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Braz. j. biol ; 84: e252555, 2024. tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1364519


The study was designed to investigate the effect of Coconut Oil on the levels of some liver and hematological parameters in carbon tetrachloride intoxicated rabbits. Also the antioxidant capacity of Coconut Oil for various concentrations was assessed on the basis of percent scavenging of (DPPH) free radical. Experimental animals were divided into five groups, eight rabbits in each group. These were: group A (Normal control), group B (Toxic control), group C (Standard control), group D (Treated with Coconut Oil 50 mL/kg body weight after CCl4 intoxication), group E (Treated with Coconut Oil 200 mL/kg body weight after CCl4 intoxication). The effects observed were compared with a standard hepatoprotective drug silymarine (50 mL/kg body weight). The Coconut Oil (200 mL/kg body weight) significantly (P<0.05) reduced the elevated serum levels of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) when compared to a toxic control rabbits. The results of extract treated rabbits were similar to silymarine administered rabbits group. Treatment with Coconut Oil root and silymarine caused no significant changes in RBC, Platelets, (Hb), (MCH) concentration and (HCT) values. However, significant (P<0.05) increase was observed in the total WBC count. The present study suggested that Coconut Oil can be used as an herbal alternative (need further exploration i.e to detect its bioactive compound and its efficacy) for hepatoprotective activit.

O estudo foi desenhado para investigar o efeito do óleo de coco nos níveis de alguns parâmetros hepáticos e hematológicos em coelhos intoxicados com tetracloreto de carbono. Também a capacidade antioxidante do óleo de coco para várias concentrações foi avaliada com base na porcentagem de eliminação de radicais livres (DPPH). Os animais experimentais foram divididos em cinco grupos, oito coelhos em cada grupo. Estes foram: grupo A (controle normal), grupo B (controle tóxico), grupo C (controle padrão), grupo D (tratado com óleo de coco 50 mL/kg de peso corporal após intoxicação por CCl4), grupo E (tratado com óleo de coco 200 mL/kg de peso corporal após intoxicação por CCl4). Os efeitos observados foram comparados com um fármaco hepatoprotetor padrão silimarina (50 mL/kg de peso corporal). O óleo de coco (200 mL/kg de peso corporal) reduziu significativamente (P<0,05) os níveis séricos elevados de alanina transaminase (ALT), aspartato transaminase (AST) e fosfatase alcalina (ALP), quando comparado a um coelho controle tóxico. Os resultados dos coelhos tratados com extrato foram semelhantes aos do grupo de coelhos administrados com silimarina. O tratamento com raiz de óleo de coco e silimarina não causou alterações significativas nos valores de RBC, Plaquetas, (Hb), (MCH) e (HCT). No entanto, observou-se aumento significativo (P<0,05) na contagem total de leucócitos. O presente estudo sugeriu que o óleo de coco pode ser usado como uma alternativa fitoterápica (precisa de mais exploração, ou seja, para detectar seu composto bioativo e sua eficácia) para atividade hepatoprotetora.

Coelhos , Tetracloreto de Carbono , Óleo de Palmeira , Biomarcadores/sangue , Fígado
J Affect Disord ; 320: 605-609, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36183819


BACKGROUND: The glial cell line-derived neurotrophic factor (GDNF) has an important role in neurons and is closely associated with psychiatric disorders. The development of bipolar disorder (BD) may differ between genders. Existing studies have shown that plasma GDNF levels are altered in patients with BD. In this study, we investigate whether the GDNF levels in patients with BD differ in terms of gender. METHODS: Participants were divided into the BD group (n = 76, with 26 males and 50 females) and healthy control (HC) group (n = 89, with 35 males and 54 females). Plasma GDNF levels were detected via multifactor assay. Clinical symptoms of patients with BD were collected and assessed using the Hamilton Depression-17 Inventory, Hamilton Anxiety-17 Inventory, Young's Mania Rating Scale, and Brief Psychiatric Rating Scale. RESULTS: The GDNF levels were significantly higher in all participants in the HC group (F = 4.262, p < 0.05) compared with those in the BD group. In the HC group, the males (t = 4.814, p < 0.001) presented significantly higher levels than the females. The plasma GDNF levels in males in the BD group (t = 3.022, p < 0.05) were significantly lower than those in males in the HC group. CONCLUSION: Differences in plasma GDNF levels are associated with the gender of patients with BD.

Transtorno Bipolar , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Feminino , Humanos , Masculino , Fator Neurotrófico Derivado de Linhagem de Célula Glial/sangue , Caracteres Sexuais
Behav Brain Res ; 437: 114126, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36167216


BACKGROUND: Vascular endothelial growth factor (VEGF) and platelets seem to reflect the Alzheimer's disease (AD) associated either with vascular impairment or disease. This study aimed to compare the circulating levels of VEGF and platelets between AD patients and healthy older adults. METHODS: Seventy-two older adults, divided in 40 older adults (Clinical Dementia Rating Scale - CDR = 0); and 32 Alzheimer's disease patients (clinically diagnosed - CRD = 1) participated in the present study. The groups were paired by sex, age, comorbidities and educational level. The primary outcomes included circulating plasma VEGF and platelet levels obtained by blood collection. RESULTS: The VEGF levels were significantly different between the groups (p = 0.03), with having a large effect size ( η2 =18.15), in which the AD patients presented lower levels compared to healthy older adults. For platelets, the comparison showed a tendency to difference (p = 0.06), with a large effect size (η2 =12.95) between the groups. CONCLUSION: The VEGF levels and the platelet numbers were reduced in AD patients, suggesting that angiogenic factors could be modified due to AD.

Doença de Alzheimer , Fator A de Crescimento do Endotélio Vascular , Idoso , Humanos , Doença de Alzheimer/sangue , Estudos de Casos e Controles , Fator A de Crescimento do Endotélio Vascular/sangue
Clin Chem Lab Med ; 61(1): 104-111, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36283061


OBJECTIVES: Accurate determination of glomerular filtration rate (GFR) is important. Several endogenous biomarkers exist for estimating GFR, yet, they have limited accuracy, especially in the paediatric population. Proenkephalin A 119-159 (PENK) is a novel and promising GFR marker, but its relation with age in children remains unknown. Also, the value of PENK has never been validated against measured GFR (mGFR) in children when compared to traditional GFR markers including serum creatinine (SCr), SCr-based estimated GFR (eGFR) and cystatin C (cysC). METHODS: Critically ill children and term-born neonates were included in this single-centre, prospective study. Iohexol-based mGFR, SCr, and cysC were determined in each patient. eGFR was calculated using the bedside Schwartz equation, incorporating SCr and height. Spearman correlation coefficients were calculated to determine the correlation between mGFR and PENK, SCr, cysC and eGFR. RESULTS: For 97 patients (56 children and 41 neonates), mGFR, SCr, cysC and PENK levels were available. PENK levels were higher in young children and decreased to adult PENK reference values around two years of age. PENK levels were highly correlated with mGFR (ρ=-0.88, p<0.001), and similar to mGFR-eGFR correlation (ρ=-0.87, p<0.001). For cysC and SCr the correlation with mGFR was lower (ρ=-0.77 and ρ=-0.46, respectively. Both p<0.001). CONCLUSIONS: The correlation of PENK with mGFR was as good as SCr-based eGFR-mGFR correlation. To determine the added value of PENK in paediatric clinical care and prior to implementation, PENK reference values are needed and the development and validation of a paediatric PENK-based eGFR equation is necessary.

Estado Terminal , Encefalinas , Taxa de Filtração Glomerular , Iohexol , Criança , Pré-Escolar , Humanos , Recém-Nascido , Biomarcadores , Creatinina , Estudos Prospectivos , Encefalinas/sangue
J Affect Disord ; 320: 647-655, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36208690


BACKGROUND: Major depressive disorder (MDD) is a recurrent disorder that incurs a high societal burden. However, the etiology of MDD remains unclear. The functioning of several systems associated with the etiopathogenesis of MDD, such as inflammatory and stress systems, is partially modulated by the dipeptide carnosine. METHODS: The study comprised 99 MDD patients and 253 non-depressed controls aged 20-71 years. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry to determine the serum levels of carnosine and its constituent, histidine. We compared these metabolites in three different settings: 1) MDD patients vs. non-depressed controls and 2) remitted vs. non-remitted MDD patients, as well as 3) changes in the metabolite levels during the follow-up period within a) the remitted group and b) the non-remitted group. In addition, we assessed the possible effect of medications on the measured metabolites. RESULTS: We observed higher serum levels of carnosine in the MDD group compared to the control group at baseline (OR = 1.895, 95%CI = 1.223-2.937, p = 0.004). Elevated serum levels of carnosine were also associated with a longer duration of the depressive episode (Z = 0.406, p = 0.001). However, the use of any antipsychotic medication (n = 36) was associated with lowered carnosine levels (p = 0.010 for use vs. non-use). At the follow-up, remitted and non-remitted participants displayed no significant differences in their carnosine levels (Z = -0.14, p = 0.891) or histidine (Z = -1.39 p = 0.164). CONCLUSIONS: An increase in circulating carnosine may characterize depressive episodes and may represent a protective homeostatic reaction against MDD-related oxidative stress and inflammation.

Carnosina , Transtorno Depressivo Maior , Humanos , Carnosina/sangue , Histidina/sangue
Artigo em Inglês | MEDLINE | ID: mdl-36376097


BACKGROUND AND OBJECTIVES: Neurodegeneration and astrocytic activation are pathologic hallmarks of progressive multiple sclerosis (MS) and can be quantified by serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). We investigated sNfL and sGFAP as tools for stratifying patients with progressive MS based on progression and disease activity status. METHODS: We leveraged our Comprehensive Longitudinal Investigation of MS at the Brigham and Women's Hospital (CLIMB) natural history study, which includes clinical, MRI data and serum samples collected over more than 20 years. We included patients with MS with a confirmed Expanded Disability Status Scale (EDSS) score ≥3 that corresponds with our classifier for patients at high risk of underlying progressive pathology. We analyzed sNfL and sGFAP within 6 months from the confirmed EDSS score ≥3 corresponding with our baseline visit. Patients who further developed 6-month confirmed disability progression (6mCDP) were classified as progressors. We further stratified our patients into active/nonactive based on new brain/spinal cord lesions or relapses in the 2 years before baseline or during follow-up. Statistical analysis on log-transformed sGFAP/sNfL assessed the baseline association with demographic, clinical, and MRI features and associations with future disability. RESULTS: We included 257 patients with MS who had an average EDSS score of 4.0 and a median follow-up after baseline of 7.6 years. sNfL was higher in patients with disease activity in the 2 years before baseline (adjusted ß = 1.21; 95% CI 1.04-1.42; p = 0.016), during the first 2 years of follow-up (adjusted ß = 1.17; 95% CI = 1.01-1.36; p = 0.042). sGFAP was not increased in the presence of disease activity. Higher sGFAP levels, but not sNfL levels, were associated with higher risk of 6mCDP (adjusted hazard ratio [HR] = 1.71; 95% CI = 1.19-2.45; p = 0.004). The association was stronger in patients with low sNfL (adjusted HR = 2.44; 95% CI 1.32-4.52; p = 0.005) and patients who were nonactive in the 2 years prior or after the sample. DISCUSSION: Higher levels of sGFAP correlated with subsequent progression, particularly in nonactive patients, whereas sNfL reflected acute disease activity in patients with MS at high risk of underlying progressive pathology. Thus, sGFAP and sNfL levels may be used to stratify patients with progressive MS for clinical research studies and clinical trials and may inform clinical care.

Proteína Glial Fibrilar Ácida , Esclerose Múltipla Crônica Progressiva , Proteínas de Neurofilamentos , Humanos , Biomarcadores/sangue , Proteína Glial Fibrilar Ácida/sangue , Imageamento por Ressonância Magnética , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Progressão da Doença , Proteínas de Neurofilamentos/sangue
Rev. bras. med. esporte ; 28(6): 775-777, Nov.-Dec. 2022. tab
Artigo em Inglês | LILACS | ID: biblio-1376766


ABSTRACT Introduction This paper studies physiological and biochemical indicators in the systematic training of sprinters. This paper analyzes the data measured during the athletes' training process and studies the detailed data of their physical functions. Objective This study aimed to find a link between exercise data and biochemical indicator data in sprinter athletes. By analyzing the data from this article, the researchers were able to find the optimal training program for the athletes. Methods High-intensity aerobic training tests were performed with statistical analysis of various physiological and biochemical indicators. Results Hemoglobin data were shown to be highly sensitive to intensity. The researchers found that long-term high-load training in athletes can lead to physical fatigue. This fatigue production is positively correlated with the intensity of the training load. Conclusion There is a strong positive correlation between biochemical and physiological indicators on performance levels in sprinter athletes. Evidence Level II; Therapeutic Studies - Investigating the results.

RESUMO Introdução Este artigo estuda o monitoramento de indicadores fisiológicos e bioquímicos no treino sistemático de velocistas. Este documento analisa os dados medidos durante o processo de treino das atletas e estuda os dados detalhados de suas funções físicas. Objetivo O objetivo deste estudo foi encontrar uma ligação entre os dados de exercício e os dados de indicadores bioquímicos nas atletas velocistas. Ao analisar as informações deste artigo, os pesquisadores conseguiram encontrar um programa de treino ideal para as atletas. Métodos Foram empegadas experiências de treino aeróbico de alta intensidade, com análise estatística de vários indicadores fisiológicos e bioquímicos. Resultados Os dados de hemoglobina mostraram-se altamente sensíveis à intensidade. Os pesquisadores descobriram que o treino a longo prazo de alta carga em atletas pode acarretar numa fadiga física. Essa produção de fadiga está positivamente correlacionada com a intensidade da carga de treino. Conclusão Há uma forte correlação positiva entre indicadores bioquímicos e fisiológicos nos níveis de desempenho em atletas velocistas. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.

RESUMEN Introducción Este trabajo estudia el seguimiento de los indicadores fisiológicos y bioquímicos en el entrenamiento sistemático de los velocistas. Este artículo analiza los datos medidos durante el proceso de entrenamiento de los atletas y estudia los datos detallados de sus funciones físicas. Objetivo El objetivo de este estudio fue encontrar una relación entre los datos del ejercicio y los datos de los indicadores bioquímicos en los atletas velocistas. Al analizar las informaciones de este artículo, los investigadores pudieron encontrar un programa de entrenamiento óptimo para los atletas. Métodos Se realizaron pruebas de entrenamiento aeróbico de alta intensidad con análisis estadístico de varios indicadores fisiológicos y bioquímicos. Resultados Los datos de la hemoglobina se mostraron muy sensibles a la intensidad. Los investigadores descubrieron que el entrenamiento de alta carga a largo plazo en los atletas puede conducir a la fatiga física. Esta producción de fatiga está positivamente correlacionada con la intensidad de la carga de entrenamiento. Conclusión Existe una fuerte correlación positiva entre los indicadores bioquímicos y fisiológicos en los niveles de rendimiento de los atletas velocistas. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

Humanos , Feminino , Adulto , Adulto Jovem , Corrida/fisiologia , Atletas , Treino Aeróbico , Monitorização Fisiológica/métodos , Testosterona/sangue , Nitrogênio da Ureia Sanguínea , Hemoglobinas/análise , Hidrocortisona/sangue , Radioimunoensaio
Actas urol. esp ; 46(9): 521-530, nov. 2022. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-211493


Introducción: La displasia urotelial y el carcinoma in situ (CIS) están relacionados con la recurrencia y la progresión del carcinoma urotelial. Diferenciar el CIS y la displasia de la atipia reactiva suele ser difícil sobre la base de las características histológicas. La integración de los hallazgos histológicos con la inmunohistoquímica se utiliza en la práctica habitual para realizar el diagnóstico del CIS y, para ello, se utilizan los marcadores inmunohistoquímicos CK20, CD44, Ki67 y p53 como complemento al estudio histológico.En este trabajo, nos propusimos evaluar CK20, CD44, Ki67 y p53 como marcadores inmunohistoquímicos en pacientes con CIS, mediante una revisión sistemática y un metaanálisis.Materiales y métodosSe realizó una revisión sistemática con búsqueda en bases de datos electrónicas de estudios en inglés publicados desde enero de 2010 hasta abril de 2021. Se consideraron elegibles los estudios que evaluaban la expresión de CK20, CD44, Ki67 y p53 en el CIS.ResultadosEn total, 15 referencias fueron aptas para la revisión cuantitativa. La tasa global de expresión de CK20, CD44, Ki67 y p53 en el CIS fue del 43%, 31%, 44% y 38%, respectivamente.ConclusionesNuestro estudio apoya el consenso de la Sociedad Internacional de Patología Urológica de 2014 sobre la evaluación histológica como método de referencia para diagnosticar el CIS urotelial, y sugiere que una correlación muy estrecha entre los datos morfológicos, inmunohistoquímicos y clínicos es esencial para proporcionar el mejor manejo de los pacientes con carcinoma vesical. (AU)

Introduction: Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive atypia is often difficult based only on histological features. The integration of histological findings with immunohistochemistry is used in routine practice to make a diagnosis of CIS and, for this purpose, the immunohistochemical markers CK20, CD44, Ki67 and p53 are used to supplement histology.In this work, we aimed to assess CK20, CD44, Ki67 and p53 as immunohistochemical markers in patients with CIS through a systematic review and meta-analysis.Materials and methodsA systematic review was performed by searching electronic databases for English-language studies published from January 2010 to April 2021. Studies were considered eligible if they evaluated the CK20, CD44, Ki67 and p53 expression in CIS.ResultsIn total, 15 references were suitable for quantitative review. The overall rate of CK20, CD44, Ki67 and p53 expression in CIS was 43%, 31%, 44%, 38%, respectively.ConclusionsOur study supports the 2014 International Society of Urologic Pathology consensus that histological assessment remains the gold standard to diagnose urothelial CIS and suggests that a very close correlation between morphological, immunohistochemical and clinical data is essential to provide the best management for patients with bladder carcinoma. (AU)

Humanos , Carcinoma in Situ/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Receptores de Hialuronatos/sangue , Biomarcadores Tumorais/sangue , Imuno-Histoquímica , Queratinas/sangue , Queratina-20/sangue , Antígeno Ki-67/sangue , Proteína Supressora de Tumor p53/sangue
Rev. esp. cardiol. (Ed. impr.) ; 75(11): 867-876, nov. 2022. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-211708


Introducción y objetivos El fenotipado avanzado de lipoproteínas es mejor predictor del riesgo aterosclerótico que el colesterol. El perfil de lipoproteínas en la insuficiencia cardiaca (IC) no está completamente caracterizado. Nuestro objetivo fue describir el perfil de lipoproteínas en IC crónica en comparación con una población de control emparejada. Métodos Estudio transversal entre mayo 2006 y abril 2014, que incluyó pacientes ambulatorios con IC crónica. Las concentraciones de lípidos y el tamaño de las principales fracciones de lipoproteínas (lipoproteínas de alta densidad [HDL], lipoproteínas de baja densidad [LDL] y lipoproteínas de muy alta densidad) y concentración de sus subfracciones (grandes, medianas y pequeñas) se evaluaron mediante espectroscopia de resonancia magnética. Resultados 429 pacientes con IC crónica se compararon con 428 controles. Los pacientes con IC crónica presentaron menor colesterol total y menor concentración de partículas de LDL (1.115 frente a 1.352 nmol/L; p <0,001) y HDL (25,7 frente a 27,9μmol/L; p <0,001), esta última mediada principalmente por la reducción de la subfracción pequeña de HDL (15,2 frente a 18,6μmol/L; p <0,001). El tamaño medio de las partículas lipoproteínas de muy alta densidad, LDL y HDL fue significativamente mayor en los pacientes con IC. Todas las diferencias relacionadas con la partícula HDL persistieron después del ajuste por clase funcional o índice de masa corporal. Encontramos fuertes correlaciones negativas entre biomarcadores cardiacos (fracción aminoterminal del propéptido natriurético cerebral y interleucina-1 tipo de receptor 1) con concentraciones de LDL y HDL, sus subfracciones pequeñas y el tamaño de la partícula HDL. Conclusione Los pacientes con IC crónica difieren significativamente en su perfil de lipoproteínas en comparación con controles emparejados. Se necesitan más investigaciones para comprender mejor la relevancia patogénica de esta diferencia (AU)

Introduction and objectives Advanced lipoprotein phenotyping is a better predictor of atherosclerotic cardiovascular risk than cholesterol concentration alone. Lipoprotein profiling in heart failure (HF) is incompletely characterized. We aimed to describe the lipoprotein profile in patients with chronic HF compared with a matched control population. Methods This cross-sectional study was performed from May 2006 to April 2014 and included ambulatory patients with chronic HF. Lipid concentrations and the size of main lipoprotein fractions (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very low-density lipoprotein) and the particle concentration of their 3 subfractions (large, medium and small) were assessed using 1H magnetic resonance spectroscopy. Results The 429 included patients with chronic HF were compared with 428 matched controls. Patients with chronic HF had lower total cholesterol and lower mean LDL (1115 vs 1352 nmol/L; P<.001) and HDL (25.7 vs 27.9μmol/L; P <.001) particle concentrations, with this last difference being mediated by a significantly lower concentration of the small subfraction of HDL (15.2 vs 18.6μmol/L; P <.001). Mean very low-density lipoprotein, LDL, and HDL particle size was significantly higher in patients with HF vs controls. All HDL-related differences from controls persisted after adjustment for New York Heart Association functional class or body mass index. We found strong negative correlations of known cardiac biomarkers (N-terminal pro-brain natriuretic peptide and interleukin-1 receptor-like 1) with total and small LDL and HDL fractions and HDL particle size. Conclusions Patients with chronic HF significantly differ in their lipoprotein profile compared with unaffected controls. Further research is needed to better understand the pathogenic relevance of this difference (AU)

Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Lipoproteína(a)/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico por imagem , Espectroscopia de Ressonância Magnética , Estudos de Casos e Controles , Estudos Transversais , Biomarcadores/sangue , Doença Crônica
Sci Rep ; 12(1): 20048, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36414650


Coronavirus disease-2019 (COVID-19) can be asymptomatic or lead to a wide symptom spectrum, including multi-organ damage and death. Here, we explored the potential of microRNAs in delineating patient condition and predicting clinical outcome. Plasma microRNA profiling of hospitalized COVID-19 patients showed that miR-144-3p was dynamically regulated in response to COVID-19. Thus, we further investigated the biomarker potential of miR-144-3p measured at admission in 179 COVID-19 patients and 29 healthy controls recruited in three centers. In hospitalized patients, circulating miR-144-3p levels discriminated between non-critical and critical illness (AUCmiR-144-3p = 0.71; p = 0.0006), acting also as mortality predictor (AUCmiR-144-3p = 0.67; p = 0.004). In non-hospitalized patients, plasma miR-144-3p levels discriminated mild from moderate disease (AUCmiR-144-3p = 0.67; p = 0.03). Uncontrolled release of pro-inflammatory cytokines can lead to clinical deterioration. Thus, we explored the added value of a miR-144/cytokine combined analysis in the assessment of hospitalized COVID-19 patients. A miR-144-3p/Epidermal Growth Factor (EGF) combined score discriminated between non-critical and critical hospitalized patients (AUCmiR-144-3p/EGF = 0.81; p < 0.0001); moreover, a miR-144-3p/Interleukin-10 (IL-10) score discriminated survivors from nonsurvivors (AUCmiR-144-3p/IL-10 = 0.83; p < 0.0001). In conclusion, circulating miR-144-3p, possibly in combination with IL-10 or EGF, emerges as a noninvasive tool for early risk-based stratification and mortality prediction in COVID-19.

COVID-19 , MicroRNAs , Humanos , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/mortalidade , Fator de Crescimento Epidérmico , Interleucina-10 , MicroRNAs/sangue
Ann Med ; 54(1): 3189-3200, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36369824


INTRODUCTION: In order to identify therapeutic targets in Coronavirus disease 2019 (COVID-19), it is important to identify molecules involved in the biological responses that are modulated in COVID-19. Lysophosphatidic acids (LPAs) are involved in the pulmonary inflammation and fibrosis are one of the candidate molecules. The aim of this study was to evaluate the association between the serum levels of autotaxin (ATX), which are enzymes involved in the synthesis of lysophosphatidic acids. MATERIAL AND METHODS: We enrolled 134 subjects with COVID-19 and 58 normal healthy subjects for the study. We measured serum ATX levels longitudinally in COVID-19 patients and investigated the time course and the association with severity and clinical parameters. RESULTS: The serum ATX levels were reduced in all patients with COVID-19, irrespective of the disease severity, and were negatively associated with the serum CRP, D-dimer, and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels. DISCUSSION: Considering the biological properties of LPAs in the pulmonary inflammation and fibrosis, modulation of ATX might be compensatory biological responses to suppress immunological overreaction especially in the lung, which is an important underlying mechanism for the mortality of the disease. CONCLUSIONS: COVID-19 patients showed a decrease in the serum levels of ATX, irrespective of the disease severity. Key MessagesAutotaxin (ATX) is an enzyme involved in the synthesis of lysophosphatidic acid (LPA), which has been reported to be involved in pulmonary inflammation and fibrosis. Patients with COVID-19 show decrease in the serum levels of ATX. Modulation of ATX might be compensatory biological responses to suppress immunological overreaction.

COVID-19 , Diester Fosfórico Hidrolases , Humanos , COVID-19/sangue , Fibrose , Pulmão , Lisofosfolipídeos , Diester Fosfórico Hidrolases/sangue , SARS-CoV-2
Sci Rep ; 12(1): 19685, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36385629


This is the first study to analyze the association of accelerometer-measured patterns of habitual physical activity (PA) and sedentary behavior (SB) with serum BDNF in individuals with coronary heart disease. A total of 30 individuals (M = 69.5 years; 80% men) participated in this pre-post study that aimed to test a multi-behavioral intervention. All participants underwent standardized measurement of anthropometric variables, blood collection, self-administered survey, and accelerometer-based measurement of PA and SB over seven days. Serum BDNF concentrations were measured using enzyme-linked immunosorbent assay kit. We applied separate multiple linear regression analysis to estimate the associations of baseline SB pattern measures, light and moderate-to-vigorous PA with serum BDNF (n = 29). Participants spent 508.7 ± 76.5 min/d in SB, 258.5 ± 71.2 min/d in light PA, and 21.2 ± 15.2 min/d in moderate-to-vigorous PA. Per day, individuals had 15.5 ± 3.2 numbers of 10-to-30 min bouts of SB (average length: 22.2 ± 2.1 min) and 3.4 ± 1.2 numbers of > 30 min bouts of SB (average length: 43.8 ± 2.4 min). Regression analysis revealed no significant associations between any of the accelerometer-based measures and serum BDNF. The findings of this study did not reveal an association of accelerometer-measured PA and SB pattern variables with serum BDNF in individuals with coronary heart disease. In addition, our data revealed a considerable variation of PA and SB which should be considered in future studies.

Fator Neurotrófico Derivado do Encéfalo , Doença das Coronárias , Exercício Físico , Comportamento Sedentário , Feminino , Humanos , Masculino , Acelerometria , Fator Neurotrófico Derivado do Encéfalo/sangue , Estudos Transversais , Idoso
Front Endocrinol (Lausanne) ; 13: 1018657, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387870


Objectives: Recent studies found that secreted protein acidic and rich in cysteine-like protein 1 (Sparcl1) could inhibit lipid droplets accumulation by peroxisome proliferator-activated receptor-gamma (PPARγ) signal pathway. However, the associations of serum Sparcl1 level with lipids profiles and other metabolic phenotypes remain unknown in human population study. Methods: We determined serum Sparcl1 using sandwich enzyme-linked immunosorbent assays among 1750 adults aged 40 years and older from a community in Shanghai, China. Generalized linear regression models were used to evaluate the association between Sparcl1 and metabolic measures. Multivariable-adjusted logistic regression analyses were performed to evaluate the relationship of serum Sparcl1 with prevalent dyslipidemia. Results: With the increment of serum Sparcl1, participants tended to have lower level of triglycerides, and higher level of high-density lipoprotein cholesterol (all P for trend < 0.01). No significant associations between serum Sparcl1 and glucose, blood pressure, or body size were observed. The generalized linear regression models suggested that per standard deviation (SD) increment of serum Sparcl1 was significantly inversely associated with triglycerides (ß= -0.06, P=0.02). The prevalence of dyslipidemia decreased across the sparcl1 quartiles (P for trend <0.01). After controlling the potential confounders, participants in the highest quartile of sparcl1 concentration had the lowest prevalence of dyslipidemia (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.52-0.91), compared with the lowest quartile. Per SD increment of Sparcl1 was associated with 20% (OR, 0.80; 95%CI, 0.69-0.94) lower prevalence of hypertriglyceridemia and 12% (OR, 0.88; 95%CI, 0.79-0.97) lower prevalence of dyslipidemia. The association between serum Sparcl1 and dyslipidemia were generally consistent across subgroups (all P for interaction > 0.05). Conclusion: Serum Sparcl1 was significantly associated with decreased risk of prevalent dyslipidemia in Chinese population. Further studies are warranted to confirm this association.

Proteínas de Ligação ao Cálcio , Dislipidemias , Proteínas da Matriz Extracelular , Adulto , Humanos , Pessoa de Meia-Idade , China/epidemiologia , Dislipidemias/epidemiologia , Triglicerídeos , Proteínas de Ligação ao Cálcio/sangue , Proteínas da Matriz Extracelular/sangue
Front Endocrinol (Lausanne) ; 13: 1048337, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387880


Objective: Abnormal levels of blood cytokines have been demonstrated to be associated with both excess weight and major depressive disorder (MDD). However, few studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode drug-naïve MDD. Methods: A total of 49 patients with first-episode drug-naïve MDD were categorized into normal weight (18.5 ≤ BMI < 25 kg/m2) and overweight (25 ≤ BMI < 30 kg/m2) groups according to WHO-criteria. The severity of depressive symptoms was assessed using the 24-items Hamilton Depression Scale (HAMD-24). A total of 37 cytokines were measured using Multiplex Luminex Assays. The scores of HAMD-24 and the levels of serum cytokines between normal weight group and overweight group were compared. Multiple linear regression analysis was performed to evaluate the association between abnormal serum cytokines levels and group after adjusting for HAMD-24 scores. The correlation between BMI and the scores of HAMD-24 and the levels of serum cytokines was evaluated using Pearson correlation analysis. Results: The scores of HAMD-24 in overweight group were significantly higher than normal weight group (t = -2.930, P = 0.005). Moreover, the levels of IL-1α, IL-1RA, IL-3, CXCL10, TNF-α, and ICAM-1 in overweight patients with MDD were significantly higher than those in normal-weight patients with MDD (all P < 0.05). Furthermore, after adjustment for HAMD-24 scores, there was a significant correlation between abnormal serum cytokines levels (IL-1α, IL-1RA, IL-3, CXCL10, TNF-α, and ICAM-1) and group (all P < 0.05). Additionally, BMI was positively correlated to the serum levels of IL-1α (r = 0.428, P = 0.002), IL-3 (r = 0.529, P < 0.001), IL-6 (r = 0.285, P = 0.050), IL-10 (r = 0.423, P = 0.003), IL-12 (r = 0.367, P = 0.010), IL-15 (r = 0.300, P = 0.036), CXCL10 (r = 0.316, P = 0.030), TNF-α (r = 0.338, P = 0.021), and ICAM-1 (r = 0.440, P = 0.002) in MDD patients. Conclusions: These results provide direct evidence, probably for the first time, that overweight may be associated with several serum cytokines in patients with first-episode drug-naïve MDD. The underlying mechanisms are unclear and require further investigation.

Citocinas , Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/complicações , Molécula 1 de Adesão Intercelular , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-3 , Sobrepeso/complicações , Fator de Necrose Tumoral alfa , Citocinas/sangue
Biochem Biophys Res Commun ; 636(Pt 1): 1-9, 2022 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-36332469


Dyslipidemia and inflammation have great roles in the development of diabetic nephropathy (DN). Oleanolic acid (OA) is a natural triterpenoid that possesses multiple pharmacological properties including anti-oxidation, anti-inflammatory and hypoglycemia. In the present study, the effects of OA on diabetic kidney disease (DKD) and its underlying mechanisms were investigated in DKD rats. Twenty-five of a total thirty-five male Sprague-Dawley (SD) rats were used to establish for Type 2 diabetes mellitus (T2DM) model by high-fat diet combined with streptozotocin (STZ). Then rats were randomly assigned into four group: control group (n = 10), T2DM group (n = 9), OA (50 mg/kg) group (n = 7), OA (100 mg/kg) group (n = 8). Rats were sacrificed at the end of 18 weeks after feeding by intraperitoneal injection of pentobarbital sodium. Body weight (BW), fasting blood glucose (FBG), kidney weight (KW), serum lipid, 24-h urinary microalbumin (UMA), serum creatinine (Scr) and uric acid (UA) were measured. Histopathological changes were observed by PAS staining and electron microscope. The expressions of nephrin, CD68, Collagen-IV, AMPK, p-AMPK, PGC-1α, TLR4, NF-κB and TGF-ß1 in kidney were also detected by immunohistochemistry or western blot. OA significantly decreased the levels of FBG, kidney index (KI), serum lipid levels, 24 h UMA, Scr, UA in diabetic rats. Additionally, OA obviously attenuated renal lipid accumulation and renal structure abnormalities in diabetic rats. Furthermore, the expression levels of nephrin, p-AMPK/AMPK, PGC-1α were elevated, while CD68, Collagen-IV, TLR4, NF-κB and TGF-ß1 expressions were decreased in renal tissues of OA treated diabetic rats. OA showed dose-independent. OA can alleviate renal injury in diabetic rats through improving lipid metabolism and inflammation via AMPK/PGC-1α and TLR4/NF-κB signaling pathway.

Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Ácido Oleanólico , Animais , Masculino , Ratos , Proteínas Quinases Ativadas por AMP/metabolismo , Colágeno/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/metabolismo , Inflamação/patologia , Rim/metabolismo , Lipídeos/sangue , NF-kappa B/metabolismo , Ácido Oleanólico/farmacologia , Ratos Sprague-Dawley , Receptor 4 Toll-Like/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
BMC Infect Dis ; 22(1): 846, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371172


BACKGROUND: African countries stand out globally as the region seemingly least affected by the COVID-19 pandemic, caused by the virus SARS-CoV-2. Besides a younger population and potential pre-existing immunity to a SARS-CoV-2-like virus, it has been hypothesized that co-infection or recent history of Plasmodium falciparum malaria may be protective of COVID-19 severity and mortality. The number of COVID-19 cases and deaths, however, may be vastly undercounted. Very little is known about the extent to which the Tanzanian population has been exposed to SARS-CoV-2. Here, we investigated the seroprevalence of IgG to SARS-CoV-2 spike protein in two Tanzanian rural communities 1½ years into the pandemic and the association of coinciding malaria infection and exposure. METHODS: During a malariometric survey in July 2021 in two villages in north-eastern Tanzania, blood samples were taken from 501 participants (0-19 years old). Malaria was detected by mRDT and microscopy. Levels of IgG against the spike protein of SARS-CoV-2 were measured by ELISA as well as IgG against five different antigens of P. falciparum; CIDRα1.1, CIDRα1.4 and CIDRα1.5 of PfEMP1 and GLURP and MSP3. RESULTS: The seroprevalence of SARS-CoV-2 IgG was 39.7% (106/267) in Kwamasimba and 32.5% (76/234) in Mkokola. In both villages the odds of being seropositive increased significantly with age (AOR = 1.12, 95% CI 1.07-1.17, p < 0.001). P. falciparum malaria prevalence by blood smear microscopy was 7.9% in Kwamasimba and 2.1% in Mkokola. 81.3% and 70.5% in Kwamasimba and Mkokola, respectively, showed recognition of minimum one malaria antigen. Residing in Kwamasimba was associated with a broader recognition (AOR = 1.91, 95% CI 1.34-2.71, p < 0.001). The recognition of malaria antigens increased significantly with age in both villages (AOR = 1.12; 95% CI 1.08-1.16, p < 0.001). Being SARS-CoV-2 seropositive did not associate with the breadth of malaria antigen recognition when adjusting for age (AOR = 0.99; 95% CI 0.83-1.18; p = 0.91). CONCLUSION: More than a third of the children and adolescents in two rural communities in Tanzania had antibodies to SARS-CoV-2. In particular, the adolescents were seropositive but being seropositive did not associate with the status of coinciding malaria infections or previous exposure. In Tanzania, natural immunity may have developed fast, potentially protecting a substantial part of the population from later variants.

Anticorpos Antivirais , COVID-19 , Malária Falciparum , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Adulto Jovem , Anticorpos Antivirais/sangue , Antígenos de Protozoários , COVID-19/epidemiologia , Imunoglobulina G , Malária Falciparum/epidemiologia , Pandemias , SARS-CoV-2 , Estudos Soroepidemiológicos , Tanzânia/epidemiologia
N Engl J Med ; 387(21): 1923-1934, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36342113


BACKGROUND: High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels. METHODS: In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or could not receive statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or lower. The primary efficacy end point was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. RESULTS: Among 10,497 patients (66.9% with previous cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterol level 33 mg per deciliter, and LDL cholesterol level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were -26.2% for triglycerides, -25.8% for very-low-density lipoprotein (VLDL) cholesterol, -25.6% for remnant cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), -27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end-point event occurred in 572 patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified subgroup. The overall incidence of serious adverse events did not differ significantly between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of nonalcoholic fatty liver disease. CONCLUSIONS: Among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels. (Funded by the Kowa Research Institute; PROMINENT number, NCT03071692.).

Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Hipertrigliceridemia , Hipolipemiantes , PPAR alfa , Humanos , Apolipoproteína C-III/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Fatores de Risco de Doenças Cardíacas , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/sangue , Hiperlipidemias/tratamento farmacológico , Hipertrigliceridemia/sangue , Hipertrigliceridemia/complicações , Hipertrigliceridemia/tratamento farmacológico , Fatores de Risco , Triglicerídeos/sangue , Hipolipemiantes/uso terapêutico , PPAR alfa/agonistas , HDL-Colesterol/sangue