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Article in Chinese | WPRIM | ID: wpr-922013


OBJECTIVE@#To explore the genetic etiology of a neonate with suggestive features of Cornelia de Lange Syndrome (CdLS).@*METHODS@#Chromosome karyotyping, copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were carried out for the child. Meanwhile, peripheral venous blood samples were taken from his parents for verifying the suspected pathogenic variants detected in the child.@*RESULTS@#The child has exhibited developmental delay, microcephaly, ptosis, micrognathia, and low ear setting, and was suspected as CdLS. No abnormality was found by karyotyping and CNV-seq analysis. WES has detected 5 heterogeneous variants and 1 hemizygous variant on the X chromosome. Combining the genetic pattern and result of family verification, a hemizygous C.3500T>C (p.ile1167thr) of the SMC1A gene was predicted to underlay the clinical manifestations of the patient. This variant was not recorded in the dbSNP and gnomAD database. PolyPhen2, Provean, SIFT all predicted the variant to be harmful, and PhastCons conservative prediction is was a conservative mutation. ACMG variant classification standard evidence supports are PM2, PP2, and PP3.@*CONCLUSION@#The novel c.3500T>C (p.Ile1167Thr) missense mutation of the SMC1A gene probably underlay the genetic etiology of CdLS in this child. Above results has enriched the mutation spectrum of CdLS type II, and facilitated clinical counseling for this family.

Cell Cycle Proteins/genetics , Child , DNA Copy Number Variations , De Lange Syndrome/genetics , Humans , Infant, Newborn , Mutation , Phenotype , Whole Exome Sequencing
Journal of Experimental Hematology ; (6): 1129-1135, 2021.
Article in Chinese | WPRIM | ID: wpr-888528


OBJECTIVE@#To investigate the effect of CDK1 interference regulation of PLK1, Aurora B and TRF1 on the proliferation of leukemia cells.@*METHODS@#The human myelogenous leukemia cell line HL-60 was selected as the research object, and the effect of TRF1 expression and its changes on cell proliferation and cycle was investigated by regulating intracellular CDK1 expression. The objects were divided into 5 groups, including control group, shRNA-NC group, CDK1-shRNA group, pcDNA group and pcDNA-CDK1 group. RT-PCR was used to detect the CDK1 expression of cells in each group; colony formation was used to detect the proliferation of the cells. Western blot was used to detect the expression of CDK1, PLK1, Aurora B, TRF1, and cyclin p53, p27, cyclinA.@*RESULTS@#The phosphorylation level of PLK1, Aurora B and the expression of TRF1 in the CDK1-shRNA group were significantly down-regulated as compared with those in the control group (P<0.05). Compared with the control group, the cells in CDK1-shRNA group showed lower clone formation rate, the increasing of cycle-associated proteins p53 and p27 and the decreasing of cyclinA expression (P<0.05). It was shown that interfered CDK1 expression could inhibit the proliferation of HL-60 cells and prolong the time that they enter mitosis, thereby extending the cell cycle. Compared with the control group, the overexpressed CDK1 in the pcDNA-CDK1 group made the phosphorylation level of PLK1, Aurora B, and TRF1 expression increase significantly (P<0.05), also the colony formation rate (P<0.05). The cycle-related proteins p53 and p27 was down-regulated, while cyclinA expression was up-regulate significantly (P<0.05). The results indicted that overexpressed CDK1 could stimulate adverse reactions, thereby promoting the proliferation of HL-60 cells and shortening the cell cycle.@*CONCLUSION@#Knocking out CDK1 can inhibit the phosphorylation of PLK1 and Aurora B and negatively regulate TRF1, thereby inhibiting the proliferation of leukemia cells.

CDC2 Protein Kinase , Cell Cycle Proteins/genetics , Cell Proliferation , Humans , Leukemia , Mitosis , Phosphorylation , Proto-Oncogene Proteins/genetics
Article in Chinese | WPRIM | ID: wpr-879534


OBJECTIVE@#To explore the genetic basis for 7 patients with Alström syndrome.@*METHODS@#DNA was extracted from peripheral blood samples of the patients and their parents. Whole exome sequencing was carried out for the patients. Suspected variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#Genetic testing revealed 12 variants of the ALMS1 gene among the 7 patients, including 7 nonsense and 5 frameshift variants, which included c.5418delC (p.Tyr1807Thrfs*23), c.10549C>T (p.Gln3517*), c.9145dupC (p.Thr3049Asnfs*12), c.10819C>T (p.Arg3607*), c.5701_5704delGAGA (p.Glu1901Argfs*18), c.9154_9155delCT (p.Cys3053Serfs*9), c.9460delG (p.Val3154*), c.9379C>T (p.Gln3127*), c.12115C>T (p.Gln4039*), c.1468dupA (p.Thr490Asnfs*15), c.10825C>T (p.Arg3609*) and c.3902C>A (p.Ser1301*). Among these, c.9154_ 9155delCT, c.9460delG, c.9379C>T, and c.1468dupA were unreported previously. Based on the standards and guidelines of American College of Medical Genetics and Genomics, the c.9379C>T and c.12115C>T variants of the ALMS1 gene were predicted to be likely pathogenic (PVS1+PM2), whilst the other 10 variants were predicted to be pathogenic (PVS1+ PM2+ PP3+PP4).@*CONCLUSION@#ALMS1 variants probably underlay the Alström syndrome in the 7 patients, and genetic testing can provide a basis for the clinical diagnosis of this syndrome. The discovery of four novel variants has expanded the mutational spectrum of Alström syndrome.

Alstrom Syndrome/genetics , Cell Cycle Proteins/genetics , Humans , Mutation , Pedigree , Whole Exome Sequencing
Article in Chinese | WPRIM | ID: wpr-879525


OBJECTIVE@#To carry out genetic testing for an abortus suspected with Cornelia de Lange syndrome (CdLS).@*METHODS@#History of gestation and the family was taken. Combined with prenatal ultrasonography and the phenotype of the abortus, a diagnosis was made for the proband. Fetal tissue and peripheral blood samples of its parents were collected for the extraction of genomic DNA. Whole exome sequencing was carried out to detect mutations related to the phenotype. Suspected mutations were verified in the parents through Sanger sequencing.@*RESULTS@#Prenatal ultrasound found that the forearms and hands of the fetus were anomalous, in addition with poorly formed vermis cerebellum, slight micrognathia, and increased echo of bilateral renal parenchyma. Examination of the abortus has noted upper limb and facial malformations. Whole exome sequencing revealed that the fetus carried a heterozygous c.2118delG (p.Lys706fs) frameshift mutation of the NIPBL gene. The same mutation was not found in either parent.@*CONCLUSION@#The heterozygous c.2118delG (p.Lys706fs) frameshift mutation of the NIPBL gene probably underlies the CdLS in the fetus. Above finding has provided a basis for the genetic counseling for the family.

Cell Cycle Proteins/genetics , DNA Mutational Analysis , De Lange Syndrome/pathology , Female , Fetus , Humans , Male , Mutation , Phenotype , Pregnancy , Whole Exome Sequencing
Chinese Journal of Biotechnology ; (12): 2298-2312, 2020.
Article in Chinese | WPRIM | ID: wpr-878487


Polo-like kinase 1 (Plk1) is widely regarded as one of the most promising targets for cancer therapy due to its essential role in cell division and tumor cell survival. At present, most Plk1 inhibitors have been developed based on kinase domain, some of which are in clinical trial. However, inhibitors targeting kinase domain face off-target effect and drug resistance owing to the conserved nature and the frequent mutations in the ATP-binding pocket. In addition to a highly conserved kinase domain, Plk1 also contains a unique Polo-Box domain (PBD), which is essential for Plk1's subcellular localization and mitotic functions. Inhibitors targeting Plk1 PBD show stronger selectivity and less drug resistance for cancer therapy. Therefore, Plk1 PBD is an attractive target for the development of anti-cancer agents. In this review, we will summarize the up-to date drug discovery for targeting Plk1 PBD, including the molecular structure and cellular functions of Plk1 PBD. Small-molecule inhibitors targeting Plk1 PBD not only provide an opportunity to specifically inhibit Plk1 activity for cancer treatment, but also unveil novel biological basis regarding the molecular recognition of Plk1 and its substrates.

Cell Cycle Proteins/genetics , Neoplasms/drug therapy , Protein Kinase Inhibitors/pharmacology , Protein-Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins/genetics
Article in Chinese | WPRIM | ID: wpr-880765


OBJECTIVE@#To screen the key genes related to the prognosis of lung adenocarcinoma through big data analysis and explore their clinical value and potential mechanism.@*METHODS@#We analyzed GSE18842, GSE27262, and GSE33532 gene expression profile data obtained from the Gene Expression Omnibus (GEO). Bioinformatics methods were used to screen the differentially expressed genes in lung adenocarcinoma tissues and KEGG and GO enrichment analysis was performed, followed by PPI interaction network analysis, module analysis, differential expression analysis, and prognosis analysis. The expressions of MAD2L1 and TTK by immunohistochemistry were verified in 35 non-small cell lung cancer specimens and paired adjacent tissues.@*RESULTS@#We identified a total of 256 genes that showed significant differential expressions in lung adenocarcinoma, including 66 up-regulated and 190 down-regulated genes. Thirty-two up-regulated core genes were screened by functional analysis, and among them 29 were shown to significantly correlate with a poor prognosis of patients with lung adenocarcinoma. All the 29 genes were highly expressed in lung adenocarcinoma tissues compared with normal lung tissues and were mainly enriched in cell cycle pathways. Seven of these key genes were closely related to the spindle assembly checkpoint (SAC) complex and responsible for regulating cell behavior in G2/M phase. We selected SAC-related proteins TTK and MAD2L1 to test their expressions in clinical tumor samples, and detected their overexpression in lung adenocarcinoma tissues as compared with the adjacent tissues.@*CONCLUSIONS@#Seven SAC complex-related genes, including TTK and MAD2L1, are overexpressed in lung adenocarcinoma tissues with close correlation with the prognosis of the patients.

Adenocarcinoma of Lung/genetics , Big Data , Cell Cycle Proteins/genetics , Computational Biology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , M Phase Cell Cycle Checkpoints , Mad2 Proteins/genetics , Protein-Serine-Threonine Kinases/genetics , Protein-Tyrosine Kinases/genetics
Biol. Res ; 53: 41, 2020. graf
Article in English | LILACS | ID: biblio-1131885


BACKGROUND: Tumor angiogenesis is an essential event for tumor growth and metastasis. It has been showed that REC8, a component of the meiotic cohesion complex, played a vital role in Epithelial-Mesenchymal Transition (EMT) in gastric cancer. However, the role of REC8 in gastric cancer angiogenesis remains to be identified. RESULTS: Inhibition of REC8 expression in gastric cancer cells contributed to tumor angiogenesis in the gastric cancer microenvironment. The clinical analysis demonstrated that the loss of REC8 in gastric cancer with enrichment of MVD. Depletion of REC8 expression in gastric cancer cells significantly increased tube formation of human umbilical vein endothelial cells (HUVECs), which is attributed to enhancement of vascular endothelial growth factor (VEGF) secretion caused by REC8 slicing. While addition of neutralizing antibody targeted VEGF into supernatant drastically reversed the effect of REC8 loss in gastric cancer cells on tube formation. Mechanistic analyses indicated that ablation of REC8 promotes nuclear factor-κB (NF-κB) p65 activity and its downstream gene VEGF expression, leading to tube formation. CONCLUSIONS: These results demonstrated a novel REC8 function that suppressed tumor angiogenesis and progression by attenuation of VEGF in gastric cancer microenvironment.

Humans , Stomach Neoplasms/pathology , NF-kappa B/genetics , Cell Cycle Proteins/genetics , Vascular Endothelial Growth Factor A/genetics , Neovascularization, Pathologic/genetics , Stomach Neoplasms/blood supply , Cell Line, Tumor , Tumor Microenvironment , Human Umbilical Vein Endothelial Cells
Rev. bras. ginecol. obstet ; 40(10): 606-613, Oct. 2018. graf
Article in English | LILACS | ID: biblio-977778


Abstract Objective The aim of the present study was to analyze the expression of the CD63, S100A6, and GNB2L1genes, which participate in mechanisms related to the complex pathophysiology of endometriosis. Methods A case-control study was conducted with 40 women who were diagnosed with endometriosis, and 15 fertile and healthy women. Paired samples of eutopic endometrium and endometriotic lesions (peritoneal and ovarian endometriotic implants) were obtained from the women with endometriosis in the proliferative (n = 20) or secretory phases (n = 20) of the menstrual cycle. As controls, paired endometrial biopsy samples were collected from the healthy women in the proliferative (n = 15) and secretory (n = 15) phases of the samemenstrual cycle.We analyzed the expression levels of the CD63, S100A6, and GNB2L1 genes by real-time polymerase chain reaction. Results An increase in CD63, S100A6, and GNB2L1 gene transcript levels was observed in the ectopic implants compared with the eutopic endometrium of the women with and without endometriosis, regardless of the phase of the menstrual cycle. Conclusion These findings suggest that the CD63, S100A6, and GNB2L1 genesmay be involved in the pathogenesis of endometriosis, since they participate in mechanisms such as inhibition of apoptosis, angiogenesis and cell proliferation, which lead to the loss of cell homeostasis in the ectopic endometrium, thus contributing to the implantation and survival of the tissue in the extrauterine environment.

Resumo Objetivo O objetivo do presente estudo foi analisar a expressão dos genes CD63, S100A6 e GNB2L1, que participam em mecanismos relacionados à complexa fisiopatologia da endometriose. Métodos Um estudo caso-controle foi realizado com 40 mulheres diagnosticadas com endometriose e 15 mulheres férteis e saudáveis. Amostras pareadas de endométrio eutópico e de lesões endometrióticas (implantes endometrióticos peritoneais e ovarianos) foram obtidas de mulheres com endometriose nas fases proliferativa (n = 20) ou secretora (n = 20) do ciclo menstrual. Como controle, amostras pareadas de biópsia endometrial foram coletadas de mulheres saudáveis nas fases proliferativa (n = 15) e secretora (n = 15) nomesmo ciclomenstrual. Foram analisados os níveis de expressão dos genes CD63, S100A6 e GNB2L1 por reação em cadeia da polimerase em tempo real. Resultados Foi observado um aumento nos níveis de transcritos dos genes CD63, S100A6 e GNB2L1 em implantes ectópicos quando comparado ao endométrio eutópico de mulheres com e sem endometriose, independente da fase do ciclo menstrual. Conclusão Estes achados sugerem que os genes CD63, S100A6 e GNB2L1 podem estar envolvidos na patogênese da endometriose, pois participam de mecanismos como inibição de apoptose, angiogênese e proliferação celular, os quais levam à perda da homeostase celular no endométrio ectópico e, portanto, contribuem para o implante e a sobrevivência do tecido no ambiente extrauterino.

Humans , Female , Adult , Apoptosis/genetics , Cell Cycle Proteins/genetics , Cell Proliferation/genetics , Endometriosis/genetics , Endometriosis/pathology , Tetraspanin 30/genetics , S100 Calcium Binding Protein A6/genetics , Receptors for Activated C Kinase/genetics , Neoplasm Proteins/genetics , Neovascularization, Pathologic/genetics , Case-Control Studies , Gene Expression
Biol. Res ; 51: 44, 2018. tab, graf
Article in English | LILACS | ID: biblio-983945


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.

Humans , Stomach Neoplasms/metabolism , Gene Expression Regulation, Neoplastic/genetics , Up-Regulation/genetics , Cell Cycle Proteins/metabolism , MicroRNAs/metabolism , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Biomarkers, Tumor/genetics , Disease Progression , Cell Cycle Proteins/genetics , Gene Expression Profiling , Real-Time Polymerase Chain Reaction , Microtubule-Associated Proteins/metabolism
Biol. Res ; 49: 1-10, 2016. ilus, graf, tab
Article in English | LILACS | ID: lil-774432


BACKGROUND: Reprimo (RPRM), a highly glycosylated protein, is a new downstream effector of p53-induced cell cycle arrest at the G2/M checkpoint, and a putative tumor suppressor gene frequently silenced via methylation of its promoter region in several malignances. The aim of this study was to characterize the epigenetic inactivation and its biological function in BC cell lines. METHODS: The correlation between RPRM methylation and loss of mRNA expression was assessed in six breast cancer cell lines by methylation specific PCR (MSP), 5'-Aza-2'-deoxycytidine treatment and RT-PCR assays. MDA-MB-231 cells were chosen to investigate the phenotypic effect of RPRM in cell proliferation, cell cycle, cell death, cell migration and invasion. RESULTS: In the cancer methylome system (CMS) (web-based system for visualizing and analyzing genome-wide methylation data of human cancers), the CpG island region of RPRM (1.1 kb) was hypermethylated in breast cancer compared to normal breast tissue; more interesting still was that ERa(+) tumors showed higher methylation intensity than ERa(-). Downregulation of RPRM mRNA by methylation was confirmed in MDA-MB-231 and BT-20 cell lines. In addition, overexpression of RPRM in MDA-MB-231 cells resulted in decreased rates of cell migration, wound healing and invasion in vitro. However, RPRM overexpression did not alter cell viability, phosphatidylserine (PS) translocation or G2/M cell cycle transition. CONCLUSION: Taken together, these data suggest that RPRM is involved in decreased cell migration and invasion in vitro, acting as a potential tumor suppressor gene in the MDA-MB-231 cell line.

Female , Humans , Breast Neoplasms/pathology , Cell Cycle Proteins/physiology , Cell Movement/physiology , Cell Proliferation/physiology , Glycoproteins/physiology , Analysis of Variance , Blotting, Western , Breast Neoplasms/genetics , Cell Cycle , Cell Line, Tumor , Cell Survival , Cell Cycle Proteins/genetics , Cell Movement/genetics , Cell Proliferation/genetics , DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Glycoproteins/genetics , Neoplasm Invasiveness , Real-Time Polymerase Chain Reaction , Statistics, Nonparametric
Egyptian Journal of Hospital Medicine [The]. 2016; 62 (January): 9-17
in English | IMEMR | ID: emr-180255


Background: examining the alteration of cell cycle genes in early hepatitis C virus [HCV] found that altered expression of mitotic checkpoint genes, MAD2L1, KNTC1, CDC16 and CDC34, KNTC1 known as "rough deal protein" [ROD] is part of a complex involved in elaborating an inhibitory signal due to improper chromosomal aligment during cell division

Aim of the work: attempt for the identification of proteins [genes], which act as predictive factors to identify patients with high risk of cell transformation and HCC development

Patients and Methods: fifty three patients with chronic HCV infection, age ranged between 18 and 58 years, time of assessment was before starting therapy of hepatitis C at the National Hepatology and Tropical Medicine Research Institute. Ten healthy individuals were included to serve as controls. All the patients and controls were subjected to the following: history, clinical examination, abdominal ultrasonography, and collection of blood samples for routine laboratory investigation; CBCs. Liver biopsy was done to all patients and controls, patients revealed mild fibrosis [Metavir fibrosis scores from F1 to F3]. Also, we used freshly frozen liver biopsies mRNA levels with perspective protein levels of four genes: P27, P15, KNTC1, MAD2L1

Results: significant association of P27, P15, KNTC1 and MAD2L-1 with the progression of liver fibrosis in chronic HCV liver biopsy was found

Conclusion: there is altered gene expression in HCV-associated liver disease

Recommendations: The emerging interest of hepatologists in the influence of genetic factors in HCV. Evaluation of the expression of key proteins related to the cell cycle and apoptosis in chronically infected patients with HCV would be of significance to understand disease pathogenesis, and will help in identifying novel prognostic indicators

Adult , Adolescent , Aged , Female , Humans , Male , Middle Aged , Cell Cycle Proteins/genetics , Cyclin-Dependent Kinase Inhibitor p15 , Microtubule-Associated Proteins , Mad2 Proteins , Cyclin-Dependent Kinase Inhibitor p27 , Cell Proliferation , Liver Cirrhosis/genetics
Cad. saúde pública ; 31(3): 620-632, 03/2015. tab
Article in Portuguese | LILACS | ID: lil-744835


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.

DNA, Fungal/chemistry , HSP90 Heat-Shock Proteins/metabolism , Nucleic Acid Conformation , Saccharomyces cerevisiae , Saccharomyces cerevisiae Proteins/metabolism , Telomere/chemistry , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Chromosomal Proteins, Non-Histone/genetics , Chromosomal Proteins, Non-Histone/metabolism , DNA, Fungal/metabolism , Enzyme Activation , HSP90 Heat-Shock Proteins/genetics , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Telomerase/metabolism , Telomere-Binding Proteins/genetics , Telomere-Binding Proteins/metabolism , Telomere/metabolism
Dental press j. orthod. (Impr.) ; 20(1): 45-51, Jan-Feb/2015. tab, graf
Article in English | LILACS | ID: lil-741446


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. .

Humans , Cell Cycle Proteins/metabolism , DNA Replication/genetics , Forkhead Transcription Factors/metabolism , G1 Phase/physiology , Gene Expression Regulation/genetics , Protein-Serine-Threonine Kinases/metabolism , Replication Origin/genetics , Signal Transduction/genetics , Blotting, Western , Cell Fractionation , Cell Line , Cell Cycle Proteins/genetics , /metabolism , DNA Primers/genetics , Fluorescent Antibody Technique , Forkhead Transcription Factors/genetics , Immunoblotting , Immunoprecipitation , Intercellular Signaling Peptides and Proteins/metabolism , Protein-Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins c-myc/metabolism , Reverse Transcriptase Polymerase Chain Reaction , RNA Interference
Article in English | WPRIM | ID: wpr-57306


Scoparone, which is a major constituent of Artemisia capillaries, has been identified as an anticoagulant, hypolipidemic, vasorelaxant, anti-oxidant and anti-inflammatory drug, and it is used for the traditional treatment of neonatal jaundice. Therefore, we hypothesized that scoparone could suppress the proliferation of VSMCs by interfering with STAT3 signaling. We found that the proliferation of these cells was significantly attenuated by scoparone in a dose-dependent manner. Scoparone markedly reduced the serum-stimulated accumulation of cells in the S phase and concomitantly increased the proportion of cells in the G0/G1 phase, which was consistent with the reduced expression of cyclin D1, phosphorylated Rb and survivin in the VSMCs. Cell adhesion markers, such as MCP-1 and ICAM-1, were significantly reduced by scoparone. Interestingly, this compound attenuated the increase in cyclin D promoter activity by inhibiting the activities of both the WT and active forms of STAT3. Similarly, the expression of a cell proliferation marker induced by PDGF was decreased by scoparone with no change in the phosphorylation of JAK2 or Src. On the basis of the immunofluorescence staining results, STAT3 proteins phosphorylated by PDGF were predominantly localized to the nucleus and were markedly reduced in the scoparone-treated cells. In summary, scoparone blocks the accumulation of STAT3 transported from the cytosol to the nucleus, leading to the suppression of VSMC proliferation through G1 phase arrest and the inhibition of Rb phosphorylation. This activity occurs independent of the form of STAT3 and upstream of kinases, such as Jak and Src, which are correlated with abnormal vascular remodeling due to the presence of an excess of growth factors following vascular injury. These data provide convincing evidence that scoparone may be a new preventative agent for the treatment of cardiovascular diseases.

Active Transport, Cell Nucleus , Animals , Biomarkers , Cell Cycle Proteins/genetics , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Coumarins/pharmacology , Gene Expression Regulation/drug effects , Hep G2 Cells , Humans , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/metabolism , Proto-Oncogene Proteins c-sis/metabolism , Rats , STAT3 Transcription Factor/genetics , Signal Transduction/drug effects , Transcription, Genetic
Article in English | WPRIM | ID: wpr-56792


Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous congenital anomaly. Mutations in the NIPBL gene account for a half of the affected individuals. We describe a family with CdLS carrying a novel pathogenic variant of the SMC1A gene identified by exome sequencing. The proband was a 3-yr-old boy presenting with a developmental delay. He had distinctive facial features without major structural anomalies and tested negative for the NIPBL gene. His younger sister, mother, and maternal grandmother presented with mild mental retardation. By exome sequencing of the proband, a novel SMC1A variant, c.3178G>A, was identified, which was expected to cause an amino acid substitution (p.Glu1060Lys) in the highly conserved coiled-coil domain of the SMC1A protein. Sanger sequencing confirmed that the three female relatives with mental retardation also carry this variant. Our results reveal that SMC1A gene defects are associated with milder phenotypes of CdLS. Furthermore, we showed that exome sequencing could be a useful tool to identify pathogenic variants in patients with CdLS.

Asian Continental Ancestry Group/genetics , Base Sequence , Cell Cycle Proteins/genetics , Child, Preschool , Chromosomal Proteins, Non-Histone/genetics , DNA , DNA Mutational Analysis , De Lange Syndrome/diagnosis , Female , Heterozygote , Humans , Male , Pedigree , Phenotype , Polymorphism, Single Nucleotide , Proteins/genetics , Republic of Korea
Rev. méd. Chile ; 141(12): 1570-1577, dic. 2013. ilus, graf
Article in Spanish | LILACS | ID: lil-705577


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.

Humans , Biomarkers, Tumor , Cell Cycle Proteins/genetics , DNA Methylation/genetics , Epigenomics , Glycoproteins/genetics , Stomach Neoplasms/genetics , Cell Cycle Proteins/metabolism , Disease Progression , Early Diagnosis , Glycoproteins/metabolism , Stomach Neoplasms/diagnosis
Mem. Inst. Oswaldo Cruz ; 107(3): 377-386, May 2012. ilus, graf, tab
Article in English | LILACS | ID: lil-624020


Anti-silencing factor 1 (ASF1) is a histone chaperone that contributes to the histone deposition during nucleosome assembly in newly replicated DNA. It is involved in chromatin disassembly, transcription activation and in the cellular response to DNA damage. In Leishmania major the ASF1 gene (LmASF1) is located in chromosome 20 and codes for a protein showing 67% of identity with the Trypanosoma brucei TbASF1a. Compared to orthologous proteins, LmASF1 conserves the main residues relevant for its various biological functions. To study ASF1 in Leishmania we generated a mutant overexpressing LmASF1 in L. major. We observed that the excess of LmASF1 impaired promastigotes growth rates and had no impact on cell cycle progress. Differently from yeast, ASF1 overproduction in Leishmania did not affect expression levels of genes located on telomeres, but led to an upregulation of proteins involved in chromatin remodelling and physiological stress, such as heat shock proteins, oxidoreductase activity and proteolysis. In addition, we observed that LmASF1 mutant is more susceptible to the DNA damaging agent, methyl methane sulphonate, than the control line. Therefore, our study suggests that ASF1 from Leishmania pertains to the chromatin remodelling machinery of the parasite and acts on its response to DNA damage.

Animals , Rabbits , Cell Cycle Proteins/genetics , DNA Damage/genetics , Histone Chaperones/physiology , Leishmania major/chemistry , Mutation/genetics , Protozoan Proteins/physiology , Blotting, Western , Electrophoresis, Gel, Two-Dimensional , Flow Cytometry , Gas Chromatography-Mass Spectrometry , Histone Chaperones/genetics , Protozoan Proteins/genetics , Real-Time Polymerase Chain Reaction
Indian J Cancer ; 2012 Jan-Mar; 49(1): 144-162
Article in English | IMSEAR | ID: sea-144565


Genetic influences on cancer development have been extensively investigated during the last decade following publication of human genome sequence. The present review summarizes case-control studies on genetic polymorphisms and cancer risk in Indians. It is observed that the most commonly studied genes in the Indian population included members of phase I and phase II metabolic enzymes. Other than these genes, genetic polymorphisms for cell cycle and apoptosis-related factors, DNA repair enzymes, immune response elements, growth factors, folate metabolizing enzymes, vitamin/hormone receptors, etc., were investigated. Several studies also evidenced a stronger risk for combined genotypes rather than a single polymorphism. Gene-environment interaction was also found to be a determining factor for cancer development in some experiments. Data for single polymorphism and single cancer type, however, was insufficient to validate an association. It appears that much more experiments involving larger sample size, cross-tabulating genetic polymorphisms and environmental factors are required in order to identify genetic markers for different cancers in Indian populations.

Cell Cycle Proteins/genetics , DNA Repair Enzymes/genetics , Genes, MHC Class II , Genetic Association Studies , Humans , India , Intercellular Signaling Peptides and Proteins/genetics , Metabolic Detoxication, Phase I/genetics , Metabolic Detoxication, Phase II/genetics , Neoplasms/genetics , Polymorphism, Genetic