine containing multiple components that contribute to its notable bioactivities. Variations of seasonal, meteorological and planting soil on the phytochemicals contents in G. biloba leaves due to the effects of growth meteorological and soil parameters were investigated in this study. The leaves of G. biloba were collected from different months and place in Zhejiang province, the contents of flavones (quercetin, kaempferol and isorhamnetin) and terpene lactones (bilobalide, ginkgolides A, B and C) were quantified by high performance liquid chromatography (HPLC) and the evaporative light scattering detector (ELSD) method. The established methods were validated with good linearity, precision, repeatability, stability, and recovery. Comprehensive analysis suggested the proper harvest time for G. biloba was in October of Zhejiang province. The result of correlation analysis with meteorological factors shows that the temperature and precipitation have non-significant effect on the main components of G. biloba. In addition, the type and content (Mn and Zn) of the soil showed significantly effect on the content of flavonoids and terpene lactones. This study enriched the knowledge on the development and utilization value of the G. biloba leaves and was useful for determining the optimal harvest time and growing condition.


Resumo Ginkgo biloba é um fitoterápico tradicional da medicina chinesa que contém vários componentes que contribuem para suas notáveis bioatividades. Variações sazonais, meteorológicos e de plantio do solo sobre os teores fitoquímicos em folhas de G. biloba, devido aos efeitos do crescimento meteorológico e parâmetros do solo, foram investigadas neste estudo. As folhas de G. biloba foram coletadas em diferentes meses e na província de Zhejiang, os teores de flavonas (quercetina, kaempferol e isorhamnetina) e lactonas terpênicas (bilobalida, ginkgolídeos A, B e C) foram quantificados por Cromatografia Líquida de Alta Eficiência (CLAE) e pelo método do detector de dispersão da luz por evaporação. Os métodos estabelecidos foram validados com boa linearidade, precisão, repetibilidade, estabilidade e recuperação. Uma análise abrangente sugeriu que o tempo de colheita adequado para G. biloba foi em outubro na província de Zhejiang. O resultado da análise de correlação com fatores meteorológicos mostra que a temperatura e a precipitação não têm efeito significativo sobre os principais componentes de G. biloba. Além disso, o tipo e composição (Mn e Zn) do solo apresentaram efeito significativo sobre o teor de flavonoides e lactonas terpênicas. Este estudo enriqueceu o conhecimento sobre o valor de desenvolvimento e utilização das folhas de G. biloba e foi útil para determinar o melhor tempo de colheita e condição de crescimento.


Assuntos
Solo , Ginkgo biloba , Estações do Ano , Extratos Vegetais , Cromatografia Líquida de Alta Pressão , Folhas de Planta
8.
Zhonghua Bing Li Xue Za Zhi ; 49(7): 710-714, 2020 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-32610383

RESUMO

Objective: To investigate the clinicopathologic and immunophenotypic features of metastatic gastrointestinal hepatoid adenocarcinomas in the liver. Methods: Eight cases of hepatic metastatic gastrointestinal hepatoid adenocarcinoma diagnosed at the Affiliated Drum Tower Hospital, Nanjing University Medical School from January 2009 to January 2019 were retrospectively analyzed. The clinical data, histopathologic features and immunohistochemical (IHC) characteristics performed by EnVision method were analyzed. Results: There were five males and three females with a mean age of 66 years. The primary sites included one case each from the distal esophagus and the right colon, and the other six cases were from the stomach. Pre-treatment serum AFP levels were increased in four patients, normal in two, and was not known in two other patients. Liver metastases occurred in all eight patients at initial diagnosis. Microscopically, the primary tumor was composed of areas showing hepatic differentiation with or without typical adenocarcinoma component; and the areas with hepatic differentiation morphologically resembled hepatocellular carcinoma (HCC). IHC staining showed variable expression of HCC markers such as Glypican 3, AFP, SALL4 and HepPar-1, and gastrointestinal adenocarcinoma markers such as CK19, CDX-2 and Villin in both the primary and metastatic foci of hepatoid adenocarcinoma. Conclusions: Hepatoid adenocarcinoma in the digestive tract gives rise to only non-specific symptoms, and shows high propensity for invasion and metastasis. When liver metastasis is the presenting symptom, it is difficult to distinguish metastatic hepatoid adenocarcinoma from the primary HCC based on histopathologic characteristics alone. The accurate diagnosis of metastatic hepatoid adenocarcinoma in the liver requires combination of clinical, radiologic, histopathologic and IHC findings.


Assuntos
Adenocarcinoma , Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Biomarcadores Tumorais , Feminino , Neoplasias Gastrointestinais , Humanos , Imuno-Histoquímica , Masculino , Estudos Retrospectivos , alfa-Fetoproteínas
9.
Braz J Biol ; 80(4): 790-797, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31800764

RESUMO

Ginkgo biloba is a traditional Chinese herbal medicine containing multiple components that contribute to its notable bioactivities. Variations of seasonal, meteorological and planting soil on the phytochemicals contents in G. biloba leaves due to the effects of growth meteorological and soil parameters were investigated in this study. The leaves of G. biloba were collected from different months and place in Zhejiang province, the contents of flavones (quercetin, kaempferol and isorhamnetin) and terpene lactones (bilobalide, ginkgolides A, B and C) were quantified by high performance liquid chromatography (HPLC) and the evaporative light scattering detector (ELSD) method. The established methods were validated with good linearity, precision, repeatability, stability, and recovery. Comprehensive analysis suggested the proper harvest time for G. biloba was in October of Zhejiang province. The result of correlation analysis with meteorological factors shows that the temperature and precipitation have non-significant effect on the main components of G. biloba. In addition, the type and content (Mn and Zn) of the soil showed significantly effect on the content of flavonoids and terpene lactones. This study enriched the knowledge on the development and utilization value of the G. biloba leaves and was useful for determining the optimal harvest time and growing condition.


Assuntos
Ginkgo biloba , Solo , Cromatografia Líquida de Alta Pressão , Extratos Vegetais , Folhas de Planta , Estações do Ano
10.
Eur Rev Med Pharmacol Sci ; 22(5): 1358-1365, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29565494

RESUMO

OBJECTIVE: We investigated the expression of human long non-coding ribonucleic acid (lncRNA), BRAF-activated non-coding RNA (BANCR) in breast cancer tissues and its effects on the in vitro proliferation, apoptosis, invasion and metastasis of breast cancer cells; also, we investigated its possible mechanism. PATIENTS AND METHODS: The expressions of BANCR in 65 pairs of breast cancer tissues and para-carcinoma normal breast tissues were detected by Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The expressions of BANCR in normal breast epithelial cells (MCF10A) and breast cancer cells (MCF-7, MDA-MB-231, SKBR3 and BT-20) were further detected. The knockdown efficiency of BANCR small interfering RNA (siRNA) in MCF-7 cells was detected by qRT-PCR. The effects of BANCR knockdown on proliferation, apoptosis, invasion and metastasis capacities of MCF-7 cells were explored via methyl thiazolyl tetrazolium (MTT) proliferation assay, cell colony formation assay, fluorescence-activated cell sorting (FACS) and transwell migration assay. Western blotting was used to detect the changes in expressions of apoptosis-related proteins, epithelial-mesenchymal transition (EMT)-related proteins and matrix metalloproteinases (MMPs) after knockdown of BANCR. RESULTS: The expression level of lncRNA BANCR in breast cancer tissues was significantly higher than that in para-carcinoma normal tissues. The prognosis of patients in low-expression BANCR group was significantly superior to that of patients in high-expression BANCR group. After BANCR knockdown in breast cancer MCF-7 cells, the cell proliferation and colony formation capacities were significantly inhibited. Further mechanism research showed that inhibiting BANCR could promote the apoptosis of MCF-7 cells. Results of Western blotting revealed that the expressions of B-cell lymphoma 2 associated X protein (BAX), cleaved-Caspase-3 and cleaved-poly adenosine diphosphate-ribose polymerase (PARP) in knockdown group were significantly up-regulated compared with those in control group. Both wound-healing assay and transwell migration assay showed that the down-regulation of lncRNA BANCR could inhibit the invasion and metastasis capacities of MCF-7 cells, whose mechanism was related to the inhibition of EMT process and down-regulation of MMP expressions in cells. CONCLUSIONS: LncRNA BANCR is highly expressed in breast cancer, which is significantly correlated with the prognosis of patients; moreover, it can promote the growth, invasion and metastasis of ovarian cancer cells. The down-regulation of BANCR can inhibit the proliferation, invasion and metastasis capacities of MCF-7 cells.


Assuntos
Neoplasias da Mama/patologia , Proliferação de Células , RNA Longo não Codificante/metabolismo , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Metaloproteinase 2 da Matriz/metabolismo , Pessoa de Meia-Idade , Poli(ADP-Ribose) Polimerases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Proteína X Associada a bcl-2/metabolismo
11.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1467368

RESUMO

Abstract Ginkgo biloba is a traditional Chinese herbal medicine containing multiple components that contribute to its notable bioactivities. Variations of seasonal, meteorological and planting soil on the phytochemicals contents in G. biloba leaves due to the effects of growth meteorological and soil parameters were investigated in this study. The leaves of G. biloba were collected from different months and place in Zhejiang province, the contents of flavones (quercetin, kaempferol and isorhamnetin) and terpene lactones (bilobalide, ginkgolides A, B and C) were quantified by high performance liquid chromatography (HPLC) and the evaporative light scattering detector (ELSD) method. The established methods were validated with good linearity, precision, repeatability, stability, and recovery. Comprehensive analysis suggested the proper harvest time for G. biloba was in October of Zhejiang province. The result of correlation analysis with meteorological factors shows that the temperature and precipitation have non-significant effect on the main components of G. biloba. In addition, the type and content (Mn and Zn) of the soil showed significantly effect on the content of flavonoids and terpene lactones. This study enriched the knowledge on the development and utilization value of the G. biloba leaves and was useful for determining the optimal harvest time and growing condition.


Resumo Ginkgo biloba é um fitoterápico tradicional da medicina chinesa que contém vários componentes que contribuem para suas notáveis bioatividades. Variações sazonais, meteorológicos e de plantio do solo sobre os teores fitoquímicos em folhas de G. biloba, devido aos efeitos do crescimento meteorológico e parâmetros do solo, foram investigadas neste estudo. As folhas de G. biloba foram coletadas em diferentes meses e na província de Zhejiang, os teores de flavonas (quercetina, kaempferol e isorhamnetina) e lactonas terpênicas (bilobalida, ginkgolídeos A, B e C) foram quantificados por Cromatografia Líquida de Alta Eficiência (CLAE) e pelo método do detector de dispersão da luz por evaporação. Os métodos estabelecidos foram validados com boa linearidade, precisão, repetibilidade, estabilidade e recuperação. Uma análise abrangente sugeriu que o tempo de colheita adequado para G. biloba foi em outubro na província de Zhejiang. O resultado da análise de correlação com fatores meteorológicos mostra que a temperatura e a precipitação não têm efeito significativo sobre os principais componentes de G. biloba. Além disso, o tipo e composição (Mn e Zn) do solo apresentaram efeito significativo sobre o teor de flavonoides e lactonas terpênicas. Este estudo enriqueceu o conhecimento sobre o valor de desenvolvimento e utilização das folhas de G. biloba e foi útil para determinar o melhor tempo de colheita e condição de crescimento.

12.
Nat Cell Biol ; 14(10): 1089-98, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23000965

RESUMO

Protein ubiquitylation has emerged as a key regulatory mechanism in DNA-damage signalling and repair pathways. We report a proteome-wide, site-specific survey of ubiquitylation changes after ultraviolet irradiation, identifying numerous upregulated and downregulated ubiquitylation sites on known components of DNA-damage signalling, as well as on proteins not previously implicated in this process. Our results uncover a critical role for PCNA-associated factor PAF15 (p15(PAF)/KIAA0101) ubiquitylation during DNA replication. During unperturbed S phase, chromatin-associated PAF15 is modified by double mono-ubiquitylation of Lys 15 and 24 templated through PCNA binding. Replication blocks trigger rapid, proteasome-dependent removal of Lys 15/24-ubiquitylated PAF15 from PCNA, facilitating bypass of replication-fork-blocking lesions by allowing recruitment of translesion DNA synthesis polymerase polη to mono-ubiquitylated PCNA at stalled replisomes. Our findings demonstrate widespread involvement of ubiquitin signalling in genotoxic-stress responses and identify a critical function for dynamic PAF15 ubiquitylation in safeguarding genome integrity when DNA replication is challenged.


Assuntos
Proteínas de Transporte/metabolismo , Dano ao DNA/fisiologia , Reparo do DNA/fisiologia , Ubiquitinação , Raios Ultravioleta/efeitos adversos , Linhagem Celular , Replicação do DNA/fisiologia , Proteínas de Ligação a DNA , DNA Polimerase Dirigida por DNA/metabolismo , Humanos , Lisina/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Fase S/fisiologia , Transdução de Sinais/fisiologia
13.
Oncogene ; 30(39): 4107-17, 2011 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-21499297

RESUMO

In an earlier study we showed that C10ORF97 (chromosome-10, open reading frame-97) was expressed in almost all of the tissues and cell lines tested, and that it inhibited the growth of seven tumor cell lines, including two lung carcinoma cell lines (A549 and PG). Here, we show that C10ORF97 is downregulated in non-small-cell lung cancer (NSCLC) tissue compared with normal lung tissue. Overexpression of C10ORF97 significantly suppressed human lung carcinoma A549 cell growth (proliferation and anchorage-independent growth in soft agar) and motility (migration and adhesion). This tumor-suppressive function of C10ORF97 was also verified in vivo. We further found that C10ORF97 caused G(1) arrest of A549 cells and modulated the expression level of several cell-cycle regulators (such as CDK2, cyclin-E and p27). These effects of C10ORF97 were mediated by physical association between C10ORF97 and Jun-activating domain-binding protein-1 (JAB1), and blocking of JAB1-mediated translocation of p27 from the nucleus to the cytoplasm. Together, these results indicated that C10ORF97 functions as a novel tumor suppressor by modulating several key G(1)/S-regulatory proteins by interacting with JAB1. These findings led us to hypothesize that a single-nucleotide polymorphism (SNP) in the C10ORF97 gene that affects its expression might be associated with susceptibility to NSCLC. SNP216 C>T (rs2297882) in the C10ORF97 Kozak sequence was identified, and allele T of SNP216 suppressed C10ORF97 expression in vitro and in vivo. Furthermore, the TT genotype of SNP216 was associated with an increased risk of NSCLC (adjusted odds ratio=1.73 (95% confidence interval: 1.33-2.25), P=4.6 × 10(-5)). These data indicated that C10ORF97 is a tumor suppressor of NSCLC progression and C10ORF97-SNP216 may serve as a predictor of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Genes Supressores de Tumor , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Pulmonares/genética , Peptídeo Hidrolases/metabolismo , Proteínas Supressoras de Tumor/genética , Idoso , Animais , Complexo do Signalossomo COP9 , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Ciclo Celular/genética , Proteínas de Ciclo Celular/biossíntese , Linhagem Celular Tumoral , Proliferação de Células , Ciclina E/biossíntese , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Proteínas Nucleares , Polimorfismo de Nucleotídeo Único , Transporte Proteico , Proteínas Supressoras de Tumor/metabolismo
14.
J Matern Fetal Neonatal Med ; 16(3): 167-70, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15590443

RESUMO

OBJECTIVE: To compare cervical length measurements obtained by transvaginal two-dimensional (2D) and transvaginal three-dimensional (3D) ultrasound. STUDY DESIGN: Thirty-four consecutive women having transvaginal assessment of cervical length as part of an obstetric ultrasound examination consented to have a 3D ultrasound scan. The cervical lengths obtained by the two methods were compared by Student's t test and regression equations. RESULTS: The mean cervical 2D length was 35.7 +/- 1.4 (SE) mm and 3D length was 43.7 +/- 1.9 mm (difference 8.0 mm +/- 0.98, p < 0.001). In the 12 women with cervical length on 2D < 35 mm, there was a 7.5 +/- 1.7 (SE) mm difference (p = 0.007). In all but one woman the 3D length obtained was the same or longer than the 2D length. The longer the cervical length on 3D imaging, the greater the difference from the 2D length (p < 0.001). CONCLUSION: The longer 3D cervical measurements may reflect the inability to measure the cervix adequately with 2D imaging, owing to anatomical factors. This finding may be useful in improving the predictive value of transvaginal ultrasound in assessing the risk for preterm delivery.


Assuntos
Colo do Útero/diagnóstico por imagem , Imageamento Tridimensional , Ultrassonografia Pré-Natal , Feminino , Humanos , Trabalho de Parto Prematuro/etiologia , Valor Preditivo dos Testes , Gravidez , Medição de Risco
15.
J Oral Rehabil ; 30(10): 978-84, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12974856

RESUMO

The present study applied a standardized test food of known hardness to evaluate the biting performance of 20 female patients who had pain mainly in the masseter muscle during palpation. Another 20 women of a similar age group who were pain-free during examination served as controls. Electromyograms (EMG) of the masseter and sternocleidomastoid (SCM) muscles and the jaw position were recorded and measured when the subjects were biting through two types of test foods with known hardness (hard type, 20 kg hardness and extra-hard type, 60 kg hardness). Pressure-pain-threshold (PPT) values of both the patients and the normal subjects were obtained with an algometer. It was found that the PPT of the patients with pain was significantly lower and that the extra-hard food took more masseter muscle activity and more working side jaw movement in both the pain and the normal groups. During both hard and extra-hard food biting, a significantly longer duration of masseter muscle activity was found in pain patients while the total muscle activity was not significantly stronger. Strong correlation existed between SCM and masseter muscle activity during both hard and extra-hard food biting in the patient group, while such correlation was very weak in the normal group. In conclusion, painful masseter muscles required longer masseter and SCM muscle contraction time for breaking through a hard food of 20 kg and more, and co-activation of SCM and masseter muscles existed and was more evident when the food was harder or the pain was more severe.


Assuntos
Força de Mordida , Dor Facial/fisiopatologia , Músculo Masseter/fisiopatologia , Adulto , Análise de Variância , Fenômenos Biomecânicos , Estatura/fisiologia , Peso Corporal/fisiologia , Eletromiografia , Músculos Faciais/fisiopatologia , Dor Facial/etiologia , Feminino , Humanos , Arcada Osseodentária/fisiopatologia , Movimento/fisiologia , Contração Muscular/fisiologia , Síndromes da Dor Miofascial/fisiopatologia , Medição da Dor/métodos , Palpação , Pressão
16.
Recept Channels ; 8(2): 79-85, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12448789

RESUMO

The voltage-sensing domains of voltage-gated potassium channels Kv2.1 (drk1) contain four transmembrane segments in each subunit, termed S1 to S4. While S4 is known as the voltage sensor, the carboxyl terminus of S3 (S3C) bears a gradually broader interest concerning the site for gating modifier toxins like hanatoxin and thus the secondary structure arrangement as well as its surrounding environment. To further examine the putative three-dimensional (3-D) structure of S3C and to illustrate the residues required for hanatoxin binding (which may, in turn, show the influence on the S4 in terms of changes in channel gating), molecular simulations and dockings were performed. These were based on the solution structure of hanatoxin and the structural information from lysine-scanning results for S3C fragment. Our data suggest that several basic and acidic residues of hanatoxin are electrostatically and stereochemically mapped onto their partner residues on S3C helix, whereas some aromatic or hydrophobic residues located on the same helical fragment interact with the hydrophobic patch of the toxin upon binding. Therefore, a slight distortion of the S3C helix, in a direction toward the N-terminus of S4, may exist. Such conformational change of S3C upon toxin binding is presented as a possible explanation for the observed shift in hanatoxin binding-induced gating.


Assuntos
Peptídeos/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio/química , Canais de Potássio/metabolismo , Animais , Sítios de Ligação , Canais de Potássio de Retificação Tardia , Técnicas In Vitro , Ativação do Canal Iônico , Substâncias Macromoleculares , Modelos Moleculares , Peptídeos/química , Conformação Proteica , Subunidades Proteicas , Canais de Potássio Shab , Eletricidade Estática , Termodinâmica
17.
J Gastroenterol Hepatol ; 16(6): 683-8, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11422623

RESUMO

AIM: To investigate the effects of somatostatin analogs (SSa) on apoptosis of pancreatic acinar cells and apoptosis-regulated gene bax, and p53 in treating acute pancreatitis in mice. METHODS: In cerulein-induced pancreatitis, with or without treatment of somatostatin, analogs (Octreotide) in CD-1 (BALB/c x DBetaAlpha/1) mice, apoptosis of pancreatic acinar cells was detected by using the TdT-mediated dUTP nick-end labeling (TUNEL) method, and the expression of apoptosis-regulated gene bax and p53 was determined by using the streptavidin-peroxidase immunohistochemical technique and the RT-PCR method, respectively. RESULTS: On HE staining, acinar cells in the pancreas showed pyknotic nuclei and the formation of apoptotic bodies, which are the typical morphological features of apoptosis. Regarding TUNEL use, the apoptotic index of pancreatic acinar cells in the non-treated group at 5 and 14 h after induction of acute pancreatitis was significantly lower than those of the SSa-treated group, respectively (P < 0.01). On immunohistochemistry and RT-PCR, there was an expression of neither bax nor p53 in normal pancreatic tissues. The expression of bax in the SSa-treated group at 5 and 14 h after treatment of SSa was markedly higher than those of the non-treated group, respectively (P < 0.01), but there was no significant difference in the expression of p53 between the SSa-treated group and the non-treated group. CONCLUSIONS: The induction of apoptosis in pancreatic acinar cells injury to reduce inflammatory reaction might be one of the mechanisms of SSa in treating acute pancreatitis in mice, and the mechanisms of apoptosis probably correlated with the expression of apoptosis-regulated gene bax, but have no relationship with the expression of p53.


Assuntos
Apoptose/efeitos dos fármacos , Hormônios/farmacologia , Octreotida/farmacologia , Pancreatite/patologia , Proteínas Proto-Oncogênicas c-bcl-2 , Doença Aguda , Animais , Apoptose/genética , Ceruletídeo , Feminino , Genes p53 , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos DBA , Octreotida/uso terapêutico , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Proteínas Proto-Oncogênicas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Somatostatina/análogos & derivados , Proteína X Associada a bcl-2
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 18(1): 28-31, 2001 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-11172638

RESUMO

OBJECTIVE: To investigate the relationship between sperm anomalies and chromosomal aberrance and to further understand the pathological changes of anomalous spermatozoa. METHODS: Light and electronic (SEM or TEM) microscopes were used for morphological analysis. Fluorescence in situ hybridization(FISH) with chromosome X-, Y-specific probes were used for aneuploidy detection in sperms of the patient. RESULTS: Ninety eight point seven five per cent of the Papanicolaou stained sperms were observed to be abnormal; 100% of the sperm heads were abnormal, measured under oil objective (1000 times); 60.25% of the sperms had two or more tails (the maximum being eight tails). SEM and TEM demonstrated that the heads contained a large amount of cytoplasmic structure, the surfaces of heads were uneven, the nuclei were of much irregular shape; besides aberrance in quantity, anomalies occurred with centromeres, mitochondria and flagella in the tails. The results of FISH showed that the aneuploidy rate of sex chromosomes was 61.41% which was parallel to the rate of polytails. CONCLUSION: Even though the chromosomes in somatic cells are normal, the chromosomes in anomalous sperms may be abnormal.


Assuntos
Aberrações Cromossômicas , Cromossomos Sexuais , Espermatozoides/anormalidades , Adulto , Aneuploidia , Humanos , Masculino , Espermatozoides/ultraestrutura
19.
20.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 21(6): 433-6, 2001 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-12577439

RESUMO

OBJECTIVE: To investigate the effect and mechanism of emodin on pancreatic repairing and remodeling in treating acute pancreatitis by analyzing the change of cytokine transforming growth factor beta 1(TGF beta 1) gene expression, DNA synthesis and protein content in pancreatic tissue. METHODS: Acute pancreatitis was induced in rats by intraperitoneal infusion of caerulein, treated or untreated by emodin. The animals were sacrificed at 6, 24, 48, 72 or 96 hrs after treatment separately. The mRNA expression of TGF beta 1, DNA synthesis and total protein content in pancreatic tissue were tested by reverse transcription-polymerase chain reaction (RT-PCR), 3H-thymidin method and Lowry's method respectively. RESULTS: Serum amylase level was decreased significantly after emodin treatment. TGF beta 1 mRNA expression was undetectable in the intact pancreas or in 6 hrs after pancreatitis induction in the non-treated group, but revealed at 24 hrs after and reached the peak at 72 hrs later. However, in the emodin treated group, TGF beta 1 mRNA expression was detected at 6 hrs after treatment, with a higher level in 24 hrs and 48 hrs as compared with the non-treated group, and reaching the peak at 48 hrs after treatment. Moreover, the DNA synthesis and total protein content in pancreatic tissue decreased significantly at 72 hrs and 48 hrs after induction respectively, but both parameters increased significantly in the emodin treated group 96 hrs after treatment. CONCLUSION: The mechanism of emodin in treating acute pancreatitis might be by way of enhancing cytokine TGF beta 1 gene expression, regulating cell growth and differentiation, stimulating the formation of extracellular matrix components, increasing DNA synthesis and protein content, and to take part in pancreatic repairing and remodeling.


Assuntos
Emodina/farmacologia , Pâncreas/metabolismo , Pancreatite/metabolismo , Fator de Crescimento Transformador beta/biossíntese , Doença Aguda , Animais , DNA/biossíntese , Masculino , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Distribuição Aleatória , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta/genética
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