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1.
J Transl Med ; 15(1): 109, 2017 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-28532453

RESUMO

BACKGROUND: Numerous studies have investigated the role of the dietary factors in the prevention of cognitive decline but the short-term effects of foods choice on cognitive performances in the elderly are poorly explored. Our aim was to investigate the choice of foods among elderly Italian individuals and the association with cognitive function. METHODS: In this longitudinal study, the participants were 214 individuals aged ≥65 years with a score >20 at the Mini Mental State Examination. The cognitive sub-test of ADAScale was used to detect cognitive decline progression over 12 months. Food choices was measured by a combination of a 24-h recall and a seven-day diet record and Principal Components Analysis. RESULTS: The Principal Components Analysis identified four food and four nutrient patterns. MMSE and ADAS-cog score after 1 year were found to be associated with legumes pattern (B = 0.25, p = 0.007; 95% CI 0.07/0.44; and B = -0.10, p = 0.006; CI -0.79/-0.30, respectively). A dietary pattern including plant proteins was independently associated with an improved ADAS-cog after 1 year (B = 0.584, p = 0.04; OR 1.79, CI 0.04-0.42). CONCLUSIONS: The Principal Components Analysis is useful to investigate the choice of foods and nutrients in the elderly. We demonstrated an association between legumes pattern with cognitive performances.


Assuntos
Cognição/fisiologia , Fabaceae/metabolismo , Comportamento Alimentar , Proteínas de Plantas/metabolismo , Idoso , Demografia , Humanos , Modelos Lineares , Análise Multivariada , Testes Neuropsicológicos , Análise de Componente Principal
2.
J Endocrinol Invest ; 39(5): 495-507, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26511999

RESUMO

Thyroid dysfunction induces several renal derangements involving all nephron portions. Furthermore, dysthyroidism is a recognized risk factor associated with the development of chronic kidney disease. Current data, in fact, demonstrate that either subclinical or overt thyroid disease is associated with significant changes in creatinine, estimated glomerular filtration rate, measured glomerular filtration rate and Cystatin C. Herein, we systematically reviewed several relevant studies aiming at the identification of the most sensitive and specific parameter for the correct renal function evaluation in patients with thyroid dysfunction, that are usually treated as outpatients. Our systematic review indicates that estimated glomerular filtration rate, preferably with CKD-EPI equation, appears to be the most reliable and wieldy renal function parameter. Instead, Cystatin C should be better used in the grading of thyroid dysfunction severity.


Assuntos
Taxa de Filtração Glomerular , Insuficiência Renal Crônica/diagnóstico , Doenças da Glândula Tireoide/fisiopatologia , Estudos de Avaliação como Assunto , Humanos , Insuficiência Renal Crônica/epidemiologia
3.
J Transl Med ; 12: 46, 2014 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-24548517

RESUMO

BACKGROUND: A positive association between handgrip strength and bone mineral density was demonstrated, but not all the investigations confirmed these results. We conducted a screening programme for osteoporosis in a large cohort of postmenopausal women to investigate the relationship between handgrip strength, other nutritional parameters and bone density. METHODS: This investigation involved 1,300 white volunteers. All participants underwent a bone mineral density evaluation at the heel and a handgrip strength measurement. RESULTS: The mean T-score value was -1.15 ± 1; a total of 181 participants reported at least one osteoporotic fracture. In the univariate analysis, both handgrip strength and body mass index were associated with the T-score value. Adjustment for confounding factors confirmed this relationship showing, in the multivariate analysis, that the body mass index was positively correlated to the T-score (B = 0.034; p = 0.001) and, in the logistic regression analysis, that handgrip strength was associated with the presence of osteoporosis (P = 0.005). CONCLUSION: Both body mass index and handgrip strength were strongly correlated to bone mineral density, assessed with ultrasound, suggesting a possible key role as bone disease predictors.


Assuntos
Programas de Rastreamento , Fenômenos Fisiológicos da Nutrição , Osteoporose/diagnóstico , Osteoporose/fisiopatologia , Densidade Óssea , Demografia , Feminino , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Análise Multivariada
4.
Clin Chem Lab Med ; 52(12): 1729-37, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24933628

RESUMO

Rheumatoid arthritis, the most prominent of systemic autoimmune rheumatic diseases, represents an important social health problem. Recent insights into the immunopathogenic mechanism of this complex and multiform illness might open new perspectives for a more appropriate laboratory approach. In this review we focus on the most relevant pathogenetic mechanism; indicating the laboratory biomarkers specifically linked to early diagnosis, prognosis, evolutive aspects of the disease, and therapeutic efficacy. Evidence based on laboratory medicine could provide the best outcome for patients.


Assuntos
Artrite Reumatoide/diagnóstico , Biomarcadores/metabolismo , Artrite Reumatoide/patologia , Citocinas/genética , Citocinas/metabolismo , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/metabolismo , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Receptores de Citocinas/genética , Receptores de Citocinas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
5.
Mediators Inflamm ; 2014: 750860, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24729662

RESUMO

Calorie restriction is a common strategy for weight loss in obese individuals. However, little is known about the impact of moderate hypocaloric diets on obesity-related laboratory parameters in a short-term period. Aim of this study was to evaluate the variation of laboratory biomarkers in obese individuals following a Mediterranean, hypocaloric (1400-1600 Kcal/die) diet. 23 obese, pharmacologically untreated patients were enrolled and subjected to the determination of anthropometric variables and blood collection at baseline, 1 and 4 months after diet initiation. After 4 months of calorie restriction, we observed a significant decrease in body weight and BMI (both P < 0.0001), insulin (P = 0.037), HOMA-IR (P = 0.026), leptin (P = 0.008), and LDH (P = 0.023) and an increase in EGF (P = 0.013). All these parameters, except LDH, varied significantly already at 1 month after diet initiation. Also, lower levels of insulin (P = 0.025), leptin (P = 0.023), and EGF (P = 0.035) were associated with a greater (>5%) weight loss. Collectively, our data support a precocious improvement of insulin and leptin sensitivity after a modest calorie restriction and weight reduction. Moreover, EGF and LDH may represent novel markers of obesity, which deserve further investigations.


Assuntos
Restrição Calórica , Dieta Mediterrânea , Resistência à Insulina , Obesidade/dietoterapia , Adipocinas/sangue , Antropometria , Biomarcadores/sangue , Índice de Massa Corporal , Dieta , Fator de Crescimento Epidérmico/sangue , Feminino , Humanos , Insulina/sangue , L-Lactato Desidrogenase/sangue , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Estudos Prospectivos , Redução de Peso
6.
Clin Chem Lab Med ; 51(7): 1363-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23399587

RESUMO

Psoriasis is an immune-mediated, chronic, inflammatory disease that affects the skin and joints. Because of its high incidence and of its clinical symptoms it has a very strong social impact. In a genetically predisposed individual, the maintenance of the skin barrier integrity is strongly compromised in response to either environmental or self-antigenic insults. A persistent dysregulation of the skin immune system causes the typical evolutive skin lesions of psoriasis and recurrence of the disease. The most efficient laboratory approach consists of a well-defined evaluation of immune response in order to help diagnosis, to monitor evolution, and to evaluate the effects of individualized therapeutic treatments.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Sistema Imunitário/efeitos dos fármacos , Psoríase/diagnóstico , Psoríase/terapia , Pele/imunologia , Biomarcadores/análise , Progressão da Doença , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Expressão Gênica , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Humanos , Interleucina-17/antagonistas & inibidores , Interleucina-17/genética , Interleucina-17/imunologia , Interleucina-23/antagonistas & inibidores , Interleucina-23/genética , Interleucina-23/imunologia , Reação em Cadeia da Polimerase , Análise Serial de Proteínas , Psoríase/imunologia , Psoríase/patologia , Pele/efeitos dos fármacos , Pele/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia
7.
Circ J ; 76(5): 1121-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22447003

RESUMO

BACKGROUND: We aimed to evaluate if the use of an intra-aortic balloon pump (IABP) during cardioplegic arrest improves organ function and reduces endothelial activation in patients undergoing coronary artery bypass graft (CABG). METHODS AND RESULTS: Five-hundred and one CABG patients were randomized into 2 groups: (Group A n=270) linear cardiopulmonary bypass (CPB); and (Group B n=231) automatic 80 beats/min IABP-induced pulsatile CPB. We evaluated hemodynamic response, coagulation and fibrinolysis, transaminase, bilirubin, amylase, lactate, renal function (estimated glomerular filtration rate [eGFR], creatinine and any possibility of renal insufficiency or failure), respiratory function and endothelial markers (vascular endothelial growth factor [VEGF] and monocyte chemotactic protein-1 [MCP-1]). IABP, which induced surplus hemodynamic energy, was 21,387 ± 4,262 ergs/cm(3). Group B showed lower chest drainage, transfusions, international normalized ratio, and antithrombin III, together with higher platelets, activated partial thromboplastin time, fibrinogen and D-dimer. Transaminases, bilirubin, amylase, lactate were lower in Group B; there were better results for eGFR in Group B from ICU-arrival to 48 h, resulting in lower creatinine from ICU-arrival to 48 h. The necessity for renal replacement therapy was lower in Group B Stage-3. Group B P(a)O(2)/F(i)O(2) and lung compliance improved with aortic de-clamping on the first day with shorter intubation time. Group B showed lower VEGF and MCP-1. CONCLUSIONS: Pulsatile flow by IABP improves whole-body perfusion and reduces endothelial activation during CPB.


Assuntos
Ponte Cardiopulmonar , Ponte de Artéria Coronária , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Balão Intra-Aórtico , Idoso , Biomarcadores/sangue , Feminino , Fibrinólise , Taxa de Filtração Glomerular , Hemodinâmica , Humanos , Masculino
8.
Minerva Med ; 113(5): 833-837, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35166100

RESUMO

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disease characterized by erythematous plaques that can extend along the entire skin surface. In the latest years, it has been shown that serum calprotectin correlated strongly with several inflammatory biomarkers. Since high levels of calprotectin have been found in psoriatic lesions, it is of paramount importance to investigate the role of serum calprotectin as a possible novel diagnostic marker of psoriasis. Aim of our prospective pilot study was to assess the level of serum calprotectin in psoriatic patients. METHODS: Between January 2018 and July 2019, 45 subjects were enrolled at the Dermatology Unit of Magna Graecia University of Catanzaro, Italy. Thirty-two of them were psoriatic patients and 13 healthy controls. Psoriasis severity was assessed by the Psoriasis Area Severity Index. RESULTS: A statistically significant difference between the two groups (P=0.01) was found in terms of body mass index, higher among patients than in controls. By performing the Student's t-test for unpaired data, serum calprotectin resulted significantly higher (P=0.033) among psoriatic patients than in controls. Furthermore, performing the receiver operator characteristic curve analysis, serum calprotectin showed a significant area under the curve, implying its possible role in finding psoriatic patients. Our study aimed to evaluate the serum levels of calprotectin in a group of psoriatic patients and in a control group. The results showed that serum calprotectin levels were significantly higher in the patient group than in the control group. This result confirms the observations present in the literature. CONCLUSIONS: In this pilot study psoriatic patients had a significant high level of serum calprotectin than healthy subjects, and this biomarker had high accuracy in identifying patients. Further studies, with larger sample size will need to confirm our data.


Assuntos
Complexo Antígeno L1 Leucocitário , Psoríase , Humanos , Itália , Complexo Antígeno L1 Leucocitário/sangue , Projetos Piloto , Estudos Prospectivos , Psoríase/diagnóstico
9.
J Immunol ; 182(8): 4529-37, 2009 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-19342626

RESUMO

Early hematopoietic zinc finger/zinc finger protein 521 (EHZF/ZNF521) is a novel zinc finger protein expressed in hematopoietic stem and progenitor cells and is down-regulated during their differentiation. Its transcript is also abundant in some hematopoietic malignancies. Analysis of the changes in the antigenic profile of cells transfected with EHZF cDNA revealed up-regulation of HLA class I cell surface expression. This phenotypic change was associated with an increased level of HLA class I H chain, in absence of detectable changes in the expression of other Ag-processing machinery components. Enhanced resistance of target cells to NK cell-mediated cytotoxicity was induced by enforced expression of EHZF in the cervical carcinoma cell line HeLa and in the B lymphoblastoid cell line IM9. Preincubation of transfected cells with HLA class I Ag-specific mAb restored target cell susceptibility to NK cell-mediated lysis, indicating a specific role for HLA class I Ag up-regulation in the NK resistance induced by EHZF. A potential clinical significance of these findings is further suggested by the inverse correlation between EHZF and MHC class I expression levels, and autologous NK susceptibility of freshly explanted multiple myeloma cells.


Assuntos
Proteínas de Ligação a DNA/imunologia , Proteínas de Ligação a DNA/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Neoplasias/imunologia , Neoplasias/metabolismo , Animais , Apresentação de Antígeno/imunologia , Linhagem Celular , Chlorocebus aethiops , Proteínas de Ligação a DNA/genética , Regulação para Baixo , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Ligantes , Neoplasias/genética , Transcrição Gênica/imunologia , Transgenes/genética , Regulação para Cima
10.
BMC Biol ; 7: 24, 2009 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-19460132

RESUMO

BACKGROUND: We previously showed that mice lacking the high mobility group A1 gene (Hmga1-knockout mice) developed a type 2-like diabetic phenotype, in which cell-surface insulin receptors were dramatically reduced (below 10% of those in the controls) in the major targets of insulin action, and glucose intolerance was associated with increased peripheral insulin sensitivity. This particular phenotype supports the existence of compensatory mechanisms of insulin resistance that promote glucose uptake and disposal in peripheral tissues by either insulin-dependent or insulin-independent mechanisms. We explored the role of these mechanisms in the regulation of glucose homeostasis by studying the Hmga1-knockout mouse model. Also, the hypothesis that increased insulin sensitivity in Hmga1-deficient mice could be related to the deficit of an insulin resistance factor is discussed. RESULTS: We first show that HMGA1 is needed for basal and cAMP-induced retinol-binding protein 4 (RBP4) gene and protein expression in living cells of both human and mouse origin. Then, by employing the Hmga1-knockout mouse model, we provide evidence for the identification of a novel biochemical pathway involving HMGA1 and the RBP4, whose activation by the cAMP-signaling pathway may play an essential role for maintaining glucose metabolism homeostasis in vivo, in certain adverse metabolic conditions in which insulin action is precluded. In comparative studies of normal and mutant mice, glucagon administration caused a considerable upregulation of HMGA1 and RBP4 expression both at the mRNA and protein level in wild-type animals. Conversely, in Hmga1-knockout mice, basal and glucagon-mediated expression of RBP4 was severely attenuated and correlated inversely with increased Glut4 mRNA and protein abundance in skeletal muscle and fat, in which the activation state of the protein kinase Akt, an important downstream mediator of the metabolic effects of insulin on Glut4 translocation and carbohydrate metabolism, was simultaneously increased. CONCLUSION: These results indicate that HMGA1 is an important modulator of RBP4 gene expression in vivo. Further, they provide evidence for the identification of a novel biochemical pathway involving the cAMP-HMGA1-RBP4 system, whose activation may play a role in glucose homeostasis in both rodents and humans. Elucidating these mechanisms has importance for both fundamental biology and therapeutic implications.


Assuntos
AMP Cíclico/metabolismo , Glucose/metabolismo , Proteína HMGA1a/metabolismo , Homeostase , Redes e Vias Metabólicas , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , AMP Cíclico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucagon/administração & dosagem , Glucagon/farmacologia , Transportador de Glucose Tipo 4/metabolismo , Proteína HMGA1a/deficiência , Proteína HMGA1a/genética , Homeostase/efeitos dos fármacos , Humanos , Injeções Intraperitoneais , Insulina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos , Camundongos Knockout , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/enzimologia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Proteínas Plasmáticas de Ligação ao Retinol/genética , Transdução de Sinais/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos
11.
Artigo em Inglês | MEDLINE | ID: mdl-31906326

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by a prothrombotic state, predisposing to vascular complications. Some related markers, linking thrombophilia to hemostasis and inflammation, however, have been poorly explored in relation to patients' glycemia. We therefore investigated the association of laboratory hemostatic parameters, circulating adhesion molecules (ADMs), white blood cell (WBC) count, and neutrophil/lymphocyte ratio (NLR) with T2DM and glycemic control. RESEARCH DESIGN: In this study, 82 subjects, grouped into T2DM patients (n = 41) and healthy individuals (n = 41) were enrolled. To evaluate glycemic control, the T2DM cohort was expanded to 133 patients and sub-classified according to glycated hemoglobin (HbA1c) <7% and ≥ 7% (n = 58 and n = 75, respectively). We assessed glycemia, HbA1c, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), platelet and leukocyte parameters, vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and selectins (E-, P-, L-). RESULTS: PT % activity, PAI-1, VCAM-1, WBC, and neutrophil counts were significantly higher in T2DM patients than in healthy subjects. Poor glycemic control (HbA1c ≥ 7%) was correlated with increased PT activity (p = 0.015), and higher levels of E-selectin (p = 0.009), P-selectin (p = 0.012), and NLR (p = 0.019). CONCLUSIONS: Both T2DM and poor glycemic control affect some parameters of hemostasis, inflammation, and adhesion molecules. Further studies are needed to establish their clinical utility as adjuvant markers for cardio-vascular risk in T2DM patients.


Assuntos
Moléculas de Adesão Celular , Diabetes Mellitus Tipo 2 , Hemostasia , Inflamação , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/sangue , Moléculas de Adesão Celular/fisiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Selectina E , Feminino , Hemoglobinas Glicadas/análise , Índice Glicêmico , Humanos , Inflamação/sangue , Molécula 1 de Adesão Intercelular , Masculino , Pessoa de Meia-Idade , Selectina-P , Inibidor 1 de Ativador de Plasminogênio , Molécula 1 de Adesão de Célula Vascular
12.
Crit Care Med ; 37(3): 902-11, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19237895

RESUMO

OBJECTIVE: The growing life expectancy has led the elderly to be increasingly referred to coronary artery bypass grafting. Preexisting comorbidities may benefit from theoretical advantages of pulsatile perfusion during cardiopulmonary bypass (CPB). DESIGN: Prospective randomized trial. SETTING: Cardiac surgery unit in a university hospital. PATIENTS: Eighty consecutive patients older than 70 years. INTERVENTIONS: Elective coronary artery bypass grafting on CPB, randomizing to conventional linear CPB (40 patients, group A) or intra-aortic balloon pump (IABP)-induced pulsatile CPB (40 patients, group B). MEASUREMENTS AND MAIN RESULTS: We evaluated hemodynamic response by pulmonary artery flotation catheter, metabolic/splanchnic response by lactate and transaminase, bilirubin, amylase, and renal function (creatinine clearance, creatinine, incidence of renal insufficiency and failure), respiratory response by Pao2/Fio2, respiratory compliance, scoring of chest radiograph, intubation time, and need for noninvasive positive-pressure ventilation, hematologic response by chest drainage, hemocoagulative and fibrinolytic cascades, and transfusions. IABP-related complications were recorded. Two minor IABP-related complications (2.5%) were registered. Hemodynamics was comparable, except for a slightly better cardiac index and indexed systemic vascular resistances at the end of CPB and at intensive therapy unit (ITU) admission (p < 0.05). Transaminases, bilirubin, amylase, proved lower in group B (p < 0.05 from ITU admission to 48 hours). Creatinine clearance, serum creatinine, and lactate were better in group B (p < 0.05), and acute renal insufficiency was accordingly lower (p = 0.02). Respiratory response demonstrated better Pao2/Fio2 and respiratory compliance from aortic declamping to 48 hours, with better scoring of chest radiograph (p < 0.05 from ITU admission to 48 hours), lower noninvasive positive-pressure ventilation (p = 0.002) and intubation time (p = 0.031) in group B. Lower chest drainage (p < 0.05 at first and second day), transfusions (p < 0.05), activated partial thromboplastin time, international normalized ratio, white blood cells, and D-dimer (p < 0.05 from ITU admission to 48 hours), together with higher platelets, fibrinogen, and antithrombin III (p < 0.05 from ITU admission to 48 hours) were demonstrated in the pulsated group. CONCLUSIONS: IABP-induced pulsatile flow significantly improves whole body perfusion in the elderly undergoing CPB.


Assuntos
Ponte Cardiopulmonar , Doença da Artéria Coronariana/cirurgia , Balão Intra-Aórtico , Fluxo Pulsátil , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Estudos Prospectivos , Resultado do Tratamento
13.
Medicine (Baltimore) ; 98(7): e14587, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30762811

RESUMO

Recently, it has been shown that some well-known pathogenic mediators in rheumatoid arthritis (RA), such as interleukin-1ß (IL-1ß) and tumor necrosis factor (TNF), could play a pathogenic role in insulin resistance and (IR) and type 2 diabetes (T2D).In this 6-month longitudinal study, we aimed at investigating if the inhibition of IL-1 or TNF is associated with an improvement of IR in RA patients with comorbid T2D and the possible effects on selected serum adipokines. RA patients with comorbid T2D were recruited among those undergoing treatment with anakinra (ANA) or with TNF inhibitor (TNFi). The 1998-updated version of the Homeostasis Model Assessment (HOMA2) was used to calculate surrogate indexes of IR (HOMA2-IR) and steady-state beta cell function (%B) from fasting values of glucose and C-peptide. Glucagon, adiponectin, adipsin, leptin, and resistin were also measured. All these parameters were collected at baseline, after 3 and 6 months of treatment.ANA-treated patients showed a significant improvement in HOMA2-%ß, HOMA2-IR, and glucagon. In TNFi-treated patients, no significant difference was observed analyzing these metabolic parameters. Adipsin and resistin decreased after 6 months in ANA-treated patients whereas, no difference was recognized analyzing adiponectin and leptin. In TNFi-treated patients, leptin and resistin significantly increased, whereas no difference was found analyzing adiponectin and adipsin, during the follow-up.Our data may suggest a beneficial effect of IL-1 inhibition on measures of metabolic derangement in RA-associated T2D. If further confirmed by larger studies, IL-1 targeting therapies may represent a tailored approach in these patients.


Assuntos
Adipocinas/metabolismo , Artrite Reumatoide/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Resistência à Insulina/fisiologia , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Interleucina-1/antagonistas & inibidores , Idoso , Artrite Reumatoide/fisiopatologia , Glicemia/efeitos dos fármacos , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/antagonistas & inibidores
14.
Front Immunol ; 10: 224, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873154

RESUMO

The ability of pathogens to sequester iron from their host cells and proteins affects their virulence. Moreover, iron is required for various innate host defense mechanisms as well as for acquired immune responses. Therefore, intracellular iron concentration may influence the interplay between pathogens and immune system. Here, we investigated whether changes in iron concentrations and intracellular ferritin heavy chain (FTH) abundance may modulate the expression of Major Histocompatibility Complex molecules (MHC), and susceptibility to Natural Killer (NK) cell cytotoxicity. FTH downregulation, either by shRNA transfection or iron chelation, led to MHC surface reduction in primary cancer cells and macrophages. On the contrary, mouse embryonic fibroblasts (MEFs) from NCOA4 null mice accumulated FTH for ferritinophagy impairment and displayed MHC class I cell surface overexpression. Low iron concentration, but not FTH, interfered with IFN-γ receptor signaling, preventing the increase of MHC-class I molecules on the membrane by obstructing STAT1 phosphorylation and nuclear translocation. Finally, iron depletion and FTH downregulation increased the target susceptibility of both primary cancer cells and macrophages to NK cell recognition. In conclusion, the reduction of iron and FTH may influence the expression of MHC class I molecules leading to NK cells activation.


Assuntos
Apoferritinas/metabolismo , Citotoxicidade Imunológica/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Ferro/metabolismo , Células Matadoras Naturais/imunologia , Animais , Apoferritinas/genética , Linhagem Celular Tumoral , Células Cultivadas , Citotoxicidade Imunológica/genética , Desferroxamina/farmacologia , Embrião de Mamíferos/citologia , Fibroblastos/citologia , Fibroblastos/imunologia , Fibroblastos/metabolismo , Expressão Gênica/efeitos dos fármacos , Células HeLa , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Interferon gama/farmacologia , Células K562 , Células Matadoras Naturais/metabolismo , Células MCF-7 , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Coativadores de Receptor Nuclear/genética , Coativadores de Receptor Nuclear/metabolismo , Interferência de RNA , Sideróforos/farmacologia
15.
Cancer Immunol Res ; 7(5): 841-852, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30940644

RESUMO

Immune checkpoint blockade therapy has changed prognoses for many melanoma patients. However, immune responses that correlate with clinical progression of the disease are still poorly understood. To identify immune responses correlating with melanoma clinical evolution, we analyzed serum cytokines as well as circulating NK and T-cell subpopulations from melanoma patients. The patients' immune profiles suggested that melanoma progression leads to changes in peripheral blood NK and T-cell subsets. Stage IV melanoma was characterized by an increased frequency of CCR7+CD56bright NK cells as well as high serum concentrations of the CCR7 ligand CCL19. CCR7 expression and CCL19 secretion were also observed in melanoma cell lines. The CCR7+ melanoma cell subpopulation coexpressed PD-L1 and Galectin-9 and had stemness properties. Analysis of melanoma-derived cancer stem cells (CSC) showed high CCR7 expression; these CSCs were efficiently recognized and killed by NK cells. An accumulation of CCR7+, PD-L1+, and Galectin-9+ melanoma cells in melanoma metastases was demonstrated ex vivo Altogether, our data identify biomarkers that may mark a CCR7-driven metastatic melanoma pathway.


Assuntos
Células Matadoras Naturais/imunologia , Melanoma/imunologia , Antígeno B7-H1/imunologia , Linhagem Celular , Quimiocina CCL19/imunologia , Técnicas de Cocultura , Citocinas/sangue , Feminino , Galectinas/imunologia , Humanos , Masculino , Melanoma/sangue , Melanoma/patologia , Células-Tronco Neoplásicas/imunologia , Receptores CCR7/imunologia
16.
Cancer Res ; 66(10): 5085-93, 2006 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-16707431

RESUMO

Various studies have shown that the insulin receptor (IR) is increased in most human breast cancers, and both ligand-dependent malignant transformation and increased cell growth occur in cultured breast cells overexpressing the IR. However, although numerous in vivo and in vitro observations have indicated an important contributory role for the IR in breast cancer cell biology, the molecular mechanisms accounting for increased IR expression in breast tumors have not previously been elucidated. Herein, we did immunoblot analyses of nuclear protein from cultured breast cancer cells and normal and tumoral tissues from breast cancer patients combined with promoter studies by using a series of human wild-type and mutant IR promoter constructs. We provide evidence that IR overexpression in breast cancer is dependent on the assembly of a transcriptionally active multiprotein-DNA complex, which includes the high-mobility group A1 (HMGA1) protein, the developmentally regulated activator protein-2 (AP-2) transcription factor and the ubiquitously expressed transcription factor Sp1. In cultured breast cancer cells and human breast cancer specimens, the expression of AP-2 was significantly higher than that observed in cells and tissues derived from normal breast, and this overexpression paralleled the increase in IR expression. However, AP-2 DNA-binding activity was undetectable with the IR gene promoter, suggesting that transactivation of this gene by AP-2 might occur indirectly through physical and functional cooperation with HMGA1 and Sp1. Our findings support this hypothesis and suggest that in affected individuals, hyperactivation of the AP-2 gene through the overexpression of IR may play a key role in breast carcinogenesis.


Assuntos
Neoplasias da Mama/metabolismo , Receptor de Insulina/biossíntese , Fator de Transcrição AP-2/biossíntese , Neoplasias da Mama/genética , Linhagem Celular Tumoral , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteína HMGA1a/genética , Proteína HMGA1a/metabolismo , Células HeLa , Humanos , Regiões Promotoras Genéticas , Receptor de Insulina/genética , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismo , Fator de Transcrição AP-2/genética , Fator de Transcrição AP-2/metabolismo
17.
Clin Mol Hepatol ; 24(2): 151-162, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29684978

RESUMO

Background/Aims: Correct renal function evaluation is based on estimated glomerular filtration rates (eGFR) and complementary renal damage biomarkers, such as neutrophil gelatinase associated lipocalin (NGAL). The aim of this study was to evaluate eGFR and NGAL modifications and renal impairment during treatment with a direct acting antiviral (DAA) for chronic hepatitis C virus (HCV) infection. METHODS: A retrospective cohort study evaluated eGFR modification during treatment with DAA. Subgroup analysis on serum NGAL was conducted in those receiving sofosbuvir/ledipasvir, with complete follow-up until week 12 after the end of treatment (FU-12). RESULTS: In the 102 enrolled patients, eGFR reduction was observed (from 86.22 mL/min at baseline to 84.43 mL/min at FU-12, P=0.049). Mean NGAL increased in 18 patients (from 121.89 ng/mL at baseline to 204.13 ng/mL at FU-12, P=0.014). At FU-12, 38.8% (7/18) of patients had a plasmatic NGAL value higher than the normal range (36-203 ng/mL) compared with 11.1% (2/18) at baseline (χ 2 =3,704; P=0.054). In contrast, eGFR did not change significantly over the follow-up in this subgroup. Conclusions: In conclusion, compared to a negligible eGFR decline observed in the entire cohort analyzed, a significant NGAL increase was observed after HCV treatment with DAA in a small subgroup. This could reflect tubular damage during DAA treatment rather than glomerular injury.


Assuntos
Rim/fisiopatologia , Lipocalina-2/sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Idoso , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Feminino , Genótipo , Taxa de Filtração Glomerular , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Índice de Gravidade de Doença
18.
Nutrients ; 9(8)2017 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-28805669

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, characterized by liver fatty acid accumulation and fibrosis, not due to excessive alcohol consumption. Notably, nutritional habits have been reported to be implicated in the onset and severity of the hepatic damage, while the Mediterranean diet has shown beneficial effects on NAFLD. Free radicals and oxidative stress were suggested to be involved in the pathogenesis and progression of NAFLD, and several data highlighted the efficacy of antioxidant supplementation in its treatment. The aim of this study was to compare the effects of the Mediterranean diet, with or without an antioxidant complex supplement, in overweight patients suffering from NAFLD. In this prospective study, fifty Caucasian overweight patients were randomized into three groups (Groups A-C). A personalized moderately hypocaloric Mediterranean diet was prescribed to all patients included in the A and B groups. In addition to the diet, Group B was administered antioxidant supplementation daily and for the period of six months. Group C did not have any type of treatment. The study proved that the Mediterranean diet alone or in association with the antioxidant complex improved anthropometric parameters, lipid profile and reduced hepatic fat accumulation and liver stiffness. However, Group B patients, in which the diet was associated with antioxidant intake, showed not only a significant improvement in insulin sensitivity, but also a more consistent reduction of anthropometric parameters when compared with Group A patients. Taken together, these results support the benefit of antioxidant supplementation in overweight patients with NAFLD.


Assuntos
Antioxidantes/uso terapêutico , Dieta Mediterrânea , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Adulto , Antioxidantes/administração & dosagem , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etiologia , Sobrepeso/complicações , Sobrepeso/dietoterapia , Estudos Prospectivos
19.
Nutrients ; 9(4)2017 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-28420140

RESUMO

Oleuropein (OLE) is the major phenolic secoiridoid of olive tree leaves, and its antioxidant and anti-inflammatory activities have been demonstrated in in vitro and in vivo animal models. The aim of this study was to investigate the activity of OLE in the colonic mucosa from patients with ulcerative colitis (UC). Biopsies obtained during colonoscopy from 14 patients with active UC were immediately placed in an organ culture chamber and challenged with lipopolysaccharide from Escherichia coli (EC-LPS) at 1 µg/mL in the presence or absence of 3 mM OLE. The expression of cyclooxygenase (COX)-2 and interleukin (IL)-17 was assessed in total protein extracts from treated colonic biopsies by Western blotting. Levels of IL-17 were also measured in culture supernatant by ELISA. A microscopic evaluation of the cultured biopsies was performed by conventional histology and immunohistochemistry. The expression of COX-2 and IL-17 were significantly lower in samples treated with OLE + EC-LPS compared with those treated with EC-LPS alone (0.80 ± 0.15 arbitrary units (a.u.) vs. 1.06 ± 0.19 a.u., p = 0.003, and 0.71 ± 0.08 a.u. vs. 1.26 ± 0.42 a.u., p = 0.03, respectively) as were the levels of IL-17 in culture supernatants of OLE + EC-LPS treated colonic samples (21.16 ± 8.64 pg/mL vs. 40.67 ± 9.24 pg/mL, p = 0.01). Histologically, OLE-treated colonic samples showed an amelioration of inflammatory damage with reduced infiltration of CD3, CD4, and CD20 cells, while CD68 numbers increased. The anti-inflammatory activity of OLE was demonstrated in colonic biopsies from UC patients. These new data support a potential role of OLE in the treatment of UC.


Assuntos
Colite Ulcerativa/metabolismo , Colo/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Interleucina-17/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Iridoides/farmacologia , Olea/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Colite Ulcerativa/tratamento farmacológico , Colo/metabolismo , Feminino , Humanos , Mucosa Intestinal/metabolismo , Glucosídeos Iridoides , Iridoides/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
20.
Artigo em Inglês | MEDLINE | ID: mdl-29375472

RESUMO

PURPOSE: Although the role of dietary factors in the prevention of bone loss and fractures has been investigated in many studies, few studies have examined the association between dietary patterns and total body bone density. Our aim was to determine the relations between dietary patterns and whole-body bone mineral density (WB-BMD) and the association between dietary patterns, fractures, and multiple fractures in the elderly. METHODS: This cross-sectional study included 177 individuals aged ≥65 years. A dual X-ray absorptiometry scan was performed to measure BMD. Dietary patterns were ascertained by a combination of dietary intake assessment and principal components analysis. RESULTS: Only three dietary patterns correlated with whole-body bone density. The multivariate-adjusted mean bone density across tertiles of these dietary patterns showed that the highest tertile of both the patterns 1 and 2 had a significantly higher bone density than the lowest tertile (pattern 1: 1.021 ± 0.01 and 1.070 ± 0.01 g/cm2 for T1 and T3, respectively; p = 0.043; pattern 2: 1.023 ± 0.01, and 1.081 ± 0.01 g/cm2 for T1 and T3, respectively; p = 0.003). We also find significant gender difference in these results. The highest adherence to the dietary pattern 5 was associated with decreased odds of having fractures (OR = 0.20, p = 0.009), and adherence to the pattern 1 was negatively associated with multiple fractures. CONCLUSION: A high adherence to the dietary pattern 1 (high intake of grains, fish and olive oil) was associated with a high BMD and a low number of fractures. The highest adherence to the dietary pattern 5 (legumes and wine) was associated with decreased odds of having fractures. Our finding would suggest a potential bone-preserving properties of specific dietary patterns in the elderly.

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