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1.
Pulm Pharmacol Ther ; : 102121, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35283292

RESUMO

BACKGROUND: Acute lung injury is an acute progressive respiratory failure caused by several of non-cardiogenic factors which involves in excessive amplification or uncontrolled inflammatory response. OBJECTIVES: In this study, we investigated the protective effect of baicalein against acute lung injury induced by LPS and explored the underlying mechanisms. METHODS: Forty-eight SPF male C57BL/6 mice were randomly divided into normal group, model group, dexamethasone group and baicalein low-dose, medium-dose and high-dose groups. After 5 days of adaptive feeding, the mice were intraperitoneally injected with LPS and dissected after 12 h. Hematoxylin-eosin staining, ELISA assay, immunofluorescence assay and Western-Blot were applied to appraise microstructural changes and protein expressions of lung tissues. Systems pharmacology study was used to evaluate the protection of baicalein on acute lung injury. FINDINGS: The results showed that baicalein administration could significantly inhibit LPS-induced lung morphological changes, inhibit inflammatory response and pyroptosis. A total of forty-three potential targets of baicalein and acute lung injury were obtained. And PI3K-Akt, TNF and NF-κB were mainly signaling pathways. It is worth mentioning that this experiment also confirmed that NLRP3, caspase-1 and other inflammasome are involved in pyroptosis. CONCLUSION: Baicalein has protected against LPS-induced lung tissues injury via inhibiting inflammatory response and pyroptosis.

2.
Lett Appl Microbiol ; 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35348232

RESUMO

Anhedonia is the core symptom of depression, which largely reflects the therapeutic effect of depression. Hypericum perforatum is one of the most important antidepressant herb that has fewer side effects than traditional antidepressants. Considering the antibacterial effect of Hypericum perforatum, we verified whether this antidepressant activity was related to intestinal microbiomics. So we established anhedonia mouse model to explore the underlying treatment mechanism of hyperforin, the key antidepressant ingredient of Hypericum perforatum and to screen new psychobiotics based on hyperforin. It was found that hyperforin prevented anhedonia induced by chronic restraint stress in mice and altered the richness and evenness of bacteria populations compared with stressed mice. Metastat analysis showed that Akkermansia muciniphila and Muribaculum intestinale were the bacterial species obviously affected by hyperforin, and their abundance in hyperforin-treated group significantly increased. The results suggest that the effect of hyperforin on anhedonia may be partly assisted by Akkermansia muciniphila. These also indicate that Muribaculum intestinale may be another important intestinal bacteria involved in the pathogenesis of anhedonia symptom and depression.

3.
J Transl Med ; 19(1): 455, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732216

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are pivotal regulators of various human cancers and circ-ERBB2 is abnormally expressed in breast cancer cells. However, the role and mechanism of circ-ERBB2 in HER2-positive breast cancer are still unknown. METHODS: The circ-ERBB2 expressions in the tumor tissues of HER2-positive breast cancer patients were tested using quantitative real-time PCR. The circ-ERBB2 function was investigated by cell counting kit 8 assay, Transwell, flow cytometry and Western blot. Mechanistically, fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down and dual-luciferase reporter gene assays were conducted to confirm the interaction between circ-ERBB2 and miR-136-5p or miR-198 in HER2-positive breast cancer cells. RESULTS: Circ-ERBB2 was elevated in the tumor tissues of HER2-positive breast cancer patients. Functionally, the interference with circ-ERBB2 repressed HER2-positive breast cancer cell proliferation, migration, invasion and accelerated cell apoptosis. Furthermore, the mechanistic analysis corroborated that circ-ERBB2 acted as a competing endogenous RNA for miR-136-5p or miR-198 to relieve the repressive influence of miR-136-5p or miR-198 on its target transcription factor activator protein 2C (TFAP2C). Meanwhile, in vivo assays further corroborated the oncogenic function of circ-ERBB2 in HER2-positive breast cancer. CONCLUSIONS: Circ-ERBB2 accelerated HER2-positive breast cancer progression through the circ-ERBB2/miR-136-5p/TFAP2C axis or the circ-ERBB2/miR-198/TFAP2C axis.


Assuntos
Neoplasias da Mama , MicroRNAs , Neoplasias da Mama/genética , Proliferação de Células , Feminino , Humanos , Hibridização in Situ Fluorescente , MicroRNAs/genética , RNA Circular , Receptor ErbB-2/genética
4.
Endocrinology ; 162(12)2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34414414

RESUMO

BACKGROUND: During the transformation to dedifferentiated thyroid cancer (TC) types, the ability of papillary thyroid carcinomas (PTCs) to concentrate radioactive iodine might be lost, raising difficulty for the current therapy. circRNAs were proved to be implicated in the progression of various cancers. In this study, we aimed to investigate the functional role and mechanism of hsa_circ_0023990 in dedifferentiated TC. METHODS: The expression pattern of genes were detected using quantitative PCR or western blot assays. Cell proliferation was determined by CCK8, colony formation, EdU, and cell-cycle assays. Glycolysis was assessed using glucose uptake and lactate production assays. Luciferase reporter assay was performed to examine the interactions between miR-485-5p and hsa_circ_0023990 or FOXM1. Xenograft assay was allowed for observation of tumor growth in vivo. RESULTS: Hsa_circ_0023990 and FOXM1 were upregulated in dedifferentiated TC tissues and cell lines. The higher level of hsa_circ_0023900 could stimulate the proliferation and glycolysis of dedifferentiated TC cells via positively regulating FOXM1. Mechanistically, miR-485-5p was demonstrated to interact with hsa_circ_0023990 and FOXM1 and involved in the regulation of has_circ_0023990 and FOXM1 in TC biological processes. CONCLUSION: Our results discovered the functional network of hsa_circ_0023990 in dedifferentiated TC development by facilitating cell proliferation and glycolysis via miR-485-5p/FOXM1 axis, implying that hsa_circ_0023990 might be a potential therapeutic target for the dedifferentiated TC treatment.


Assuntos
Proteína Forkhead Box M1/genética , MicroRNAs/genética , RNA Circular/fisiologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Desdiferenciação Celular/genética , Proliferação de Células/genética , Células Cultivadas , Feminino , Regulação Neoplásica da Expressão Gênica , Glicólise/genética , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética
5.
Mol Neurobiol ; 58(11): 5649-5666, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34383254

RESUMO

The sigma-1 receptor (Sig-1R) is encoded by the SIGMAR1 gene and is a nonopioid transmembrane receptor located in the mitochondrial-associated endoplasmic reticulum membrane (MAM). It helps to locate endoplasmic reticulum calcium channels, regulates calcium homeostasis, and acts as a molecular chaperone to control cell fate and participate in signal transduction. It plays an important role in protecting neurons through a variety of signaling pathways and participates in the regulation of cognition and motor behavior closely related to neurodegenerative diseases. Based on its neuroprotective effects, Sig-1R has now become a breakthrough target for alleviating Alzheimer's disease and other neurodegenerative diseases. This article reviews the most cutting-edge research on the function of Sig-1R under normal or pathologic conditions and target drugs of the sigma-1 receptor in neurodegenerative diseases.


Assuntos
Proteínas do Tecido Nervoso/agonistas , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Receptores sigma/agonistas , Animais , Autofagia , Bulimia/tratamento farmacológico , Bulimia/fisiopatologia , Cálcio/metabolismo , Cognição/efeitos dos fármacos , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/fisiopatologia , Avaliação Pré-Clínica de Medicamentos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Humanos , Canais Iônicos/metabolismo , Microdomínios da Membrana , Atividade Motora/efeitos dos fármacos , Fatores de Crescimento Neural/biossíntese , Proteínas do Tecido Nervoso/fisiologia , Neuralgia/tratamento farmacológico , Neuralgia/fisiopatologia , Doenças Neurodegenerativas/fisiopatologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Ratos , Receptores sigma/fisiologia , Degeneração Retiniana/tratamento farmacológico , Degeneração Retiniana/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Resposta a Proteínas não Dobradas
6.
BMC Cardiovasc Disord ; 20(1): 300, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32560699

RESUMO

BACKGROUND: Coronary artery disease (CAD) remains one of the major causes of death in humans. Genetic testing may allow early detection and prevention of this disease. This study aimed to investigate the association between the macrophage migration inhibitory factor (MIF) -173G/C (rs755622) polymorphism and susceptibility to CAD based on a meta-analysis. METHODS: We searched several databases to identify observational case-control studies investigating the association between the MIF -173G > C (rs755622) polymorphism and CAD risk published before July 30, 2019. Data were analyzed using the STATA software. RESULTS: Six studies, comprising a total of 1172 CAD cases and 1564 controls evaluated for MIF polymorphisms, were included. The occurrence of CAD was found to be associated with the C allele of the MIF rs755622 SNP in the total population (C/G, OR = 1.489, 95% CI = 1.223-1.813). Further, MIF -173G/C polymorphism was significantly associated with CAD under the allelic model in the Asian (C/G, OR = 1.775, 95% CI = 1.365-2.309) and Caucasian (C/G, OR = 1.288, 95% CI 1.003-1.654) subgroups. The data showed that the risk of CAD was higher in the population carrying the C allele. CONCLUSIONS: We found evidence of associations between MIF -173C/G and CAD susceptibility in the Asian and Caucasian populations.


Assuntos
Doença da Artéria Coronariana/genética , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Polimorfismo de Nucleotídeo Único , /genética , Estudos de Casos e Controles , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/etnologia , Estudos de Associação Genética , Predisposição Genética para Doença , Fatores de Risco de Doenças Cardíacas , Humanos , Estudos Observacionais como Assunto , Medição de Risco , /genética
7.
Curr Med Sci ; 38(4): 704-713, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30128882

RESUMO

This study aims to explore the effect and mechanism of Jiao-tai-wan (JTW) on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant (OR) rats with chronic partial sleep deprivation (PSD). OR rats with PSD were orally given JTW and Estazolam for 4 weeks. The amount of food intake and metabolic parameters such as body weight increase rate, fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR) and plasma inflammatory markers were measured. The expression levels of circadian proteins cryptochrome 1 (Cryl) and cryptochrome 2 (Cry2) in hypothalamus, adipose and liver tissues were also determined. Meanwhile, the mRNA expression of inflammatory markers, activity of nuclear factor kappa B (NF-κB) p65 protein, as well as the expression levels of insulin signaling pathway proteins in hypothalamus, adipose and liver tissues were measured. Additionally, cyclic adenosine 3', 5'-monophosphate (cAMP) and activity of vasodilator-stimulated phosphoprotein (VASP) in hypothalamus tissue were measured. JTW significantly decreased the body weight increase rate and food intake, ameliorated systemic inflammation and insulin resistance. JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus, adipose and liver. Interestingly, all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression. We also found that in hypothalamus tissue of PSD rats, down-regulation of Cryl and Cry2 activated cAMP/PKA signaling and then led to inflammation, while JTW inhibited this signaling. These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.


Assuntos
Criptocromos/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Hipotálamo/efeitos dos fármacos , Privação do Sono/tratamento farmacológico , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Criptocromos/genética , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Glucose/metabolismo , Hipotálamo/metabolismo , Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Regulação para Cima
8.
BMC Complement Altern Med ; 18(1): 128, 2018 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-29636055

RESUMO

BACKGROUND: Lysimachia christinae Hance is a traditional Chinese medicine with diuretic, detumescent, and detoxifying effects. Our aimed to optimize the extraction protocol to maximize the yield of flavonoids from Lysimachia christinae Hance, and evaluate the pharmacological activities of four fractions, namely, petroleum ether (PE), ethyl acetate (EA), n-butanol (NB), and aqueous (AQ) fractions, of the ethanolic extract of Lysimachia christinae Hance. METHODS: The flavonoid monomers in the crude extract were characterized via high performance liquid chromatography (HPLC), were used as markers for extract quality control and standardization. The total flavonoid, total phenolic, and total polysaccharide contents of each fraction were determined by spectrophotometry. Further, the in vitro free radical (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), superoxide, and hydroxyl radicals) scavenging activities, and antioxidant capacity in endothelial cells were evaluated for each fraction. RESULTS: After optimizing the extraction protocol to maximize the total flavonoid yield from L. christinae Hance, the NB fractions had the highest total flavonoid (39.4 ± 4.55 mg RE/g), total phenolic (41.1 ± 3.07 mg GAE/g) and total polysaccharide (168.1 ± 7.07 mg GE/g); In addition, the NB fraction of the ethanolic extract of L. christinae Hance reveal the strongest radical-scavenging activity, antioxidant activity and protective effects against H2O2-induced injury in HUVECs. CONCLUSIONS: Among the four fractions of L. christinae Hance, the NB fraction showed the most potent antioxidant and endothelial protective effects, which may be attributed to its high flavonoid, phenolic contents and optimal portfolio of different active ingredients of NB fractions of the ethanolic extract of L. christinae Hance. This study might improve our understanding of the pharmacological activities of L. christinae Hance, thereby facilitating its use in disease prevention and treatment.


Assuntos
Antioxidantes , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais , Primulaceae/química , Antioxidantes/química , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Flavonoides/análise , Células Endoteliais da Veia Umbilical Humana , Humanos , Fenóis/análise , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/análise
9.
Oncotarget ; 8(62): 105809-105818, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29285294

RESUMO

The aim of the present study was to investigate the predictive value of the plasma matrix metalloproteinase-9 (MMP-9) level at admission for in-hospital mortality in patients who received emergency percutaneous coronary intervention (PCI) following AMI. A single blood sample was collected at admission from 155 consecutive AMI patients who underwent emergent PCI. The plasma levels of MMP-9 value (528.9±191.6 ng/ml) were significantly higher in the patients who died (n=24) than in the survivors (385.4±236.0 ng/ml) during 14 days of hospitalization (P=0.005). The age, left ventricle wall motion score index (WMIS), Global Registry of Acute Coronary Events (GRACE) score and B-type natriuretic peptide (BNP) levels and GENSINI score at admission were significantly different between the patients who died and those who survived (P<0.001, P=0.004, P<0.001 and P<0.001, respectively). Cut-off concentrations for prediction of death was identified from receiver operator characteristic (ROC) curves. Using the cut-off value (MMP-9 level 398.2 ng/ml) to stratify the patients into two groups, the group with higher MMP-9 levels had a greater rate of in-hospital mortality than the lower level group (P<0.001). With the exception of the GRACE score, among all biomarkers measured, in stepwise multiple logistic regressions, only the MMP-9 level predicted the risk of in-hospital death after adjustment for all other risk factors (odds ratio 5.02, 95% CI 1.44 to 17.55). In conclusion, a higher MMP-9 level is an independent predictor of in-hospital death in AMI patients who received emergency PCI.

10.
BMC Med Genet ; 18(1): 98, 2017 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-28874128

RESUMO

BACKGROUND: Chromosomal disorders in non obstructive azoospermia (NOA) may have an important influence on spermatogenesis, which may be reflected by the serum inhibin B levels. Till now, few studies have concerned the relationship of genetic causes and inhibin B in NOA. METHODS: In this retrospective study, 322 men with NOA in Center for Reproductive Medicine, Nanfang Hospital, Southern Medical University were collected. The level of follicle stimulating hormone (FSH), inhibin B, Y chromosome microdeletion test (YCMD) and karyotype were measured. RESULTS: Abnormal karyotypes were present in 38.5% of NOA, and YCMD were present in 18.0%, there was a high correlation between karyotypes and YCMD (χ2 = 11.892, P < 0.001). The level of inhibin B in chromosomal abnormality from lowest to highest was 46,XX (or 45,X), 47, XXY, mosaics, polymorphisms, inversion and translocation. And the level of inhibin B within Non-AZF a&b region deletion was higher than AZF a&b microdeletion. CONCLUSION: According to the level of inhibin B, spermatogenesis in chromosomal abnormality from lowest to highest was 46,XX (or 45,X), 47, XXY, mosaics, polymorphisms, inversion and translocation. And spermatogenesis within Non-AZF a&b region deletion was better than AZF a&b microdeletion.


Assuntos
Azoospermia/genética , Inibinas/sangue , Adulto , Azoospermia/sangue , Deleção Cromossômica , Cromossomos Humanos Y , Hormônio Foliculoestimulante , Humanos , Cariotipagem , Masculino , Estudos Retrospectivos , Aberrações dos Cromossomos Sexuais , Espermatogênese/genética
12.
Sci Rep ; 7(1): 3285, 2017 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-28607442

RESUMO

We aimed to investigate whether the prognostic nutritional index (PNI), a combined nutritional-inflammatory score based on serum albumin levels and lymphocyte count, was associated with mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). From September 2011 to November 2014, 309 consecutive patients with STEMI undergoing pPCI were prospectively enrolled. Patients with a combined score of albumin (g/L) + 5 × total lymphocyte count × 109/L ≥ 45 or <45 were assigned a PNI score of 0 or 1, respectively. Of the 309 STEMI patients, 24 (7.74%) died in the hospital, and 15 (4.83%) died during long-term follow-up (median follow-up time, 19.5 [3-36] months). Compared to patients with a PNI of 0, patients with a PNI of 1 had significantly higher in-hospital (14.2% vs. 3.7%; P < 0.001) and long-term follow-up (21.7% vs. 6.9%, P < 0.001) mortality rates. PNI (1/0, HR, 2.414; 95% CI, 1.016 to 5.736; P = 0.046) was a significant independent predictor of mortality in patients with STEMI undergoing pPCI. Moreover, cumulative survival was significantly lower for patients with a PNI of 1 compared to patients with a PNI of 0 (78.3% vs. 93.1%, log-rank P < 0.001). PNI appears useful for the risk stratification of STEMI patients undergoing pPCI.


Assuntos
Estado Nutricional , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Idoso , Biomarcadores , Comorbidade , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Intervenção Coronária Percutânea/métodos , Prognóstico , Modelos de Riscos Proporcionais , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Índice de Gravidade de Doença , Resultado do Tratamento
13.
Oncotarget ; 8(19): 31449-31464, 2017 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-28418905

RESUMO

In this study, we examined the long noncoding RNA (lncRNA) expression pattern in Uyghur patients (a minority of China) with acute myocardial infarction (AMI) on a genome-wide scale. Total RNAs were extracted from the peripheral blood of 55 Uyghur AMI patients and 55 healthy volunteers. The expression levels of genome-wide scale lncRNAs and mRNAs were determined by microarray in 10 samples (5 AMI and 5 controls). qRT-PCR was used to validate lncRNA expression levels in 100 samples (50 AMI and 50 controls). Data analyses were performed using R and Bioconductor. A total of 3624 up- and 1637 down-regulated lncRNAs were identified to be significantly and differentially expressed between these two groups. The annotation result of their co-expressed mRNAs showed that the most significantly related category of GO analysis was regulation of biological processes, and the most significantly related pathway was apoptosis and its corresponding p53. The microarray identified ENST00000416860.2, ENST00000421157.1 and TCONS_00025701 lncRNAs were confirmed by qRT-PCR. Our study indicated that clusters of lncRNAs were significantly and differentially expressed in the peripheral blood of AMI patients when compared with healthy controls within the Uyghur population. These newly identified lncRNAs may have a potential role in the development of AMI.


Assuntos
Estudo de Associação Genômica Ampla , Infarto do Miocárdio/genética , RNA Longo não Codificante/genética , Transcriptoma , Adulto , Idoso , Estudos de Casos e Controles , China , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , RNA Mensageiro/genética
14.
DNA Cell Biol ; 36(1): 67-76, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27828735

RESUMO

With the rapid development of imaging diagnosis and interventional therapy, contrast media (CM) are widely used in clinics. However, contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure accounting for 10-12% of all causes of hospital-acquired renal failure. Recent study found that inflammation may participate in the pathogenesis of CIN, but the role of it remains unclear. HK-2 cells were treated with Iohexol, Urografin, and mannitol. Two types of CM increased the release of HMGB1 in cell supernatant accompanied by increased expression of TLR2 and CXCR4. Iohexol and Urografin also caused a significant increase in NF-κB followed by the release of IL-6 and MCP-1. To clarify the role of HMGB1, TLR2, and CXCR4, glycyrrhizin, anti-TLR2-IgG, and AMD3100 were used to inhibit HMGB1, TLR2, and CXCR4, respectively. Significant decrease in the expression of TLR2, CXCR4, nuclear NF-κB, and the release of IL-6 and MCP-1 were observed. These results indicate that TLR2 and CXCR4 signaling are involved in CM-induced HK-2 cell injury model in an HMGB1-dependent pathway, which may provide a new target for the prevention and the treatment of CIN.


Assuntos
Meios de Contraste/farmacologia , Proteína HMGB1/metabolismo , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Quimiocina CCL2/metabolismo , Diatrizoato de Meglumina/farmacologia , Células Epiteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glicirrízico/farmacologia , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Interleucina-6/metabolismo , Túbulos Renais/metabolismo , Necrose/induzido quimicamente , Necrose/metabolismo , Receptores CXCR4/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 2 Toll-Like/metabolismo , Fator de Transcrição RelA/metabolismo
15.
Cell Physiol Biochem ; 38(2): 763-76, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26871894

RESUMO

BACKGROUND/AIMS: The function of BRAF V600E as a prognostic biomarker continues controversial by reason of conflicting results in the published articles. METHODS: A systematical literature search for relevant articles was performed in PubMed, Cochrane Library, Google Scholar, Medline and Embase updated to August 5, 2015. The Chi-square test and I2 were employed to examine statistical heterogeneity. Pooled ORs with their corresponding 95% confidence intervals (95%CIs) were calculated to assess the relationship between clinicopathological features and BRAF(V600E) mutation. Subgroup analyses by ethnicity were also performed to explore the potential sources of heterogeneity. Furthermore, publication bias was detected using the funnel plot and all statistical analyses were conducted by the software of R 3.12. RESULTS: Of 25,241 cases with PTC, 15,290 (60.6%) were positive for BRAF mutation and 9,951 (39.4%) were tested negative for BRAF mutation. Negative status of BRAF(V600E) mutation negative was significantly associated with gender (OR = 0.90, 95%CI = 0.83-0.97) and concomitant hashimoto thyroiditis (OR = 0.53, 95%CI = 0.43-0.64). By contrast, positive status of BRAF(V600E) mutation was a significant predictor of multifocality (OR = 1.23; 95%CI = 1.14-1.32), extrathyroidal extension (OR = 2.23; 95%CI = 1.90-2.63), TNM stage (OR = 1.67; 95%CI = 1.53-1.81), lymph node metastasis (OR = 1.67; 95%CI = 1.45-1.93), vascular invasion (OR = 1.47; 95%CI = 1.22-1.79) and recurrence/persistence (OR = 2.33; 95%CI = 1.71-3.18). However, there was no significant association between BRAF(V600E) mutation and factors including age > 45 (OR = 0.98; 95%CI = 0.89-1.07), tumor size (OR = 0.84; 95%CI = 0.64-1.09) and distant metastasis (OR = 1.23; 95%CI = 0.67-2.27). CONCLUSION: This meta-analysis confirmed significant associations between BRAF(V600E) mutation and female gender, multifocality, ETE, LNM, TNM stage, concomitant hashimoto thyroiditis, vascular invasion and recurrence/persistence, suggesting the predictive value of BRAF(V600E) mutation for PTC prognosis.


Assuntos
Carcinoma/genética , Carcinoma/patologia , Mutação Puntual , Proteínas Proto-Oncogênicas B-raf/genética , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Fatores Etários , Carcinoma/diagnóstico , Carcinoma/epidemiologia , Carcinoma Papilar , Feminino , Humanos , Metástase Linfática/diagnóstico , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores Sexuais , Câncer Papilífero da Tireoide , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia
16.
Int J Environ Res Public Health ; 13(2): 235, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26907312

RESUMO

Elevated LDL-C/HDL-C ratio has been shown to be a marker of lipid metabolism as well as a good predictor of coronary artery disease (CAD). Thus, the aim of this study was to investigate whether the LDL-C/HDL-C ratio is useful for detecting cardiovascular disease (CVD) risk factors in general healthy Uygur adults in Xinjiang. A total of 4047 Uygur subjects aged ≥35 years were selected from the Cardiovascular Risk Survey (CRS) study which was carried out from October 2007 to March 2010. Anthropometric data, blood pressure, lipid profile and fasting glucose were measured in all participants. The prevalence, sensitivity, specificity and distance on the receiver operating characteristic (ROC) curve of each LDL-C/HDL-C ratio were calculated. The prevalence of high LDL-C and low HDL-C cholesterol was high and positively correlated with higher LDL-C/HDL-C ratio in the Uygur population. In both men and women, we detected a slight apparent trend of high prevalence of hypertension and hypercholesterolemia with higher LDL-C/HDL-C ratio. Our study also demonstrated that the discriminatory power of the LDL-C/HDL-C ratio for CVD risk factors was slightly stronger in men than in women. Analysis of the shortest distance in the ROC curves for hypertension, dyslipidemia, diabetes, or ≥two of these risk factors suggested a LDL-C/HDL-C ratio cutoff of 2.5 for both men and women. The results of this study showed that a LDL-C/HDL-C ratio cut-off of 2.5 might be used as the predictive marker to detect CVD risk factors among Uygur adults in Xinjiang.


Assuntos
Doenças Cardiovasculares/etiologia , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Adulto , Antropometria , Pressão Sanguínea , China/epidemiologia , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Prevalência , Curva ROC , Fatores de Risco
17.
Genet Test Mol Biomarkers ; 20(3): 105-11, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26799199

RESUMO

BACKGROUND: Inflammation plays an important role in the pathophysiology of coronary artery disease (CAD). NF-κB is a central regulator of inflammation. Thus the aim of this study was to conduct a systematic review and meta-analysis investigating whether the polymorphism in the NFKB1 promoter region (NFKB1-94ins(I)/del(D)ATTG, rs28362491) is associated with CAD susceptibility. METHODS: PubMed, Embase, Cochrane Library and CNKI databases were searched up to 30 July 2015. All observational case-control studies that investigated the association of NFKB1 I/D polymorphism and CAD risk were included. Two reviewers independently selected the studies and extracted the data. RESULTS: A total of 7 studies were included in this meta-analysis. Comparison between alleles showed a 13% increased risk of CAD for D vs. I (OR = 1.13, 95% CI 1.06-1.19, PH = 0.318), and comparisons among genotypes showed a 26% increased risk of CAD for DD vs. II (OR = 1.26, 95% CI 1.12-1.43, PH = 0.125) and in the heterozygote model ID vs. II had an 11% increased risk (OR = 1.11, 95% CI 1.01-1.21, PH = 0.751). In the dominant model the risk of CAD risk was reduced by 13% (OR = 0.87, 95%CI 0.80-0.95, PH = 0.814) across the total population. Subgroup analysis by ethnicity indicated that the additive model was associated with a 21% increased risk for CAD in the Caucasian population (OR = 1.21, 95% CI 1.09-1.34, PH = 0.522), while the homozygote model gave a 47% increased risk for CAD in Asian population (OR = 1.47, 95% CI 1.21-1.78, PH = 0.314). CONCLUSIONS: Our results indicated that the NFKB1-94ins/del ATTG polymorphism was associated with susceptibility to CAD in both Asian and Caucasian populations.


Assuntos
Doença da Artéria Coronariana/genética , Subunidade p50 de NF-kappa B/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Mutação INDEL , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Fatores de Risco
18.
Blood Coagul Fibrinolysis ; 27(6): 653-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26575495

RESUMO

Type A acute aortic dissection is a life-threatening vascular emergency because of its high morbidity and mortality. Platelet is a pivotal ingredient involved in the development of acute aortic dissection. In this study, we aimed to investigate whether mean platelet volume (MPV)/platelet count ratio predicts in-hospital complications and long-term mortality in type A acute aortic dissection. In this single-center and prospective cohort study, 106 consecutive patients with Stanford type A acute aortic dissection admitted to the hospital within 12 h after onset were recruited. The best cut-off value of MPV/platelet count ratio predicting all-cause mortality was determined by the receiver operator characteristic analysis. Patients were divided into high (H-MPV/platelet count) and low (L-MPV/platelet count) groups based on the cut-off value of 7.49 (10 fl/10/l). Patients were followed up for 3.5 years. Of the 106 acute aortic dissection patients, 71 (67.0%) died during the study period, with a median follow-up duration of 570 days. Compared to the L-MPV/platelet count group, patients with H-MPV/platelet count had a higher risk of in-hospital complications including hypotension, hypoxemia, myocardial ischemia/infarction, conscious disturbance, pericardial tamponade, paraplegia, and poor survival (all P < 0.05). In multivariable Cox regression models adjusted for potential confounders, MPV/platelet count ratio was positively associated with the hazard of all-cause mortality, irrespective of interventions either with medication only or urgent surgery, and the hazard ratios were 2.81 (95% confidence interval 1.28-4.48) for the H-MPV/platelet count group when taking L-MPV/platelet count group as the reference (P = 0.005). The MPV/platelet count ratio was a strong independent predictor for in-hospital complications and long-term mortality in patients with type A acute aortic dissection.


Assuntos
Aneurisma Dissecante/complicações , Aneurisma Aórtico/complicações , Tamponamento Cardíaco/etiologia , Volume Plaquetário Médio , Infarto do Miocárdio/etiologia , Paraplegia/etiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Aneurisma Dissecante/tratamento farmacológico , Aneurisma Dissecante/mortalidade , Aneurisma Dissecante/cirurgia , Aorta/efeitos dos fármacos , Aorta/patologia , Aorta/cirurgia , Aneurisma Aórtico/tratamento farmacológico , Aneurisma Aórtico/mortalidade , Aneurisma Aórtico/cirurgia , Aspirina/uso terapêutico , Biomarcadores/análise , Plaquetas/patologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Tamponamento Cardíaco/tratamento farmacológico , Tamponamento Cardíaco/mortalidade , Tamponamento Cardíaco/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/cirurgia , Paraplegia/tratamento farmacológico , Paraplegia/mortalidade , Paraplegia/cirurgia , Contagem de Plaquetas , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Curva ROC
19.
Blood Coagul Fibrinolysis ; 27(1): 5-12, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26258675

RESUMO

Impaired myocardial reperfusion, defined angiographically by myocardial blush grade (MBG) 0 or 1, is associated with adverse clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to investigate the impact of admission mean platelet volume (MPV) on the myocardial reperfusion and 30-day all-cause mortality in patients with STEMI with successful epicardial reperfusion after primary percutaneous coronary intervention (PCI). A total of 453 patients with STEMI who underwent primary PCI within 12 h of symptoms onset and achieved thrombolysis in myocardial infarction (TIMI) 3 flow at infarct-related artery after PCI were enrolled and divided into two groups based on postinterventional MBG: those with MBG 2/3 and those with MBG 0/1. Admission MPV was measured before coronary angiography. The primary endpoint was all-cause mortality at 30 days. MPV was significantly higher in patients with MBG 0/1 than in patients with MBG 2/3 (10.38 ± 0.98 vs. 9.59 ± 0.73, P < 0.001). The cumulative 30-day all-cause mortality rate was significantly higher in the groups with high MPV and MBG 0/1 (6.8 vs. 1.5%, P = 0.005, 7.6 vs. 1.9%, P = 0.006, respectively). Multivariate logistic regression analysis demonstrated MPV was independently associated with postinterventional impaired myocardial reperfusion (odds ratio 2.684, 95% confidence interval 2.010-3.585, P < 0.001) and 30-day all-cause mortality (hazard ratio 1.763, 95% confidence interval 1.009-3.079, P = 0.046). Increased MPV on admission is an independent predictor of impaired myocardial reperfusion and short-term mortality in patients with STEMI with successful epicardial reperfusion after primary PCI. Admission MPV may be additive to conventional risk factors in patients with STEMI undergoing PCI.


Assuntos
Volume Plaquetário Médio/métodos , Infarto do Miocárdio/sangue , Reperfusão Miocárdica/métodos , Intervenção Coronária Percutânea/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento
20.
Int J Clin Exp Pathol ; 8(9): 9912-21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26617700

RESUMO

OBJECTIVE: NF-κB signaling plays a central role in the regulation of inflammatory responses in atherosclerosis. R65 ribozyme gene suppresses activation of NF-κB pathway, therefore we studied whether R65 gene therapy can ameliorate oxidized low-density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVECs) injury. METHODS AND RESULTS: Recombinant adeno-associated virus serotype 9 (rAVV9) vector was used to transfect the R65 ribozyme gene (rAVV9-R65) into HUVECs then following ox-LDL stimulation, expression of NF-κB p65 and p50 subunits, inflammatory mediators and cell apoptosis were examined. First, rAVV9-enhanced green fluorescent protein (eGFP)-R65 at 1×10(7) v.g./cell multiplicity of infection reached a long-lasting and significant increase in R65 gene expression. Second, ox-LDL treatment led to time- and dose-dependent activation of NF-κB pathway, and enhanced inflammatory response and cell death evidenced by increased expression of nuclear NF-κB p65 and p50 subunits, greater production of tumor necrosis factor α, interleukin-6 and von willebrand factor and 20.57% increased apoptotic HUVECs. Third, over-expression of R65 gene was 2-fold increased in HUVECs attenuated ox-LDL induced unclear accumulation and expression of p65 subunit and ameliorated inflammation and cell death (all P < 0.05). CONCLUSION: rAAV9-mediated R65 ribozyme gene transfection in cultured HUVECs effectively inhibits ox-LDL induced activation of NF-κB and production of inflammatory cytokines and prevents cell apoptosis.


Assuntos
Aterosclerose , Células Endoteliais da Veia Umbilical Humana/metabolismo , Lipoproteínas LDL/metabolismo , NF-kappa B/metabolismo , RNA Catalítico/genética , Western Blotting , Dependovirus , Citometria de Fluxo , Imunofluorescência , Terapia Genética/métodos , Vetores Genéticos , Humanos , Inflamação/metabolismo
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