RESUMO
The mammary gland is an exocrine gland whose main function is to produce milk. Breast morphogenesis begins in the embryonic period; however, its greatest development takes place during the lactation period. Studies have found the expression of serum amyloid A protein (SAA) in both breast cells and breast milk, yet the function of this protein in these contexts remains unknown. Insufficient milk production is one of the most frequent reasons for early weaning, a problem that can be related to the mother, the newborn, or both. This study aims to investigate the relationship between lactogenesis II (the onset of milk secretion) and the role of SAA in the human breast. To this end, mammary epithelial cell cultures were evaluated for the expression of SAA and the influence of various cytokines. Additionally, we sought to assess the activation pathway through which SAA acts in the breast, its glucose uptake capacity, and the morphological changes induced by SAA treatment. SAA expression was observed in mammary epithelial cells; however, it was not possible to establish its activation pathway, as treatments with inhibitors of the ERK1/2, p38MAPK, and PI3K pathways did not alter its expression. This study demonstrated that SAA can stimulate IL-6 expression, inhibit glucose uptake, and cause morphological changes in the cells, indicative of cellular stress. These mechanisms could potentially contribute to early breastfeeding cessation due to reduced milk production and breast involution.
Assuntos
Interleucina-6 , Glândulas Mamárias Humanas , Proteína Amiloide A Sérica , Proteína Amiloide A Sérica/metabolismo , Humanos , Feminino , Interleucina-6/metabolismo , Glândulas Mamárias Humanas/metabolismo , Leite Humano/metabolismo , Células Epiteliais/metabolismo , Lactação/metabolismo , Mama/metabolismo , Glucose/metabolismoRESUMO
Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An adequate T cell response is essential not only for fighting disease but also for the creation of immune memory. Thus, the present study aims to evaluate the T cells of patients with moderate, severe and critical COVID-19 not only at the time of illness but also 2 months after diagnosis to observe whether changes in this compartment persist. In this study, 166 COVID-19 patients were stratified into moderate/severe and critical disease categories. The maturation and activation of T cells were evaluated through flow cytometry. In addition, Treg cells were analysed. Until 15 days after diagnosis, patients presented a reduction in absolute and relative T lymphocyte counts. After 2 months, in moderate/severe patients, the counts returned to a similar level as that of the control group. In convalescent patients who had a critical illness, absolute T lymphocyte values increased considerably. Patients with active disease did not show differentiation of T cells. Nonetheless, after 2 months, patients with critical COVID-19 showed a significant increase in CD4+ EMRA (CD45RA+ effector memory) T lymphocytes. Furthermore, COVID-19 patients showed delayed T cell activation and reduced CD8+ suppressor T cells even 2 months after diagnosis. A reduction in CD4+ Treg cells was also observed, and their numbers returned to a similar level as that of healthy controls in convalescent patients. The results demonstrate that COVID-19 patients have a delayed activation and differentiation of T cells. In addition, these patients have a great reduction of T cells with a suppressor phenotype.
Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Diferenciação CelularRESUMO
Imidazo[1,2-a]pyridines (IPs) have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of IP derivatives by screening their ability as a pro-oxidant. IP derivatives were synthesized and oral bioavailability and toxicity were analyzed in silico. Redox screening was performed on human Kasumi, KG-1, K562, and Jurkat leukemia cells. The IP derivative and the most responsive leukemic cell were selected for cytotoxicity, cell proliferation, cell senescence, and oxidative stress assays. The predictive toxicity analysis showed a possible effect on the reproductive system, but without mutagenic, carcinogenic, or irritability effects. MRK-107 against K562 cells was the compound that showed the best redox profile. MRK-107 did not induce cell death in K562 and monocyte cells. However, this compound was able to decrease cell proliferation and increase cell senescence after 48 and 72 h. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72 h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress is a possible mechanism of action, addressing this compound as a potential antitumor drug against chronic myeloid leukemia.
Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide , Humanos , Apoptose , Estresse Oxidativo , Antineoplásicos/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Proliferação de Células , Senescência Celular , Piridinas/farmacologia , Células K562RESUMO
Exclusive breast milk is the diet recommended by the World Health Organization (WHO) until 6 months of age. However, breastfeeding has the potential of transferring certain toxic chemicals from the mother to the infant. Bisphenol A (BPA) is a synthetic chemical used as a monomer in polycarbonate plastics and epoxy resins. Information on BPA concentration in the breast milk of lactating mothers is very limited; thus, this study aimed to determine the concentration of BPA in the colostrum of 64 post-partum women at a university-affiliated tertiary hospital in South Brazil. The results showed that all the breast milk samples contained a high concentration of BPA with a median value of 34.18 ng/mL. Furthermore, the concentration of BPA in mothers was influenced by the consumption of foods packaged in plastic packaging, especially when the plastic is heated (p = 0.0182). The total daily intake of BPA in breastfed infants was 19.5 µg/kg/day and 28.5 µg/kg/day was recorded at the 95th percentile of body weight per day, which is higher than the maximum daily intake estimated by the European Authority of Food Safety. These data showed a high concentration of BPA in the breastmilk of the lactating mothers which might be through the use of plastic containers as food/drink packages. This is of public health importance as the high concentration of BPA in their breast milk can be an indicator of potentially serious health problems in these mothers and much more in the babies breastfed with BPA-contaminated breast milk.
Assuntos
Lactação , Mães , Lactente , Humanos , Feminino , Carga Corporal (Radioterapia) , Brasil , Leite Humano/química , Compostos Benzidrílicos/análise , PlásticosRESUMO
The present study investigated the effects of perinatal exposure to glyphosate-based herbicide (GBH) in offspring's liver. Pregnant Wistar rats were exposed to GBH (70 mg glyphosate/Kg body weight/day) in drinking water from gestation day 5 to postnatal day 15. The perinatal exposure to GBH increased 45Ca2+ influx in offspring's liver. Pharmacological tools indicated a role played by oxidative stress, phospholipase C (PLC) and Akt pathways, as well as voltage-dependent Ca2+ channel modulation on GBH-induced Ca2+ influx in offspring's liver. In addition, changes in the enzymatic antioxidant defense system, decreased GSH content, lipid peroxidation and protein carbonylation suggest a connection between GBH-induced hepatotoxic mechanism and redox imbalance. The perinatal exposure to GBH also increased the enzymatic activities of transaminases and gamma-glutamyl transferase in offspring's liver and blood, suggesting a pesticide-induced liver injury. Moreover, we detected increased iron levels in liver, blood and bone marrow of GBH-exposed rats, which were accompanied by increased transferrin saturation and decreased transferrin levels in blood. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were increased in the liver of rats perinatally exposed to GBH, which were associated with. Increased phospho-p65NFκB immunocontent. Therefore, we propose that excessive amounts of iron in offspring's liver, blood and bone marrow induced by perinatal exposure to GBH may account for iron-driven hepatotoxicity, which was associated with Ca2+ influx, oxidative damage and inflammation. Further studies will clarify whether these events can ultimately impact on liver function.
Assuntos
Água Potável , Herbicidas , Hepatopatias , Praguicidas , Animais , Antioxidantes , Feminino , Glicina/análogos & derivados , Herbicidas/toxicidade , Interleucina-6 , Ferro , Gravidez , Proteínas Proto-Oncogênicas c-akt , Ratos , Ratos Wistar , Transaminases , Transferrinas , Fator de Necrose Tumoral alfa , Fosfolipases Tipo C , GlifosatoRESUMO
Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and marked by an intense inflammatory response and immune dysregulation in the most severe cases. In order to better clarify the relationship between peripheral immune system changes and the severity of COVID-19, this study aimed to evaluate the frequencies and absolute numbers of peripheral subsets of neutrophils, monocytes, and dendritic cells (DCs), in addition to quantifying the levels of inflammatory mediators. One hundred fifty-seven COVID-19 patients were stratified into mild, moderate, severe, and critical disease categories. The cellular components and circulating cytokines were assessed by flow cytometry. Nitric oxide (NOx) and myeloperoxidase (MPO) levels were measured by colourimetric tests. COVID-19 patients presented neutrophilia, with signs of emergency myelopoiesis. Alterations in the monocytic component were observed in patients with moderate to critical illness, with an increase in classical monocytes and a reduction in nonclassical monocytes, in addition to a reduction in the expression of HLA-DR in all subtypes of monocytes, indicating immunosuppression. DCs, especially plasmacytoid DCs, also showed a large reduction in moderate to critical patients. COVID-19 patients showed an increase in MPO, interleukin (IL)-12, IL-6, IL-10, and IL-8, accompanied by a reduction in IL-17A and NOx. IL-10 levels ≥14 pg/ml were strongly related to the worst outcome, with a sensitivity of 78·3% and a specificity of 79·1%. The results of this study indicate the presence of systemic effects induced by COVID-19, which appear to be related to the pathophysiology of the disease, highlighting the potential of IL-10 as a possible prognostic biomarker for COVID-19.
Assuntos
COVID-19 , SARS-CoV-2 , Estudos Transversais , Citocinas/metabolismo , Humanos , Imunidade , Índice de Gravidade de DoençaRESUMO
Chalcones and their derivatives have been described as promising compounds with antiproliferative activity against leukemic cells. This study aimed to investigate the cytotoxic effect of three synthetic chalcones derived from 1-naphthylacetophenone (F07, F09, and F10) in acute leukemia cell lines (K562 and Jurkat) and examine the mechanisms of cell death induced by these compounds. The three compounds were cytotoxic to K562 and Jurkat cells, with IC50 values ranging from 1.03 to 31.66 µM. Chalcones induced intrinsic and extrinsic apoptosis, resulting in activation of caspase-3 and DNA fragmentation. F07, F09, and F10 were not cytotoxic to human peripheral blood mononuclear cells, did not produce any significant hemolytic activity, and did not affect platelet aggregation after ADP stimulation. These results, combined with calculations of molecular properties, suggest that chalcones F07, F09, and F10 are promising molecules for the development of novel antileukemic drugs.
Assuntos
Acetofenonas/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Chalconas/farmacologia , Acetofenonas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Chalconas/síntese química , Chalconas/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Obesity is a global health problem and is associated with a chronic low-grade inflammatory state. Surgical obesity treatment is being increasingly common due to its efficacy. From this, we evaluate the metabolic state improvement and inflammation remission in patients with obesity undergoing bariatric surgery. Methods: The clinical data and serum levels of leptin and adiponectin were assessed in patients with obesity before and one, three and six months after bariatric surgery. Also, serum amyloid A (SAA), monocyte chemoattractant protein-1 (MCP-1) levels were measured during the follow-up surgery and compared with a lean group of individuals. Results: Weight loss decreased body mass index (BMI), comorbidities percentage, drugs use and leptin levels. Adiponectin levels increased after surgery. SAA and MCP-1 showed no difference after surgery, but a trend decrease for MCP-1 and a significant decrease was observed when the patients with obesity were compared to the lean participants. Conclusion: Bariatric surgery alters metabolic status improving obesity-related comorbidities and the adiposity biomarkers leptin and adiponectin, but not inflammatory cytokines SAA and MCP-1.
Assuntos
Adiposidade/fisiologia , Cirurgia Bariátrica , Quimiocina CCL2/sangue , Inflamação/sangue , Proteína Amiloide A Sérica/análise , Adiponectina/sangue , Adulto , Biomarcadores/sangue , Comorbidade , Feminino , Seguimentos , Derivação Gástrica , Humanos , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Adulto JovemRESUMO
Liver cirrhosis is often complicated by an immunological imbalance known as cirrhosis-associated immune dysfunction. This study aimed to investigate disturbances in circulating monocytes and dendritic cells in patients with acute decompensation (AD) of cirrhosis. The sample included 39 adult cirrhotic patients hospitalized for AD, 29 patients with stable cirrhosis (SC), and 30 healthy controls (CTR). Flow cytometry was used to analyze monocyte and dendritic cell subsets in whole blood and quantify cytokines in plasma samples. Cirrhotic groups showed higher frequencies of intermediate monocytes (iMo) than CTR. AD patients had lower percentages of nonclassical monocytes than CTR and SC. Cirrhotic patients had a profound reduction in absolute and relative dendritic cell numbers compared with CTR and showed higher plasmacytoid/classical dendritic cell ratios. Increased plasma levels of IL-6, IL-10, and IL-17A, elevated percentages of CD62L+ monocytes, and reduced HLA-DR expression on classical monocytes (cMo) were also observed in cirrhotic patients. Patients with more advanced liver disease showed increased cMo and reduced tissue macrophages (TiMas) frequencies. It was found that cMo percentages greater than 90.0% within the monocyte compartment and iMo and TiMas percentages lower than 5.7% and 8.6%, respectively, were associated with increased 90-day mortality. Monocytes and dendritic cells are deeply altered in cirrhotic patients, and subset profiles differ between stable and advanced liver disease. High cMo and low TiMas frequencies may be useful biomarkers of disease severity and mortality in liver cirrhosis.
Assuntos
Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Adulto , Idoso , Biomarcadores , Estudos de Casos e Controles , Contagem de Células , Plasticidade Celular , Citocinas/metabolismo , Suscetibilidade a Doenças , Feminino , Humanos , Imunofenotipagem , Mediadores da Inflamação/metabolismo , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de DoençaRESUMO
ABSTRACT Acute promyelocytic leukemia is a subtype of acute myeloid leukemia, characterized by the presence of neoplastic promyelocytes, due to the reciprocal balanced translocation between chromosomes 15 and 17. Currently, with the use of agents that act directly on this molecular change, such as all-trans retinoic acid and arsenic trioxide, APL has shifted from a highly mortal to a curable disease. However, some cases are still at high risk of death, especially early death, and acquiring a better understanding of the clinical and biological factors involving APL is needed to correctly identify and treat such cases. The early suspected diagnosis and prompt initiation of the target therapy are important for better response rates. The follow-up and outcomes, using real-life data from 44 consecutive APL patients, were studied between 2001 and 2013. The overall survival rate was 82.7% and early death was 16%. Almost all patient deaths were due to severe bleeding, which was confirmed by multivariate analysis, as the most important prognostic factor leading to death. A better understanding the pathogenesis of the hemorrhagic complications in APL is needed, as well as the risk factors associated with early death in APL patients, as this has become synonymous with overall mortality.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/terapia , Proteína SUMO-1RESUMO
Thrombophilic disorders are found in 50% of patients with venous thromboembolism, and factor V Leiden (FVL) is the most common genetic risk factor for the development of these conditions. FVL prevalence varies according to population group. In Europe, many countries have a high prevalence of the mutation, including Portugal, Germany, and Italy. Santa Catarina State, southern Brazil, was colonized by different European nations; most inhabitants are descendants of Portuguese, Italian, and German immigrants. There are, however, no data on the prevalence of FVL in the state. This study aimed to determine FVL prevalence in a healthy population in Santa Catarina and assess whether there is an association between the mutation and demographic characteristics, thereby contributing to the understanding of the heterogeneity of prevalence of this important VTE risk factor and racial or geographical differences in the incidence of thrombotic diseases. Analysis of the FVL mutation was performed on 400 blood donors using the PCR technique followed by enzymatic digestion. The findings show that 2.5% of the participants were heterozygous for FVL, and none were homozygous. No association was found between the presence of FVL in heterozygosis and individual characteristics. In conclusion, this study found a prevalence of FVL in heterozygosis of 2.5% among healthy individuals in Santa Catarina, Brazil. Further studies are needed to assess the prevalence of FVL in other regions of the country, determine the distribution of the mutation among population groups, and evaluate how these factors affect the incidence of thrombotic diseases.
Assuntos
Deficiência do Fator V/epidemiologia , Deficiência do Fator V/genética , Fator V/genética , Sistema ABO de Grupos Sanguíneos/genética , Adulto , Tipagem e Reações Cruzadas Sanguíneas , Brasil/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Adulto JovemRESUMO
Acute promyelocytic leukemia is a subtype of acute myeloid leukemia, characterized by the presence of neoplastic promyelocytes, due to the reciprocal balanced translocation between chromosomes 15 and 17. Currently, with the use of agents that act directly on this molecular change, such as all-trans retinoic acid and arsenic trioxide, APL has shifted from a highly mortal to a curable disease. However, some cases are still at high risk of death, especially early death, and acquiring a better understanding of the clinical and biological factors involving APL is needed to correctly identify and treat such cases. The early suspected diagnosis and prompt initiation of the target therapy are important for better response rates. The follow-up and outcomes, using real-life data from 44 consecutive APL patients, were studied between 2001 and 2013. The overall survival rate was 82.7% and early death was 16%. Almost all patient deaths were due to severe bleeding, which was confirmed by multivariate analysis, as the most important prognostic factor leading to death. A better understanding the pathogenesis of the hemorrhagic complications in APL is needed, as well as the risk factors associated with early death in APL patients, as this has become synonymous with overall mortality.
RESUMO
ABSTRACT Objective: The aim of this study was to describe the characteristics of blood donors and the serological profile of the blood donations at the blood bank of the University Hospital Polydoro Ernani de São Thiago of the Federal University of Santa Catarina from January 2011 to December 2016. Methods: The characteristics of donors and the serological results of the donated blood were compiled from databases. Only donations with a negative serology or a positive serology confirmed by second-sample testing were included in the study. Results: A total of 14,368 donations were included in the study, of which 118 (0.8%) had a confirmed positive serology. Of the total donations, 94.3% were from spontaneous donations and 5.7% from replacement donation. Donations were predominantly from men (54.1%), individuals aged 18 to 29 years (69.1%), and repeat donors (47.7%). Detection rates were higher for HBV (0.63%), followed by syphilis (0.13%), HIV (0.05%), HCV (0.02%), and Chagas disease (0.01%). With the exception of HIV, positive results were more frequent in the older age groups. Positive results for HBV, HCV, and HIV were more frequent among first-time donors. Replacement donations were more likely to have HBV (OR 7.7; 95% CI 4.9-12.1, p < 0.0001) and HIV (OR 6.7; 95% CI 1.3-34.7; p = 0.02) than spontaneous donations. Conclusion: This study showed that the frequency of infections in blood donations at the HU-UFSC blood bank was lower than the national estimates and that our population may have a greater prevalence of syphilis among older donors
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Sorologia , Bancos de Sangue , Doadores de SangueRESUMO
OBJECTIVE: The aim of this study was to describe the characteristics of blood donors and the serological profile of the blood donations at the blood bank of the University Hospital Polydoro Ernani de São Thiago of the Federal University of Santa Catarina from January 2011 to December 2016. METHODS: The characteristics of donors and the serological results of the donated blood were compiled from databases. Only donations with a negative serology or a positive serology confirmed by second-sample testing were included in the study. RESULTS: A total of 14,368 donations were included in the study, of which 118 (0.8%) had a confirmed positive serology. Of the total donations, 94.3% were from spontaneous donations and 5.7% from replacement donation. Donations were predominantly from men (54.1%), individuals aged 18 to 29 years (69.1%), and repeat donors (47.7%). Detection rates were higher for HBV (0.63%), followed by syphilis (0.13%), HIV (0.05%), HCV (0.02%), and Chagas disease (0.01%). With the exception of HIV, positive results were more frequent in the older age groups. Positive results for HBV, HCV, and HIV were more frequent among first-time donors. Replacement donations were more likely to have HBV (OR 7.7; 95% CI 4.9-12.1, pâ¯<â¯0.0001) and HIV (OR 6.7; 95% CI 1.3-34.7; pâ¯=â¯0.02) than spontaneous donations. CONCLUSION: This study showed that the frequency of infections in blood donations at the HU-UFSC blood bank was lower than the national estimates and that our population may have a greater prevalence of syphilis among older donors.
RESUMO
In 2010, new monoclonal antibodies were submitted to the 9th International Workshop on Human Leukocyte Differentiation Antigens, and there are few studies demonstrating normal expression patterns of these markers. Thus, the objective of this study was to determine the normal patterns of cell expression of CD86, CD210a, CD261, CD262, CD264, CD358, and CD361 in peripheral blood (PB) and bone marrow (BM) samples by flow cytometry. In the present study, CD86 was expressed only in monocytes and B lymphocytes in PB and in monocytes and plasma cells in BM. Regarding CD210a expression, in PB samples, monocytes and NK cells showed weak expression, while neutrophils, B and T lymphocytes, and basophils showed weak and partial expression. In BM samples, expression of CD210a was observed in eosinophils, monocytes, and B and T/NK lymphocytes. Weak expression of CD210a was also observed in neutrophilic cells and plasma cells. All B cell maturation stages had weak expression of CD210a except for immature B cells, which did not express this marker. In the present study, no cell type in PB samples showed positivity for CD261 and, in BM samples, there was very weak expression in neutrophilic series, monocytes, and B lymphocytes. Conversely, plasma cells showed positivity for CD261 with a homogeneous expression. For CD262, there was weak expression in monocytes, neutrophils, and B lymphocytes in PB samples and weak expression in monocytes, B lymphocytes, and plasma cells in BM samples. The evaluation of CD264 showed very weak expression in B cells in PB samples and no expression in BM cells. Very weak expression of CD358 was observed in neutrophils, monocytes, and B lymphocytes in PB and BM samples. In addition, in BM samples, plasma cells and T lymphocytes showed weak expression of CD358. In relation to the maturation stages of B cells, there was weak expression in pro-B cel, pre-B cell, and mature B cell. In the present study, it was possible to observe expression of CD361 in all cell types analyzed in PB and BM samples. The analyzed markers presented varied profiles of expression and, in some cases, these profiles were different from those observed in other studies. Further studies are needed to evaluate these molecules, mainly in relation to a possible application in the diagnosis of hematological malignancies or as new therapeutic targets for the treatment of hematological neoplasms or autoimmune diseases.
Assuntos
Antígenos CD/imunologia , Células Sanguíneas/imunologia , Células da Medula Óssea/imunologia , Citometria de Fluxo , Regulação da Expressão Gênica/imunologia , Adolescente , Adulto , Idoso , Células Sanguíneas/citologia , Células da Medula Óssea/citologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: B cell lymphomas' (BCL) current diagnosis is usually based on a combination of morphology, immunophenotype, recurrent cytogenetic aberration and clinical features. However, even with these diagnostic tools, a definitive diagnosis can be difficult to achieve. Therefore, the aim of this study was to assess the profile of CD39, CD43, CD81, and CD95 expressions in diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and Burkitt lymphoma (BL) cases. METHODS: To address this issue, we investigated the expression of CD39, CD43, CD81, and CD95 by eight-color flow cytometry in retrospective cases from 2014 to 2016. RESULTS: The study included 27 adult patients diagnosed with DLBCL, FL, and BL during the study period. Four patients were diagnosed with germinal center B cell-like DLBCL (GCB DLBCL), seven with non-GCB DLBCL, nine with FL, and seven with BL. CD39 seems to be especially relevant to differentiate non-GCB DLBCL from BL and from FL. BL showed stronger expression of CD43 when compared to FL and GCB DLBCL. Moreover, CD43 may help to distinguish non-GCB DLBCL from GCB DLBCL. CD81 expression was much stronger in BL when compared to the other three groups of patients. Lastly, CD95 may also help to distinguish BL from the other subtypes, as BL cells expressed this antigen at low levels. CONCLUSIONS: In combination, CD39, CD43, CD81, and CD95 expressions appear to be helpful to distinguish CD10+ BCL, particularly BL. Phenotypic distinction between FL and GCB DLBCL remains challenging and requires further studies. © 2017 International Clinical Cytometry Society.
Assuntos
Apirase/metabolismo , Leucossialina/metabolismo , Linfoma Difuso de Grandes Células B/metabolismo , Tetraspanina 28/metabolismo , Receptor fas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/metabolismo , Biomarcadores Tumorais/metabolismo , Linfoma de Burkitt/metabolismo , Feminino , Citometria de Fluxo/métodos , Centro Germinativo/metabolismo , Humanos , Imunofenotipagem/métodos , Linfoma Folicular/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVES: Since complement system has been recently associated with metabolic and cardiovascular diseases, and closely related to insulin resistance, we investigated the association of plasma complement factor 3 (C3) and factor 4 (C4) with insulin sensibility and weight loss after bariatric surgery. METHODS: Serum levels of C3, C4, total cholesterol, triacylglycerol, HDL-cholesterol, LDL-cholesterol and homeostatic model assessment (HOMA-IR) measurements were assessed in morbidly obese patients before and after bariatric surgery, including a 6-month follow-up period, as well as a comparison with a lean group. RESULTS: Weight loss decreased body mass index (BMI), serum triacylglycerol, and increased serum HDL-cholesterol and insulin sensitivity, as expected. C3 and C4 were significantly higher in obese individuals when compared to lean subjects (p<0.001). In addition, C3 and C4 positively correlated with BMI and HOMA-IR, however, only C3 were significantly decreased 6months after surgery. CONCLUSION: C3 was strongly associated with insulin sensitivity after bariatric surgery.
Assuntos
Cirurgia Bariátrica , Complemento C3/metabolismo , Resistência à Insulina , Obesidade Mórbida/sangue , Obesidade Mórbida/cirurgia , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Complemento C4/metabolismo , Feminino , Seguimentos , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Período Pós-OperatórioRESUMO
Pyrazoline is an important 5-membered nitrogen heterocycle that has been extensively researched. Ten derivatives were synthesized and tested for antileukemic effects on 2 human acute leukemia cell lines, K562 and Jurkat. The most cytotoxic of these derivatives, compound 21, was chosen for investigation of cytotoxicity mechanisms. The results obtained with selectivity calculations revealed that compound 21 is more selective for acute leukemia (K562 and Jurkat cell lines) than for other tumor cell lines. Moreover, compound 21 was not cytotoxic to normal cell lines, indicating a potential use in clinical tests. Compound 21 caused a significant cell cycle arrest in the S-phase in Jurkat cells and increased the proportion of cells in the sub G0/G1 phase in both cell lines. Cells treated with compound 21 demonstrated morphological changes characteristic of apoptosis in the EB/AO assay, confirmed by externalization of phosphatidylserine by the annexin V - fluorescein isothiocyanate method and by DNA fragmentation. An investigation of cytotoxicity mechanisms suggests the involvement of an intrinsic apoptosis pathway due to mitochondrial damage and an increase in the ratio of mitochondrial Bax/Bcl2. Pyrazoline 21 obeyed Lipinski's "rule of five" for drug-likeness. Based on these preliminary results, the antileukemic activity of compound 21 makes it a potential anticancer agent.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Leucemia/patologia , Pirazóis/química , Pirazóis/farmacologia , Antineoplásicos/farmacocinética , Coagulação Sanguínea/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Simulação por Computador , Fragmentação do DNA/efeitos dos fármacos , Humanos , Células Jurkat , Células K562 , Pirazóis/farmacocinética , Transdução de Sinais/efeitos dos fármacosRESUMO
ABSTRACT When the FLT3 gene is mutated, it originates a modified receptor with structural changes, which give survival advantage and malignant hematopoietic cell proliferation. Thus, the presence of mutations in this gene is considered an unfavorable prognostic factor. A total of 85 consecutive samples of newly diagnosed untreated patients with AL were included in the study after they provided their informed consent. FLT3 gene mutations were detected by PCR. For the pediatric group, a positive correlation was observed between WBC count and the presence of FLT3-ITD in patients with AML and ALL. Furthermore, children with AML who had the FLT3-ITD mutation showed a tendency to express CD34 in blast cells. In the adult group, the AML patients with FLT3-ITD who expressed CD34 in blast cells had a tendency to worse progression. The present data indicate no association between the prognostic factors evaluated and FLT3 gene mutations in adult with AL. Yet, the presence of FLT3-ITD mutation was significantly related with WBC count in the pediatric group. These findings demonstrate that FLT3 gene mutations can be considered as independent poor prognostic factors.