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1.
Bioengineered ; 12(1): 4054-4069, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34369278

RESUMO

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 infection, while little is known about ACE2 in hepatocellular carcinoma (HCC). The detailed mechanism among ACE2 and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, ACE2 expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = -0.41). With the area under the curve of summary receiver operating characteristic = 0.82, ACE2 expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of ACE2 was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan-Meier survival, Cox regression analyses. The potential molecular mechanism of ACE2 may be relevant to catabolic and cell division. In all, decreasing ACE2 expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , Carcinoma Hepatocelular/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Proteínas de Neoplasias/genética , Receptores Virais/genética , alfa-Fetoproteínas/genética , Fatores Etários , Idoso , Enzima de Conversão de Angiotensina 2/metabolismo , Área Sob a Curva , COVID-19/virologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Bases de Dados Genéticas , Conjuntos de Dados como Assunto , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/classificação , Proteínas de Neoplasias/metabolismo , Fatores de Proteção , Mapeamento de Interação de Proteínas , Curva ROC , Receptores Virais/metabolismo , SARS-CoV-2/patogenicidade , Análise de Sobrevida , alfa-Fetoproteínas/metabolismo
2.
Theranostics ; 11(11): 5539-5552, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859762

RESUMO

Rationale: We developed a cocktail of soluble molecules mimicking the in vivo milieu supporting liver regeneration that could convert mature hepatocytes to expandable liver progenitor-like cells in vitro. This study aimed to induce endogenous liver progenitor cells by the administration of the soluble molecules to provide an alternative approach for the resolution of liver fibrosis. Methods: In vitro cultured hepatocyte-derived liver progenitor-like cells (HepLPCs) were transplanted into CCL4-treated mice to investigate the therapeutic effect against liver fibrosis. Next, we used HGF in combination with a cocktail of small molecules (Y-27632, A-83-01, and CHIR99021 (HACY)) to induce endogenous CD24+ liver progenitor cells and to inhibit the activation of hepatic stellate cells (HSCs) during CCL4-induced hepatic injury. RNA sequencing was performed to further clarify the features of HACY-induced CD24+ cells compared with CCL4-induced CD24+ cells and in vitro derived HepLPCs. Finally, we evaluated the expansion of HACY-induced CD24+ cells in human hepatocyte-spheroids from fibrotic liver tissues. Results: HepLPCs exhibited the capacity to alleviate liver fibrosis after transplantation into CCL4-treated mice. The in vivo administration of HACY not only induced the conversion of mature hepatocytes (MHs) to CD24+ progenitor cells but prevented the activation of HSCs, thus leading to enhanced improvement of liver fibrosis in CCL4-treated mice. Compared to CD24+ cells induced by CCL4 alone, HACY-induced CD24+ cells retained an enhanced level of hepatic function and could promote the restoration of liver function that exhibited comparable gene expression profiles with HepLPCs. CD24+ cells were also observed in human liver fibrotic tissues and were expanded in three-dimensional (3D) hepatic spheroids in the presence of HACY in vitro. Conclusions: Hepatocyte-derived liver progenitor-like cells are crucial for liver regeneration during chronic hepatic injuries. The administration of HACY, which allowed the induction of endogenous CD24+ progenitor cells and the inactivation of HSCs, exerts beneficial effects in the treatment of liver fibrosis by re-establishing a balance favoring liver regeneration while preventing fibrotic responses.


Assuntos
Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Fígado/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Células-Tronco/efeitos dos fármacos , Amidas/farmacologia , Animais , Antígeno CD24/metabolismo , Tetracloreto de Carbono/farmacologia , Células Cultivadas , Expressão Gênica/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Fígado/metabolismo , Cirrose Hepática/metabolismo , Regeneração Hepática/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piridinas/farmacologia , Pirimidinas/farmacologia , Células-Tronco/metabolismo
3.
Heart Vessels ; 36(5): 686-692, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33394104

RESUMO

The aim of this study is to assess serum human epididymis protein 4 (HE-4) levels as a biomarker for predicting the recurrence of atrial fibrillation (AF) after catheter ablation. This was a prospective observational study that enrolled one hundred eighty-four consecutive nonvalvular AF patients (65 persistent, 119 paroxysmal) who were eligible for their first ablation. Multiple Cox proportional hazards models and Kaplan-Meier curve analyses were used to test the association between serum HE-4 levels and AF recurrence after catheter ablation. During the 12-month follow-up, we observed that 47 patients (25.5%) experienced AF recurrence. Patients were divided into tertiles of HE-4 level (T1: < 50 pmol/L; T2: ≥ 50 pmol/L). The AF recurrence rate of higher serum HE-4 level patients was significantly increased (34.6% vs 13.8%, P < 0.001). Generalized additive models were used to visually assess functional relationships between the serum HE-4 levels and the risk of AF recurrence. When stratified with serum levels as the cut-off value, Kaplan-Meier analysis showed that patients with serum HE-4 levels (> 50 pmol/L) had a significantly increased risk of AF recurrence. In addition, multivariate Cox proportional hazard modelling revealed that HE-4 (≥ 50 pmol/L) (HR 2.65; 95% CI 1.34, 5.27, P = 0.005) was independent predictors of AF recurrence. Serum HE-4 levels in patients with AF are associated with postoperative recurrence of AF, and high HE-4 levels are an independent predictor of AF recurrence after ablation.


Assuntos
Fibrilação Atrial/sangue , Ablação por Cateter/métodos , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/metabolismo , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recidiva , Estudos Retrospectivos , Fatores de Risco
4.
Sci Transl Med ; 12(551)2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641490

RESUMO

Clinical advancement of the bioartificial liver is hampered by the lack of expandable human hepatocytes and appropriate bioreactors and carriers to encourage hepatic cells to function during extracorporeal circulation. We have recently developed an efficient approach for derivation of expandable liver progenitor-like cells from human primary hepatocytes (HepLPCs). Here, we generated immortalized and functionally enhanced HepLPCs by introducing FOXA3, a hepatocyte nuclear factor that enables potentially complete hepatic function. When cultured on macroporous carriers in an air-liquid interactive bioartificial liver (Ali-BAL) support device, the integrated cells were alternately exposed to aeration and nutrition and grew to form high-density three-dimensional constructs. This led to highly efficient mass transfer and supported liver functions such as albumin biosynthesis and ammonia detoxification via ureagenesis. In a porcine model of drug overdose-induced acute liver failure (ALF), extracorporeal Ali-BAL treatment for 3 hours prevented hepatic encephalopathy and led to markedly improved survival (83%, n = 6) compared to ALF control (17%, n = 6, P = 0.02) and device-only (no-cell) therapy (0%, n = 6, P = 0.003). The blood ammonia concentrations, as well as the biochemical and coagulation indices, were reduced in Ali-BAL-treated pigs. Ali-BAL treatment attenuated liver damage, ameliorated inflammation, and enhanced liver regeneration in the ALF porcine model and could be considered as a potential therapeutic avenue for patients with ALF.


Assuntos
Falência Hepática Aguda , Fígado Artificial , Albuminas , Animais , Hepatócitos , Humanos , Fígado , Falência Hepática Aguda/terapia , Suínos
5.
Minerva Cardioangiol ; 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32643894

RESUMO

BACKGROUND: Admission blood pressure was closely associated with adverse cardiac events in acute coronary syndrome (ACS) patients. However, data regarding comparison of resting postoperative systolic, diastolic, and mean blood pressure and pulse pressure with short- and long-term mortality in patients with acute coronary syndrome undergoing primary percutaneous coronary intervention (PCI) was still lacking. METHODS: 1,987 ACS patients undergoing primary PCI were analyzed, between January 2014 and October 2018. The primary outcomes were in-hospital cardiac and long-term all-cause mortality. RESULTS: Bar tendency chart and adjusted odds ratios showed that the resting postoperative SBP≤100mmHg, PP≤30mmHg and MAP≤70mmHg have higher in hospital cardiac (SBP: adjusted OR=9.42, 95%CI 1.95-45.53, p<0.01; PP: adjusted OR=8.61, 95%CI 2.53-29.30, p<0.01; MAP: adjusted OR=4.01, 95%CI 1.61-9.98, p<0.01) and long-term all-cause mortality (SBP: adjusted HR=4.18, 95%CI 1.43- 12.23, p<0.01; PP: adjusted HR=3.71, 95%CI 1.66-8.24, p<0.01; MAP: adjusted HR=2.54, 95%CI 1.14-5.65, p<0.01) , and the relationship between resting postoperative SBP and in-hospital cardiac or long-term all-cause mortality seemed to follow a J-shaped curve with increased event rates at low and high groups. CONCLUSIONS: The resting postoperative SBP≤100mmHg, PP≤30mmHg and MAP≤70mmHg are independent adverse prognosticators in ACS patients undergoing primary PCI, and the relationship between SBP and mortality looks like a J-shaped curve.

6.
J Cardiovasc Electrophysiol ; 31(5): 1062-1067, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32108393

RESUMO

INTRODUCTION: The incidence and clinical outcome of pericardial and pleural effusion after cryoballoon ablation (CBA) or radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) have not been fully investigated. METHODS: A total of 60 patients with paroxysmal AF were treated with either CBA (n = 30) or RFCA (n = 30) groups, with assessment of serum troponin I level, left atrial pulmonary vein computed tomography (CT) angiography and echocardiography within 24 hours before ablation, and serum troponin I level at 12 hours, and chest CT and echocardiography within 24 hours postablation. Repeat chest CT was performed 1 month after the index procedure in patients with pericardial or pleural effusion. RESULTS: With similarly distributed baseline characteristics, the CBA group relative to the RFCA group had postablation: higher serum troponin I level (13.48 vs 1.84 µg/L, P < .001); similarly high pericardial effusion rates on chest CT (80% vs 93.3%, P > .05), with chest CT yielding significantly higher detection rate than echocardiography; similarly high pleural effusion rates on chest CT (73.3% vs 80%, P > .05); and smaller maximum depths on chest CT cross-section of pericardial effusion (5.21 ± 3.37 vs 7.13 ± 2.68 mm, P < .05) and pleural effusion bilaterally (left: 4.16 ± 4.90 vs 6.96 ± 5.42 mm; right: 5.04 ± 4.46 vs 7.55 ± 4.95 mm, both P < .05). The effusions self-resolved within a mean period of 1 month. CONCLUSIONS: Both CBA and RFCA were associated with high rates of pericardial and pleural effusion, with RFCA yielding numerically higher incidence and significantly higher effusion extent, and chest CT significantly higher detection rates than echocardiography.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Criocirurgia/efeitos adversos , Derrame Pericárdico/epidemiologia , Derrame Pleural/epidemiologia , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Biomarcadores/sangue , China/epidemiologia , Ecocardiografia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Derrame Pericárdico/diagnóstico por imagem , Derrame Pleural/diagnóstico por imagem , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Troponina I/sangue
7.
Artigo em Inglês | MEDLINE | ID: mdl-32087972

RESUMO

In both normal turnover of the hepatic tissue and acute hepatic injury, the liver predominantly activates terminally differentiated hepatocytes to proliferate and repair. However, in chronic and severe chronic injury, this capacity fails, and liver progenitor cells (LPCs) can give rise to hepatocytes to restore both hepatic architecture and liver metabolic function. Although the promotion of LPC-to-hepatocyte differentiation to acquire a considerable number of functional hepatocytes could serve as a potentially new therapeutic option for patients with end-stage liver disease, its development first requires the identification of the molecular mechanisms driving this process. Here, we found that the epithelial cell adhesion molecule (EpCAM), a progenitor cell marker, regulates the differentiation of LPCs into hepatocytes through Notch1 signaling pathway. Western blotting (WB) revealed a consistent expression pattern of EpCAM and Notch1 during LPC-to-hepatocyte differentiation in vitro. Additionally, overexpression of EpCAM blocked LPC-to-hepatocyte differentiation, which was in consistent with the repressive role of Notch signaling during hepatic differentiation. WB and immunofluorescence data also showed that the upregulation of EpCAM expression increased the generation of Notch intracellular domain (N1ICD), indicating the promotion of Notch1 activity. Our results established the EpCAM-Notch1 signaling axis as an inhibitory mechanism preventing LPC-to-hepatocyte differentiation in vitro.

8.
Oncol Rep ; 43(2): 405-414, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894341

RESUMO

Living tumors are of great scientific value for clinical medicine and basic research, especially for drug testing. An increasing number of drug tests fail due to the use of imperfect models. The aim of the present study was to develop a novel method combining vitrification­based cryopreservation of tumor biopsies and precision­cut slice cultivation for the assessment of anticancer drug responses. Biological characteristics of rectal cancer liver metastasis biopsies could be retained by vitrification­based cryopreservation. The patient­derived xenograft models were successfully established using both fresh and warmed biopsy tissues. Precision­cut slicing provided a similar three­dimensional architecture and heterogeneity to the original tumor. The positive drug responses in the xenograft model were consistent with those in precision­cut slice cultures in vitro. The present study demonstrated that live tumor biopsies could be preserved using vitrification­based cryopreservation. The warmed tissues developed xenograft tumors, which were also useful for either in vivo or in vitro anticancer drug testing. Precision­cut slices derived from the warmed tissues provided an efficient tool to assess anticancer drug response in vitro.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Técnicas de Cultura de Tecidos/métodos , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biópsia , Criopreservação , Feminino , Humanos , Neoplasias Hepáticas/secundário , Masculino , Camundongos , Pessoa de Meia-Idade , Resultado do Tratamento , Vitrificação , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Int Heart J ; 60(5): 1192-1195, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31447464

RESUMO

Here we report two young patients with atrial fibrillation/atrial flutter complicated with cardiogenic cerebral embolism. Electrophysiological study revealed a large area of low-voltage zone or area of electric silence in both sides of the atrium during restoration of sinus rhythm, and the echocardiogram showed loss of mechanical function of the atrium. The electrical-mechanical dysfunction of the atrium was considered to be the cause of embolic event in this type of patient who was "very low" stroke risk atrial fibrillation or atrial flutter. The idiopathic, fibrotic atrial cardiomyopathy may be underlying in these patients.


Assuntos
Fibrilação Atrial/complicações , Flutter Atrial/complicações , Ablação por Cateter/métodos , Eletrocardiografia/métodos , Acidente Vascular Cerebral/etiologia , Adulto , Fatores Etários , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Flutter Atrial/diagnóstico , Flutter Atrial/cirurgia , Mapeamento Potencial de Superfície Corporal/métodos , China , Feminino , Seguimentos , Humanos , Masculino , Doenças Raras , Medição de Risco , Amostragem , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia
10.
Coron Artery Dis ; 30(6): 398-405, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31206405

RESUMO

BACKGROUND: Early identification of high-risk patients provides clinicians with greater decision-making time and better informs strategies to cope with disease. The predictive values of age shock index (age SI) and age-modified shock index (age MSI) in ST-segment elevation myocardial infarction (STEMI) patients undergoing emergency percutaneous coronary intervention (PCI) have rarely been reported, especially compared with those for SI, MSI, and the Global Registry of Acute Coronary Events (GRACE) risk score. PATIENTS AND METHODS: Nine hundred and eighty-three STEMI patients undergoing emergency PCI between January 2014 and September 2017 were analyzed in a retrospective cohort study. The primary outcomes were rates of in-hospital cardiovascular events, and 6-month and long-term all-cause mortality. RESULTS: In multivariate analyses, the predictive values of age SI and age MSI were comparable to that of the GRACE score, but superior to those of SI and MSI for in-hospital cardiac mortality [age SI: odds ratio (OR) = 1.05, P < 0.001, area under the receiver operating characteristic (ROC-AUC) = 0.805, P < 0.001; age MSI: OR = 1.04, P < 0.001, ROC-AUC = 0.813, P < 0.001; GRACE score: OR = 1.03, P < 0.001, ROC-AUC = 0.827, P < 0.001], 6-month all-cause mortality (age SI: OR = 1.04, P < 0.001, ROC-AUC = 0.791, P < 0.001; age MSI: OR = 1.03, P < 0.001, ROC-AUC = 0.801, P < 0.001; GRACE score: ROC-AUC = 0.828, P < 0.001), long-term all-cause mortality [age SI: hazard ratio (HR) = 1.06, P < 0.001, ROC-AUC = 0.798, P < 0.001; age MSI: HR = 1.04, P < 0.001, ROC-AUC = 0.84, P < 0.001; GRACE score: ROC-AUC = 0.822, P < 0.001] and post-discharge all-cause mortality (age SI: HR = 1.05, P < 0.001, ROC-AUC = 0.78, P = 0.001; age MSI: HR = 1.05, P < 0.001, ROC-AUC = 0.789, P < 0.001; GRACE score: ROC-AUC = 0.812, P < 0.001). CONCLUSION: Age SI and age MSI are stronger predictors than SI and MSI for in-hospital cardiovascular events, and 6-month and long-term all-cause mortality in STEMI patients undergoing emergency PCI. Age SI and age MSI appear to be convenient and simpler indicators than the GRACE score.


Assuntos
Técnicas de Apoio para a Decisão , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Fatores Etários , Idoso , Pressão Arterial , Tomada de Decisão Clínica , Emergências , Feminino , Frequência Cardíaca , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
11.
Cell Res ; 29(1): 8-22, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30361550

RESUMO

The study of pathophysiological mechanisms in human liver disease has been constrained by the inability to expand primary hepatocytes in vitro while maintaining proliferative capacity and metabolic function. We and others have previously shown that mouse mature hepatocytes can be converted to liver progenitor-like cells in vitro with defined chemical factors. Here we describe a protocol achieving efficient conversion of human primary hepatocytes into liver progenitor-like cells (HepLPCs) through delivery of developmentally relevant cues, including NAD + -dependent deacetylase SIRT1 signaling. These HepLPCs could be expanded significantly during in vitro passage. The expanded cells can readily be converted back into metabolically functional hepatocytes in vitro and upon transplantation in vivo. Under three-dimensional culture conditions, differentiated cells generated from HepLPCs regained the ability to support infection or reactivation of hepatitis B virus (HBV). Our work demonstrates the utility of the conversion between hepatocyte and liver progenitor-like cells for studying HBV biology and antiviral therapies. These findings will facilitate the study of liver diseases and regenerative medicine.


Assuntos
Vírus da Hepatite B/fisiologia , Hepatite B/patologia , Hepatócitos , Fígado/patologia , Células-Tronco , Animais , Diferenciação Celular , Células Cultivadas , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Camundongos , Sirtuína 1/metabolismo , Células-Tronco/citologia , Células-Tronco/patologia
13.
Cancer Lett ; 420: 26-37, 2018 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-29409972

RESUMO

Obesity is a major risk factor for hepatocellular carcinoma (HCC) and is typically accompanied by higher levels of serum dipeptidyl peptidase 4 (DPP4). However, the role of DPP4 in obesity-promoted HCC is unclear. Here, we found that consumption of a high-fat diet (HFD) promoted HCC cell proliferation and metastasis and led to poor survival in a carcinogen-induced model of HCC in rats. Notably, genetic ablation of DPP4 or treatment with a DPP4 inhibitor (vildagliptin) prevented HFD-induced HCC. Moreover, HFD-induced DPP4 activity facilitated angiogenesis and cancer cell metastasis in vitro and in vivo, and vildagliptin prevented tumor progression by mediating the pro-angiogenic role of chemokine ligand 2 (CCL2). Loss of DPP4 effectively reversed HFD-induced CCL2 production and angiogenesis, indicating that the DPP4/CCL2/angiogenesis cascade had key roles in HFD-associated HCC progression. Furthermore, concomitant changes in serum DPP4 and CCL2 were observed in 210 patients with HCC, and high serum DPP4 activity was associated with poor clinical prognosis. These results revealed a link between obesity-related high serum DPP4 activity and HCC progression. Inhibition of DPP4 may represent a novel therapeutic intervention for patients with HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Quimiocina CCL2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Dipeptidil Peptidase 4/sangue , Dipeptidil Peptidase 4/genética , Neoplasias Hepáticas/patologia , Obesidade/complicações , Animais , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/prevenção & controle , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/prevenção & controle , Masculino , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Obesidade/sangue , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Prognóstico , Ratos , Vildagliptina/administração & dosagem , Vildagliptina/farmacologia
15.
Heart Vessels ; 32(12): 1506-1512, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28689282

RESUMO

Heart failure (HF) has a significant effect on the prognosis of the patients with atrial fibrillation (AF), and also it is an important risk factor for overall mortality. High molecular weight fibroblast growth factor-2 (Hi-FGF-2) is emerging as a prognostic marker with HF and AF. The aim of this study was to prove that Hi-FGF-2 would predict occurrence of HF in the patients with AF. Subjects diagnosed with paroxysmal AF (Group paAF), persistent AF (Group peAF) and sinus rhythm (Group SR) were enrolled in the study. Serum Hi-FGF-2 concentration was measured by ELISA at baseline. Multivariable logistic models and receiver operating characteristic (ROC) curve analysis were established to predict the prognosis of AF subjects. 260 patients were enrolled in the study: 104 (40.0%) admitted for sinus rhythm (Group SR) and 156 (60.0%) with AF (Group paAF and Group peAF). The Hi-FGF-2 levels were much lower in the Group SR (58.2 ± 27.1 ng/L) than in the Group AF. Furthermore, the Group peAF (84.3 ± 34.1 ng/L) had higher Hi-FGF-2 levels than the Group paAF (72.9 ± 35.8 ng/L). Serum Hi-FGF-2 levels were classified into trisection in the multivariable logistic model (T1 < 57.3 ng/L, 57.3 < T2 < 86.5 ng/L, and T3 > 86.5 ng/L). Hi-FGF-2 showed good predictive ability for new-onset HF in the patients with AF. The occurrence of HF was associated significantly with increased tertile of serum Hi-FGF-2 levels (T2: OR 5.922, 95% CI 1.109-31.626, P = 0.037 and T3: OR 8.262, 95% CI 1.735-39.343, P = 0.008). ROC curve analysis showed that the area under curves for Hi-FGF-2 were 0.720 (P < 0.0001). Hi-FGF-2 has a significant meaning in AF subjects. Further to this, higher circulating Hi-FGF-2 was highly related to persistent AF, and Hi-FGF-2 may be an independent risk factor of occurrence HF in AF subjects.


Assuntos
Fibrilação Atrial/complicações , Fator 2 de Crescimento de Fibroblastos/sangue , Átrios do Coração/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Taquicardia Paroxística/complicações , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Biomarcadores/sangue , China/epidemiologia , Ecocardiografia , Eletrocardiografia Ambulatorial , Feminino , Fibrose/sangue , Fibrose/complicações , Fibrose/diagnóstico , Seguimentos , Átrios do Coração/fisiopatologia , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/epidemiologia , Humanos , Imunoensaio , Incidência , Masculino , Pessoa de Meia-Idade , Peso Molecular , Prognóstico , Estudos Prospectivos , Curva ROC , Taxa de Sobrevida/tendências , Taquicardia Paroxística/sangue , Taquicardia Paroxística/diagnóstico
16.
Cryobiology ; 78: 41-46, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28716599

RESUMO

Tumor tissue has great clinical and scientific value which relies highly on the proper preservation of primary materials. Conventional tumor tissue cryopreservation using slow-freezing method has yielded limited success, leading to significant cell loss and morphological damage. Here we report a standardized vitrification-based cryopreservation method, by which we have successfully vitrified and warmed 35 intrahepatic cholangiocarcinoma (ICC) tissues with up to 80% viability of the fresh tumor tissues. Cryopreserved ICC tissue could generate patient-derived xenografts (PDXs) with take rates of 68.2% compared to 72.7% using fresh tumor tissues. Histological and genetic analyses showed that no significant alterations in morphology and gene expression were introduced by this cryopreservation method. Our procedure may facilitate collection, long-time storage and propagation of cholangiocarcinoma or other tumor specimens for (pre)clinical studies of novel therapies or for basic research.


Assuntos
Colangiocarcinoma/patologia , Criopreservação/métodos , Transplante de Neoplasias/métodos , Vitrificação , Animais , Sobrevivência Celular , Congelamento , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante Heterólogo/métodos , Células Tumorais Cultivadas
17.
Expert Rev Gastroenterol Hepatol ; 11(9): 857-864, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28597703

RESUMO

BACKGROUND: Critically ill cirrhotic patients have a high mortality, particularly with concomitant respiratory failure on admission. There are no specific models in use for mortality risk assessment in critically ill cirrhotic patients with acute respiratory failure (CICRF). The aim is to develop a risk prediction model specific to CICRF in order to quantify the severity of illness. METHODS: We analyzed 949 CICRF patients extracted from the MIMIC-III database. The novel model (ARF-CLIF-SOFA) was developed from the CLIF-SOFA score. Cox regression analysis and AUROC were implemented to test the predictive accuracy, compared with existing scores including the CLIF-SOFA score and MELD-related scores. RESULTS: ARF-CLIF-SOFA contains PaO2/FiO2 ratio, lactate, MAP, vasopressor therapy, bilirubin and creatinine (1 point each; score range: 0-6). Based on our patient cohort, the ARF-CLIF-SOFA score had good predictive accuracy for predicting the 30-, 90-day and 1-year mortality (AUROC = 0.767 at 30-day, 0.768 at 90-day, 0.765 at 1-year, respectively). Additionally, the performance of the ARF-CLIF-SOFA is superior to existing scores (all P < 0.001). CONCLUSION: The ARF-CLIF-SOFA score can be considered a CICRF specific score with a better predictive accuracy compared to the existing scores.


Assuntos
Cirrose Hepática/mortalidade , Insuficiência Respiratória/mortalidade , Índice de Gravidade de Doença , Idoso , Estado Terminal/mortalidade , Feminino , Indicadores Básicos de Saúde , Humanos , Cirrose Hepática/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Respiratória/diagnóstico , Estudos Retrospectivos , Medição de Risco
18.
Front Aging Neurosci ; 9: 90, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28420984

RESUMO

Objective: To explore serum caveolin-3 (Cav-3) levels in patients with atrial fibrillation (AF) and to evaluate the role of Cav-3 as a biomarker for AF and incident heart failure (HF). Methods: Three hundred and five patients were enrolled in the study and divided into three groups: sinus rhythm (Group SR), paroxysmal AF (Group paAF), and persistent AF (Group peAF). Serum Cav-3 concentrations were measured by enzyme-linked immunosorbent assay at baseline. Clinical characteristics, and laboratory data were collected during hospitalization, and a follow-up of 12-months was carried out. Results: Serum Cav-3 concentrations were significantly decreased on the Group SR and the highest concentrations of Cav-3 in patients were found on the Group peAF (516.7 ± 274.0 vs. 609.3 ± 287.0 vs. 688.3 ± 264.6 ng/L, P < 0.05). Left atrial diameter (LAD) in the Group peAF was significantly higher than in the Group paAF, and the Group SR had significantly lower LAD than the Group paAF and Group peAF. The risks of new-onset HF in the Group SR, Group paAF, and Group peAF were 8.1, 14.5, and 28.6%, respectively. There was a significant difference between the Group peAF and the other two groups. Serum Cav-3 concentrations were trisected in AF participants (lower tertile: ≤498, middle tertile: >498-703, upper tertile: ≥703). In further tertile studies, subjects in the lower tertile of Cav-3 concentrations were more likely to become paroxysmal AF and had much lower LAD (P < 0.05). And in the middle and upper tertiles, participants with AF tended to suffer from HF compared to the lower group (P < 0.05). Conclusion: We provide evidence that Cav-3 has a significant meaning in AF patients. The levels of Cav-3 may be related to the LAD and new-onset HF.

19.
Eur J Gastroenterol Hepatol ; 29(6): 698-705, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28240612

RESUMO

BACKGROUND AND AIM: Critically ill cirrhosis patients have an increased risk of morbidity and mortality, even after admission to the ICU. Our objectives were to compare the predictive accuracy of model for end-stage liver disease (MELD), MELD-Na, UK model for end-stage liver disease, and chronic liver failure-sequential organ failure assessment (CLIF-SOFA) by the development and validation of an easy-to-use prognostic model [named quick CLIF-SOFA (qCLIF-SOFA)] for early risk prediction in critically ill patients with cirrhosis. PATIENTS AND METHODS: Overall, 1460 patients were extracted from the MIMIC-III database and enrolled in this study at 30-day and 90-day follow-up. qCLIF-SOFA was developed in the established cohort (n=730) and a performance analysis was completed in the validation cohort (n=730) using area under the receiver operating characteristic curve. Results were compared with CLIF-SOFA. RESULTS: The performance of CLIF-SOFA was significantly better than that of MELD, MELD-Na, and UK model for end-stage liver disease for predicting both 30-day and 90-day mortality (all P<0.05). qCLIF-SOFA consisted of five independent factors (bilirubin, creatinine, international normalized ratio, mean arterial pressure, and vasopressin) associated with mortality. In the established cohort, CLIF-SOFA and qCLIF-SOFA predicted mortality with area under the receiver operating characteristic curve values of 0.768 versus 0.743 at 30-day, 0.747 versus 0.744 at 90-day, and 0.699 versus 0.706 at 1 year, respectively (all P>0.05). A similar result was observed in the validation cohort (0.735 vs. 0.734 at 30 days, 0.723 vs. 0.737 at 90 days, and 0.682 vs. 0.700 at 1 year, respectively, all P>0.05). CONCLUSION: The utility of CLIF-SOFA was further shown to predict mortality for critically ill cirrhosis patients. The novel and simpler qCLIF-SOFA model showed comparable accuracy compared with existing CLIF-SOFA for prognostic prediction.


Assuntos
Técnicas de Apoio para a Decisão , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Falência Hepática/diagnóstico , Falência Hepática/mortalidade , Modelos Biológicos , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/mortalidade , Escores de Disfunção Orgânica , Idoso , Área Sob a Curva , Pressão Arterial , Bilirrubina/sangue , Biomarcadores/sangue , Creatinina/sangue , Estado Terminal , Bases de Dados Factuais , Feminino , Humanos , Coeficiente Internacional Normatizado , Estimativa de Kaplan-Meier , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Falência Hepática/sangue , Falência Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo
20.
Eur J Gastroenterol Hepatol ; 29(4): 464-471, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28030513

RESUMO

BACKGROUND AND AIM: Acute circulatory failure (ACF) is associated with high mortality rates in critically ill cirrhotic patients. Only a few accurate scoring models exist specific to critically ill cirrhotic patients with acute circulatory failure (CICCF) for mortality risk assessment. The aim was to develop and evaluate a novel model specific to CICCF. PATIENTS AND METHODS: This study collected and analyzed the data on CICCF from the Multiparameter Intelligent Monitoring in Intensive Care-III database. The acute circulatory failure-chronic liver failure-sequential organ failure assessment (ACF-CLIF-SOFA) score was derived by Cox's proportional hazards regression. Performance analysis of ACF-CLIF-SOFA against CLIF-SOFA and model for end-stage liver disease systems was completed using area under the receiver operating characteristic curve. RESULTS: ACF-CLIF-SOFA identified six independent factors: mean arterial pressure [hazard ratio (HR)=0.984, 95% confidence interval (CI): 0.978-0.990, P<0.001], vasopressin (HR=1.548, 95% CI: 1.273-1.883, P<0.001), temperature (HR=0.764, 95% CI: 0.694-0.840, P<0.001), bilirubin (HR=1.031, 95% CI: 1.022-1.041, P<0.001), lactate (HR=1.113, 95% CI: 1.084-1.142, P<0.001), and urine output (HR=0.854, 95% CI: 0.767-0.951, P=0.004). ACF-CLIF-SOFA showed a better predictive performance than CLIF-SOFA and model for end-stage liver disease in terms of predicting mortality (0.769 vs. 0.729 vs. 0.713 at 30 days, 0.757 vs. 0.707 vs. 0.698 at 90 days, 0.733 vs. 0.685 vs. 0.691 at 1 year, respectively, all P<0.05). CONCLUSION: ACF-CLIF-SOFA, as the first model specific to CICCF, enables a more accurate prediction at 30-day, 90-day, and 1-year follow-up periods than other existing scoring systems.


Assuntos
Cirrose Hepática/complicações , Insuficiência de Múltiplos Órgãos/etiologia , Choque/etiologia , Doença Aguda , Adulto , Idoso , Bases de Dados Factuais , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/mortalidade , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/mortalidade , Prognóstico , Medição de Risco/métodos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Choque/mortalidade
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