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1.
Cancer Biomark ; 29(2): 221-233, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32623389

RESUMO

BACKGROUND: Alimentary tract cancers (ATCs) are the most malignant cancers in the world. Numerous studies have revealed the tumorigenesis, diagnosis and treatment of ATCs, but many mechanisms remain to be explored. METHODS: To identify the key genes of ATCs, microarray datasets of oesophageal cancer, gastric cancer and colorectal cancer were obtained from the Gene Expression Omnibus (GEO) database. In total, 207 differentially expressed genes (DEGs) were screened. KEGG and GO function enrichment analyses were conducted, and a protein-protein interaction (PPI) network was generated and gene modules analysis was performed using STRING and Cytoscape. RESULTS: Five hub genes were screened, and the associated biological processes indicated that these genes were mainly enriched in cellular processes, protein binding and metabolic processes. Clinical survival analysis showed that COL10A1 and KIF14 may be significantly associated with the tumorigenesis or pathology grade of ATCs. In addition, relative human ATC cell lines along with blood samples and tumour tissues of ATC patients were obtained. The data proved that high expression of COL10A1 and KIF14 was associated with tumorigenesis and could be detected in blood. CONCLUSION: In conclusion, the identification of hub genes in the present study helped us to elucidate the molecular mechanisms of tumorigenesis and identify potential diagnostic indicators and targeted treatment for ATCs.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Gastrointestinais/diagnóstico , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Recidiva Local de Neoplasia/epidemiologia , Biomarcadores Tumorais/sangue , Carcinogênese/genética , Linhagem Celular Tumoral , Colágeno Tipo X/sangue , Colágeno Tipo X/genética , Biologia Computacional , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/mortalidade , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Cinesinas/sangue , Cinesinas/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Oncogênicas/sangue , Proteínas Oncogênicas/genética , Prognóstico , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genética
2.
J Diabetes Res ; 2020: 6978128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32215272

RESUMO

Diabetic peripheral neuropathy is one of the most common chronic complications of diabetics which causes nerve damage and muscle strength decrease in patients. This in turn results in imbalance leading to the diabetic patients' daily activity disparity. The present investigation was conducted to specifically study the effects of combined training (resistance-aerobic) on serum kinesin-1 and physical function in type 2 diabetes patients with diabetic peripheral neuropathy. 24 diabetic neuropathic females were randomly to be selected out and divided into two experimental and control groups. The experimental group received resistance-aerobic training for 3 sessions during eight weeks. The exercise training included resistance exercises with 2-3 sets, 6-7 exercise stations, 8-12 repetitions (reps), and 3-5 minutes of rest in between the exercises, and the aerobic exercises contained 50-65% of heart rate reserve (HRR) for 3 minutes with 30 seconds of rest interval between sets and 5-10 repetitions. Results show that the serum kinesin-1 level and aerobic endurance declined after eight weeks of combined (resistance-aerobic) exercise training, but this decrease was not significant. The upper body strength increased but it was not significant, while the lower body showed a significant strength increase. With regard to the progressive nature of diabetic peripheral neuropathy, it seems that even the little changes resulting from the combined exercise training can be useful. Nevertheless, more research is required in this area.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Terapia por Exercício/métodos , Cinesinas/sangue , Desempenho Físico Funcional , Idoso , Diabetes Mellitus Tipo 2/sangue , Neuropatias Diabéticas/sangue , Exercício Físico , Feminino , Humanos , Pessoa de Meia-Idade , Força Muscular/fisiologia , Músculo Esquelético/fisiopatologia , Treinamento Resistido/métodos , Resultado do Tratamento
3.
Med Sci Monit ; 24: 8190-8197, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30427826

RESUMO

BACKGROUND Kid (kinesin-like DNA binding protein), a member of microtubule-dependent molecular motor proteins, also known as KIF22, is reported to be associated with carcinogenesis and cancer progression in different types of malignant tumor, but the biologic behavior and clinical outcome of KIF22 in prostate cancer (PCa) has not been well studied. This study aimed to analyze the association between KIF22 and clinical outcome in PCa patients. MATERIAL AND METHODS The expression of KIF22 in tumor specimens compared with paired paracancerous tissue from 114 patients undergoing radical prostatectomy was detected by immunohistochemistry; results were verified using The Cancer Genome Atlas (TCGA) database. Subsequently, the relationship between KIF22 expression and clinical prognosis of PCa patients was then statistically analyzed. RESULTS Both immunohistochemistry and database analysis showed that KIF22 was obviously overexpressed in PCa tissues compared with paracancerous tissue. The overexpression of KIF22 at the protein level was significantly related to higher clinical stage (P=0.025), Gleason score (P=0.002), seminal vesicle invasion (P=0.007), and lymph node metastasis (P=0.009). Furthermore, with the overexpression of KIF22 mRNA level in PCa patients, the oncological prognosis of PCa patients was much poorer. CONCLUSIONS High-level expression of KIF22 was related to both tumor progression and adverse clinical outcome. For this reason, KIF22 may become a potential prognostic factor for PCa.


Assuntos
Proteínas de Ligação a DNA/sangue , Cinesinas/sangue , Neoplasias da Próstata/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Progressão da Doença , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Cinesinas/genética , Cinesinas/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Antígeno Prostático Específico/metabolismo , Prostatectomia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Transcriptoma
4.
PLoS One ; 13(10): e0205430, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30304062

RESUMO

INTRODUCTION: The therapeutic response to statins has a high interindividual variability with respect to reductions in plasma LDL-cholesterol (c-LDL) and increases in HDL cholesterol (c-HDL). Many studies suggest that there is a relationship between the rs20455 KIF6 gene variant (c.2155T> C, Trp719Arg) and a lower risk of cardiovascular disease in patients being treated with statins. AIM: The aim of this study was to investigate whether or not the c.2155T> C KIF6 gene variant modulates the hypercholesteremic effects of treatment with simvastatin, atorvastatin, or rosuvastatin. MATERIALS AND METHODS: This was a prospective, observational and multicenter study. Three hundred and forty-four patients who had not undergone prior lipid-lowering treatment were recruited. Simvastatin, atorvastatin or rosuvastatin were administered. Lipid profiles and multiple clinical and biochemical variables were assessed before and after treatment. RESULTS: The c.2155T> C variant of the KIF6 gene was shown to influence physiological responses to treatment with simvastatin and atorvastatin. Patients who were homozygous for the c.2155T> C variant (CC genotype, ArgArg) had a 7.0% smaller reduction of LDL cholesterol levels (p = 0.015) in response to hypolipidemic treatment compared to patients with the TT (TrpTrp) or CT (TrpArg) genotype. After pharmacological treatment with rosuvastatin, patients carrying the genetic variant had an increase in c-HDL that was 21.9% lower compared to patients who did not carry the variant (p = 0.008). CONCLUSION: Being a carrier of the c.2155T> C variant of the KIF6 gene negatively impacts patient responses to simvastatin, atorvastatin or rosuvastatin in terms of lipid lowering effect. Increasing the intensity of hypolipidemic therapy may be advisable for patients who are positive for the c.2155T> C variant.


Assuntos
Anticolesterolemiantes/uso terapêutico , Biomarcadores Farmacológicos/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Cinesinas/genética , Atorvastatina/uso terapêutico , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , DNA/sangue , DNA/genética , Feminino , Humanos , Cinesinas/sangue , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Testes Farmacogenômicos , Estudos Prospectivos , Rosuvastatina Cálcica/uso terapêutico , Sinvastatina/uso terapêutico
5.
Arterioscler Thromb Vasc Biol ; 38(5): 1037-1051, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29519941

RESUMO

OBJECTIVE: Platelet secretion is crucial for many physiological platelet responses. Even though several regulators of the fusion machinery for secretory granule exocytosis have been identified in platelets, the underlying mechanisms are not yet fully characterized. APPROACH AND RESULTS: By studying a mouse model (cKO [conditional knockout]Kif5b) lacking Kif5b (kinesin-1 heavy chain) in its megakaryocytes and platelets, we evidenced unstable hemostasis characterized by an increase of blood loss associated to a marked tendency to rebleed in a tail-clip assay and thrombus instability in an in vivo thrombosis model. This instability was confirmed in vitro in a whole-blood perfusion assay under blood flow conditions. Aggregations induced by thrombin and collagen were also impaired in cKOKif5b platelets. Furthermore, P-selectin exposure, PF4 (platelet factor 4) secretion, and ATP release after thrombin stimulation were impaired in cKOKif5b platelets, highlighting the role of kinesin-1 in α-granule and dense granule secretion. Importantly, exogenous ADP rescued normal thrombin induced-aggregation in cKOKif5b platelets, which indicates that impaired aggregation was because of defective release of ADP and dense granules. Last, we demonstrated that kinesin-1 interacts with the molecular machinery comprising the granule-associated Rab27 (Ras-related protein Rab-27) protein and the Slp4 (synaptotagmin-like protein 4/SYTL4) adaptor protein. CONCLUSIONS: Our results indicate that a kinesin-1-dependent process plays a role for platelet function by acting into the mechanism underlying α-granule and dense granule secretion.


Assuntos
Plaquetas/enzimologia , Hemostasia , Cinesinas/metabolismo , Megacariócitos/enzimologia , Ativação Plaquetária , Vesículas Secretórias/enzimologia , Trombose/enzimologia , Trifosfato de Adenosina/sangue , Animais , Plaquetas/ultraestrutura , Modelos Animais de Doenças , Humanos , Cinesinas/sangue , Cinesinas/deficiência , Cinesinas/genética , Megacariócitos/ultraestrutura , Camundongos Endogâmicos C57BL , Camundongos Knockout , Selectina-P/sangue , Agregação Plaquetária , Fator Plaquetário 4/sangue , Via Secretória , Vesículas Secretórias/genética , Vesículas Secretórias/ultraestrutura , Transdução de Sinais , Trombose/sangue , Trombose/genética , Trombose/patologia , Proteínas de Transporte Vesicular/sangue , Proteínas rab27 de Ligação ao GTP/sangue
6.
Inflamm Res ; 65(10): 815-25, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27342824

RESUMO

BACKGROUND: Some studies have indicated that glucose metabolism plays an important role in the pathogenesis of rheumatoid arthritis (RA). This study aimed to find the novel genes affecting glucose metabolism in RA. MATERIALS/METHODS: Synovial tissues of collagen-induced arthritis (CIA) were analyzed with Rat Glucose Metabolism RT(2) Profiler™ PCR Array to screen those genes with special expressions in glucose metabolism. Real-time PCR, western blotting, and ELISA were used to confirm the result in synovial tissues and blood of human RA. Culture synovial fibroblast cells (RASF) was treated with siRNA to suppress expressions of the target genes. CCK-8 cell proliferation assay and two-compartment transwell system were performed to examine cell proliferation and cell migration of the treated RASF. RESULTS: Both PCR array and real-time PCR detected the up-regulation of ENO1, HK2, and PGK1 and the down-regulation of PCK1 and PDK4 in synovial tissues of CIA rats. Real-time PCR and western blotting detected the increased expression of ENO1 and PGK1 in RA synovial tissues. ELISA detected a high level of PGK1 in the blood of RA patients. Decreased cell proliferation and cell migration capabilities were significantly detected in RASF following treatment of anti-PGK1 siRNA. IL-1ß and IFN-γ rather than TNF-α and IL-1α levels were significantly declined in supernatants of the treated RASF. CONCLUSIONS: PGK1, a glycolytic enzyme catalyzing the conversion of 3-phosphoglycerate into 2-phosphoglycerate, has increased expression in synovial tissues and blood of RA, which may be involved in pro-inflammation and synovial hyperplasia of the disease.


Assuntos
Artrite Reumatoide/metabolismo , Fosfoglicerato Quinase/metabolismo , Membrana Sinovial/metabolismo , Adulto , Idoso , Animais , Artrite , Artrite Experimental/genética , Artrite Experimental/metabolismo , Artrite Reumatoide/sangue , Artrite Reumatoide/genética , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Colágeno , Citocinas/metabolismo , Proteínas de Ligação a DNA/sangue , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Glucose/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Cinesinas/sangue , Cinesinas/genética , Cinesinas/metabolismo , Masculino , Pessoa de Meia-Idade , Fosfoenolpiruvato Carboxiquinase (GTP)/genética , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Fosfoglicerato Quinase/sangue , Fosfoglicerato Quinase/genética , Fosfopiruvato Hidratase/sangue , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Proteínas Serina-Treonina Quinases/sangue , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil , Ratos Wistar , Proteínas Supressoras de Tumor/sangue , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Adulto Jovem
7.
J Matern Fetal Neonatal Med ; 26(14): 1410-5, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23480690

RESUMO

AIM: To search a specific gene expression profile in women with intrahepatic cholestasis of pregnancy (ICP) and to evaluate the maternal and foetal outcome. METHODS: We consecutively enrolled 12 women with ICP and 12 healthy pregnant controls. The gene expression profile was assayed with the microarray technique including a panel of 5541 human genes. Microarray data were validated by real-time PCR technique. RESULTS: Caesarean delivery was performed in eight patients with ICP versus three controls (p = 0.05). ICP women delivered at earlier gestational age than control (p < 0.001). Foetal distress was recorded in two babies, but we failed to find any correlation between bile salt concentration and foetal distress. Twenty genes potentially correlated with ICP were found differentially expressed (p < 0.05). Among these, three belong to genetic classes involved in pathogenic mechanisms of ICP: (1) pathophysiology of pruritus (GABRA2, cases versus controls = 2, upregulated gene); (2) lipid metabolism and bile composition (HLPT, cases versus controls = 0.6, down-regulated gene) and (3) protein trafficking and cytoskeleton arrangement (KIFC3, cases versus controls = 0.5, down-regulated gene). CONCLUSIONS: Different gene expression may contribute to the complex pathogenesis of ICP. An upregulation of GABRA2 receptor may indicate that GABA may play a role in the pathogenesis of pruritus in this condition.


Assuntos
Colestase Intra-Hepática/etiologia , Colestase Intra-Hepática/genética , Complicações na Gravidez/etiologia , Complicações na Gravidez/genética , Prurido , Receptores de GABA-A/sangue , Adulto , Estudos de Casos e Controles , Colestase Intra-Hepática/sangue , Feminino , Perfilação da Expressão Gênica , Humanos , Cinesinas/sangue , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas de Transferência de Fosfolipídeos/sangue , Gravidez , Complicações na Gravidez/sangue , Prurido/sangue , Prurido/etiologia , Prurido/genética , Receptores de GABA-A/fisiologia , Sinaptotagminas/sangue , Adulto Jovem
8.
Biomarkers ; 16(2): 181-91, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21231887

RESUMO

OBJECTIVES: To identify biomarkers for cancer in asbestosis patients. METHODS: SELDI-TOF and CART were used to identify serum biomarker profiles in 35 asbestosis patients who subsequently developed cancer and 35 did not develop cancer. RESULTS: Three polypeptide peaks (5707.01, 6598.10, and 20,780.70 Da) could predict the development of cancer with 87% sensitivity and 70% specificity. The first two peaks were identified as KIF18A and KIF5A, respectively, and are part of the Kinesin Superfamily of proteins. CONCLUSIONS: We identified two Kinesin proteins that can be potentially used as blood biomarkers to identify asbestosis patients at risk of developing lung cancer.


Assuntos
Asbestose/sangue , Biomarcadores Tumorais/sangue , Proteínas Sanguíneas/análise , Cinesinas/sangue , Neoplasias Pulmonares/sangue , Adenocarcinoma/sangue , Adenocarcinoma/etiologia , Adenocarcinoma/fisiopatologia , Adenocarcinoma de Pulmão , Asbestose/complicações , Asbestose/fisiopatologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Finlândia , Humanos , Estudos Longitudinais , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Proteômica , Fatores de Risco , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
9.
Zhongguo Zhong Yao Za Zhi ; 28(11): 1050-3, 2003 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-15615415

RESUMO

OBJECTIVE: To study the effects of Si-Wu-Tang on serum protein of blood deficient mice b y proteomicstechnique and study the enriching and regulating blood mechanism of Si-Wu-Tang on mocular level. METHOD: The blood deficient mice was induced by using a single dose of 3.5 Gy radiation from a 60Cogamma source, and high resolution two-dimensional polyacryamide gel electrophoresis (2-DE), computer-assisted image analysis, and mass spectrometry were used to detect regulated protein by Si-Wu-Tang. RESULT: 12 lower and 4 higher protein in sera could be recovered by Si-Wu-Tang, 4 protein might be DNA-dependent protein kinase catalytic subunit, Dystrophin, KIF13A, dystonin. They play a part in DNA double-stranded break repair, recombination and modulation of transcription, transportation of mannose-6-phosphate receptor, etc. CONCLUSION: Si-Wu-Tang can regulate serum protein in blood deficient mice, resulting in improving hematopoiesis and lessening irradiated injury.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Lesões Experimentais por Radiação/sangue , Protetores contra Radiação/farmacologia , Irradiação Corporal Total , Animais , Autoantígenos/sangue , Proteínas de Transporte , Proteínas do Citoesqueleto , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/isolamento & purificação , Distonina , Distrofina/sangue , Feminino , Cinesinas/sangue , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso , Colágenos não Fibrilares/sangue , Plantas Medicinais/química , Colágeno Tipo XVII
10.
J Leukoc Biol ; 53(4): 372-80, 1993 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8482917

RESUMO

Studies of granule-microtubule interactions in human neutrophils have suggested that mechanochemical ATPases such as kinesin or dynein may play a role in granule mobilization during neutrophil activation by inflammatory signals. In this study we show that proteins extracted from the surface of neutrophil granules, found previously to contain microtubule-dependent ATPase activity, caused microtubules polymerized from phosphocellulose-purified rat brain tubulin to move across glass slides. Antibodies were generated against peptides based on two regions of the amino acid sequence of Drosophila kinesin: the ATPase active site (amino acids 86-99) in the head of the kinesin heavy chain and the tail of the heavy chain (residues 913-933). These antibodies were found to recognize kinesin in rat brain extracts as well as kinesin-like polypeptides in extracts of human neutrophils. Furthermore, when used in immunoaffinity chromatography, these antibodies permitted the isolation of a protein from neutrophil granule extracts that was recognized by Drosophila kinesin antibodies. Subcellular localization by immunofluorescence microscopy showed this protein to be associated principally with the cytoplasmic granules of neutrophils.


Assuntos
Cinesinas/sangue , Microtúbulos/fisiologia , Neutrófilos/metabolismo , Animais , Anticorpos , Encéfalo/fisiologia , Bovinos , Galinhas , Cromatografia de Afinidade , Drosophila , Eletroforese em Gel de Poliacrilamida , Eritrócitos/fisiologia , Imunofluorescência , Humanos , Cinesinas/análise , Cinesinas/isolamento & purificação , Microtúbulos/ultraestrutura , Peso Molecular , Neutrófilos/citologia , Neutrófilos/ultraestrutura , Frações Subcelulares/química , Frações Subcelulares/ultraestrutura
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