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1.
Zhonghua Nei Ke Za Zhi ; 62(11): 1329-1334, 2023 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-37935500

RESUMO

Objective: To explore the value of the aMAP risk score (age, male, albumin-bilirubin, and platelets) to predict early recurrence within one year after microwave ablation in patients with small hepatocellular carcinoma. Methods: This was a retrospective study that enrolled 142 patients diagnosed with hepatocellular carcinoma who were treated with microwave ablation in the Department of Hepatology Unit of Nanfang Hospital, Southern Medical University from July 2016 to July 2021. The cohort enrolled 121 male and 21 female patients, including 110 patients that were <60 years old. All the patients were followed-up after microwave ablation to evaluate residual tumor and recurrence of tumor by computed tomography or magnetic resonance imaging. The observation indices mainly included general data and imaging data of patients. Using the X-tile tools, patients were divided into two groups: a high aMAP score group and a low aMAP score group. Multivariate Cox regression analysis was conducted for comparison of independent risk factors. Results: Multivariate Cox regression showed that high aMAP score, maximum tumor diameter >20 mm, and high AFP were the independent risk factors of early recurrence (all P<0.05). Kaplan-Meier survival curves showed that the median recurrence-free survival was 25.5 months in the low aMAP score group and 6.1 months in the high aMAP score group (P=0.001). Conclusions: The aMAP score could predict the early recurrence within 1 year of small hepatocellular carcinoma after microwave ablation. Patients with high aMAP score should undergo rigorous postoperative follow-up evaluations..


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Resultado do Tratamento , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Ablação por Cateter/métodos , Recidiva Local de Neoplasia/cirurgia
2.
SAR QSAR Environ Res ; 34(1): 65-89, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36762439

RESUMO

Probing binding modes of GDP, GTP and GNP to NRAS are of significance for understanding the regulation mechanism on the activity of RAS proteins. Four separate Gaussian accelerated molecular dynamics (GaMD) simulations were performed on the apo, GDP-, GTP- and GNP-bound NRAS. Dynamics analyses suggest that binding of three ligands highly affects conformational states of the switch domains from NRAS, which disturbs binding of NRAS to its effectors. The analyses of free energy landscapes (FELs) indicate that binding of GDP, GTP and GNP induces more energetic states of NRAS compared to the apo NRAS but the presence of GNP makes the switch domains more ordered than binding of GDP and GNP. The information of interaction networks of ligands with NRAS reveals that the π-π interaction of residue F28 and the salt bridge interactions of K16 and D119 with ligands stabilize binding of GDP, GTP and GNP to NRAS. Meanwhile magnesium ion plays a bridge role in interactions of ligands with NRAS, which is favourable for associations of GDP, GTP and GNP with NRAS. This work is expected to provide useful information for deeply understanding the function and activity of NRAS.


Assuntos
Simulação de Dinâmica Molecular , Relação Quantitativa Estrutura-Atividade , Guanosina Difosfato/química , Guanosina Difosfato/metabolismo , Conformação Molecular , Guanosina Trifosfato/química , Guanosina Trifosfato/metabolismo , Conformação Proteica
3.
Zhonghua Gan Zang Bing Za Zhi ; 31(11): 1163-1168, 2023 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-38238949

RESUMO

Objective: To compare the postoperative liver function injury condition in patients with intermediate-and advanced-stage hepatocellular carcinoma (HCC) treated with hepatic artery infusion chemotherapy (HAIC) and hepatic artery chemoembolization (TACE) combined with immune checkpoint inhibitors (ICIs) and multi-target tyrosine kinase inhibitors (TKIs). Methods: Patients with intermediate-and advanced-stage HCC who were admitted and treated with HAIC/TACE+ICIs+TKIs therapy at Nanfang Hospital of Southern Medical University from January 2019 to November 2021, with follow-up up to July 2023, were retrospectively enrolled. The results of liver function tests within one week before interventional surgery and on the first day after surgery were recorded. The degree of postoperative liver injury was graded according to the common terminology criteria for adverse events 5.0 (CTCAE 5.0). The treatment efficacy was evaluated according to RECIST 1.1 criteria. Measurement data were compared between groups using a t-test or a non-parametric rank sum test. Enumeration data were compared between the groups using the χ(2) test or Fisher's exact probability method. The survival condition differences were analyzed by the log-rank method. Results: This study included 82 and 77 cases in the HAIC and TACE groups. There were no statistically significant differences between the two groups of patients in terms of gender, age, physical condition score, number of tumors, presence or absence of liver cirrhosis, Child-Pugh grade, albumin-bilirubin (ALBI) grade, and combined ICIs and TKIs . The HAIC group had later tumor staging, a greater tumor burden, poorer liver reserve function, and a larger proportion of patients in stage C (81.7% vs. 63.6%), χ(2)=6.573, P = 0.01). There were 53 cases (64.6% vs. 32.5%) with a maximum tumor diameter of ≥ 10cm, χ(2)=16.441, P < 0.001), and more patients had a retention rate of ≥ 10% for indocyanine green (ICG) at 15 minutes (68.3% vs. 51.9%, P = 0.035). The postoperative incidence rate of increased levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin was significantly lower in the HAIC group than that in the TACE group (28.0% vs. 63.6%, χ(2)=20.298, P < 0.001, 54.9% vs. 85.7%, χ(2)=17.917, P < 0.001;40.2% vs. 55.8%, χ(2)=3.873, P = 0.049). The number of patients with postoperative ALBI grade 3 was significantly lower in the HAIC group than that in the TACE group (6.1% vs. 16.9%, χ(2)=4.601, P = 0.032). There was no statistically significant difference in the incidence rate of postoperative hypoalbuminemia, activated partial thromboplastin time, or increased international standardized ratio between the two groups of patients. There was no statistically significant difference in median progression-free survival (7.3 months vs. 8.2 months, P = 0.296) or median overall survival (16.5 months vs. 21.9 months, P = 0.678) between the two groups of patients. Conclusion: The incidence rate of postoperative liver injury is higher in patients with intermediate-and advanced-stage HCC treated with TACE combined with ICIs and TKIs than in patients with HAIC combined with ICIs and TKIs.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/patologia , Artéria Hepática , Estudos Retrospectivos , Quimioembolização Terapêutica/métodos , Resultado do Tratamento , Perfusão , Imunoterapia , Bilirrubina
5.
Planta ; 256(5): 89, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36169724

RESUMO

MAIN CONCLUSION: CgVPE1 is important in the differentiation of TE cells in C. grandis 'Tomentosa' fruits as it may directly affects secondary cell wall construction while participating in PCD. The vacuolar processing enzyme (VPE) plays an important role in both developmental and environmentally inducible programmed cell death (PCD); it was originally identified as a cysteine protease localized in the vacuole to activate and mature vacuolar proteins in plants. Interestingly, we found a VPE called CgVPE1 to be associated with deposition of the secondary cell wall in tracheary element (TE) cells in the pericarp of Citrus grandis 'Tomentosa' fruits. We then used ultrathin sections and the TUNEL assay to verify that PCD is involved in TE development. Furthermore, CgVPE1 was found to be mainly expressed in secretory cavities and TEs in the pericarp of Citrus grandis 'Tomentosa' fruits. Immunolocalization of CgVPE1 in the pericarp indicated that CgVPE1 is mainly distributed in the central large vacuole, endoplasmic reticulum, Golgi vesicles, cytosol, and secondary wall before TE maturation. CgVPE1 appeared earlier in the endoplasmic reticulum and Golgi vesicles of TEs cells. The vesicles containing CgVPE1 near the large central vacuole and secondary wall were observed, respectively. CgVPE1 proteins content in the cytoplasm decreased sharply, while the CgVPE1 content in the secondary cell wall did not change significantly after vacuole rupture. CgVPE1 protein contents in the secondary cell wall were significantly reduced until the TE cells developed into hollow thick-walled cells. Furthermore, labeling of VPE homologues in Arabidopsis thaliana using immunoelectron microscopy with anti-CgVPE1 antibody revealed that VPE homologues were specifically distributed in the secondary cell wall of stem TEs. Overall, these results suggested that CgVPE1 is not only involved PCD during TE cell development; furthermore, it may directly participate in the construction of plant secondary cell walls.


Assuntos
Arabidopsis , Citrus , Arabidopsis/metabolismo , Diferenciação Celular , Parede Celular/metabolismo , Frutas
6.
Nat Ecol Evol ; 6(4): 427-438, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35210579

RESUMO

Fitness landscapes, mappings of genotype/phenotype to their effects on fitness, are invaluable concepts in evolutionary biochemistry. Although widely discussed, measurements of phenotype-fitness landscapes in proteins remain scarce. Here, we quantify all single mutational effects on fitness and phenotype (EC50) of VIM-2 ß-lactamase across a 64-fold range of ampicillin concentrations. We then construct a phenotype-fitness landscape that takes variations in environmental selection pressure into account. We found that a simple, empirical landscape accurately models the ~39,000 mutational data points, suggesting that the evolution of VIM-2 can be predicted on the basis of the selection environment. Our landscape provides new quantitative knowledge on the evolution of the ß-lactamases and proteins in general, particularly their evolutionary dynamics under subinhibitory antibiotic concentrations, as well as the mechanisms and environmental dependence of non-specific epistasis.


Assuntos
Epistasia Genética , Aptidão Genética , Modelos Genéticos , Mutação , Fenótipo , Proteínas
7.
Zhonghua Gan Zang Bing Za Zhi ; 29(11): 1059-1062, 2021 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-34933423

RESUMO

Objective: To explore the clinical effect of microwave ablation in the treatment of early small liver cancer (≤3 cm). Methods: 103 cases with small liver cancer (tumor number < 3 and maximum tumor diameter < 3 cm) who underwent microwave ablation from November 2016 to November 2018 were retrospectively collected. The rate of residual lesions, recurrence rate one-year after the operation, and surgical complications were observed and grouped according to tumor size (< 2 cm and≥2 cm group) and tumor numbers (solitary and 2 ~ 3 lesion groups). The therapeutic effects of each group were compared and analyzed. Results: The tumor residual rate and one-year recurrence rate of small liver cancer after microwave ablation were 11.7% and 35.0%, respectively. The post-ablation syndrome incidence rate was 52.4%, with no serious adverse events. Compared with tumors < 2 cm, patients with≥2 cm had a higher postoperative residual rate (χ(2) = 7.651, P = 0.006), and the one-year recurrence rate of more solitary nodular tumors was lower (χ(2) = 10.125, P = 0.001). Conclusion: Microwave ablation is a safe and effective treatment for early small liver cancer, and it is more effective for small solitary nodules (< 2 cm).


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Micro-Ondas , Estudos Retrospectivos , Resultado do Tratamento
8.
Zhonghua Gan Zang Bing Za Zhi ; 29(10): 1031-1034, 2021 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-34814404

RESUMO

Molecular targeted drugs are the first choice for systemic treatment of liver cancer. In the past decade, several anti-liver cancer targeted drugs have been launched. More recently, immunotherapy has become a dazzling nova in the field of systemic treatment of liver cancer. Nivolumab and pembrolizumab have been approved as second-line treatments for patients with advanced hepatocellular carcinoma treated with sorafenib. However, the effect of single-agent treatment is always unsatisfactory in advanced liver cancer. An increasing number of evidences suggests that molecular targeted drugs have important immunomodulatory effects for liver cancer, and several targeted combined immunotherapies have also shown promising clinical effectiveness. This paper reviews the immunomodulatory effects of several molecular targeted drugs in the field of liver cancer.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Preparações Farmacêuticas , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Sistema Imunitário , Neoplasias Hepáticas/tratamento farmacológico , Terapia de Alvo Molecular
9.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(6): 505-512, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34148315

RESUMO

Objective: Transanal total mesorectal excision (taTME) was a very hot topic in the first few years since its appearance, but now more introspections and controversies on this procedure have emerged. One of the reasons why the Norwegian Ministry of Health stopped taTME was the high incidence of postoperative anastomotic leak. In current study, the incidence and risk factors of anastomotic leak after taTME were analyzed based on the data registered in the Chinese taTME Registry Collaborative (CTRC). Methods: A case-control study was carried out. Between November 15, 2017 and December 31, 2020, clinical data of 1668 patients undergoing taTME procedure registered in the CTRC database from 43 domestic centers were collected retrospectively. After excluding 98 cases without anastomosis and 109 cases without complete postoperative complication data, 1461 patients were finally enrolled for analysis. There were 1036 males (70.9%) and 425 females (29.1%) with mean age of (58.2±15.6) years and mean body mass index of (23.6±3.8) kg/m(2). Anastomotic leak was diagnosed and classified according to the International Study Group of Rectal Cancer (ISREC) criteria. The risk factors associated with postoperative anastomotic leak cases were analyzed. The impact of the cumulative number of taTME surgeries in a single center on the incidence of anastomotic leak was evaluated. As for those centers with the number of taTME surgery ≥ 40 cases, incidence of anastomic leak between 20 cases of taTME surgery in the early and later phases was compared. Results: Of 1461 patients undergoing taTME, 103(7.0%) developed anastomotic leak, including 71 (68.9%) males and 32 (31.1%) females with mean age of (59.0±13.9) years and mean body mass index of (24.5±5.7) kg/m(2). The mean distance between anastomosis site and anal verge was (2.6±1.4) cm. Thirty-nine cases (37.9%) were classified as ISREC grade A, 30 cases (29.1%) as grade B and 34 cases (33.0%) as grade C. Anastomotic leak occurred in 89 cases (7.0%,89/1263) in the laparoscopic taTME group and 14 cases (7.1%, 14/198) in the pure taTME group. Multivariate analysis showed that hand-sewn anastomosis (P=0.004) and the absence of defunctioning stoma (P=0.013) were independently associated with anastomotic leak after taTME. In the 16 centers (37.2%) which performed ≥ 30 taTME surgeries with cumulative number of 1317 taTME surgeries, 86 cases developed anastomotic leak (6.5%, 86/1317). And in the 27 centers which performed less than 30 taTME surgeries with cumulative number of 144 taTME surgeries, 17 cases developed anastomotic leak (11.8%, 17/144). There was significant difference between two kinds of center (χ(2)=5.513, P=0.019). Thirteen centers performed ≥ 40 taTME surgeries. In the early phase (the first 20 cases in each center), 29 cases (11.2%, 29/260) developed anastomotic leak, and in the later phase, 12 cases (4.6%, 12/260) developed anastomotic leak. The difference between the early phase and the later phase was statistically significant (χ(2)=7.652, P=0.006). Conclusion: The incidence of anastomotic leak after taTME may be reduced by using stapler and defunctioning stoma, or by accumulating experience.


Assuntos
Laparoscopia , Neoplasias Retais , Adulto , Idoso , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/cirurgia , Reto/cirurgia , Estudos Retrospectivos , Fatores de Risco
10.
SAR QSAR Environ Res ; : 1-22, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34130570

RESUMO

Cyclin-dependent kinase 2 (CDK2) has been regarded as a promising drug target for anti-tumour agents. In this study, molecular dynamics (MD) simulations and principal component (PC) analysis were used to explore binding mechanism of three inhibitors 1PU, CDK, 50Z to CDK2 and influences of their bindings on conformational changes of CDK2. The results show that bindings of inhibitors yield obvious impacts on internal dynamics, movement patterns and conformational changes of CDK2. In addition, molecular mechanics generalized Born surface area (MM-GBSA) was applied to calculate binding free energies between three inhibitors and CDK2 and evaluate their binding ability to CDK2. The results show that CDK has the strongest binding to CDK2 among the current three inhibitors. Residue-based free energy decomposition method was further utilized to decode the contributions of a single residue to binding of inhibitors, and it was found that three inhibitors not only produce hydrogen bonding interactions and hydrophobic interactions with key residues of CDK2, which promotes binding of three inhibitors to CDK2, but also share similar binding modes. This work is expected to be helpful for design of efficient drugs targeting CDK2.

11.
Zhonghua Gan Zang Bing Za Zhi ; 29(4): 326-331, 2021 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-33979958

RESUMO

Objective: To analyze the clinical efficacy and safety of camrelizumab combined with apatinib as a second-line therapy for unresectable hepatocellular carcinoma (HCC). Methods: Ninety-four cases with mid-and advanced-stage HCC who received camrelizumab combined with apatinib as second-line treatment were enrolled. Routine blood test, blood biochemical indexes, tumor stage, tumor imaging characteristics, previous treatment strategies and other clinical data before treatment were documented. Imaging examination follow-up results and adverse reactions during treatment were followed up until the end of follow-up or loss of follow-up or death. Kaplan-Meier method was used to analyze the clinical efficacy. Results: As of the last follow-up, 94 cases with mid-and advanced-stage HCC had received camrelizumab combined with apatinib as second-line treatment. Among them, 15 cases were lost to follow-up, 31 cases died, and 48 cases survived. The overall remission rate was 31.9%. The overall disease control rate was 71.3%. The median time to disease-free progression was 6.6 months. The median time to disease progression was not yet available. The 1-year cumulative survival rate was 62.3%. Grade 3 and above adverse reactions mainly included were thrombocytopenia (7.4%), abdominal pain (4.3%), active hepatitis (4.3%), leukopenia (4.3%), diarrhea (3.2%), hand-foot syndrome (3.2%). All adverse reactions were effectively controlled. Conclusion: Camrelizumab combined with apatinib can effectively prolong the survival period of patients with mid-and advanced-stage HCC, and it is well tolerated.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Piridinas , Estudos Retrospectivos , Resultado do Tratamento
12.
Br J Nutr ; 126(4): 510-517, 2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-33143765

RESUMO

To evaluate the impacts of guanidinoacetic acid (GAA) and coated folic acid (CFA) on growth performance, nutrient digestion and hepatic gene expression, fifty-two Angus bulls were assigned to four groups in a 2 × 2 factor experimental design. The CFA of 0 or 6 mg/kg dietary DM folic acid was supplemented in diets with GAA of 0 (GAA-) or 0·6 g/kg DM (GAA+), respectively. Average daily gain (ADG), feed efficiency and hepatic creatine concentration increased with GAA or CFA addition, and the increased magnitude of these parameters was greater for addition of CFA in GAA- diets than in GAA+ diets. Blood creatine concentration increased with GAA or CFA addition, and greater increase was observed when CFA was supplemented in GAA+ diets than in GAA- diets. DM intake was unchanged, but rumen total SCFA concentration and digestibilities of DM, crude protein, neutral-detergent fibre and acid-detergent fibre increased with the addition of GAA or CFA. Acetate:propionate ratio was unaffected by GAA, but increased for CFA addition. Increase in blood concentrations of albumin, total protein and insulin-like growth factor-1 (IGF-1) was observed for GAA or CFA addition. Blood folate concentration was decreased by GAA, but increased with CFA addition. Hepatic expressions of IGF-1, phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin and ribosomal protein S6 kinase increased with GAA or CFA addition. Results indicated that the combined supplementation of GAA and CFA could not cause ADG increase more when compared with GAA or CFA addition alone.


Assuntos
Ração Animal , Bovinos/crescimento & desenvolvimento , Ácido Fólico/administração & dosagem , Glicina/análogos & derivados , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Creatina , Detergentes , Dieta/veterinária , Suplementos Nutricionais , Digestão , Expressão Gênica , Glicina/administração & dosagem , Fator de Crescimento Insulin-Like I , Fígado , Masculino , Nutrientes , Fosfatidilinositol 3-Quinases , Rúmen
13.
Eur Rev Med Pharmacol Sci ; 24(8): 4263-4270, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32373962

RESUMO

OBJECTIVE: To elucidate the molecular mechanism of Simvastatin on inhibiting malignant progression of lung cancer. PATIENTS AND METHODS: Relative levels of METTL3 and EZH2 in lung cancer tissues and adjacent normal ones were detected by quantitative real-time polymerase chain reaction (qRT-PCR). In addition, their levels in lung cancer patients with different pathological stages were determined as well. A549 cells were induced with different doses of Simvastatin for 24 h. Subsequently, relative levels of METTL3 and EZH2 in cells were detected. Proliferative and metastatic abilities in A549 cells were examined by cell counting kit-8 (CCK-8), 5-Ethynyl-2'- deoxyuridine (EdU) and transwell assay, respectively. RIP assay was conducted to detect the presence of m6A modification on EZH2 mRNA and the interaction between IGF2BP2 and EZH2. Relative levels of EZH2 and epithelial-mesenchymal transition (EMT)-associated genes (E-cadherin and N-cadherin), and metastatic abilities were detected in Simvastatin-induced A549 cells transfected with pcDNA-METTL3. RESULTS: METTL3 and EZH2 levels were upregulated in lung cancer tissues, which were higher in advanced stage lung cancer patients. Their levels, as well as cell proliferative and metastatic abilities, were dose-dependently inhibited in Simvastatin-induced A549 cells. METTL3 positively regulated EZH2 level, and m6A modification on its mRNA. Moreover, the interaction between IGF2BP2 and EZH2 could be inhibited by knockdown of METTL3. Simvastatin could abolish the role of METTL3 in regulating relative levels of EZH2 and EMT-associated genes, as well as metastatic abilities in A549 cells. CONCLUSIONS: Simvastatin induces METTL3 down-regulation in lung cancer tissues, which further influences EMT via m6A modification on EZH2 mRNA and thus inhibits the malignant progression of lung cancer.


Assuntos
Adenosina/análogos & derivados , Antineoplásicos/farmacologia , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Metiltransferases/antagonistas & inibidores , RNA Mensageiro/metabolismo , Sinvastatina/farmacologia , Células A549 , Adenosina/metabolismo , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metiltransferases/metabolismo , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , Células Tumorais Cultivadas
14.
Nanoscale ; 10(15): 7026-7032, 2018 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-29611859

RESUMO

Tuning of molecular conductance in a liquid environment is a hot topic in molecular electronics. In this article, we explore a new concept where the Fermi level positions of the metallic ends are varied simply by modifying the electroactive salt concentration in solution. We rely on the electrochemical scanning tunneling microscope break junction method that allows the construction in solution of copper atomic contacts that can be then bridged by single molecules. The experimental conductance evolution is first confronted with an analytical formulation that allows the deduction of the molecule's LUMO position and electronic coupling factors. These parameters are in close agreement with those obtained by independent DFT calculations.

15.
Genet Mol Res ; 15(3)2016 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-27706695

RESUMO

The present study clearly showed that chronic exposure to polychlorinated biphenyls (PCBs) at environmentally relevant concentrations can damage juvenile tilapia livers by modulating antioxidant enzyme activities and gene transcription, which affects toxic bioaccumulation and histological congestion. The results suggest that PCBs caused a decrease in the activity of some hepatic antioxidative and biotransformation enzymes (SOD, CAT, GST, T-GSH, and MDA) in tilapia at 7 days, as well as transcriptional changes (sod, cat, and gst). Except for some antioxidant parameters (T-GSH, GSH/GSSG, T-AOC, and MDA), significant declines and increases occurred at 14 and 21 days, respectively. Most of the antioxidant enzymatic signatures and genotoxicity significantly increased at 14 and 21 days. This study presented evidence that PCBs could result in hepatic toxicity through oxidative stress in the early growth stages of tilapia, and we speculated that oxidative stress plays an important role in embryonic developmental toxicity induced by PCBs.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Animais Recém-Nascidos , Antioxidantes/metabolismo , Catalase/genética , Catalase/metabolismo , Ciclídeos , Dano ao DNA , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Fígado/patologia , Malondialdeído/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Transcrição Gênica
16.
Genet Mol Res ; 15(1)2016 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-27051032

RESUMO

In the present study, the tissue-specific and temporal gene expression profiles of four catalogues of gonadal development-related genes (sex differentiation-related, steroid receptor, steroidogenic, and structural genes) were detected in nine tissues and during 11 successive developmental stages in the Pengze crucian carp (Pcc) (a triploid mono-female gynogenic fish). The results showed that these target genes exhibited overlapping distributions in various tissues, with the exception of Pcc-vasa and Pcc-cyp17a1. Gene expression profiling of the developmental stages showed that all of the target genes simultaneously reached peak expression levels at 40 and 48 days post hatching (dph). Both 40 and 48 dph appeared to be two key time points associated with the process of Pcc gonadal development. These data will provide a clear understanding of gene expression patterns associated with the gonadal development-related genes of this gynogenic teleost.


Assuntos
Carpas/genética , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Animais , Carpas/crescimento & desenvolvimento , Carpas/metabolismo , Feminino , Proteínas de Peixes/genética , Perfilação da Expressão Gênica , Gônadas/crescimento & desenvolvimento , Gônadas/metabolismo , Masculino , Especificidade de Órgãos
17.
Cell Death Differ ; 23(8): 1347-57, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26915297

RESUMO

Deafness or hearing loss is a major issue in human health. Inner ear hair cells are the main sensory receptors responsible for hearing. Defects in hair cells are one of the major causes of deafness. A combination of induced pluripotent stem cell (iPSC) technology with genome-editing technology may provide an attractive cell-based strategy to regenerate hair cells and treat hereditary deafness in humans. Here, we report the generation of iPSCs from members of a Chinese family carrying MYO15A c.4642G>A and c.8374G>A mutations and the induction of hair cell-like cells from those iPSCs. The compound heterozygous MYO15A mutations resulted in abnormal morphology and dysfunction of the derived hair cell-like cells. We used a CRISPR/Cas9 approach to genetically correct the MYO15A mutation in the iPSCs and rescued the morphology and function of the derived hair cell-like cells. Our data demonstrate the feasibility of generating inner ear hair cells from human iPSCs and the functional rescue of gene mutation-based deafness by using genetic correction.


Assuntos
Células Ciliadas Auditivas Internas/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Miosinas/genética , Sequência de Bases , Sistemas CRISPR-Cas/genética , Diferenciação Celular , Reprogramação Celular , Pré-Escolar , Derme/citologia , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Células Ciliadas Auditivas Internas/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Mutação , Miosinas/metabolismo , Fator de Transcrição PAX2/genética , Fator de Transcrição PAX2/metabolismo , Fator de Transcrição PAX8/genética , Fator de Transcrição PAX8/metabolismo , Linhagem , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 30(17): 1343-1345;1351, 2016 Sep 05.
Artigo em Chinês | MEDLINE | ID: mdl-29798453

RESUMO

Objective:To investigate the etiology,clinical presentations,diagnosis and treatment of delayed epistaxis after craniocerebral trauma.Method:A retrospective analysis was made including 16 cases who had the traumatic carotid artery injury with massive delayed epistaxis.All of them were finally diagnosed by digital substraction angiography(DSA).Final clinical outcome,radiographic data and follow-up data were analyzed.Result:Two cases of traumatic pesudoaneurysm from internal maxillary artery were embolized with polyvinyl alcohol particles and gelatin sponge.Fourteen cases of traumatic pesudoaneurysm located in ICA cavernous segment was embolized by covered stent.The covered stent placement was successful in all 14 pseudoaneurysms.No procedure-related complications or deaths occurred during follow-up except one of the case with visual field defects and another case with vision loss.Conclusion:Patients with delayed massive epistaxis or recurrent epistaxis after craniofacial trauma which cause pesudoaneurysm should undergo CTA,MRA or DSA examination,and it is would help to get proper diagnosis and treatment as early as possible.No recurrence was found after successful endovascular techniques.

19.
Pathol Biol (Paris) ; 63(1): 21-3, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25553645

RESUMO

OBJECTIVE: Multidrug-resistant organisms (MDROs) have become a widespread serious problem in recent years. Our objective was to determine the prevalence and clinical distribution of MDROs in a tertiary care hospital in China from January 1, 2012 to December 31, 2013. METHODS: The strains were cultured according to standard methods; bacterial identification and susceptibility testing were detected by Vitek 2 system. The prevalence and clinical distribution of extended-spectrum ß-lactamases (ESBLs)-producing enterobacteriaceae, carbapenem-resistant enterobacteriaceae (CRE), multiple-drug/pan-drug resistant P. aeruginosa (MDR/PDR-PA), carbapenem-resistant A. baumannii (CR-AB), methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococcus (VRE) were analyzed by WHONET 5.6. RESULTS: A total of 3537 (33.4%) MDROs were found among 10,594 microbial isolates. ESBLs producing E. coli (ESBLs-ECO) (1153 cases) were the most frequent MDROs, followed by CR-AB (827 cases). The proportion of acquired resistance of A. baumannii (48.9%) accounted for the highest in all the MDROs. These MDROs were mainly isolated from respiratory (70.3%) and secretions (12.7%). Various types of intensive care unit (ICU) and surgery were the main source departments. The proportion of CRE and VRE were relatively few. CRE was most isolated from respiratory tract and closed body cavity fluid, while the distribution of VRE was relatively dispersed. CONCLUSION: High prevalence of MDROs has emerged in our hospital, particular in various ICU and surgical department. The effective way to prevent the further spread of MDROs is to strengthen the protection of respiratory tract and surgical wounds.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Farmacorresistência Bacteriana Múltipla , Centros de Atenção Terciária/estatística & dados numéricos , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , China/epidemiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Testes de Sensibilidade Microbiana , Prevalência , Estudos Retrospectivos , Centro Cirúrgico Hospitalar/estatística & dados numéricos , beta-Lactamases/genética , beta-Lactamases/metabolismo
20.
Int Urol Nephrol ; 46(10): 1969-75, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25150849

RESUMO

Renal biopsy is a very important diagnostic tool in the evaluation of renal diseases. However, bleeding remains to be one of the most serious complications in this procedure. Many new techniques have been improved to make it safer. The risk factors and predictors of bleeding after percutaneous renal biopsy have been extensively reported in many literatures, and generally speaking, the common risk factors for renal biopsy complications focus on hypertension, high serum creatinine, bleeding diatheses, amyloidosis, advanced age, gender and so on. Our primary purpose of this review is to summarize current measures in recent years literature aiming at minimizing the bleeding complication after the renal biopsy, including the drug application before and after renal biopsy, operation details in percutaneous renal biopsies, nursing and close monitoring after the biopsy and other kinds of biopsy methods.


Assuntos
Biópsia , Nefropatias/diagnóstico , Hemorragia Pós-Operatória/prevenção & controle , Humanos , Nefropatias/patologia , Fatores de Risco
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