CDK10, CDK11, FOXO1, and FOXO3 Gene Expression in Alzheimer's Disease Encephalic Samples.

Alzheimer's disease (AD) is a progressive neuroinflammatory and neurodegenerative disorder that affects different regions of the brain. Its pathophysiology includes the accumulation of ß-amyloid protein, formation of neurofibrillary tangles, and inflammatory processes. Genetic factors are involved in the onset of AD, but they are not fully elucidated. Identification of gene expression in encephalic tissues of patients with AD may help elucidate its development. Our objectives were to characterize and compare the gene expression of CDK10, CDK11, FOXO1, and FOXO3 in encephalic tissue samples from AD patients and elderly controls, from the auditory cortex and cerebellum. RT-qPCR was used on samples from 82 individuals (45 with AD and 37 controls). We observed a statistically significant increase in CDK10 (p = 0.029*) and CDK11 (p = 0.048*) gene expression in the AD group compared to the control, which was most evident in the cerebellum. Furthermore, the Spearman test demonstrated the presence of a positive correlation of gene expression both in the auditory cortex in the AD group (r = 0.046/p = 0.004) and control group (r = 0.454/p = 0.005); and in the cerebellum in the AD group (r = 0.654 /p < 0.001). There was no statistically significant difference and correlation in the gene expression of FOXO1 and FOXO3 in the AD group and the control. In conclusion, CDK10 and CDK11 have high expression in AD patients compared to control, and they present a positive correlation of gene expression in the analyzed groups and tissues, which suggests that they play an important role in the pathogenesis of AD.

Lack of Association between IL-6 Polymorphisms and Haplotypes with Gastric Cancer.

The process of combating neoplasms and mononuclear cells, and during H. pylori infection, several pro-inflammatory and anti-inflammatory cytokines are synthesized. In view of the involvement of the IL-6 law and the presence of H. pylori in the development of gastric diseases, the present study aimed to characterize the promoter-region polymorphism -597 (G/A) (rs1800797), -572 (C/G) (rs1800796), and -174 (G/C) (rs1800795) by PCR-RFLP in 375 gastric biopsy specimens from patients with peptic symptoms. A total of 375 samples were analyzed: 87 patients (without lesion without gastric tissue); 236 patients with gastritis and 52 patients with gastric cancer analyzed the PCR-RFLP techniques. All the results were normalized in relation to the presence of H. pylori. The frequencies of the three polymorphisms were compared in the Control vs Gastritis groups and a statistically significant test observed: -174 (G/C) (OR: 1.27; 95% CI: 0.84-1.93; P = 0.26), 572 (C/G) (OR: 1.42; 95% CI: 0.78-2.59; P = 0.25), and 597 (G/A) (OR: 0.98; 95% CI, 0.64-1.52; P = 0.94). Similar results were obtained when the gastric cancer group was compared to the control group: -174 (G/C) (OR: 1.27; 95% CI: 0.66-2.47; P = 0.47), -572 (C/G) (OR: 1.07; 95% CI: 0.43-2.68; P = 0.88), and -597 (G/A) (OR: 1.01; 95% CI, 0.5-0.9; P = 0.99). The haplotypes were and were not observed statistically significant differences. In conclusion, we found no correlations between any of the three polymorphisms in the IL-6 gene analyzed in this study and a higher risk of gastritis or gastric cancer.

Expression of miRNA-146a, miRNA-155, IL-2, and TNF-α in inflammatory response to Helicobacter pylori infection associated with cancer progression.

miRNAs appear to play an important role in controlling the expression of several genes, and they are a potential biomarker and prognostic tool in gastric diseases. We analyzed 53 controls, 86 patients with gastritis, and 19 patients with gastric cancer. Real-time-PCR was used to determine the expression levels of miRNA-146a, miRNA-155, IL-2, and TNF-α. The subsequent analysis of the target genes was performed using the bioinformatics approach. There was no difference in IL-2 expression between the groups. However, there was a significant increase in TNF-α expression in the gastritis group relative to the control and a significant decrease in the gastric cancer group relative to the control. There was also a statistically significant increase in miRNA-146a and miRNA-155 expression in the gastritis group relative to the control, but not in the gastric cancer group. Similar results were found when the presence of H. pylori was considered. The data revealed an increase in miRNA-146a and miRNA-155 expression but not enough to control the expression of TNF-α. The presence of H. pylori was found to affect increases in TNF-α and microRNA expression, and miRNA-146a and miRNA-155 alone were not able to eliminate bacteria or restore tissue homeostasis.

Changes in Expression of Key Genes in Alzheimer's Disease: A Specific Brain Tissue Change.

Alzheimer's disease (AD) is an irreversible and neurodegenerative disorder. Its etiology is not clear, but the involvement of genetic components plays a central role in the onset of the disease. In the present study, the expression of 10 genes (APP, PS1 and PS2, APOE, APBA2, LRP1, GRIN2B, INSR, GJB1, and IDE) involved in the main pathways related to AD were analyzed in auditory cortices and cerebellum from 29 AD patients and 29 healthy older adults. Raw analysis revealed tissue-specific changes in genes LRP1, INSR, and APP. A correlation analysis showed a significant effect also tissue-specific AD in APP, GRIN2B, INSR, and LRP1. Furthermore, the E4 allele of the APOE gene revealed a significant correlation with change expression tissue-specific in ABPA2, APP, GRIN2B, LRP1, and INSR genes. To assess the existence of a correction between changes in target gene expression and a probability of AD in each tissue (auditory cortices and cerebellum) an analysis of the effect of expressions was realized and showed that the reduction in the expression of the APP in auditory cortex and GRIN2B cerebellum had a significant effect in increasing the probability of AD, in the same logic, our result also suggesting that increased expression of the LRP1 and INSR genes had a significant effect on increasing the probability of AD. Our results showed tissue-specific gene expression alterations associated with AD and certainly opened new perspectives to characterize factors involved in gene regulation and to obtain possible biomarkers for AD.

DECREASED EXPRESSION OF MICRORNA-629 IN GASTRIC CANCER SAMPLES POTENTIATED BY THE VIRULENCE MARKER OF H. PYLORI, CAGA GENE.

BACKGROUND: Helicobacter pylori (H. pylori) is a gram-negative bacterium associated with the etiology of several gastrointestinal tract pathologies, and cagA-positive (cagA+) strains are found in populations with gastric ulcers and precancerous lesions, inducing pro-inflammatory responses. The development of neoplasms is related to microRNA (miRNA) dysregulation, indicating highly expressed miRNA-629. The article aims to correlate the expression level of miRNA-629 with the presence of H. pylori and the pathogenicity marker cagA. METHODS: 203 gastric biopsy samples were evaluated from individuals with normal gastric tissue (n=60), gastritis (n=96), and gastric cancer (n=47) of both genders and over 18 years old. The samples were subdivided according to the presence or absence of H. pylori, detected by polymerase chain reaction (PCR). RNA was extracted using a commercial kit and quantified. Complementary DNA (cDNA) was synthesized using commercial kits, and the relative expression was calculated using the 2-ΔΔCt method. RESULTS: Individuals infected with H. pylori are nine times more likely to develop gastric cancer. Cancer patients appeared to have decreased expression of miRNA-629; however, the presence of the bacterium would not influence this reduction. Individuals in the cancer group showed lower miRNA-629 expression when cagA+; however, in the control group, the expression was higher when cagA+. CONCLUSION: H. pylori is a factor involved in the etiology and progression of gastric diseases. Reduction in miRNA-629 expression in cancer patients occurs independent of the presence of the bacterium, but when the cagA pathogenicity marker is present, it induces changes in the gene expression of the respective miRNA.

MYC, FBXW7 and TP53 copy number variation and expression in gastric cancer.

BACKGROUND: MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation. METHODS: We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines. RESULTS: MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. In vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells. CONCLUSION: In conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer.

Is there an association between cortical thickness, age of onset, and duration of illness in schizophrenia?

OBJECTIVE: Several studies have shown cortical volume loss in frontotemporal regions in schizophrenia patients, and it is known that these reductions may be associated with disease symptoms and cognitive deficits. The aim of this study was to investigate possible cortical thickness correlations in frontotemporal regions in relation to age at onset and duration of illness. METHODS: One hundred forty-eight schizophrenia patients (97 males; age and SD 36.30 ± 10.06) and 87 (57 males; age and SD 36.48 ± 10.10) age-matched healthy subjects underwent a brain MRI scan. Cortical segmentation and surface statistical analysis were performed using the FreeSurfer software package. Results were corrected for multiple comparisons using the Monte Carlo method considering a cluster-corrected Type I Error of 5%. RESULTS: Compared to controls, schizophrenia patients presented significant cortical thinning in the frontotemporal, parietal, and occipital cortices. No correlation between prefrontal cortex thickness and duration of illness in patients with schizophrenia or between frontotemporal cortical thickness and age at onset was found. However, a significant interaction between age and diagnosis was observed on frontal cortical thickness with patients presenting a thinner cortex than expected for age. CONCLUSION: Although there was no correlation between age of onset and duration of illness with brain volume, our findings suggest that there is an accelerated cortical loss in schizophrenia, thus reinforcing the progressive processes of the disease.

Histone Modifications in Alzheimer's Disease.

Since Late-onset Alzheimer's disease (LOAD) derives from a combination of genetic variants and environmental factors, epigenetic modifications have been predicted to play a role in the etiopathology of LOAD. Along with DNA methylation, histone modifications have been proposed as the main epigenetic modifications that contribute to the pathologic mechanisms of LOAD; however, little is known about how these mechanisms contribute to the disease's onset or progression. In this review, we highlighted the main histone modifications and their functional role, including histone acetylation, histone methylation, and histone phosphorylation, as well as changes in such histone modifications that occur in the aging process and mainly in Alzheimer's disease (AD). Furthermore, we pointed out the main epigenetic drugs tested for AD treatment, such as those based on histone deacetylase (HDAC) inhibitors. Finally, we remarked on the perspectives around the use of such epigenetics drugs for treating AD.

Metastasis-associated lung adenocarcinoma transcript 1 molecular mechanisms in gastric cancer progression.

Gastric cancer (GC) remains among the most common cancers worldwide with a high mortality-to-incidence ratio. Accumulated evidence suggests that long noncoding RNAs (lncRNAs) are involved in gastric carcinogenesis. These transcripts are longer than 200 nucleotides and modulate gene expression at multiple molecular levels, inducing or inhibiting biological processes and diseases. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is one of the best-studied lncRNAs with comprehensive actions contributing to cancer progression. This lncRNA regulates gene expression at the transcriptional and posttranscriptional levels through interactions with microRNAs and proteins. In the present review, we discussed the molecular mechanism of MALAT1 and summarized the current knowledge of its expression in GC. Moreover, we highlighted the potential use of MALAT1 as a biomarker, including liquid biopsy.

PPARα polymorphisms as risk factors for dyslipidemia in a Brazilian population.

BACKGROUND AND AIMS: Peroxisome proliferator-activated receptor α is a nuclear receptor involved in the regulation of several biochemical pathways. Polymorphisms within its gene have been associated with several metabolic traits. We aimed to investigate the association of L162V and Intron 7G>C polymorphisms with serum level markers and common morbidities affecting an older adult/elderly cohort from Cuiaba City, Mato Grosso State, Brazil, as well as to compare the results with a previously studied population from São Paulo City, Brazil. METHODS AND RESULTS: The studied population consisted of 570 subjects from Cuiaba City, Brazil, who were subjected to clinical interviews and blood collection for laboratory examinations and DNA extraction. Dyslipidemia was defined when participants were taking oral hypolipemiants or those with total cholesterol above 200mg/dL, HDL-c below 40 mg/dL, LDL-c above 130 mg/dL and TG above 150 mg/dL. Restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) was used for polymorphism genotyping. Individual polymorphism and haplotype data were available for analyses. In the studied sample, allele frequencies were 0.052 and 0.292 for 162V and Intron 7C, respectively. In brief, 162V allele was associated with dyslipidemia (p=0.025), and after correction for alcohol consumption and waist-to-rip ratio, a tendency of association could still be observed (p=0.050). In addition, Intron 7C allele was associated with dyslipidemia even after correction for the same variables (p=0.029). When compared to our previous study from São Paulo, we found some divergences regarding these results, which may be explained by differences between the two populations. Haplotype association analyses revealed an association between L/C haplotype and dyslipidemia (p=0.021) and between V/C haplotype and lower LDL-c levels when compared to L/G haplotype (p=0.044). CONCLUSION: These results may help to clarify the role of PPARα gene in lipid and lipoprotein metabolism and the evaluation of its polymorphisms and haplotypes as being characterized as genetic risk factors for metabolic disturbances.

SMARCA5 methylation and expression in gastric cancer.

Here, we first evaluated SMARCA5 expression and promoter DNA methylation in gastric carcinogenesis. Immunohistochemistry and methylation-specific PCR were analyzed in 19 and 48 normal mucosa and in 52 and 92 gastric cancer samples, respectively. We observed higher immunoreactivity of SMARCA5 in gastric cancer samples than in normal mucosa. Moreover, SMARCA5 promoter methylation was associated with the absence of protein expression. Our findings suggest that SMARCA5 has a potential role in proliferation and malignancy in gastric carcinogenesis.

Decrease of miR-125a-5p in Gastritis and Gastric Cancer and Its Possible Association with H. pylori.

PURPOSE: The aim of this study was to evaluate the expression of miR-125a-5p in patients with dyspeptic symptoms and gastric cancer, correlating them with the development of this cancer and H. pylori. METHODS: Patients were divided in groups according to histopathological analysis (control, gastritis, and cancer groups). Polymerase chain reaction was performed to detect H. pylori and real-time quantitative PCR to determine miR-125a-5p expression. RESULTS: H. pylori was detected in 44% of the patients, with prevalence in the gastritis and cancer groups. A statistically significant decrease of miR-125a-5p expression was found in the control positive (p = 0.0183*), gastritis positive (p = 0.0380*), and cancer positive (p = 0.0288*) groups when compared with the control negative group. CONCLUSION: We suggest that decreased expression of the miRNA-125a-5p associated with the presence of the H. pylori is an important mechanism in gastric diseases and could be a possible marker for early diagnosis of gastric cancer.

Association of PPARalpha gene polymorphisms and lipid serum levels in a Brazilian elderly population.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear transcription factor strictly involved in lipid and lipoprotein metabolisms. Thus, PPARalpha gene polymorphisms have been investigated as cardiovascular risk factors. We aimed to investigate associations of L162V and intron 7G>C polymorphisms with common morbidities affecting a Brazilian elderly cohort as well as with lipid and protein serum levels. Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP), and allele frequencies were determined. In addition, we performed the linkage disequilibrium analysis. Descriptive statistics, logistic regression analysis, and Student's t-test were used. Rare alleles for L162V and intron 7 G>C polymorphisms showed frequencies of 0.047 and 0.199, respectively. Our data showed that these polymorphisms were in linkage disequilibrium (p=0.0002). Intron 7 G>C polymorphism presented a tendency of association with neoplasia (p=0.053), and C allele was associated with higher HDL (p=0.010), lower triglycerides (p=0.001), and VLDL levels (p=0.003) compared to G allele. These data might suggest a protective role of intron 7 G>C polymorphism in the development of cardiovascular diseases and will help to clarify the importance of PPARalpha polymorphisms as key modulators of lipid metabolism in Brazilian population.

Helicobacter pylori detection in gastric biopsies, saliva and dental plaque of Brazilian dyspeptic patients.

Helicobacter pylori is an important human pathogen that causes chronic gastritis and is associated with the development of peptic ulcer disease and gastric malignancies. The oral cavity has been implicated as a potential H. pylori reservoir and may therefore be involved in the reinfection of the stomach, which can sometimes occur following treatment of an H. pylori infection. The objectives of this paper were (i) to determine the presence of H. pylori in the oral cavity and (ii) to examine the relationship between oral H. pylori and subsequent gastritis. Gastric biopsies, saliva samples and dental plaques were obtained from 78 dyspeptic adults. DNA was extracted and evaluated for the presence of H. pylori using polymerase chain reaction and Southern blotting methods. Persons with gastritis were frequently positive for H. pylori in their stomachs (p < 0.0001) and there was a statistically significant correlation between the presence of H. pylori in gastric biopsies and the oral cavity (p < 0.0001). Our results suggest a relationship between gastric infection and the presence of this bacterium in the oral cavity. Despite this, H. pylori were present in the oral cavity with variable distribution between saliva and dental plaques, suggesting the existence of a reservoir for the species and a potential association with gastric reinfection.

hTERT methylation and expression in gastric cancer.

Gastric cancer is the second most prevalent cause of cancer death worldwide. DNA methylation is a common event in gastric carcinogenesis. hTERT seems to be the rate-limiting determinant of telomerase activation, which is responsible for stability and life span. hTERT hypermethylation has been associated with telomerase expression. In the present study, we investigated the promoter methylation status and hTERT protein expression in gastric cancer and normal mucosa samples. One hundred and nine gastric cancer and 53 normal mucosa samples were investigated through methylation-specific PCR. Immunohistochemistry was analysed using peroxidase in 55 gastric cancer and 18 normal gastric mucosa samples. This is the first study evaluating hTERT methylation status in gastric carcinogenesis. We did not observe hTERT protein expression in normal gastric mucosa. Moreover, hTERT expression was observed in 80% of tumours and was associated with gastric cancer (p < 0.0001). Partial methylation was the most frequent pattern in gastric samples, even in normal mucosa. The frequency of specimens presenting hypermethylation was significantly higher in tumours than in normal mucosa samples (p = 0.0002), although the presence of hypermethylated promoter was not associated with a higher frequency of hTERT expression. A low correlation between hTERT protein expression and methylation was verified in gastric cancer samples. There was a clear difference in the frequency of hTERT expression and methylation within tumoral and non-tumoral tissues. Methylation status and telomerase expression may be useful for the diagnosis of gastric cancer and may have an impact on the anti-telomerase strategy for cancer therapy.

Low frequency of human papillomavirus detection in prostate tissue from individuals from Northern Brazil.

The presence of human papillomavirus (HPV) was evaluated in 65 samples of prostate tumours and six samples of prostates with benign prostatic hyperplasia from individuals from Northern Brazil. We used a highly sensitive test, the Linear Array HPV Genotyping Test, to detect 37 high and low-risk HPV types. In this study, only 3% of tumour samples showed HPV infection. Our findings support the conclusion that, despite the high incidence of HPV infection in the geographic regions studied, HPV was not associated with a higher risk of prostate cancer. To our knowledge, this is the first study evaluating the frequency of HPV detection in prostatic tissue of individuals from Brazil.

Lymphocyte proliferation stimulated by activated human macrophages treated with Canova.

INTRODUCTION: Canova (CA) is a homeopathic medication with immunomodulatory properties, recommended for patients with a depressed immune system. CA has been reported to increase in leukocyte numbers, cellular differentiation and reduction in tumor size. AIM AND METHOD: Since CA may stimulate lymphocyte differentiation, proliferation, and/or survival, the aim of the present study was to compare the mitotic index (MI) of phytohemagglutinin-stimulated human lymphocytes cultured in a medium supplemented with human macrophages activated by CA, with lymphocytes cultured in a medium without CA-treated macrophages. RESULTS: In this study, the MI of lymphocyte cultured received the medium containing CA-stimulated macrophages showed a higher proliferation index (p<0.01) than the lymphocytes cultured in a medium without CA-treated macrophages. Our results suggest that CA treatment, in addition to activating macrophages, indirectly induces lymphocyte proliferation and has potential as a new adjuvant therapeutic approach.

Diminuição da expressão do microRNA-629 em amostras de câncer gástrico potencializada pelo marcador de virulências do H. pylori, gene cagA / Decreased expression of microrna-629 in gastric cancer samples potentiated by the virulence marker of h. pylori, caga gene

ABSTRACT Background: Helicobacter pylori (H. pylori) is a gram-negative bacterium associated with the etiology of several gastrointestinal tract pathologies, and cagA-positive (cagA+) strains are found in populations with gastric ulcers and precancerous lesions, inducing pro-inflammatory responses. The development of neoplasms is related to microRNA (miRNA) dysregulation, indicating highly expressed miRNA-629. The article aims to correlate the expression level of miRNA-629 with the presence of H. pylori and the pathogenicity marker cagA. Methods: 203 gastric biopsy samples were evaluated from individuals with normal gastric tissue (n=60), gastritis (n=96), and gastric cancer (n=47) of both genders and over 18 years old. The samples were subdivided according to the presence or absence of H. pylori, detected by polymerase chain reaction (PCR). RNA was extracted using a commercial kit and quantified. Complementary DNA (cDNA) was synthesized using commercial kits, and the relative expression was calculated using the 2-ΔΔCt method. Results: Individuals infected with H. pylori are nine times more likely to develop gastric cancer. Cancer patients appeared to have decreased expression of miRNA-629; however, the presence of the bacterium would not influence this reduction. Individuals in the cancer group showed lower miRNA-629 expression when cagA+; however, in the control group, the expression was higher when cagA+. Conclusion: H. pylori is a factor involved in the etiology and progression of gastric diseases. Reduction in miRNA-629 expression in cancer patients occurs independent of the presence of the bacterium, but when the cagA pathogenicity marker is present, it induces changes in the gene expression of the respective miRNA.

RESUMO Contexto: Helicobacter pylori (H. pylori) é uma bactéria gram-negativa associada à etiologia de várias patologias do trato gastrointestinal, e cepas positivas para cagA (cagA+) são encontradas em populações com úlceras gástricas e lesões pré-cancerígenas, induzindo respostas pró-inflamatórias. O desenvolvimento de neoplasias está relacionado à desregulação do microRNA (miRNA), indicando miRNA-629 altamente expresso. O artigo tem como objetivo correlacionar o nível de expressão do miRNA-629 com a presença de H. pylori e o marcador de patogenicidade cagA. Métodos: Foram avaliadas 203 amostras de biópsia gástrica de indivíduos com tecido gástrico normal (n=60), gastrite (n=96) e câncer gástrico (n=47) de ambos os sexos e com mais de 18 anos. As amostras foram subdivididas de acordo com a presença ou ausência de H. pylori, detectado por reação em cadeia da polimerase (PCR). O RNA foi extraído usando um kit comercial e quantificado. O DNA complementar (cDNA) foi sintetizado usando kits comerciais, e a expressão relativa foi calculada usando o método 2-ΔΔCt. Resultados: Indivíduos infectados com H. pylori têm nove vezes mais chances de desenvolver câncer gástrico. Pacientes com câncer parecem ter diminuição da expressão do miRNA-629; no entanto, a presença da bactéria não influenciaria essa redução. Indivíduos no grupo do câncer apresentaram menor expressão do miRNA-629 quando cagA+; no entanto, no grupo controle, a expressão foi maior quando cagA+. Conclusão: H. pylori é um fator envolvido na etiologia e progressão das doenças gástricas. A redução na expressão do miRNA-629 em pacientes com câncer ocorre independentemente da presença da bactéria, mas quando o marcador de patogenicidade cagA está presente, induz mudanças na expressão gênica do respectivo miRNA.

Promoter methylation analysis of SIRT3, SMARCA5, HTERT and CDH1 genes in aging and Alzheimer's disease.

Longevity related genes were investigated concerning promoter methylation. SIRT3, SMARCA5, HTERT and CDH1 promoters were analyzed in peripheral blood in relation to gender, age and Alzheimer's disease (AD). Methylation Specific PCR assay (MSP) was used. There were no significant differences in methylation frequencies of SIRT3, SMARCA5 and CDH1 among young, elderly and AD groups (p> 0.05), showing no association with aging or AD. On the other hand, HTERT methylation frequency was associated with the aging process, in that AD patients differed from elderly controls (p=0.0086), probably due to telomere and immune dysfunctions involved in AD pathogenesis.

Can the rDNA methylation pattern be used as a marker for Alzheimer's disease?

BACKGROUND: Differential methylation activity of the human rDNA in Alzheimer's disease (AD) patients has been demonstrated by classic cytogenetic tools, indicating a decrease in rRNA gene expression. Methylation of CpGs is an important epigenetic mechanism involved in gene expression repression of tandem repeating genes during ageing. Thus, rDNA specific methylation pattern could be involved in AD and be used as a marker of the disease or of its progression. METHODS: The methylation pattern of three rDNA regions, including the promoter, 18S, and 28S, was investigated with the use of restriction endonucleases sensitive to methylation and Southern blotting from DNA extracted from total peripheral blood cells of 28 AD patients and 28 elderly and young controls. RESULTS: We did not find a significant divergence in the methylation pattern of the studied regions and in the relative amount of rDNA methylated copies among the individuals' groups. CONCLUSIONS: No differential methylation pattern of rDNA genes was observed in total peripheral blood cells in aged and AD subjects by the methodology used.