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1.
Trials ; 22(1): 673, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593030

RESUMO

BACKGROUND: Metabolic syndrome is a combination of metabolic risk factors causing a pathological condition that increases the risk of non-communicable diseases, such as diabetes and cardiovascular diseases. A variety of dietary approaches have been examined to halt this rapid trend; however, the effects of modified-Paleo diet and medium-carbohydrate diet on inflammation, adipokines, hepatokines, and the profile of endothelial microparticles in individuals with metabolic syndrome have not been investigated in detail. The present study is designed to examine the effect of modified-Paleo and moderate-carbohydrate diet with two delivery modes: "fixed diet plan" vs "calorie counting" on weight, body composition, serum levels of some hepatokines and adipocytokines, and flow cytometric analysis of endothelial microparticles in adults with metabolic syndrome. METHODS: Eighty metabolic syndrome patients will be recruited in this study. They will be randomly allocated to one of the following 4 groups: (1) receiving a modified-Paleo diet with calorie counting, (2) receiving a modified-Paleo diet with a fixed diet plan, (3) receiving a medium-carbohydrate diet with calorie counting, and (4) receiving a medium-carbohydrate diet with a fixed diet plan for 10 weeks. Weight, height, waist circumference, and body composition will be assessed at the study baseline and at the end of the trial. Serum insulin, asprosin, chemerin, FGF-21, CTRP-1, PYY, ghrelin, plasma EMPs (CD31+/CD42b- and CD144+/CD42b-), lipid profile, glycemic indices, hs-CRP, leptin, vitamin C, creatinine and satiety, hunger, fullness, and desire to eat (via visual analog scales) will be measured at the study baseline and at the end of the trial. Insulin resistance and insulin sensitivity will be determined using the HOMA-IR and QUICKI equations. DISCUSSION: To the best of our knowledge, this is the first randomized controlled trial that will determine the effect of modified-Paleo and moderate-carbohydrate diet on weight, body composition, serum levels of some hepatokines and adipocytokines, and the profile of EMPs in adults with metabolic syndrome. Moreover, the effects of different diet delivery modes, including "fixed diet plan" and "calorie counting" will also be analyzed. The results of this trial can provide clinical witnesses on the effectiveness of carbohydrate-restricted diets in ameliorating metabolic status and prevent the development of chronic diseases. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT2016121925267N4 . Registered on 26 July 2017.


Assuntos
Síndrome Metabólica , Hormônios Peptídicos , Adipocinas , Adulto , Composição Corporal , Carboidratos , Quimiocinas , Dieta com Restrição de Carboidratos , Fibrilina-1 , Humanos , Irã (Geográfico) , Síndrome Metabólica/diagnóstico , Proteínas dos Microfilamentos , Fragmentos de Peptídeos , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
BMC Infect Dis ; 21(1): 1055, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635070

RESUMO

BACKGROUND: Diagnosing tuberculosis (TB) in children is challenging due to paucibacillary disease, and lack of ability for microbiologic confirmation. Hence, we measured the plasma chemokines as biomarkers for diagnosis of pediatric tuberculosis. METHODS: We conducted a prospective case control study using children with confirmed, unconfirmed and unlikely TB. Multiplex assay was performed to examine the plasma CC and CXC levels of chemokines. RESULTS: Baseline levels of CCL1, CCL3, CXCL1, CXCL2 and CXCL10 were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver operating characteristics curve analysis revealed that CCL1, CXCL1 and CXCL10 could act as biomarkers distinguishing confirmed or unconfirmed TB from unlikely TB with the sensitivity and specificity of more than 80%. In addition, combiROC exhibited more than 90% sensitivity and specificity in distinguishing confirmed and unconfirmed TB from unlikely TB. Finally, classification and regression tree models also offered more than 90% sensitivity and specificity for CCL1 with a cutoff value of 28 pg/ml, which clearly classify active TB from unlikely TB. The levels of CCL1, CXCL1, CXCL2 and CXCL10 exhibited a significant reduction following anti-TB treatment. CONCLUSION: Thus, a baseline chemokine signature of CCL1/CXCL1/CXCL10 could serve as an accurate biomarker for the diagnosis of pediatric tuberculosis.


Assuntos
Tuberculose , Biomarcadores , Estudos de Casos e Controles , Quimiocinas , Criança , Humanos , Plasma , Tuberculose/diagnóstico
3.
J Biomed Nanotechnol ; 17(8): 1574-1583, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544535

RESUMO

Cytokine-induced killer cell immunotherapy is an ideal candidate for adoptive cell transfer therapy. However, therapeutic approaches to enhance the anti-tumor activity of cytokine-induced killer cells remain to be explored. Here, we described the successful development of a novel antibody-chemokine fusion protein containing the anti-human Endoglin antibody in the single-chain variable fragment format and human interferon-gamma-induced protein 10 (hENG scFv/hIP-10). Its anti-Endoglin immunoreactivity and chemotactic activity against the cytokine-induced killer cells were characterized in vitro. To evaluate the anti-tumor effect in vivo, cytokine-induced killer cells were intravenously injected into human hepatocellular carcinoma-bearing nude mice, together with intratumoral administration of the fusion protein hENG scFv/hIP-10 as an enhancer. The tumor volume and survival time of the mice were monitored, whilst the tumor-infiltrating cytokine-induced killer cells, serum levels of interferon-gamma, tumor cell proliferation, apoptosis, and angiogenesis were measured. The results demonstrated that hENG scFv/hIP-10 and cytokine-induced killer cells synergistically inhibited tumor growth and prolonged survival of tumor-bearing mice. Moreover, the number of tumor-infiltrating cytokine-induced killer cells, serum levels of interferon-gamma, and tumor cell apoptosis were increased, accompanied with decreased tumor proliferation and angiogenesis. Thus, our study suggests that hENG scFv/hIP-10 could enhance the anti-tumor activity of cytokine-induced killer cells against human hepatocellular carcinoma.


Assuntos
Células Matadoras Induzidas por Citocinas , Neoplasias Hepáticas , Anticorpos de Cadeia Única , Animais , Linhagem Celular Tumoral , Quimiocinas , Endoglina , Humanos , Camundongos , Camundongos Nus , Anticorpos de Cadeia Única/genética
4.
Molecules ; 26(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34500609

RESUMO

Chemokines and chemokine receptors have been recognized as critical signal components that maintain the physiological functions of various cells, particularly the immune cells. The signals of chemokines/chemokine receptors guide various leukocytes to respond to inflammatory reactions and infectious agents. Many chemokine receptors play supportive roles in the differentiation, proliferation, angiogenesis, and metastasis of diverse tumor cells. In addition, the signaling functions of a few chemokine receptors are associated with cardiac, pulmonary, and brain disorders. Over the years, numerous promising molecules ranging from small molecules to short peptides and antibodies have been developed to study the role of chemokine receptors in healthy states and diseased states. These drug-like candidates are in turn exploited as radiolabeled probes for the imaging of chemokine receptors using noninvasive in vivo imaging, such as positron emission tomography (PET). Recent advances in the development of radiotracers for various chemokine receptors, particularly of CXCR4, CCR2, and CCR5, shed new light on chemokine-related cancer and cardiovascular research and the subsequent drug development. Here, we present the recent progress in PET radiotracer development for imaging of various chemokine receptors.


Assuntos
Quimiocinas/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Receptores de Quimiocinas/metabolismo , Animais , Doenças Cardiovasculares/metabolismo , Humanos , Neoplasias/metabolismo , Transdução de Sinais/fisiologia
5.
Front Immunol ; 12: 681516, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489933

RESUMO

Coronavirus disease 2019 (COVID-19) broke out and then became a global epidemic at the end of 2019. With the increasing number of deaths, early identification of disease severity and interpretation of pathogenesis are very important. Aiming to identify biomarkers for disease severity and progression of COVID-19, 75 COVID-19 patients, 34 healthy controls and 23 patients with pandemic influenza A(H1N1) were recruited in this study. Using liquid chip technology, 48 cytokines and chemokines were examined, among which 33 were significantly elevated in COVID-19 patients compared with healthy controls. HGF and IL-1ß were strongly associated with APACHE II score in the first week after disease onset. IP-10, HGF and IL-10 were correlated positively with virus titers. Cytokines were significantly correlated with creatinine, troponin I, international normalized ratio and procalcitonin within two weeks after disease onset. Univariate analyses were carried out, and 6 cytokines including G-CSF, HGF, IL-10, IL-18, M-CSF and SCGF-ß were found to be associated with the severity of COVID-19. 11 kinds of cytokines could predict the severity of COVID-19, among which IP-10 and M-CSF were excellent predictors for disease severity. In conclusion, the levels of cytokines in COVID-19 were significantly correlated with the severity of the disease in the early stage, and serum cytokines could be used as warning indicators of the severity and progression of COVID-19. Early stratification of disease and intervention to reduce hypercytokinaemia may improve the prognosis of COVID-19 patients.


Assuntos
COVID-19/imunologia , Citocinas/genética , Citocinas/imunologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Transcriptoma/imunologia , Adulto , Idoso , Biomarcadores/sangue , Quimiocinas/sangue , Quimiocinas/genética , Quimiocinas/imunologia , Citocinas/sangue , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Influenza Humana/sangue , Influenza Humana/imunologia , Masculino , Pessoa de Meia-Idade
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(8): 828-834, 2021 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34511173

RESUMO

OBJECTIVES: To study the expression of adipokines in children with primary nephrotic syndrome (PNS) before and after treatment and its correlation with blood lipids, as well as the role of adipokines in PNS children with hyperlipidemia. METHODS: A total of 90 children who were diagnosed with incipient PNS or recurrence of PNS after corticosteroid withdrawal for more than 6 months were enrolled as subjects. Thirty children who underwent physical examination were enrolled as the control group. Venous blood samples were collected from the children in the control group and the children with PNS before corticosteroid therapy (active stage) and after urinary protein clearance following 4 weeks of corticosteroid therapy (remission stage). ELISA was used to measure the levels of adipokines. An automatic biochemical analyzer was used to measure blood lipid levels. RESULTS: Compared with the control group, the children with PNS had a significantly lower level of omentin-1 in both active and remission stages, and their level of omentin-1 in the active stage was significantly lower than that in the remission stage (P<0.001). For the children with PNS, the level of chemerin in the active stage was significantly higher than that in the remission stage, and the children with PNS in the active stage had a significantly higher level of chemerin than the control group (P<0.001). For the children with PNS, atherogenic index of plasma, atherogenic coefficient (AC), castelli risk index-1 (CRI-1), castelli risk index-2 (CRI-2), and non-high-density lipoprotein in the active stage were significantly higher than those in the remission stage (P<0.001), and these indices in the children with PNS in the active stage were significantly higher than those in the control group (P<0.001). The children with PNS in the remission stage had significantly higher atherogenic index of plasma, AC, CRI-1, and non-high-density lipoprotein than the control group (P<0.001). Compared with the control group, the children with PNS in the remission stage had significantly higher serum levels of total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, apolipoprotein B, and apolipoprotein A (P<0.01). In the children with PNS, the ratio of omentin-1 before and after corticosteroid therapy was positively correlated with that of high-density lipoprotein, 24-hour urinary protein excretion, and high-density lipoprotein/apolipoprotein A before and after treatment, and it was negatively correlated with the ratio of AC and CRI-1 before and after treatment (P<0.05). The PNS children with low omentin-1 levels in the active stage had significantly higher levels of CRI-1, CRI-2, AC, and apolipoprotein B/apolipoprotein A ratio than those with high omentin-1 levels (P<0.05). CONCLUSIONS: Omentin-1 may be associated with disease activity, dyslipidemia, and proteinuria in children with PNS. Blood lipid ratios may be more effective than traditional blood lipid parameters in monitoring early cardiovascular risk in children with PNS.


Assuntos
Citocinas/metabolismo , Hiperlipidemias , Lectinas/metabolismo , Síndrome Nefrótica , Adipocinas , Quimiocinas , Criança , Citocinas/genética , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Humanos , Lectinas/genética , Lipídeos , Síndrome Nefrótica/tratamento farmacológico , Proteinúria
7.
J Infect Dis ; 224(5): 777-782, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34467988

RESUMO

We analyzed plasma levels of interferons (IFNs) and cytokines, and expression of IFN-stimulated genes in peripheral blood mononuclear cells in patients with coronavirus disease 2019 of varying disease severity. Patients hospitalized with mild disease exhibited transient type I IFN responses, while intensive care unit patients had prolonged type I IFN responses. Type II IFN responses were compromised in intensive care unit patients. Type III IFN responses were induced in the early phase of infection, even in convalescent patients. These results highlight the importance of early type I and III IFN responses in controlling coronavirus disease 2019 progression.


Assuntos
COVID-19/imunologia , Interferon Tipo I/imunologia , Interferon gama/imunologia , Interferons/imunologia , COVID-19/sangue , Quimiocinas/sangue , Citocinas/sangue , Humanos , Interferon Tipo I/sangue , Interferon Tipo I/genética , Interferon gama/sangue , Interferon gama/genética , Interferons/sangue , Leucócitos Mononucleares/imunologia , SARS-CoV-2/isolamento & purificação
8.
Nat Commun ; 12(1): 5205, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471128

RESUMO

Molecular mechanisms associated with human germ cell aplasia in infertile men remain undefined. Here we perform single-cell transcriptome profiling to highlight differentially expressed genes and pathways in each somatic cell type in testes of men with idiopathic germ cell aplasia. We identify immaturity of Leydig cells, chronic tissue inflammation, fibrosis, and senescence phenotype of the somatic cells, as well markers of chronic inflammation in the blood. We find that deregulated expression of parentally imprinted genes in myoid and immature Leydig cells, with relevant changes in the ratio of Lamin A/C transcripts and an active DNA damage response in Leydig and peritubular myoid cells are also indicative of senescence of the testicular niche. This study offers molecular insights into the pathogenesis of idiopathic germ cell aplasia.


Assuntos
Envelhecimento/fisiologia , Dano ao DNA , Inflamação , Testículo/metabolismo , Envelhecimento/genética , Comunicação Celular , Quimiocinas , Perfilação da Expressão Gênica , Células Germinativas , Humanos , Inflamação/patologia , Células Intersticiais do Testículo , Masculino , Fenótipo , Alinhamento de Sequência , Espermatogênese/genética , Espermatogênese/fisiologia , Espermatogônias/metabolismo , Transcriptoma
9.
PLoS One ; 16(8): e0256784, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34460840

RESUMO

Viral sepsis has been proposed as an accurate term to describe all multisystemic dysregulations and clinical findings in severe and critically ill COVID-19 patients. The adoption of this term may help the implementation of more accurate strategies of early diagnosis, prognosis, and in-hospital treatment. We accurately quantified 110 metabolites using targeted metabolomics, and 13 cytokines/chemokines in plasma samples of 121 COVID-19 patients with different levels of severity, and 37 non-COVID-19 individuals. Analyses revealed an integrated host-dependent dysregulation of inflammatory cytokines, neutrophil activation chemokines, glycolysis, mitochondrial metabolism, amino acid metabolism, polyamine synthesis, and lipid metabolism typical of sepsis processes distinctive of a mild disease. Dysregulated metabolites and cytokines/chemokines showed differential correlation patterns in mild and critically ill patients, indicating a crosstalk between metabolism and hyperinflammation. Using multivariate analysis, powerful models for diagnosis and prognosis of COVID-19 induced sepsis were generated, as well as for mortality prediction among septic patients. A metabolite panel made of kynurenine/tryptophan ratio, IL-6, LysoPC a C18:2, and phenylalanine discriminated non-COVID-19 from sepsis patients with an area under the curve (AUC (95%CI)) of 0.991 (0.986-0.995), with sensitivity of 0.978 (0.963-0.992) and specificity of 0.920 (0.890-0.949). The panel that included C10:2, IL-6, NLR, and C5 discriminated mild patients from sepsis patients with an AUC (95%CI) of 0.965 (0.952-0.977), with sensitivity of 0.993(0.984-1.000) and specificity of 0.851 (0.815-0.887). The panel with citric acid, LysoPC a C28:1, neutrophil-lymphocyte ratio (NLR) and kynurenine/tryptophan ratio discriminated severe patients from sepsis patients with an AUC (95%CI) of 0.829 (0.800-0.858), with sensitivity of 0.738 (0.695-0.781) and specificity of 0.781 (0.735-0.827). Septic patients who survived were different from those that did not survive with a model consisting of hippuric acid, along with the presence of Type II diabetes, with an AUC (95%CI) of 0.831 (0.788-0.874), with sensitivity of 0.765 (0.697-0.832) and specificity of 0.817 (0.770-0.865).


Assuntos
COVID-19/patologia , Metabolômica , Sepse/diagnóstico , Adulto , Área Sob a Curva , COVID-19/complicações , COVID-19/virologia , Quimiocinas/sangue , Citocinas/sangue , Feminino , Humanos , Cinurenina/sangue , Linfócitos/citologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Sepse/etiologia , Índice de Gravidade de Doença , Triptofano/sangue
10.
Immunol Res ; 69(5): 457-460, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34357535

RESUMO

In this manuscript, COVID-19, Ebola virus disease, Nipah virus infection, SARS, and MERS are suggested to be considered for a novel immunological reclassification as acute onset immune dysrhythmia syndrome (n-AIDS) due to altered monocytic, Th1/Th2, as well as cytokines and chemokines balances. n-AIDs is postulated to be the cause of the acute respiratory distress and multi-inflammatory syndromes which are described with fatal COVID-19, and immunomodulators are suggested to effectively manage the mentioned diseases as well as for other disorders caused by Th1/Th2 imbalance. Meanwhile, para COVID syndrome is suggested to describe various immune-related complications, whether before or after recovery, and to embrace a potential of a latent infection, that might be discovered later, as occurred with Ebola virus disease. Finally, our hypothesis has evolved out of our real-life practice that uses immunomodulatory drugs to manage COVID-19 safely and effectively.


Assuntos
COVID-19/imunologia , Citocinas/imunologia , Doença pelo Vírus Ebola/imunologia , Infecções por Henipavirus/imunologia , Síndrome de Imunodeficiência Adquirida/imunologia , COVID-19/tratamento farmacológico , Quimiocinas/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Doença pelo Vírus Ebola/tratamento farmacológico , Infecções por Henipavirus/tratamento farmacológico , Humanos , Fatores Imunológicos/uso terapêutico , Linfócitos/imunologia , SARS-CoV-2/fisiologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/imunologia
11.
BMC Infect Dis ; 21(1): 738, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344353

RESUMO

BACKGROUND: COVID-19 has spread widely worldwide, causing millions of deaths. We aim to explore the association of immunological features with COVID-19 severity. METHODS: We conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed, Web of Science, Scopus, the Cochrane Library and the grey literature. RESULTS: A total of 21 studies with 2033 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of immune cells including CD3+ T cell (× 106, MD, - 413.87; 95%CI, - 611.39 to - 216.34), CD4+ T cell (× 106, MD, - 203.56; 95%CI, - 277.94 to - 129.18), CD8+ T cell (× 106, MD, - 128.88; 95%CI, - 163.97 to - 93.79), B cell (× 106/L; MD, - 23.87; 95%CI, - 43.97 to - 3.78) and NK cell (× 106/L; MD, - 57.12; 95%CI, - 81.18 to - 33.06), and significantly higher levels of cytokines including TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75), and significantly higher levels of chemokines as MCP-1 (SMD, 3.41; 95%CI, 2.42 to 4.40), IP-10 (SMD, 2.82; 95%CI, 1.20 to 4.45) and eotaxin (SMD, 1.55; 95%CI, 0.05 to 3.05). However, no significant difference was found in other indicators such as Treg cell (× 106, MD, - 0.13; 95%CI, - 1.40 to 1.14), CD4+/CD8+ ratio (MD, 0.26; 95%CI, - 0.02 to 0.55), IFN-γ (pg/ml; MD, 0.26; 95%CI, - 0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, - 0.49 to 0.60), IL-4 (pg/ml; MD, - 0.03; 95%CI, - 0.68 to 0.62), GM-CSF (SMD, 0.44; 95%CI, - 0.46 to 1.35), and RANTES (SMD, 0.94; 95%CI, - 2.88 to 4.75). CONCLUSION: Our meta-analysis revealed significantly lower levels of immune cells (CD3+ T, CD4+ T, CD8+ T, B and NK cells), higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases in comparison to mild cases of COVID-19. Measurement of immunological features could help assess disease severity for effective triage of COVID-19 patients.


Assuntos
COVID-19 , Quimiocinas , Citocinas , Humanos , Células Matadoras Naturais , SARS-CoV-2
12.
J Infect Dis ; 224(4): 606-615, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398245

RESUMO

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe clinical phenotype of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that remains poorly understood. METHODS: Hospitalized children <18 years of age with suspected coronavirus disease 2019 (COVID-19) (N = 53) were recruited into a prospective cohort study; 32 had confirmed COVID-19, with 16 meeting the US Centers for Disease Control criteria for MIS-C. Differences in nasopharyngeal viral ribonucleic acid (RNA) levels, SARS-CoV-2 seropositivity, and cytokine/chemokine profiles were examined, including after adjustments for age and sex. RESULTS: The median ages for those with and without MIS-C were 8.7 years (interquartile range [IQR], 5.5-13.9) and 2.2 years (IQR, 1.1-10.5), respectively (P = .18), and nasopharyngeal levels of SARS-CoV-2 RNA did not differ significantly between the 2 groups (median 63 848.25 copies/mL versus 307.1 copies/mL, P = .66); 75% of those with MIS-C were antibody positive compared with 44% without (P = .026). Levels of 14 of 37 cytokines/chemokines (interleukin [IL]-1RA, IL-2RA, IL-6, IL-8, tumor necrosis factor-α, IL-10, IL-15, IL-18, monocyte chemoattractant protein [MCP]-1, IP-10, macrophage-inflammatory protein [MIP]-1α, MCP-2, MIP-1ß, eotaxin) were significantly higher in children with MIS-C compared to those without, irrespective of age or sex (false discovery rate <0.05; P < .05). CONCLUSIONS: The distinct pattern of heightened cytokine/chemokine dysregulation observed with MIS-C, compared with acute COVID-19, occurs across the pediatric age spectrum and with similar levels of nasopharyngeal SARS-CoV-2 RNA.


Assuntos
COVID-19/metabolismo , COVID-19/virologia , Quimiocinas/metabolismo , Citocinas/metabolismo , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/virologia , Adolescente , Fatores Etários , Anticorpos Antivirais/imunologia , Biomarcadores , COVID-19/diagnóstico , COVID-19/epidemiologia , Criança , Pré-Escolar , Interações Hospedeiro-Patógeno , Humanos , Masculino , RNA Viral , Testes Sorológicos , Índice de Gravidade de Doença , Fatores Sexuais , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Carga Viral
13.
Medicina (Kaunas) ; 57(8)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34440960

RESUMO

By participating in both the recruitment and activation of T lymphocytes, macrophages and neutrophils at the site of psoriatic inflammation, chemokines play an important role in the pathogenesis of psoriasis and, crucially, may be one indicator of the response to the systemic treatment of the disease. As a result of their major involvement in both physiological and pathological processes, both chemokines and their receptors have been identified as possible therapeutic targets. Due to their presence in the inflammatory process, they play a role in the pathogenesis of diseases that often coexist with psoriasis, such as atherosclerosis and psoriatic arthritis. Chemokines, cytokines and adhesion molecules may be biological markers of disease severity in psoriasis. However, the mechanism of inflammation in psoriasis is too complex to select only one marker to monitor the disease process and improvement after treatment. The aim of this review was to summarize previous reports on the role of chemokines in the pathogenesis of psoriasis, its treatment and comorbidities.


Assuntos
Artrite Psoriásica , Psoríase , Quimiocinas , Citocinas , Humanos , Inflamação
14.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360900

RESUMO

Endometriosis is a common gynaecological disorder characterized by the ectopic growth of endometrial tissue outside the uterine cavity. It is associated with chronic pelvic inflammation and autoimmune reactivity manifesting by autoantibody production and abrogated cellular immune responses. Endometriotic peritoneal fluid contains various infiltrating leucocyte populations and a bulk of proinflammatory and immunoregulatory cytokines. However, the nature and significance of the peritoneal milieu in women with endometriosis still remains obscure. Therefore, the aim of the present study was to investigate the immunoregulatory activity of the peritoneal fluid (PF) from women with endometriosis. The peritoneal fluid samples were collected during laparoscopic surgery from 30 women with and without endometriosis. Immunoregulatory cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF) and chemokines (CCL2, CCL5, CXCL8 and CXCL9) were evaluated in PF and culture supernatants generated by unstimulated and CD3/CD28/IL-2-stimulated CD4+ T cells cultured in the presence of PF. The effect of PF on the generation of Treg and Th17 cells in CD4+ T cell cultures, as well as the natural cytotoxic activity of peripheral blood mononuclear cells, was also investigated. Concentrations of IL-6, IL-10, CCL2, CXCL8 and CXCL9 were significantly upregulated in the PF from women with endometriosis when compared to control women, whereas concentrations of other cytokines and chemokines were unaffected. The culturing of unstimulated and CD3/CD28/IL-2-stimulated CD4+ T cells in the presence of endometriotic PF resulted in the downregulation of their IL-2, IFN-γ, IL-17A and TNF production as compared to culture medium alone. On the other side, endometriotic PF significantly stimulated the production of IL-4 and IL-10. Endometriotic PF also stimulated the release of CCL2 and CXCL8, whereas the production of CCL5 and CXCL9 was downregulated. Endometriotic PF stimulated the generation of Treg cells and had an inhibitory effect on the generation of Th17 cells in cultures of CD4+ T cells. It also inhibited the NK cell cytotoxic activity of the peripheral blood lymphocytes. These results strongly imply that the PF from patients with endometriosis has immunoregulatory/immunosuppressive activity and shifts the Th1/Th2 cytokine balance toward the Th2 response, which may account for deviation of local and systemic immune responses. However, a similar trend, albeit not a statistically significant one, was also observed in case of PF from women without endometriosis, thus suggesting that peritoneal milieu may in general display some immunoregulatory/immunosuppressive properties. It should be stressed, however, that our present observations were made on a relatively small number of PF samples and further studies are needed to reveal possible mechanism(s) responsible for this phenomenon.


Assuntos
Líquido Ascítico/imunologia , Quimiocinas/metabolismo , Endometriose/imunologia , Tolerância Imunológica , Células Th2/imunologia , Adulto , Líquido Ascítico/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Regulação para Cima , Adulto Jovem
15.
Nat Commun ; 12(1): 4852, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381028

RESUMO

Oncogenic activation of KRAS and its surrogates is essential for tumour cell proliferation and survival, as well as for the development of protumourigenic microenvironments. Here, we show that the deubiquitinase USP12 is commonly downregulated in the KrasG12D-driven mouse lung tumour and human non-small cell lung cancer owing to the activation of AKT-mTOR signalling. Downregulation of USP12 promotes lung tumour growth and fosters an immunosuppressive microenvironment with increased macrophage recruitment, hypervascularization, and reduced T cell activation. Mechanistically, USP12 downregulation creates a tumour-promoting secretome resulting from insufficient PPM1B deubiquitination that causes NF-κB hyperactivation in tumour cells. Furthermore, USP12 inhibition desensitizes mouse lung tumour cells to anti-PD-1 immunotherapy. Thus, our findings propose a critical component downstream of the oncogenic signalling pathways in the modulation of tumour-immune cell interactions and tumour response to immune checkpoint blockade therapy.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Microambiente Tumoral/imunologia , Ubiquitina Tiolesterase/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiocinas/metabolismo , Regulação para Baixo , Humanos , Tolerância Imunológica , Imunoterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Proteína Fosfatase 2C/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Ubiquitina Tiolesterase/antagonistas & inibidores
16.
Front Immunol ; 12: 720716, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381462

RESUMO

Objetive: To address the prevalence of SARS-CoV-2 and the evolutionary profile of immune compounds in breastmilk of positive mothers according to time and disease state. Methods: Forty-five women with term pregnancies with confirmed non-severe SARS-CoV-2 infection (case group), and 96 SARS-CoV-2 negative women in identical conditions (control group) were approached, using consecutive sample. Weekly (1st to 5th week postpartum) reverse transcription polymerase chain reaction (RT-PCR) in nasopharyngeal swabs (cases) and breastmilk (cases and controls) were obtained. Concentration of cytokines, chemokines, and growth factors in breastmilk (cases and controls) were determined at 1st and 5th week post-partum. Results: Thirty-seven (study group) and 45 (control group) women were enrolled. Symptomatic infection occurred in 56.8% of women in the study group (48% fever, 48% anosmia, 43% cough). SARS-CoV-2 RNA was not found in breastmilk samples. Concentrations of cytokines (IFN-γ, IL-1ra, IL-4, IL-6, IL-9, IL-13, and TNF-α) chemokines (eotaxin, IP-10, MIP-1α, and RANTES) and growth factors (FGF, GM-CSF, IL7, and PDGF-BB) were higher in breastmilk of the study compared with the control group at 1st week postpartum. Immune compounds concentrations decreased on time, particularly in the control group milk samples. Time of nasopharyngeal swab to become negative influenced the immune compound concentration pattern. Severity of disease (symptomatic or asymptomatic infection) did not affect the immunological profile in breast milk. Conclusions: This study confirms no viral RNA and a distinct immunological profile in breastmilk according to mother's SARS-CoV-2 status. Additional studies should address whether these findings indicate efficient reaction against SARS-CoV-2 infection, which might be suitable to protect the recipient child.


Assuntos
Quimiocinas/análise , Citocinas/análise , Peptídeos e Proteínas de Sinalização Intercelular/análise , Leite Humano/química , Leite Humano/imunologia , Adulto , Aleitamento Materno , COVID-19 , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Mães , Gravidez , Estudos Prospectivos , RNA Viral
17.
Pan Afr Med J ; 39: 40, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34422163

RESUMO

In its severe form, corona virus disease-19 (COVID-19) is characterized by various immunological abnormalities, dominated by massive pro-inflammatory cytokine and chemokine release, such as IL-6, TNF-α, IL-1b, IFN-y and monocyte chemoattractant protein-1 (MCP-1), associated with T CD3, T CD4 and T CD8 lymphopenia. These two abnormalities are significantly associated with COVID-19 acute severe respiratory syndrome. Conversely, these markers decrease during the favorable course of the disease. Coupled with other biological parameters such as leukopenia, increased level of CRP (C Reactive Protein), ferritin and D-dimers, high levels of IL-6 with CD4 and CD8 T cell lymphopenia may be considered as criteria of disease severity, justifying a rapid admission to the intensive care unit, and are also useful for patient monitoring.


Assuntos
COVID-19/imunologia , Quimiocinas/imunologia , Citocinas/imunologia , Biomarcadores/metabolismo , COVID-19/fisiopatologia , Humanos , Índice de Gravidade de Doença
18.
Talanta ; 234: 122705, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364500

RESUMO

This paper reports the preparation of the first dual electrochemical immunosensor for the simultaneous determination of the CXCL7 chemokine and the MMP3 metalloproteinase as relevant biomarkers for the better diagnosis and monitoring of rheumatoid arthritis derived from the multiple biomarkers measurement. The developed immunosensor involves the use of carboxylated magnetic beads (MBs) and dual screen-printed carbon electrodes (SPdCEs). Sandwich-type configurations implied the covalent immobilization of specific anti-CXCL7 (cAb1) or anti-MMP3 (cAb2) capture antibodies onto MBs and the use of biotinylated detection antibodies with further labelling with HRP-Strept conjugates. The resulting MBS bioconjugates were magnetically captured on the respective working electrode of the SPdCE and the determination of the antigens was accomplished by measuring the amperometric responses of H2O2 mediated by hydroquinone (HQ) at a potential value of -0.20 V. The dual immunosensor provided calibration plots with linear ranges between 1 and 75 ng mL-1 (CXCL7) (R2 = 0.997) and from 2.0 to 2000 pg mL-1 (MMP3) (R2 = 0.998) with detection limits of 0.8 ng mL-1 and 1.2 pg mL-1, respectively. The assay took 2 h 20 min for the simultaneous determination of both biomarkers. The dual immunosensor was successfully applied to the analysis of human serum from positive and negative RA patients.


Assuntos
Artrite Reumatoide , Técnicas Biossensoriais , Artrite Reumatoide/diagnóstico , Biomarcadores , Quimiocinas , Técnicas Eletroquímicas , Eletrodos , Humanos , Peróxido de Hidrogênio , Imunoensaio , Limite de Detecção , Metaloproteinase 3 da Matriz , beta-Tromboglobulina
19.
Life Sci ; 284: 119897, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34450172

RESUMO

AIM: Contradiction overwhelms chemerin link to feeding behavior. Neither the chemerin central role on appetite regulation nor its relation to hypothalamic histamine and AMPK is verified. MAIN METHODS: Food intake, body weight and hypothalamic biochemical changes were assessed after a single intra-cerebroventricular or intraperitoneal injection (ip) (1 µg/kg or 16 µg/kg, respectively) or chronic ip administration (8 µg/kg/day) of chemerin for 14 or 28 days. Hypothalamic neurobiochemical changes in chemerin/histamine/AMPK induced by either 8-week high fat diet (HFD) or food restriction were also investigated. To confirm chemerin-histamine crosstalk, these neurobiochemical changes were assessed under settings of H1-receptor agonism and/or antagonism by betahistine and/or olanzapine, respectively for 3 weeks. KEY FINDINGS: Chemerin-injected rats exhibited anorexigenic behavior in both acute and chronic studies that was associated with a decreased AMPK activity in the arcuate nucleus (ARC). However, with long-term administration, chemerin anorexigenic effect gradually ceased. Contrarily to food restriction, 8-week HFD increased ARC expression of chemerin and its receptor CMKLR1, reducing food intake via an interplay of H1-receptors and AMPK activity. Blockage of H1-receptors by olanzapine disrupted chemerin signaling pathway with an increased AMPK activity, augmenting food intake. These changes were reversed to normal by betahistine coadministration. SIGNIFICANCE: Chemerin is an anorexigenic adipokine, whose dysregulation is implicated in diet, and olanzapine-induced obesity through a histamine/AMPK axis in the ARC. Hypothalamic chemerin/CMKLR1 expression is a dynamic time-dependent response to changes in body weight and/or food intake. Targeting chemerin as a novel therapeutic approach against antipsychotic- or diet-induced obesity is worth to be further delineated.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Quimiocinas/metabolismo , Dieta , Histamina/metabolismo , Hipotálamo/metabolismo , Obesidade/induzido quimicamente , Obesidade/metabolismo , Olanzapina/efeitos adversos , Animais , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Núcleo Arqueado do Hipotálamo/metabolismo , beta-Histina/administração & dosagem , Peso Corporal/efeitos dos fármacos , Restrição Calórica , Quimiocinas/administração & dosagem , Dieta Hiperlipídica , Comportamento Alimentar/efeitos dos fármacos , Feminino , Antagonistas dos Receptores Histamínicos H1/farmacologia , Injeções Intraperitoneais , Ratos Wistar , Receptores de Quimiocinas/metabolismo , Receptores Histamínicos H1/metabolismo
20.
Biomolecules ; 11(8)2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34439815

RESUMO

BACKGROUND: Chemerin is an adipokine and a chemoattractant for leukocytes. Increased chemerin levels were observed in patients with coronary artery disease (CAD). We investigated associations between chemerin and biochemical measurements or body composition in CAD patients. METHODS: In the study, we included patients with stable CAD who had undergone percutaneous coronary intervention (PCI) in the past. All patients had routine blood tests, and their insulin and chemerin serum levels were routinely measured. Body composition was assessed with the DEXA method. RESULTS: The study group comprised 163 patients (mean age 59.8 ± years, 26% of females, n = 43). There was no significant difference in serum chemerin concentrations between patients with diabetes and the remaining ones: 306.8 ± 121 vs. 274.15 ± 109 pg/mL, p = 0.1. Chemerin correlated positively with the white blood cell (WBC) count, the neutrophil to lymphocyte ratio, hsCRP, all fractions of cholesterol, triglycerides, platelet count, fasting insulin, and c-peptide. Chemerin levels were also correlated with total fat mass but only in a subgroup with normal glucose metabolism. CONCLUSION: In patients with CAD, serum chemerin levels are correlated with inflammation markers, insulin resistance, and an unfavorable lipid profile. Correlation with fat mass is dependent on glucose metabolism status. Depending on the presence of diabetes/prediabetes, the mechanisms regulating chemerin secretion may be different.


Assuntos
Plaquetas/metabolismo , Quimiocinas/genética , Doença da Artéria Coronariana/sangue , Diabetes Mellitus Tipo 2/sangue , Linfócitos/metabolismo , Neutrófilos/metabolismo , Idoso , Glicemia/metabolismo , Plaquetas/patologia , Composição Corporal , Peptídeo C/sangue , Proteína C-Reativa/metabolismo , Quimiocinas/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/terapia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/terapia , Feminino , Humanos , Inflamação , Insulina/sangue , Resistência à Insulina , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Intervenção Coronária Percutânea , Projetos Piloto , Triglicerídeos/sangue
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