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Abstract Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), is the largest pandemic in modern history with very high infection rates and considerable mortality. The disease, which emerged in China’s Wuhan province, had its first reported case on December 29, 2019, and spread rapidly worldwide. On March 11, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic and global health emergency. Since the outbreak, efforts to develop COVID-19 vaccines, engineer new drugs, and evaluate existing ones for drug repurposing have been intensively undertaken to find ways to control this pandemic. COVID-19 therapeutic strategies aim to impair molecular pathways involved in the virus entrance and replication or interfere in the patients’ overreaction and immunopathology. Moreover, nanotechnology could be an approach to boost the activity of new drugs. Several COVID-19 vaccine candidates have received emergency-use or full authorization in one or more countries, and others are being developed and tested. This review assesses the different strategies currently proposed to control COVID-19 and the issues or limitations imposed on some approaches by the human and viral genetic variability.

https://doi.org/10.1590/1678-4685-gmb-2020-0452

Inulin Induces IL-10 Secretion and Increased FOXP3 Gene Expression in Human Peripheral Blood Mononuclear Cells
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Amarante, Marla Karine

; Ariza, Carolina Batista

; Oliveira, Carlos Eduardo Coral de

; Gualtieri, Karina de Almeida

; Oda, Julie Massayo Maeda

; Watanabe, Maria Angelica Ehara

Brazilian Archives of Biology and Technology

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2018, Volume 61 elocation e18160591

Resumo: En | Texto: En | PDF: En

ABSTRACT Inulin is an effective prebiotic and its potential in modulating systemic immunity have been proposed. A subpopulation of T cells, named T regulatory cells (Tregs), expressing the Forkhead boxP3 transcription factor are key mediators of peripheral tolerance and suppress undesirable immune responses. These Tregs can be induced by cytokine transforming growth factor beta (TGF-β) and interleukin 10 (IL-10). This work aimed to evaluate inulin effects on human peripheral blood mononuclear cells (PBMC) in vitro. PBMC were incubated with inulin, and the expression of TGF-(1, FOXP3 and IL-10 was analyzed. Increased supernatant IL-10 levels were observed in PBMC of inulin-treated group (p=0.03). Moreover, FOXP3 gene expression was 7.6 fold higher in inulin-treated PBMC, whereas a trend in TGF-β1 expression was detected (p=0.055). These data suggest that inulin induces an immunosuppressive environment in cultured PBMC by promoting FOXP3 gene expression and IL-10 secretion. These studies offer prospects for further fundamental research in this field.

https://doi.org/10.1590/1678-4324-2018160591 3025 downloads

Prevalence of Torque teno virus in healthy donors of Paraná State, southern Brazil
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Mazzola, Jocimara Costa

; Saito, Patrícia Keiko

; Yamakawa, Roger Haruki

; Watanabe, Maria Angélica Ehara

; Silva Junior, Waldir Veríssimo da

; Matta, Alessandra Cristina Gobbi

; Borelli, Sueli Donizete

Revista Brasileira de Hematologia e Hemoterapia

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Out 2015, Volume 37 Nº 5 Páginas 336 - 340

Resumo: En | Texto: En | PDF: En

OBJECTIVE: To determine the prevalence of the Torque teno virus in healthy donors in the northern and northwestern regions of the state of Paraná, southern Brazil.METHODS: The Torque teno virus was detected by a nested polymerase chain reaction using a set of oligoprimers for the N22 region.RESULTS: The prevalence of the virus was 69% in 551 healthy blood donors in southern Brazil. There was no statistically significant difference between the presence of the virus and the variables gender, ethnicity and marital status. There was significant difference in the prevalence of the virus regarding the age of the donors (p-value = 0.024) with a higher incidence (74.7%) in 18- to 24-year-old donors.CONCLUSION: A high prevalence of Torque teno virus was observed in the population studied. Further studies are needed to elucidate the routes of contamination and the clinical implications of the virus in the healthy population.

https://doi.org/10.1016/j.bjhh.2015.07.005 1276 downloads

Involvement of transforming growth factor beta-1 (TGFβ1) cytokine and FOXP3 transcription factor genetic polymorphisms in hematological malignancies
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Vitiello, Glauco Akelinghton Freire

; Guembarovski, Roberta Losi

; Oliveira, Carlos Eduardo Coral de

; Amarante, Marla Karine

; Perim, Aparecida de Lourdes

; Watanabe, Maria Angelica Ehara

Brazilian Archives of Biology and Technology

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Ago 2015, Volume 58 Nº 4 Páginas 553 - 561

Resumo: En | Texto: En | PDF: En

Hematological malignancies (HM) are a group of neoplastic diseases that arise from hematologic cell lineages. Transforming growth factor beta 1 (TGFβ1) is shown to negatively regulate normal and malignant hematopoiesis and, in immunological context, to promote T cell exhaustion and generation of regulatory T cells, which are shown to be deleterious in cancer, by the induction of transcription factor FOXP3 expression. The present study aimed to evaluate TGFB1 exon-1 rs1800470 and FOXP3 intron-1 rs2232365 polymorphisms in relation to HM susceptibility. DNA was extracted from blood samples of 43 HM patients and 142 neoplasia-free individuals and polymorphisms were analyzed by allelic-specific PCR. Association analysis was assessed by the Odds Ratio (OR) with significance level of 5%. Regarding FOXP3 polymorphism, no significant differences were observed in genotype or allele distribution among the patients and controls. However, there was a positive association between TGFB1 TT genotype and HM susceptibility (OR = 4.07; CI95% = 1.94 - 8.52). In the combined analysis, a positive association was also observed for TGFB1 TT and FOXP3 GG genotypes (OR = 4.00; CI95% = 1.54 - 10.41) in relation to HM susceptibility. Our results indicated promising new markers to be further investigated in hematological malignancies.

https://doi.org/10.1590/S1516-8913201500287 2008 downloads

Torque teno virus among dialysis and renal-transplant patients
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Takemoto, Angélica Yukari

; Okubo, Patrícia

; Saito, Patricia Keiko

; Yamakawa, Roger Haruki

; Watanabe, Maria Angélica Ehara

; Veríssimo da Silva Junior, Waldir

; Borelli, Sueli Donizete

; Bedendo, João

Brazilian Journal of Microbiology

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Mar 2015, Volume 46 Nº 1 Páginas 307 - 311

Resumo: En | Texto: En | PDF: En

Patients who undergo dialysis treatment or a renal transplant have a high risk of blood-borne viral infections, including the Torque teno virus (TTV). This study identified the presence of TTV and its genome groups in blood samples from 118 patients in dialysis and 50 renal-transplant recipients. The research was conducted in a hospital in the city of Maringá, state of Paraná. The viral DNA, obtained from whole blood, was identified by using two nested Polymerase Chain Reactions (PCR). The frequencies of TTV were 17% and 36% in dialysis patients using the methodology proposed by Nishizawa et al. (1997) and Devalle and Niel (2004), respectively, and 10% and 54% among renal-transplant patients. There was no statistically significant association between the frequency of the pathogen and the variables: gender, time in dialysis, time since transplant, blood transfusions, and the concomitant presence of hepatitis B, for either the dialysis patients or the renal-transplant recipients. Among dialysis patients and renal-transplant recipients, genogroup 5 was predominant (48% and 66% respectively), followed by genogroup 4 (37% and 48%) and genogroup 1 (23% and 25%). Genogroup 2 was present in both groups of patients. Some patients had several genogroups, but 46% of the dialysis patients and 51% of the renal-transplant recipients had only a single genogroup. This study showed a high prevalence of TTV in dialysis patients and renal-transplant recipients.

https://doi.org/10.1590/S1517-838246120131195 1477 downloads

Protein Expression and Codon 72 Polymorphism of TP53 Gene in Triple Negative Breast Cancer
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Lopes, Leandra Fiori

; Guembarovski, Roberta Losi

; Guembarovski, Alda Losi

; Kishima, Marina Okuyama

; Campos, Clodoaldo Zago

; Derossi, Daniela Rudgeri

; Ariza, Carolina Batista

; Ozawa, Patricia Midori Murobushi

; Oliveira, Carlos Eduardo Coral de

; Banin-Hirata, Bruna Karina

; Vitiello, Glauco Akelinghton Freire

; Borelli, Sueli Donizete

; Watanabe, Maria Angelica Ehara

Brazilian Archives of Biology and Technology

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Dez 2014, Volume 57 Nº 6 Páginas 895 - 899

Resumo: En | Texto: En | PDF: En

A subgroup of tumor that has received attention is triple-negative breast cancer (TNBC), which presents phenotype of negative estrogen receptor, negative progesterone receptor and has no overexpression of HER2. TP53 acts as a tumor suppressor limiting the proliferation of damaged cells. A polymorphic site (rs1042522) of TP53 encodes either an arginine or a proline amino acid, but its biological significance remains unclear. This study aimed to investigate this variant and its expression in search for a possible involvement in TNBC susceptibility and clinical outcome. Genetic polymorphism was evaluated in 50 patients and 115 controls by PCR based methodology and immunohistochemistry was done with monoclonal antibody. Case-control study showed no positive or negative association (OR= 0.95; CI95%= 0.48-1.89). Comparison of genotypes and clinical outcome showed no significant results. Despite most of patients presented p53 positive staining by immunohistochemistry, there was no significant association in relation to prognostic parameters. Results demonstrated a lack of association between codon 72 polymorphism, susceptibility and prognosis of TNBC. Immunohistochemistry analysis should be done more carefully, since most of the patients had the somatic mutation of p53, which could be an indicator of prognostic value in TNBC.

https://doi.org/10.1590/S1516-8913201402559 2001 downloads

TT virus in peripheral blood cells from patients with human papillomavirus (HPV): investigating association with cervical carcinoma
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Suzuki, Patrícia Sayuri

; Oliveira, Karen Brajão de

; Herrera, Ana Cristina do Amaral

; Borelli, Sueli Donizete

; Guembarovski, Roberta Losi

; Oliveira, Carlos Eduardo Coral de

; Oda, Julie Massayo Maeda

; Ozawa, Patricia Midori Murobushi

; Watanabe, Maria Angelica Ehara

Brazilian Archives of Biology and Technology

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Abr 2014, Volume 57 Nº 2 Páginas 228 - 232

Resumo: En | Texto: En | PDF: En

Torque Teno Virus (TTV) presence was investigated in peripheral blood of 117 brazilian women by nested polymerase chain reaction. TTV DNA was observed in 18.6% of healthy donors and in 24.32% Human Papillomavirus (HPV) patients. TTV presence was also investigated in the HPV positive group for comparison between the cervical cancer and noncancerous patients. TTV DNA prevalence was significantly higher among the HPV positive patients with cervical cancer (57.14%) than in HPV noncancerous patients (16.67%). Thus, the presence of TTV infection could be a risk factor for cancer development in the patients presenting HPV-TTV coinfection. Further studies are required to clarify the TTV influence in HPV pathogenesis.

1760 downloads

Higher than normal plasma Iinterleukin-6 concentrations in brazilian patients with mood disorders
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Miranda, Helen Cristina

; Nunes, Sandra Odebrecht Vargas

; Reiche, Edna Maria Vissoci

; Oda, Julie Massayo Maeda

; Watanabe, Maria Angelica Ehara

Brazilian Archives of Biology and Technology

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Ago 2011, Volume 54 Nº 4 Páginas 717 - 722

Resumo: En | Texto: En | PDF: En

The aim of this work was to study the plasma concentration of IL-6 by ELISA in the patients with mood disorders and normal healthy donors. The plasma concentration of IL-6 was higher in the patients than in the control healthy group. Results suggested that IL-6 could serve as an immunological marker in mood disorder pathogenesis as well.

2691 downloads

The effects of nitric oxide on the immune response during giardiasis
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Pavanelli, Wander Rogério

; Gutierrez, Fredy Roberto Salazar

; Silva, Jean Jerley Nogueira da

; Costa, Ivete Conchon

; Menezes, Maria Claudia Noronha Dutra de

; Oliveira, Francisco José de Abreu

; Itano, Eiko Nakagawa

; Watanabe, Maria Angélica Ehara

Brazilian Journal of Infectious Diseases

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Dez 2010, Volume 14 Nº 6 Páginas 606 - 612

Resumo: En | Texto: En | PDF: En

Nitric oxide (NO) is a free radical synthesized from L-arginine by different isoforms NO-synthases. NO possesses multiple and complex biological functions. NO is an important mediator of homeostasis, and changes in its generation or actions can contribute or not to pathological states. The knowledge of effects of NO has been not only important to our understanding of immune response, but also to new tools for research and treatment of various diseases. Knowing the importance of NO as inflammatory mediator in diverse infectious diseases, we decided to develop a revision that shows the participation/effect of this mediator in immune response induced against Giardia spp. Several studies already demonstrated the participation of NO with microbicidal and microbiostatic activity in giardiasis. On the other hand, some works report that Giardia spp. inhibit NO production by consuming the intermediate metabolite arginine. In fact, studies in vitro showed that G. lamblia infection of human intestinal epithelial cells had reduced NO production. This occurs due to limited offer of the crucial substrate arginine (essential aminoacid for NO production), consequently reducing NO production. Therefore, the balance between giardial arginine consumption and epithelial NO production could contribute to the variability of the duration and severity of infections by this ubiquitous parasite.

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Detection of GBV-C/HGV RNA in cervico-vaginal smears from healthy individuals
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Watanabe, Maria Angelica Ehara

; Miquelão, Ana Karina Melim Benthien

; Oliveira, Carlos Eduardo Coral de

; Oliveira, Karen Brajão de

; Nasser, Thiago Franco

; Aoki, Mateus Nóbrega

; Suzuki, Patrícia Sayuri

; Amarante, Marla Karine

; Venâncio, Emerson José

; Azevedo, Elbens Marcos Minoreli de

Brazilian Archives of Biology and Technology

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Out 2008, Volume 51 Nº 5 Páginas 917 - 922

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

O objetivo do presente estudo foi avaliar a transmissão sexual de GBV-C/HBV, através da detecção do RNA viral em raspados cérvico-vaginais. Portanto, a presença do RNA GBV-C/HGV foi investigada em raspados cérvico-vaginais em mulheres aparentemente saudáveis que realizaram exames preventivos para câncer cervical. GBV-C/HGV RNA foi detectado por reação de transcriptase reversa e reação em cadeia da polimerase (RT-PCR). Apenas uma mulher apresentou a co-infecção com o papiloma vírus humano (HPV). O RNA GBV-C/HGV foi detectado em 13/73 (17,57%) mulheres saudáveis e sua prevalência entre participantes da idade de 28-43 anos foi de 53,85%. Não foi observada relação entre a presença do RNA GBV-C/HGV com a idade de primeira relação sexual, nem com o número de gestações. Entre as mulheres que apresentavam o RNA viral, 69,23% eram casadas. O presente estudo demonstrou que secreções cérvico-vaginais podem conter o RNA viral GBV-C/HBV.

The purpose of the present study was to evaluate the sexual transmission of GBV-C/HGV, through RNA detection in cervicovaginal smears. Therefore the GBV-C/HGV RNA in cervicovaginal smears from apparently healthy women was investigated using routine proceedings for prophylactic screening to cervical cancer. GBV-C/HGV RNA was detected by reverse transcriptase and polymerase chain reaction (RT-PCR). Only one woman presented co-infection with human papilloma virus (HPV). The GBV-C/HGV RNA was detected in 13/73 (17.57%) healthy women and it's prevalence in participating women between 28-43 years old was 53.85%. No association was found with GBV-C/HGV for the age of first sexual intercourse and number of pregnancies. In GBV-C/HGV RNA positive women, 69.23% were married. In conclusion, the present findings show that cervical and vaginal specimens could contain the GBV-C/HGV RNA.

3234 downloads

11.

Socio-demographic and epidemiological characteristics associated with human immunodeficiency virus type I (HIV-1) infection in HIV-1-explosed but uninfected individuals, and in HIV-1-infected patients from a southern brasilian population
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Reiche, Edna Maria Vissoci

; Bonametti, Ana Maria

; Watanabe, Maria Angélica Ehara

; Morimoto, Helena Kaminami

; Morimoto, Arilson Akira

; Wiechmann, Susana Lilian

; Breganó, José Wander

; Matsuo, Tiemi

; Reiche, Fernando Vissoci

Revista do Instituto de Medicina Tropical de São Paulo

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Out 2005, Volume 47 Nº 5 Páginas 239 - 246

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

Este estudo transversal descreve as principais características sociodemográficas e epidemiológicas associadas com a infecção pelo HIV-1 em 1.061 indivíduos atendidos em Londrina e região, Sul do Brasil: 136 indivíduos saudáveis (Grupo 1), 147 indivíduos expostos ao HIV-1 mas não infectados (Grupo 2), 161 pacientes infectados pelo HIV-1 assintomáticos (Grupo 3) e 617 pacientes com aids (Grupo 4). Os dados foram obtidos pela aplicação de um questionário padronizado e realização de testes sorológicos. A idade dos indivíduos variou de 15,1 a 79,5 anos; 54,0% e 56,1% dos pacientes dos Grupos 3 e 4, respectivamente, eram homens. As principais características dos indivíduos dos Grupos 2, 3 e 4 foram o predomínio do nível educacional com até oito anos de escolaridade (58,8%, 60,2% e 62,4%, respectivamente), a via sexual de transmissão (88,4%, 87,0% e 82,0%, respectivamente), o comportamento heterossexual (91,8%, 75,2% e 83,7%, respectivamente) e antecedentes de doenças sexualmente transmissíveis (20,4%, 32,5% e 38,1%, respectivamente). Os pacientes com aids apresentaram os valores mais elevados de soropositividade para sífilis (25,6%), anti-HCV (22,3%) e anti-HTLV I/II em dois testes de triagem sorológica (6,2% e 6,8%, respectivamente). Os resultados documentando as características predominantes associadas com a infecção pelo HIV-1 observada nos indivíduos de Londrina e região, poderá ser útil na melhoria dos atuais programas de prevenção, monitoramento e de tratamento da infecção pelo HIV-1 dirigidos a esta população.

The ability to control human immunodeficiency virus type 1 (HIV-1) infection and progression of the disease is regulated by host and viral factors. This cross-sectional study describes the socio-demographic and epidemiological characteristics associated with HIV-1 infection in 1,061 subjects attended in Londrina and region, south of Brazil: 136 healthy individuals (Group 1), 147 HIV-1-exposed but uninfected individuals (Group 2), 161 HIV-1-infected asymptomatic patients (Group 3), and 617 patients with AIDS (Group 4). Data were obtained by a standardized questionnaire and serological tests. The age of the individuals ranged from 15.1 to 79.5 years, 54.0% and 56.1% of the Groups 3 and 4 patients, respectively, were men. The major features of groups 2, 3, and 4 were a predominance of education level up to secondary school (55.8%, 60.2% and 62.4%, respectively), sexual route of exposure (88.4%, 87.0% and 82.0%, respectively), heterosexual behavior (91.8%, 75.2% and 83.7%, respectively), and previous sexually transmitted diseases (20.4%, 32.5%, and 38.1%, respectively). The patients with AIDS showed the highest rates of seropositivity for syphilis (25.6%), of anti-HCV (22.3%), and anti-HTLV I/II obtained by two serological screening tests (6.2% and 6.8%, respectively). The results documenting the predominant characteristics for HIV-1 infection among residents of Londrina and region, could be useful for the improvement of current HIV-1 prevention, monitoring and therapeutic programs targeted at this population.

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12.

Aspectos patológicos, imunológicos e propriedades moleculares do TT vírus
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Watanabe, Maria Angelica Ehara

; Miranda, Helen Cristina

; Oliveira, Karen Brajão de

; Oliveira, Carlos Eduardo Coral de

; Tristão, Fabrine Sales Massafera

; Duarte, Leila Maria

; Silva, Ligiane de Lourdes

; Corte, Andréia Corrêa

; Guarnier, Flávia Alessandra

; Kaminami, Mari Sumigawa

Jornal Brasileiro de Patologia e Medicina Laboratorial

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Ago 2005, Volume 41 Nº 4 Páginas 223 - 228

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

O TT vírus (TTV) foi primeiramente descrito no Japão, em 1997, por T. Nishizawa, no soro de pacientes com hepatite, pós-transfusão, não-A-G. Tem sido intensivamente investigado, desde então, como uma possível adição à lista dos vírus indutores de hepatite. O TTV é um vírus DNA não-envelopado, de fita simples. Uma considerável variabilidade genética tem sido demonstrada por parte do TTV, o que tem levado pesquisadores a agrupar isolados do vírus em inúmeros genótipos e subtipos. No entanto a significância clínica da infecção por TTV permanece desconhecida. Ele é freqüentemente detectado em fluidos corporais e seu componente mais bem elucidado atualmente é o genoma. Conhecimentos relacionados ao TTV têm aumentado constantemente, porém vários aspectos fundamentais permanecem obscuros. Esta revisão apresenta algumas das propriedades moleculares do TT vírus.

TT virus (TTV) was first reported in Japan in 1997 by T. Nishizawa in sera from non-A to non-G post-transfusion hepatitis patients. It has been intensively investigated, ever since, as a possible addition to the list of hepatitis-inducing viruses. The TTV is an unenveloped, single-stranded DNA virus. Considerable genetic variability of TTV has been demonstrated and has led investigators to group its isolates into numerous genotypes and subtypes. However, the clinical significance of TTV infection remains unknown. It is frequently detected in the serum and in other body fluids of humans. The component of TTV currently best understood is its genome. Knowledge related to TTV has increased rapidly, but many fundamental aspects remain unclear. This review shows some of the molecular properties of TT virus.

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