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1.
Zhonghua Yu Fang Yi Xue Za Zhi ; 56(12): 1889-1892, 2022 Dec 06.
Artigo em Chinês | MEDLINE | ID: mdl-36536583

RESUMO

Diabetic retinopathy (DR), one of the chronic complications of diabetes, is a serious and irreversible blinding disease. It is difficult to detect in the early stage, to control in the progressive stage, to operate in the advanced stage of DR. Recently, the "14th Five-year plan" for National Eye Health proposed to "improve the management mode of chronic eye disease, and build a chronic disease management system". The project team used artificial intelligence technology based on cloud platform, joint outpatient service, virtual ward to explore the comprehensive management of DR from the aspects of early screening, multidisciplinary collaborative diagnosis and treatment, and refined blood glucose management during perioperative period. In the future, it is urgent to integrate DR chronic disease management with other systemic chronic diseases to reduce the blindness caused by DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Inteligência Artificial , Programas de Rastreamento , Cegueira/complicações , Cegueira/prevenção & controle
2.
Zhonghua Yi Xue Za Zhi ; 102(6): 393-398, 2022 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-35144337

RESUMO

Objective: To explore the effect of neoadjuvant immunotherapy on pulmonary function and the efficacy in patients with resectable non-small cell lung cancer. Methods: Data of 30 patients with non-small cell lung cancer (NSCLC) who received neoadjuvant immunotherapy before surgery in the Chest Hospital of Shanghai Jiaotong University from March 2018 to September 2021 were retrospectively collect. The efficacy and safety of neoadjuvant immunotherapy in the perioperative period and changes in pulmonary function of patients before and after neoadjuvant treatment were valuated. Results: The patients were all-male with age of (61±8)years old, The major pathological response (MPR) rate of patients receiving neoadjuvant immunotherapy was 43%(13 cases), the pathologic complete response (pCR) rate was 37% (11 cases), disease control rate (DCR) was 97% (29 cases), objective response rate (ORR) was 67% (20 cases). The forced expiratory volume in one second (FEV1) after treatment was (2.59±0.63) L, and the ratio of FEV1 to the predicted value (FEV1%pred) was 85.27%±15.86%, which were significantly higher than those before treatment [(2.48±0.59)L, 81.73%±15.94%, respectively] (P=0.013, 0.022, respectively). Forced vital capacity (FVC) after treatment was (3.59±0.77) L, which was also significantly higher than before [(3.47±0.76) L,P=0.036]; while there were no statistical difference in FEV1/FVC and FVC accounted for the proportion of predicted values (FVC%pred) between before and after treatment (P=0.084, 0.344, respectively). The ratio of carbon monoxide dispersion (DLCO) to the predicted value (DLCO%pred) decreased from 83.61%±13.10% to 78.69%±13.85% after treatment (P=0.023). There was no significant difference in the incidence of postoperative complications between the DLCO%pred decreased group and the non-decreased group (3/18 vs 0/6; P=0.546). Conclusions: Neoadjuvant immunotherapy can increase the rate of MPR and PCR, significantly increase FEV1 and FEV1%pred, but also lead to a decrease in DLCO%pred; neoadjuvant immunotherapy does not increase the incidence of postoperative complications.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Carcinoma Pulmonar de Células não Pequenas/terapia , China , Volume Expiratório Forçado , Humanos , Imunoterapia , Pulmão , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Retrospectivos
3.
Rev Sci Instrum ; 92(4): 043519, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34243364

RESUMO

The impurity radiation from the divertor region of the EAST tokamak is dominantly in the wavelength range of vacuum ultraviolet (VUV) due to the elevated edge electron temperature. A space-resolved VUV spectroscopy is developed to measure impurity radiation in the divertor region. An eagle-type VUV spectrometer with a focal length of 1 m is adopted in this system, equipped with a spherical grating and a charged-coupled device (CCD) detector. The performance of the VUV spectrometer is preliminarily tested on a synchrotron radiation facility. The wavelength calibration is conducted near 65 nm. It is found that the wavelength range observed by the CCD detector is about 11.07 nm around the central wavelength of about 65 nm. With a linear dispersion of 0.0053 nm/pixel, it is possible to measure the ion temperature lower than 20 eV at the edge region by analyzing the Doppler broadening of a carbon line. These test results show that the performance of the VUV spectrometer is capable of measuring divertor radiation and analyzing the ion temperature of edge impurity ions.

4.
Ann Oncol ; 31(3): 334-351, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32067677

RESUMO

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Ásia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , China , Humanos , Índia , Japão , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Malásia , Oncologia , República da Coreia , Taiwan
5.
Zhonghua Yi Xue Za Zhi ; 100(2): 104-109, 2020 Jan 14.
Artigo em Chinês | MEDLINE | ID: mdl-31937048

RESUMO

Objective: To investigate differential genes (DEGs) between no/mild and severe emphysema by bioinformatics analysis. Methods: The microarray dataset GSE1650, of lung tissue in no/mild and severe emphysema, was downloaded from the GEO database, and DEGs were obtained by t test. Analysis of DEGs based on DAVID database was used to obtain gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway. The protein-protein interaction network (PPI) was established using STRING database to identify hub genes. Results: A total of 76 DEGs were obtained, of which 62 genes were up-regulated and 14 genes were down-regulated in severe emphysema group. Gene ontology showed that the DEGs were mainly involved in neutrophil chemotaxis, cellular response to interleukin-1, extracellular matrix organization, immune response, and KEGG pathway involved cytokine-cytokine receptor interaction, ECM-receptor interaction, PI3K-Akt signaling pathway, platelet activation. Seventeen hub genes were recognized by PPI analysis, including CXCL8, RRAD, CLU, TIMP1, SEPP1, ISLR, BGN, COL1A1, COLIA2, ACTA2, ACTN1, FIGF, TPM1, TPM2, LUM, COL6A3 and TAGLN. Among them, fifteen genes (CLU, TIMP1, SEPP1, ISLR, BGN, COLIA2, COL1A1, ACTA2, ACTN1, FIGF, TPM1, TPM2, LUM, COL6A3, TAGLN) were up-regulated and two genes (CXCL8, RRAD) were down-regulated. Conclusion: Bioinformatics analysis based on GEO database showed that there were DEGs between non/mild and severe emphysema patients.


Assuntos
Biologia Computacional , Enfisema , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Fosfatidilinositol 3-Quinases , Proteínas ras
6.
Zhonghua Yi Xue Za Zhi ; 100(2): 116-120, 2020 Jan 14.
Artigo em Chinês | MEDLINE | ID: mdl-31937050

RESUMO

Objective: To investigate the association of plasma roundabout 4 concentration with pulmonary ventilation function decline in chronic obstructive pulmonary disease (COPD) patients. Methods: To get the effective data, the study was conducted in the outpatient department of West China Hospital from September 2017 to September 2018. The subjects meeting the inclusion and exclusion criteria were continuously included. Among them, the COPD group (75 cases) was from the respiratory outpatient department, and the healthy control group (57 cases) was from the health examination center at the same time. Data of basic demographic characteristics, clinical characteristics, pulmonary ventilation function parameters and blood samples were collected. The concentrations of roundabout 4, C reactive protein (CRP), interleukin (IL)-6, IL-8, IL-1b and tumor necrosis factor (TNF)-α in plasma were detected, and the differences among groups were compared, the correlation between plasma roundabout 4 and pulmonary ventilation function parameters and inflammatory factors was analyzed. The diagnostic efficiency of roundabout 4 to COPD was analyzed according to receiver operating characteristic (ROC) curve. Results: The plasma concentration of roundabout 4 in COPD group was significantly higher than that in healthy control group [(41.3±14.2) vs (27.7±13.3) ng/L; P<0.001], the sensitivity and specificity of roundabout 4 in the diagnosis of COPD were 0.827 and 0.702 respectively. Correlation analysis showed that the plasma concentration of roundabout 4 was negatively correlated with lung function parameters forced expiratory volume in one second/forced vital capacity (FEV(1)/FVC), the first second forced expiratory volume as a percentage of the estimated value (FEV(1)%pred), forced exhalation of 50% and 25% lung capacity (MEF50, MEF25) and maximal mid-expiratory flow (MMEF) (r=-0.399, -0.321, -0.439, -0.363, -0.458; all P<0.001), positively correlated with CRP (adjusted r=0.311, P<0.001). Conclusion: The increased concentration of roundabout 4 in plasma leads to the decline of pulmonary ventilation function in COPD patients.


Assuntos
Doença Pulmonar Obstrutiva Crônica , China , Volume Expiratório Forçado , Humanos , Pulmão , Testes de Função Respiratória
7.
Diabetes Metab ; 46(1): 41-45, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31200113

RESUMO

AIM: Under-management of diabetes can lead to a hyperglycaemic episode (HCE), which could be further strengthened in the presence of schizophrenia and the use of antipsychotics. This study aims to investigate the risk of HCE in diabetic patients with schizophrenia. Additionally, the duration of antipsychotic use on the risk of HCE is examined. MATERIALS AND METHODS: A total of 13858 diabetic patients with schizophrenia and 55407 controls (without schizophrenia) matched by gender, age, index year, and Charlson Comorbidity Index score were included between 1999 and 2010 and followed to the end of 2013 using from the Taiwan National Health Insurance Research Database. During the follow-up period, participants who developed HCE were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (95% CI) of the HCE incidence rate between the two groups studied. RESULTS: Diabetic patients with schizophrenia were associated with an increased risk of HCE compared with unaffected controls after adjusted for baseline demographics and duration of antipsychotic use (4.73 versus 2.43 per 1,000 person-years, HR: 2.16, 95% CI: 1.85-2.51). Also, in diabetic patients with schizophrenia, a longer duration of antipsychotic use was associated with a lower risk of HCE after adjustment for the above-mentioned variables, suggesting a protective effect of antipsychotics against HCE during prolonged use. CONCLUSION: This study highlights the need to pay more attention to the risk of HCE in diabetic patients with schizophrenia and the importance of proper use of antipsychotics may reduce the risk of HCE.


Assuntos
Complicações do Diabetes/complicações , Hiperglicemia , Esquizofrenia/complicações , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Hiperglicemia/epidemiologia , Hiperglicemia/etiologia , Incidência , Masculino , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológico
9.
QJM ; 112(7): 489-495, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30821331

RESUMO

BACKGROUND: Kidney transplantation (KT) has been found to reduce cardiovascular events and mortality in chronic dialysis patients. There is little data, however, regarding the risk reduction of cerebrovascular events after KT in Asian populations. This study evaluates the risk of cerebrovascular events after KT in Taiwan. METHODS: Tapping Taiwan's National Health Insurance claims data of patients with a diagnosis of end-stage renal disease (ESRD), we enrolled all KT recipients from 1999 to 2011 (n = 2908). For each KT patient, four controls (patients also diagnosed with ESRD) without KT were propensity matched by birth date, sex, selected comorbidities and duration of dialysis. All subjects were followed to the end of 2011. RESULTS: The incidence rate for stroke in the KT recipients and comparison group were 52.63 and 137.26 per 10 000 person-years, respectively. After adjustment for age, gender and comorbidities with competing mortality, KT recipients had 60% reduction in all kinds of stroke, compared to those who did not receive procedure. They were found to have a 48 and 74% reduction in ischemic and hemorrhagic stroke risk, respectively. Subgroup analyses also showed similar trends in the improvement of stroke after KT. While elderly patients, men, and those with diabetes, hypertension and coronary artery disease are at increased risk for stroke, our log-rank test revealed those that received KT had significantly lower cumulative incidence rates of stroke than those that did not (P < 0.001). CONCLUSIONS: KT was associated with reduced risk of new onset stroke in chronic dialysis patients in Taiwan.


Assuntos
Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Transplante de Rim , Acidente Vascular Cerebral/epidemiologia , Adulto , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Diálise Renal , Taiwan/epidemiologia , Transplantados
10.
Transplant Proc ; 50(8): 2489-2492, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30316383

RESUMO

This study evaluates the incidence of BK polyomavirus (BKV) and prognosis of BKV infection in kidney transplant recipients (KTRs) who received transplantation in our hospital before and after regular BKV nucleic acid test (NAT) was implemented. METHODS: The study included 74 KTRs who received a single kidney either from standard- or expanded-criteria deceased donor between March 2011 and March 2017. BKV NATs were regularly checked in 26 patients (group 1) in the first posttransplant year in accordance with current guidelines since NAT was implemented in our laboratory in 2014. We retrospectively compared 48 KTRs (group 2) who either received NAT when necessary in another laboratory or were not checked before 2014. RESULTS: There was no significant difference in patient characteristics between groups. BKV viruria were confirmed in 8 of 26 (30.8%) group 1 patients, whereas only 2 of 48 (4.2%) BKV infections were confirmed in group 2. None of the BKV(+) KTRs in group 1 developed BK polyomavirus-associated nephropathy (BKVAN), whereas 2 BKV(+) patients (100%) of group 2 developed BKVAN, which indicates renal function deterioration and biopsy-validated nephropathy. There was no significant difference in graft survival and renal function between the 2 groups. CONCLUSIONS: The risk of BKV infection is considerably higher in KTRs using NAT. Because there is no approval treatment, early diagnosis of BKV infection and early reduction of immunosuppression agents is critical for KTRs. Implementation of regular BKV NAT is mandatory before BKVAN and malignant neoplasms develop.


Assuntos
DNA Viral/análise , Hospedeiro Imunocomprometido/imunologia , Transplante de Rim , Infecções por Polyomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Adulto , Vírus BK/genética , Morte , Diagnóstico Precoce , Feminino , Humanos , Imunossupressores/uso terapêutico , Incidência , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/imunologia , Estudos Retrospectivos , Doadores de Tecidos , Transplantados , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/imunologia
12.
13.
Eur Rev Med Pharmacol Sci ; 21(14): 3253-3261, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28770957

RESUMO

OBJECTIVE: Procalcitonin (PCT) is a useful biomarker for systemic bacterial infection, and many studies have described the correlation between high serum PCT level and Gram-negative bloodstream infection (BSI), whereas the diagnostic accuracy of PCT for this kind of episode has not been summarized. This study aimed to estimate the overall accuracy of serum PCT for diagnosing Gram-negative BSI through a meta-analysis. MATERIALS AND METHODS: We searched PubMed, EMBASE, Web of Science, and Scopus database for studies that met the inclusion criteria. The pooled sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR) were calculated using bivariate random-effects models. Summary receiver operating characteristic (SROC) curve and area under the curve (AUC) were used to summarize overall diagnostic accuracy. RESULTS: Our meta-analysis included 13 studies involving 4,513 subjects. Summary estimates for PCT in diagnosing Gram-negative BSI were as follows: sensitivity, 0.73 (95% CI 0.68 to 0.78); specificity, 0.74 (95% CI 0.64 to 0.81); PLR, 2.77 (95% CI 2.07 to 3.70); NLR, 0.37 (95% CI 0.31 to 0.42); DOR, 7.59 (95% CI 5.31 to 10.85); AUC, 0.79 (95% CI 0.75 to 0.82). The corresponding summary performance estimates for using PCT in differentiating Gram-negative BSI from gram-positive BSI were as follows: sensitivity, 0.73 (95% CI 0.66 to 0.78); specificity, 0.70 (95% CI 0.59 to 0.78); PLR, 2.40 (95% CI, 1.83 to 3.15); NLR, 0.39 (95% CI 0.33 to 0.46); DOR, 6.15 (95% CI 4.40 to 8.60); AUC, 0.77 (95% CI 0.73 to 0.81). CONCLUSIONS: PCT may have a limited diagnostic value for Gram-negative BSI.


Assuntos
Bacteriemia/diagnóstico , Calcitonina/sangue , Infecções por Bactérias Gram-Negativas/diagnóstico , Bacteriemia/sangue , Biomarcadores/sangue , Infecções por Bactérias Gram-Negativas/sangue , Humanos
14.
Rev Sci Instrum ; 87(11): 11E326, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27910526

RESUMO

A two-crystal assembly was deployed on the tangential X-ray crystal spectrometer to measure both helium-like and hydrogen-like spectra on EAST. High-quality helium-like and hydrogen-like spectra were observed simultaneously for the first time on one detector for a wide range of plasma parameters. Profiles of line-integrated core ion temperatures inferred from two spectra were consistent. Since tungsten was adopted as the upper divertor material, one tungsten line (W XLIV at 4.017 Å) on the short-wavelength side of the Lyman-α line (Lα1) was identified for typical USN discharges, which was diffracted by a He-like crystal (2d = 4.913 Å). Another possible Fe XXV line (1.85 Å) was observed to be located on the long-wavelength side of resonance line (w), which was diffracted from a H-like crystal (2d = 4.5622 Å) on the second order. Be-like argon lines were also observable that fill the detector space between the He-like and H-like spectra.

16.
Eur Rev Med Pharmacol Sci ; 20(1): 44-53, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26813452

RESUMO

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is both a pulmonary and systematic disease, which will cause abnormal expression of some circulating factors. Angiopoietin-like protein 4 (ANGPTL4) has been reported to play important role in inflammatory responses and several diseases. However, whether it contributes to COPD is an open question. The aim of this study is to explore the potential relationship between ANGPTL4 and COPD. PATIENTS AND METHODS: In this study, circulating levels of ANGPTL4, C-reactive protein (CRP), adiponectin, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-9 and monocyte chemotactic protein (MCP)-1 in 73 COPD patients and 40 healthy volunteers were investigated using multiplex enzyme-linked immunosorbent assay Kits. Then, we analyzed the correlations between ANGPTL4 with other inflammatory mediators and pulmonary function. RESULTS: Serum ANGPTL4 levels were significantly elevated in COPD patients compared with healthy controls (122.86 ± 38.59 ng/mL versus 99.03 ± 31.84 ng/mL, p = 0.001). Besides, serum ANGTPL4 levels were much higher in ever-smokers with COPD than in never-smokers with COPD (131.71 ± 32.92 ng/mL versus 113.25 ± 42.34 ng/mL, p = 0.03). More importantly, the concentrations of circulating ANGPLT4 correlated inversely with forced expiratory volume in 1 second (FEV1) % predicted, an index of lung function in COPD (r = -0.450, p < 0.001) and in all participants (r = -0.369, p < 0.001), while correlated positively with CRP (r = 0.312, p = 0.007 for COPD; r = 0.404, p < 0.001 for total subjects), adiponectin (r = 0.266, p = 0.004 for total subjects), and MMP-9 (r = 0.254, p = 0.03 for COPD). CONCLUSIONS: Our results suggest that circulating ANGPTL4 levels are up-regulated in COPD patients, and have correlations with pulmonary function and systematic inflammation in COPD, which provides a novel idea to further dig the pathogenic mechanisms of COPD, and justifies more studies to determine how ANGPTL4 contributes to COPD.


Assuntos
Angiopoietinas/biossíntese , Doença Pulmonar Obstrutiva Crônica/metabolismo , Proteína 4 Semelhante a Angiopoietina , Angiopoietinas/sangue , Biomarcadores/sangue , Humanos , Inflamação/sangue , Pulmão/metabolismo , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória
17.
Anaesthesia ; 71(1): 31-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26460721

RESUMO

In patients with limited mouth opening, traditional laryngoscopy and videolaryngoscopes are not useful when performing nasotracheal intubation. Eighty patients with limited mouth opening who required nasotracheal intubation were randomly assigned to either fibreoptic intubation (n = 40) or the Trachway(®) (n = 40). Using the modified nasal intubation difficulty scale, 22 (55%) patients who received fibreoptic intubation were categorised as no difficulty compared with 40 (100%) patients in the Trachway group (p < 0.001). Mean (SD) total intubation time was 71.8 (23.3) s in patients who received fibreoptic intubation compared with 35.4 (9.8) s in the Trachway group (p < 0.001). We conclude that the Trachway technique for nasotracheal intubation is quicker and easier compared with fibreoptic intubation in patients with limited mouth opening.


Assuntos
Intubação Intratraqueal/métodos , Gravação em Vídeo/instrumentação , Adulto , Idoso , Feminino , Tecnologia de Fibra Óptica , Humanos , Intubação Intratraqueal/instrumentação , Masculino , Pessoa de Meia-Idade , Boca , Fatores de Tempo
18.
Eur Rev Med Pharmacol Sci ; 19(18): 3515-21, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26439051

RESUMO

OBJECTIVE: Hypoxia is an important risk factor for pulmonary arterial remodeling in pulmonary arterial hypertension (PAH). Pulmonary artery smooth muscle cell (PASMC) proliferation is a major contributor to pulmonary vascular remodeling. The intermediate-conductance Ca2+-activated K+ channel (Kca3.1) has been implicated in disease states characterized by excessive cell proliferation, but its role in hypoxia-induced PASMC proliferation is unknown. In the present study, we sought to investigate the effect of TRAM-34 (triarylmethane-34), a selective blocker of Kca3.1, on hypoxia-induced PASMC proliferation and underlying mechanisms. METHODS: PASMC was exposed to hypoxia (2% O2) for 24 hours, cell proliferation and cell cycle analysis were measured by cell counting kit (CCK-8) and flow cytometry. Cell signaling were examined using Quantitative real-time PCR and Western blotting. RESULTS: CCK8 results showed that TRAM-34 reduced PASMC proliferation under hypoxia. Flow cytometry revealed that TRAM-34 inhibited PASMC proliferation by G0/G1 arrest. Quantitative real-time PCR and western blotting results showed that Kca3.1 mRNA and protein levels were greater in PASMC after hypoxia exposure for 24 hours. Elevated BMP2 (bone morphogenetic protein 2) levels and decreased BMPR2/Smad1 signaling activation were also observed under hypoxia, which were significantly attenuated by TRAM-34 intervention. CONCLUSIONS: These results suggest that Kca3.1 inhibition with TRAM-34 inhibited hypoxia-induced PASMC proliferation in the G0/G1 phase. The capability of TRAM-34 to increase BMPR2/p-Smad1 signaling may be part of the mechanisms for hypoxia-induced cell proliferation. Thus, our study implies that blockade of kca3.1 might provide benefits to attenuating PAH vascular remodeling.


Assuntos
Hipóxia Celular/fisiologia , Hipertensão Pulmonar/genética , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/patologia , Pirazóis/química , Proliferação de Células , Humanos , Hipertensão Pulmonar/metabolismo , Artéria Pulmonar/metabolismo , Transdução de Sinais
19.
Eur Rev Med Pharmacol Sci ; 19(17): 3194-200, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26400522

RESUMO

OBJECTIVE: The gene product of the AT-rich interactive domain 1A (SWI-like) gene (ARID1A) is a member of the SWI/SNF adenosine triphosphate-dependent chromatin-remodeling complexes, which plays an essential role in controlling gene expression and is also involved in cancer development. ARID1A is frequently mutated in a wild variety of cancers and function as a tumor suppressor in several kinds of cancers. ARID1A was down-regulated in gastric cancer, and associated poor patient prognosis. However, how ARID1A protein is regulated in gastric cancer remains largely unknown. MATERIALS AND METHODS: Here, we show that ARID1A protein is rapidly ubiquitinated and degradated in gastric cancer cells in response to DNA damage treatment. RESULTS: Using genetic and pharmacologic Cullin inactivation coupled with in vitro ubiquitination assay, we demonstrate that ARID1A is a substrate of the Cullin-SKP1-F-box protein (SCF) complexes. Moreover, gastric cancer cells with forced expression of ARID1A showed an increased sensitivity to DNA damage reagents. Thus, our data uncovered a previous unknown posttranscriptional regulation of ARID1A by SCF E3 ligase in gastric cancer cells in DNA damage response. CONCLUSIONS: These findings suggest ARID1A might be a promising drug target in gastric cancer treatment.


Assuntos
Dano ao DNA/genética , Proteínas Nucleares/genética , Proteínas Ligases SKP Culina F-Box/genética , Fatores de Transcrição/genética , Apoptose , Linhagem Celular Tumoral , Proteínas de Ligação a DNA , Humanos , Proteínas Nucleares/metabolismo , Proteínas Ligases SKP Culina F-Box/metabolismo , Neoplasias Gástricas/patologia , Fatores de Transcrição/metabolismo , Transfecção
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