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  1. Article ; Online: Altered RNome expression in Murine Gastrocnemius Muscle following Exposure to Jararhagin, a Metalloproteinase from Bothrops jararaca Venom

    Andrezza Nascimento / Bianca Cestari Zychar / Rodrigo Pessôa / Alberto José da Silva Duarte / Patricia Bianca Clissa / Sabri Saeed Sanabani

    Toxins, Vol 14, Iss 472, p

    2022  Volume 472

    Abstract: Small RNAs (sRNAs) and microRNAs (miRNAs) are small endogenous noncoding single-stranded RNAs that regulate gene expression in eukaryotes. Experiments in mice and humans have revealed that a typical small RNA can affect the expression of a wide range of ... ...

    Abstract Small RNAs (sRNAs) and microRNAs (miRNAs) are small endogenous noncoding single-stranded RNAs that regulate gene expression in eukaryotes. Experiments in mice and humans have revealed that a typical small RNA can affect the expression of a wide range of genes, implying that small RNAs function as global regulators. Here, we used small RNA deep sequencing to investigate how jararhagin, a metalloproteinase toxin produced from the venom of Bothrops jararaca , affected mmu-miRNAs expression in mice 2 hours (Jar 2hrs) and 24 hours (Jar 24hrs) after injection compared to PBS control. The findings revealed that seven mmu-miRNAs were substantially differentially expressed ( p value ( p (Corr) cut-off 0.05, fold change ≥ 2) at 2 hrs after jararhagin exposure and that the majority of them were upregulated when compared to PBS. In contrast to these findings, a comparison of Jar 24hrs vs. PBS 24hrs demonstrated that the majority of identified mmu-miRNAs were downregulated. Furthermore, the studies demonstrated that mmu-miRNAs can target the expression of several genes involved in the MAPK signaling pathway. The steady antithetical regulation of mmu-miRNAs may correlate with the expression of genes that trigger apoptosis via MAPK in the early stages, and this effect intensifies with time. The findings expand our understanding of the effects of jararhagin on local tissue lesions at the molecular level.
    Keywords small RNAs ; jararhagin ; venom ; Medicine ; R
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Small RNA Profiling in an HTLV-1-Infected Patient with Acute Adult T-Cell Leukemia-Lymphoma at Diagnosis and after Maintenance Therapy

    Rodrigo Pessôa / Daniela Raguer Valadão de Souza / Youko Nukui / Juliana Pereira / Lorena Abreu Fernandes / Rosa Nascimento Marcusso / Augusto César Penalva de Oliveira / Jorge Casseb / Alberto José da Silva Duarte / Sabri Saeed Sanabani

    International Journal of Molecular Sciences, Vol 24, Iss 10643, p

    A Case Study

    2023  Volume 10643

    Abstract: Small RNAs (sRNAs) are epigenetic regulators of essential biological processes associated with the development and progression of leukemias, including adult T-cell leukemia/lymphoma (ATLL) caused by human T-cell lymphotropic virus type 1 (HTLV-1), an ... ...

    Abstract Small RNAs (sRNAs) are epigenetic regulators of essential biological processes associated with the development and progression of leukemias, including adult T-cell leukemia/lymphoma (ATLL) caused by human T-cell lymphotropic virus type 1 (HTLV-1), an oncogenic human retrovirus originally discovered in a patient with adult T-cell leukemia/lymphoma. Here, we describe the sRNA profile of a 30-year-old woman with ATLL at the time of diagnosis and after maintenance therapy with the aim of correlating expression levels with response to therapy.
    Keywords small RNA ; HTLV-1 ; ATLL ; massive parallel sequencing ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Cost-Effective Trap qPCR Approach to Evaluate Telomerase Activity

    Thalyta Nery Carvalho Pinto / Juliana Ruiz Fernandes / Liã Barbara Arruda / Alberto José da Silva Duarte / Gil Benard

    Clinics, Vol

    an Important Tool for Aging, Cancer, and Chronic Disease Research

    2021  Volume 76

    Abstract: OBJECTIVES: Telomeres are a terminal “DNA cap” that prevent chromosomal fusion and degradation. However, aging is inherent to life, and so is the loss of terminal sequences. Telomerase is a specialized reverse transcriptase encoded by self-splicing ... ...

    Abstract OBJECTIVES: Telomeres are a terminal “DNA cap” that prevent chromosomal fusion and degradation. However, aging is inherent to life, and so is the loss of terminal sequences. Telomerase is a specialized reverse transcriptase encoded by self-splicing introns that counteract chromosome erosion. Telomerase activity is observed during early embryonic development, but after the blastocyst stage, the expression of telomerase reduces. The consequences of either insufficient or unrestrained telomerase activity underscore the importance of ongoing studies aimed at elucidating the regulation of telomerase activity in humans. In the present study, we aimed to standardize a simplified telomerase repeat-amplification protocol (TRAP) assay to detect telomerase activity in unstimulated and PHA-stimulated mononuclear cells. METHODS and RESULTS: Our optimized qPCR-based can efficiently evaluate telomerase activity. Quantification of protein and DNA between unstimulated and PHA-stimulated peripheral blood mononuclear cells revealed cellular activation and cell-cycle entry. The assay also showed that relative telomerase activity is significantly different between these two conditions, supporting the applicability of the assay. Furthermore, our findings corroborated that telomerase activity decreases with age. CONCLUSIONS: Telomeres and telomerase are implicated in aging and development of chronic diseases and cancer; however, difficulty in accessing commercial kits to investigate these aspects is a critical constraint in health surveillance studies. Our optimized assay was successfully used to differentiate telomerase activity between unstimulated and stimulated cells, clearly showing the reactivation of telomerase upon cell activation. This assay is affordable, reproducible, and can be executed in resource-limited settings.
    Keywords Telomerase ; Telomere ; Aging ; Real-Time Polymerase Chain Reaction ; Medicine (General) ; R5-920
    Subject code 570
    Language English
    Publishing date 2021-02-01T00:00:00Z
    Publisher Elsevier España
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: IgG from Adult Atopic Dermatitis (AD) Patients Induces Thymic IL-22 Production and CLA Expression on CD4+ T Cells

    Thamires Rodrigues de Sousa / Beatriz Oliveira Fagundes / Andrezza Nascimento / Lorena Abreu Fernandes / Fábio da Ressureição Sgnotto / Raquel Leão Orfali / Valéria Aoki / Alberto José da Silva Duarte / Sabri Saeed Sanabani / Jefferson Russo Victor

    International Journal of Molecular Sciences, Vol 23, Iss 6867, p

    Possible Epigenetic Implications Mediated by miRNA

    2022  Volume 6867

    Abstract: Atopic dermatitis (AD) is a common relapsing inflammatory skin disorder characterized by immune-mediated inflammation and epidermal barrier dysfunction. The pathogenesis of AD is multifactorial and has not been fully elucidated to date. This study aimed ... ...

    Abstract Atopic dermatitis (AD) is a common relapsing inflammatory skin disorder characterized by immune-mediated inflammation and epidermal barrier dysfunction. The pathogenesis of AD is multifactorial and has not been fully elucidated to date. This study aimed to evaluate whether serum IgG from adult AD patients could modulate the thymic maturation of IL-22-producing T cells and CLA+ T cells of non-atopic infants. Given that miRNAs regulate immune response genes, we evaluated whether miRNA expression is also altered in cultured thymocytes. Thymocytes were cultured with purified IgG from AD patients or control conditions (mock, Intravenous-IgG (IVIg), non-atopic IgG, or atopic non-AD IgG). Using flow cytometry analysis, we assessed the expression of CLA and intracellular levels of IL-4, IFN-γ, and IL-22 on double-positive T cells (DP T), CD4 T cells, or CD8 T cells. We also investigated the frequency of IgG isotypes and their direct interaction with the thymic T cells membrane. The miRNA profiles were evaluated by the Illumina small RNA-seq approach. MiRNA target gene prediction and enrichment analyses were performed using bioinformatics. Increased frequencies of IL-22 and CLA+ producing CD4+ T cells cultured with IgG of AD patients was seen in non-atopic infant thymocytes compared to all control conditions. No alterations were observed in the frequency of IgG isotypes among evaluated IgG pools. Evidence for a direct interaction between IgG and thymic DP T, CD4 T, and CD8 T cells is presented. The small RNA-seq analysis identified ten mature miRNAs that were modulated by AD IgG compared to mock condition (miR-181b-5p, hsa-miR-130b-3p, hsa-miR-26a-5p, hsa-miR-4497, has-miR-146a, hsa-let-7i-5p, hsa-miR-342-3p, has-miR-148a-3p, has-miR-92a and has-miR-4492). The prediction of the targetome of the seven dysregulated miRNAs between AD and mock control revealed 122 putative targets, and functional and pathway enrichment analyses were performed. Our results enhance our understanding of the mechanism by which IgG can ...
    Keywords human ; thymus ; Th22 ; IL-22 ; atopic dermatitis ; miRNA ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Long-term effects of COVID-19 in diabetic and non-diabetic patients

    Ricardo Wesley Alberca / Yasmim Álefe Leuzzi Ramos / Nátalli Zanete Pereira / Danielle Rosa Beserra / Anna Cláudia Calvielli Castelo Branco / Raquel Leão Orfali / Valeria Aoki / Alberto Jose da Silva Duarte / Maria Notomi Sato

    Frontiers in Public Health, Vol

    2022  Volume 10

    Abstract: The literature presents several reports of the impact of glycemic control and diabetes in the inflammatory and coagulatory response during coronavirus disease 2019 (COVID-19). Nevertheless, the long-term impact of the COVID-19 in diabetic patients is ... ...

    Abstract The literature presents several reports of the impact of glycemic control and diabetes in the inflammatory and coagulatory response during coronavirus disease 2019 (COVID-19). Nevertheless, the long-term impact of the COVID-19 in diabetic patients is still to be explored. Therefore, we recruited 128 patients and performed a longitudinal analysis on COVID-19-associated biomarkers of patients with COVID-19, tree and 6 months after COVID-19 recovery and put into perspective the possible long-term complication generated after COVID-19. In our investigation, we failed to verify any long-term modification on inflammatory biomarkers, but detected an increase in the glycemia and glycated hemoglobin in patients without any pre-existing history or diagnosis of diabetes (non-diabetic patients). Although diabetic and non-diabetic patients presented elevated levels of glycated hemoglobin, the c-peptide test indicated a normal beta cell function in all patients.
    Keywords SARS-CoV-2 ; COVID-19 ; complications ; glycemic control ; infection ; Public aspects of medicine ; RA1-1270
    Subject code 610 ; 616
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Characterization of Bacterial Communities from the Surface and Adjacent Bottom Layers of Water in the Billings Reservoir

    Marta Angela Marcondes / Andrezza Nascimento / Rodrigo Pessôa / Jefferson Russo Victor / Alberto José da Silva Duarte / Patricia Bianca Clissa / Sabri Saeed Sanabani

    Life, Vol 12, Iss 8, p

    2022  Volume 1280

    Abstract: Here, we describe the bacterial diversity and physicochemical properties in freshwater samples from the surface and bottom layers of the Billings Reservoir, the largest open-air storage ecosystem in the São Paulo (Brazil) metropolitan area. Forty-four ... ...

    Abstract Here, we describe the bacterial diversity and physicochemical properties in freshwater samples from the surface and bottom layers of the Billings Reservoir, the largest open-air storage ecosystem in the São Paulo (Brazil) metropolitan area. Forty-four samples (22 from the surface and 22 from the bottom layers) were characterized based on 16S rRNA gene analysis using Illumina MiSeq. Taxonomical composition revealed an abundance of the Cyanobacteria phylum, followed by Proteobacteria , which were grouped into 1903 and 2689 different genera in the surface and the deep-water layers, respectively. Chroobacteria , Actinobacteria , Betaproteobacteria , and Alphaproteobacteria were the most dominant classes. The Shannon diversity index was in the range of 2.3–5.39 and 4.04–6.86 in the surface and bottom layers, respectively. Flavobacterium was the most predominant pathogenic genus. Temperature and phosphorus concentrations were among the most influential factors in shaping the microbial communities of both layers. Predictive functional analysis suggests that the reservoir is enriched in motility genes involved in flagellar assembly. The overall results provide new information on the diversity composition, ecological function, and health risks of the bacterial community detected in the Billings freshwater reservoir. The broad bacterial diversity indicates that the bacterioplankton communities in the reservoir were involved in multiple essential environmental processes.
    Keywords bacterial composition ; bacterial diversity ; 16S rRNA gene ; Illumina MiSeq ; billings reservoir ; Science ; Q
    Subject code 550
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Imbalanced IL-1B and IL-18 Expression in Sézary Syndrome

    Kelly Cristina Gomes Manfrere / Marina Passos Torrealba / Frederico Moraes Ferreira / Emanuella Sarmento Alho de Sousa / Denis Miyashiro / Franciane Mouradian Emidio Teixeira / Ricardo Wesley Alberca Custódio / Helder I. Nakaya / Yasmin Alefe Leuzzi Ramos / Mirian Nacagami Sotto / Anders Woetmann / Niels Ødum / Alberto José da Silva Duarte / José Antonio Sanches / Maria Notomi Sato

    International Journal of Molecular Sciences, Vol 24, Iss 4674, p

    2023  Volume 4674

    Abstract: Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and ...

    Abstract Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and cleave to the active form by inflammasomes. In this study, we assessed the skin, serum, peripheral mononuclear blood cell (PBMC) and lymph-node samples of SS patients and control groups (healthy donors (HDs) and idiopathic erythroderma (IE) nodes) to investigate the inflammatory markers IL-1B and IL-18 at the protein and transcript expression levels, as potential markers of inflammasome activation. Our findings showed increased IL-1B and decreased IL-18 protein expression in the epidermis of SS patients; however, in the dermis layer, we detected increased IL-18 protein expression. In the lymph nodes of SS patients at advanced stages of the disease (N2/N3), we also detected an enhancement of IL-18 and a downregulation of IL-1B at the protein level. Moreover, the transcriptomic analysis of the SS and IE nodes confirmed the decreased expression of IL1B and NLRP3 , whereas the pathway analysis indicated a further downregulation of IL1B -associated genes. Overall, the present findings showed compartmentalized expressions of IL-1B and IL-18 and provided the first evidence of their imbalance in patients with Sézary syndrome.
    Keywords Sézary syndrome ; lymph nodes ; inflammasome ; IL-1B ; IL-18 ; erythroderma skin ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2023-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Preconceptional Immunization Can Modulate Offspring Intrathymic IL-17-Producing γδT Cells with Epigenetic Implications Mediated by microRNAs

    Thamires Rodrigues de-Sousa / Rodrigo Pessôa / Andrezza Nascimento / Beatriz Oliveira Fagundes / Fábio da Ressureição Sgnotto / Alberto José da Silva Duarte / Sabri Saeed Sanabani / Jefferson Russo Victor

    International Journal of Molecular Sciences, Vol 22, Iss 6633, p

    2021  Volume 6633

    Abstract: The mechanisms through which maternal immunization can modulate offspring thymic maturation of lymphocytes are not fully understood. Here, we aimed to evaluate whether maternal OVA-immunization can inhibit the maturation of IL-17-producing γδT cells in ... ...

    Abstract The mechanisms through which maternal immunization can modulate offspring thymic maturation of lymphocytes are not fully understood. Here, we aimed to evaluate whether maternal OVA-immunization can inhibit the maturation of IL-17-producing γδT cells in offspring thymus, and if this mechanism has epigenetic implications mediated by microRNAs (miRNAs) expression. Wild-type (WT) C57BL/6 females were immunized with OVA in Alum or Alum alone and were mated with normal WT males. Evaluating their offspring thymus at 3 or 20 days old (d.o.), we observed that maternal OVA immunization could inhibit the thymic frequency of offspring CD27- and IL-17 + γδT cells at the neonatal and until 20 days old. Furthermore, we evaluated the expression of function-related γ and δ variable γδTCR chains (Vγ1, Vγ2, Vγ3, Vδ4, and Vδ6.3), observing that maternal OVA-immunization inhibits Vγ2 chains expression. The small RNAs (sRNAs), particularly miRNAs, and messenger RNAs (mRNA) expression profiles by pools of thymus tissue samples (from 9 to 11 mice) from offspring OVA-immunized or Alum-immunized mothers were analyzed via Illumina sequencing platform and bioinformatics approaches. Using a fold change >4, our results showed that seven miRNAs (mmu-miR-126a-3p, 101a-3p, 744-3p,142-5p, 15a-5p, 532-5p, and 98-5p) were differentially expressed between both groups. Ten target genes were predicted to interact with the seven selected miRNAs. There were no enriched categories of gene ontology functional annotation and pathway enrichment analysis for the target genes. Interestingly, four of the identified miRNAs (mmu-miR-15a, mmu-miR-101 mmu-miR-126, and mmu-miR-142) are related to IL-17 production. Our data is of significance because we demonstrate that maternal immunization can modulate offspring thymic maturation of IL-17-producing γδT cells possibly by an epigenetic mechanism mediated by miRNAs.
    Keywords mice ; thymus ; gamma-delta T cells ; IL-17 ; microRNA ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 500
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Bacterial community composition and potential pathogens along the Pinheiros River in the southeast of Brazil

    Rafaela Garrido Godoy / Marta Angela Marcondes / Rodrigo Pessôa / Andrezza Nascimento / Jefferson Russo Victor / Alberto José da Silva Duarte / Patricia Bianca Clissa / Sabri Saeed Sanabani

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 9

    Abstract: Abstract The Pinheiros River in São Paulo, Brazil, crosses through the capital city and has its confluence with the River Tiete, which comprises several reservoirs along its course. Although Pinheiros River is considered one of the heaviest polluted ... ...

    Abstract Abstract The Pinheiros River in São Paulo, Brazil, crosses through the capital city and has its confluence with the River Tiete, which comprises several reservoirs along its course. Although Pinheiros River is considered one of the heaviest polluted rivers in Brazil, little is known about its bacterial composition, their metabolic functions or how these communities are affected by the physicochemical parameters of the river. In this study, we used the 16S rRNA gene Illumina MiSeq sequencing to profile the bacterial community from the water surface at 11 points along the course of the River. Taxonomical composition revealed an abundance of Proteobacteria phyla, followed by Firmicutes and Bacteroidetes, with a total of 233 classified bacterial families and 558 known bacterial genera. Among the 35 potentially pathogenic bacteria identified, Arcobacter was the most predominant genus. The disrupted physicochemical parameters detected in this study may possibly contribute to the composition and distribution of the bacterial community in the Pinheiros River. Predictive functional analysis suggests the River is abundant in motility genes, including bacterial chemotaxis and flagellar assembly. These results provide novel and detailed insights into the bacterial communities and putative function of the surface water in the Pinheiros River.
    Keywords Medicine ; R ; Science ; Q
    Subject code 550
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: The Potential of IgG to Induce Murine and Human Thymic Maturation of IL-10+ B Cells (B10) Revealed in a Pilot Study

    Amanda Harumi Sabô Inoue / Aline Aparecida de Lima Lira / Marília Garcia de-Oliveira / Thamires Rodrigues de Sousa / Fábio da Ressureição Sgnotto / Alberto José da Silva Duarte / Jefferson Russo Victor

    Cells, Vol 9, Iss 2239, p

    2020  Volume 2239

    Abstract: Regulatory B (B10) cells can control several inflammatory diseases, including allergies; however, the origin of peripheral B10 cells is not fully understood, and the involvement of primary lymphoid organs (PLOs) as a primary site of maturation is not ... ...

    Abstract Regulatory B (B10) cells can control several inflammatory diseases, including allergies; however, the origin of peripheral B10 cells is not fully understood, and the involvement of primary lymphoid organs (PLOs) as a primary site of maturation is not known. Here, using a murine model of allergy inhibition mediated by maternal immunization with ovalbumin (OVA), we aimed to evaluate whether B10 cells can mature in the thymus and whether IgG can mediate this process. Female mice were immunized with OVA, and offspring thymus, bone marrow, spleen, lung, and serum samples were evaluated at different times and after passive transfer of purified IgG or thymocytes. A translational approach was implemented using human nonatopic thymus samples, nonatopic peripheral blood mononuclear cells (PBMCs), and IgG from atopic or nonatopic individuals. Based on the expression of CD1d on B cells during maturation stages, we suggest that B10 cells can also mature in the murine thymus. Murine thymic B10 cells can be induced in vitro and in vivo by IgG and be detected in the spleen and lungs in response to an allergen challenge. Like IgG from atopic individuals, human IgG from nonatopic individuals can induce B10 cells in the infant thymus and adult PBMCs. Our observations suggest that B10 cells may mature in the thymus and that this mechanism may be mediated by IgG in both humans and mice. These observations may support the future development of IgG-based immunoregulatory therapeutic strategies.
    Keywords IgG ; thymus ; B cells ; B10 cells ; mouse ; human ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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