Mario Hirata

University of São Paulo | USP · Departamento de Análises Clínicas e Toxicológicas (FBC) (Sao Paulo)

Statins are the first-line treatment for familial hypercholesterolemia (FH), but response is highly variable due to genetic and nongenetic factors. Here, we explored the association between response and genetic variability in 114 Brazilian adult FH patients. Specifically, a panel of 84 genes was analyzed by exon-targeted gene sequencing (ETGS), and...

The Carnitine Palmitoyltranferase I (CPT1) catalyzes the rate-limiting step of long-chain fatty acid (LCFA) mitochondrial β-oxidation. The enzyme promotes the conjugation of LCFA with l-carnitine, which allows LCFA to enter the mitochondria matrix. The structural features involved in CPT1 and LCFA-CoA interactions have not been fully elucidated, ma...

Aim This study aimed to evaluate the association of toll-like receptor (TLR) inflammatory cascade with the development of diabetic kidney disease (DKD) in children and adolescents with type 1 diabetes (T1D). Methods A total of 49 T1D patients and 49 normoglycaemic (NG) subjects aged 5–20 years old were recruited. TLR2, TLR4, MYD88, NFKB, MCP1/CCL2...

Background The available antihypertensive drugs are effective and well tolerated agents. However, only about half of patients with treated hypertension achieve appropriate blood pressure control. Genetic and non-genetic factors contribute to the interindividual variability of the therapeutic response Objective This review constitutes a comprehensi...

Chagas disease, caused by Trypanosoma cruzi, is an endemic parasitical disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including Chronic Chagasic Cardiomyopathy (CCC), which ranges from moderate to severe stages depending on the cardiac ejection fraction. The pathogenic proce...

Considering the multifactorial nature of the development of coronary artery calcificatioN (CAD), and the difficulty in making its early diagnosis, this study sought to investigate the role of the TREML4 in the development of atherosclerotic lesions by genotyping of two main variants associated with this gene (rs2803495 and rs2803496), mRNA expressi...

SARS-CoV-2’s main protease (Mpro) interaction with ligands has been explored with a myriad of crystal structures, most of the monomers. Nonetheless, Mpro is known to be active as a dimer but the relevance of the dimerization in the ligand-induced conformational changes has not been fully elucidated. We systematically simulated different Mpro-ligand...

Despite the high number of individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) symptoms worldwide, many exposed individuals remain asymptomatic and/or uninfected and seronegative. This could be explained by a combination of environmental (exposure), immunological (prev...

Statins are inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, a key enzyme in cholesterol biosynthesis, that are highly effective in reducing plasma low-density lipoprotein (LDL) cholesterol and decreasing the risk of cardiovascular events. In recent years, a multitude of variants in genes involved in pharmacokinetics (PK) and pharmacodynamic...

Anticoagulant and antiplatelet drugs effectively prevent thrombotic events in patients with cardiovascular diseases, ischemic stroke, peripheral vascular diseases, and other thromboembolic diseases. However, genetic and non-genetic factors affect the response to antithrombotic therapy and can increase the risk of adverse events. This narrative revi...

Background No biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin. Methods We performed microRNA (miRNA) sequencing using plasma collected 5 days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥ 2 increased seru...

Aim: Functional analysis of PCSK9 3′UTR variants and mRNA–miRNA interactions were explored in patients with familial hypercholesterolemia (FH). Materials & methods:PCSK9 3′UTR variants were identified by exon-targeted gene sequencing. Functional effects of 3′UTR variants and mRNA–miRNA interactions were analyzed using in silico and in vitro studies...

Background Despite the high number of individuals infected by SARS-CoV-2 who develop COVID-19 symptoms worldwide, many exposed individuals remain asymptomatic and/or stay uninfected. This could be explained by a combination of environmental (exposure, previous infection), epigenetic, and genetic factors. Aiming to identify genetic variants involved...

The risk of developing severe forms of tuberculosis has increased by the acquired immunodeficiency syndrome (AIDS) epidemic, lack of effective drugs to eliminate latent infection and the emergence of drug-resistant mycobacterial strains. Excessive inflammatory response and tissue damage associated with severe tuberculosis contribute to poor outcome...

Background Statins are potent cholesterol-lowering drugs that prevent cardiovascular events. microRNAs (miRNAs) modulate the expression of genes involved in metabolic pathways and cardiovascular functions post-transcriptionally. This study explored the effects of statins on the expression of miRNAs and their target genes involved in lipid metabolis...

Extracellular vesicles (EVs) are composed of a lipid bilayer containing transmembrane and soluble proteins. Subtypes of EVs include ectosomes (microparticles/microvesicles), exosomes, and apoptotic bodies that can be released by various tissues into biological fluids. EV cargo can modulate physiological and pathological processes in recipient cells...

We investigated the antioph idic properties of isohemigossypolone (ISO), a naph thoquinone isolated from the outer bark of the Pachira aquatic Aubl. The inhibition of ph osph olipase A 2 , coagulant, fibrinogenolytic, hemorrhagic and myotoxic activities indu ced by Bothrops pauloensis venom (Pb) was investigated. For this, we use samples resulting...

This study explored circulating miRNAs and target genes associated with metabolic syndrome (MetS) and cardiometabolic risk in obese patients. Small-RNA sequencing was used to assess the peripheral blood miRNome of 12 obese subjects (6 MetS and 6 non-MetS). Differentially expressed miRNAs and target genes were further analyzed by qPCR in a larger sa...

Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy (LVH) and is one of the major causes of sudden cardiac death (SCD). An exon-targeted gene sequencing strategy was used to investigate the association of functional variants in sarcomeric genes (MYBPC3, MYH7 and TNNT2) with severe LVH and other SCD-related...

We measured plasma-derived extracellular vesicle (EV) proteins and their microRNA (miRNA) cargos in normoglycemic (NG), glucose intolerant (GI), and newly diagnosed diabetes mellitus (DM) in middle-aged male participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brazil). Mass spectrometry revealed decreased IGHG-1 and increased ITIH...

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) have the ability to increase vascular proliferation and permeability. The aim of this study was to quantify the release of two diffusible angiogenic growth factors (VEGF and FGF-2) after rapid maxillary expansion (RME). Thirty animals were randomly assigned to two...

Previous studies have demonstrated the potential antiophidic activity of Zanthoxylum monogynum A.St.-Hil. a tree from the Rutaceae family native to South America. In this present contribution, we demonstrate the activity of the metabolite lupeol, a triterpenoid isolated from the stem bark of Z. monogynum against the harmful effects of the Bothrops...

No biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin. We performed microRNA (miRNA) sequencing using plasma collected five days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥2 increased serum creatinine). The...

Background: No biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin. Methods: We performed microRNA (miRNA) sequencing using plasma collected five days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥2 increased s...

Background Recent experimental evidence shows that sevoflurane can reduce the inflammatory response during cardiac surgery with cardiopulmonary bypass. However, this observation so far has not been assessed in an adequately powered randomized controlled trial. Methods We plan to include one hundred patients undergoing elective coronary artery bypa...

Statins are the most widely used cholesterol-lowering drugs for cardiovascular diseases prevention. However, some patients are refractory to treatment, whereas others experience statin-related adverse events (SRAE). It has been increasingly important to identify pharmacogenetic biomarkers for predicting statin response and adverse events. This case...

Aim: To analyze the expression of urinary exosome-derived miRNAs (exo-miRs) in kidney recipients on tacrolimus-based therapy. Patients & methods: Clinical and drug monitoring data were recorded from 23 kidney recipients. Expression of 93 exo-miRs was measured by quantitative PCR array and mRNA targets were explored. Results: 16 exo-miRs were differ...

Several circulating miRNAs identified in the plasma of smokers have been implicated as promoters of nasopharyngeal and lung carcinoma. To investigate the plasma profile of miRNAs in subjects who reduces the number of smoked cigarettes and who quit after six months. We accompanied 28 individuals enrolled in a Smoking Cessation Program over 6 months....

Violence and drug abuse are highly destructive phenomena found world-wide, especially in Brazil. They seem to rise proportionally to one another and possibly related. Additionally, genetics may also play a role in drug abuse. This study has focused on identifying the use of cocaine within postmortem cases arriving at the Institute of Legal Medicine...

Objectives Minimum alveolar concentration (MAC) of volatile anesthetic agents (VAA) to maintain BIS below 50 in 50% of patients was defined as MACBIS50. The primary objective of this study is to determine the minimum alveolar concentration of sevoflurane as a single hypnotic agent to maintain BIS below 50 in patients during normothermic cardiopulmo...

Background The role of myeloid-derived suppressor cells (MDSCs) in severe tuberculosis patients who suffer from uncontrolled pulmonary inflammation caused by hypervirulent mycobacterial infection remains unclear. Methods This issue was addressed using C57BL/6 mice infected with highly virulent Mycobacterium bovis strain MP287/03. Results CD11b +G...

Background Familial hypercholesterolemia (FH) is a genetic disease that affects millions of people worldwide. Objectives The study protocol FHBGEP was design to investigate the main genomic, epigenomic, and pharmacogenomic factors associated with FH and polygenic hypercholesterolemia (PH). Methods FH patients will be enrolled at six research cent...

Adenovirus 36 (Ad-36) is related to human obesity due to its adipogenic activity mediated by the early 4 open reading frame 1 (E4orf1) protein. Mechanisms underlying the adipogenic effect of E4orf1 are not completely understood; however, the proliferation and differentiation of fat cells are increased through the activation of the phosphatidyl inos...

[This corrects the article DOI: 10.3389/fimmu.2020.01386.].

Background: Genetic and epigenetics factors have been implicated in drug response, graft function and rejection in solid organ transplantation. Differential expression of genes involved in calcineurin and mTOR signaling pathway and regulatory miRNAs was analyzed in the peripheral blood of kidney recipient cohort (n=36) under tacrolimus-based thera...

Vitamin D supplementation is widely used. However, there is no consensus on the use and dosage of this supplement and the existing recommendations arise from studies based on the benefits that this nutrient can facilitate in bones. In addition, individual genetics can influence the response to supplementation, therefore, research involving monozygo...

Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is the most important clinical consequence of T. cruzi infection, while the others remain asymptomatic (ASY). IFN-γ and IF...

Palmitoleic acid (POA, 16:1n-7) is a lipokine that has potential nutraceutical use to treat non-alcoholic fatty liver disease. We tested the effects of POA supplementation (daily oral gavage, 300 mg/Kg, 15 days) on murine liver inflammation induced by a high fat diet (HFD, 59% fat, 12 weeks). In HFD-fed mice, POA supplementation reduced serum insul...

Objectives: We sought to assess the effects of a high loading dose of rosuvastatin (40 mg) on acute inflammatory response after coronary stenting. Methods: Patients with stable coronary disease without statin use (≥7 days) and undergoing elective percutaneous coronary intervention (PCI) in a native coronary artery were randomized to receive a lo...

This study was performed as a contribution for a better understanding of Chlamydia pneumoniae frequency in children with respiratory infections. A total of 416 children were recruited from two clinical centers in Sao Luis, Brazil. Of these patients, 165 children had upper respiratory tract infections (URTI), 150 had community-acquired pneumonia (CA...

Mycophenolic acid (MPA) is a potent antiproliferative drug prescribed to prevent acute rejection in kidney transplantation. MPA reversibly inhibits the enzymes involved in the synthesis of guanosine nucleotides, thus preventing DNA replication of immune cells. Consequently, the repression of both cell and humoral immunity induces renal allograft to...

Background Abdominal aortic aneurysm (AAA) is a pathological enlargement of infrarenal aorta close to the aortic bifurcation, and it is an important cause of mortality in the elderly. Therefore, the biomarker identification for early diagnosis is of great interest for clinical benefit. It is known that microRNAs (miRNAs) have important roles via ta...

Drug-induced arrhythmia is an adverse drug reaction that can be potentially fatal since it is mostly related to drug-induced QT prolongation, a known risk factor for Torsade de Pointes and sudden cardiac death (SCD). Several risk factors have been described in association to these drug-induced events, such as preexistent cardiac disease and genetic...

Members of the triggering receptor expressed on myeloid cells (TREM) family are associated with atherosclerosis risk and progression. TREML4 is upregulated in the early phase of acute coronary syndrome. We investigated the relationship between the mRNA expression of 13 genes in blood leukocytes, TREML4 polymorphisms, and coronary artery lesion exte...

Background: There is no strong evidence on the link between inflammatory profile and pattern of drug treatment response in depressive patients that could result in Coronary Artery Disease occurrence. Objective: This study aimed to compare the subclinical atherosclerosis markers, inflammatory profile, and BDNF production in Resistant Depression (...

Hyaluronic Acid, HA is a major component of the extracellular matrix of vertebrates. It is a glycosaminoglycan hydrolyzed by enzymes of the hyaluronidase family, involved in the regulation of important biological processes such as angiogenesis and vascular permeability. As interest in the development of a synthesis route for this enzyme, we aim to...

O objetivo deste estudo é verificar possível relação dos polimorfismos do gene ABCB1 com as toxicidades induzidas por cisplatina em pacientes com câncer de cabeça e pescoço. Alem de caracterizar os pacientes quanto à nefrotoxicidade, mielotoxicidade, hepatotoxicidade e toxicidades gastrointestinais à cisplatina após primeiro ciclo de quimioterapia....

Background and aims : Fat-soluble vitamins play an important role in the pathogenesis of cardiovascular disease and progression of atherosclerosis. This study aimed at investigating the relationship of the serum levels of alpha-tocopherol and retinol with the extent of coronary lesions in patients with coronary artery disease. Methods . Patients wi...

Nanotechnology is a multidisciplinary scientific field based on the development, characterization, production and application of structures, devices and systems with shape and size at the nanoscale. Polymeric systems with therapeutic purpose have been widely used since they allow a slow and gradual release of drug and allow the transport of drugs t...

Tuberculosis (TB) is an infectious disease in which the molecular typing methods allow to have important information about the dynamics of transmission and to assist properly in disease control. Although the ERIC-PCR (Enterobacterial repetitive intergenic consensus-PCR) assay is fast and easy to perform, scarce studies have reported its use in epid...

Monitoring of immunosuppressive drugs, such as calcineurin and mTOR inhibitors, is essential to avoid undesirable kidney transplant outcomes. Polymorphisms in pharmacokinetics-related genes have been associated with variability in blood levels of immunosuppressive drugs and adverse effects, but influence of pharmacodynamics-related genes remains to...

Dyslipidemia, diabetes, obesity and hypertension are common metabolic diseases. In the last decades, unhealthy lifestyle and aging have leads to an increased incidence of these diseases, increasing morbidity and mortality by cardiovascular causes. The treatment of metabolic diseases includes lifestyle interventions as healthy diet and physical exer...

Background: Tuberculous pneumonia, necrotic granulomatous lesions, and bacterial dissemination characterize severe forms of mycobacterial infection. Methods: To evaluate the pulmonary CD4+ T-cell response during severe tuberculosis, C57BL/6 mice were infected with approximately 100 bacilli of 3 hypervirulent mycobacterial isolates (Mycobacterium...

Purpose. Cardiovascular fitness (maximal oxygen uptake [VO 2 max]) is linked with health indicators and the 2 subunit of the AMP-activated protein kinase (AMPK 2), encoded by the PRKAA2 gene, is an important metabolic sensor and can mediate part of exercise effect. It has been proposed that changes in the metabolic process bound with exercise might...

Objective: The present study has investigated the association between low-density lipoprotein receptor-related protein 5 (LRP5) 4037C>T polymorphism and type 1 diabetes mellitus (T1DM) susceptibility in a Brazilian population. Subjects and methods: A total number of 134 T1DM patients and 180 normoglycemic individuals (NG) aged 6-20 years were st...

Background: Studies have pointed out a higher mortality after coronary artery bypass surgery (CABG) in patients with stent. Objective: To evaluate inflammatory markers in peripheral blood cells and in coronary artery tissue samples obtained during CABG in patients with stent compared to controls. Methods: The case series consisted of two group...

This work studied the cell transport of peptidase-generated peptides from cowpea bean proteins and their effects on mRNA expression of cholesterol-related genes in intestinal and liver cells. The ≤3 kDa hydrolysate was obtained and incubated with Caco-2 intestinal cells using Transwell® plates. HepG2 liver cells were incubated with synthetic analog...

OBJECTIVES Inflammatory molecules play a role in the development of atherosclerosis, which is the primary origin of cardiovascular disorders. However, to the best of our knowledge, no study has attempted to investigate the relationship between these circulating molecules and the prediction of cardiovascular risk. The present study aimed to i