DSpace Coleção: PMPGCF

Interações imunoendócrinas entre leptina e céluls NK na obesidade

Wed, 25 Feb 2026 00:00:00 GMT

Título: Interações imunoendócrinas entre leptina e céluls NK na obesidade Autor(es): Andrade, Arthur Gomes de Orientador: Lima, Tatjana Keesen de Souza Abstract: Obesity is a chronic disease with a high global prevalence, affecting more than 700 million people worldwide and over 40 million in Brazil. Associated with profound metabolic alterations, excessive adiposity promotes the development of a state of chronic low-grade inflammation and sustained hyperleptinemia, conditions that contribute to the dysregulation of immune homeostasis. Natural Killer (NK) cells are particularly sensitive to metabolic signals, and obese individuals frequently exhibit impaired NK cell activity. In this study, we investigated, in vitro, how leptin modulates the frequency, activation, effector molecules, and intracellular signaling of NK cells from normal-weight (NP) and obese (OB) adults. To this end, cells were exposed to two concentrations of leptin, 10 nM and 50 nM, mimicking physiological and pathophysiological levels, respectively. Sex-stratified analyses were also conducted to evaluate potential effects related to sexual dimorphism. Obesity was found to reduce the frequency of circulating NK cells, particularly in women, along with decreased expression of the activating receptors CD16 and NKp46. Upon leptin exposure, NK cells from obese donors exhibited lower granzyme B intensity and reduced IFN-y production. Leptin further modulated these responses in an adiposity-dependent manner: whereas high leptin concentrations (50 nM) increased IFN-y production in NK cells from normal-weight individuals, an opposite response was observed in cells from obese individuals. Nevertheless, no differences were observed in CD107a and TNF-a levels following leptin treatment. At the level of intracellular signaling. NK cells from obese individuals showed reduced phosphorylation of ERK 1/2 and p38 after leptin treatment, correlating with impaired cytotoxic responses and IFN-y production, respectively. In contrast, mTOR phosphorylation was intrinsically reduced in NK cells from obese donors, regardless of leptin exposure. Regarding NF-kB, no differences were observed after treatment. Sex-stratified analyses revealed higher mTOR activation and greater granzyme B expression in NK cells from normal-weight men compared with normal-weight women at high leptin concentrations, whereas leptin-mediated suppression of IFN-y production was more pronounced in men, irrespective of body phenotype. No modulation was observed in other immunological parameters in the sex-based analyses. Taken together, these findings demonstrate that leptin exerts divergent effects on NK cells depending on the metabolic context and sex, contributing to the functional impairment observed in obesity. Editor: Universidade Federal da Paraíba Tipo: Dissertação

Atividade imunomoduladora do esteroide cardiotônico BD-8 in vitro e in vivo

Fri, 26 Sep 2025 00:00:00 GMT

Título: Atividade imunomoduladora do esteroide cardiotônico BD-8 in vitro e in vivo Autor(es): Medeiros, Anna Beatriz Araujo Orientador: Mascarenhas, Sandra Rodrigues Abstract: Cardiotonic steroids (CTS) are compounds known to bind to the Na+/K+-ATPase and modulate various biological processes, including the immune response. γ-Benzylidene digoxin 8 (BD-8) is a synthetic CTS with immunomodulatory activity. Its action has been shown to reduce phagocytic activity, nitric oxide (NO) levels, and the pro-inflammatory cytokine IL-1β in murine peritoneal macrophages. Furthermore, BD-8 also reduced iNOS expression and the phosphorylation of NF-κB, ERK, and p38; however, further studies are needed to elucidate its action. Therefore, the objective of this study was to evaluate the immunomodulatory activity of BD-8 in murine peritoneal macrophages in vitro by analyzing Akt, mTOR, and Src proteins and in vivo in models of paw edema and acute lung injury (ALI). For in vitro tests, female Swiss albino mice were previously stimulated with an intraperitoneal (i.p.) injection of 4% thioglycolate. Macrophages from peritoneal lavage were cultured and stimulated with zymosan (0.2 mg/mL) and/or treated with BD-8 (10 μM) for 24 hours, for subsequent analysis of Akt, mTOR, and Src proteins by flow cytometry. For in vivo tests, in the paw edema model, the mice were treated with an i.p. injection of BD-8 (1.12 mg/kg; 0.56 mg/kg, and 0.28 mg/kg) and stimulated with an intraplantar injection of carrageenan (2.5%). Paw thickness was quantified using a digital caliper, and histological analysis of the paw was also performed. In the ALI model, the animals were stimulated with LPS via nasal instillation (5 mg/kg) and treated (i.p.) with BD-8 (0.56 mg/kg and 0.28 mg/kg) at 1, 24, and 48 hours after the LPS challenge. Bronchoalveolar lavage fluid (BALF) was collected and a blood smear was performed for analysis. As a result, it was seen that BD-8 negatively modulated Akt, mTOR, and Src proteins in vitro. Furthermore, this molecule also reduced paw edema at doses of 0.56 mg/kg and 0.28 mg/kg, showing a greater effect at the lowest dose tested; this result was also seen in the histological analysis. In the ALI model, BD-8, at the lowest dose tested, reduced cell migration, and at doses of 0.56 mg/kg and 0.28 mg/kg, it reduced neutrophils in bronchoalveolar lavage fluid (BALF). Additionally, the lowest dose tested also reduced total protein levels and the pro-inflammatory cytokine TNF-α in BALF. Histological analysis of lung tissue showed a reduction in ALI characteristics. Treatment with BD-8 did not modulate the number of blood leukocytes, indicating local action of the compound during the period tested. Therefore, this work contributes to the development of new substances with therapeutic potential, in addition to expanding the understanding of the BD-8 molecule and its ability to modulate biological and inflammatory processes. Editor: Universidade Federal da Paraíba Tipo: Dissertação

Efeitos do consumo de Konjac glucomanano (Konjac Massa mf®) sobre o perfil glicêmico e parâmetros metabólicos de camundongos com diabetes tipo 1 induzido por STZ

Thu, 29 Feb 2024 00:00:00 GMT

Título: Efeitos do consumo de Konjac glucomanano (Konjac Massa mf®) sobre o perfil glicêmico e parâmetros metabólicos de camundongos com diabetes tipo 1 induzido por STZ Autor(es): Andrade, Juliana Teles Orientador: Cruz, Josiane Campos Abstract: Type 1 diabetes mellitus (T1DM) is a metabolic condition characterized by immune- mediated destruction of pancreatic beta cells. Therapies aimed at enhancing insulin levels and sensitivity are essential for individuals with T1DM. Dietary interventions, particularly those involving dietary fibers, have emerged as promising non-pharmacological approaches for glycemic control. Konjac glucomannan (KGM) has shown notable hypoglycemic properties in animal models of T1DM. Thus, this study aimed to evaluate the effects of KGM, in the form of the commercial product Konjac Massa MF®, on the glycemic and lipid profiles of mice with STZ-induced T1DM. Male C57BL/6J mice rendered diabetic with streptozotocin (STZ) were treated with Konjac Massa MF® (120 mg/kg/day intragastric way) for four weeks. During the treatment period, glycemia, weight gain, water and food consumption were monitored. Glucose (IPGTT) and insulin (IPITT) tolerance tests were performed, followed by plasma collection for biochemical analyses. The results demonstrated a significant reduction in fasting glycemia in diabetic mice treated from the third week compared to untreated diabetics (245.20 ± 26.91 vs. 412.10 ± 25.18 mg/dL). However, no significant difference in glucose tolerance was observed between treated and untreated diabetic groups. The treated group exhibited improved insulin sensitivity (209.90 ± 57.20 vs. 378.50 ± 61.97 mg/dL; 60 min: 213.70 ± 48.49 vs. 361.00 ± 61.34 mg/dL; 90 min: 197.90 ± 51.85 vs. 316.30 ± 60.74 mg/dL; 120 min: 234.50 ± 59.23 vs. 318.30 ± 54.78 mg/dL). Treatment also resulted in reduced levels of serum MDA (17.10 ± 1.51 vs. 26.42 ± 1.48 nmol/dL), cholesterol (59.39 ± 8.61 vs. 156.83 ± 32.42 mg/dL), creatinine (1.46 ± 0.14 vs. 2.08 ± 0.23 nmol/dL), and ALT (39.39 ± 6.89 vs. 82.83 ± 25.19 nmol/dL). In conclusion, Konjac Massa MF® shows promise as a therapeutic agent for enhancing insulin sensitivity and hepatic function in T1DM models. Further research is warranted to elucidate the underlying protective mechanisms of KGM and to determine its clinical applicability in managing T1DM and its associated complications. Editor: Universidade Federal da Paraíba Tipo: Dissertação

Avaliação da variabilidade da frequência cardíaca e da pressão arterial em pacientes com teste positivo para COVID-19 em Unidade de Saúde da Família de João Pessoa - Paraíba

Fri, 04 Oct 2024 00:00:00 GMT

Título: Avaliação da variabilidade da frequência cardíaca e da pressão arterial em pacientes com teste positivo para COVID-19 em Unidade de Saúde da Família de João Pessoa - Paraíba Autor(es): Aguiar, Cecília Burle de Orientador: Balarini, Camille de Moura Abstract: The COVID-19 pandemic has significantly impacted public health, including cardiovascular autonomic dysfunctions. This study evaluated the effects of COVID-19 on autonomic regulation in patients approximately 113 days post-infection using heart rate variability (HRV) parameters and the Valsalva maneuver response. Fifty-eight participants were analyzed, comprising 29 previously infected individuals and 29 healthy controls recruited from the Verde Vida Family Health Unit in João Pessoa, Paraíba. Post-COVID-19 patients exhibited autonomic imbalance characterized by reduced vagal modulation, as evidenced by decreased RMSSD (control group: 41.63 ± 4.92; COVID-19 group: 29.98 ± 4.32; p = 0.048) and SD1 (control group: 29.47 ± 3.48; COVID-19 group: 21.22 ± 3.06; p = 0.048), positively correlated with the parasympathetic nervous system (PNS) index (control group: -0.64 (-1.40 – 0.49); COVID-19 group: -1.14 (-1.57 – (-0.64)); p = 0.029). Baroreflex sensitivity was also reduced, demonstrated by the lack of pressure reduction after the Valsalva maneuver in post-COVID-19 patients (mean arterial pressure, MAP, at rest: 94.98 ± 3.11 mmHg; post-MV: 93.31 ± 2.76 mmHg; p = 0.159), unlike the control group (MAP at rest: 93.32 ± 2.46 mmHg; post-MV: 88.47 ± 2.39 mmHg; p = 0.005). Infection severity correlated positively with age (r = 0.717; p < 0.001), resting systolic blood pressure (SBP; r = 0.458; p = 0.013), and stress index (r = 0.411; p = 0.027), suggesting sympathetic hyperactivity and greater cardiovascular burden in more severely affected individuals. This study underscores the association between COVID-19 and autonomic regulation alterations, irrespective of initial infection severity. Despite limitations such as small sample size and lack of pre-infection data, the findings enhance the understanding of the disease's long-term effects. HRV emerges as a non-invasive tool applicable to autonomic nervous system (ANS) monitoring, with potential to guide management strategies across all levels of post-COVID-19 healthcare. Editor: Universidade Federal da Paraíba Tipo: Tese