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1.
Bioeng Transl Med ; 8(5): e10567, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37693063

RESUMO

Low-flow removal of refractory ascites is critical to treating cirrhosis and digestive system tumor, and thus, commercial ascites pump emerged lately. The rigid structure of clinically available pumps rises complication rate and lack of flow rate monitoring hinders early warning of abnormalities. Herein, a soft artificial system was proposed inspired by lymph for interactive ascites transfer with great biocompatibility. The implantable system is composed of pump cavity, valves and tubes, which are soft and flexible made by silica gel. Therefore, the system possesses similar modulus to tissues and can naturally fit surrounding tissues. The cavity with magnetic tablet embedded is driven by extracorporeal magnetic field. Subsequently, the system can drain ascites with a top speed of 23 mL min-1, much higher than that of natural lymphatic system and state-of-art devices. Moreover, integrated flexible sensors enable wireless, real-time flow rate monitoring, serving as proof of treatment adjustment, detection and locating of malfunction at early stage. The liver function of experimental objects was improved, and no severe complications occurred for 4 weeks, which proved its safety and benefit to treatment. This artificial lymphatic system can serve as a bridge to recovery and pave the way for further clinical research.

2.
ACS Omega ; 8(8): 7699-7713, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36872968

RESUMO

Nickel-catalyzed amidation of aryl alkynyl acids using tetraalkylthiuram disulfides as the amine source is described, affording a series of aryl alkynyl amides in good to excellent yields under mild conditions. This general methodology provides an alternative pathway for the synthesis of useful aryl alkynyl amides in an operationally simple manner, which shows its practical synthetic value in organic synthesis. The mechanism of this transformation was explored through control experiments and DFT calculations.

3.
Cell Mol Biol (Noisy-le-grand) ; 69(14): 293-299, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38279416

RESUMO

Worldwide, the non-small-cell lung cancers (NSCLC) is considered one of the deadliest cancers. Very early onset of distant metastasis is an important reason for the lower survival rate of NSCLC patients. Kinesin family member C1 (KIFC1) with highly protein levels in various of cancers contributes to the initiation and development of many cancers. KIFC1 has also been suggested as a possible marker of NSCLC. Nevertheless, the effects of KIFC1 on NSCLC metastasis has not been researched. To investigate the role of KIFC1 in NSCLC and related mechanisms. Westernblot and quantitative real-time PCR were conducted to test the levels of KIFC1 in NSCLC cancerous tissues and NSCLC cancerous cell lines. Colony formation assay, CCK-8, transwell assay and wound healing assay was conducted to detect the functions of KIFC1 on proliferation, migration and invasion of NSCLC cell lines. WesternBlot was conducted to test the role of KIFC1in EMT and TGF-ß/SMAD pathway. We discovered that the protein levels of KIFC1 were upregulated in NSCLC cancerous cell lines and cancerous tissues from mankind. KIFC1 was positively related with worse clinical staging and lymphnode metastasis of NSCLC patients in clinical data. Overexpressed KIFC1 aggravated expansion, migration and invasion in NSCLC cells, whereas silencing of KIFC1 had the opposite effect in vitro. Mechanistically, the progression of NSCLC was promoted by KIFC1 through induction of EMT and TGF-ß/SMAD signal. KIFC1 promoted proliferation and metastasis through accommodating TGF-ß/SMAD signal, which is a hint that KIFC1 might offer a prospective therapeutic target for the NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Fator de Crescimento Transformador beta/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica
4.
Medicine (Baltimore) ; 99(17): e19802, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332622

RESUMO

To identify the risk factors of pneumonia in patients with Anti-N-methyl-D-aspartate (Anti-NMDA) receptor encephalitis.This is a retrospective study.Department of Neurology in West China Hospital of Sichuan University.Patients with a definitive diagnosis of anti-NMDA receptor encephalitis.Risk factors associated with pneumonia were examined by bivariate analysis and multivariate logistic regression model.A total of 104 patients were included in this study, of which 41% patients (n = 43) were diagnosed with pneumonia at 7 days (range: 4-40 days) after admission. The occurrence of pneumonia was associated with prolonged hospital stays, a higher rate of poor outcome, and extra healthcare costs. Risk factors associated with pneumonia included Glasgow coma scale score (GCS), abnormal movements and hypokalemia.Pneumonia is a common complication in anti-NMDA receptor encephalitis. In the present study, we found that disorders of consciousness, abnormal movements, and hypokalemia were independent risk factors for pneumonia in inpatients with anti-NMDA receptor encephalitis. Pneumonia prolongs the patients' hospital stay, hospitalization expenditures, and affects the patients' prognosis.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Pneumonia/etiologia , Adolescente , Adulto , Idoso , Encefalite Antirreceptor de N-Metil-D-Aspartato/fisiopatologia , Criança , China , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pneumonia/fisiopatologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco
5.
Medicine (Baltimore) ; 98(45): e17683, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702621

RESUMO

A majority of nurses struggled with a negative emotion of anger, doubt, fear, or anxious, uncomfortable in the face of death and dying. However, little was known about community health care providers' in China. Therefore, we conducted a study to investigate their knowledge and attitudes toward end-of-life care and analyze its influencing factors. To provide reference for developing effective strategies to promote end-of-life care in China.A total of 132 community health care providers of 10 community health care centers in Changzhi city were investigated by a Questionnaire of Knowledge and Attitudes toward Caring for the Dying from May, 2017 to December, 2017, and data was analyzed by SPSS 22.0 software.Of the 132 community health care providers who were under investigation, 70 knew about hospice care, but they rated their overall content on end-of-life care as inadequacy, especially in communication skills and knowledge of pain management. The average score of attitudes was 3.47 (SD = 0.44), the lowest score was in the subscale of nurse-patient communication, which was 2.91 (SD = 0.65). Health care providers who had worked for more than 11 years, who had experiences of the death of relatives or friends, and who had previous experiences of caring for terminal patients had more positive attitudes toward caring for the dying (P < .05 for all). There was a significant relationship between community health care providers' attitudes toward death and their attitudes toward end-of-life care (r = -0.282, P < .01). The significant predictors of attitudes toward end-of-life care were attitudes toward death (ß = -0.342), experiences of the death of relatives (ß=-0.207), experiences of caring for the dying (ß = 0.185), and working experience (ß = 0.171).Community health care providers had positive attitudes toward end-of-life care, but they lacked systematic and professional knowledge and skills of caring for the terminal patients. Education is the top priority. It is imperative to set up palliative care courses and life-death education courses, establish an indigenous end-of-life care model, and improve policies, systems, and laws to promote end-of-life care.


Assuntos
Pessoal de Saúde/psicologia , Cuidados Paliativos/psicologia , Assistência Terminal/psicologia , Adulto , Atitude do Pessoal de Saúde , Atitude Frente a Morte , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
Muscle Nerve ; 59(1): 95-99, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30055010

RESUMO

INTRODUCTION: We sought to translate, cross-culturally adapt, and evaluate the internal consistency and validity of the Chinese version of the 15-Item Myasthenia Gravis Quality of Life (MG-QOL15). METHODS: Translation and cross-cultural adaptation of the MG-QOL15 were performed. We used Cronbach's α to test internal consistency, one-way analysis of variance to test construct validity, and Pearson or Spearman correlations to test discriminant and concurrent validity. RESULTS: We enrolled 168 outpatients. Internal consistency was excellent (Cronbach's α = 0.928). The MG-QOL15 discriminated MG severity as stratified by the MG Composite (MGC; P < 0.001) and Osserman class (P = 0.01). Concurrent validity was low to moderate with the subscales of the 36-item Short Form (-0.31 to ∼-0.59), MGC (r = 0.46), and Myasthenia Gravis Activities of Daily Living profile (r = 0.54). DISCUSSION: The Chinese MG-QOL15 showed comparable construct, discriminant and concurrent validity, and internal consistency with to the original version. Muscle Nerve 59:95-99, 2019.


Assuntos
Comparação Transcultural , Miastenia Gravis/psicologia , Qualidade de Vida/psicologia , Inquéritos e Questionários , Tradução , Atividades Cotidianas , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/epidemiologia , Reprodutibilidade dos Testes
7.
J Neuroimmunol ; 325: 64-68, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30408708

RESUMO

Currently, no data are available regarding the expression levels of CD40L on CD4+ T cells in patients with neuromyelitis optica spectrum disorders (NMOSD). The percentage of circulating CD40L+CD4+ T cells was measured by flow cytometry in 23 NMOSD patients and 10 healthy controls. The ratio of CD40L+CD4+ to CD4+ T cells in patients at acute phase (18.28 ±â€¯15.56%) was significantly higher than that in healthy controls (7.23 ±â€¯5.94%, P = .032) and was positively correlated with disease severity (r = 0.532, P = .041). Thus, our results suggest an important role of this molecule in acute attacks of NMOSD.


Assuntos
Aquaporina 4/sangue , Linfócitos T CD4-Positivos/metabolismo , Ligante de CD40/sangue , Imunoglobulina G/sangue , Neuromielite Óptica/sangue , Neuromielite Óptica/diagnóstico , Doença Aguda , Adulto , Biomarcadores/sangue , Ligante de CD40/biossíntese , Ligante de CD40/genética , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade
8.
J Mol Neurosci ; 63(3-4): 396-402, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29032462

RESUMO

The tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene encodes a vital co-stimulatory molecule of the immune system and has been identified as a susceptibility locus for systemic lupus erythematosus, systemic sclerosis, and primary Sjögren's syndrome. However, the association of TNFSF4 polymorphisms with neuromyelitis optica spectrum disorders (NMOSD), an inflammatory, demyelinating autoimmune disease of the central nervous system, has not yet been investigated. To evaluate whether TNFSF4 polymorphisms contribute to risk of NMOSD, four single-nucleotide polymorphisms (SNPs) (rs1234315, rs2205960, rs704840, and rs844648) were selected and genotyped in a cohort of 312 patients with NMOSD and 487 healthy controls. Our study showed that rs844648 was associated with an increased risk of NMOSD, according to the allelic model (OR = 1.30, 95% CI 1.06-1.59, P = 0.011, Pcorr = 0.044). Significant associations of rs844648 (OR = 1.67, 95% CI 1.17-2.38, P = 0.005, Pcorr = 0.02) and rs704840 (OR = 1.75, 95% CI 1.17-2.63, P = 0.007, Pcorr = 0.027) with NMOSD occurrence were also observed under the recessive model. Moreover, linkage disequilibrium analysis revealed two blocks within TNFSF4; in one block, the haplotype Ars844648Grs704840 significantly increased the risk of NMOSD, whereas Grs844648Trs704840 reduced the risk. This study demonstrates an association between TNFSF4 polymorphisms and susceptibility for the development of NMOSD in the Chinese population.


Assuntos
Neuromielite Óptica/genética , Ligante OX40/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Neuromolecular Med ; 19(4): 493-500, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28852993

RESUMO

STAT4 plays a crucial role in the functioning of the innate and adaptive immune cells and has been identified as a susceptibility gene in numerous autoimmune disorders. However, its association with neuromyelitis optica spectrum disorders (NMOSD) remains uncertain. Here, we performed a case-control study to determine whether STAT4 contributed to the risk of NMOSD. We tested five STAT4 SNPs in 233 patients with established NMOSD and 492 healthy controls. Chi-square tests and logistic regression analyses were performed with four genetic models, including allelic, additive, dominant, and recessive models, to identify associations with NMOSD. The results of multiple test comparisons were corrected using the Benjamini and Hochberg false discovery rate (FDR-BH). After correcting for multiple test comparisons, the minor alleles of four STAT4 SNPs exhibited significant association with increased risk of NMOSD (rs7574865 T, odds ratio [OR] = 1.66, 95% confidence interval [CI] 1.32-2.08, P corr = 0.000; rs10181656 G, OR = 1.62, 95% CI 1.29-2.03, P corr = 0.000; rs10168266 T, OR = 1.59, 95% CI 1.27-2.00, P corr = 0.001; and rs13426947 A, OR = 1.51, 95% CI 1.21-1.90, P corr = 0.004). Identical results were observed in the dominant, recessive, and additive models. In contrast, the G allele of rs7601754 displayed a protective effect against NMOSD (OR = 0.53, 95% CI 0.36-0.76, P corr = 0.006). Our study indicates that STAT4 polymorphisms are associated with the risk of NMOSD, which provides novel insights into the underlying mechanisms of this disease.


Assuntos
Neuromielite Óptica/genética , Polimorfismo de Nucleotídeo Único , Fator de Transcrição STAT4/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Mielite Transversa/genética , Risco , Fator de Transcrição STAT4/fisiologia
10.
Afr J Tradit Complement Altern Med ; 14(2): 319-324, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28573248

RESUMO

BACKGROUND: The demand for the chemopreventive drug from the plant source is increasing in recent times, owing to its various biological activities without any adverse effect. The intention of this current study was to examine the anti-glioma effect of Withaferin A (WFA) on C6 glioma cell line model. MATERIALS AND METHODS: C6 glioma cells were administrated with different concentration of WFA (50, 100, 200 and 500 µg/mL) and DMSO (control) group to examine its anti-proliferative, anti-inflammatory and pro-apoptotic activities. RESULTS: Treatment with WFA showed a significant decline in the glioma cell count in a dose-dependent manner and thus proving its anti-proliferative effect. Similarly, inflammatory markers were also substantially lowered upon treatment with different concentration of WFA. However, DNA fragmentation and apoptotic markers like Caspase-3 and 9 were concomitantly enhanced after co-cultured with different concentration of WFA and thus exhibiting its cytotoxicity efficacy. Furthermore, the protein expression of Bcl2 and Bax were markedly downregulated and upregulated respectively; upon treatment with WFA on C6 glioma cells. CONCLUSION: The outcome of this study evidently demonstrates that C6 glioma cells co-cultured with increased concentration of WFA, showed an anti-proliferative, anti-inflammatory and pro-apoptotic effect in a dose-dependent fashion.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Apoptose , Caspases/metabolismo , Glioma/tratamento farmacológico , NF-kappa B/metabolismo , Fitoterapia , Vitanolídeos/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacologia , Transporte Biológico , Linhagem Celular Tumoral , Proliferação de Células , Fragmentação do DNA/efeitos dos fármacos , Ativação Enzimática , Glioma/metabolismo , Inflamação/etiologia , Inflamação/prevenção & controle , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Withania/química , Vitanolídeos/farmacologia , Proteína X Associada a bcl-2/metabolismo
11.
Mol Neurobiol ; 54(7): 5236-5242, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-27578014

RESUMO

The CD40 gene is associated with many autoimmune diseases; however, there are few studies in literatures that investigate the association between CD40 and neuromyelitis optica spectrum disorders (NMOSD). This study aimed to estimate the potential association of CD40 gene polymorphisms with susceptibility to NMOSD. Four SNPs (rs1883832, rs3765459, rs4810485, and rs6074022) were selected and genotyped in a Chinese cohort comprising 162 patients with NMOSD and 237 healthy controls. P values, odds ratios (ORs), and 95 % confidential intervals (CI) for four test models (allelic, additive, dominant, and recessive) were used to assess relationships between CD40 and NMOSD. Results showed that the rs3765459 variant was significantly associated with increased risk of NMOSD in allelic model (OR = 1.48, 95 % CI 1.10-1.98, P = 0.009, P corr = 0.037), and similar results were detected in the additive and recessive models (OR = 1.47, 95 % CI 1.09-1.97, P = 0.010, P corr = 0.042; OR = 2.12, 95 % CI 1.18-3.8, P = 0.012, P corr = 0.048, respectively). Other three SNPs showed protections on NMOSD in dominant models (rs6074022, OR = 0.64, 95 % CI 0.42-0.95, P = 0.031; rs1883832, OR = 0.65, 95 % CI 0.43-0.97, P = 0.036; and rs4810485, OR = 0.63, 95 % CI 0.42-0.95, P = 0.029, respectively), but not significantly after Bonferroni corrections for multiple tests. In addition, haplotype analysis of these SNPs in tight linkage did not reveal significant association with NMOSD. This study indicates that the rs3765459 variant in CD40 gene is associated with susceptibility to NMOSD. Larger sample size studies in other ethnicities are needed to verify this association.


Assuntos
Antígenos CD40/genética , Haplótipos/genética , Neuromielite Óptica/genética , Polimorfismo de Nucleotídeo Único/genética , Alelos , Povo Asiático/genética , Etnicidade , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
12.
Tumour Biol ; 37(11): 15079-15085, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27658779

RESUMO

The aim of this study was to investigate the prognostic value of dicarbonyl/L-xylulose reductase (DCXR) in human hepatocellular carcinoma (HCC). Immunohistochemistry and tissue microarrays were used to evaluate DCXR protein expression levels. Image-Pro Plus was used to calculate the integral optic density (IOD) in each tissue sample, which represented the expression level of DCXR. DCXR proteins were found to be significantly lower in HCC tumor tissues (P < 0.0001) according to immunohistochemical analysis of DCXR protein levels in 74 paired HCC tissue and peritumoral non-cancer tissues. The prognostic value of DCXR in HCC was assessed in 290 cases of the training cohort and 74 cases of the validation cohort. Shorter overall survival (OS) time and shorter time to recurrence (TTR) in both the training and validation set were found to be associated with lower expression levels of DCXR. In the training set, the expression level of DCXR in HCC was an independent prognostic factor for OS according to univariate and multivariate analyses. In conclusion, DCXR expression is an independent prognostic factor for OS and TTR of post-operative HCC patients, and low expression levels of DCXR in HCC may indicate poor outcome of HCC patients after surgical resection.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Desidrogenase do Álcool de Açúcar/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Análise Serial de Tecidos
13.
Oncotarget ; 7(41): 66623-66634, 2016 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-27579613

RESUMO

This study aimed to investigate whether the inclusion of tumor size could improve the prognostic accuracy in patients with esophageal squamous cell cancer (ESCC). A total of 387 patients with ESCC who underwent curative resection were enrolled in this analysis. The patients were categorized into small-sized tumors (SSTs) and large-sized tumors (LSTs) using an appropriate cut-off point for tumor size. Kaplan-Meier survival curve and log-rank test were used to evaluate the prognostic value of tumor size. A Cox regression model was adopted for multivariate analysis. Their accuracy was compared based on the presence or absence of tumor size. Using 3.5 cm as the optimal cut-off point, 228 and 159 patients presented with LSTs (≥ 3.5 cm) and SSTs (< 3.5 cm), respectively. The patients with LSTs had significantly worse prognoses than patients with SSTs (23.9% vs. 43.2%, P < 0.001). Multivariate analysis revealed that tumor size, histological type, invasion depth, and lymph node metastasis were independent predictors of overall survival. The addition of tumor size to the AJCC TNM staging improved the predictive accuracy of the 5-year survival rate by 3.9%. Further study showed that tumor size and T stage were independent predictors of the prognosis of node-negative patients, and the combination of tumor size and T stage improved the predictive accuracy by 3.7%. In conclusion, tumor size is indeed a simple and practical prognostic factor in patients with ESCC. It can be used to improve the prognostic accuracy of the current TNM staging, especially for patients with node-negative disease.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esôfago/cirurgia , Carga Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Esôfago/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sensibilidade e Especificidade
14.
Cell Physiol Biochem ; 39(2): 768-79, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27467187

RESUMO

BACKGROUND/AIMS: Neural precursor cell-expressed developmentally down-regulated gene 4 (NEDD4) plays an important role in tumor cell growth, yet its role in hepatocellular carcinoma (HCC) remains unclear. This study is to establish NEDD4 as a prognostic biomarker by which the survival of HCC patients can be predicted and to reveal the role of NEDD4 in hepatocellular carcinoma cell growth. METHODS: The expression of NEDD4 in 219 HCC specimens was assessed by immunohistochemistry. Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses. The roles of NEDD4 in hepatocellular carcinoma cell proliferation and invasion were determined. RESULTS: The patients with low NEDD4 expression tumors had an average cumulative survival of 64.9 ± 6.5 months during follow-up while the patients with high NEDD4 expression tumors had an average cumulative survival of 20.3 ± 15.8 months. NEDD4 silencing inhibited Huh7 cell proliferation and altered cell cytoskeletal assembly, and NEDD4 depletion furthermore seemed to suppress cell migration and invasion. A possible molecular mechanism for the observed effects might be that NEDD4 silence led to an increase in PTEN (phosphatase and tensin homologue) expression, which in turn resulted in the inactivation of STAT3, AKT, and ERK1/2. CONCLUSION: Our findings indicate that NEDD4 may participate in the HCC progression and may therefore be a potential target for HCC therapy.


Assuntos
Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Neoplasias Hepáticas/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Citoesqueleto de Actina/metabolismo , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirurgia , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Ubiquitina-Proteína Ligases Nedd4 , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Ubiquitina-Proteína Ligases/genética
15.
Mol Cell Biochem ; 392(1-2): 117-24, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24652103

RESUMO

In hypertensive animals and patients, oxidative stress represents the primary risk factor for progression of renal disease. Recently, it has been demonstrated that hydrogen, as a novel antioxidant, can selectively reduce hydroxyl radicals and peroxynitrite anion to exert therapeutic antioxidant activity. Herein, we investigated the protective effect of hydrogen-rich water (HW) against renal injury in spontaneously hypertensive rats (SHR). The 8-week-old male SHR and age-matched Wistar-Kyoto rats were randomized into HW-treated (1.3 ± 0.2 mg/l for 3 months, drinking) and vehicle-treated group. Although treatment with HW had no significant effect on blood pressure, it significantly ameliorated renal injury in SHR. Treatment with HW lowered reactive oxygen species formation, upregulated the activities of superoxide dismutase, glutathione peroxidase, glutathione-S-epoxide transferase, and catalase, and suppressed NADPH oxidase activity. Treatment with HW in SHR depressed pro-inflammatory cytokines expression including TNF-α, IL-6, IL-1ß, and macrophage chemoattractant protein 1, which might be mediated by suppressing nuclear factor-κB activation. In addition, treatment with HW had protective effect on mitochondrial function including adenosine triphosphate formation and membrane integrity in SHR. In conclusion, consumption of HW is a promising strategy to alleviate renal injury as a supplement for anti-hypertensive therapy.


Assuntos
Água Potável/química , Hidrogênio/análise , Rim/lesões , Animais , Sequência de Bases , Pressão Sanguínea , Quimiocina CCL2/sangue , Citocinas/sangue , Primers do DNA , Rim/metabolismo , Rim/fisiopatologia , Masculino , Mitocôndrias/fisiologia , NADPH Oxidases/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
16.
Chin Med J (Engl) ; 125(17): 3143-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22932196

RESUMO

BACKGROUND: Can single-agent maintenance therapy be considered as an ideal strategy for non-small cell lung cancer (NSCLC) treatment to achieve prolonged survival and tolerated toxicity? A systematic review and meta-analysis was performed to elucidate this issue. METHODS: The electronic databases were searched for RCTs comparing single-agent maintenance therapy with placebo, best support care or observation. The required data for estimation of response, survival and toxicity were extracted from the publications and the combined data were calculated. RESULTS: Eleven RCTs involving 3686 patients were identified. We found a statistically significant higher probability of tumor response for patients with maintenance therapy versus control patients (OR: 2.80, 95%CI: 2.15 - 3.64). Patients receiving maintenance therapy had significantly longer progression-free survival (PFS) (HR: 0.67, 95%CI: 0.62 - 0.71) and overall survival (OS) (HR: 0.84, 95%CI: 0.78 - 0.90). However, maintenance therapy was associated with more severe toxicities (OR: 6.45, 95%CI: 4.61 - 9.01). CONCLUSION: In patients with advanced NSCLC, the use of single-agent maintenance therapy is associated with higher response rate and significantly prolongs PFS and OS despite of the risk of additional toxicity.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Humanos , Neoplasias Pulmonares/mortalidade , Viés de Publicação
17.
J Thorac Dis ; 4(3): 265-71, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22754665

RESUMO

INTRODUCTION: Lung cancer is the leading cause of cancer-associated death. In many countries, adenocarcinoma is the most common histologic type in lung cancer. Previously, few factors are identified to be prognostic indicators for the patients with small lung adenocarcinoma. Recently, the ground glass opacity (GGO) area found on high-resolution computed tomography (HRCT) scanning was identified as a prognostic indicator in some studies. But no clear consensus has been defined. METHODS: The PubMed/MEDLINE, EMBASE, Cochrane library and SpringerLink electronic databases were searched for articles related to ground glass opacity on computed tomography in patients with small lung adenocarcinoma. Data was extracted and analyzed independently by two investigators. An estimate of the hazard ratio (HR) for comparing high GGO ratio with low GGO ratio was extracted. The respective HRs was combined into a pooled HR, and 95% confidence interval (CI) was calculated for each study. The publication heterogeneity was assessed graphically using performing Beggs' funnel plot. All the statistical tests used in our meta-analysis were performed with STATA version 11. RESULTS: Thirteen studies, encompassing 2,027 patients, were included in our meta-analysis. Ten of these studies revealed that the GGO ratio in small lung adenocarcinoma is a good prognostic indicator. Seven studies were combined in a meta-analysis using overall survival (OS) as the end point of interest. The weighted HR of 7 studies was 0.85, with relative 95% CI ranging from 0.78 to 0.93 (P=0.009). For the surgical patient population, the primary endpoint of relapse-free survival (RFS) was superior with high GGO area on computed tomography (The combined HR 0.82, 95% CI 0.74-0.90; P=0.007). CONCLUSIONS: The result of our meta-analysis suggested that the GGO area measured on HRCT had a prognostic value of overall survival and relapse-free survival in small lung adenocarcinoma. The GGO ratio may be an independent prognostic factor for small lung adenocarcinoma.

18.
PLoS One ; 7(4): e35065, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22493729

RESUMO

BACKGROUND: Lysine specific demethylase 1 (LSD1) has been identified and biochemically characterized in epigenetics, but the pathological roles of its dysfunction in lung cancer remain to be elucidated. The aim of this study was to evaluate the prognostic significance of LSD1 expression in patients with non-small cell lung cancer (NSCLC) and to define its exact role in lung cancer proliferation, migration and invasion. METHODS: The protein levels of LSD1 in surgically resected samples from NSCLC patients were detected by immunohistochemistry or Western blotting. The mRNA levels of LSD1 were detected by qRT-PCR. The correlation of LSD1 expression with clinical characteristics and prognosis was determined by statistical analysis. Cell proliferation rate was assessed by MTS assay and immunofluorescence. Cell migration and invasion were detected by scratch test, matrigel assay and transwell invasion assay. RESULTS: LSD1 expression was higher in lung cancer tissue more than in normal lung tissue. Our results showed that over-expression of LSD1 protein were associated with shorter overall survival of NSCLC patients. LSD1 was localized mainly to the cancer cell nucleus. Interruption of LSD1 using siRNA or a chemical inhibitor, pargyline, suppressed proliferation, migration and invasion of A549, H460 and 293T cells. Meanwhile, over-expression of LSD1 enhanced cell growth. Finally, LSD1 was shown to regulate epithelial-to-mesenchymal transition in lung cancer cells. CONCLUSIONS: Over-expression of LSD1 was associated with poor prognosis in NSCLC, and promoted tumor cell proliferation, migration and invasion. These results suggest that LSD1 is a tumor-promoting factor with promising therapeutic potential for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Regulação Neoplásica da Expressão Gênica , Histona Desmetilases/genética , Neoplasias Pulmonares/metabolismo , Pulmão/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Histona Desmetilases/antagonistas & inibidores , Humanos , Imuno-Histoquímica , Pulmão/efeitos dos fármacos , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Pargilina/farmacologia , Prognóstico , RNA Interferente Pequeno/genética , Taxa de Sobrevida
19.
Thorac Cancer ; 3(4): 341-347, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28920278

RESUMO

BACKGROUND: Abraxane is a novel Cremophor-free nanoparticle paclitaxel that has been demonstrated to improve efficacy in the treatment of solid tumors. We undertook this retrospective study to evaluate the efficacy and safety of Abraxane in the progressive or recurrent non-small cell lung cancer (NSCLC) patients. METHODS: From August 2009 to April 2011, 33 patients who were diagnosed with progressive or recurrent NSCLC and treated with one or more prior platinum-based chemotherapies, were enrolled. The patients were injected with Abraxane, 260 mg/m2 , d1, and were evaluated for efficacy and safety. The treatment was repeated every three weeks unless progressive lesions or unacceptable toxicities were found. RESULTS: There were no complete response and 11 partial responses (33.3%). Patients with squamous cell carcinoma showed better responses than those with adenocarcinoma (41.7% and 21.1%, respectively). Fourteen patients had stable disease, and the disease control rate was 75.8%. The median progression-free survival was five months (95% confidence interval [CI]: 3.5-6.5). Four patients (12.1%) experienced grade 3-4 hematologic toxicities; one anemia (3.0%), two leucopenia (6.1%) and one thrombocytopenia (3.0%). Six patients (18.2%) experienced grade 3-4 non-hematologic toxicities; two abnormal hepatic functions (6.1%), one fatigue (3.0%), one peripheral neuropathy (3.0%), and two alopecia (6.1%). CONCLUSION: Recurrent and progressive NSCLC patients pretreated with platinum-based chemotherapy might benefit from Abraxane with tolerable adverse events.

20.
J Gastrointestin Liver Dis ; 20(3): 271-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21961095

RESUMO

BACKGROUND AND AIMS: RNA interference (RNAi) has emerged as a potential new approach against hepatitis B virus (HBV) infection but unfortunately it also selects resistant virus mutants. In this study we combined the advantages of artificial micro RNAs (amiRNAs) reported previously with the purpose of constructing a more practical amiRNA with high inhibition effects against HBV. METHOD: Aiming at conserved sites, we constructed singular-sequence vectors amiRNA-HBV1, amiRNA-HBV2, amiRNA-HBV3 and amiRNA-HBV4. We chose the two sequences of high efficiency, then built the tandem-sequence vector amiRNA-HBV3-HBV4. These vectors were transfected into HepG2.2.15 transiently. The secreted HBV surface antigen (HBsAg) and HBV 'e' antigen (HBeAg) were measured with a chemiluminescent microparticle immunoassay, and intracellular and extracellular HBV DNA was quantified by real-time PCR. RESULTS: Our results demonstrated that amiRNA-HBV1, amiRNA-HBV2, amiRNA-HBV3, and amiRNA-HBV4 achieved a maximum inhibition of HBV mRNA expression of 29.3%, 14.9%, 61.2%, and 75.6%, respectively, while the tandem amiRNA-HBV3-HBV4 vector led to an inhibition of 87.2%. CONCLUSION: Taken together, our data suggest that vector-based multiple artificial microRNAs are a promising therapeutic approach for chronic HBV infection.


Assuntos
Vírus da Hepatite B/genética , Hepatite B/terapia , MicroRNAs/genética , Sequência de Bases , Replicação do DNA , DNA Viral/análise , Vetores Genéticos , Células Hep G2 , Humanos , Dados de Sequência Molecular , Mutação , Interferência de RNA , Transfecção
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