EVERIDIENE KINVERLLY VIEIRA BORGES DA SILVA
Projetos de Pesquisa
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Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject RENAL SUBCAPSULAR ADMINISTRATION OF ADIPOSE DERIVED MESENCHYMAL STEM CELLS PREVENTED THE PROGRESSION OF RENAL DAMAGE IN AN EXPERIMENTAL MODEL OF CKD(2020) CLARO, Marina P.; PEREIRA, Krislley R.; SILVA, Everidiene K. V. B.; TELES, Flavio; BARBOSA, Paulyana F.; NORONHA, Irene L.; FANELLI, Camilla- Synergic Renoprotective Effects of Combined ASC Therapy with RAAS Blockade in Experimental Advanced CKD(2022) MAIRES, Marina P. C.; PEREIRA, Krislley R.; SILVA, Everidiene K. V. B.; SOUZA, Victor H. R.; TELES, Flavio; BARBOSA, Paulyana F.; GARNICA, Margoth R.; ORNELLAS, Felipe M.; NORONHA, Irene L.; FANELLI, CamillaGlobal prevalence of chronic kidney disease (CKD) has increased considerably in the recent decades. Overactivity of the renin-angiotensin-aldosterone system (RAAS), associated to renal inflammation and fibrosis, contributes to its evolution. The treatments currently employed to control CKD progression are limited and mainly based on the pharmacological inhibition of RAAS, associated with diuretics and immunosuppressive drugs. However, this conservative management promotes only partial deceleration of CKD evolution and does not completely avoid the progression of the disease and the loss of renal function, which motivates the medical and scientific community to investigate new therapeutic approaches to detain renal inflammation/fibrosis and CKD progression. Recent studies have shown the application of mesenchymal stem cells (mSC) to exert beneficial effects on the renal tissue of animals submitted to experimental models of CKD. In this context, the aim of the present study was to evaluate the effects of subcapsular application of adipose tissue-derived mSC (ASC) in rats submitted to the 5/6 renal ablation model, 15 days after the establishment of CKD, when the nephropathy was already severe. We also verify whether ASC associated to Losartan would promote greater renoprotection when compared to the respective monotherapies. Animals were followed until 30 days of CKD, when body weight, systolic blood pressure, biochemical, histological, immunohistochemical, and gene expression analysis were performed. The combination of ASC and Losartan was more effective than Losartan monotherapy in reducing systolic blood pressure and glomerulosclerosis and also promoted the complete normalization of proteinuria and albuminuria, a significant reduction in renal interstitial macrophage infiltration and downregulation of renal IL-6 gene expression. The beneficial effects of ACS are possibly due to the immunomodulatory and anti-inflammatory role of factors secreted by these cells, modulating the local immune response. Although studies are still required, our results demonstrated that a subcapsular inoculation of ASC, associated with the administration of Losartan, exerted additional renoprotective effect in rats submitted to a severe model of established CKD, when compared to Losartan monotherapy, thus suggesting ASC may be a potential adjuvant to RAAS-blockade therapy currently employed in the conservative management of CKD.
- SARS-CoV-2 Nucleocapsid Protein is Associated With Lower Testosterone Levels: An Experimental Study(2022) CARRASCO, Caio Henrique Lucio; NODA, Paloma; BARBOSA, Ana Paula; SILVA, Everidiene Kinverlly Vieira Borges da; BOMFIM, Camila Gasque; FERNANDES, Bianca Helena Ventura; TEIXEIRA, Thiago Afonso; NETO, Amaro Nunes Duarte; SALDIVA, Paulo Hilario Nascimento; ACHOA FILHO, Kamal; GUZZO, Cristiane Rodrigues; DURIGON, Edison Luiz; FONSECA, Fernando Luiz Affonso; CORAZZINI, Roseli; FANELLI, Camilla; NORONHA, Irene Lourdes; HALLAK, JorgeThe ongoing COVID-19 pandemic represents an extra burden in the majority of public and private health systems worldwide beyond the most pessimistic expectations, driving an urgent rush to develop effective vaccines and effective medical treatments against the SARS-CoV-2 pandemic. The Nucleocapsid structural viral protein is remarkably immunogenic and hugely expressed during infection. High IgG antibodies against Nucleocapsid protein (N protein) levels were detected in the serum of COVID-19 patients, confirming its pivotal antigen role for a T lymphocyte response in a vaccine microenvironment. Currently, adverse events associated with immunizations have raised some degree of concern, irrespective of its huge benefits in dealing with disease severity and decreasing mortality and morbidity. This hitherto study evaluates histological changes in rats' testes, epididymis, prostate, and seminal vesicles and analyzes hormone levels after solely N protein inoculation. Therefore, we exposed a group of Lewis rats to weekly injections of the recombinant N protein for 28 days, while a control group was inoculated with a buffer solution. The N group revealed a more significant number of spermatozoa. Spermatozoa in the seminiferous tubules were counted in twenty 400 x microscopy fields (mean of 9.2 vs. 4.6 in the control group; p < 0,01), but significantly lower testosterone levels (mean of 125.70 ng/dl vs. 309,00 ng/dl in the control group; p < 0,05) were found. No other histological and biochemical changes were displayed. Conclusively, these data suggest testicular hormonal imbalance mediated by the SARS-CoV-2 N protein that could be linked to reported post-COVID-19 syndrome hypogonadism. More relevant research might be performed to confirm this viral antigen's deleterious mechanism in the human testicular microenvironment, particular in Leydig cell function.
conferenceObject RENAL SUBCAPSULAR ADIPOSE-DERIVED MESENCHYMAL STEM CELLS (ASC) ADMINISTRATION, ASSOCIATED TO LOSARTAN TREATMENT, PREVENTED THE PROGRESSION OF RENAL DAMAGE IN AN EXPERIMENTAL MODEL OF CHRONIC KIDNEY DISEASE (CKD)(2020) CLARO, Marina P.; PEREIRA, Krislley R.; SILVA, Everidiene K. V. B.; TELES, Flavio; BARBOSA, Paulyana F.; NORONHA, Irene L.; FANELLI, Camilla- Immunization with SARS-CoV-2 Nucleocapsid protein triggers a pulmonary immune response in rats(2022) SILVA, E. K. V. B.; BOMFIM, C. G.; BARBOSA, A. P.; NODA, P.; NORONHA, I. L.; FERNANDES, B. H. V.; MACHADO, R. R. G.; DURIGON, E. L.; CATANOZI, S.; RODRIGUES, L. G.; PIERONI, F.; LIMA, S. G.; TEODORO, W. R.; QUEIROZ, Z. A. J.; SILVEIRA, L. K. R.; CHARLIE-SILVA, I.; CAPELOZZI, V. L.; GUZZO, C. R.; FANELLI, C.The SARS-CoV-2 pandemic have been affecting millions of people worldwide, since the beginning of 2020. COVID-19 can cause a wide range of clinical symptoms, which varies from asymptomatic presentation to severe respiratory insufficiency, exacerbation of immune response, disseminated microthrombosis and multiple organ failure, which may lead to dead. Due to the rapid spread of SARS-CoV-2, the development of vaccines to minimize COVID-19 severity in the world population is imperious. One of the employed techniques to produce vaccines against emerging viruses is the synthesis of recombinant proteins, which can be used as immunizing agents. Based on the exposed, the aim of the present study was to verify the systemic and immunological effects of IM administration of recombinant Nucleocapsid protein (NP), derived from SARS-CoV-2 and produced by this research group, in 2 different strains of rats (Rattus norvegicus); Wistar and Lewis. For this purpose, experimental animals received 4 injections of NP, once a week, and were submitted to biochemical and histological analysis. Our results showed that NP inoculations were safe for the animals, which presented no clinical symptoms of worrying side effects, nor laboratorial alterations in the main biochemical and histological parameters, suggesting the absence of toxicity induced by NP. Moreover, NP injections successfully triggered the production of specific anti-SARS-CoV-2 IgG antibodies by both Wistar and Lewis rats, showing the sensitization to have been well sufficient for the immunization of these strains of rats. Additionally, we observed the local lung activation of the Bronchus-Associated Lymphoid Tissue (BALT) of rats in the NP groups, suggesting that NP elicits specific lung immune response. Although pre-clinical and clinical studies are still required, our data support the recombinant NP produced by this research group as a potential immunizing agent for massive vaccination, and may represent advantages upon other recombinant proteins, since it seems to induce specific pulmonary protection. © 2022 Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.