Seroprevalence trends of anti-SARS-CoV-2 antibodies in the adult population of the São Paulo Municipality, Brazil: Results from seven serosurveys from June 2020 to April 2022. The SoroEpi MSP Study.

BACKGROUND: Sequential population-based household serosurveys of SARS-CoV-2 covering the COVID-19 pre- and post-vaccination periods are scarce in Brazil. This study investigated seropositivity trends in the municipality of São Paulo. METHODS: We conducted seven cross-sectional surveys of adult population-representative samples between June 2020 and April 2022. The study design included probabilistic sampling, test for SARS-CoV-2 antibodies using the Roche Elecsys anti-nucleocapsid assay, and statistical adjustments for population demographics and non-response. The weighted seroprevalences with 95% confidence intervals (CI) were estimated by sex, age group, race, schooling, and mean income study strata. Time trends in seropositivity were assessed using the Joinpoint model. We compared infection-induced seroprevalences with COVID-19 reported cases in the pre-vaccination period. RESULTS: The study sample comprised 8,134 adults. The overall SARS-CoV-2 seroprevalence increased from 11.4% (95%CI: 9.2-13.6) in June 2020 to 24.9% (95%CI: 21.0-28.7) in January 2021; from 38.1% (95%CI: 34.3-41.9) in April 2021 to 77.7% (95%CI: 74.4-81.0) in April 2022. The prevalence over time was higher in the subgroup 18-39 years old than in the older groups from Survey 3 onwards. The self-declared Black or mixed (Pardo) group showed a higher prevalence in all surveys compared to the White group. Monthly prevalence rose steeply from January 2021 onwards, particularly among those aged 60 years or older. The infection-to-case ratios ranged from 8.9 in June 2020 to 4.3 in January 2021. CONCLUSIONS: The overall seroprevalence rose significantly over time and with age and race subgroup variations. Increases in the 60 years or older age and the White groups were faster than in younger ages and Black or mixed (Pardo) race groups in the post-vaccination period. Our data may add to the understanding of the complex and changing population dynamics of the SARS-CoV-2 infection, including the impact of vaccination strategies and the modelling of future epidemiological scenarios.

Entre o espírito público e o discurso político: as estratégias de comunicação da pandemia no canal de jair bolsonaro no telegram

Este artigo analisa a comunicação feita pelo ex-presidente brasileiro, Jair Bolsonaro, sobre a Covid-19. O corpus do estudo se circunscreve às mensagens publicadas pelo político no Telegram, durante os 100 primeiros dias de sua atuação na plataforma. Analisamos o fenômeno a partir dos conceitos de comunicação pública e governamental (Duarte, 2007; Brandão, 2007, 2016; Oliveira, 2013) e comunicação política (Gerstlé, 2005; Freeman, 2019), confrontandoos com entendimentos sobre o populismo (Waisbord, 2018; 2020; Laclau, 2005; Jagers & Walgrave, 2007; Innerarity, 2015). O estudo utiliza como metodologia a análise de conteúdo (Benoit, 2011; Alonso, 2012; Sampaio & Lycarião, 2021). Os resultados mostram que Bolsonaro não produz comunicação pública ou governamental, mas sim comunicação política a partir de seu canal na plataforma, que é usado para estabelecer uma disputa narrativa pela construção de sentidos da população sobre a crise sanitária.

Este artículo analiza la comunicación realizada por el expresidente brasileño Jair Bolsonaro, sobre el Covid-19. El corpus del estudio se circunscribe a los mensajes publicados por el político en Telegram durante sus primeros 100 días en la plataforma. Analizamos el fenómeno a partir de los conceptos de comunicación pública y gubernamental (Duarte, 2007;Brandão, 2007, 2016;Oliveira, 2013) y comunicación política (Gerstlé, 2005;Freeman, 2019), confrontándolos con comprensiones de populismo (Waisbord, 2018;2020;Laclau, 2005;Jagers & Walgrave, 2007eInnerarity, 2015). El estudio utiliza como metodología el análisis de contenido (Benoit, 2011;Alonso, 2012;Sampaio & Lycarião, 2021). Los resultados muestran que Bolsonaro no produce comunicación pública o gubernamental, sino comunicación política desde su canal en la plataforma, que se utiliza para establecer una disputa narrativa para la construcción de significados de la población sobre la crisis sanitaria.

Effect of ZEB1 Associated with microRNAs on Tumor Stem Cells in Head and Neck Cancer.

Cancer biologists have focused on studying cancer stem cells (CSCs) because of their ability to self-renew and recapitulate tumor heterogeneity, which increases their resistance to chemotherapy and is associated with cancer relapse. Here, we used two approaches to isolate CSCs: the first involved the metabolic enzyme aldehyde dehydrogenase ALDH, and the second involved the three cell surface markers CD44, CD117, and CD133. ALDH cells showed a higher zinc finger E-box binding homeobox 1 (ZEB1) microRNA (miRNA) expression than CD44/CD117/133 triple-positive cells, which overexpressed miRNA 200c-3p: a well-known microRNA ZEB1 inhibitor. We found that ZEB1 inhibition was driven by miR-101-3p, miR-139-5p, miR-144-3p, miR-199b-5p, and miR-200c-3p and that the FaDu Cell Line inhibition occurred at the mRNA level, whereas HN13 did not affect mRNA expression but decreased protein levels. Furthermore, we demonstrated the ability of the ZEB1 inhibitor miRNAs to modulate CSC-related genes, such as TrkB, ALDH, NANOG, and HIF1A, using transfection technology. We showed that ALDH was upregulated upon ZEB1-suppressed miRNA transfection (Mann-Whitney ** p101 = 0.009, t-test ** p139 = 0.009, t-test ** p144 = 0.002, and t-test *** p199 = 0.0006). Overall, our study enabled an improved understanding of the role of ZEB1-suppressed miRNAs in CSC biology.

Use of histone methyltransferase inhibitors in cancer treatment: A systematic review.

Histone modifications are an epigenetic mechanism, and the dysregulation of these proteins is known to be associated with the initiation and progression of cancer. In the search for the development of new and more effective drugs, histone modifications were identified as possible therapeutic targets. Histone methyltransferase (HMT) inhibitors correspond to the third generation of epigenetic drugs capable of writing or deleting epigenetic information. This systematic review summarized the development and prospect for the use of different HMT inhibitors in cancer therapy. An electronic search was applied across CENTRAL, Clinical Trials, Embase, LILACS, LIVIVO, Open Gray, PubMed, Scopus, and Web of Science. Based on the title and abstracts, two authors independently selected eligible studies. After the complete reading of the articles, based on the eligibility criteria, 11 studies were included in the review. Different inhibitors of HMT have been explored in multiple clinical studies, and have shown considerable anti-tumor effects. However, few phase 2 studies have been completed and/or have available results. The most advanced clinical trials mainly include tazemetostat, an Enhancer of zeste homolog 2 (EZH2) inhibitor approved for follicular lymphoma (FL). The use of HMT inhibitors has presented, so far, concise results in the treatment of hematological cancers, moreover, the adverse effects presented after the use of these medicines (alone or in combination) did not show a high level of risk for the patient. These findings, in addition to ongoing clinical studies, can represent a promising future regarding the use of HMT inhibitors in treating different types of cancer.

Inferring the ecological quality status based on living benthic foraminiferal indices in transitional areas of the Guanabara bay (SE Brazil).

Using benthic foraminifera, we evaluate the ecological quality status (EcoQS) of transitional waters of the Guanabara Bay (SE Brazil) by applying the diversity-based index exp (H'bc) and the sensitivity-based Foram-AMBI for the first time in South America. The Guanabara Bay was selected for this study as it is one of the largest transitional ecosystems in the State of Rio de Janeiro and has been severely impacted by anthropogenic activities. Concentrations of potentially toxic elements (PTEs) were assessed by sequential chemical extraction in three phases (i.e., dissolved in water, adsorbed on organic matter, and Mn oxy-hydroxides). Total organic carbon, total nitrogen, and stable isotope (δ13C and δ15N) signatures of organic matter were analyzed to trace environmental stress. The Ammonia/Elphidium ratio suggests hypoxic conditions at most of the sampled sites. Principal component analysis identifies the first component as environmental stress underlying organic matter and PTE enrichment (in all three phases), which is positively related to Foram-AMBI and negatively to exp (H'bc). The exp (H'bc) and Foram-AMBI indices reveal that stations near the Governador Island and Niterói margin have the worst EcoQS, showing medium to extreme pollution. Additionally, Foram-AMBI and exp (H'bc) provide a congruent EcoQS classification for ∼64% of the sites. Although these results are promising, they suggest that a significant effort should be made to obtain better knowledge of foraminiferal ecological requirements to employ benthic foraminifera as a biomonitoring and management method.

Treatment effects of the EGFR pathway drugs on head and neck cancer stem cells.

(1) Head and neck cancer (HNC) is the sixth most common cancer worldwide and show low survival rates and drug resistance, which can be due to the presence of cancer stem cells (CSCs), a small cell population with metastatic potential, invasion and self-renewal ability. (2) Here, seven tumor cells were sorted as CD44+/CD117+/CD133+ or ALDH+, considered as HNC stem cells (HNCSCs), and as CD44-/CD117-/CD133- or ALDH-, considered non-HNCSCs after both cells sorted criteria was compared to evaluate cell migration, invasion, and colony forming assays. These subpopulations were treated with Cetuximab, Paclitaxel, or a combination of both drugs and evaluated for cell viability. Quantitative PCR and western blot were performed to evaluate EGFR, TRKB, KRAS and HIF-1α gene and protein expression. (3) HNCSCs presented more colonies and appeared to be more sensitive to the drug combination when compared with non-HNCSCs, regardless cells sorted criteria and primary tumor subsite. The EGFR, TRKB, KRAS and HIF-1α genes and proteins were upregulated in CSCs compared with non-HNCSCs, thus explaining the drug resistance. (4) This study contributes to the better development of specific therapeutic protocols based on Cetuximab and Paclitaxel drugs in the treatment of HNC in the presence of CSCs and cell proliferation biomarkers.

Regulation of VEGFA, KRAS, and NFE2L2 Oncogenes by MicroRNAs in Head and Neck Cancer.

Mutations and alterations in the expression of VEGFA, KRAS, and NFE2L2 oncogenes play a key role in cancer initiation and progression. These genes are enrolled not only in cell proliferation control, but also in angiogenesis, drug resistance, metastasis, and survival of tumor cells. MicroRNAs (miRNAs) are small, non-coding regulatory RNA molecules that can regulate post-transcriptional expression of multiple target genes. We aimed to investigate if miRNAs hsa-miR-17-5p, hsa-miR-140-5p, and hsa-miR-874-3p could interfere in VEGFA, KRAS, and NFE2L2 expression in cell lines derived from head and neck cancer (HNC). FADU (pharyngeal cancer) and HN13 (oral cavity cancer) cell lines were transfected with miR-17-5p, miR-140-5p, and miR-874-3p microRNA mimics. RNA and protein expression analyses revealed that miR-17-5p, miR-140-5p and miR-874-3p overexpression led to a downregulation of VEGFA, KRAS, and NFE2L2 gene expression in both cell lines analyzed. Taken together, our results provide evidence for the establishment of new biomarkers in the diagnosis and treatment of HNC.

Acidentes com animais peçonhentos no Brasil: uma revisão integrativa / Accidents with venomous animals in Brazil: an integrative review

Considerados como doenças negligenciadas pela Organização Mundial de Saúde, os acidentes com animais peçonhentos são de grande relevância média por apresentarem altos índices de mortalidade e morbidade. Objetivo - O objetivo desta revisão é apresentar os aspectos epidemiológicos e clínicos dos acidentes com animais peçonhentos no Brasil nos últimos dez anos. Métodos - Foram utilizadas publicações que compreendessem os aspectos clínicos e epidemiológicos de estados, regiões ou municípios brasileiros. Para a revisão foram os artigos foram selecionados em maio de 2020, compreendendo os anos de 2010 a 2020. Resultados e Discussão - Os principais acidentes foram relacionados às serpentes peçonhentas e escorpiões. Nas regiões Sudeste, Norte, Centro-Oeste os acidentes ofídicos foram os mais recorrentes, enquanto que, na região Nordeste, os acidentes com escorpiões e um estudo da região Sul um estudo destacou o araneísmo como principal acidente. Os sinais e sintomas do ofidismo variaram de acordo com o gênero das serpentes, sendo os acidentes com o gênero Bothrops predominante. Os sintomas recorrentes foram: dor, edema, equimose, hemorragia local e sistêmica e alterações na coagulação. O escorpionismo foi causado principalmente pelo gênero Tityus, sendo os casos graves relacionados ao comprometimento pulmonar. Conclusão - Os tipos de acidentes, bem como os sinais e sintomas do envenenamento apresentam muitas variáveis, como região geográfica, gênero e espécie dos animais. A melhoria da qualidade dos dados epidemiológicos e ampliação da assistência em saúde são fatores essenciais para a redução no número de casos de mortalidade e morbidades decorrentes do envenenamento por animais peçonhentos.

Considered as neglected by the World Health Organization, accidents with venomous animals are of great relevance because they have high mortality and morbidity rates. Purpose - This review has the purpose to present the epidemiological and clinical aspects of accidents with venomous animals in Brazil in the past ten years. Methods - Publications were used that understood the clinical and epidemiological aspects of Brazilian states, regions or municipalities. For the review, articles were selected in May 2020, covering the years 2010 to 2020. Results and Discussion - The main accidents were related to venomous snakes and scorpions. In the Southeast, North, and Center-West regions, snakebite accidents were the most recurrent, while in the Northeast region, accidents involving scorpions and a study in the Southern region highlighted accidents with arachnids as the most frequent type of incident. Signs and symptoms of snakebite varied according to the gender of the snakes, with predominance for accidents with the Bothrops genus. Recurring symptoms included pain, edema, ecchymosis, local and systemic hemorrhage, and changes in coagulation. Scorpionism was mainly caused by the Tityus genus, with severe cases presenting pulmonary involvement. Conclusion - The types of accidents, as well as the signs and symptoms of envenomation, present many variables which included geographic region, gender and species of animals. Improving the quality of epidemiological data and expanding health care are essential factors for reducing the number of mortality and morbidity cases resulting from envenomation by venomous animals.

MiR-612, miR-637, and miR-874 can Regulate VEGFA Expression in Hepatocellular Carcinoma Cell Lines.

MicroRNAs (miRNAs) are short non-coding RNA molecules acting as important posttranscriptional gene and protein expression regulators in cancer. The study goal was to examine VEGFA (vascular endothelial growth factor A) expression in hepatocellular carcinoma (HCC) cell lines upon transfection miR-612, miR-637, or miR-874. Methods: MiR-612 mimics, miR-637 mimics, or miR-874 inhibitors were transfected using Lipofectamine RNAiMax in both HCC cell lines, HepG2 and HuH-7. Real-time PCR, Western blotting, and ELISA methods were used to evaluate VEGFA regulation by the miRNAs. Results: Gene and protein expression levels of VEGFA were down-expressed in both cell lines, HepG2 and HuH-7, transfected with miR-612 or miR-637. Transfection with miR-874 inhibitor showed an increase in VEGFA gene expression in HepG2 and HuH-7 cell lines; however, no regulation was observed on VEGFA protein expression by miR-874 inhibition. Correlation analysis between miRNAs and VEGFA protein expression showed that miR-637 and miR-874 expression present inversely correlated to VEGFA protein expression. Conclusions: VEGFA was down-regulated in response to hsa-miR-612 or hsa-miR-637 overexpression; however, the modulation of VEGFA by miR-874 was observed only at the gene expression and thus, needs further investigation.

Association between folate metabolism polymorphisms and breast cancer: a case-control study.

We investigated the association between methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthetase (MTR A2756G), and methionine synthase reductase (MTRR A66G) polymorphisms involved in folate pathway and breast cancer risk, and the interaction between these polymorphisms and tobacco and alcohol consumption. Furthermore, we evaluated the association between these polymorphisms and clinicopathological variables. This case-control study included 606 Brazilian women, comprising 128 patients with breast cancer and 478 controls. MTHFR and MTR polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and MTRR polymorphisms using real-time PCR. Age ≥50 years (odds ratio [OR]: 2.65; 95% confidence interval [CI]: 1.65-4.26; p<0.001) and alcohol consumption (OR: 1.76; 95% CI: 1.0-2.85; p=0.021) were associated with an increased risk of breast cancer. For MTHFR A1298C, we observed a reduced risk of developing breast cancer in the codominant model (genotype CC-OR: 0.22; 95% CI: 0.06-0.74; p=0.014), recessive model (OR: 0.22; 95% CI: 0.07-0.76 p=0.004), and log-additive model (OR: 0.70; 95% CI: 0.49-0.98; p=0.035). Women aged ≥50 years and those who are alcohol consumers had increased susceptibility to breast cancer, and MTHFR A1298C modulated the risk for this disease. This is the first study to evaluate the association between polymorphisms in folate metabolism and breast cancer in the northwest region of São Paulo State, Brazil.

Assessment of initial SARS-CoV-2 seroprevalence in the most affected districts in the municipality of São Paulo, Brazil.

BACKGROUND: São Paulo city has been one of the regions most affected by the COVID-19 pandemic in Brazil. Frequent asymptomatic and oligosymptomatic infections and poor access to diagnostic tests make serosurveys crucial to monitor the magnitude of the epidemic and to inform public health policies, such as vaccination plans. OBJECTIVES: To estimate, early in the epidemic, the seroprevalence of antibodies to SARS-CoV-2 in adults living in the six most affected districts in São Paulo city, and to assess potential associated risk factors. METHODS: This was a cross-sectional population-based survey of 1,152 households randomly selected from 72 census tracts. During the period May 4-12, 2020, 463 participants completed a questionnaire on sociodemographic characteristics and history of symptoms in the past two weeks, and provided a blood sample. Prevalence of SARS-CoV-2 antibodies was the outcome of interest and was estimated based on results of two immunoassays, Maglumi SARS-CoV-2 chemiluminescence assay Immunoglobulin (Ig) M (IgM) and IgG, and Roche electrochemiluminescence assay total Ig. Serum samples reactive to either assay were considered positive. RESULTS: Weighted overall seroprevalence was 6% (95%CI 3.9-8.3%). No association was observed between seropositivity and sex, age group or education level. Participants who reported black and brown skin color showed a 2.7 fold higher prevalence than people with white skin (p = 0.007). Among the 30 seropositive individuals, 14 (46.6%) reported no COVID-19 compatible symptoms in the past two weeks. CONCLUSION: This study represents the first assessment of SARS-CoV-2 seroprevalence in the city of São Paulo and 6% is the baseline estimate of a series of population-based seroprevalence surveys. Serological screening using sound serological assays is the key tool to monitoring temporal and geographic changes in the spread of the virus through an important epicenter of the COVID-19 pandemic in Brazil. Ultimately, it may inform prevention and control efforts.

Evaluation of molecular markers GSTM1 and GSTT1 and clinical factors in breast cancer: case-control study and literature review.

The study was conducted to evaluate the frequency of polymorphisms in GSTM1 and GSTT1 genes in patients with breast cancer compared with individuals without history of cancer, and the association of these polymorphisms with clinical/epidemiological parameters.There were evaluated 752 women (219 patients and 533 controls). Molecular analysis was performed by the Polymerase Chain Reaction (PCR). Statistical analysis was used multiple logistic regression and descriptive statistics.Age ≥ 50 years (OR = 3.22, 95% CI = 2.30-4.51, p < 0.001) and alcohol consumption (OR = 1.60, 95% CI = 1.13-2.27, p = 0.008) were associated to the development of breast cancer, while smoking and null genotypes GSTM1 and GSTT1 presented no association. GSTM1 and GSTT1 polymorphisms presented no relationship with the clinical and histopathological parameters or molecular subtypes of breast cancer. Ninety-two percent of tumours were invasive ductal, 66% were grade II, 65% were larger than 2 cm, the stages II (35.3%) and III (31.2%) were the most prevalent, and 47.7% were molecular subtype luminal B.Individuals aged ≥ 50 years and alcohol consumers have more chance to developing breast cancer. GSTM1 and GSTT1 polymorphisms are not associated to the risk of breast cancer.

Polymorphisms in xenobiotic metabolism-related genes in patients with hepatocellular carcinoma: a case-control study.

This study was performed to investigate the relationship between polymorphisms in microsomal epoxide hydrolase (mEH; Tyr113His and His139Arg substitution) and glutathione S-transferase (GST; GSTM1 deletion, GSTT1 deletion, and GSTP1.Ala114Val substitution) and their correlation with clinico-histopathological features in hepatocellular carcinoma (HCC).We evaluated environmental risk factors and genetic alterations in 556 individuals (86 cases and 470 controls). PCR multiplex for GSTM1 and GSTT1, polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) for GSTP1, and real-time PCR for mEH were performed. Statistical analyses were performed using multiple logistic regression tests.Age over 48 years (p < 0.001) and alcohol consumption (p = 0.021) were the predictors of increased risk of developing HCC. GSTP1.Ala114Val for all regression models (p < 0.05), except the recessive model, and the GSTT1 null genotype (odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.21-0.87, p = 0.019) were predictors of an increased risk of developing HCC. Polymorphic GSTT1, GSTM1, GSTP1.Ala114Val, and mEH.His139Arg and wild-type mEH.Tyr113His (OR = 5.04; 95% CI = 1.59-16.04; p = 0.006) were associated with HCC.Age over 48 years, alcohol consumption, and the presence of polymorphic variants of GSTP1 and GSTT1 were associated with the risk of developing HCC.

Assessment of initial SARS-CoV-2 seroprevalence in the most affected districts in the municipality of São Paulo, Brazil

ABSTRACT Background: São Paulo city has been one of the regions most affected by the COVID-19 pandemic in Brazil. Frequent asymptomatic and oligosymptomatic infections and poor access to diagnostic tests make serosurveys crucial to monitor the magnitude of the epidemic and to inform public health policies, such as vaccination plans. Objectives: To estimate, early in the epidemic, the seroprevalence of antibodies to SARS-CoV-2 in adults living in the six most affected districts in São Paulo city, and to assess potential associated risk factors. Methods: This was a cross-sectional population-based survey of 1,152 households randomly selected from 72 census tracts. During the period May 4-12, 2020, 463 participants completed a questionnaire on sociodemographic characteristics and history of symptoms in the past two weeks, and provided a blood sample. Prevalence of SARS-CoV-2 antibodies was the outcome of interest and was estimated based on results of two immunoassays, Maglumi SARS-CoV-2 chemiluminescence assay Immunoglobulin (Ig) M (IgM) and IgG, and Roche electrochemiluminescence assay total Ig. Serum samples reactive to either assay were considered positive. Results: Weighted overall seroprevalence was 6% (95%CI 3.9-8.3%). No association was observed between seropositivity and sex, age group or education level. Participants who reported black and brown skin color showed a 2.7 fold higher prevalence than people with white skin (p = 0.007). Among the 30 seropositive individuals, 14 (46.6%) reported no COVID-19 compatible symptoms in the past two weeks. Conclusion: This study represents the first assessment of SARS-CoV-2 seroprevalence in the city of São Paulo and 6% is the baseline estimate of a series of population-based seroprevalence surveys. Serological screening using sound serological assays is the key tool to monitoring temporal and geographic changes in the spread of the virus through an important epicenter of the COVID-19 pandemic in Brazil. Ultimately, it may inform prevention and control efforts.

Differential expression of angiogenesis-related miRNAs and VEGFA in cirrhosis and hepatocellular carcinoma.

INTRODUCTION: Liver cirrhosis (LC) is a heterogeneous liver disease, the last stage of liver fibrosis, and the major risk factor for hepatocellular carcinoma (HCC). Our study aimed to evaluate the expression of microRNAs and the endothelial vascular growth factor (VEGFA) gene in LC and HCC. MATERIAL AND METHODS: The sample group consisted of 46 tissue samples: 21 of LC, 15 of HCC, and 10 of non-tumoural and non-cirrhotic liver tissue (control group). MiRNAs were chosen based on a mirDIP prediction database as regulators of the VEGFA gene. Gene expression of VEGF and miRNAs was quantified by real-time quantitative polymerase chain reaction. VEGFA protein expression was evaluated by ELISA. RESULTS: VEGFA gene expression was significantly overexpressed in LC compared to the control group (p < 0.0001). Hsa-miR-206 (p = 0.0313) and hsa-miR-637 (p = 0.0156) were down-expressed in LC. In HCC, hsa-miR-15b (p = 0.0010), hsa-miR-125b (p = 0.0010), hsa-miR-423-3p (p = 0.0010), hsa-miR-424 (p = 0.0313), hsa-miR-494 (p < 0.0001), hsa-miR-497 (p < 0.0001), hsa-miR-612 (p = 0.0078), hsa-miR-637 (p < 0.0001), and hsa-miR-1255b (p = 0.0156) presented down-expression. CONCLUSIONS: Overexpression of VEGFA in LC suggests impairment of angiogenesis in this tissue. The differential expression of microRNAs in LC and HCC observed in our study can lead to the evaluation of possible biomarkers for these diseases.

VEGFA and NFE2L2 Gene Expression and Regulation by MicroRNAs in Thyroid Papillary Cancer and Colloid Goiter.

Deregulation of VEGFA (Vascular Endothelial Growth Factor A) and NFE2L2 (Nuclear Factor (Erythroid-derived 2)-Like 2), involved in angiogenesis and oxidative stress, can lead to thyroid cancer progression. MiR-17-5p and miR-612 are possible regulators of these genes and may promote thyroid disorders. In order to evaluate the involvement of VEGFA, NFE2L2, hsa-miR-17-5p, and hsa-miR-612 in thyroid pathology, we examined tissue samples from colloid goiter, papillary thyroid cancer (PTC), and a normal thyroid. We found higher levels of VEGFA and NFE2L2 transcripts and the VEGFA protein in goiter and PTC samples than in normal tissue. In the goiter, miR-612 and miR-17-5p levels were lower than those in PTC. Tumors, despite showing lower VEGFA mRNA expression, presented higher VEGFA protein levels compared to goiter tissue. In addition, NRF2 (Nuclear Related Transcription Factor 2) protein levels in tumors were higher than those in goiter and normal tissues. Inhibition of miR-17-5p resulted in reduced NFE2L2 expression. Overall, both transcript and protein levels of NFE2L2 and VEGFA were elevated in PTC and colloid goiter. Hsa-miR-612 showed differential expression in PTC and colloid goiter, while hsa-miR-17-5p showed differential expression only in colloid goiter, suggesting that hsa-miR-17-5p may be a positive regulator of NFE2L2 expression in PTC.

MicroRNAs as regulators of VEGFA and NFE2L2 in cancer.

MicroRNAs (miRNAs) are small non-coding RNAs that are involved in post-transcriptional regulation of various genes, and their deregulation can lead to tumorigenesis. They may play the role of oncogenes or tumor suppressors by regulating different genes involved in cellular processes. One of the genes regulated by the miRNAs is the vascular endothelial growth factor A (VEGFA), which is responsible for angiogenesis. Angiogenesis is the process of formation of new blood vessels from pre-existing ones. This process plays an important role in tumor development, since it is responsible for the transport of nutrients required for tumor growth. Several studies have shown an increased expression of VEGFA in various cancers. Another gene regulated by miRNAs, the nuclear factor erythroid 2-like-2 (NFE2L2/NRF2), has a cytoprotective function and regulates cellular defense against oxidative stress. The NFE2L2 is the major regulator of cytoprotective agents and their oxidative damage to cells, which is down-regulated by Kelch-like ECH-associated protein 1 (KEAP1) at the post-transcriptional level. Regulation of the VEGFA and NFE2L2 by miRNAs has been observed in hepatocellular carcinoma and breast, lung, esophageal, endometrial, gastric, and ovarian cancer. This review highlights the role of miRNAs in the regulation of VEGFA and NFE2L2 and their relevance as therapeutic targets in various cancers.

Polymorphisms in MTHFR, MTR, RFC1 and CßS genes involved in folate metabolism and thyroid cancer: a case-control study.

INTRODUCTION: Polymorphisms in genes coding enzymes involved in folate metabolism may cause alterations in this metabolic pathway and contribute to carcinogenesis, because folate is essential for DNA synthesis, methylation and repair. The objective of this study was to investigate the association of MTHFR 677C>T (rs1801133), MTR 2756A>G (rs1805087), RFC1 80A>G (rs1051266) and CßS 844ins(68) (no rs#) polymorphisms and thyroid cancer development. The association of these polymorphisms with demographic risk factors and clinical histopathological parameters was also evaluated. MATERIAL AND METHODS: The study is a case-control analysis with a total of 462 individuals (151 patients and 311 controls). Polymerase chain reaction-restriction fragment length polymorphism technique was used for genotyping. The χ2 and multiple logistic regression were utilized for statistical analysis. RESULTS: The polymorphisms analysis revealed an association between the MTHFR 677C>T polymorphism (OR = 2.87, 95% CI: 1.50-5.48, p < 0.01, codominant model), (OR = 1.76, 95% CI: 1.18-2.64, p < 0.01, dominant model), (OR = 2.37, 95% CI: 1.28-4.39, p < 0.01, recessive model) and thyroid cancer. RFC1 80A>G polymorphism also was associated with thyroid cancer under recessive mode of inheritance (OR = 1.55; 95% CI: 1.02-2.38; p = 0.04); however, this polymorphism showed Hardy-Weinberg disequilibrium in the control group (χ2 = 24.71, p < 0.001). Furthermore, alcohol (OR = 1.56, 95% CI: 1.36-1.89, p < 0.01) and tobacco consumption (OR = 1.97, 95% CI: 1.28-3.04, p < 0.01) were associated with increased risk for thyroid cancer. The MTR 2756A>G polymorphism showed an association with tumor extent (OR = 2.69, 95% CI: 1.27-5.71, p < 0.01) and aggressiveness (OR = 4.51, 95% CI: 1.67-12.1, p < 0.01). CONCLUSIONS: MTHFR 677C>T is significantly associated with increased risk for thyroid cancer and MTR 2756A>G is associated with tumor extent and aggressiveness. In addition, alcohol and tobacco consumption were associated with increased risk of thyroid cancer. These results may contribute to a better prognosis for thyroid cancer.

Redes de apoio ao usuário com doença renal crônica na perspectiva ecossistêmica / Support networks to user with chronic kidney disease in the ecosystemic perspective / Redes de apoyo al usuario con enfermedad renal crónica desde la perspectiva ecosistémica

Objetivo: identificar e analisar as redes de apoio utilizadas pelo usuário renal crônico e família, a partir da perspectiva ecossistêmica. Método: estudo qualitativo desenvolvido no domicílio de três usuários com doença renal crônica em dois municípios do sul do Rio Grande do Sul. A coleta de dados ocorreu no período de maio a junho de 2016, por meio de entrevista semiestruturada. A análise de dados foi realizada pelo método da análise temática. Resultados: foi possível identificar várias redes de apoio ao portador de doença renal crônica e família, que se constituem em uma importante estratégia para as ações do cuidado, estimulando o enfrentamento da doença. Os vínculos relacionais interativos que se estabelecem entre os componentes do ecossistema domiciliar exercem influências no processo saúde-doença-cuidado do usuário com doença renal crônica quando exercidos com confiança, reciprocidade e afeto. Conclusão: essa relação de interdependência e interconexão entre os elementos, constituintes do ecossistema domiciliar, proporciona intercâmbio de informações, cooperação, parceria e compartilhamento de vivências e configura-se na rede de apoio familiar, social e de suporte aos profissionais de saúde.(AU)

Objective: identify and analyze the support networks used by the chronic renal user and family, from the ecosystemic perspective. Method: qualitative study developed at the household of three users with chronic kidney disease in two municipalities in southern Rio Grande do Sul. Data collection took place in the period from May to June 2016, through a semi-structured interview. Data analysis was performed using the thematic analysis method. Results: it was possible to identify several support networks for patients with chronic kidney disease and family, which constitute an important strategy for the actions of care, stimulating the coping of the disease. The interactive relational bonds established among the components of the household ecosystem exert influences in the health-disease-care process of the user with chronic kidney disease when exercised with confidence, reciprocity and affection. Conclusion: this relationship of interdependence and interconnection between the elements, constituents of the household ecosystem, provides information exchange, cooperation, partnership and sharing of experiences and configures itself in the family, social and support network to health professionals.(AU)

Objetivo: identificar y analizar las redes de apoyo utilizadas por el usuario renal crónico y su familia desde la perspectiva ecosistémica. Método: estudio cualitativo llevado a cabo en el domicilio de tres usuarios con enfermedad renal crónica en dos municipios del sur del estado de Rio Grande do Sul. La recogida de datos se efectuó entre mayo y junio de 2016 por medio de entrevistas semiestructuradas. El análisis de datos se realizó según el método del análisis temático. Resultados: se identificaron varias redes de apoyo que fomentan el afrontamiento de la enfermedad. Los vínculos de confianza, reciprocidad y afecto que se establecen en las relaciones interactivas entre los componentes del ecosistema familiar influyen en el proceso salud-enfermedad-cuidados del usuario con enfermedad renal crónica. Conclusión: la relación de interdependencia e interconexión entre los elementos que constituyen el ecosistema domiciliario proporciona intercambio de información, cooperación, alianza, posibilidad de compartir experiencias y se configura en red de apoyo familiar, social y de respaldo a los profesionales de salud.(AU)

Differential Expression of Prostaglandin I2 Synthase Associated with Arachidonic Acid Pathway in the Oral Squamous Cell Carcinoma.

INTRODUCTION: Differential expression of genes encoding cytochrome P450 (CYP) and other oxygenases enzymes involved in biotransformation mechanisms of endogenous and exogenous compounds can lead to oral tumor development. OBJECTIVE: We aimed to identify the expression profile of these genes, searching for susceptibility biomarkers in oral squamous cell carcinoma. PATIENTS AND METHODS: Sixteen oral squamous cell carcinoma samples were included in this study (eight tumor and eight adjacent non-tumor tissues). Gene expression quantification was performed using TaqMan Array Human CYP450 and other Oxygenases 96-well plate (Applied Biosystems) by real time qPCR. Protein quantification was performed by ELISA and IHC methods. Bioinformatics tools were used to find metabolic pathways related to the enzymes encoded by differentially expressed genes. Results. CYP27B1, CYP27A1, CYP2E1, CYP2R1, CYP2J2, CYP2U1, CYP4F12, CYP4X1, CYP4B1, PTGIS, ALOX12, and MAOB genes presented differential expression in the oral tumors. After correction by multiple tests, only the PTGIS (Prostaglandin I2 Synthase) gene presented significant differential expression (P < 0.05). The PTGIS gene and protein were reduced in oral tumors. CONCLUSION: PTGIS presents downexpression in oral tumors. PTGIS play an important role in the arachidonic acid metabolism. Arachidonic acid and/or metabolites are derived from this pathway, which can influence the regulation of important physiological mechanisms in tumorigenesis process.