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Chronic ethanol exposure often triggers neuroinflammation in the brain's reward system, potentially promoting the drive for ethanol consumption. A main marker of neuroinflammation is the microglia-derived monocyte chemoattractant protein 1 (MCP1) in animal models of alcohol use disorder in which ethanol is forcefully given. However, there are conflicting findings on whether MCP1 is elevated when ethanol is taken voluntarily, which challenges its key role in promoting motivation for ethanol consumption. Here, we studied MCP1 mRNA levels in areas implicated in consumption motivation-specifically, the prefrontal cortex, hippocampus, and striatum-as well as in the cerebellum, a brain area highly sensitive to ethanol, of C57BL/6 mice subjected to intermittent and voluntary ethanol consumption for two months. We found a significant increase in MCP1 mRNA levels in the cerebellum of mice that consumed ethanol compared to controls, whereas no significant changes were observed in the prefrontal cortex, hippocampus, or striatum or in microglia isolated from the hippocampus and striatum. To further characterize cerebellar neuroinflammation, we measured the expression changes in other proinflammatory markers and chemokines, revealing a significant increase in the proinflammatory microRNA miR-155. Notably, other classical proinflammatory markers, such as TNFα, IL6, and IL-1ß, remained unaltered, suggesting mild neuroinflammation. These results suggest that the onset of neuroinflammation in motivation-related areas is not required for high voluntary consumption in C57BL/6 mice. In addition, cerebellar susceptibility to neuroinflammation may be a trigger to the cerebellar degeneration that occurs after chronic ethanol consumption in humans.
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Consumo de Bebidas Alcoólicas , Cerebelo , Quimiocina CCL2 , Corpo Estriado , Etanol , Hipocampo , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal , Animais , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/patologia , Camundongos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Cerebelo/metabolismo , Cerebelo/efeitos dos fármacos , Cerebelo/patologia , Masculino , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Corpo Estriado/efeitos dos fármacos , Etanol/efeitos adversos , Consumo de Bebidas Alcoólicas/efeitos adversos , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/patologia , Microglia/metabolismo , Microglia/efeitos dos fármacos , Microglia/patologia , Inflamação/metabolismo , Inflamação/patologia , Inflamação/induzido quimicamenteRESUMO
Leprosy is a chronic infectious disease caused by the intracellular bacillus Mycobacterium leprae (M. leprae), which is known to infect skin macrophages and Schwann cells. Although adipose tissue is a recognized site of Mycobacterium tuberculosis infection, its role in the histopathology of leprosy was, until now, unknown. We analyzed the M. leprae capacity to infect and persist inside adipocytes, characterizing the induction of a lipolytic phenotype in adipocytes, as well as the effect of these infected cells on macrophage recruitment. We evaluated 3T3-L1-derived adipocytes, inguinal adipose tissue of SWR/J mice, and subcutaneous adipose tissue biopsies of leprosy patients. M. leprae was able to infect 3T3-L1-derived adipocytes in vitro, presenting a strong lipolytic profile after infection, followed by significant cholesterol efflux. This lipolytic phenotype was replicated in vivo by M. leprae injection into mice inguinal adipose tissue. Furthermore, M. leprae was detected inside crown-like structures in the subcutaneous adipose tissue of multibacillary patients. These data indicate that subcutaneous adipose tissue could be an important site of infection, and probably persistence, for M. leprae, being involved in the modulation of the innate immune control in leprosy via the release of cholesterol, MCP-1, and adiponectin.
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Hanseníase , Mycobacterium leprae , Camundongos , Animais , Humanos , Mycobacterium leprae/fisiologia , Lipólise , Adipócitos/patologia , Imunidade , ColesterolRESUMO
Leprosy is a chronic infectious disease caused by the intracellular bacillus Mycobacterium leprae (M. leprae), which is known to infect skin macrophages and Schwann cells. Although adipose tissue is a recognized site of Mycobacterium tuberculosis infection, its role in the histopathology of leprosy was, until now, unknown. We analyzed the M. leprae capacity to infect and persist inside adipocytes, characterizing the induction of a lipolytic phenotype in adipocytes, as well as the effect of these infected cells on macrophage recruitment. We evaluated 3T3-L1-derived adipocytes, inguinal adipose tissue of SWR/J mice, and subcutaneous adipose tissue biopsies of leprosy patients. M. leprae was able to infect 3T3-L1-derived adipocytes in vitro, presenting a strong lipolytic profile after infection, followed by significant cholesterol efflux. This lipolytic phenotype was replicated in vivo by M. leprae injection into mice inguinal adipose tissue. Furthermore, M. leprae was detected inside crown-like structures in the subcutaneous adipose tissue of multibacillary patients. These data indicate that subcutaneous adipose tissue could be an important site of infection, and probably persistence, for M. leprae, being involved in the modulation of the innate immune control in leprosy via the release of cholesterol, MCP-1, and adiponectin.
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Humanos , Animais , Ratos , Mycobacterium leprae/fisiologia , Adipócitos/patologia , LipóliseRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emergent viral disease in which the host inflammatory response modulates the clinical outcome. Severe outcomes are associated with an exacerbation of inflammation in which chemokines play an important role as the attractants of immune cells to the tissues. OBJECTIVE: To evaluate the relationship of the chemokines IL-8, RANTES, MIG, MCP-1, and IP-10 with COVID-19 severity and outcomes in Mexican patients. METHODS: We analyzed the serum levels of IL-8, RANTES, MIG, MCP-1 and IP-10 in 148 COVID-19 hospitalized patients classified as mild (n=20), severe (n=61), and critical (n=67), as well as in healthy individuals (n=10), by flow cytometry bead array assay. RESULTS: Chemokine levels were higher in patients than in the healthy individuals, but only MIG, MCP-1, and IP-10 increased according to the disease severity, showing the highest levels in the critical group. MIG, MCP-1, and IP-10 levels were also higher in COVID-19 patients with comorbidities such as renal disease, type 2 diabetes, and hypertension. Moreover, elevated MIG levels seem to be related to organic failure/shock, and an increased risk of death. CONCLUSIONS: Our results suggest that the increased levels of MCP-1, IP-10, and especially MIG might be useful in predicting severe COVID-19 outcomes and could be promising therapeutic targets.
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COVID-19 , Quimiocina CXCL9 , COVID-19/mortalidade , Quimiocina CCL5 , Quimiocina CXCL10 , Quimiocina CXCL9/metabolismo , Humanos , Interleucina-8 , MéxicoRESUMO
Maternal nutritional programming by energy-dense foods leads to the transgenerational heritance of addiction-like behavior. Exposure to energy-dense foods also activates systemic and central inflammation in the offspring. This study aimed to characterize pro- and anti-inflammatory cytokine profiles in blood and their correlation to the transgenerational heritance of the addiction-like behavior in rats. F1 offspring of male Wistar diagnosed with addiction-like behavior were mated with virgin females to generate the F2 and the F3 offspring, respectively. Diagnosis of addiction-like behavior was performed by the operant training schedule (FR1, FR5 and PR) and pro- and anti-inflammatory cytokine profiles in blood were measured by multiplex platform. Multiple linear models between behavior, fetal programming by diet and pro- and anti-inflammatory cytokine profiles were performed. We found that the addiction-like behavior found in the F1 male offspring exposed to energy-dense food (cafeteria, CAF) diet during fetal programing is transgenerational inherited to the F2 and F3 generations. Blood from addiction-like behavior subjects of F2 and F3 generations exposed to CAF diet during maternal programming showed decrease in the anti-inflammatory IL-10 in the plasma. Conversely, decreased levels of the pro-inflammatory MCP-1 was identified in non-addiction-like subjects. No changes were found in plasmatic TNF-α levels in the F2 and F3 offspring of non-addiction-like and addiction-like subjects. Finally, biological modeling between IL-10 or MCP-1 plasma levels and prenatal diet exposure on operant training responses confirmed an association of decreased IL-10 levels on addiction-like behavior in the F2 and F3 generations. Globally, we identified decreased anti-inflammatory IL-10 cytokine in the blood of F2 and F3 offspring subjects diagnosed with addiction-like behavior for food rewards.
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Dependência de Alimentos , Efeitos Tardios da Exposição Pré-Natal , Animais , Anti-Inflamatórios , Condicionamento Operante , Feminino , Humanos , Interleucina-10 , Masculino , Gravidez , Ratos , Ratos WistarRESUMO
Autism spectrum disorder (ASD) is a disease characterized by reduced social interaction and stereotypic behaviors and related to macroscopic volumetric changes in cerebellar and somatosensory cortices (SPP). Epidemiological and preclinical models have confirmed that a proinflammatory profile during fetal development increases ASD susceptibility after birth. Here, we aimed to globally identify the effect of maternal exposure to high-energy dense diets, which we refer to as cafeteria diet (CAF) on peripheral and central proinflammatory profiles, microglia reactivity, and volumetric brain changes related to assisting defective social interaction in the mice offspring. We found a sex-dependent effect of maternal exposure to CAF diet or inoculation of the dsARN mimetic Poly (I:C) on peripheral proinflammatory and social interaction in the offspring. Notably, maternal exposure to CAF diet impairs social interaction and favors an increase in anxiety in male but not female offspring. Also, CAF diet exposure or Poly (I:C) inoculation during fetal programming promote peripheral proinflammatory profile in the ASD-diagnosed male but not in females. Selectively, we found a robust accumulation of the monocyte chemoattractant protein-1 (MCP-1) in plasma of ASD-diagnosed males exposed to CAF during fetal development. Biological assessment of MCP-1 signaling in brain confirms that systemic injection of MCP-1-neutralizing antibody reestablished social interaction and blocked anxiety, accompanied by a reduction in cerebellar lobule X (CbX) volume and an increase volume of the primary somatosensory (SSP) cortex in male offspring. These data highlight the contribution of diet-dependent MCP-1 signaling on volumetric brain changes and microglia morphology promoting ASD-like behavior in male mice.
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Transtorno do Espectro Autista , Quimiocina CCL2 , Efeitos Tardios da Exposição Pré-Natal , Animais , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/patologia , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Quimiocina CCL2/metabolismo , Feminino , Masculino , Camundongos , Microglia/citologia , Gravidez , Comportamento SocialRESUMO
Variations in levels of some adipokines, myokines, osteokines, hepatokines and inflammatory cytokines contribute to abnormal glucose and lipid metabolism. The aim of this study was to determine the pattern of adiponectin, osteocalcin (OCN), irisin, FGF-21, and MCP-1 according to the body size phenotype of middle-aged women, and their associations with BMI, visceral adipose tissue (VAT), and HOMA-IR. A cross-sectional study in 265 women aged from 40 to 65 years was performed. The biochemical characteristics were evaluated in metabolically healthy normal weight, metabolically unhealthy normal weight, metabolically healthy obese, and metabolically unhealthy obese women. There was an association of OCN with BMI (r = -0.107; p = 0.047); adiponectin with BMI (r = -0.217; p = 0.001), insulin (r = -0.415; p = 0.0001), HOMA-IR (r = -0.429; p = 0.0001), and VAT (r = -0.134; p = 0.025); irisin with BMI (r = 0.604; p = 0.001), insulin (r = 0.446; p = 0.0001), HOMA-IR (r = 0.452; p = 0.0001), and VAT (r = 0.645; p = 0.0001); FGF-21 with insulin (r = -0.337; p= 0.030) and HOMA-IR (r = -0.341; p = 0.03); and MCP-1 with BMI (r = 0.481; p = 0.0001), VAT (r = 0.497; p = 0.001), insulin (r = 0.298; p= 0.001), and HOMA-IR (r = 0.255; p = 0.004). A multivariate analysis showed that an elevation of OCN (OR 1.4 (95%CI 1.06-1.81)) and a reduction of adiponectin (OR 0.9 (0.84-0.96)) were associated factors for a metabolic unhealthy phenotype in normal weight participants. Likewise, higher irisin (OR 1.007 (1.003-1.011)) and MCP-1 (1.044 (1.008-1.083)) were risk factors for a metabolic unhealthy phenotype in woman with obesity. OCN, adiponectin, irisin, FGF-21, and MCP-1 are associated with some metabolic parameters such as BMI, HOMA-IR, and VAT, and could be possible biomarkers of an unhealthy metabolic phenotype in middle-aged women.
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Background: Most of the explanatory and prognostic models of COVID-19 lack of a comprehensive assessment of the wide COVID-19 spectrum of abnormalities. The aim of this study was to unveil novel biological features to explain COVID-19 severity and prognosis (death and disease progression). Methods: A predictive model for COVID-19 severity in 121 patients was constructed by ordinal logistic regression calculating odds ratio (OR) with 95% confidence intervals (95% CI) for a set of clinical, immunological, metabolomic, and other biological traits. The accuracy and calibration of the model was tested with the area under the curve (AUC), Somer's D, and calibration plot. Hazard ratios with 95% CI for adverse outcomes were calculated with a Cox proportional-hazards model. Results: The explanatory variables for COVID-19 severity were the body mass index (BMI), hemoglobin, albumin, 3-Hydroxyisovaleric acid, CD8+ effector memory T cells, Th1 cells, low-density granulocytes, monocyte chemoattractant protein-1, plasma TRIM63, and circulating neutrophil extracellular traps. The model showed an outstanding performance with an optimism-adjusted AUC of 0.999, and Somer's D of 0.999. The predictive variables for adverse outcomes in COVID-19 were severe and critical disease diagnosis, BMI, lactate dehydrogenase, Troponin I, neutrophil/lymphocyte ratio, serum levels of IP-10, malic acid, 3, 4 di-hydroxybutanoic acid, citric acid, myoinositol, and cystine. Conclusions: Herein, we unveil novel immunological and metabolomic features associated with COVID-19 severity and prognosis. Our models encompass the interplay among innate and adaptive immunity, inflammation-induced muscle atrophy and hypoxia as the main drivers of COVID-19 severity.
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COVID-19 , SARS-CoV-2 , Índice de Gravidade de Doença , Adulto , Coagulação Sanguínea , Índice de Massa Corporal , COVID-19/sangue , COVID-19/imunologia , COVID-19/metabolismo , Citocinas/sangue , Armadilhas Extracelulares/imunologia , Feminino , Hemoglobinas/análise , Humanos , Masculino , Metaboloma , Pessoa de Meia-Idade , Atrofia Muscular , Neutrófilos/imunologia , Fenótipo , Prognóstico , Albumina Sérica Humana/análise , Linfócitos T/imunologia , Valeratos/sangueRESUMO
The coronavirus family has tropism for the Central Nervous System (CNS), however, there is no solid evidence demonstrating that the neurological effects of COVID-19 result from direct viral infection or systemic inflammation. The goals of this study were to examine the cytokine profile and the presence of SARS-CoV-2 messenger ribonucleic acid (mRNA) in cerebrospinal fluids (CSF) from two patients with cerebrovascular disease and COVID-19. Although the SARS-CoV-2 mRNA was not detected in CSF of both patients, we found abnormally high levels of numerous proinflammatory cytokines and chemokines, especially IL-8 and MCP-1. Since these chemokines mediate activation and recruitment of neutrophils, monocytes, and macrophages, it is feasible that cerebrovascular disease related-neuroinflammation found in both patients results from an exacerbated inflammatory response instead of SARS-CoV-2 direct invasion to CNS. These results suggest that neuroinflammation plays a key role in cerebrovascular disease and COVID-19.
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OBJECTIVES: To utilize a Luminex platform to examine multiple cytokines simultaneously as well as clinical laboratory testing to identify markers that predict acute pancreatitis severity in the pediatric population on admission. STUDY DESIGN: Patients (<19 years of age) prospectively enrolled over a 4-year period in a single institution acute pancreatitis database were included in separate derivation and validation cohorts. Plasma samples were obtained within 48 hours of admission and stored for analysis. Samples from mild acute pancreatitis and severe acute pancreatitis (moderately severe and severe combined) were analyzed using Luminex panels and C-reactive protein (CRP) testing. RESULTS: The derivation cohort examined 62 cytokines in 66 subject samples (20 control, 36 mild acute pancreatitis, 10 severe acute pancreatitis) and identified interleukin 6 (IL-6) (P = .02) and monocyte chemotactic protein-1 (MCP-1) (P = .02) as cytokines that were differentially expressed between mild and severe acute pancreatitis. Our validation cohort analyzed 76 cytokines between 10 controls, 19 mild acute pancreatitis, and 6 severe acute pancreatitis subjects. IL-6 (P = .02) and MCP-1 (P = .007) were again found to differentiate mild acute pancreatitis from severe acute pancreatitis. CRP values were obtained from 53 of the subjects, revealing a strong association between elevated CRP values and progression to severe disease (P < .0001). CONCLUSIONS: This study identified and validated IL-6 and MCP-1 as predictors of severe acute pancreatitis using 2 distinct cohorts and showed that CRP elevation is a marker of progression to severe acute pancreatitis. These biomarkers have not been extensively studied in the pediatric acute pancreatitis population. Our data allows for risk-stratification of patients with acute pancreatitis, and represent novel insight into the immunologic response in severe acute pancreatitis.
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Quimiocina CCL2/sangue , Interleucina-6/sangue , Pancreatite/sangue , Receptores Imunológicos/sangue , Adolescente , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Criança , Progressão da Doença , Feminino , Humanos , Masculino , Pancreatite/diagnóstico , Estudos Prospectivos , Curva ROCRESUMO
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.
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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
BACKGROUND: Long non-coding RNAs (lncRNAs) govern fundamental biochemical and cellular biology processes, for example, participate in chromatin remodeling, imprinting, splicing, transcriptional regulation and translation. Dysregulation of lncRNA expression is act as a feature of various diseases and cancers, including hematopoietic malignancies. However, the clinical relevance of myelodysplastic syndrome (MDS) and acute myeloid leukemia preceded by MDS (MDS-AML) requires further research. Recently, lncRNAs have been demonstrated, which play an important role in hematopoiesis, thus, to further finding more functional lncRNA seemed particularly important. METHODS: Western blotting, real-time PCR, RNA-pulldown, RIP (RNA immunoprecipitation), Chromatin immunoprecipitation (ChIP), cellular compartments extraction assays, SA-ß-gal staining, lentivirus transfection, cell viability assay and cell proliferation assays were used to examine the relationship between lncRNA LINC01255 and its regulation of p53-p21 pathway in human mesenchymal stromal and acute myeloid leukemia cells. RESULTS: LncRNA LINC01255 is highly expressed in bone marrow cells of AML patients, CD34+ cells of MDS-AML patients and AML cell lines and the higher expression of LINC01255 is associated with poor survival rate of AML patients. LINC01255 can interact with BMI1 and repress the transcription of MCP-1 to active p53-p21 pathway, thus inhibiting the senescence of human mesenchymal stromal and proliferation of acute myeloid leukemia cell. CONCLUSIONS: We discovered a novel functional lncRNA LINC01255, which can regulate the senescence of human mesenchymal stromal and the proliferation of acute myeloid leukemia cell through inhibiting the transcription of MCP-1.
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Proliferação de Células , Senescência Celular/genética , Quimiocina CCL2/genética , Leucemia Mieloide Aguda/patologia , Células-Tronco Mesenquimais/patologia , Complexo Repressor Polycomb 1/fisiologia , RNA Longo não Codificante/fisiologia , Transcrição Gênica , Humanos , Células Tumorais CultivadasRESUMO
INTRODUCTION: In light of the current COVID-19 pandemic, during which the world is confronted with a new, highly contagious virus that suppresses innate immunity as one of its initial virulence mechanisms, thus escaping from first-line human defense mechanisms, enhancing innate immunity seems a good preventive strategy. METHODS: Without the intention to write an official systematic review, but more to give an overview of possible strategies, in this review article we discuss several interventions that might stimulate innate immunity and thus our defense against (viral) respiratory tract infections. Some of these interventions can also stimulate the adaptive T- and B-cell responses, but our main focus is on the innate part of immunity. We divide the reviewed interventions into: 1) lifestyle related (exercise, >7 h sleep, forest walking, meditation/mindfulness, vitamin supplementation); 2) Non-specific immune stimulants (letting fever advance, bacterial vaccines, probiotics, dialyzable leukocyte extract, pidotimod), and 3) specific vaccines with heterologous effect (BCG vaccine, mumps-measles-rubeola vaccine, etc). RESULTS: For each of these interventions we briefly comment on their definition, possible mechanisms and evidence of clinical efficacy or lack of it, especially focusing on respiratory tract infections, viral infections, and eventually a reduced mortality in severe respiratory infections in the intensive care unit. At the end, a summary table demonstrates the best trials supporting (or not) clinical evidence. CONCLUSION: Several interventions have some degree of evidence for enhancing the innate immune response and thus conveying possible benefit, but specific trials in COVID-19 should be conducted to support solid recommendations.
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Metabolic syndrome comprises a cluster of metabolic disorders related to the development of cardiovascular disease and type 2 diabetes mellitus. In latter years, plant secondary metabolites have become of special interest because of their potential role in preventing and managing metabolic syndrome. Sesquiterpene lactones constitute a large and diverse group of biologically active compounds widely distributed in several medicinal plants used for the treatment of metabolic disorders. The structural diversity and the broad spectrum of biological activities of these compounds drew significant interests in the pharmacological applications. This review describes selected sesquiterpene lactones that have been experimentally validated for their biological activities related to risk factors of metabolic syndrome, together with their mechanisms of action. The potential beneficial effects of sesquiterpene lactones discussed in this review demonstrate that these substances represent remarkable compounds with a diversity of molecular structure and high biological activity, providing new insights into the possible role in metabolic syndrome management.
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Lupus nephritis (LN) is a major contributor to morbidity and mortality in patients with Systemic Lupus Erythematosus (SLE). This study aims to investigate the possible role of a functional polymorphism in the regulatory region of the monocyte chemo-attractant protein-1 (MCP-1) gene and MCP-1 blood level in the diagnosis of LN and in correlating the MCP-1 blood levels with disease activity. The study included 56 SLE patients and 56 controls. All the SLE patients suffered from LN. An analysis of MCP-1 gene polymorphism by polymerase chain reaction was performed followed by restriction fragment length polymorphism (PCR-RFLP) analysis and MCP-1 blood level was determined using the ELISA technique. Calculation of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was performed. Serologic tests included the determination of antinuclear antibody (ANA) and anti-double-stranded (ds) DNA antibodies, Complement C3 and C4 levels. A significant increase in the frequency of genotype A/G and a decrease in the frequency of genotype A/A were found among patients with active LN compared to inactive LN. There was a statistically significant difference in the blood level of MCP-1 between LN patients and controls. Also, MCP-1 blood levels were significantly higher in active LN patients than inactive LN. A significant positive linear correlation was detected between MCP-1 blood level and SLEDAI, creatinine, and 24 hours protein in LN patients. These results suggest that an A/G genotype together with the measurement of the blood level of MCP-1 can be a useful tool for detection and follow up of active LN.
A nefrite do lúpus (LN) é um dos principais contribuintes para a morbidade e mortalidade em pacientes com o Lúpus Eritematoso Sistémico (LES). Este estudo tem como objetivo investigar o possível papel de um polimorfismo funcional na região reguladora do gene da proteína quimioatraente de monócitos-1 (MCP-1) e do nível sanguíneo de MCP-1 no diagnóstico de LN e na correlação do sangue de MCP-1 níveis com atividade da doença. O estudo incluiu 56 pacientes com LES e 56 controles. Todos os pacientes com LES sofriam de LN. Uma análise do polimorfismo do gene MCP-1 por reação em cadeia da polimerase foi realizada seguida pela análise do polimorfismo do comprimento do fragmento de restrição (PCR-RFLP) e o nível sanguíneo do MCP-1 foi determinado pela técnica ELISA. O cálculo do índice de atividade da doença sistêmica do lúpus eritematoso (SLEDAI) foi realizado. Os testes sorológicos incluíram a determinação de anticorpos antinucleares (ANA) e anticorpos anti-DNA de fita dupla (ds), níveis de Complemento C3 e C4. Um aumento significativo na frequência do genótipo A/G e uma diminuição na frequência do genótipo A/A foram encontrados entre os pacientes com LN ativo em comparação com o LN inativo. Houve uma diferença estatisticamente significante no nível sanguíneo de MCP-1 entre pacientes com LN e controles. Além disso, os níveis sanguíneos de MCP-1 foram significativamente mais altos em pacientes com LN ativo do que com LN inativo. Uma correlação linear positiva significativa foi detectada entre o nível sanguíneo de MCP-1 e SLEDAI, creatinina e proteína de 24 horas em pacientes com LN. Esses resultados sugerem que um genótipo A/G, juntamente com a medição do nível sanguíneo de MCP-1, pode ser uma ferramenta útil para a detecção e acompanhamento do LN ativo
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Polimorfismo Genético , Nefrite Lúpica , Receptores CCR2RESUMO
OBJECTIVE: To describe the main neurological manifestations related to coronavirus infection in humans. METHODOLOGY: A systematic review was conducted regarding clinical studies on cases that had neurological manifestations associated with COVID-19 and other coronaviruses. The search was carried out in the electronic databases PubMed, Scopus, Embase, and LILACS with the following keywords: "coronavirus" or "Sars-CoV-2" or "COVID-19" and "neurologic manifestations" or "neurological symptoms" or "meningitis" or "encephalitis" or "encephalopathy," following the Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Seven studies were included. Neurological alterations after CoV infection may vary from 17.3% to 36.4% and, in the pediatric age range, encephalitis may be as frequent as respiratory disorders, affecting 11 % and 12 % of patients, respectively. The Investigation included 409 patients diagnosed with CoV infection who presented neurological symptoms, with median age range varying from 3 to 62 years. The main neurological alterations were headache (69; 16.8 %), dizziness (57, 13.9 %), altered consciousness (46; 11.2 %), vomiting (26; 6.3 %), epileptic crises (7; 1.7 %), neuralgia (5; 1.2 %), and ataxia (3; 0.7 %). The main presumed diagnoses were acute viral meningitis/encephalitis in 25 (6.1 %) patients, hypoxic encephalopathy in 23 (5.6 %) patients, acute cerebrovascular disease in 6 (1.4 %) patients, 1 (0.2 %) patient with possible acute disseminated encephalomyelitis, 1 (0.2 %) patient with acute necrotizing hemorrhagic encephalopathy, and 2 (1.4 %) patients with CoV related to Guillain-Barré syndrome. CONCLUSION: Coronaviruses have important neurotropic potential and they cause neurological alterations that range from mild to severe. The main neurological manifestations found were headache, dizziness and altered consciousness.
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The aim of this study was to evaluate the impact of creatine supplementation (CS) on renal function in young, healthy, and active subjects. We used a randomized, double-blind, placebo-controlled clinical trial as the study design. Thirty-six healthy male university students were recruited and divided into three groups: group placebo, group G3 (3 g/day of CS), and group G5 (5 g/day of CS). To assess renal function, new kidney biomarkers, kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1), were quantified. Serum albumin, serum creatinine, serum urea, estimated glomerular filtration rate (eGFR), proteinuria, and albuminuria were also measured. All groups were evaluated at two times: prior CS or placebo (pre) and after 35 days on CS or placebo (post). After 35 days of intervention, all characteristics were maintained without significant difference (P > 0.05) between the groups, including serum creatinine, eGFR, and more sensitive kidney biomarker concentrations (KIM-1 and MCP-1). The paired analysis showed that the supplemented groups (G3 and 5G) had increased serum creatinine and decreased eGFR levels (P < 0.05). However, the values were still within the normal reference range. In conclusion, the results of renal function evaluation did not show any difference between the evaluated groups. Increased serum creatinine and decreased eGFR levels in CS groups can be explained by increased creatine stores and metabolism, since creatinine is a by-product of creatine metabolism. These findings indicate that the use of CS at doses of 3 g and 5 g/day for a short period (35 days) is safe and did not impair the kidneys or renal function in young healthy subjects.
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PURPOSE: The present study measured 41 soluble mediators in the tear of 19 patients with age-related cataract and 32 healthy adults as controls. MATERIALS AND METHODS: This was a prospective, case-control study in which, using multiple immunoassays, we measured in tear samples the following molecules: EGF, FGF-2, Eotaxin, TGF-α, G-CSF, Flt-3L, GM-CSF, Fractalkine, IFN-α2, IFN-γ, GRO, IL-10, MCP-3, IL-12p40, MDC, IL-12p70, PDGF-AA, IL-13, PDGF-AB/BB, IL-15, sCD40L, IL-17a, IL-1ra, IL-1α, IL-9, IL-1ß, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IP-10, MCP-1, MIP-1α, MIP-1ß, RANTES, TNFα, TNFß, VEGF. Statistical analyses were done by multiple adjusted models and p values were corrected by the Benjamini and Hochberg method. RESULTS: We did not find significant differences in the amount of the tested molecules in the tear fluid between cataract patients and controls. Correlation analyses relative to age were carried out for both groups. Analysis of MCP-1 tear levels revealed a direct correlation with age for normal healthy controls as well as for cataract patients. But IL-6 tear levels correlated with age only in the group of cataract patients. In addition, IL1-ra tear levels correlated with cataract nuclear grade; higher grades were associated with higher IL-1ra concentrations. CONCLUSIONS: Our results suggest that ocular aging is accompanied by increased production of IL-6 and MCP-1, which can be measured in tear fluid. ABBREVIATIONS: AMD: Age-Related Macular Degeneration; EGF: Epidermal growth factor; Eotaxin: Eosinophil chemotactic proteins; FasL: Fas ligand; FGF-2: Basic fibroblast growth factor 2; Flt-3L: Fms related tyrosine kinase 3 ligand; G-CSF: Granulocyte colony stimulating factor; GM-CSF: Granulocyte macrophage colony stimulating factor; GRO: Growth regulated protein; HGF: Human growth factor; ICAM-1: Intercellular adhesion molecule-1; IFNα2: Interferon alpha 2; IFNγ: Interferon gamma; IL: Interleukin; IL-1ra: Interleukin-1 receptor antagonist; IL-12p40: Interleukin-12 subunit p40; IL-12p70: Interleukin-12 subunit p70; IP-10: Interferon gamma-induced protein 10; MCP-1: Monocyte chemotactic protein 1; MCP-3: Monocyte chemotactic protein 3; MDC: Macrophage derived chemokine; MIG: Monokine induced by gamma interferon; MIP-1α: Macrophage inflammatory proteins 1 alpha; MIP-1ß: Macrophage inflammatory proteins 1 beta; MMPs: Matrix metalloproteinases; MMP-9: Matrix metalloproteinase 9; PAI1: Plasminogen activator inhibitor 1; PDGF-AA: Platelet-derived growth factor subunit AA; PDGF-AB/BB: Platelet-derived growth factor subunit AB and BB; PIGF: Placenta growth factor; RANTES: Regulated on activation, normal T cell expressed and secreted; SAA: Serum amyloid A; sCD40L: Soluble CD40 ligand; sTNF-RII: Soluble tumor necrosis factor receptor; TBUT Tear breakup time; TGF-α: Transforming growth factor alpha; TGF-ß: Transforming growth factor beta; TNFα: Tumor necrosis factor alpha; TNFß: Tumor necrosis factor beta; VCAM: Vascular cell adhesion molecule; VEGF: Vascular endothelium growth factor.
Assuntos
Catarata/metabolismo , Citocinas/metabolismo , Proteínas do Olho/metabolismo , Lágrimas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Biomarcadores/metabolismo , Estudos de Casos e Controles , Quimiocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
INTRODUCTION: Hemodialysis (HD) is associated with high risk for cardiovascular diseases including acute myocardial infarction, stroke and congestive heart failure. C-C Motif Chemokine Ligand 2 (CCL2), also known monocyte chemotactic protein-1 (MCP-1) can be produced by a variety of cells, reaching increased levels in dyslipidemic chronic kidney disease (CKD) patients undergoing HD treatment. The main of this study was to evaluate the association between of CCL2 plasma levels and dyslipidemia in CKD patients undergoing HD. METHODS: A cross-sectional study enrolled 160 Brazilian HD patients. CCL2 plasma levels were measured by capture ELISA. The association between CCL2 levels and dyslipidemia was investigated using linear regression, adjusted for classic and non-classical CVD risk factors. RESULTS: A significant association was observed between CCL2 levels and dyslipidemia (Pâ¯=â¯0.029), even after adjustment for possible confounding variables, such as age, gender, body mass index, diabetes mellitus, HD time, urea pre-hemodialysis and interdialytic weight gain (Pâ¯=â¯0.045). CONCLUSION: Our findings show that CCL2 levels are associated with dyslipidemia, which suggests a role of this cytokine in the pathogenesis of cardiovascular disease in HD patients. A better understanding of this pathogenesis could contribute to the discovery of new therapeutic targets that would reduce cardiovascular complications in these patients.
Assuntos
Doenças Cardiovasculares/etiologia , Quimiocina CCL2/sangue , Dislipidemias/sangue , Falência Renal Crônica/sangue , Adulto , Brasil , Doenças Cardiovasculares/complicações , Correlação de Dados , Estudos Transversais , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Fatores de RiscoRESUMO
Obesity is defined as a condition of abnormal or excessive fat accumulation in white adipose tissue that results from the exacerbated consumption of calories associated with low energy expenditure. Fat accumulation in both adipose tissue and other organs contributes to a systemic inflammation leading to the development of metabolic disorders such as type 2 diabetes, hypertension, and dyslipidemia. Melatonin is a potent antioxidant and improves inflammatory processes and energy metabolism. Using male mice fed a high-fat diet (HFD-59% fat from lard and soybean oil; 9:1) as an obesity model, we investigated the effects of melatonin supplementation on the prevention of obesity-associated complications through an analysis of plasma biochemical profile, body and fat depots mass, adipocytes size and inflammatory cytokines expression in epididymal (EPI) adipose depot. Melatonin prevented a gain of body weight and fat depot mass as well as adipocyte hypertrophy. Melatonin also reversed the increase of total cholesterol, triglycerides and LDL-cholesterol. In addition, this neurohormone was effective in completely decreasing the inflammatory cytokines leptin and resistin in plasma. In the EPI depot, melatonin reversed the increase of leptin, Il-6, Mcp-1 and Tnf-α triggered by obesity. These data allow us to infer that melatonin presents an anti-obesity effect since it acts to prevent the progression of pro-inflammatory markers in the epididymal adipose tissue together with a reduction in adiposity.