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1.
Q J Nucl Med Mol Imaging ; 65(2): 172-177, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30916535

RESUMO

BACKGROUND: 18F-FDG PET/CT metabolic characteristics provide the crucial biologic and molecular information for tumors. To explore the relationships between 18F-FDG PET/CT derived parameters such as maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) of primary tumor and clinical stage in different histopathologic subtypes of lung cancer. METHODS: A total of 97 newly diagnosed lung cancer patients (69 males, 28 females; average age 65.1 years) with pathologically proven were retrospectively analyzed, who had undergone 18F-FDG PET/CT scan before treatment from September 2016 to November 2017. SUVmax, MTV and TLG of primary tumor were measured. Clinical stage was mainly determined by 18F-FDG PET/CT, in conjunction with conventional imaging and endoscopic biopsy. Mann-Whitney U test, χ2 test, Spearman correlation test and ROC curve analysis were used for statistical analysis. RESULTS: There were 53 adenocarcinomas (AC), 28 squamous carcinomas (SCC), 13 small cell carcinomas (SCLC), one adenosquamous carcinoma, one mucoepidermoid carcinoma, and one sarcomatoid carcinoma in 97 patients. Both AC and SCLC revealed more cases in stage IV than in stage I-III (P<0.01). There was no significant difference in four stages of SCC (P>0.05). Metabolic parameters of SCC were higher than AC including SUVmax, MTV and TLG (P<0.01). SCLC showed a higher value than AC in TLG (P<0.05). No significant differences were found between AC and SCLC in SUVmax and MTV, also between SCC and SCLC in SUVmax, MTV and TLG (P>0.05). MTV and TLG except SUVmax were positively correlated with stage in AC (P≤0.001). Only MTV showed a positive correlation with stage in SCC (P<0.05). Whereas there were no definitive relationships between metabolic parameters and stage in SCLC (P>0.05). AC with a higher MTV (MTV≥5.965 cm3) indicated a significantly higher rate of distant metastasis than those with a lower MTV (77.5% (31/40) vs. 30.8% (4/13), χ2=9.553, P<0.01), as well as AC with a higher TLG (TLG≥46.922) than those with a lower TLG (88.5% (23/26) vs. 44.4% (12/27), χ2=11.422, P<0.01). CONCLUSIONS: Histopathologic subtypes have a significant influence on the relationships between MTV/TLG not SUVmax of primary foci and stage in lung cancer. Primary MTV/TLG is related to clinical stage closely in AC, and a higher MTV/TLG results in a higher risk of distant metastasis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Fluordesoxiglucose F18/química , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glicólise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Carga Tumoral
2.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414762

RESUMO

BACKGROUND: Hyperuricemia (HUA) is a metabolic disease caused by a disorder of purine metabolism, which increases the risk of cardio-cerebrovascular disease. Serum lipids and blood glucose are risk factors for metabolic syndrome. Thus, this study aimed to assess the prevalence of HUA and its relationship with serum lipids and blood glucose. METHODS: A total of 59,074 cases (32,623 males and 26,451 females) from three hospitals in Lanzhou city from January 2015 to December 2018 were grouped according to serum uric acid (SUA) level to analyze the differences in age, total cholesterol (TC), triacylglycerol (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), fasting blood glucose (FBG), creatinine (Cr), and blood urea nitrogen (BUN). The changes of prevalence of HUA among different age and gender groups was analyzed. Pearson's correlation analysis was used to analyze the correlation of SUA level with clinical indicators. The risk factors of HUA were analyzed by using binary logistic regression analysis. ROC curve was used to analyze the independent risk factors of elevated SUA. RESULTS: The overall prevalence rate of HUA was 19.87% and the prevalence rate of males was significantly higher than that of females (28.35% vs. 9.41%, χ2 = 3,289.143, p < 0.01). The prevalence rates of HUA from 2015 - 2018 were 19.54%, 19.31%, 18.64%, and 21.81%, respectively. Compared with the normal SUA group, TC, TG, and LDL significantly increased in the HUA group. The correlation analysis showed that SUA was negatively correlated with gender and HDL, and positively correlated with age, FBG, TC, TG, and LDL. The logistic regression analysis revealed that TG, TC, and LDL were risk factors for HUA. The ROC curve analysis showed that the risk of HUA significantly increased when TG was above 1.645 mmol/L. CONCLUSIONS: The overall prevalence of HUA in physical examination population has generally been at a high level in the past 4 years. Serum lipids and blood glucose may be independent risk factors for predicting HUA.


Assuntos
Biomarcadores/sangue , Glicemia/metabolismo , Hiperuricemia/sangue , Lipídeos/sangue , Exame Físico/estatística & dados numéricos , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
3.
BMC Genomics ; 17(Suppl 13): 1027, 2016 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-28155665

RESUMO

BACKGROUND: Bisulfite sequencing (BS-seq) has become a standard technology to profile genome-wide DNA methylation at single-base resolution. It allows researchers to conduct genome-wise cytosine methylation analyses on issues about genomic imprinting, transcriptional regulation, cellular development and differentiation. One single data from a BS-Seq experiment is resolved into many features according to the sequence contexts, making methylome data analysis and data visualization a complex task. RESULTS: We developed a streamlined platform, TEA, for analyzing and visualizing data from whole-genome BS-Seq (WGBS) experiments conducted in the model plant Arabidopsis thaliana. To capture the essence of the genome methylation level and to meet the efficiency for running online, we introduce a straightforward method for measuring genome methylation in each sequence context by gene. The method is scripted in Java to process BS-Seq mapping results. Through a simple data uploading process, the TEA server deploys a web-based platform for deep analysis by linking data to an updated Arabidopsis annotation database and toolkits. CONCLUSIONS: TEA is an intuitive and efficient online platform for analyzing the Arabidopsis genomic DNA methylation landscape. It provides several ways to help users exploit WGBS data. TEA is freely accessible for academic users at: http://tea.iis.sinica.edu.tw .


Assuntos
Arabidopsis/genética , Biologia Computacional/métodos , Metilação de DNA , Epigênese Genética , Epigenômica/métodos , Arabidopsis/metabolismo , Análise por Conglomerados , Ontologia Genética , Fluxo de Trabalho
4.
Mol Ecol ; 25(23): 5944-5958, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27778414

RESUMO

As significant anthropogenic pressures are putting undue stress on the world's oceans, there has been a concerted effort to understand how marine organisms respond to environmental change. Transcriptomic approaches, in particular, have been readily employed to document the mRNA-level response of a plethora of marine invertebrates exposed to an array of simulated stress scenarios, with the tacit and untested assumption being that the respective proteins show a corresponding trend. To better understand the degree of congruency between mRNA and protein expression in an endosymbiotic marine invertebrate, mRNAs and proteins were sequenced from the same samples of the common, Indo-Pacific coral Seriatopora hystrix exposed to stable or upwelling-simulating conditions for 1 week. Of the 167 proteins downregulated at variable temperature, only two were associated with mRNAs that were also differentially expressed between treatments. Of the 378 differentially expressed genes, none were associated with a differentially expressed protein. Collectively, these results highlight the inherent risk of inferring cellular behaviour based on mRNA expression data alone and challenge the current, mRNA-focused approach taken by most marine and many molecular biologists.


Assuntos
Antozoários/genética , Proteoma/genética , Simbiose , Temperatura , Transcriptoma , Animais , Regulação da Expressão Gênica , Oceanos e Mares
5.
BMC Genomics ; 16 Suppl 12: S8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26678286

RESUMO

Enteroviruses (EV) with different genotypes cause diverse infectious diseases in humans and mammals. A correct EV typing result is crucial for effective medical treatment and disease control; however, the emergence of novel viral strains has impaired the performance of available diagnostic tools. Here, we present a web-based tool, named EVIDENCE (EnteroVirus In DEep conception, http://symbiont.iis.sinica.edu.tw/evidence), for EV genotyping and recombination detection. We introduce the idea of using mixed-ranking scores to evaluate the fitness of prototypes based on relatedness and on the genome regions of interest. Using phylogenetic methods, the most possible genotype is determined based on the closest neighbor among the selected references. To detect possible recombination events, EVIDENCE calculates the sequence distance and phylogenetic relationship among sequences of all sliding windows scanning over the whole genome. Detected recombination events are plotted in an interactive figure for viewing of fine details. In addition, all EV sequences available in GenBank were collected and revised using the latest classification and nomenclature of EV in EVIDENCE. These sequences are built into the database and are retrieved in an indexed catalog, or can be searched for by keywords or by sequence similarity. EVIDENCE is the first web-based tool containing pipelines for genotyping and recombination detection, with updated, built-in, and complete reference sequences to improve sensitivity and specificity. The use of EVIDENCE can accelerate genotype identification, aiding clinical diagnosis and enhancing our understanding of EV evolution.


Assuntos
Enterovirus/classificação , Enterovirus/genética , Técnicas de Genotipagem/métodos , Biologia Computacional/métodos , Bases de Dados Genéticas , Evolução Molecular , Genoma Viral , Filogenia , RNA Viral/análise , Recombinação Genética , Software
6.
BMC Genomics ; 16: 1029, 2015 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-26630941

RESUMO

BACKGROUND: Microbial diversity and community structures in acidic hot springs have been characterized by 16S rRNA gene-based diversity surveys. However, our understanding regarding the interactions among microbes, or between microbes and environmental factors, remains limited. RESULTS: In the present study, a metagenomic approach, followed by bioinformatics analyses, were used to predict interactions within the microbial ecosystem in Shi-Huang-Ping (SHP), an acidic hot spring in northern Taiwan. Characterizing environmental parameters and potential metabolic pathways highlighted the importance of carbon assimilatory pathways. Four distinct carbon assimilatory pathways were identified in five dominant genera of bacteria. Of those dominant carbon fixers, Hydrogenobaculum bacteria outcompeted other carbon assimilators and dominated the SHP, presumably due to their ability to metabolize hydrogen and to withstand an anaerobic environment with fluctuating temperatures. Furthermore, most dominant microbes were capable of metabolizing inorganic sulfur-related compounds (abundant in SHP). However, Acidithiobacillus ferrooxidans was the only species among key rare microbes with the capability to fix nitrogen, suggesting a key role in nitrogen cycling. In addition to potential metabolic interactions, based on the 16S rRNAs gene sequence of Nanoarchaeum-related and its potential host Ignicoccus-related archaea, as well as sequences of viruses and CRISPR arrays, we inferred that there were complex microbe-microbe interactions. CONCLUSIONS: Our study provided evidence that there were numerous microbe-microbe and microbe-environment interactions within the microbial community in an acidic hot spring. We proposed that Hydrogenobaculum bacteria were the dominant microbial genus, as they were able to metabolize hydrogen, assimilate carbon and live in an anaerobic environment with fluctuating temperatures.


Assuntos
Fontes Termais/microbiologia , Metabolômica , Metagenômica , Microbiota , Microbiologia da Água , Biodiversidade , Carbono/metabolismo , Ciclo do Carbono , Genoma Bacteriano , Genômica/métodos , Interações Microbianas , Nitrogênio/metabolismo , Ciclo do Nitrogênio , Filogenia , Polimorfismo de Nucleotídeo Único , RNA Ribossômico 16S/genética , Taiwan
7.
Pacing Clin Electrophysiol ; 38(9): 1029-38, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25953101

RESUMO

BACKGROUND: Premature ventricular contractions (PVCs) originating from aortic sinus cusps (ASCs) can exhibit preferential conduction to right ventricular outflow tract (RVOT). OBJECTIVES: This study aimed to examine the electrophysiological characteristics for guiding catheter ablation in patients with two morphological types of PVCs that originate from ASCs or the great cardiac vein (GCV). METHODS: We analyzed electrocardiogram from 10 patients with PVCs of two QRS morphologies. The patients who exhibited dominant left bundle branch block (LBBB) QRS morphology and less right bundle branch block (RBBB) morphology were designated as group 1 (n = 7), and those with dominant RBBB QRS morphology were designated as group 2 (n = 3). During PVCs, electroanatomical mapping was performed in both RVOT and ASC in group 1 and only performed in ASC or GCV in group 2. RESULTS: In group 1, the earliest ventricular activation preceding the onset of the QRS complex (V-QRS) was recorded for 27 ± 6 ms (range 18-36 ms) in RVOT and 25 ± 6 ms (range 18-34 ms) in the ASC, while V-QRS was recorded for 28 ms, 42 ms, 40 ms in the ASC or GCV in group 2. All patients were successfully ablated at one site finally, including left coronary cusp in seven, left-right coronary cusp commissure in two, and GCV in one. None of the patients experienced recurrence or complications during the 18.4 ± 5.1 (range 6-24 months) months of follow-up. CONCLUSIONS: Two QRS morphologies (LBBB and RBBB with inferior axis) in PVCs could be a predictor of PVCs originating from ASC or GCV.


Assuntos
Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/cirurgia , Anomalias dos Vasos Coronários/cirurgia , Seio Aórtico/cirurgia , Complexos Ventriculares Prematuros/diagnóstico , Complexos Ventriculares Prematuros/cirurgia , Adulto , Mapeamento Potencial de Superfície Corporal/métodos , Ablação por Cateter/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Seio Aórtico/anormalidades , Cirurgia Assistida por Computador/métodos
8.
Mol Ecol ; 23(23): 5816-30, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25354956

RESUMO

Although rising ocean temperatures threaten scleractinian corals and the reefs they construct, certain reef corals can acclimate to elevated temperatures to which they are rarely exposed in situ. Specimens of the model Indo-Pacific reef coral Pocillopora damicornis collected from upwelling reefs of Southern Taiwan were previously found to have survived a 36-week exposure to 30°C, a temperature they encounter infrequently and one that can elicit the breakdown of the coral-dinoflagellate (genus Symbiodinium) endosymbiosis in many corals of the Pacific Ocean. To gain insight into the subcellular pathways utilized by both the coral hosts and their mutualistic Symbiodinium populations to acclimate to this temperature, mRNAs from both control (27°C) and high (30°C)-temperature samples were sequenced on an Illumina platform and assembled into a 236 435-contig transcriptome. These P. damicornis specimens were found to be ~60% anthozoan and 40% microbe (Symbiodinium, other eukaryotic microbes, and bacteria), from an mRNA-perspective. Furthermore, a significantly higher proportion of genes from the Symbiodinium compartment were differentially expressed after two weeks of exposure. Specifically, at elevated temperatures, Symbiodinium populations residing within the coral gastrodermal tissues were more likely to up-regulate the expression of genes encoding proteins involved in metabolism than their coral hosts. Collectively, these transcriptome-scale data suggest that the two members of this endosymbiosis have distinct strategies for acclimating to elevated temperatures that are expected to characterize many of Earth's coral reefs in the coming decades.


Assuntos
Aclimatação/genética , Antozoários/genética , Temperatura Alta , Simbiose , Transcriptoma , Animais , Antozoários/fisiologia , Recifes de Corais , Bases de Dados Genéticas , Dinoflagellida/fisiologia , Análise de Sequência de DNA , Taiwan
9.
Hepatogastroenterology ; 61(131): 880-4, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-26176090

RESUMO

BACKGROUND/AIMS: To observe the effects of DcR3 gene on the occurrence and progression of gastric cancer and explore its mechanism. METHODOLOGY: DcR3 mRNA expressions in both gastric normal tissue and gastric cancer tissue were detected with RT-PCR. Apoptosis index (AI) was determined with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). RESULTS: Positive rate of DcR3 mRNA expression was significantly higher in gastric cancer tissue than in gastric normal tissue (P < 0.01). The level of DcR3 mRNA expression was related to differentiation, lymphatic metastasis and TNM staging (P < 0.05). The level of DcR3 mRNA expression was inversely correlated with AI (P < 0.01). CONCLUSION: DcR3 plays an important role in the occurrence and progression of gastric cancer possibly through inhibiting gastric cancer cell apoptosis.


Assuntos
Membro 6b de Receptores do Fator de Necrose Tumoral/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Apoptose , Estudos de Casos e Controles , Diferenciação Celular , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/análise , Neoplasias Gástricas/patologia
10.
Chem Pharm Bull (Tokyo) ; 62(6): 524-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24694376

RESUMO

1,3,4-Thiadiazole and urea group were hybridized to form new molecular skeleton and 11 compounds were synthesized and evaluated as acetylcholinesterase (AChE) inhibitors. Most of them showed comparable effects in inhibition of AChE, especially compound 6b which exhibited activity with IC50 value 1.17 µM, as strong as galanthamine. This information offered by our research would be valuable for further investigation of structure-activity relationship (SAR) and useful in future research of AChE inhibitors.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Tiadiazóis/farmacologia , Ureia/análogos & derivados , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Relação Estrutura-Atividade , Tiadiazóis/síntese química , Tiadiazóis/química , Ureia/síntese química , Ureia/química , Ureia/farmacologia
11.
Int J Toxicol ; 33(2): 98-105, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24563414

RESUMO

Toxicity is one of the major reasons for failure in drug development. Zebrafish, as an ideal vertebrate model, could also be used to evaluate drug toxicity. In this study, we aimed to show the predictability and highlight novel findings of toxicity in zebrafish model. Seven anticancer compounds, including triptolide (TP), gambogic acid (GA), mycophenolic acid (MPA), curcumin, auranofin, thalidomide, and taxol, were assessed in zebrafish for their toxicity. Three compounds (GA, TP, and taxol) showed highest acute lethality, with 50% lethal concentration ≈ 1 µmol/L. Missing tails, severe pericardial edema, and enlarged yolk sacs were observed in MPA-treated embryos. The development of pectoral fins was severely disturbed in thalidomide-, GA-, and TP-treated embryos. Bradycardia was observed in MPA- and thalidomide-treated groups. Our findings suggested that the zebrafish are a good model for toxicity assessment of anticancer compounds.


Assuntos
Antineoplásicos/toxicidade , Peixe-Zebra/fisiologia , Animais , Doenças Cardiovasculares/induzido quimicamente , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Larva/anatomia & histologia , Larva/efeitos dos fármacos , Dose Letal Mediana , Teratogênicos/toxicidade
12.
J Clin Nurs ; 23(9-10): 1257-62, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24033817

RESUMO

AIMS AND OBJECTIVES: To provide a theoretical basis for the clinical care of patients with late stomach cancer, we investigated the life quality and analysed its related factor in the patients with late stomach cancer. BACKGROUND: Due to the lack of effective screening methods, stomach cancer usually has been in the advanced stage when patients are diagnosed. However, the treatment for late stomach cancer is a tough problem in today's medicine. Chemotherapy or radiotherapy brings patients physiological and psychological distress and heavy financial burden, affecting patients' therapeutic effects, prognosis and life quality. DESIGN: The patients with late stomach cancer were included, and then, questionnaires about the life quality were completed. METHODS: Questionnaires including European Organisation for Research on Treatment of Cancer Quality of Life Questionnaire-Core 30, Social Support Rating Scale, Medical Coping Modes Questionnaire and Self-rating Anxiety Scale were completed by 173 patients with late stomach cancer who received treatment in our hospital between May 2010 and May 2011. Correlation analyses were performed. RESULTS: The overall score of the life quality of the patients with late stomach cancer was only 29·54 ± 12·21. The social support, medical coping modes, anxiety and patients' clinical data (except radiotherapy) markedly affected the overall life quality of the patients with late stomach cancer (p < 0·05). CONCLUSION: The life quality of the patients with late stomach cancer is poor and is associated with many factors. RELEVANCE TO CLINICAL PRACTICE: This study provides a theoretical basis for better nursing the patients with late stomach cancer and improving their life quality.


Assuntos
Qualidade de Vida , Neoplasias Gástricas/psicologia , Adaptação Psicológica , Adulto , Ansiedade/etiologia , Estudos de Coortes , Humanos , Apoio Social , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Inquéritos e Questionários
13.
Chem Biol Drug Des ; 103(1): e14325, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37907334

RESUMO

Gastric cancer (GC) is a gastric epithelium-derived malignancy insensitive to post-surgical radiotherapy. Paclitaxel, an anti-microtubule drug, has been proven to induce apoptosis of GC cells; however, its exact mechanism of action is unclear. Therefore, the molecular mechanism by which paclitaxel inhibits the proliferation, migration and invasion of GC cells was investigated in this study. First off, SNU-719 cells were co-cultured with paclitaxel and/or Caspase1 inhibitor VX765. Then the proliferation ability of the cells was detected by MTT after paclitaxel treatment (0, 10, 20, 40, and 80 nM), the migration ability by scratch assay, and the invasion ability by Transwell assay. Next, the levels of interleukin (IL)-1ß and IL-18 in cell culture supernatant were detected by the enzyme linked immunosorbent assay (ELISA). And the level of lactate dehydrogenase (LDH) in the supernatant was measured by a corresponding kit. Finally, western blot was performed to detect the concentrations of Gasdermin E (GSDME), GSDME-N, nod-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1, cleaved caspase-1 protein in GC cells. As a result, paclitaxel inhibited the proliferation, migration, and invasion of SNU-719 cells in a concentration-dependent manner. Moreover, it induced the pyroptosis of SNU-719 cells. After cell co-culture with VX765 paclitaxel showed decreased inhibitory effect on the migration and invasion of SNU-719 cells. VX765, additionally, suppressed the NLRP3/caspase-1/GSDME mediated pyroptosis pathway activated by paclitaxel. In a nutshell, paclitaxel may inhibit the migration and invasion of GC cells SNU-719 through the NLRP3/caspase-1/GSDME mediated pyroptosis pathway.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Neoplasias Gástricas , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Proteínas NLR/metabolismo , Caspase 1/metabolismo , Caspase 1/farmacologia , Paclitaxel/farmacologia , Gasderminas , Neoplasias Gástricas/tratamento farmacológico , Domínio Pirina
14.
J Neurosci ; 32(35): 11919-29, 2012 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-22933778

RESUMO

It is well known that NMDA receptors (NMDARs) can both induce neurotoxicity and promote neuronal survival under different circumstances. Recent studies show that such paradoxical responses are related to the receptor location: the former to the extrasynaptic and the latter to the synaptic. The phosphoinositide 3-kinase (PI3K)/Akt kinase cascade is a key pathway responsible for the synaptic NMDAR-dependent neuroprotection. However, it is still unknown how synaptic NMDARs are coupled with the PI3K/Akt pathway. Here, we explored the role of an adaptor protein-adaptor protein containing pH domain, PTB domain, and leucine zipper motif (APPL1)-in this signal coupling using rat cortical neurons. We found that APPL1 existed in postsynaptic densities and associated with the NMDAR complex through binding to PSD95 at its C-terminal PDZ-binding motif. NMDARs, APPL1, and the PI3K/Akt cascade formed a complex in rat cortical neurons. Synaptic NMDAR activity increased the association of this complex, induced activation of the PI3K/Akt pathway, and consequently protected neurons against starvation-induced apoptosis. Perturbing APPL1 interaction with PSD95 by a peptide comprising the APPL1 C-terminal PDZ-binding motif dissociated the PI3K/Akt pathway from NMDARs. Either the peptide or lentiviral knockdown of APPL1 blocked synaptic NMDAR-dependent recruitment and activation of PI3K/Akt pathway, and consequently blocked synaptic NMDAR-dependent neuroprotection. These results suggest that APPL1 contributes to connecting synaptic NMDARs with the intracellular PI3K/Akt cascade and the downstream prosurvival signaling pathway in rat cortical neurons.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Neurônios/fisiologia , Fosfatidilinositol 3-Quinase/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapses/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Sequência de Aminoácidos , Animais , Sobrevivência Celular/fisiologia , Células Cultivadas , Feminino , Células HEK293 , Humanos , Líquido Intracelular/enzimologia , Líquido Intracelular/metabolismo , Masculino , Camundongos , Dados de Sequência Molecular , Neurônios/citologia , Fosfatidilinositol 3-Quinase/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Receptores de N-Metil-D-Aspartato/genética , Transdução de Sinais/fisiologia , Sinapses/enzimologia
15.
J Biol Chem ; 287(41): 34189-201, 2012 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-22891245

RESUMO

The finding that eukaryotic lanthionine synthetase C-like protein 1 (LanCL1) is a glutathione-binding protein prompted us to investigate the potential relationship between LanCL1 and cystathionine ß-synthase (CBS). CBS is a trans-sulfuration enzyme critical for the reduced glutathione (GSH) synthesis and GSH-dependent defense against oxidative stress. In this study we found that LanCL1 bound to CBS in mouse cortex and HEK293 cells. Mapping studies revealed that the binding region in LanCL1 spans amino acids 158-169, and that in CBS contains N-terminal and C-terminal regulatory domains. Recombinant His-LanCL1 directly bound endogenous CBS from mouse cortical lysates and inhibited its activity. Overexpression of LanCL1 inhibited CBS activity in HEK293 cells. CBS activity is reported to be regulated by oxidative stress. Here we found that oxidative stress induced by H(2)O(2) or glutamate lowered the GSH/GSSG ratio, dissociated LanCL1 from CBS, and elevated CBS activity in primary rat cortical neurons. Decreasing the GSH/GSSG ratio by adding GSSG to cellular extracts also dissociated LanCL1 from CBS. Either lentiviral knockdown of LanCL1 or specific disruption of the LanCL1-CBS interaction using the peptide Tat-LanCL1(153-173) released CBS activity in neurons but occluded CBS activation in response to oxidative stress, indicating the major contribution of the LanCL1-CBS interaction to the regulation of CBS activity. Furthermore, LanCL1 knockdown or Tat-LanCL1(153-173) treatment reduced H(2)O(2) or glutamate-induced neuronal damage. This study implies potential therapeutic value in targeting the LanCL1-CBS interaction for neuronal oxidative stress-related diseases.


Assuntos
Córtex Cerebral/metabolismo , Cistationina beta-Sintase/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Antioxidantes/metabolismo , Córtex Cerebral/citologia , Cistationina beta-Sintase/genética , Feminino , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Peróxido de Hidrogênio/farmacologia , Masculino , Camundongos , Proteínas do Tecido Nervoso/genética , Neurônios/citologia , Oxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/genética
16.
Hepatogastroenterology ; 60(121): 197-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22784942

RESUMO

BACKGROUND/AIMS: To observe the expression of differentiation inhibiting factor 1 (DIF1) and vascular endothelial growth factor (VEGF) and explore the relation between them and microvessel density (MVD) in gastric cancer tissue. METHODOLOGY: The expression of DIF1, VEGF, CD34 and MVD in gastric cancer and peri-cancerous tissues was qualitatively analyzed with immunohistochemistry. The protein expression of DIF1 and VEGF in gastric cancer and peri-cancerous tissue was semi-quantitatively analyzed with Western blot. RESULTS: The expression of DIF1 and VEGF, and MVD were significantly higher in gastric cancer tissue than in peri-cancerous tissue (p<0.05). MVD was significantly higher in DIF-positive gastric cancer tissue than in DIF-negative gastric cancer tissue (p<0.001). CONCLUSIONS: In gastric cancer, DIF1 expression is related to VEGF expression and MVD. DIF1 may promote angiogenesis in gastric cancer.


Assuntos
Microvasos/patologia , Neoplasias Gástricas/irrigação sanguínea , Fator A de Crescimento do Endotélio Vascular/análise , Antígenos CD34/análise , Western Blotting , Feminino , Humanos , Masculino , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Fator A de Crescimento do Endotélio Vascular/fisiologia
17.
Hepatogastroenterology ; 60(128): 2125-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24088315

RESUMO

BACKGROUND/AIMS: To explore the expression of protein-activated receptor-2 (PAR-2) in human gastric stromal tumor and its clinicopathological significance. METHODOLOGY: The expression of PAR-2 was detected with immunohistochemisty, RT-PCR and Western blot in tumor tissue, peritumoral tissue and gastric normal tissue from 72 patients with gastric stromal tumor. RESULTS: PAR-2 expression was significantly higher in peritumoral tissue (p < 0.05) and tumor tissue (p < 0.01) than in gastric normal tissue, and significantly higher in tumor tissue than in peritumoral tissue (p < 0.01). With the increase in NIH grade, PAR-2 expression was elevated in tumor tissues. PAR-2 expression was strongly associated with mucosal invasion. CONCLUSIONS: PAR-2 expression is significantly higher in gastric stromal tumor tissue than in peritumoral tissue and gastric normal tissue. The high expression of PAR-2 may be associated with the invasion and metastasis of gastric stromal tumor.


Assuntos
Biomarcadores Tumorais/análise , Tumores do Estroma Gastrointestinal/química , Receptor PAR-2/análise , Neoplasias Gástricas/química , Adulto , Idoso , Biomarcadores Tumorais/genética , Western Blotting , Feminino , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/secundário , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , RNA Mensageiro/análise , Receptor PAR-2/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Regulação para Cima
18.
Zhonghua Xin Xue Guan Bing Za Zhi ; 41(1): 13-7, 2013 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-23651961

RESUMO

OBJECTIVE: The purpose of this study was to explore the relationship between originate and breakout and radiofrequency catheter ablation strategy in patients undergoing radiofrequency ablation for premature ventricular contractions originating from the aortic sinus cusp (ASC) using 3-dimensional electro anatomic mapping. METHODS: This study included 21 consecutive patients (10 male) underwent ablation for frequent PVCs originating from ASC in our hospital between May 2009 and February 2012. Electro anatomic mapping and ablation of right ventricular outflow track (RVOT) and left ventricular outflow track (LVOT) were performed with the 7F 4-mm-tip ablation catheter from right femoral vein and artery. Activation mapping and pacing mapping were performed in all patients. RESULTS: Ablation was successful in all 21 patients successful ablation target in left coronary sinus cusp (LCC, n = 17), in right coronary sinus cusp (RCC, n = 2) and in noncoronary sinus cusp (NCC, n = 2). Seven patients showed a RBBB morphology (group A) and 14 patients showed a LBBB morphology (group B). In group A, earliest ventricular activation (EVA) was recorded 22 - 34 (27.4 ± 4.6) ms earlier before QRS at the site of catheter ablation in ASC. In group B, EVA was later in RVOT than that in ASC in 5 patients and EVA at the site of catheter ablation in RVOT and ASC was 22 - 28 (25.2 ± 2.7) ms and 26 - 40 (32.8 ± 5.2) ms, respectively (t = -3.6, P = 0.024) while EVA was earlier in the remaining 9 patients and EVA recorded in RVOT and ASC was 22 - 38 (28.7 ± 5.9) ms and 18 - 28 (22.7 ± 3.6) ms, respectively (t = 3.8, P = 0.005). CONCLUSION: Patients with premature ventricular contractions originating from the ASC often show preferential conduction to the RVOT, which may explain the LBBB morphology of ECG in these patients.


Assuntos
Bloqueio de Ramo/patologia , Complexos Ventriculares Prematuros/patologia , Adulto , Idoso , Bloqueio de Ramo/etiologia , Bloqueio de Ramo/fisiopatologia , Ablação por Cateter/métodos , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seio Aórtico/fisiopatologia , Complexos Ventriculares Prematuros/complicações , Complexos Ventriculares Prematuros/fisiopatologia , Adulto Jovem
19.
Zhonghua Xin Xue Guan Bing Za Zhi ; 41(5): 382-6, 2013 May.
Artigo em Chinês | MEDLINE | ID: mdl-24021119

RESUMO

OBJECTIVE: To explore the electrocardiogram and 3-dimensional electroanatomic mapping features and radiofrequency catheter ablation efficacy of patients with premature ventricular contractions (PVCs ) originating from His bundle region. METHODS: Between February 2009 and February 2011, 10 consecutive patients ( 4 male, aged from 19 to 59 years) who underwent ablation for frequent PVCs originating close to His bundle region in our department were included. Electroanatomic mapping of RVOT and ASC, ablation was performed with the 7F 4-mm-tip ablation catheter. RESULTS: Among these 10 patients with PVCs originating from His bundle region, 6 originated from the RVOT, 1 from NCC and 3 from RCC. Eight patients showed LBBB morphology,1 patient with PVCs originated from RCC and 1 patient with PVCs originated from NCC showed RBBB morphology. At the successful ablation sites, local ventricular activation v wave was detected 22-52 (32.6 ± 10.2) ms earlier than the QRS wave in the surface electrocardiogram. The distance between target and His bundle was 5.0-8.4(7.0 ± 1.1)mm. Ablation was successful in all 10 patients without complications (PVCs < 500 beats/24 h post ablation). CONCLUSION: PVCs originating near the His bundle have similar electrocardiographic and electrophysiological characteristics for PVSc originated from the RVOT or ASC. Because of the close anatomical relationship between RVOT and ASC, it is necessary to mapping both RVOT and ASC to accurately identify the site of PVCs origin and to guild successful ablation.


Assuntos
Fascículo Atrioventricular/cirurgia , Ablação por Cateter/métodos , Complexos Ventriculares Prematuros/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
20.
Foods ; 12(17)2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37685146

RESUMO

The effects of far infrared radiation drying (FID) on physical properties (drying kinetics, color, shrinkage ratio, rehydration ratio, and microstructural characterization) and volatile odor characteristics (volatile odor profile distinction and volatile compounds) of shiitake mushrooms were evaluated in this study. During the FID, the drying time decreased with the increase in drying temperature, and it had a less significant effect in the lower temperature range. The increase in drying temperature led to increasing shrinkage and collapse in the microstructure, resulting in a decreased rehydration rate and highlighting the influence of microstructure characteristics on macroscopic properties. Higher drying temperatures employed in the FID process were found to be associated with a decreasing L* value and an increasing ΔE value. The application of principal component analysis can effectively distinguish the significant effect of FID on the volatile odor profiles of shiitake mushrooms. Compared to raw shiitake mushrooms, FID treatment has endowed samples with a greater variety of volatile compounds. After processing with FID, there have been increases in volatile components such as sulfur compounds, acids, nitrogen compounds, and aldehydes, while volatile components like alcohols, ketones, and hydrocarbons have shown decreases.

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