THAIS MARTINS DE LIMA
Projetos de Pesquisa
Unidades Organizacionais
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
LIM/02 - Laboratório de Anatomia Médico-Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
LIM/02 - Laboratório de Anatomia Médico-Cirúrgica, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- BONE MARROW CELLS TRANSPLANT IN SEPTIC MICE MODULATES SYSTEMIC INFLAMMATORY RESPONSE VIA CELL-CELL CONTACT(2019) LORIGADOS, Clara B.; ARIGA, Suely K. K.; LIMA, Thais M. de; BARBEIRO, Denise F.; KRIEGER, Jose E.; SORIANO, Francisco G.Sepsis is a dynamic disease, displaying an inflammatory profile that varies over time and for each organ. Controlling the inflammatory response based in targeting a single molecule has been proved useless. We hypothesized that treatment with bone marrow-derived mononuclear cells (BMDMCs) may be more efficient to modulate the systemic inflammatory response to infection. Adult male Balb/c mice were subjected to cecal ligation and puncture (CLP) or endotoxemia model of experimental sepsis. BMDMCs were separated under Ficoll gradient and injected intravenously 1 h after the procedures. Cytokines concentration was quantified in plasma, lungs, heart, and gut. Spleens, lymph nodes, and thymus were used for lymphocytes isolation and cell death assessment. All measurements were performed 2 h after BMDMCs injection. RAW264.7 macrophages and BMDMCs were cocultivated in vitro to investigate the mechanisms involved. Our data showed that an early single intravenous injection of BMDMCs in animals submitted to the murine model of endotoxemia led to the improvement of survival rate; BMDMCs persistency in lung, liver, and spleen after 24 h; decreased necrosis and apoptosis of mononuclear cells; lower TNF-a, but increased IL-10 concentration in plasma; and tissue-specific cytokine profile. In vitro experiments demonstrated that IL-6, IL-10, and nitric oxide production depends on direct contact of BMDMCs to macrophages and that TNF-a production is negatively regulated by PGE2. BMDMCs are efficient in protecting animals from endotoxemia and sepsis, reducing systemic inflammation as well as specifically modulating tissue inflammation, producing the necessary immune regulation to re-equilibrate the inflammatory response.
- The PARP inhibitor olaparib exerts beneficial effects in mice subjected to cecal ligature and puncture and in cells subjected to oxidative stress without impairing DNA integrity: A potential opportunity' for repurposing a clinically used oncological drug for the experimental therapy of sepsis(2019) AHMAD, Akbar; VIEIRA, Juliana de Camargo; MELLO, Aline Haas de; LIMA, Thais Martins de; ARIGA, Suely Kubo; BARBEIRO, Denise Frediani; BARBEIRO, Hermes Vieira; SZCZESNY, Bartosz; TORO, Gabor; DRUZHYNA, Nadiya; RANDI, Elisa B.; MARCATTI, Michela; TOLIVER-KINSKY, Tracy; KISS, Andras; LIAUDET, Lucas; SALOMAO, Reinaldo; SORIANO, Francisco Garcia; SZABO, CsabaPoly(ADP-ribose) polymerase (PARP) is involved in the pathogenesis of cell dysfunction, inflammation and organ failure during septic shock. The goal of the current study was to investigate the efficacy and safety of the clinically approved PARP inhibitor olaparib in experimental models of oxidative stress in vitro and in sepsis in vivo. In mice subjected to cecal ligation and puncture (CLP) organ injury markers, circulating and splenic immune cell distributions, circulating mediators, DNA integrity and survival was measured. In U937 cells subjected to oxidative stress, cellular bioenergetics, viability and DNA integrity were measured. Olaparib was used to inhibit PARP. The results show that in adult male mice subjected to CLP, olaparib (1-10 mg/kg i.p.) improved multiorgan dysfunction. Olaparib treatment reduced the degree of bacterial CFUs. Olaparib attenuated the increases in the levels of several circulating mediators in the plasma. In the spleen, the number of CD4 + and CD8 + lymphocytes were reduced in response to CLP; this reduction was inhibited by olaparib treatment. Treg but not Th17 lymphocytes increased in response to CLP; these cell populations were reduced in sepsis when the animals received olaparib. The Th17/Treg ratio was lower in CLP-olaparib group than in the CLP control group. Analysis of miRNA expression identified a multitude of changes in spleen and circulating white blood cell miRNA levels after CLP; olaparib treatment selectively modulated these responses. Olaparib extended the survival rate of mice subjected to CLP. In contrast to males, in female mice olaparib did not have significant protective effects in CLP. In aged mice olaparib exerted beneficial effects that were less pronounced than the effects obtained in young adult males. In in vitro experiments in U937 cells subjected to oxidative stress, olaparib (1-100 mu M) inhibited PARP activity, protected against the loss of cell viability, preserved NAD+ levels and improved cellular bioenergetics. In none of the in vivo or in vitro experiments did we observe any adverse effects of olaparib on nuclear or mitochondrial DNA integrity. In conclusion, olaparib improves organ function and extends survival in septic shock. Repurposing and eventual clinical introduction of this clinically approved PARP inhibitor may be warranted for the experimental therapy of septic shock.
- The mechanisms involved in the increased adiposity induced by interruption of regular physical exercise practice(2019) SERTIE, Rogerio A. L.; CURI, Rui; OLIVEIRA, Ariclecio C.; ANDREOTTI, Sandra; CAMINHOTTO, Rennan O.; LIMA, Thais Martins de; PROENCA, Andre R. G.; REIS, Gabriela B.; LIMA, Fabio B.Aims: We investigated the effects of physical detraining on lipogenesis/lipolysis and cellularity (apoptosis/adipogenesis) in rat subcutaneous (inguinal; SC) and visceral (retroperitoneal; RP) white adipose depots. Main methods: Three groups of male Wistar rats (6-wk old) were studied: (1) (T) trained for 12 weeks; (2) (D) trained for 8 weeks and detrained for 4 weeks; and (3) (S) age-matched sedentary. Training consisted of treadmill running sessions (1 h/day, 5 days/week, 50-60% maximal race capacity). Key findings: Physical detraining increased glucose oxidation, lipogenesis, and adipocyte size in the SC and RP depots. The number of apoptotic SC adipocytes was reduced by 53% in the T (p < 0.0001) and by 43% in the D (p < 0.001) as compared with S. RP adipocyte apoptosis in the T and D was 9.48% and 10.9% greater compared to the S, respectively (p < 0.05). In the SC stromal vascular fraction (SVF) of D rats, adiponectin, sterol regulatory element binding protein (SREBP)-1c, Peroxisome proliferator-activated receptor gamma (PPAR.), and Perilipin A mRNA expressions were more pronounced than S group, suggesting a more intense adipogenesis. This putative adipogenic effect was not observed in the RP depot. The physical detraining promoted rapid increase in the SC and RP depots however not through the same mechanisms. Significance: Physical detraining induced fat cell hypertrophy (increase of lipogenesis) in both SC and RP whereas hyperplasia (increase of adipogenesis and reduction of apoptosis) was found in SC only. These results indicate the mechanism associated with obesogenic effects of detraining varies with the fat depot.
- Chemical composition and cytotoxic screening of Musa cavendish green peels extract: Antiproliferative activity by activation of different cellular death types(2019) BARROSO, Wermerson Assuncao; ABREU, Iracelle Carvalho; RIBEIRO, Larissa Sousa; ROCHA, Claudia Quintino da; SOUZA, Heraldo Possolo de; LIMA, Thais Martins deMusa cavendish, commonly known as banana, is a fruit with nutritional and therapeutic properties. We investigated the chemical composition and in vitro cytotoxic effect of M. cavendish green peel extract (MHE) on cancer cells for the first time. The compounds characterization was performed by HPLC-UV/Vis and FIA-ESI-IT-MSn. We investigated in vitro cytotoxic effect of Musa cavendish green peels extract (MHE) in HepG2, A-375, MCF-7 and Caco-2 cancer cells. We evaluated the effect of MHE on proliferation of different cell lines through apoptosis, necrosis, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) content determination. We identified 12 compounds from different classes in the extract, including derivatives of phenolic acids, aglycone flavonoids, glycoside flavonoids and catecholamines. Our results indicate that MHE exerts, after 48 h treatment, an accentuated antiproliferative effect from the dose of 100 mu g/mL in all cell lines tested. In HepG2 cells, these effects were related to the induction of cell death, both necrotic and apoptotic, and remarkable changes in cell morphology. Depolarization of MMP and high ROS content were also observed in the cells in a dose-dependent manner. Our results show that MHE may be used as a source of new drugs with anticancer activity.
- Syzygium cumini Leaf Extract Reverts Hypertriglyceridemia via Downregulation of the Hepatic XBP-1s/PDI/MTP Axis in Monosodium L-Glutamate-Induced Obese Rats(2019) FRANCA, Lucas Martins; COELHO, Caio Fernando Ferreira; FREITAS, Larissa Nara Costa; SOUZA, Ivana Leticia Santos; CHAGAS, Vinicyus Teles; DEBBAS, Victor; LIMA, Thais Martins de; SOUZA, Heraldo Possolo de; LAURINDO, Francisco Rafael Martins; PAES, Antonio Marcus de AndradeSyzygium cumini is used worldwide for the treatment of metabolic syndrome-associated outcomes. Previously, we described the antihypertriglyceridemic effect of the hydroethanolic extract of S. cumini leaf (HESc) in monosodium L-glutamate- (MSG-) induced obese rats. This study sought to investigate the molecular mechanisms underlying the antihypertriglyceridemic effect of HESc in MSG-obese rats. Newborn male Wistar rats were injected subcutaneously with MSG (4.0 g/kg/day, obese group) or saline 1.25% (1.0 mL/kg/day, lean group), from 2nd through 10th postnatal day. At 8 weeks old, obese rats started to be orally treated with HESc (0.5 or 1.0 g/kg/day, n = 7) or saline 0.9% (1 mL/kg/day, n = 7). Lean rats received saline solution (1 mL/kg/day, n = 7). Upon 8-week treatment, animals were euthanized for blood and tissue collection. Another set of adult nonobese Wistar rats was used for the assessment of HESc acute effects on Triton WR1339-induced hypertriglyceridemia. HESc reduced weight gain, as well as adipose tissue fat pads, without altering food intake of obese rats. HESc restored fasting serum glucose, triglycerides, total cholesterol, and free fatty acids, as well as insulin sensitivity, to levels similar to lean rats. Additionally, HESc halved the triglyceride content into very low-density lipoprotein particles, as well as healed liver steatosis, in obese rats. Hepatic protein expression of the endoplasmic reticulum chaperone GRP94 was decreased by HESc, which also downregulated the hepatic triglyceride secretion pathway by reducing the splicing of X-box binding protein 1 (XBP-1s), as well as protein disulfide isomerase (PDI) and microsomal triglyceride transfer protein (MTP) translational levels. This action was further corroborated by the acute inhibitory effect of HESc on triglyceride accumulation on Triton WR1339-treated rats. Our data support the downregulation of the XBP- ls/PDI/MTP axis in the liver of MSG-obese rats as a novel feasible mechanism for the antihypertriglyceridemic effect promoted by the polyphenolic phytocomplex present in S. cumini leaf.
- CD4(+)CD69(+) T cells and CD4(+)CD25(+)FoxP3(+) Treg cells imbalance in peripheral blood, spleen and peritoneal lavage from pristane-induced systemic lupus erythematosus (SLE) mice(2019) PEIXOTO, Tatiana Vasconcelos; CARRASCO, Solange; BOTTE, Domingos Alexandre Ciccone; CATANOZI, Sergio; PARRA, Edwin Roger; LIMA, Thais Martins; UGRIUMOV, Natasha; SORIANO, Francisco Garcia; MELLO, Suzana Beatriz Verissimo de; RODRIGUES, Caio Manzano; GOLDENSTEIN-SCHAINBERG, ClaudiaBackground: Adaptive immune cells, including CD4(+)CD69(+) and CD4(+)CD25(+)FoxP3(+) regulatory T (Treg) cells, are important for maintaining immunological tolerance. In human systemic lupus erythematosus (SLE), CD4(+)CD25(+)FoxP3(+) Treg cells are reduced, whereas CD69 expression is increased, resulting in a homeostatic immune imbalance that may intensify autoreactive T cell activity. To analyze the mechanisms implicated in autotolerance failure, we evaluated CD4(+)CD69(+) and CD4(+)CD25(+)FoxP3(+) T cells and interleukin profiles in a pristane-induced SLE experimental model. Methods: For lupus induction, 26 female Balb/c mice received a single intraperitoneal 0.5 ml dose of pristane, and 16 mice received the same dose of saline. Blood and spleen samples were collected from euthanized mice 90 and 120 days after pristane or saline inoculation. Mononuclear cells from peripheral blood (PBMC), peritoneal lavage (PL) and splenocytes were obtained by erythrocyte lysis and cryopreserved for further evaluation by flow cytometry using the GuavaEasyCyte TM HT. After thawing, cells were washed and stained with monoclonal antibodies against CD3, CD4, CD8, CD25, CD28, CD69, FoxP3, CD14 and Ly6C (BD Pharmingen TM). Interleukins were quantified using Multiplex (R) MAP. The Mann-Whitney test and the Pearson coefficient were used for statistical analysis, and p < 0.05 considered significant. Results: Compared with the controls, SLE-induced animals presented increased numbers of CD4(+)CD69(+) T cells in the blood on T90 and T120 (p = 0.022 and p = 0.008) and in the spleen on T120 (p = 0.049), but there were decreased numbers in the PL (p = 0.049) on T120. The percentage of Treg was lower in blood (p < 0.005 and p < 0.012) on T90 and T120, in spleen (p = 0.043) on T120 and in PL (p = 0.001) on T90. Increased numbers of CD4+ CD69+ T cells in the PL were positively associated with high IL-2 (p = 0.486) and IFN-gamma (p = 0.017) levels, whereas reduced Treg cells in the blood were negatively correlated with TNF alpha levels (p = 0.043) and positively correlated with TGF beta 1 (p = 0.038). Conclusion: Increased numbers of CD4(+)CD69(+) T cells and reduced numbers of CD4(+)CD25(+)FoxP3(+) Treg cells with an altered interleukin profile suggests loss of autotolerance in pristane-induced lupus mice, which is similar to human lupus. Therefore, this model is useful in evaluating mechanisms of cellular activation, peripheral tolerance and homeostatic immune imbalance involved in human SLE.