Association of Alcohol Consumption with Cognition and Functionality in Older Adults Aged 75+ Years: The Pietà Study.

The relationship between alcohol consumption and cognition is still controversial. This is a cross-sectional population-based study conducted in Caeté (MG), Brazil, where 602 individuals aged 75+ years, 63.6% female, and with a mean education of 2.68 years, were submitted to thorough clinical assessments and categorized according to the number of alcoholic beverages consumed weekly. The prevalence rates of previous and current alcohol consumption were 34.6% and 12.3%, respectively. No association emerged between cognitive diagnoses and current/previous alcohol consumption categories. Considering current alcohol intake as a dichotomous variable, the absence of alcohol consumption was associated with dementia (OR = 2.34; 95%CI: 1.39-3.90) and worse functionality (p = 0.001). Previous consumption of cachaça (sugar cane liquor) increased the risk of dementia by 2.52 (95%CI: 1.25-5.04). The association between the consumption of cachaça and dementia diagnosis has not been described before.

Role of long non-coding RNAs in the pathophysiology of Alzheimer's disease and other dementias.

Dementia is the term used to describe a group of cognitive disorders characterized by a decline in memory, thinking, and reasoning abilities that interfere with daily life activities. Examples of dementia include Alzheimer's Disease (AD), Frontotemporal dementia (FTD), Amyotrophic lateral sclerosis (ALS), Vascular dementia (VaD) and Progressive supranuclear palsy (PSP). AD is the most common form of dementia. The hallmark pathology of AD includes formation of ß-amyloid (Aß) oligomers and tau hyperphosphorylation in the brain, which induces neuroinflammation, oxidative stress, synaptic dysfunction, and neuronal apoptosis. Emerging studies have associated long non-coding RNAs (lncRNAs) with the pathogenesis and progression of the neurodegenerative diseases. LncRNAs are defined as RNAs longer than 200 nucleotides that lack the ability to encode functional proteins. LncRNAs play crucial roles in numerous biological functions for their ability to interact with different molecules, such as proteins and microRNAs, and subsequently regulate the expression of their target genes at transcriptional and post-transcriptional levels. In this narrative review, we report the function and mechanisms of action of lncRNAs found to be deregulated in different types of dementia, with the focus on AD. Finally, we discuss the emerging role of lncRNAs as biomarkers of dementias.

miRNAs in cerebrospinal fluid associated with Alzheimer's disease: A systematic review and pathway analysis using a data mining and machine learning approach.

Alzheimer's disease (AD) is the most common type and accounts for 60%-70% of the reported cases of dementia. MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in gene expression regulation. Although the diagnosis of AD is primarily clinical, several miRNAs have been associated with AD and considered as potential markers for diagnosis and progression of AD. We sought to match AD-related miRNAs in cerebrospinal fluid (CSF) found in the GeoDataSets, evaluated by machine learning, with miRNAs listed in a systematic review, and a pathway analysis. Using machine learning approaches, we identified most differentially expressed miRNAs in Gene Expression Omnibus (GEO), which were validated by the systematic review, using the acronym PECO-Population (P): Patients with AD, Exposure (E): expression of miRNAs, Comparison (C): Healthy individuals, and Objective (O): miRNAs differentially expressed in CSF. Additionally, pathway enrichment analysis was performed to identify the main pathways involving at least four miRNAs selected. Four miRNAs were identified for differentiating between patients with and without AD in machine learning combined to systematic review, and followed the pathways analysis: miRNA-30a-3p, miRNA-193a-5p, miRNA-143-3p, miRNA-145-5p. The pathways epidermal growth factor, MAPK, TGF-beta and ATM-dependent DNA damage response, were regulated by these miRNAs, but only the MAPK pathway presented higher relevance after a randomic pathway analysis. These findings have the potential to assist in the development of diagnostic tests for AD using miRNAs as biomarkers, as well as provide understanding of the relationship between different pathophysiological mechanisms of AD.

The role of neurotrophin polymorphisms and susceptibility to neural damage in leprosy.

OBJECTIVES: Mycobacterium leprae is able to infect Schwann cells leading to neural damage. Neurotrophins are involved in nervous system plasticity and impact neural integrity during diseases. Investigate the association between single nucleotide polymorphisms in neurotrophin genes and leprosy phenotypes, especially neural damage. DESIGN: We selected single nucleotide polymorphisms in neurotrophins or their receptors genes associated with neural disorders: rs6265 and rs11030099 of brain-derived neurotrophic factor (BDNF), rs6330 of BDNF, rs6332 in NT3 and rs2072446 of P75NTR. The association of genetic frequencies with leprosy phenotypes was investigated in a case-control study. RESULTS: An association of the BDNF single nucleotide polymorphism rs11030099 with the number of affected nerves was demonstrated. The "AA+AC" genotypes were demonstrated to be protective against nerve impairment. However, this variation does not affect BDNF serum levels. BDNF is an important factor for myelination of Schwann cells and polymorphisms in this gene can be associated with leprosy outcome. Moreover, rs11030099 is located in the binding region for micro-RNA (miRNA) 26a that could be involved in control of BDNF expression. We demonstrated different expression levels of this miRNA in polar forms of leprosy. CONCLUSION: Our findings demonstrate for the first time an association between the polymorphism rs11030099 in the BDNF gene and neural commitment in leprosy and may indicate a possible role of miRNA-26a acting synergistically to these genetic variants in neural damage development.

Novos Biomarcadores Cardiovasculares em Pacientes com Câncer de Mama Submetidas a Quimioterapia à Base de Doxorrubicina / New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy

Resumo Fundamento As doenças cardiovasculares (DCV) são relevantes para o manejo do tratamento do câncer de mama, uma vez que um número significativo de pacientes desenvolve essas complicações após a quimioterapia. Objetivo Este estudo teve como objetivo avaliar novos biomarcadores cardiovasculares, sendo eles CXCL-16 (ligante de motivo C-X-C 16), FABP3 (proteína de ligação a ácidos graxos 3), FABP4 (proteína de ligação a ácidos graxos 4), LIGHT (membro da superfamília do fator de necrose tumoral 14/TNFS14), GDF-15 (fator de crescimento/diferenciação 15) , sCD4 (forma solúvel de CD14) e ucMGP (matriz Gla-proteína não carboxilada) em pacientes com câncer de mama tratadas com doxorrubicina (DOXO). Métodos Este estudo de caso-controle foi realizado em uma clínica oncológica, incluindo 34 mulheres com diagnóstico de câncer de mama tratadas com quimioterapia com DOXO e 34 mulheres controle, sem câncer ou DCV. Os marcadores foram determinados imediatamente após o último ciclo de quimioterapia. O nível de significância estatística adotado foi de 5%. Resultados O grupo com câncer de mama apresentou níveis mais elevados de GDF-15 (p<0,001), enquanto os indivíduos controle apresentaram níveis mais elevados de FABP3 (p=0,038), FABP4 (p=0003), sCD14 e ucMGP (p<0,001 para ambos). Correlações positivas foram observadas entre FABPs e IMC no grupo com câncer. Conclusão GDF15 é um biomarcador emergente com potencial aplicabilidade clínica neste cenário. FABPs são proteínas relacionadas à adiposidade, potencialmente envolvidas na biologia do câncer de mama. sCD14 e ucMGP estão envolvidos na calcificação inflamatória e vascular. Acima de tudo, a avaliação destes novos biomarcadores cardiovasculares pode ser útil no tratamento da quimioterapia do câncer de mama com DOXO.

Abstract Background Cardiovascular diseases (CVDs) are relevant to the management of breast cancer treatment since a substantial number of patients develop these complications after chemotherapy. Objective This study aims to evaluate new cardiovascular biomarkers, namely CXCL-16 (C-X-C motif ligand 16), FABP3 (fatty acid binding protein 3), FABP4 (fatty acid binding protein 4), LIGHT (tumor necrosis factor superfamily member 14/TNFS14), GDF-15 (Growth/differentiation factor 15), sCD4 (soluble form of CD14), and ucMGP (uncarboxylated Matrix Gla-Protein) in breast cancer patients treated with doxorubicin (DOXO). Methods This case-control study was conducted in an oncology clinic that included 34 women diagnosed with breast cancer and chemotherapy with DOXO and 34 control women without cancer and CVD. The markers were determined immediately after the last cycle of chemotherapy. The statistical significance level adopted was 5%. Results The breast cancer group presented higher levels of GDF-15 (p<0.001), while control subjects had higher levels of FABP3 (p=0.038), FABP4 (p=0003), sCD14, and ucMGP (p<0.001 for both). Positive correlations were observed between FABPs and BMI in the cancer group. Conclusion GDF15 is an emerging biomarker with potential clinical applicability in this scenario. FABPs are proteins related to adiposity, which are potentially involved in breast cancer biology. sCD14 and ucMGP engage in inflammatory and vascular calcification. The evaluation of these novel cardiovascular biomarkers could be useful in the management of breast cancer chemotherapy with DOXO.

Lipids, Gut Microbiota, and the Complex Relationship with Alzheimer's Disease: A Narrative Review.

Alzheimer's Disease (AD) is a multifactorial, progressive, and chronic neurodegenerative disorder associated with the aging process. Memory deficits, cognitive impairment, and motor dysfunction are characteristics of AD. It is estimated that, by 2050, 131.5 million people will have AD. There is evidence that the gastrointestinal microbiome and diet may contribute to the development of AD or act preventively. Communication between the brain and the intestine occurs through immune cells in the mucosa and endocrine cells, or via the vagus nerve. Aging promotes intestinal dysbiosis, characterized by an increase in pro-inflammatory pathogenic bacteria and a reduction in anti-inflammatory response-mediating bacteria, thus contributing to neuroinflammation and neuronal damage, ultimately leading to cognitive decline. Therefore, the microbiota-gut-brain axis has a significant impact on neurodegenerative disorders. Lipids may play a preventive or contributory role in the development of AD. High consumption of saturated and trans fats can increase cortisol release and lead to other chronic diseases associated with AD. Conversely, low levels of omega-3 polyunsaturated fatty acids may be linked to neurodegenerative diseases. Unlike other studies, this review aims to describe, in an integrative way, the interaction between the gastrointestinal microbiome, lipids, and AD, providing valuable insights into how the relationship between these factors affects disease progression, contributing to prevention and treatment strategies.

Influence of polymorphisms in CYP2C9, VKORC1, MDR1 and APOE genes on the warfarin maintenance dose in Brazilian patients.

Background: Polymorphisms in the CYP2C9, VKORC1, MDR1 and APOE genes may impact warfarin dose. Aim: To investigate the influence of sociodemographic, clinical factors and polymorphisms *1, *2 and *3 for CYP2C9, -1639G>A for VKORC1, 3435C>T for MDR1, and ϵ2, ϵ3 and ϵ4 for APOE genes on the mean weekly warfarin maintenance dose in adults. Methods: This cross-sectional study recruited a calculated sample of 315 patients in three anticoagulation clinics in Brazil. A model containing the variables significantly associated with warfarin dose was estimated. Results: The mean age of patients was 64.1 ± 13.1 years, with 173 (54.9%) women. Age, use of amiodarone, genotype VKORC1 GA, genotype VKORC1 AA, genotypes CYP2C9*1/*2 or *1/*3 and genotypes CYP2C9*2/*2 or *2/*3 or *3/*3 were associated with a reduced warfarin dose. Conclusion: This study pointed out factors that could impact the management of oral anticoagulation.

Evaluation of the RDW Index (Red Cell Distribution Width) in Women with Breast Cancer Treated with Doxorubicin in a One-Year Follow-Up Study.

Breast cancer is the most common cancer and the most frequent cause of death in women. Doxorubicin, an anthracycline, is an important drug due to its efficacy in treating solid cancers, especially breast cancer. However, this drug is often responsible for cardiotoxicity that may affect more than 25% of patients. This study aimed to evaluate the red cell distribution width (RDW) in women with breast cancer to monitor adverse events associated with the use of doxorubicin. A prospective study of 80 women with breast malignancy undergoing neoadjuvant doxorubicin-based chemotherapy was conducted. The patients were evaluated at baseline (T0), just after the last cycle of chemotherapy with doxorubicin (T1), and 1 year after the treatment (T2). There was a significant increase over the time points for the RDW (p < 0.001). There was a negative correlation between the RDW and C-reactive protein (CRP) levels at T1. The RDW did not show a significant difference between the groups classified according to cardiotoxicity. Based on these results, the RDW is a cost-effective test that shows a relationship with the doxorubicin response, but not with cardiotoxicity. It is a potential biomarker to evaluate patients with breast cancer after they receive chemotherapy with doxorubicin.

Machine Learning-Based Routine Laboratory Tests Predict One-Year Cognitive and Functional Decline in a Population Aged 75+ Years.

BACKGROUND: Cognitive and functional decline are common problems in older adults, especially in those 75+ years old. Currently, there is no specific plasma biomarker able to predict this decline in healthy old-age people. Machine learning (ML) is a subarea of artificial intelligence (AI), which can be used to predict outcomes Aim: This study aimed to evaluate routine laboratory variables able to predict cognitive and functional impairment, using ML algorithms, in a cohort aged 75+ years, in a one-year follow-up study. METHOD: One hundred and thirty-two older adults aged 75+ years were selected through a community-health public program or from long-term-care institutions. Their functional and cognitive performances were evaluated at baseline and one year later using a functional activities questionnaire, Mini-Mental State Examination, and the Brief Cognitive Screening Battery. Routine laboratory tests were performed at baseline. ML algorithms-random forest, support vector machine (SVM), and XGBoost-were applied in order to describe the best model able to predict cognitive and functional decline using routine tests as features. RESULTS: The random forest model showed better accuracy than other algorithms and included triglycerides, glucose, hematocrit, red cell distribution width (RDW), albumin, hemoglobin, globulin, high-density lipoprotein cholesterol (HDL-c), thyroid-stimulating hormone (TSH), creatinine, lymphocyte, erythrocyte, platelet/leucocyte (PLR), and neutrophil/leucocyte (NLR) ratios, and alanine transaminase (ALT), leukocyte, low-density lipoprotein cholesterol (LDL-c), cortisol, gamma-glutamyl transferase (GGT), and eosinophil as features to predict cognitive decline (accuracy = 0.79). For functional decline, the most important features were platelet, PLR and NLR, hemoglobin, globulin, cortisol, RDW, glucose, basophil, B12 vitamin, creatinine, GGT, ALT, aspartate transferase (AST), eosinophil, hematocrit, erythrocyte, triglycerides, HDL-c, and monocyte (accuracy = 0.92). CONCLUSIONS: Routine laboratory variables could be applied to predict cognitive and functional decline in oldest-old populations using ML algorithms.

Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS): Study design and harmonization.

INTRODUCTION: Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first non-pharmacological multicenter randomized clinical trial (RCT) to prevent cognitive impairment in Latin America (LA). Our aim is to present the study design and discuss the strategies used for multicultural harmonization. METHODS: This 1-year RCT (working on a 1-year extension) investigates the feasibility of a multi-domain lifestyle intervention in LA and the efficacy of the intervention, primarily on cognitive function. An external harmonization process was carried out to follow the FINGER model, and an internal harmonization was performed to ensure this study was feasible and comparable across the 12 participating LA countries. RESULTS: Currently, 1549 participants have been screened, and 815 randomized. Participants are ethnically diverse (56% are Nestizo) and have high cardiovascular risk (39% have metabolic syndrome). DISCUSSION: LatAm-FINGERS overcame a significant challenge to combine the region's diversity into a multi-domain risk reduction intervention feasible across LA while preserving the original FINGER design.

New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy. / Novos Biomarcadores Cardiovasculares em Pacientes com Câncer de Mama Submetidas a Quimioterapia à Base de Doxorrubicina.

BACKGROUND: Central Illustration : New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy. Cardiovascular diseases (CVDs) are relevant to the management of breast cancer treatment since a substantial number of patients develop these complications after chemotherapy. OBJECTIVE: This study aims to evaluate new cardiovascular biomarkers, namely CXCL-16 (C-X-C motif ligand 16), FABP3 (fatty acid binding protein 3), FABP4 (fatty acid binding protein 4), LIGHT (tumor necrosis factor superfamily member 14/TNFS14), GDF-15 (Growth/differentiation factor 15), sCD4 (soluble form of CD14), and ucMGP (uncarboxylated Matrix Gla-Protein) in breast cancer patients treated with doxorubicin (DOXO). METHODS: This case-control study was conducted in an oncology clinic that included 34 women diagnosed with breast cancer and chemotherapy with DOXO and 34 control women without cancer and CVD. The markers were determined immediately after the last cycle of chemotherapy. The statistical significance level adopted was 5%. RESULTS: The breast cancer group presented higher levels of GDF-15 (p<0.001), while control subjects had higher levels of FABP3 (p=0.038), FABP4 (p=0003), sCD14, and ucMGP (p<0.001 for both). Positive correlations were observed between FABPs and BMI in the cancer group. CONCLUSION: GDF15 is an emerging biomarker with potential clinical applicability in this scenario. FABPs are proteins related to adiposity, which are potentially involved in breast cancer biology. sCD14 and ucMGP engage in inflammatory and vascular calcification. The evaluation of these novel cardiovascular biomarkers could be useful in the management of breast cancer chemotherapy with DOXO.

FUNDAMENTO: Figura Central: Novos Biomarcadores Cardiovasculares em Pacientes com Câncer de Mama Submetidas a Quimioterapia à Base de Doxorrubicina. As doenças cardiovasculares (DCV) são relevantes para o manejo do tratamento do câncer de mama, uma vez que um número significativo de pacientes desenvolve essas complicações após a quimioterapia. OBJETIVO: Este estudo teve como objetivo avaliar novos biomarcadores cardiovasculares, sendo eles CXCL-16 (ligante de motivo C-X-C 16), FABP3 (proteína de ligação a ácidos graxos 3), FABP4 (proteína de ligação a ácidos graxos 4), LIGHT (membro da superfamília do fator de necrose tumoral 14/TNFS14), GDF-15 (fator de crescimento/diferenciação 15) , sCD4 (forma solúvel de CD14) e ucMGP (matriz Gla-proteína não carboxilada) em pacientes com câncer de mama tratadas com doxorrubicina (DOXO). MÉTODOS: Este estudo de caso-controle foi realizado em uma clínica oncológica, incluindo 34 mulheres com diagnóstico de câncer de mama tratadas com quimioterapia com DOXO e 34 mulheres controle, sem câncer ou DCV. Os marcadores foram determinados imediatamente após o último ciclo de quimioterapia. O nível de significância estatística adotado foi de 5%. RESULTADOS: O grupo com câncer de mama apresentou níveis mais elevados de GDF-15 (p<0,001), enquanto os indivíduos controle apresentaram níveis mais elevados de FABP3 (p=0,038), FABP4 (p=0003), sCD14 e ucMGP (p<0,001 para ambos). Correlações positivas foram observadas entre FABPs e IMC no grupo com câncer. CONCLUSÃO: GDF15 é um biomarcador emergente com potencial aplicabilidade clínica neste cenário. FABPs são proteínas relacionadas à adiposidade, potencialmente envolvidas na biologia do câncer de mama. sCD14 e ucMGP estão envolvidos na calcificação inflamatória e vascular. Acima de tudo, a avaliação destes novos biomarcadores cardiovasculares pode ser útil no tratamento da quimioterapia do câncer de mama com DOXO.

SARS-CoV-2 Omicron BA.1, BA.2, and XAG identification during routine surveillance on a university campus in Belo Horizonte, Brazil, 2022.

We report SARS-CoV-2 genomic surveillance results between Belo Horizonte, Brazil's third and fourth case waves. Samples were obtained through a routine university monitoring COVID-19 program from the 9th to the 22nd epidemiological weeks (March and June 2022). We identified ten samples from the BA.1 clade (BA.1, BA.1.1, and BA.1.14.1 lineages) and 45 samples from the BA.2 clade (BA.2, BA.2.56, BA.2.9, BA.2.62, BA.2.23, BA.2.81, and BA.2.10). We observed progressive replacement of the BA.1 by the BA.2 clade. Furthermore, two XAG recombinants were found in the 22nd week. Diversification of the omicron variant seems to have contributed to the resurgence of cases in Belo Horizonte, similarly to what has been reported in South Africa.

Recent advances in point of care testing for COVID-19 detection.

The World Health Organizations declaration of the COVID-19 pandemic was a milestone for the scientific community. The high transmission rate and the huge number of deaths, along with the lack of knowledge about the virus and the evolution of the disease, stimulated a relentless search for diagnostic tests, treatments, and vaccines. The main challenges were the differential diagnosis of COVID-19 and the development of specific, rapid, and sensitive tests that could reach all people. RT-PCR remains the gold standard for diagnosing COVID-19. However, new methods, such as other molecular techniques and immunoassays emerged. Also, the need for accessible tests with quick results boosted the development of point of care tests (POCT) that are fast, and automated, with high precision and accuracy. This assay reduces the dependence on laboratory conditions and mass testing of the population, dispersing the pressure regarding screening and detection. This review summarizes the advances in the diagnostic field since the pandemic started, emphasizing various laboratory techniques for detecting COVID-19. We reviewed the main existing diagnostic methods, as well as POCT under development, starting with RT-PCR detection, but also exploring other nucleic acid techniques, such as digital PCR, loop-mediated isothermal amplification-based assay (RT-LAMP), clustered regularly interspaced short palindromic repeats (CRISPR), and next-generation sequencing (NGS), and immunoassay tests, and nanoparticle-based biosensors, developed as portable instruments for the rapid standard diagnosis of COVID-19.

Frequency of germline genetic variants in women with a personal or family history of breast cancer from Brazil.

BACKGROUND: About 5-10% of breast cancer cases are related to genetic and hereditary factors. The application of Next Generation Sequencing (NGS) in oncology has allowed the identification of genetic variants present in several genes related to the increased risk of breast cancer. This study aimed to determine the frequency of germline genetic variants in patients with a family and/or personal history of breast cancer. METHODS: An analysis of positive reports from NGS panels was carried out in female individuals with a personal and/or family history of breast cancer, present in the database of a private laboratory in Brazil. RESULTS: From about 2000 reports, 183 individuals presented 219 different germline genetic variants. The genes with the highest number of variants were BRCA2 (16.0%), ATM (15.0%) and BRCA1 (12.8%). Among the variants found, 78 were either pathogenic or probably pathogenic, accounting for 35% of all variants discovered. The gene with the highest proportion of pathogenic/probably pathogenic variants was TP53 (80%) and the most frequent pathogenic variant was also reported in this gene (c.1010G > A p.(Arg337His)). Furthermore, the study obtained a high proportion of variants of uncertain significance (VUS) (65%) and approximately 32% of the variants found were in genes of moderate penetrance. CONCLUSIONS: Our results could improve the risk estimation and clinical follow-up of Brazilian patients with a history of breast cancer.

A Novel Panel of Plasma Proteins Predicts Progression in Prodromal Alzheimer's Disease.

BACKGROUND: A cheap and minimum-invasive method for early identification of Alzheimer's disease (AD) pathogenesis is key to disease management and the success of emerging treatments targeting the prodromal phases of the disease. OBJECTIVE: To develop a machine learning-based blood panel to predict the progression from mild cognitive impairment (MCI) to dementia due to AD within a four-year time-to-conversion horizon. METHODS: We created over one billion models to predict the probability of conversion from MCI to dementia due to AD and chose the best-performing one. We used Alzheimer's Disease Neuroimaging Initiative (ADNI) data of 379 MCI individuals in the baseline visit, from which 176 converted to AD dementia. RESULTS: We developed a machine learning-based panel composed of 12 plasma proteins (ApoB, Calcitonin, C-peptide, CRP, IGFBP-2, Interleukin-3, Interleukin-8, PARC, Serotransferrin, THP, TLSP 1-309, and TN-C), and which yielded an AUC of 0.91, accuracy of 0.91, sensitivity of 0.84, and specificity of 0.98 for predicting the risk of MCI patients converting to dementia due to AD in a horizon of up to four years. CONCLUSION: The proposed machine learning model was able to accurately predict the risk of MCI patients converting to dementia due to AD in a horizon of up to four years, suggesting that this model could be used as a minimum-invasive tool for clinical decision support. Further studies are needed to better clarify the possible pathophysiological links with the reported proteins.

microRNA miR-133a as a Biomarker for Doxorubicin-Induced Cardiotoxicity in Women with Breast Cancer: A Signaling Pathway Investigation.

Cardiovascular toxicity is the main adverse effect of Doxorubicin (DOX) in cancer patients. microRNAs (miRNAs) are promising biomarkers to identify cardiac injury induced by DOX in breast cancer patients during the subclinical phase. Using RT-qPCR, we compared the expression of circulating miR-208a5p, miR-133a, miR-499a5p, miR-15a, miR-133b, and miR-49a3p in serum samples from DOX-induced cardiotoxicity (case) compared to the non-cardiotoxicity group (control). To further explore the potential roles of these circulating miRNA in cardiotoxicity, we searched the miRTarBase for experimentally validated miRNA-target interactions and performed a functional enrichment analysis based on those interactions. miR-133a was significantly upregulated in case compared to control group. The most relevant pathway regulated by miR-133a was ErbB2 signaling, whose main genes involved are EGFR, ERBB2, and RHOA, which are possibly downregulated by miR133a. The other miRNAs did not show significant differential expression when compared on both groups. The data suggest that miR-133a is associated with DOX-based cardiotoxicity during chemotherapy in breast cancer patients through ErbB2 signaling pathway. Moreover, miR-133a may be a future marker of DOX-induced cardiotoxicity in women with breast cancer.

Evaluation of serum haptoglobin levels and Hp1-Hp2 polymorphism in the haptoglobin gene in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is an arrhythmia that involves structural and electrophysiological abnormalities. Many of the AF-related clinical conditions are associated with an increase in inflammatory and oxidative factors. Haptoglobin (Hp) is an acute phase protein whose biological role is to promote clearance of free hemoglobin (Hb). In addition, for being considered an inflammatory marker, Hp represents a protective mechanism against the oxidative effects of Hb. The Hp1-Hp2 polymorphism at Hp locus can lead to three phenotypes related to structural and functional differences in the protein. The objective of this study were to evaluate Hp levels and Hp1-Hp2 polymorphism at Hp locus in patients with AF compared to a control group. METHODS AND RESULTS: This study included 65 patients with AF and 54 individuals without the arrhythmia. Biochemical parameters were determined using Vitros system, plasma levels of Hp were measured in serum samples by using ELISA method and polymorphisms were verified by PCR technique. Plasma Hp levels, as well as allelic and genotypic frequency, were not associated with AF. The levels of Hp also did not differ among the genotypes according to the applied models. CONCLUSIONS: The results suggest that Hp levels and Hp1-Hp2 polymorphism are not associated to AF.

Effects of Resveratrol Supplementation on the Cognitive Function of Patients with Alzheimer's Disease: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Alzheimer's disease (AD) comprises 60-70% of diagnosed dementia cases, and is characterized by the deposition of ß-amyloid peptide and the formation of neurofibrillary tangles of tau protein. Resveratrol is a neuroprotective agent acting in the prevention of redox impairment in addition to exerting anti-apoptotic actions on brain cells. An ability to reduce neuronal damage in patients with AD has been suggested by preclinical studies. OBJECTIVES: The aim of this systematic review was to investigate the evidence in the published literature from studies that evaluated the effects of supplementation with resveratrol, alone or in a solution with glucose and malate (RGM), on the functional and cognitive performance of patients with AD, as assessed by validated instruments. METHODS: A systematic literature search was performed in MEDLINE, CENTRAL, Embase, CINAHL, Web of Science, and Scopus databases including articles published up to August 2021. Randomized, placebo-controlled, clinical trials that reported cognitive and functional performance, as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Cooperative Study of Alzheimer's Disease-Activities of Daily Living (ADCS-ADL), or the Mini Mental State Examination (MMSE), in AD patients treated with resveratrol, alone or as RGM, were included. RESULTS: After 1855 studies were identified, 24 RCTs underwent full-text review, with 20 studies excluded because they did not meet the inclusion criteria. Thus, four RCTs were included in the qualitative analyses. The findings demonstrate that there are still few studies in humans, but they showed that this polyphenol acts in the delay of cognitive impairment in patients with AD, when administered alone or in combination with glucose and malate. CONCLUSIONS: Supplementation with resveratrol seems to influence the progressive cognitive and functional decline in AD patients, when compared with a placebo group. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021229234.

Interleukin-10 Levels are Associated with Doxorubicin-Related Cardiotoxicity in Breast Cancer Patients in a One-Year Follow-Up Study.

BACKGROUND: Myocardial toxicity is a common side effect of doxorubicin (DOXO) therapy in breast cancer patients. We hypothesized that DOXO-induced cardiotoxicity may be related to the release of inflammatory cytokines in response to the treatment. This study aimed to assess changes in plasma levels of interleukin (IL)-1ß, IL-6, IL-10 and tumor necrosis factor (TNF) after chemotherapy and to correlate these levels with cardiac biomarkers and clinical data. METHODS: Sixty-four patients with breast cancer treated with DOXO were included. Twenty-two subjects (cases) developed cardiotoxicity until one year after the end of DOXO treatment. Cytokines and cardiac markers were evaluated before starting chemotherapy (T0), up to 7 days after the last infusion (T1) and 12 months after the last infusion (T2). RESULTS: Higher IL-10 levels were observed in the case group compared to controls at T1 (p = .006) and T2 (p = .046). The IL-1ß, IL-6 and TNF levels did not change during treatment in each group (p > .05), nor between the case and control groups. The IL-10 levels were higher at T1 than at T0 and T2 (p < .05 for both) in the cardiotoxicity group. A correlation between IL-10 and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at T0 and T2 in the cardiotoxicity group was observed (p = .048 and p = .004, respectively). CONCLUSION: Our study demonstrated that DOXO induced an increase in plasma IL-10 levels in patients who presented cardiotoxicity after treatment, which correlated with NT-proBNP levels.

Identification of Clinical and Laboratory Variables Associated with Cardiotoxicity Events Due to Doxorubicin in Breast Cancer Patients: A 1-Year Follow-Up Study.

Cardiovascular adverse events in patients with breast cancer undergoing chemotherapy (CT) are frequent due to the high cardiotoxic potential of treatments, especially doxorubicin (DOXO). This study aimed to evaluate the association of plasma levels of various biomarkers with cardiotoxicity in women with breast cancer on DOXO-based chemotherapy. In this single center prospective cohort, 80 breast cancer patients who used DOXO as a first-line treatment for cancer were evaluated. Patients were assessed at three time points: before CT (T0), 1 week after (T1) and 12 months after DOXO treatment (T2). The predominant histological classification was ductal carcinoma, n = 72 (90.0%); the most frequent molecular classification was Human epidermal growth factor receptor-type 2 positive (HER2+), n = 34 (43.0%). In patients submitted to complementary treatment with trastuzumab (n = 23), there was no association with cardio-specific biomarkers. Evaluating the clinical variables and the laboratory parameters in T1 and T2 in relation to T0, the reduction any time of N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP), triglycerides and hematocrit levels showed an association with higher cardiotoxicity risk. In addition, increased levels of troponin I (cTnI) and glycated hemoglobin (HbA1c) showed an independent association with the occurrence of cardiotoxicity. These results suggest that the evaluation of these laboratory tests should be included routinely to identify breast cancer patients under DOXO treatment at cardiotoxicity risk.