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1.
Chinese Medical Journal ; (24): 222-231, 2024.
Article Dans Anglais | WPRIM | ID: wpr-1007744

Résumé

BACKGROUND@#Radiation (IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment (TME). Wee1, a cell cycle regulator, can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1 (CDK1). Meanwhile, programed death-1/programed death ligand-1 (PD-1/PDL-1) blockade is closely related to TME. This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody (anti-PD-1 Ab) on radiosensitization of hepatoma.@*METHODS@#The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay on human and mouse hepatoma cells HepG2, Hepa1-6, and H22. The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro . A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice, which were divided into control group, IR group, AZD1775 group, IR + AZD1775 group, IR + anti-PD-1 Ab group, and the IR + AZD1775 + anti-PD-1 Ab group. Cytotoxic CD8 + T cells in TME were analyzed by flow cytometry.@*RESULTS@#Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro . AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage. AZD1775 treatment also reduced the proportion of PD-1 + /CD8 + T cells in the spleen of hepatoma subcutaneous xenograft mice. Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferon γ (IFNγ) + or Ki67 + CD8 T cells and decreasing the levels of CD8 + Tregs cells in the tumor and spleen of the hepatoma mice model, indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγ expression, enhancing CD8 + T cells proliferation, and weakening CD8 + T cells depletion.@*CONCLUSIONS@#This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improving cytotoxic CD8 + T cells in TME.


Sujets)
Humains , Animaux , Souris , Carcinome hépatocellulaire/radiothérapie , Protéines du cycle cellulaire/métabolisme , Protein-tyrosine kinases/génétique , Apoptose , Récepteur-1 de mort cellulaire programmée , Lignée cellulaire tumorale , Points de contrôle de la phase G2 du cycle cellulaire , Tumeurs du foie/radiothérapie , Microenvironnement tumoral , Pyrazoles , Pyrimidinones
2.
Neuroscience Bulletin ; (6): 1333-1347, 2023.
Article Dans Anglais | WPRIM | ID: wpr-1010605

Résumé

Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD.


Sujets)
Souris , Animaux , Microcéphalie/génétique , Trouble autistique/métabolisme , Trouble du spectre autistique/métabolisme , Protéines de tissu nerveux/métabolisme , Encéphale/métabolisme , Souris knockout , Protéines du cycle cellulaire/métabolisme
3.
Protein & Cell ; (12): 51-63, 2023.
Article Dans Anglais | WPRIM | ID: wpr-971605

Résumé

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.


Sujets)
Animaux , Souris , Régions 3' non traduites/génétique , Protéines du cycle cellulaire/métabolisme , Gamétogenèse/génétique , Méiose/génétique , Protéines nucléaires/génétique , Protéines de liaison à l'ARN/génétique
4.
Chinese Journal of Biotechnology ; (12): 1525-1547, 2023.
Article Dans Chinois | WPRIM | ID: wpr-981152

Résumé

Cell cycle plays a crucial role in cell development. Cell cycle progression is mainly regulated by cyclin dependent kinase (CDK), cyclin and endogenous CDK inhibitor (CKI). Among these, CDK is the main cell cycle regulator, binding to cyclin to form the cyclin-CDK complex, which phosphorylates hundreds of substrates and regulates interphase and mitotic progression. Abnormal activity of various cell cycle proteins can cause uncontrolled proliferation of cancer cells, which leads to cancer development. Therefore, understanding the changes in CDK activity, cyclin-CDK assembly and the role of CDK inhibitors will help to understand the underlying regulatory processes in cell cycle progression, as well as provide a basis for the treatment of cancer and disease and the development of CDK inhibitor-based therapeutic agents. This review focuses on the key events of CDK activation or inactivation, and summarizes the regulatory processes of cyclin-CDK at specific times and locations, as well as the progress of research on relevant CDK inhibitor therapeutics in cancer and disease. The review concludes with a brief description of the current challenges of the cell cycle process, with the aim to provide scientific references and new ideas for further research on cell cycle process.


Sujets)
Kinases cyclines-dépendantes/métabolisme , Cyclines/métabolisme , Protein-Serine-Threonine Kinases , Protéines du cycle cellulaire/métabolisme , Cycle cellulaire/physiologie , Kinase-2 cycline-dépendante
5.
Frontiers of Medicine ; (4): 317-329, 2023.
Article Dans Anglais | WPRIM | ID: wpr-982568

Résumé

Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.


Sujets)
Humains , Athérosclérose/génétique , Autophagie/génétique , Protéines du cycle cellulaire/métabolisme , Cellules endothéliales/métabolisme , Endothélium/métabolisme , microARN/métabolisme , Protéines de répression/métabolisme , Facteurs d'épissage des ARN , Facteurs d'épissage riches en sérine-arginine/génétique , ARN long non codant/métabolisme
6.
Protein & Cell ; (12): 202-216, 2023.
Article Dans Anglais | WPRIM | ID: wpr-982531

Résumé

Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders, the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown. Here, we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem cells (hMSCs). Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration, increases mitochondrial reactive oxygen species (ROS) production, and accelerates cellular senescence. Mechanistically, the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes, especially several key subunits of complex III including UQCRC2. Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs. These f indings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis, particularly for the mitochondrial respiration complex III, thus providing a new potential target to counteract human stem cell senescence.


Sujets)
Humains , Cellules souches mésenchymateuses/physiologie , Vieillissement de la cellule , Homéostasie , Protéines du cycle cellulaire/métabolisme , Protéines adaptatrices de la transduction du signal/métabolisme , Mitochondries/métabolisme , Complexe III de la chaîne respiratoire/métabolisme , Cellules cultivées
7.
Chinese Journal of Biotechnology ; (12): 132-148, 2023.
Article Dans Chinois | WPRIM | ID: wpr-970364

Résumé

The bromodomain and extraterminal domain (Bet) family are the regulators of the epigenome and also the pivotal driving factors for the expression of tumor related genes that tumor cells depend on for survival and proliferation. Bromodomain-containing protein 4 (Brd4) is a member of the Bet protein family. Generally, Brd4 identifies acetylated histones and binds to the promoter or enhancer region of target genes to initiate and maintain expression of tumor related genes. Brd4 is closely related to the regulation of multiple transcription factors and chromatin modification and is involved in DNA damage repair and maintenance of telomere function, thus maintaining the survival of tumor cells. This review summarizes the structure and function of Brd4 protein and the application of its inhibitors in tumor research.


Sujets)
Humains , Facteurs de transcription/métabolisme , Protéines nucléaires/métabolisme , Histone , Protéines du cycle cellulaire/métabolisme , Tumeurs/métabolisme , Domaines protéiques
8.
Chinese Journal of Lung Cancer ; (12): 310-318, 2023.
Article Dans Chinois | WPRIM | ID: wpr-982161

Résumé

Spindle assembly checkpoint (SAC) is a protective mechanism for cells to undergo accurate mitosis. SAC prevented chromosome segregation when kinetochores were not, or incorrectly attached to microtubules in the anaphase of mitosis, thus avoiding aneuploid chromosomes in daughter cells. Aneuploidy and altered expression of SAC component proteins are common in different cancers, including lung cancer. Therefore, SAC is a potential new target for lung cancer therapy. Five small molecule inhibitors of monopolar spindle 1 (MPS1), an upstream component protein of SAC, have entered clinical trials. This article introduces the biological functions of SAC, summarizes the abnormal expression of SAC component proteins in various cancers and the research progress of MPS1 inhibitors, and expects to provide a reference for the future development of lung cancer therapeutic strategies targeting SAC components.
.


Sujets)
Humains , Protéines du cycle cellulaire/métabolisme , Appareil du fuseau/métabolisme , Protein-Serine-Threonine Kinases/métabolisme , Points de contrôle de la phase M du cycle cellulaire/génétique , Tumeurs du poumon/métabolisme
9.
Journal of Zhejiang University. Science. B ; (12): 39-48, 2019.
Article Dans Anglais | WPRIM | ID: wpr-1010442

Résumé

Interferon-γ (IFN-γ) has been used to control cancers in clinical treatment. However, an increasing number of reports have suggested that in some cases effectiveness declines after a long treatment period, the reason being unclear. We have reported previously that long-term IFN-γ treatment induces malignant transformation of healthy lactating bovine mammary epithelial cells (BMECs) in vitro. In this study, we investigated the mechanisms underlying the malignant proliferation of BMECs under IFN-γ treatment. The primary BMECs used in this study were stimulated by IFN-γ (10 ng/mL) for a long term to promote malignancy. We observed that IFN-γ could promote malignant cell proliferation, increase the expression of cyclin D1/cyclin-dependent kinase 4 (CDK4), decrease the expression of p21, and upregulate the expression of cellular-abelsongene (c-Abl) and histone deacetylase 2 (HDAC2). The HDAC2 inhibitor, valproate (VPA) and the c-Abl inhibitor, imatinib, lowered the expression level of cyclin D1/CDK4, and increased the expression level of p21, leading to an inhibitory effect on IFN-γ-induced malignant cell growth. When c-Abl was downregulated, the HDAC2 level was also decreased by promoted proteasome degradation. These data suggest that IFN-γ promotes the growth of malignant BMECs through the c-Abl/HDAC2 signaling pathway. Our findings suggest that long-term application of IFN-γ may be closely associated with the promotion of cell growth and even the carcinogenesis of breast cancer.


Sujets)
Animaux , Bovins , Femelle , Carcinogenèse/anatomopathologie , Protéines du cycle cellulaire/métabolisme , Prolifération cellulaire/effets des médicaments et des substances chimiques , Transformation cellulaire néoplasique/anatomopathologie , Cellules cultivées , Cellules épithéliales/anatomopathologie , Histone Deacetylase 2/métabolisme , Mésilate d'imatinib/pharmacologie , Interféron gamma/pharmacologie , Glandes mammaires animales/anatomopathologie , Tumeurs expérimentales de la mamelle/anatomopathologie , Protéines proto-oncogènes c-abl/métabolisme , Transduction du signal , Acide valproïque/pharmacologie
10.
Biol. Res ; 51: 44, 2018. tab, graf
Article Dans Anglais | LILACS | ID: biblio-983945

Résumé

BACKGROUND: Emerging evidence indicate that miRNAs play an important role on gastric cancer (GC) progression via regulating several downstream targets, but it is still partially uncovered. This study aimed to explore the molecular mechanisms of GC by comprehensive analysis of mRNAs and miRNA expression profiles. METHODS: The mRNA and miRNA expression profiles of GSE79973 and GSE67354 downloaded from Gene Expression Omnibus were used to analyze the differentially expressed genes (DEGs) and DE-miRNAs among GC tissues and normal tissues. Then, targets genes of DE-miRNAs were predicted and the DE-miRNA-DEG regulatory network was constructed. Next, function enrichment analysis of the overlapped genes between the predicted DE-miRNAs targets and DEGs was performed and a protein-protein interactions network of overlapped genes was constructed. Finally, RT-PCR analysis was performed to detect the expression levels of several key DEGs and DE-miRNAs. RESULTS: A set of 703 upregulated and 600 downregulated DEGs, as well as 8 upregulated DE-miRNAs and 27 downregulated DE-miRNAs were identified in GC tissue. hsa-miR-193b-3p and hsa-miR-148a-3p, which targeted most DEGs, were highlighted in the DE-miRNA-DEG regulatory network, as well as hsa-miR-1179, which targeted KNL1, was newly predicted to be associated with GC. In addition, NCAPG, which is targeted by miR-193b-3p, and KNL1, which is targeted by hsa-miR-1179, had higher degrees in the PPI network. RT-qPCR results showed that hsa-miR-148a-3p, hsa-miR-193b-3p, and hsa-miR-1179 were downregulated, and NCAPG and KNL1 were upregulated in GC tissues; this is consistent with our bioinformatics-predicted results. CONCLUSIONS: The downregulation of miR-193b-3p might contribute to GC cell proliferation by mediating the upregulation of NCAPG; as additionally, the downregulation of miR-193b-3p might contribute to the mitotic nuclear division of GC cells by mediating the upregulation of KNL1.


Sujets)
Humains , Tumeurs de l'estomac/métabolisme , Régulation de l'expression des gènes tumoraux/génétique , Régulation positive/génétique , Protéines du cycle cellulaire/métabolisme , microARN/métabolisme , Tumeurs de l'estomac/diagnostic , Tumeurs de l'estomac/génétique , Marqueurs biologiques tumoraux/génétique , Évolution de la maladie , Protéines du cycle cellulaire/génétique , Analyse de profil d'expression de gènes , Réaction de polymérisation en chaine en temps réel , Protéines associées aux microtubules/métabolisme
11.
Int. braz. j. urol ; 43(6): 1060-1067, Nov.-Dec. 2017. graf
Article Dans Anglais | LILACS | ID: biblio-892928

Résumé

ABSTRACT Objective: miR-483-5p has been identified as a miRNA oncogene in certain cancers. However, its role in prostate cancer has not been sufficiently investigated. In this study, we investigated the role of miR-483-5p in prostate cancer and examined RBM5 regulation by miR-483-5p. Material and methods: Expression levels of miR-483-5p were determined by quantitative real-time PCR. The effect of miR-483-5p on proliferation was evaluated by MTT assay, cell invasion was evaluated by trans-well invasion assays, and target protein expression was determined by western blotting in LNCaP, DU-145, and PC-3 cells. Luciferase reporter plasmids were constructed to confirm the action of miR-483-5p on downstream target gene RBM5 in HEK-293T cells. Results: we observed that miR-483-5p was upregulated in prostate cancer cell lines and tissues. A miR-483-5p inhibitor inhibited prostate cancer cell growth and invasion in DU-145 and PC-3 cells. miR-483-5p directly bound to the 3' untranslated region (3'UTR) of RBM5 in HEK-293T cells. RBM5 overexpression inhibited prostate cancer cell growth and invasion in LNCaP cells. Enforced RBM5 expression alleviated miR-483-5p promotion of prostate cancer cell growth and invasion in LNCaP cells. Conclusion: The present study describes a potential mechanism underlying a miR-483-5p/RBM5 link that contributes to prostate cancer development.


Sujets)
Humains , Mâle , Tumeurs de la prostate/génétique , Tumeurs de la prostate/anatomopathologie , Régulation de l'expression des gènes tumoraux/génétique , Protéines du cycle cellulaire/métabolisme , Régions non traduites/génétique , Protéines suppresseurs de tumeurs/métabolisme , microARN/physiologie , Prolifération cellulaire/génétique , Protéines de liaison à l'ADN/métabolisme , Réaction de polymérisation en chaine en temps réel , Tumeurs de la prostate/mortalité , Régulation négative , Régulation positive , Protéines de liaison à l'ARN/métabolisme , microARN/antagonistes et inhibiteurs , Lignée cellulaire tumorale , Invasion tumorale
12.
Cad. saúde pública ; 31(3): 620-632, 03/2015. tab
Article Dans Portugais | LILACS | ID: lil-744835

Résumé

O estudo descreve os pontos de venda de alimentos e sua associação com sobrepeso/obesidade em escolares de Florianópolis, Santa Catarina, Brasil. Desenho transversal com amostra probabilística de 2.506 escolares de escolas públicas (n = 19) e privadas (n = 11). O sobrepeso/obesidade foi classificado pela referência da Organização Mundial da Saúde de 2007. Foram realizadas análises brutas e ajustadas por meio de regressão de Poisson. A prevalência de sobrepeso/obesidade foi de 34,2%. Na rede pública, foram verificados 19,6% de sobrepeso e 13,5% de obesidade. Na rede privada, observaram-se 22,4% de sobrepeso e 11,1% de obesidade. Na rede pública, foi encontrada associação entre sobrepeso/obesidade e utilização da padaria (p = 0,004). Na rede privada, observou-se que os escolares de famílias que utilizaram o supermercado apresentaram 26% menos de sobrepeso/obesidade do que os escolares que não utilizam esses pontos de venda de alimentos (p = 0,003). Os dados encontrados evidenciam a existência de associação entre a utilização de alguns tipos de pontos de venda de alimentos (supermercado e padaria) e a prevalência de sobrepeso/obesidade na população escolar.


The study analyzes retail food outlets and their association with overweight/obesity in schoolchildren from Florianópolis, Santa Catarina State, Brazil. The study used a cross-sectional design with a random sample of 2,506 schoolchildren from public (n = 19) and private schools (n = 11). Overweight and obesity were classified according to World Health Organization guidelines for 2007, and crude and adjusted analyses were performed using Poisson regression. Prevalence of overweight/obesity was 34.2%. In public schools, 19.6% of the children were overweight and 13.5% were obese, as compared to 22.4% and 11.1% in private schools. An association was found in the public school system between overweight/obesity and the use of bakeries for food purchases (p = 0.004). In the private school system, children of families that bought groceries at the supermarket showed 26% less overweight/obesity compared to those who did not (p = 0.003). The data show an association between some types of food outlets (supermarkets and bakeries) and prevalence of overweight/obesity in the school-age population.


El estudio describe los puntos de venta de alimentos y su asociación con el sobrepeso/obesidad en escolares de Florianópolis, Santa Catarina, Brasil. Se trata de un estudio transversal con una muestra aleatoria de 2.506 escolares de las escuelas públicas (n = 19) y privadas (n = 11). El sobrepeso/obesidad se clasifica, en función de la OMS en 2007, con análisis ajustados y crudos que se realizaron mediante la regresión de Poisson. La prevalencia de sobrepeso/obesidad fue de un 34,2%. En el sistema público el resultado fue de un 19,6% sobrepeso y un 13,5% obesidad. En el privado se observó un 22,4% de sobrepeso y 11,1% obesidad. En el primero se encontró una correlación entre el sobrepeso/obesidad y el consumo de bollería (p = 0,004). En las escuelas privadas se observó que los escolares de familias que habían utilizado el supermercado tenían un 26% menos de sobrepeso/ obesidad que los niños en edad escolar que no utilizaron este punto de venta de alimentos (p = 0,003). En el momento del estudio existe una asociación entre el uso de algunos tipos de punto de venta de alimentos (supermercado y panadería) y la prevalencia de sobrepeso/obesidad en escolares.


Sujets)
ADN fongique/composition chimique , Protéines du choc thermique HSP90/métabolisme , Conformation d'acide nucléique , Saccharomyces cerevisiae , Protéines de Saccharomyces cerevisiae/métabolisme , Télomère/composition chimique , Protéines du cycle cellulaire/génétique , Protéines du cycle cellulaire/métabolisme , Protéines chromosomiques nonhistones/génétique , Protéines chromosomiques nonhistones/métabolisme , ADN fongique/métabolisme , Activation enzymatique , Protéines du choc thermique HSP90/génétique , Protéines de Saccharomyces cerevisiae/génétique , Saccharomyces cerevisiae/génétique , Saccharomyces cerevisiae/métabolisme , Telomerase/métabolisme , Protéines télomériques/génétique , Protéines télomériques/métabolisme , Télomère/métabolisme
13.
Dental press j. orthod. (Impr.) ; 20(1): 45-51, Jan-Feb/2015. tab, graf
Article Dans Anglais | LILACS | ID: lil-741446

Résumé

INTRODUCTION: The consensus about the relationship between TMD and orthodontic treatment has gone from a cause and effect association between TMD and orthodontic treatment to the idea that there is no reliable evidence supporting this statement. OBJECTIVE: To assess the beliefs, despite scientific evidence, of Brazilian orthodontists about the relationship between TMD and orthodontic treatment with regards to treatment, prevention and etiology of TMD. METHODS: A survey about the relationship between TMD and orthodontic treatment was prepared and sent to Brazilian orthodontists by e-mail and social networks. Answers were treated by means of descriptive statistics and strong associations between variables were assessed by qui-square test. RESULTS: The majority of orthodontists believe that orthodontic treatment not only is not the best treatment option for TMD, but also is not able to prevent TMD. Nevertheless, the majority of orthodontists believe that orthodontic treatment can cause TMD symptoms. CONCLUSION: This study suggests that orthodontists' beliefs about the relationship between orthodontic treatment and TMD are in accordance with scientific evidence only when referring to treatment and prevention of TMD. The majority of orthodontists believe that, despite scientific evidence, orthodontic treatment can cause TMD. .


INTRODUÇÃO: o consenso sobre a relação entre DTM e tratamento ortodôntico foi de uma associação de causa e efeito à ideia de que não há evidências confiáveis que suportem essa afirmação. OBJETIVO: avaliar as crenças, sem considerar as evidências, de ortodontistas brasileiros sobre a relação entre DTM e tratamento ortodôntico com relação ao tratamento, prevenção e etiologia da DTM. MÉTODOS: um questionário sobre a relação entre DTM e tratamento ortodôntico foi preparado e enviado a ortodontistas brasileiros por meio de e-mail e mídias sociais. As respostas foram analisadas por estatística descritiva, e fortes associações entre as variáveis foram verificadas pelo teste χ2. RESULTADOS: a maioria dos ortodontistas acredita que o tratamento ortodôntico não é o melhor tratamento para DTM. Além disso, acreditam que não é a melhor forma para sua prevenção. Também, a maioria dos ortodontistas acredita que o tratamento ortodôntico pode causar sintomas de DTM. CONCLUSÃO: este estudo sugere que as crenças dos ortodontistas sobre a relação entre tratamento ortodôntico e DTM estão de acordo com as evidências científicas apenas quando se trata do tratamento e da prevenção de DTM. A maioria dos ortodontistas acredita que, apesar das evidências científicas, o tratamento ortodôntico pode causar DTM. .


Sujets)
Humains , Protéines du cycle cellulaire/métabolisme , Réplication de l'ADN/génétique , Facteurs de transcription Forkhead/métabolisme , Phase G1/physiologie , Régulation de l'expression des gènes/génétique , Protein-Serine-Threonine Kinases/métabolisme , Origine de réplication/génétique , Transduction du signal/génétique , Technique de Western , Fractionnement cellulaire , Lignée cellulaire , Protéines du cycle cellulaire/génétique , /métabolisme , Amorces ADN/génétique , Technique d'immunofluorescence , Facteurs de transcription Forkhead/génétique , Immunotransfert , Immunoprécipitation , Protéines et peptides de signalisation intercellulaire/métabolisme , Protein-Serine-Threonine Kinases/génétique , Protéines proto-oncogènes c-myc/métabolisme , RT-PCR , Interférence par ARN
14.
Experimental & Molecular Medicine ; : e166-2015.
Article Dans Anglais | WPRIM | ID: wpr-30204

Résumé

CCCTC-binding factor (CTCF) is a highly conserved zinc finger protein and is best known as a transcription factor. It can function as a transcriptional activator, a repressor or an insulator protein, blocking the communication between enhancers and promoters. CTCF can also recruit other transcription factors while bound to chromatin domain boundaries. The three-dimensional organization of the eukaryotic genome dictates its function, and CTCF serves as one of the core architectural proteins that help establish this organization. The mapping of CTCF-binding sites in diverse species has revealed that the genome is covered with CTCF-binding sites. Here we briefly describe the diverse roles of CTCF that contribute to genome organization and gene expression.


Sujets)
Animaux , Humains , Protéines du cycle cellulaire/métabolisme , Protéines chromosomiques nonhistones/métabolisme , Régulation de l'expression des gènes , Génome , Liaison aux protéines , Cartes d'interactions protéiques , Protéines de répression/analyse
15.
Biol. Res ; 47: 1-12, 2014. ilus, graf, tab
Article Dans Anglais | LILACS | ID: biblio-950760

Résumé

BACKGROUND: Interactions between genes and their products give rise to complex circuits known as gene regulatory networks (GRN) that enable cells to process information and respond to external stimuli. Several important processes for life, depend of an accurate and context-specific regulation of gene expression, such as the cell cycle, which can be analyzed through its GRN, where deregulation can lead to cancer in animals or a directed regulation could be applied for biotechnological processes using yeast. An approach to study the robustness of GRN is through the neutral space. In this paper, we explore the neutral space of a Schizosaccharomyces pombe (fission yeast) cell cycle network through an evolution strategy to generate a neutral graph, composed of Boolean regulatory networks that share the same state sequences of the fission yeast cell cycle. RESULTS: Through simulations it was found that in the generated neutral graph, the functional networks that are not in the wildtype connected component have in general a Hamming distance more than 3 with the wildtype, and more than 10 between the other disconnected functional networks. Significant differences were found between the functional networks in the connected component of the wildtype network and the rest of the network, not only at a topological level, but also at the state space level, where significant differences in the distribution of the basin of attraction for the G1 fixed point was found for deterministic updating schemes. CONCLUSIONS: In general, functional networks in the wildtype network connected component, can mutate up to no more than 3 times, then they reach a point of no return where the networks leave the connected component of the wildtype. The proposed method to construct a neutral graph is general and can be used to explore the neutral space of other biologically interesting networks, and also formulate new biological hypotheses studying the functional networks in the wildtype network connected component.


Sujets)
Schizosaccharomyces/physiologie , Cycle cellulaire/physiologie , Kinases cyclines-dépendantes/métabolisme , Réseaux de régulation génique/physiologie , Modèles biologiques , Schizosaccharomyces/génétique , Infographie , Simulation numérique , Phase G1/physiologie , , Protéines du cycle cellulaire/métabolisme , Biologie informatique
16.
Rev. méd. Chile ; 141(12): 1570-1577, dic. 2013. ilus, graf
Article Dans Espagnol | LILACS | ID: lil-705577

Résumé

Gastric cancer is the first cause of death for cancer in Chile. The recently identified genetic alterations in these tumors have not yielded new biomarkers for the disease. Epigenetics or the study of reversible genomic changes that do not affect protein codifying DNA sequences but cause phenotypic disturbances, is identifying new cancer biomarkers. Specifically, the loss of expression caused by the covalent link of a methyl group to carbon 5 of cytosine (DNA hypermethylation) is extensively evaluated. Performing an epigenetic evaluation of 24 genes, we have identified eight genes associated to the aggressive signet ring cell type gastric cancer, the association between APC hypermethylation and worse prognosis and BRCA1 hypermethylation association with early onset of gastric cancer. The most interesting findings are the hypermethylation of Reprimo gene in plasma as a population biomarker and the tissue over expression of p73 gene (as a consequence of hypomethylation) as a high risk indicator of progression to gastric cancer. All these findings are indicating an important role of epigenetics in the pathogenesis and early detection of gastric cancer.


Sujets)
Humains , Protéines du cycle cellulaire/génétique , Méthylation de l'ADN/génétique , Épigénomique , Glycoprotéines/génétique , Tumeurs de l'estomac/génétique , Marqueurs biologiques tumoraux , Protéines du cycle cellulaire/métabolisme , Évolution de la maladie , Diagnostic précoce , Glycoprotéines/métabolisme , Tumeurs de l'estomac/diagnostic
17.
Clinics ; 68(6): 825-833, jun. 2013. graf
Article Dans Anglais | LILACS | ID: lil-676926

Résumé

OBJECTIVES: MiRNAs are intrinsic RNAs that interfere with protein translation. Few studies on the synergistic effects of miRNAs have been reported. Both miR-424 and miR-381 have been individually reported to be involved in carcinogenesis. They share a common putative target, WEE1, which is described as an inhibitor of G2/M progression. Here, we studied the synergistic effects of miR-424 and miR-381 on renal cancer cells. METHODS: The viability of 786-O cells was analyzed after transfection with either a combination of miR-424 and miR-381 or each miRNA alone. We investigated cell cycle progression and apoptosis with flow cytometry. To confirm apoptosis and the abrogation of G2/M arrest, we determined the level of pHH3, which is an indicator of mitosis, and caspase-3/7 activity. The expression levels of WEE1, Cdc25, γH2AX, and Cdc2 were manipulated to investigate the roles of these proteins in the miRNA-induced anti-tumor effects. To verify that WEE1 was a direct target of both miR-424 and miR-381, we performed a dual luciferase reporter assay. RESULTS: We showed that the combination of these miRNAs synergistically inhibited proliferation, abrogated G2/M arrest, and induced apoptosis. This combination led to Cdc2 activation through WEE1 inhibition. This regulation was more effective when cells were treated with both miRNAs than with either miRNA alone, indicating synergy between these miRNAs. WEE1 was verified to be a direct target of each miRNA according to the luciferase reporter assay. CONCLUSIONS: These data clearly demonstrate that these two miRNAs might synergistically act as novel modulators of tumorigenesis by down-regulating WEE1 expression in renal cell cancer cells. .


Sujets)
Humains , Néphrocarcinome/génétique , Protéines du cycle cellulaire/métabolisme , Cycline B/métabolisme , Tumeurs du rein/génétique , microARN/pharmacologie , Protéines nucléaires/métabolisme , Protein-tyrosine kinases/métabolisme , Technique de Western , Lignée cellulaire tumorale , Phénomènes physiologiques cellulaires , Transformation cellulaire néoplasique , Régulation négative , Cytométrie en flux , Régulation de l'expression des gènes tumoraux , microARN/métabolisme , Réaction de polymérisation en chaine en temps réel , Facteurs temps , Régulation positive
18.
Journal of Korean Medical Science ; : 1037-1043, 2012.
Article Dans Anglais | WPRIM | ID: wpr-154187

Résumé

The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), inhibits the growth of several types of human cancer cells in vitro, but its therapeutic use is limited because it causes hypercalcemia. Among its analogs, 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol), has fewer calcemic effects and exhibits an activity equipotent to that of calcitriol. We assessed the antitumor and anti-inflammatory effects of paricalcitol in gastric cancer cells, and evaluated the potential role of vitamin D in the treatment of peritoneal metastatic gastric cancer. In this study, treatment with paricalcitol inhibited gastric cancer cell growth and induced cell cycle arrest. Paricalcitol also induced apoptosis and showed anti-inflammatory activity. Moreover, the growth of intraperitoneal metastases in vivo was reduced in mice treated with paricalcitol. 18F-FDG uptake was significantly lower in the paricalcitol group compared to control group (SUV; control group 13.2 +/- 5.3 vs paricalcitol group 4.5 +/- 3.0). Intraperitoneal tumor volume was significantly lower in paricalcitol treated mice (control group 353.2 +/- 22.9 mm3 vs paricalcitol group 252.0 +/- 8.4 mm3). These results suggest that the vitamin D analog, paricalcitol, has anticancer activity on gastric cancer cells by regulation of the cell cycle, apoptosis, and inflammation.


Sujets)
Animaux , Humains , Souris , Antinéoplasiques/composition chimique , Apoptose/effets des médicaments et des substances chimiques , Points de contrôle du cycle cellulaire/effets des médicaments et des substances chimiques , Protéines du cycle cellulaire/métabolisme , Lignée cellulaire tumorale , Prolifération cellulaire/effets des médicaments et des substances chimiques , Modèles animaux de maladie humaine , Ergocalciférol/composition chimique , Fluorodésoxyglucose F18/composition chimique , Souris de lignée BALB C , Tumeurs du péritoine/traitement médicamenteux , Tomographie par émission de positons , Tumeurs de l'estomac/traitement médicamenteux , Transplantation hétérologue
19.
Experimental & Molecular Medicine ; : 389-392, 2011.
Article Dans Anglais | WPRIM | ID: wpr-102685

Résumé

Cellular senescence is a tumor-suppressive process instigated by proliferation in the absence of telomere replication, by cellular stresses such as oncogene activation, or by activation of the tumor suppressor proteins, such as Rb or p53. This process is characterized by an irreversible cell cycle exit, a unique morphology, and expression of senescence-associated-beta-galactosidase (SA-beta-gal). Despite the potential biological importance of cellular senescence, little is known of the mechanisms leading to the senescent phenotype. p41-Arc has been known to be a putative regulatory component of the mammalian Arp2/3 complex, which is required for the formation of branched networks of actin filaments at the cell cortex. In this study, we demonstrate that p41-Arc can induce senescent phenotypes when it is overexpressed in human tumor cell line, SaOs-2, which is deficient in p53 and Rb tumor suppressor genes, implying that p41 can induce senescence in a p53-independent way. p41-Arc overexpression causes a change in actin filaments, accumulating actin filaments in nuclei. Therefore, these results imply that a change in actin filament can trigger an intrinsic senescence program in the absence of p53 and Rb tumor suppressor genes.


Sujets)
Humains , Cytosquelette d'actine/métabolisme , Complexe Arp-2-3/métabolisme , Vieillissement de la cellule , Protéines du cycle cellulaire/métabolisme , Lignée cellulaire tumorale , Noyau de la cellule/métabolisme , Fibroblastes/physiologie , Protéines recombinantes/génétique , Protéine du rétinoblastome/déficit , Protéine p53 suppresseur de tumeur/déficit
20.
Clinics ; 65(8): 757-762, June 2010. ilus, graf, tab
Article Dans Anglais | LILACS | ID: lil-557000

Résumé

OBJECTIVES: The aim of this study was to examine the expression of the N-myc downstream-regulated gene 1 protein in benign and malignant lesions of the thyroid gland by immunohistochemistry. INTRODUCTION: N-myc downstream-regulated gene 1 encodes a protein whose expression is induced by various stimuli, including cell differentiation, exposure to heavy metals, hypoxia, and DNA damage. Increased N-myc downstream-regulated gene 1 expression has been detected in various types of tumors, but the role of N-myc downstream-regulated gene 1 expression in thyroid lesions remains to be determined. METHODS: A tissue microarray paraffin block containing 265 tissue fragments corresponding to normal thyroid, nodular goiter, follicular adenoma, papillary thyroid carcinoma (classical pattern and follicular variant), follicular carcinoma, and metastases of papillary and follicular thyroid carcinomas were analyzed by immunohistochemistry using a polyclonal anti- N-myc downstream-regulated gene 1 antibody. RESULTS: The immunohistochemical expression of N-myc downstream-regulated gene 1 was higher in carcinomas compared to normal thyroid glands and nodular goiters, with higher expression in classical papillary thyroid carcinomas and metastases of thyroid carcinomas (P < 0.001). A combined analysis showed higher immunohistochemical expression of NDRG1 in malignant lesions (classical pattern and follicular variant of papillary thyroid carcinomas, follicular carcinomas, and metastases of thyroid carcinomas) compared to benign thyroid lesions (goiter and follicular adenomas) (P = 0.043). In thyroid carcinomas, N-myc downstream-regulated gene 1 expression was significantly correlated with a more advanced TNM stage (P = 0.007) and age, metastasis, tumor extent, and size (AMES) high-risk group (P = 0.012). CONCLUSIONS: Thyroid carcinomas showed increased immunohistochemical N-myc downstream-regulated gene 1 expression compared to normal and benign thyroid lesions and is correlated with more advanced tumor stages.


Sujets)
Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Adénomes/métabolisme , Protéines du cycle cellulaire/métabolisme , Protéines et peptides de signalisation intracellulaire/métabolisme , Protéines tumorales/métabolisme , Tumeurs de la thyroïde/métabolisme , Adénomes/anatomopathologie , Immunohistochimie , Métastase lymphatique , Analyse sur microréseau , Protéines tumorales/génétique , Inclusion en paraffine , Tumeurs de la thyroïde/anatomopathologie
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