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1.
Biol. Res ; 53: 14, 2020. graf
Article in English | LILACS | ID: biblio-1100920

ABSTRACT

BACKGROUND: Previous studies have shown that long noncoding RNA (IncRNA) LINC00483 was aberrantly expressed in human cancers, including gastric cancer. However, the regulatory mechanism of this IncRNA in gastric cancer remains largely unknown. The present study aimed to investigate the effect of LINC00483 on gastric cancer development and explore the potential regulatory network of LINC00483/microRNA (miR)-490-3p/mitogen-activated protein kinase 1 (MAPK1). METHODS: Thirty patients with gastric cancer were recruited for tissues collection. The expression levels of LINC00483, miR-490-3p and MAPK1 were detected by quantitative real-time polymerase chain reaction or western blot. Cell viability, apoptosis, migration and invasion were determined by MTT, flow cytometry, transwell assays and western blot, respectively. The target association between miR-490-3p and LINC00483 or MAPK1 was confirmed by luciferase reporter assay. Xenograft model was established to assess the function of LINC00483 in vivo. RESULTS: LINC00483 and MAPK1 levels were increased in gastric cancer tissues and cells. Knockdown of LINC00483 or MAPK1 inhibited cells viability, migration and invasion but promoted apoptosis in gastric cancer cells. Moreover, MAPK1 overexpression attenuated the effect of LINC00483 knockdown on gastric cancer development. LINC00483 could increase MAPK1 expression by competitively sponging miR-490-3p. miR-490-3p overexpression suppressed gastric cancer development, which was abated by introduction of LINC00483. Besides, inhibition of LINC00483 decreased xenograft tumor growth by regulating miR-490-3p/MAPK1 axis. CONCLUSION: Knockdown of LINC00483 inhibited gastric cancer development in vitro and in vivo by increasing miR- 490-3p and decreasing MAPK1, elucidating a novel mechanism for understanding the development of gastric cancer.


Subject(s)
Humans , Animals , Male , Stomach Neoplasms/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , Stomach Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Cell Movement , Cell Survival , Apoptosis , Xenograft Model Antitumor Assays , MicroRNAs/genetics , Cell Line, Tumor/metabolism , Epithelial Cells/metabolism , RNA, Long Noncoding/genetics , Carcinogenesis/metabolism , Luciferases/metabolism , Mice, Inbred BALB C
2.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 41(6): 485-493, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1055347

ABSTRACT

Objective: Cocaine use disorders (CUDs) represent a major public health problem in many countries. To better understand the interaction between the environmental modulations and phenotype, the aim of the present study was to investigate the DNA methylation pattern of CUD patients, who had concomitant cocaine and crack dependence, and healthy controls. Methods: We studied DNA methylation profiles in the peripheral blood of 23 CUD patients and 24 healthy control subjects using the Illumina Infinium HumanMethylation450 BeadChip arrays. Results: Comparison between CUD patients and controls revealed 186 differentially methylated positions (DMPs; adjusted p-value [adjP] < 10-5) related to 152 genes, with a subset of CpGs confirmed by pyrosequencing. DNA methylation patterns discriminated CUD patients and control groups. A gene network approach showed that the EHMT1, EHMT2, MAPK1, MAPK3, MAP2K1, and HDAC5 genes, which are involved in transcription and chromatin regulation cellular signaling pathways, were also associated with cocaine dependence. Conclusion: The investigation of DNA methylation patterns may contribute to a better understanding of the biological mechanisms involved in CUD.


Subject(s)
Humans , Male , Adult , Young Adult , Crack Cocaine , DNA Methylation , Cocaine-Related Disorders/genetics , Cocaine-Related Disorders/blood , Genome-Wide Association Study/methods , Case-Control Studies , Linear Models , Histone-Lysine N-Methyltransferase/genetics , Statistics, Nonparametric , Mitogen-Activated Protein Kinase 1/genetics , MAP Kinase Kinase 1/genetics , Mitogen-Activated Protein Kinase 3/genetics , Gene Regulatory Networks , High-Throughput Nucleotide Sequencing , Histocompatibility Antigens/genetics , Histone Deacetylases/genetics
3.
Clinical Psychopharmacology and Neuroscience ; : 364-368, 2019.
Article | WPRIM | ID: wpr-763557

ABSTRACT

OBJECTIVE: Genetics factors are likely to play a role in the risk, clinical presentation and treatment outcome in major depressive disorder (MDD). In this study, we investigated the role of three candidate genes for MDD; calcium voltage-gated channel subunit alpha1 C (CACNA1C), cholinergic receptor nicotinic alpha 7 subunit (CHRNA7), and mitogen-activated protein kinase 1 (MAPK1). METHODS: Two-hundred forty-two MDD patients and 326 healthy controls of Korean ancestry served as samples for the analyses. Thirty-nine single nucleotide polymorphisms (SNPs) within CACNA1C, CHRNA7, and MAPK1 genes were genotyped and subsequently tested for association with MDD (primary analysis) and other clinical features (symptoms’ severity, age of onset, history of suicide attempt, treatment outcome) (secondary analyses). Single SNPs, haplotypes and epistatic analyses were performed. RESULTS: Single SNPs were not associated with disease risk and clinical features. However, a combination of alleles (haplotype) within MAPK1 was found associated with MDD-status. Secondary analyses detected a possible involvement of CACNA1C haplotype in resistance to antidepressant treatment. CONCLUSION: These data suggest a role for MAPK1 and CACNA1C in MDD risk and treatment resistance, respectively. However, since many limitations characterize the analysis, the results must be considered with great caution and verified.


Subject(s)
Humans , Age of Onset , Alleles , Calcium , Depression , Depressive Disorder, Major , Genetics , Haplotypes , Mitogen-Activated Protein Kinase 1 , Neuronal Plasticity , Polymorphism, Single Nucleotide , Suicide , Treatment Outcome
4.
National Journal of Andrology ; (12): 199-205, 2018.
Article in Chinese | WPRIM | ID: wpr-689777

ABSTRACT

<p><b>Objective</b>To explore the inhibitory effect of polyphyllin Ⅰ (PPⅠ) on the proliferation of castration-resistant prostate cancer PC3 cells and its molecular mechanism.</p><p><b>METHODS</b>We cultured human prostate cancer PC3 cells in vitro and treated them with PPⅠ at the concentrations of 0 (blank group), 0.4, 0.8, 1.2, 1.6, 2.0, and 2.4 μmol/L for 24, 48, and 72 hours, respectively. Then we detected the proliferation of the cells by MTT assay, measured their apoptosis by flow cytometry, and determined the expressions of p-ERK1/2, ERK1/2, NF-κB/p65 and DNMT1 proteins as well as the level of NF-κB/p65 in the cells additionally treated with the ERK1/2 inhibitor SP600125 by Western blot.</p><p><b>RESULTS</b>Compared with the blank control group, the PPⅠ-treated PC3 cells showed a concentration- and time-dependent reduction of the survival rate (1.00 ± 0.00 vs 0.85 ± 0.05, P < 0.01) at 0.4 μmol/L after 48 hours of intervention, concentration-dependent early apoptosis at 0.8 μmol/L (4.83 ± 0.95 vs 13.83 ± 2.97, P < 0.01), time-dependent increase of the expressions of p-ERK1/2 (1.00 ± 0.00 vs 1.73 ± 0.17, P < 0.01) and ERK1/2 (1.00 ± 0.00 vs 1.36 ± 0.12, P < 0.01) at 2 hours, and concentration-dependent decrease of the expressions of NF-κB/p65 and DNMT1 at 1.2 μmol/L (1.00 ± 0.00 vs 0.78 ± 0.10 and 0.63 ± 0.06, P < 0.01) and 1.6 μmol/L (1.00 ± 0.00 vs 0.67 ± 0.11 and 0.52 ± 0.09, P<0.01). Inhibition of ERK1/2 phosphorylation with PD98059 markedly reversed PPⅠ-induced decrease of the NF-κB/p65 expression as compared with that in the PPⅠ group (0.86 ± 0.18 vs 0.43 ± 0.09, P < 0.05).</p><p><b>CONCLUSIONS</b>PPⅠ induces the early apoptosis and suppresses the proliferation of PC3 cells, probably by activating the ERK1/2 pathway and inhibiting the expressions of the NF-κB/p65 and DNMT1 proteins.</p>


Subject(s)
Humans , Male , Apoptosis , Cell Proliferation , DNA (Cytosine-5-)-Methyltransferase 1 , Metabolism , Diosgenin , Pharmacology , Flavonoids , Metabolism , MAP Kinase Signaling System , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , NF-kappa B , Metabolism , PC-3 Cells , Phosphorylation , Prostatic Neoplasms, Castration-Resistant , Drug Therapy , Metabolism , Pathology , Signal Transduction , Transcription Factor RelA , Metabolism
5.
Braz. j. med. biol. res ; 51(3): e6426, 2018. tab, graf
Article in English | LILACS | ID: biblio-889045

ABSTRACT

Occupational noise-induced hearing loss (ONIHL) is a prevalent occupational disorder that impairs auditory function in workers exposed to prolonged noise. However, serum microRNA expression in ONIHL subjects has not yet been studied. We aimed to compare the serum microRNA expression profiles in male workers of ONIHL subjects and controls. MicroRNA microarray analysis revealed that four serum microRNAs were differentially expressed between controls (n=3) and ONIHL subjects (n=3). Among these microRNAs, three were upregulated (hsa-miR-3162-5p, hsa-miR-4484, hsa-miR-1229-5p) and one was downregulated (hsa-miR-4652-3p) in the ONIHL group (fold change >1.5 and Pbon value <0.05). Real time quantitative PCR was conducted for validation of the microRNA expression. Significantly increased serum levels of miR-1229-5p were found in ONIHL subjects compared to controls (n=10 for each group; P<0.05). A total of 659 (27.0%) genes were predicted as the target genes of miR-1229-5p. These genes were involved in various pathways, such as mitogen-activated protein kinase (MAPK) signaling pathway. Overexpression of miR-1229-5p dramatically inhibited the luciferase activity of 3′ UTR segment of MAPK1 (P<0.01). Compared to the negative control, HEK293T cells expressing miR-1229-5p mimics showed a significant decline in mRNA levels of MAPK1 (P<0.05). This preliminary study indicated that serum miR-1229-5p was significantly elevated in ONIHL subjects. Increased miR-1229-5p may participate in the pathogenesis of ONIHL through repressing MAPK1 signaling.


Subject(s)
Humans , Male , Adult , Middle Aged , Occupational Exposure/adverse effects , Mitogen-Activated Protein Kinase 1/analysis , MicroRNAs/blood , Hearing Loss, Noise-Induced/blood , Occupational Diseases/blood , Biomarkers/blood , Case-Control Studies , Gene Expression Regulation , MicroRNAs/genetics , Real-Time Polymerase Chain Reaction , Gene Ontology , Hearing Loss, Noise-Induced/genetics , Occupational Diseases/genetics
6.
J. appl. oral sci ; 26: e20170231, 2018. graf
Article in English | LILACS, BBO | ID: biblio-893679

ABSTRACT

Abstract We previously reported that elevated extracellular calcium (Ca2+) levels increase bone morphogenetic protein 2 expression in human dental pulp (hDP) cells. However, it is unknown whether extracellular Ca2+ affects the expression of other growth factors such as fibroblast growth factor 2 (FGF2). Objective: The present study aimed to examine the effect of extracellular Ca2+ on FGF2 gene expression in hDP and immortalized mouse dental papilla (mDP) cells. Materials and Methods: Cells were stimulated with 10 mM CaCl2 in the presence or absence of cell signaling inhibitors. FGF2 gene expression was assessed using real-time polymerase chain reaction. The phosphorylation status of signaling molecules was examined by Western blotting. Results: Extracellular Ca2+ increased FGF2 gene expression in mDP and hDP cells. Gene expression of the calcium-sensing receptor and G protein-coupled receptor family C group 6 member A, both of which are extracellular Ca2+ sensors, was not detected. Ca2+-mediated Fgf2 expression was reduced by pretreatment with the protein kinase A (PKA) inhibitor H-89 or extracellular signal-regulated kinase (ERK) 1/2 inhibitor PD98059 but not by pretreatment with the protein kinase C inhibitor GF-109203X or p38 inhibitor SB203580. Extracellular Ca2+ increased PKA activity and ERK1/2 phosphorylation. Ca2+-induced PKA activity decreased by pretreatment with PD98059. Conclusions: These findings indicate that elevated extracellular Ca2+ levels led to increased Fgf2 expression through ERK1/2 and PKA in mDP cells and that this mechanism may be useful for designing regenerative therapies for dentin.


Subject(s)
Animals , Mice , Gene Expression/drug effects , Calcium/pharmacology , Fibroblast Growth Factor 2/drug effects , Cyclic AMP-Dependent Protein Kinases/drug effects , Mitogen-Activated Protein Kinase 1/drug effects , Dental Papilla/drug effects , Mitogen-Activated Protein Kinase 3/drug effects , Time Factors , Calcium Chloride/pharmacology , Enzyme-Linked Immunosorbent Assay , Cells, Cultured , Blotting, Western , Reproducibility of Results , Fibroblast Growth Factor 2/analysis , Fibroblast Growth Factor 2/genetics , Cyclic AMP-Dependent Protein Kinases/analysis , Mitogen-Activated Protein Kinase 1/analysis , MAP Kinase Signaling System/drug effects , Mitogen-Activated Protein Kinase 3/analysis , Real-Time Polymerase Chain Reaction
7.
Chinese journal of integrative medicine ; (12): 40-47, 2017.
Article in English | WPRIM | ID: wpr-301012

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the effects of salvianolate on myocardial infarction in a murine in vivo model of ischemia and reperfusion (I/R) injury.</p><p><b>METHODS</b>Myocardial I/R injury model was constructed in mice by 30 min of coronary occlusion followed by 24 h of reperfusion and pretreated with salvianolate 30 min before I/R (SAL group). The SAL group was compared with SHAM (no I/R and no salvianolate), I/R (no salvianolate), and ischemia preconditioning (IPC) groups. Furthermore, an ERK1/2 inhibitor PD98059 (1 mg/kg), and a phosphatidylinositol-3-kinase (PI3-K) inhibitor, LY294002 (7.5 mg/kg), were administered intraperitoneal injection (i.p) for 30 min prior to salvianolate, followed by I/R surgery in LY and PD groups. By using a double staining method, the ratio of the infarct size (IS) to left ventricle (LV) and of risk region (RR) to LV were compared among the groups. Correlations between IS and RR were analyzed. Western-blot was used to detect the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (AKT) phosphorylation changes.</p><p><b>RESULTS</b>There were no significant differences between RR to LV ratio among the SHAM, I/R, IPC and SAL groups (P>0.05). The SAL and IPC groups had IS of 26.1%±1.4% and 22.3%±2.9% of RR, respectively, both of which were significantly smaller than the I/R group (38.5%±2.9% of RR, P<0.05, P<0.01, respectively). Moreover, the phosphorylation of ERK1/2 was increased in SAL group (P<0.05), while AKT had no significant change. LY294002 further reduced IS, whereas the protective role of salvianolate could be attenuated by PD98059, which increased the IS. Additionally, the IS was not linearly related to the RR (r=0.23, 0.45, 0.62, 0.17, and 0.52 in the SHAM, I/R, SAL, LY and PD groups, respectively).</p><p><b>CONCLUSION</b>Salvianolate could reduce myocardial I/R injury in mice in vivo, which involves an ERK1/2 pathway, but not a PI3-K signaling pathway.</p>


Subject(s)
Animals , Male , Blotting, Western , Cardiotonic Agents , Pharmacology , Therapeutic Uses , Flavonoids , Pharmacology , Heart Ventricles , Pathology , MAP Kinase Signaling System , Mice, Inbred C57BL , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , Myocardial Reperfusion Injury , Drug Therapy , Pathology , Organ Size , Phosphorylation , Plant Extracts , Chemistry , Pharmacology , Therapeutic Uses , Protein Kinase Inhibitors , Pharmacology , Staining and Labeling
8.
Chinese Medical Journal ; (24): 1236-1243, 2017.
Article in English | WPRIM | ID: wpr-330638

ABSTRACT

<p><b>BACKGROUND</b>Surfactant protein-A (SP-A) contributes to the regulation of sepsis-induced acute kidney injury. In a previous study, we demonstrated that the expression of SP-A in the human renal tubular epithelial (HK-2) cells can be stimulated by lipopolysaccharide (LPS). The present study evaluated the possible signal-transducing mechanisms of LPS-induced SP-A biosynthesis in the HK-2 cells.</p><p><b>METHODS</b>Tetrazolium salt colorimetry (MTT) assay was used to detect cell viability of HK-2 cells after LPS stimulation on different time points. HK-2 cells were stimulated with 100 ng/ml of LPS for different durations to determine the effects of LPS on SP-A and toll-like receptor 4 (TLR4) messenger RNA (mRNA) expression, as well as phosphorylation of mitogen-activated/extracellular signal-regulated kinase (MEK) 1, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38MAPK), and nuclear factor-kappa B (NF-κB) inhibitor-alpha (IkB-α). Then, HK-2 cells were pretreated with CLI-095, a TLR4 inhibitor, to analyze mRNA and protein levels of SP-A and TLR4 and expression of NF-κB in the cytoplasm and nucleus of HK-2 before LPS exposure.</p><p><b>RESULTS</b>HK-2 cells exposed to 100 ng/ml of LPS for 1, 6, and 24 h did not affect cell viability which showed no toxic effect of 100 ng/ml LPS on cells (P = 0.16); however, the biosynthesis of SP-A mRNA and protein in HK-2 cells was significantly increased (P = 0.02). As to the mechanism, LPS enhanced transmembrane receptor TLR4 protein expression. Sequentially, LPS time dependently augmented phosphorylation of MEK1, ERK1/2, and p38MAPK. In addition, levels of phosphorylated IκB-α and nuclear NF-κB were augmented with LPS exposure for 2 h. LPS-induced SP-A and TLR4 mRNA as well as NF-κB expression were significantly inhibited by pretreatment with CLI-095.</p><p><b>CONCLUSIONS</b>The present study exhibited that LPS can increase SP-A synthesis in human renal epithelial cells through sequentially activating the TLR4-related MEK1-ERK1/2-NF-κB-dependent pathway.</p>


Subject(s)
Humans , Cell Line , Cell Survival , Physiology , Colorimetry , Kidney , Cell Biology , Metabolism , Lipopolysaccharides , Toxicity , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , NF-kappa B , Metabolism , Pulmonary Surfactant-Associated Protein A , Metabolism , Sulfonamides , Pharmacology , Tetrazolium Salts , Chemistry , Toll-Like Receptor 4 , Metabolism
9.
National Journal of Andrology ; (12): 406-411, 2017.
Article in Chinese | WPRIM | ID: wpr-812752

ABSTRACT

Objective@#To investigate the expressions of extracellular signal-regulated kinase (ERK) and p-ERK in benign and malignant prostate tissues, and whether it can be used as a marker for the prognosis of advanced prostate cancer (PCa).@*METHODS@#Using immunohistochemical Envision, we detected the expressions of ERK1/2 and p-ERK1/2 in 20 cases of benign prostatic hyperplasia (BPH) and 40 cases of advanced PCa and analyzed their correlation with PCa metastasis, Gleason score, PSA level, and prognosis.@*RESULTS@#The expression of ERK1/2 was remarkably higher in the advanced PCa than in the BPH cases (82.5% vs 55%, P5 yr, and survival ≤ 5 yr groups were 61.9%, 89.5%, 57.9%, and 90.5%, respectively, with statistically significant differences among these groups (P<0.05).@*CONCLUSIONS@#ERK1/2 and p-ERK1/2 proteins are highly expressed in advanced PCa and p-ERK1/2 is associated with the metastasis and prognosis of advanced PCa.


Subject(s)
Humans , Male , Biomarkers, Tumor , Metabolism , Extracellular Signal-Regulated MAP Kinases , Metabolism , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , Neoplasm Grading , Neoplasm Metastasis , Prognosis , Prostate , Prostate-Specific Antigen , Metabolism , Prostatic Hyperplasia , Pathology , Prostatic Neoplasms , Mortality , Pathology
10.
Biomedical and Environmental Sciences ; (12): 473-481, 2017.
Article in English | WPRIM | ID: wpr-311389

ABSTRACT

<p><b>OBJECTIVE</b>Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance greatly limits the clinical therapeutic efficacy of TRAIL. Elucidating the molecular mechanism underlying TRAIL resistance will be fundamental to resolving this problem.</p><p><b>METHODS</b>Nuclear and cytoplasmic protein extraction and immuno?uorescence (IF) assay were used to detect changes in heterogeneous nuclear ribonucleoprotein K (hnRNPK) localization in H1299 cells. The evaluation of cell apoptosis in cells transfected with GFP-hnRNPK, GFP-hnRNPK S284/353A, or GFP-hnRNPK S284/353D mutant was performed using cleaved caspase-3 antibody. The gene expression of XIAP was tested by quantitative RT-PCR.</p><p><b>RESULTS</b>Previously, we reported that hnRNPK antagonized TRAIL-induced apoptosis through inhibition of PKC-mediated GSK3β phosphorylation. In this study, we further demonstrate that TRAIL treatment induces cytoplasmic accumulation of hnRNPK in H1299 cells. The hnRNPK localized in the cytoplasm has a higher capacity to antagonize TRAIL-induced apoptosis. Both ERK1/2 signaling inhibitor U0126 and ERK-phosphoacceptor-site mutant (GFP-hnRNPK S284/353A) diminish cytoplasmic accumulation of hnRNPK induced by TRAIL. Moreover, we show that XIAP is involved in hnRNPK-mediated TRAIL resistance in H1299 cells.</p><p><b>CONCLUSION</b>Taken together, these results give new insights into the understanding of the molecular mechanism associated with TRAIL resistance in lung adenocarcinoma.</p>


Subject(s)
Humans , Apoptosis , Physiology , Cell Line, Tumor , Gene Expression Regulation , Physiology , Heterogeneous-Nuclear Ribonucleoprotein K , Genetics , Metabolism , Mitogen-Activated Protein Kinase 1 , Genetics , Metabolism , Mitogen-Activated Protein Kinase 3 , Genetics , Metabolism , TNF-Related Apoptosis-Inducing Ligand , Genetics , Metabolism , Up-Regulation , Physiology , X-Linked Inhibitor of Apoptosis Protein , Genetics , Metabolism
11.
Cell Journal [Yakhteh]. 2017; 19 (Supp. 1): 106-112
in English | IMEMR | ID: emr-189346

ABSTRACT

We studied effect of high glucose levels on coronary artery endothelial cell proliferation and human colon cancer cell proliferation. To examine the long-term effect of glucose exposure on cell growth, cells were cultured for 14 days in the absence or presence of 183 mg/dL D-glucose addition in the culture medium. Short effect of elevated glucose levels was examined by addition of 183 mg/dL D-glucose addition in the culture medium for just one hour per day followed by changing the culture to standard medium [5.5 mM D-glucose] during the next 23-hours period. Cell proliferation was estimated by 2,3-Bis [2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carbox-anilide [XTT] assay and phosphor-Erk western blot analysis. We found that coronary artery endothelial cell proliferation was significantly increased in the culture medium with the acute one-hour addition of 183 mg/dL D-glucose compared to the absence or chronic presence of 183 mg/dL D-glucose addition in the culture medium. In contrast, colon cancer cell proliferation was significantly increased in the continuous presence of 183 mg/dL D-glucose addition in the culture medium compared to the acute one-hour addition of glucose. The extent of Erk2 phosphorylation paralleled with the relative changes in cellular proliferation in both cell types. Taken together, these results suggested that continuous or transient high level of glucose exposure differentially effects coronary artery endothelial and human colon cancer cell proliferation


Subject(s)
Humans , Cell Proliferation , Endothelium , Coronary Vessels , Colonic Neoplasms , Mitogen-Activated Protein Kinase 1 , Proto-Oncogene Proteins c-akt
12.
Rev. Hosp. Ital. B. Aires (2004) ; 36(3): 84-90, sept. 2016. ilus
Article in Spanish | LILACS | ID: biblio-1146685

ABSTRACT

El melanoma ha experimentado un aumento constante en su tasa de incidencia en las últimas cinco décadas a nivel mundial. El pronóstico del paciente con melanoma se relaciona con el estadio de la enfermedad al momento del diagnóstico, con una sobrevida global media de 6,2 meses en pacientes con melanoma metastásico. El avance en las investigaciones sobre la biología y el comportamiento tumoral permitió el desarrollo de nuevas terapias con distintos mecanismos de acción y mayor eficacia. En esta revisión se abordan las terapias biológicas en melanoma metastásico, su mecanismo de acción y principales resultados en ensayos clínicos. (AU)


Melanoma has experienced a consistent increase in incidence over the past five decades worldwide. The prognosis of patients with melanoma is related to the stage of disease at diagnosis, with a median overall survival of 6.2 months in metastatic melanoma. Progress in research on tumor biology allowed the development of new therapies with different mechanisms of action and greater efficiency. In this review, biologic therapies in metastatic melanoma, its mechanism of action and main results in clinical trials are discussed. (AU)


Subject(s)
Humans , Biological Therapy , Melanoma/therapy , Neoplasm Metastasis/therapy , Incidence , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Dacarbazine/adverse effects , Dacarbazine/therapeutic use , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Ipilimumab/adverse effects , Ipilimumab/therapeutic use , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Vemurafenib/adverse effects , Vemurafenib/therapeutic use , Nivolumab/adverse effects , Nivolumab/therapeutic use , Immunotherapy
13.
Braz. j. med. biol. res ; 49(3): e4861, Mar. 2016. tab, graf
Article in English | LILACS | ID: lil-771938

ABSTRACT

The present study screened potential genes related to lung adenocarcinoma, with the aim of further understanding disease pathogenesis. The GSE2514 dataset including 20 lung adenocarcinoma and 19 adjacent normal tissue samples from 10 patients with lung adenocarcinoma aged 45-73 years was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) between the two groups were screened using the t-test. Potential gene functions were predicted using functional and pathway enrichment analysis, and protein-protein interaction (PPI) networks obtained from the STRING database were constructed with Cytoscape. Module analysis of PPI networks was performed through MCODE in Cytoscape. In total, 535 upregulated and 465 downregulated DEGs were identified. These included ATP5D, UQCRC2, UQCR11 and genes encoding nicotinamide adenine dinucleotide (NADH), which are mainly associated with mitochondrial ATP synthesis coupled electron transport, and which were enriched in the oxidative phosphorylation pathway. Other DEGs were associated with DNA replication (PRIM1, MCM3, and RNASEH2A), cell surface receptor-linked signal transduction and the enzyme-linked receptor protein signaling pathway (MAPK1, STAT3, RAF1, and JAK1), and regulation of the cytoskeleton and phosphatidylinositol signaling system (PIP5K1B, PIP5K1C, and PIP4K2B). Our findings suggest that DEGs encoding subunits of NADH, PRIM1, MCM3, MAPK1, STAT3, RAF1, and JAK1 might be associated with the development of lung adenocarcinoma.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Adenocarcinoma/genetics , Gene Expression Profiling/methods , Lung Neoplasms/genetics , Microfilament Proteins/genetics , Down-Regulation/genetics , Gene Regulatory Networks , Mitogen-Activated Protein Kinase 1/genetics , NAD/genetics , Protein Interaction Maps/genetics , Proto-Oncogene Proteins c-raf/genetics , Up-Regulation/genetics
14.
Journal of Southern Medical University ; (12): 735-743, 2016.
Article in Chinese | WPRIM | ID: wpr-263969

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of silencing ADP-ribosylation factor 6 (Arf6) on the proliferation, migration, and invasion of prostate cancer cell line PC-3 and the possible molecular mechanisms.</p><p><b>METHODS</b>Three Arf6-specific small interfering RNA (siRNA) were transfected into cultured prostate cancer cell line PC-3. Arf6 expression was examined by real-time PCR and Western blotting. MTT assay, wound healing assay, and Transwell migration and invasion assay were used to observe the effect of Arf6 silencing on the proliferation, migration, and invasion ability of PC-3 cells. The levels of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), ERK1/2, p-AKT, AKT and Rac1 were detected by Western blotting.</p><p><b>RESULTS</b>Transfection of siRNA-3 resulted in significantly decreased Arf6 mRNA and protein expression with inhibition rates of (91.88±3.13)% and (86.37±0.57)%, respectively. Arf6 silencing by siRNA-3 markedly suppressed the proliferation, migration and invasion of PC-3 cells and reduced the expression levels of p-ERK1/2 and Rac1.</p><p><b>CONCLUSION</b>Silencing of Arf6 efficiently inhibits the proliferation, migration, and invasion of PC-3 cells in vitro, and the underlying mechanisms may involve the down-regulation of p-ERK1/2 and Rac1.</p>


Subject(s)
Humans , Male , ADP-Ribosylation Factors , Genetics , Metabolism , Cell Line, Tumor , Cell Movement , Down-Regulation , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , Neoplasm Invasiveness , Prostatic Neoplasms , Pathology , RNA Interference , RNA, Messenger , Genetics , Metabolism , RNA, Small Interfering , Genetics , Real-Time Polymerase Chain Reaction , Transfection , Wound Healing , rac1 GTP-Binding Protein , Metabolism
15.
Biomedical and Environmental Sciences ; (12): 877-884, 2016.
Article in English | WPRIM | ID: wpr-296528

ABSTRACT

<p><b>OBJECTIVE</b>This paper aims to investigate the apoptotic effect of inactivated Sendai virus (hemagglutinating virus of Japan-enveloped, HVJ-E) on murine melanoma cells (B16F10) and the possible mechanisms involved in the putative apoptotic reactions.</p><p><b>METHODS</b>B16F10 cells were treated with HVJ-E at various multiplicities of infection (MOI), and the reactive oxygen species (ROS), cell viability, and apoptosis were measured. Next, the roles of ROS in the regulation of Bcl-2/Bax and the activation of mitogen-activated protein kinase (MAPK) pathways in HVJ-E-treated B16F10 cells were analyzed. To further evaluate the cytotoxic effect of HVJ-E-generated ROS on B16F10 cells, HVJ-E was intratumorally injected, both with and without N-acetyl-L-cysteine (NAC), into melanoma tumors on BALB/c mice. Tumor volume was then monitored for 3 weeks, and the tumor proteins were separated for immunoblot assay.</p><p><b>RESULTS</b>Treatment of B16F10 cells with HVJ-E resulted in a dose-dependent inhibition of cell-viability and an induction of apoptosis. The latter effect was associated with the generation of ROS. Inhibition of ROS generation by NAC resulted in a significant reduction of HVJ-E-induced Erk1/2, JNK, and p38 MAPK activation. Additionally, ROS inhibition caused a decrease in the Bcl-2/Bax ratio as well as promoting activation of apoptosis both in vitro and in vivo.</p><p><b>CONCLUSION</b>These results suggest that HVJ-E possesses potential anticancer activity in B16F10 cells through ROS-mediated mitochondrial dysfunction involving the MAPK pathway.</p>


Subject(s)
Animals , Mice , Apoptosis , Cell Line, Tumor , Mitogen-Activated Protein Kinase 1 , Genetics , Metabolism , Reactive Oxygen Species , Metabolism , Respirovirus Infections , Virology , Sendai virus , Physiology , Virus Inactivation
16.
Acta Physiologica Sinica ; (6): 27-34, 2016.
Article in English | WPRIM | ID: wpr-331686

ABSTRACT

The aim of the present study was to investigate the mechanism of the inhibitory effect of luteolin on the proliferation of breast cancer cells induced by epidermal growth factor (EGF) in vitro. MTT assay was used to detect the inhibitory effect of luteolin on the proliferation of MCF-7 and MDA-MB-231 cells as well as the effect on the proliferation of MCF-7 cells induced by EGF. Western blotting was used to detect the effects of luteolin on the expression of epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinases (Erk) 1/2 and signal transducers and activators of transcription-3 (STAT3) in MCF-7 cells induced by EGF. The results showed that luteolin could significantly inhibit the proliferation of MCF-7 and MDA-MB-231 cells, and the inhibitory effect on MCF-7 cells was more prominent. Moreover, luteolin could inhibit the proliferation of MCF-7 cells induced by EGF. Western blotting results showed that luteolin and AG1478 (an inhibitor of EGFR signaling) could inhibit the expression of p-EGFR and p-STAT3 in MCF-7 cells induced by EGF. Luteolin, LY294002 (an inhibitor of Akt signaling) and PD98059 (an inhibitor of Erk1/2 signaling) could inhibit the expression of p-Akt and p-Erk1/2 respectively in MCF-7 cells induced by EGF. Our data suggest that luteolin may inhibit EGF-induced activities of EGFR signaling pathway in human breast cancer cell lines, and PI3K/Akt, MAPK/Erk1/2, STAT3 signal pathways may be the major pathways that mediate the inhibitory effect of luteolin on EGFR signaling. Overall, our results may provide a theoretical foundation for the development of luteolin as anti-tumor drug.


Subject(s)
Humans , Breast Neoplasms , Cell Line, Tumor , Cell Proliferation , Chromones , Epidermal Growth Factor , Luteolin , MAP Kinase Signaling System , Mitogen-Activated Protein Kinase 1 , Mitogen-Activated Protein Kinase 3 , Morpholines , Phosphatidylinositol 3-Kinases , Quinazolines , ErbB Receptors , Tyrphostins
17.
Biol. Res ; 49: 1-10, 2016. ilus, graf
Article in English | LILACS | ID: biblio-950844

ABSTRACT

BACKGROUND: In China, mesangial proliferative glomerulonephritis (MsPGN) is one of the most common kidney diseases. In this study, we treated a rat model of chronic anti-Thy-1 MsPGN with Shenhua Tablet and evaluated whether the tablet was able to protect the kidney function. Thirty-six Wistar rats were randomly divided into six groups: (1) Sham surgery (Sham); (2) anti-Thy-1 nephritis model (Thy-1); (3) anti-Thy-1 nephritis model + irbesartan-treated (Irb); (4) anti-Thy-1 nephritis model + low-dose of Shenhua Tablet (SHL); (5) anti-Thy-1 nephritis model + medium-dose of Shenhua Tablet (SHM); (6) anti-Thy-1 nephritis model + high-dose of Shenhua Tablet (SHH). RESULTS: Thirteen weeks after drug treatment, urinary proteins were quantified and renal pathological changes were thoroughly examined at the time point of 24 h. Meanwhile, the expression levels of p-Erk1/2, cyclin D1 and p21 at the renal cortex were also tested. The levels of urinary proteins and total cholesterol in the blood were significantly reduced in rats treated with any drug tested in this study. The level of triglyceride was significantly reduced in all three Shenhua Tablet-treated groups. Renal pathomorphological scores were significantly improved in groups of Irb, SHM and SHH. Mesangial cell proliferation was significantly inhibited in any drug-treated group. p-Erk1/2 and cyclin D1 were downregulated whereas p21 was upregulated in the renal cortex. CONCLUSIONS: Our study indicated that Shenhua Tablet is able to inhibit the abnormal proliferation of mesangial cells and to prevent kidney damage, which is likely associated with downregulation of p-Erk1/2 and reduced activity of its downstream target-cyclin D1.


Subject(s)
Animals , Male , Drugs, Chinese Herbal/pharmacology , Glomerulonephritis, Membranoproliferative/drug therapy , Cell Proliferation/drug effects , Mesangial Cells/drug effects , Isoantibodies , Time Factors , Serum Albumin/analysis , Drugs, Chinese Herbal/therapeutic use , Glomerulonephritis, Membranoproliferative/pathology , Chronic Disease , Reproducibility of Results , Rats, Wistar , Mitogen-Activated Protein Kinase 1/analysis , Cyclin D1/analysis , Computers, Handheld , p21-Activated Kinases/analysis
18.
Rev. bras. epidemiol ; 18(1): 234-247, Jan-Mar/2015. tab
Article in Portuguese | LILACS | ID: lil-736431

ABSTRACT

OBJETIVO: Estimar a prevalência de dor crônica e sua associação com a situação socioeconômica, demográfica e atividade física no lazer em idosos. MÉTODOS: Este estudo é parte do inquérito epidemiológico e transversal de base populacional e domiciliar EpiFloripa Idoso 2009-2010 realizado com 1.705 idosos (≥ 60 anos), residentes em Florianópolis, Santa Catarina. A partir da resposta afirmativa de dor crônica, foram investigadas as associações com as variáveis obtidas por meio de entrevista estruturada. Realizou-se a estatística descritiva, incluindo cálculos de proporções e intervalos de confiança 95% (IC95%). Na análise bruta e ajustada, empregou-se regressão de Poisson, estimando-se as razões de prevalência, com intervalos de confiança de 95% e valores p ≤ 0,05. RESULTADOS: Dentre os idosos investigados, 29,3% (IC95% 26,5 - 32,2) relataram dor crônica. Na análise ajustada, observou-se que as variáveis sexo feminino, menor escolaridade e pior situação econômica ficaram associadas significativamente com maior prevalência de dor crônica; ser fisicamente ativo no lazer ficou associado significativamente com menor prevalência do desfecho. CONCLUSÕES: Percebe-se que a dor crônica é um agravo que acomete considerável parcela de idosos, havendo desigualdades sociais na sua frequência e sendo beneficamente afetada pela atividade física no lazer. É necessário que políticas públicas de saúde subsidiem programas multidisciplinares de controle da dor incluindo a prática regular de atividade física, voltada especificamente à promoção da saúde do idoso, evitando assim que a dor crônica comprometa a qualidade de vida desta população. .


OBJECTIVE: To estimate the prevalence of chronic pain and its association with socioeconomic and demographic status, and leisure physical activity in the elderly population. METHODS: This study is part of an epidemiological cross-sectional population-based household survey called EpiFloripa Elderly 2009-2010, which was conducted with 1,705 elderly individuals (≥ 60 years) residents of Florianópolis, Santa Catarina. From the positive response to chronic pain, the associations with the variables were investigated through a structured interview. Descriptive statistics were conducted, including ratio calculation and 95% confidence intervals. In crude and adjusted analysis, Poisson regression was utilized, estimating prevalence ratios, with 95% confidence intervals and ≤ 0.05 p-values. RESULTS: Among the subjects, 29.3% (IC95% 26.5 - 32.2) reported chronic pain. Adjusted analysis showed that being female, having less years of schooling, and being in worse economic situation were significantly associated with a higher prevalence of chronic pain. Being physically active during leisure time was significantly associated with lower prevalence of the outcome. CONCLUSIONS: Therefore, it is clear that chronic pain affects a considerable amount of elderly individuals. Social inequalities are a harmful influence in these individuals' quality of life, inasmuch as those inequalities increase the frequency with which chronic pain afflicts them. At the same time, physical activity during leisure time decreases chronic pain frequency. It is fundamental that public health policies subsidize multidisciplinary pain management programs, which should include health targeted physical activity for the elderly, thus preventing the decrease in quality of life that chronic pain brings to this population. .


Subject(s)
Animals , Humans , Early Growth Response Protein 1/genetics , Epithelial Cells/drug effects , Mitogen-Activated Protein Kinase 1/metabolism , /metabolism , Sulindac/analogs & derivatives , Apoptosis/drug effects , Blotting, Western , Butadienes/pharmacology , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Early Growth Response Protein 1/metabolism , Epithelial Cells/cytology , Epithelial Cells/metabolism , Imidazoles/pharmacology , Intestines/cytology , Intestines/drug effects , Intestines/metabolism , Luciferases/genetics , Luciferases/metabolism , Microscopy, Confocal , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , /antagonists & inhibitors , Nitriles/pharmacology , Pyridines/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , RNA, Messenger/genetics , RNA, Messenger/metabolism , Signal Transduction/drug effects , Sulindac/pharmacology , Transfection , Up-Regulation/drug effects , ets-Domain Protein Elk-1/genetics , ets-Domain Protein Elk-1/metabolism
19.
Clinics ; 70(3): 157-161, 03/2015. tab
Article in English | LILACS | ID: lil-747105

ABSTRACT

OBJECTIVE: To determine whether Tai Chi Chuan or ballroom dancing promotes better performance with respect to postural balance, gait, and postural transfer among elderly people. METHODS: We evaluated 76 elderly individuals who were divided into two groups: the Tai Chi Chuan Group and the Dance Group. The subjects were tested using the NeuroCom Balance Master¯ force platform system with the following protocols: static balance tests (the Modified Clinical Tests of Sensory Interaction on Balance and Unilateral Stance) and dynamic balance tests (the Walk Across Test and Sit-to-stand Transfer Test). RESULTS: In the Modified Clinical Test of Sensory Interaction on Balance, the Tai Chi Chuan Group presented a lower sway velocity on a firm surface with open and closed eyes, as well as on a foam surface with closed eyes. In the Modified Clinical Test of Sensory Interaction on Unilateral Stance, the Tai Chi Chuan Group presented a lower sway velocity with open eyes, whereas the Dance Group presented a lower sway velocity with closed eyes. In the Walk Across Test, the Tai Chi Chuan Group presented faster walking speeds than those of the Dance Group. In the Sit-to-stand Transfer Test, the Tai Chi Chuan Group presented shorter transfer times from the sitting to the standing position, with less sway in the final standing position. CONCLUSION: The elderly individuals who practiced Tai Chi Chuan had better bilateral balance with eyes open on both types of surfaces compared with the Dance Group. The Dance Group had better unilateral postural balance with eyes closed. The Tai Chi Chuan Group had faster walking speeds, shorter transfer times, and better postural balance in the final standing position during the Sit-to-stand Test. .


Subject(s)
/metabolism , Cyclic AMP/metabolism , Dictyostelium/enzymology , Dictyostelium/genetics , GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , Protozoan Proteins/metabolism , /genetics , Dictyostelium/growth & development , Dictyostelium/metabolism , Down-Regulation/drug effects , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Folic Acid/pharmacology , /deficiency , /genetics , /metabolism , GTP-Binding Protein alpha Subunits, Gi-Go/deficiency , GTP-Binding Protein alpha Subunits, Gi-Go/genetics , Mutation , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Protozoan Proteins/genetics , Signal Transduction , Spores, Protozoan/enzymology , Spores, Protozoan/genetics , Vitamin B Complex/pharmacology
20.
Acta Physiologica Sinica ; (6): 393-400, 2015.
Article in English | WPRIM | ID: wpr-255934

ABSTRACT

The changes of serum cyclophilin A (CyPA), its receptor CD147 and the downstream signaling pathway during the process of cardiac hypertrophy remain unknown. The present study aims to investigate the relationships between CyPA-CD147-ERK1/2-cyclin D2 signaling pathway and the development of cardiac hypertrophy. Left ventricular hypertrophy was prepared by 2-kidney, 2-clip in Sprague-Dawley rats and observed for 1 week, 4 and 8 weeks. Left ventricular hypertrophy was evaluated by ratio of left ventricular heart weight to body weight (LVW/BW) and cardiomyocyte cross sectional area (CSA). CyPA levels in serum were determined with a rat CyPA ELISA kit. Expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular myocytes were determined by Western blot and immunostaining. Compared with sham groups, systolic blood pressure reached hypertensive levels at 4 weeks in 2K2C groups. LVW/BW and CSA in 2K2C groups were significantly increased at 4 and 8 weeks after clipping. ELISA results indicated a prominent increase in serum CyPA level associated with the degree of left ventricular hypertrophy. Western blot revealed that the expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular tissues were also remarkably increased as the cardiac hypertrophy developed. The results of the present study demonstrates that serum CyPA and CyPA-CD147-ERK1/2-cyclin D2 signaling pathway in ventricular tissues are time-dependently upregulated and activated with the process of left ventricular hypertrophy. These data suggest that CyPA-CD147 signaling cascade might play a role in the pathogenesis of left ventricular hypertrophy, and CyPA might be a prognosticator of the degree of left ventricular hypertrophy.


Subject(s)
Animals , Rats , Basigin , Metabolism , Blood Pressure , Cyclin D2 , Cyclophilin A , Metabolism , Hypertension , Hypertrophy, Left Ventricular , Metabolism , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , Myocytes, Cardiac , Rats, Sprague-Dawley , Signal Transduction , Up-Regulation
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