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2.
Artigo em Inglês | MEDLINE | ID: mdl-32067095

RESUMO

PURPOSE: Despite advances in the treatment of laryngeal squamous-cell carcinoma (LSCC), the survival rate of LSCC remains poor. Thereby, it is urgent to identify novel diagnostic and prognostic biomarkers for LSCC. The study aimed to identify potential core genes associated with the pathogenesis and prognosis of LSCC. METHODS: Differentially expressed genes between LSCC and normal laryngeal tissue samples were screened by an integrated analysis of data from GEO and TCGA databases. Core genes related to the pathogenesis and prognosis of LSCC were identified by employing protein-protein interaction network and Cox proportional hazards model analyses. RESULTS: Ten hub genes (AURKA, AURKB, CDC45, KIF2C, NDC80, EXO1, TYMS, RAD51AP1, ITGA3, and UBE2T) that might be highly related to the pathogenesis of LSCC were identified. An eight-gene prognostic signature consisted of ZG16B, STATH, RTN4R, MSRA, CBX8, SLC5A1, EFNB1 and CNTFR was constructed with a good performance in predicting overall survivals. CONCLUSION: Our findings might shed some new light on the pathogenesis of LSCC and help identify new therapeutic targets of LSCC.

3.
Ann Thorac Surg ; 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31991134

RESUMO

BACKGROUND: The efficacy of hemiarch replacement combined with a modified triple-branched stent graft in Debakey type I aortic dissection remains to be confirmed. METHODS: From January 2016 to December 2017, 167 patients with acute Debakey type I aortic dissection underwent hemiarch replacement combined with a modified triple-branched stent graft. The clinical and imaging data were retrospectively analyzed. The early composite endpoint was defined to comprise perioperative mortality, permanent neurological deficits, and renal failure requiring hemodialysis at discharge. RESULTS: The overall 30-day mortality was 4.2% (7/167). The incidence of the composite endpoint was 11.4% (19/167). The risk factors for the composite endpoint were malperfusion syndrome (odds ratio [OR], 5.17; 95% confidence interval [CI] 1.46-18.35, P=0.011) and Creatine > 1.5 mg/dl (OR, 5.44; 95% CI 2.27-13.06, P<0.001). The overall survival was 94.0% at 1 year and 92.2% 2 years during a median follow-up of 20.9±9.6 months. Three patients required distal aorta re-intervention. Complete thrombosis in the false lumen of the descending aorta at the level of the pulmonary bifurcation and at the level of the celiac trunk was observed in 98.8% and 10.8% of the patients respectively. CONCLUSIONS: Hemiarch replacement combined with a modified triple-branched stent graft is a reliable technique for acute Debakey type I aortic dissection as indicated by two years' follow up.

4.
Biosci Rep ; 39(11)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31710082

RESUMO

We performed long non-coding RNA (lncRNA) microarray assay to identify lncRNAs with differential expression between patients with intracranial aneurysm (IA) and healthy control individuals to evaluate their potential use as biomarkers of IA. Arraystar Human lncRNA Microarray v3.0 was performed to identify differentially expressed lncRNAs and mRNAs in plasma samples (4 ml). lncRNAs with the most pronounced differential expression were used to select gene markers, and results were validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Plasma levels of TCONS_00000200 (fold change: 2.28) and ENST00000511927 (fold change: 2.50) were significantly higher in IA patients than in healthy individuals (P<0.001), and plasma levels of ENST00000421997 (fold change: 0.45) and ENST00000538202 (fold change: 0.43) were significantly lower in IA patients than in healthy individuals (P<0.001). qRT-PCR confirmed the same trends of up- and down-regulation of these four lncRNAs. A receiver operating characteristic (ROC) curve for TCONS_00000200 showed that the area under the curve (AUC) was 0.963 (95% confidence interval, 0.919-1.000), optimal cut-off point was 0.0081, sensitivity was 90.0%, and specificity was 96.7%. These results indicate that the lncRNA TCONS_00000200 is differentially expressed in the plasma of IA patients and could serve as a biomarker of IA.

5.
Medicine (Baltimore) ; 98(39): e17130, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574813

RESUMO

Animal studies have demonstrated that autophagy was involved in neuronal damage after intracerebral hemorrhage (ICH). Several studies showed thrombin-antithrombin (TAT) plasma levels were elevated in patients with ICH. In this study, we aimed to evaluate if autophagy occurred in patients with ICH; and the relationship between the severity of brain injury and plasma TAT levels.A novel tissue harvesting device was used during hematoma removal surgery to collect loose fragments of tissue surrounding the affected brain area in 27 ICH patients with hematoma volumes of >30 mL in the basal ganglia. Control tissues were obtained from patients who underwent surgery for arteriovenous malformation (n = 25). Transmission electron microscopy (TEM) and immunohistochemistry for autophagy-related proteins were used to evaluate the ultrastructural and morphologic cellular characteristics; and the extent of autophagy in the recovered tissue specimens. Stroke severity was assessed by using the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS). An enzyme-linked immunosorbent assay (ELISA) was used to measure plasma TAT levels.Transmission electron microscopy showed autophagosomes and autolysosomes exist in neurons surrounding the hematoma, but not in the control tissues. The number of cells containing autophagic vacuoles correlated with the severity of brain injury. Immunohistochemistry showed strong LC3, beclin 1, and cathepsin D staining in ICH tissue specimens. Plasma TAT levels correlated positively with autophagic cells and ICH severity (P < .01).Autophagy was induced in perihematomal neurons after ICH. Autophagy and plasma TAT levels correlated positively with severity of brain injury. These results suggest that autophagy and increased plasma TAT levels may contribute to the secondary damage in ICH patients.


Assuntos
Autofagia , Hemorragia Cerebral/sangue , Hematoma/sangue , Neurônios/fisiologia , Peptídeo Hidrolases/sangue , Adulto , Idoso , Antitrombina III , Gânglios da Base/metabolismo , Hemorragia Cerebral/fisiopatologia , Hemorragia Cerebral/cirurgia , Feminino , Escala de Coma de Glasgow , Hematoma/fisiopatologia , Hematoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade
6.
Surg Endosc ; 33(7): 2304-2312, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30361966

RESUMO

BACKGROUND: NCCN Guidelines of esophageal cancer recommend that endoscopic therapy is considered "preferred" for patients with limited early-stage disease less than or equal to 2 cm. However, there is currently no definite evidence to support either endoscopic therapy or esophagectomy for early esophageal cancer larger than 2 cm. We aimed to explore the optimal treatment for this condition. METHODS: From January 2010 to June 2016, 116 patients with early esophageal neoplasia [high-grade dysplasia (HGD), lamina propria and muscularis mucosae (T1a) cancer, selected superficial submucosa (T1b) cancer without lymph node metastases] larger than 2 cm and treated either surgically or endoscopically were included. RESULTS: Endoscopic therapy was performed in 69 patients and esophagectomy in 47 patients, respectively. The median follow-up time was 43.8 months in the endoscopic cohort and 49.4 months in the surgical cohort. The overall survival was similar between the two cohorts (97.1% vs. 91.5%, P = 0.18). Survival without readmission for treatment-related complicates was also similar. Minor and severe procedure-related complications occurred more often in the surgical cohort than in the endoscopic cohort (63.8% vs. 43.5% and 8.5% vs. 0 respectively, P < 0.05 for both). Four patients in the endoscopic cohort had to undergo additional esophagectomy and were alive during follow-up. There were no procedure-related deaths in the endoscopic cohort, whereas two deaths occurred in the surgical cohort. Recurrence occurred in nine patients in the endoscopic group (13%): six with local recurrence, one with residual neoplasia and two with metachronous neoplasia. None of them died after repeated endoscopic treatments. CONCLUSIONS: Efficacy was similar between endoscopic therapy and esophagectomy in the treatment of early esophageal squamous cell neoplasia larger than 2 cm and endoscopic therapy was associated with fewer and manageable complications. We recommend endoscopic treatment should be preferred selected for early esophageal neoplasia larger than 2 cm.

7.
BMC Cardiovasc Disord ; 18(1): 177, 2018 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-30170545

RESUMO

BACKGROUND: Patients with frequent premature ventricular contractions (PVCs) are often symptomatic. Catheter ablation was usually indicated to eliminate symptoms in patients with PVCs-induced cardiomyopathy. Currently, PVCs-ablation is also applied for patients with PVCs and no structural heart diseases (SHD); however, the safety and efficacy of ablation in these patients remains unclear. METHODS: In this retrospective study, data from patients who underwent ablation for PVCs from January 2010 to December 2016 at our hospital was retrieved. Predictors of complications and acute procedural success were evaluated. RESULTS: A total of 1231 patients (mean age 47.8 ± 16.8 years, 59% female) were included. The overall complication rate was 2.7%, and the most common complication was hydropericardium. Two ablation-related mortalities occurred. One patient died of coronary artery injury during the procedure and the other died from infectious endocarditis. Location (left ventricle and epicardium) was the main predictor of complications, with right ventricular outflow tract (RVOT) predicting fewer complications. The acute procedural success rate was 94.1% in all patients. The main predictor of acute procedural success was RVOT origin, while an epicardial origin was a predictor of procedural failure. CONCLUSION: Locations of left ventricle and epicardium were predictors of procedural complications for patients with PVCs. Therefore, ablation is not recommended in these patients. For other origins of PVCs, particularly RVOT origin, ablation is a safety and effective treatment.


Assuntos
Ablação por Cateter , Complexos Ventriculares Prematuros/cirurgia , Adulto , Idoso , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Tomada de Decisão Clínica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/mortalidade , Complexos Ventriculares Prematuros/fisiopatologia
8.
JCI Insight ; 3(3)2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29415891

RESUMO

BACKGROUND: DC-based tumor vaccines have had limited clinical success thus far. SOCS1, a key inhibitor of inflammatory cytokine signaling, is an immune checkpoint regulator that limits DC immunopotency. METHODS: We generated a genetically modified DC (gmDC) vaccine to perform immunotherapy. The adenovirus (Ad-siSSF) delivers two tumor-associated antigens (TAAs), survivin and MUC1; secretory bacterial flagellin for DC maturation; and an RNA interference moiety to suppress SOCS1. A 2-stage phase I trial was performed for patients with relapsed acute leukemia after allogenic hematopoietic stem cell transplantation: in stage 1, we compared the safety and efficacy between gmDC treatment (23 patients) and standard donor lymphocyte infusion (25 patients); in stage 2, we tested the efficacy of the gmDC vaccine for 12 acute myeloid leukemia (AML) patients with early molecular relapse. RESULTS: gmDCs elicited potent TAA-specific CTL responses in vitro, and the immunostimulatory activity of gmDC vaccination was demonstrated in rhesus monkeys. A stage 1 study established that this combinatory gmDC vaccine is safe in acute leukemia patients and yielded improved survival rate. In stage 2, we observed a complete remission rate of 83% in 12 relapsed AML patients. Overall, no grade 3 or grade 4 graft-versus-host disease incidence was detected in any of the 35 patients enrolled. CONCLUSIONS: This study, with combinatory modifications in DCs, demonstrates the safety and efficacy of SOCS1-silenced DCs in treating relapsed acute leukemia. TRIAL REGISTRATION: ClinicalTrials.gov NCT01956630. FUNDING: National Institute of Health (R01CA90427); the Key New Drug Development and Manufacturing Program of the "Twelfth Five-Year Plan" of China (2011ZX09102-001-29); and Clinical Application Research of Beijing (Z131107002213148).


Assuntos
Vacinas Anticâncer/administração & dosagem , Células Dendríticas/imunologia , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adenoviridae/genética , Adolescente , Adulto , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Engenharia Celular/métodos , Criança , Células Dendríticas/transplante , Feminino , Seguimentos , Vetores Genéticos/genética , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunoterapia Adotiva/métodos , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/mortalidade , Transfusão de Linfócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
9.
J Affect Disord ; 229: 403-409, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29331700

RESUMO

RATIONALE: Depression is associated with coronary artery disease and increases adverse outcomes and mortality in patients with acute myocardial infarction, but the underlying pathophysiological mechanisms remain unclear. OBJECTIVE: To evaluate the effect of macrophage migration inhibitory factor (MIF) on cardiac ischemia-reperfusion (I/R) injury in mice with constant darkness-induced depression. METHODS AND RESULTS: Twenty C57BL/6 mice (8 weeks old, male) were randomly divided into 2 groups: one group was housed in a 12h light/dark cycle environment (LD) and the other in a constant darkness environment (DD). After 3 weeks, constant darkness-exposed (DD) mice displayed depression-like behavior as indicated by increased immobility in the forced swim test (FST) and lower sucrose preference rate. Western blotting revealed cardiac MIF expression was significantly lower in the DD mice than that in the LD mice. Next, 84 mice were randomly divided into 4 groups: LD sham group, LD I/R group, DD sham group, and DD I/R group. Following ischemia and reperfusion, mice in the DD I/R group had a larger infarct area and lower heart function index than mice in the LD I/R group (P < 0.05 for both). The cardiac pAMPK and pACC expression levels of the DD I/R group were also lower in the DD I/R group (P < 0.05). CONCLUSION: DD-induced depression might cause decreased expression of MIF in the heart, resulting in downregulation of MIF-AMPK signaling and a subsequent adverse outcome after a cardiac I/R injury.


Assuntos
Escuridão , Depressão/metabolismo , Fatores Inibidores da Migração de Macrófagos/biossíntese , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão/metabolismo , Proteínas Quinases Ativadas por AMP/biossíntese , Animais , Depressão/complicações , Depressão/patologia , Masculino , Camundongos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Traumatismo por Reperfusão/patologia
10.
Oncotarget ; 8(28): 46461-46467, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28515348

RESUMO

Data on the association between using PDE5 inhibitors and malignant melanoma are conflicting. To estimate the relation of using PDE5 inhibitors with risk of malignant melanoma, Medline (Ovid) and Embase (Ovid) databases were searched up to February 2017, and a random effects model was used to calculate the summary risk estimates. Five observational studies were included. Five studies reports encompassed a total of 15,979 melanoma cases occurring among 1, 188,414 participants. The pooled multivariable-adjusted RR of melanoma in patients with using PDE5 inhibitors was 1.12 (95% CI: 1.03-1.21, I2 = 0.48). Findings from this systematic review support that PDE5 inhibitor use is associated with increased risk of melanoma in ED patients, the result remains inclusive and warrants further study in the future.


Assuntos
Melanoma/epidemiologia , Melanoma/etiologia , Inibidores da Fosfodiesterase 5 , Estudos de Casos e Controles , Humanos , Melanoma/patologia , Inibidores da Fosfodiesterase 5/efeitos adversos , Risco
11.
Oncol Lett ; 13(5): 3261-3268, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28529567

RESUMO

Fuzheng Qingjie (FZQJ) is a polyherbal Chinese medicine that has previously been implemented as an adjuvant therapy for gastrointestinal cancer. The present study investigated whether FZQJ is able to potentiate the anticancer effect of cyclophosphamide (CTX). Hepatoma 22 tumor-bearing mice were randomly divided into a vehicle group, CTX group, FZQJ group and combination (CTX+FZQJ) group. In addition, untreated mice without H22 cells served as blank controls. Seven days post-treatment, the mice were sacrificed and the tumors were weighed. Blood cells were evaluated using an automatic hemocytometer analyzer and flow cytometer. The expression levels of interleukin (IL)-2 and tumor necrosis factor (TNF)-α were evaluated using a radioimmunoassay. Apoptotic cells were observed using a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Alanine transaminase, aspartate aminotransferase, blood urea nitrogen and creatinine were examined using an automatic biochemical analyzer. The results demonstrated that the tumor inhibitory rate and apoptosis index were higher in the combination group, compared with those in the CTX group. Notably, FZQJ was able to alleviate CTX-induced decreases in the numbers of white blood cells and platelets, CD3+ and CD4+ T lymphocyte subsets, and the concentration of hemoglobin, body weight and thymus index, and increase serum TNF-α and IL-2 levels without overt hepatorenal toxicity. These results suggest that FZQJ granules may enhance the anticancer effect of CTX, in addition to alleviating the side effects.

12.
BMC Cardiovasc Disord ; 17(1): 109, 2017 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-28482812

RESUMO

BACKGROUND: Long-term recurrence (LR) is a tendency that re-occurs within 3 months after catheter ablation for atrial fibrillation (AF). Whether very early recurrence (VER) within 7 days of post ablation is a prognostic factor of LR or not is unclear. For this reason, present study sought to examine the relationship between VER and LR. METHODS: In this prospective analysis 378 consecutive patients underwent an initial catheter ablation for paroxysmal or persistent AF. The association between VER and LR was analyzed by univariate and multivariate Cox regression, as well as time-dependent receiver operator characteristic (ROC) analysis. RESULTS: After a mean follow-up of 14.71 ± 8.58 months, 81 (65.90%) patients with VER experienced LR and were associated with lower event of free survival from LR (Log rank test, P < 0.001). Multivariate Cox regression analysis revealed that VER (HR = 7.02, 95% CI = 4.78-10.31; P < 0.001), left atrial enlargement (HR = 2.92, 95% CI = 1.88-4.54; P < 0.001), tendency in advanced age (HR = 1.50, 95% CI = 0.99-2.28; P = 0.054), and tendency in male (HR = 0.71, 95% CI = 0.50-1.01; P = 0.060) were independent predictors of LR. According to time-dependent ROC analysis, it was found that VER was more sensitive than common risk factors in predicting LR (0.74 vs 0.66, P < 0.001) and combination model further improved the C statistic for predicting LR (0.82 vs 0.66, P < 0.001). CONCLUSIONS: After a single procedure of catheter ablation, patients with VER were strongly associated with LR and combination of VER and common risk factors could further improve prediction of patients who were at high risk for LR.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Idoso , Área Sob a Curva , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Prospectivos , Curva ROC , Recidiva , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
13.
BMC Cardiovasc Disord ; 17(1): 127, 2017 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-28521773

RESUMO

BACKGROUND: About 10-15% patients who take statins experience skeletal muscle problems. Red yeast rice has a good safety profile could provide a compromise therapeutic strategy. Therefore, the aim of this study was to evaluate the effects of red yeast rice, when compared to simvastatin, on the muscle fatigue symptom and the serum lipid level in dyslipidemic patients with low to moderate cardiovascular risk. METHODS: A total of 60 dyslipidemic patients with low to moderate cardiovascular risk were recruited and randomly assigned to receive either simvastatin (n = 33) or red yeast rice (n = 27) for 4 weeks. The muscle fatigue score, the physical activity, the serum lipid profile and the safety profile were then evaluated. RESULTS: At the end of study, the fatigue score was significantly increased in patients treated with simvastatin, whereas no significant change was observed in patients receiving red yeast rice. In addition, the physical activity level was significantly decreased in patients from simvastatin group when compared to those from red yeast rice group. Similar lipid-lowering effects were observed in two groups. The safety profile was not affected after the treatments. CONCLUSIONS: Among dyslipidemic patients with low to moderate cardiovascular risk, red yeast rice induced less fatigue side effect and exerted comparable lipid-lowering effects when compared to simvastatin in this pilot primary prevention study. TRIAL REGISTRATION: NCT01686451 .


Assuntos
Produtos Biológicos/uso terapêutico , Suplementos Nutricionais , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Fadiga Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Sinvastatina/uso terapêutico , Adulto , Produtos Biológicos/efeitos adversos , Biomarcadores/sangue , China , Suplementos Nutricionais/efeitos adversos , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Projetos Piloto , Sinvastatina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
14.
Integr Cancer Ther ; 16(3): 329-338, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-27335087

RESUMO

Fuzheng Qingjie (FZQJ) granules, a compound Chinese medicine, have been used as an adjuvant therapy for alimentary tract cancers. However, the underlying anticancer mechanisms are still not well understood. In the present study, HepG2 cells were treated with FZQJ-containing serum. Cell proliferation was evaluated using MTT assay. Apoptosis was analyzed using a flow cytometer. Cell ultrastructure was observed under a transmission electron microscope. The mitochondrial membrane potential (Δψ) was examined with JC-1 dye. In H22 tumor-bearing mice, CD4+ T cells, CD8+ T cells, CD3+ T cells, and natural killer (NK) cells in peripheral blood were evaluated cytometrically. Interleukin (IL)-2 and tumor necrosis factor (TNF)-α levels were measured using radioimmunoassay.The mRNA levels of Bax and Bcl-2 were examined by reverse transcription-polymerase chain reaction. The protein levels of Bax, Bcl-2, cytochrome C, caspase 3 and 9, PARP, and CD69 were examined by Western blotting. The apoptotic cells in tissues were observed using TUNEL method. Alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), and creatinine (CRE) were detected by an automatic biochemical analyzer. The results showed that FZQJ-containing serum remarkably inhibited proliferation of HepG2 cells in dose- and time-dependent manners, induced HepG2 cell apoptosis and caused a decrease of Δψ. Analysis of tumor tissue showed that FZQJ-induced apoptosis was accompanied by downregulation of Bcl-2 and upregulation of Bax, release of cytochrome c, activation of caspase 3 and 9, and cleavage of PARP. In addition, FZQJ increased the percentages of CD4+ T and NK cells, the ratio of CD4+/CD8+ T cells as well as the levels of serum TNF-α. FZQJ also increased CD69 expression in tumor tissue. No hepatorenal toxicity was observed in H22 tumor-bearing mice. These results indicated that FZQJ could inhibit the growth of hepatoma cells via regulating immune function and inducing mitochondria mediated apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Imunidade/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Apoptose/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Células Hep G2 , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/metabolismo , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/imunologia , Camundongos , Mitocôndrias/imunologia , Mitocôndrias/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismo
15.
Psychogeriatrics ; 17(1): 3-8, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26757022

RESUMO

BACKGROUND: Cerebralcare Granule (CG) is a polyherbal Chinese medicine that has been shown to have neuroprotective effects in experimental models of stroke. We compared the efficacy and safety of CG with aspirin in patients with acute stroke. METHODS: For this open-label, controlled trial, we recruited patients with angiographically confirmed strokes and US National Institutes of Health Stroke Scale (NIHSS) scores of 4-22 within 2 weeks of symptom onset; recruitment was performed at 55 sites in China. Patients received CG or aspirin. The primary efficacy end-point was neurological function. Analyses were done by intention to treat. Patients were measured for NIHSS, Montreal Cognitive Assessment, and Mini-Mental State Examination scores and Barthel index at baseline and at 4, 8, and 12 weeks after treatment. RESULTS: Between January 2013 and January 2014, we treated 1963 patients with CG and 1288 patients with aspirin. Baseline NIHSS, Mini-Mental State Examination, and Montreal Cognitive Assessment scores were comparable between the two groups. Patients in the CG group had a greater improvement than the aspirin group in terms of NIHSS (P < 0.01) and Barthel index at 4, 8, and 12 weeks. At 12 weeks, patients in the CG group had a greater improvement than the aspirin group in terms of Mini-Mental State Examination (P < 0.01) and Montreal Cognitive Assessment (P < 0.05). Adverse reactions were similar between the two groups. CONCLUSIONS: This large-scale, controlled trial indicated that CG may be a useful treatment in the management of post-stroke patients.


Assuntos
Aspirina/uso terapêutico , Cognição/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Fármacos Neuroprotetores/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , China , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/efeitos adversos , Testes Neuropsicológicos , Inibidores da Agregação de Plaquetas/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento
16.
Oncol Rep ; 37(2): 754-760, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28035399

RESUMO

It is well documented that A proliferation-inducing ligand (APRIL), a member of the tumor necrosis factor superfamily, plays a crucial role in the occurrence and development of tumors. In the present study, we evaluated the synergistic effect of APRIL knockdown and Jiedu Xiaozheng Yin (JXY), a Traditional Chinese Medicinal recipe, on the inhibition of hepatocellular carcinoma (HCC) cell proliferation and elucidated the underlying mechanism. The results demonstrated that both APRIL knockdown using small interfering RNA (siRNA) and JXY treatment could trigger cell cycle arrest and cell apoptosis, and suppress HCC cell proliferation through an NF-κB-related pathway. Synergism was further demonstrated between APRIL knockdown and JXY treatment. In conclusion, these results indicate that APRIL is a target gene for HCC and combination of siRNA-APRIL and JXY application holds great promise as a novel approach for the treatment of APRIL-positive HCC.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Neoplasias Hepáticas/patologia , Extratos Vegetais/farmacologia , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/antagonistas & inibidores , Animais , Apoptose/genética , Western Blotting , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Proliferação de Células/genética , Terapia Combinada , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Masculino , Camundongos , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Eur J Pharmacol ; 783: 23-32, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27131827

RESUMO

Type 2 diabetes mellitus is a risk factor for Alzheimer's disease (AD). The glucagon-like peptide-1 analog liraglutide, a novel long-lasting incretin hormone, has been used to treat type 2 diabetes mellitus. In addition, liraglutide has been shown to be neurotrophic and neuroprotective. Here, we investigated the effects of liraglutide on amyloid ß protein (Aß)-induced AD in mice and explored its mechanism of action. The results showed that subcutaneous administration of liraglutide (25nmol/day), once daily for 8 weeks, prevented memory impairments in the Y Maze and Morris Water Maze following Aß1-42 intracerebroventricular injection, and alleviated the ultra-structural changes of pyramidal neurons and chemical synapses in the hippocampal CA1 region. Furthermore, liraglutide reduced Aß1-42-induced tau phosphorylation via the protein kinase B and glycogen synthase kinase-3ß pathways. Thus liraglutide may alleviate cognitive impairment in AD by at least decreasing the phosphorylation of tau.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Liraglutida/farmacologia , Memória/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Proteínas tau/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Liraglutida/administração & dosagem , Liraglutida/uso terapêutico , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/ultraestrutura , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Aprendizagem Espacial/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Sinapses/metabolismo
18.
Lancet ; 387(10017): 431-2, 2016 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-26869568
19.
Diabetes Care ; 39(1): 149-57, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26628416

RESUMO

OBJECTIVE: To determine the safety and effects on insulin secretion of umbilical cord (UC) mesenchymal stromal cells (MSCs) plus autologous bone marrow mononuclear cell (aBM-MNC) stem cell transplantation (SCT) without immunotherapy in established type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Between January 2009 and December 2010, 42 patients with T1D were randomized (n = 21/group) to either SCT (1.1 × 10(6)/kg UC-MSC, 106.8 × 10(6)/kg aBM-MNC through supraselective pancreatic artery cannulation) or standard care (control). Patients were followed for 1 year at 3-month intervals. The primary end point was C-peptide area under the curve (AUC(C-Pep)) during an oral glucose tolerance test at 1 year. Additional end points were safety and tolerability of the procedure, metabolic control, and quality of life. RESULTS: The treatment was well tolerated. At 1 year, metabolic measures improved in treated patients: AUCC-Pep increased 105.7% (6.6 ± 6.1 to 13.6 ± 8.1 pmol/mL/180 min, P = 0.00012) in 20 of 21 responders, whereas it decreased 7.7% in control subjects (8.4 ± 6.8 to 7.7 ± 4.5 pmol/mL/180 min, P = 0.013 vs. SCT); insulin area under the curve increased 49.3% (1,477.8 ± 1,012.8 to 2,205.5 ± 1,194.0 mmol/mL/180 min, P = 0.01), whereas it decreased 5.7% in control subjects (1,517.7 ± 630.2 to 1,431.7 ± 441.6 mmol/mL/180 min, P = 0.027 vs. SCT). HbA1c decreased 12.6% (8.6 ± 0.81% [70.0 ± 7.1 mmol/mol] to 7.5 ± 1.0% [58.0 ± 8.6 mmol/mol], P < 0.01) in the treated group, whereas it increased 1.2% in the control group (8.7 ± 0.9% [72.0 ± 7.5 mmol/mol] to 8.8 ± 0.9% [73 ± 7.5 mmol/mol], P < 0.01 vs. SCT). Fasting glycemia decreased 24.4% (200.0 ± 51.1 to 151.2 ± 22.1 mg/dL, P < 0.002) and 4.3% in control subjects (192.4 ± 35.3 to 184.2 ± 34.3 mg/dL, P < 0.042). Daily insulin requirements decreased 29.2% in only the treated group (0.9 ± 0.2 to 0.6 ± 0.2 IU/day/kg, P = 0.001), with no change found in control subjects (0.9 ± 0.2 to 0.9 ± 0.2 IU/day/kg, P < 0.01 vs. SCT). CONCLUSIONS: Transplantation of UC-MSC and aBM-MNC was safe and associated with moderate improvement of metabolic measures in patients with established T1D.


Assuntos
Transplante de Medula Óssea , Diabetes Mellitus Tipo 1/terapia , Transplante de Células-Tronco Mesenquimais , Adolescente , Adulto , Peptídeo C/sangue , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/metabolismo , Insulina/uso terapêutico , Secreção de Insulina , Masculino , Projetos Piloto , Qualidade de Vida , Transplante Autólogo , Cordão Umbilical/citologia , Adulto Jovem
20.
J Clin Oncol ; 33(34): 3999-4006, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26392095

RESUMO

PURPOSE: For recipients of allogeneic hematopoietic stem-cell transplantation (alloHSCT), we hypothesized that prophylactic therapy during neutropenia with granulocyte-macrophage colony-stimulating factor (GM-CSF) decreases invasive fungal disease (IFD). PATIENTS AND METHODS: We randomly assigned 206 patients undergoing alloHSCT to receive once-daily subcutaneous GM-CSF (5 to 7 µg/kg per day), granulocyte colony-stimulating factor (G-CSF; 5 to 7 µg/kg per day), or a combination of G-CSF and GM-CSF (2 to 3 µg/kg per day each). Treatment was started on day 5 after transplantation and was continued until the absolute neutrophil count was ≥ 1.5 × 10(9)/L for 2 consecutive days. The primary outcomes were 100-day incidence of proven and probable IFD and response rate of antifungal treatment. RESULTS: For the intent-to-treat population, there was no significant difference in 100-day incidences of proven and probable IFD among the three groups. The antifungal treatment response was better in the GM-CSF group and G-CSF+GM-CSF group than in G-CSF group from day 22 to day 100 (P = .009). The 100-day cumulative mortality after transplantation was lower in the GM-CSF group than in the G-CSF group (10.3% v 24.6%, respectively; P = .037). The GM-CSF and G-CSF+GM-CSF groups had lower 100-day transplantation-related mortality than the G-CSF group (8.8%, 8.7%, and 21.7%, respectively; P = .034). After a median follow-up of 600 days, IFD-related mortality was lower in the groups that received GM-CSF or G-CSF+GM-CSF compared with G-CSF (1.47%, 1.45%, and 11.59%, respectively; P = .016). There were no significant differences in relapse, graft-versus-host disease, or hemorrhage-related mortality among the three groups of patients. CONCLUSION: For recipients of alloHSCT, compared with G-CSF, prophylactic GM-CSF was associated with lower 100-day transplantation-related mortality, lower 100-day cumulative mortality, and lower 600-day IFD-related mortality.


Assuntos
Antifúngicos/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Micoses/tratamento farmacológico , Adolescente , Adulto , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Doenças Hematológicas/mortalidade , Doenças Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/etiologia , Micoses/mortalidade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Transplante Homólogo , Adulto Jovem
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