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1.
Sci Rep ; 13(1): 599, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635313

RESUMO

There is a lack of objective tools for monitoring treatment response in extrapulmonary tuberculosis (EPTB). This study aimed to explore the utility of inflammatory biomarkers from the dry blood spots (DBS) as a tool for monitoring treatment response in EPTB. In a prospective cohort study, 40 inflammatory biomarkers were investigated in DBS samples from 105 EPTB cases using a Luminex platform. The samples were taken before, and, at the end of the 2nd and 6th months of treatment. A total of 11 inflammatory host biomarkers changed significantly with treatment in all EPTB patients. CXCL9/MIG, CCL20, CCL23, CXCL10/IP-10, CXCL1, CXCL2, and CXCL8 significantly declined in our cohort of EPTB (48 TB pleuritis and 57 TB lymphadenitis) patients at both time points. A biosignature consisting of MIG, CCL23, and CXCL2, corresponded with the treatment response in 81% of patients in the 2nd month and 79% of patients at the end of treatment. MIG, CCL23, IP-10, and CXCL2 changed significantly with treatment in all patients including those showing partial clinical response at the 2nd month of treatment. The changes in the levels of inflammatory biomarkers in the DBS correspond with the treatment success and can be developed as a routine test in low-resource settings.


Assuntos
Tuberculose Pleural , Humanos , Biomarcadores , Quimiocina CXCL10 , Estudos Prospectivos , /diagnóstico , Tuberculose Pleural/sangue , Tuberculose Pleural/diagnóstico , Teste em Amostras de Sangue Seco , Quimiocinas/sangue
2.
Int J Mol Sci ; 23(19)2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36232755

RESUMO

Compelling evidence supports the health benefits of physical exercise on the immune system, possibly through the molecules secreted by the skeletal muscles known as myokines. Herein, we assessed the impact of exercise interventions on plasma Heat shock protein 90 (Hsp90) levels in 27 patients with idiopathic inflammatory myopathies (IIM) compared with 23 IIM patients treated with standard-of-care immunosuppressive therapy only, and in 18 healthy subjects undergoing strenuous eccentric exercise, and their associations with the traditional serum markers of muscle damage and inflammation. In contrast to IIM patients treated with pharmacotherapy only, in whom we demonstrated a significant decrease in Hsp90 over 24 weeks, the 24-week exercise program resulted in a stabilization of Hsp90 levels. These changes in Hsp90 levels were associated with changes in several inflammatory cytokines/chemokines involved in the pathogenesis of IIM or muscle regeneration in general. Strenuous eccentric exercise in healthy volunteers induced a brief increase in Hsp90 levels with a subsequent return to baseline levels at 14 days after the exercise, with less pronounced correlations to systemic inflammation. In this study, we identified Hsp90 as a potential myokine and mediator for exercise-induced immune response and as a potential biomarker predicting improvement after physiotherapy in muscle endurance in IIM.


Assuntos
Terapia por Exercício , Proteínas de Choque Térmico HSP90 , Inflamação , Músculo Esquelético , Miosite , Biomarcadores/sangue , Biomarcadores/metabolismo , Quimiocinas/sangue , Quimiocinas/metabolismo , Citocinas/sangue , Citocinas/metabolismo , Proteínas de Choque Térmico HSP90/sangue , Proteínas de Choque Térmico HSP90/metabolismo , Voluntários Saudáveis , Humanos , Imunossupressores/uso terapêutico , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/terapia , Músculo Esquelético/metabolismo , Miosite/sangue , Miosite/tratamento farmacológico , Miosite/metabolismo , Miosite/terapia
3.
Int J Mol Sci ; 23(16)2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-36012323

RESUMO

BACKGROUND: Infection caused by SARS-CoV-2 mostly affects the upper and lower respiratory tracts and causes symptoms ranging from the common cold to pneumonia with acute respiratory distress syndrome. Chemokines are deeply involved in the chemoattraction, proliferation, and activation of immune cells within inflammation. It is crucial to consider that mutations within the virion can potentially affect the clinical course of SARS-CoV-2 infection because disease severity and manifestation vary depending on the genetic variant. Our objective was to measure and assess the different concentrations of chemokines involved in COVID-19 caused by different variants of the virus. METHODS: We used the blood plasma of patients infected with different variants of SARS-CoV-2, i.e., the ancestral Wuhan strain and the Alpha, Delta, and Omicron variants. We measured the concentrations of 11 chemokines in the samples: CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, and CX3CL1/Fractalkine. RESULTS: We noted a statistically significant elevation in the concentrations of CCL2/MCP-1, CXCL8/IL-8, and CXCL1/IP-10 independently of the variant, and a drop in the CCL22/MDC concentrations. CONCLUSIONS: The chemokine concentrations varied significantly depending on the viral variant, leading us to infer that mutations in viral proteins play a role in the cellular and molecular mechanisms of immune responses.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/imunologia , Quimiocina CXCL10 , Quimiocinas/sangue , Humanos , Interleucina-8 , Plasma
4.
Exp Gerontol ; 164: 111771, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35351526

RESUMO

The ageing process is a complex phenomenon that impacts the immune system, leading to changes in the pattern of serum soluble mediators. In the present study, the serum levels of several chemokines, pro-inflammatory/regulatory cytokines and growth factors were quantified by high-throughput microbeads array in serum samples from 541 healthy subjects at distinct age ranges (3Yrs to >70Yrs). A broad increase in serum soluble mediators was observed at 6-10Yrs with subsequent decline at 11-20Yrs and 21-30Yrs followed by a second round of upregulation starting at 31-40Yrs, with a large increase at 51-60Yrs and a marked decline at age >70Yrs. Heatmap and signatures of serum soluble mediators demonstrated a bimodal profile with one peak at 6-10Yrs and a second wave around 61-70Yrs. A universal decline was observed later at age >70Yrs. In males, the second wave started earlier at 31-40Yrs with a peak at 51-60Yrs and a further smooth decline towards >70Yrs. Conversely, in females, the first peak extended from 3-5Yrs to 6-10Yrs and the second wave starting around 41-50Yrs with a peak at 61-70Yrs followed by a sharp decline at >70Yrs. Overall, CCL11, CXCL8, IL-1ß, IL-6 were underscored as universal age-related biomarkers with higher levels observed at later age ranges (after 31-40Yrs) and TNF with increased levels starting at early age ranges. Data analysis demonstrated that the highest neighborhood connectivity amongst soluble mediators occurred at 3-5Yrs, with distinct declining and strengthening rhythm in males and females. Notably, rebuilding re-arrangements were usually earlier and more frequent in females (at 11-20Yrs, 51-60Yrs and >70Yrs) than in males (at 21-30Yrs, 61-70Yrs). Overall, this study provided a comprehensive landscape of evidence portrayed by distinct waves, rhythms and dynamic network connectivity along healthy ageing with differences in magnitude and timing reported for sexes.


Assuntos
Quimiocinas , Citocinas , Envelhecimento Saudável , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Quimiocinas/sangue , Criança , Pré-Escolar , Citocinas/sangue , Feminino , Envelhecimento Saudável/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Sci Rep ; 12(1): 3954, 2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35273264

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a variety of clinical symptoms ranging from no or mild to severe disease. Currently, there are multiple postulated mechanisms that may push a moderate to severe disease into a critical state. Human serum contains abundant evidence of the immune status following infection. Cytokines, chemokines, and antibodies can be assayed to determine the extent to which a patient responded to a pathogen. We examined serum and plasma from a cohort of patients infected with SARS-CoV-2 early in the pandemic and compared them to negative-control sera. Cytokine and chemokine concentrations varied depending on the severity of infection, and antibody responses were significantly increased in severe cases compared to mild to moderate infections. Neutralization data revealed that patients with high titers against an early 2020 SARS-CoV-2 isolate had detectable but limited neutralizing antibodies against the emerging SARS-CoV-2 Alpha, Beta and Delta variants. This study highlights the potential of re-infection for recovered COVID-19 patients.


Assuntos
Anticorpos Amplamente Neutralizantes/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/imunologia , Quimiocinas/sangue , Citocinas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Adulto Jovem
6.
Lipids Health Dis ; 21(1): 27, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35236351

RESUMO

BACKGROUND AND OBJECTIVES: Chemerin is a brand-new adipokine that has been linked to both inflammation and metabolic dysfunction. Even though a rising number of studies have connected chemerin to metabolic-associated fatty liver disease (MAFLD), formerly referred to as non-alcoholic fatty liver disease (NAFLD), this association has been controversial. METHODS: A comprehensive literature search was undertaken up to February 1, 2022, in the PubMed, Embase, Web of Science, CNKI, WANFANG, and CBM library databases. Circulating chemerin levels were obtained and summarized using the standardized mean difference (SMD) and 95% confidence interval (CI). Subgroup and meta-regression analyses were conducted to examine the possibility of heterogeneity. RESULTS: A total of 17 studies involving 2580 participants (1584 MAFLD patients and 996 controls) evaluated circulating chemerin levels in patients with MAFLD. The present study showed that higher chemerin levels were found in patients with MAFLD (SMD: 1.32; 95% CI: 0.29, 2.35) and nonalcoholic fatty liver (NAFL) (SMD: 0.75; 95% CI: 0.01, 1.50) compared to controls. However, circulating chemerin levels did not differ significantly in the following comparisons: nonalcoholic steatohepatitis (NASH) patients and controls (SMD: 0.75; 95% CI: -0.52, 2.03); NASH patients and NAFL patients (SMD: 0.16; 95% CI: -0.39, 0.70); moderate to severe steatosis and mild steatosis (SMD: 0.55; 95% CI: -0.59, 1.69); present liver fibrosis and absent liver fibrosis (SMD: 0.66; 95% CI: -0.42, 1.74); present lobular inflammation and absent lobular inflammation (SMD: 0.45; 95% CI: -0.53, 1.42); and present portal inflammation and absent portal inflammation (SMD: 1.92; 95% CI: -0.85, 4.69). CONCLUSIONS: Chemerin levels were considerably greater in patients with MAFLD than in controls, despite the fact that they were not significantly linked to different liver tissue lesions of MAFLD. In different subtypes of MAFLD, in comparison to healthy controls, the chemerin levels of NAFL patients were higher, whereas, there was no obvious difference in chemerin levels between NASH patients and controls. It is possible that chemerin will be used as a biomarker in the future to track the development and progression of MAFLD.


Assuntos
Adipocinas , Hepatopatia Gordurosa não Alcoólica , Biomarcadores , Quimiocinas/sangue , Quimiocinas/metabolismo , Humanos , Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica/patologia
7.
J Trop Pediatr ; 68(2)2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35179604

RESUMO

Predictors of early diagnosis and severe infection in children with coronavirus disease 2019 (COVID-19), which has killed more than 4 million people worldwide, have not been identified. However, some biomarkers, including cytokines and chemokines, are associated with the diagnosis, pathogenesis and severity of COVID-19 in adults. We examined whether such biomarkers can be used to predict the diagnosis and prognosis of COVID-19 in pediatric patients. Eighty-nine children were included in the study, comprising three patient groups of 69 patients (6 severe, 36 moderate and 27 mild) diagnosed with COVID-19 by real-time polymerase chain reaction observed for 2-216 months and clinical findings and 20 healthy children in the same age group. Hemogram, coagulation, inflammatory parameters and serum levels of 16 cytokines and chemokines were measured in blood samples and were analyzed and compared with clinical data. Interleukin 1-beta (IL-1ß), interleukin-12 (IL-12) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in the COVID-19 patients (p = 0.035, p = 0.006 and p < 0.001). Additionally, D-dimer and IP-10 levels were higher in the severe group (p = 0.043 for D-dimer, area under the curve = 0.743, p = 0.027 for IP-10). Lymphocytes, C-reactive protein and procalcitonin levels were not diagnostic or prognostic factors in pediatric patients (p = 0.304, p = 0.144 and p = 0.67). Increased IL-1ß, IL-12 and IP-10 levels in children with COVID-19 are indicators for early diagnosis, and D-dimer and IP-10 levels are predictive of disease severity. In children with COVID-19, these biomarkers can provide information on prognosis and enable early treatment.


Assuntos
Biomarcadores , COVID-19 , Citocinas/sangue , Biomarcadores/sangue , COVID-19/diagnóstico , Quimiocina CXCL10 , Quimiocinas/sangue , Criança , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Interleucina-12 , Interleucina-1beta , Prognóstico , SARS-CoV-2 , Índice de Gravidade de Doença
8.
Sci Rep ; 12(1): 2437, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35165387

RESUMO

Previous studies have highlighted the role of pre-infection systemic inflammation on HIV acquisition risk, but the extent to which it predicts disease progression outcomes is less studied. Here we examined the relationship between pre-infection plasma cytokine expression and the rate of HIV disease progression in South African women who seroconverted during the CAPRISA 004 tenofovir gel trial. Bio-Plex 200 system was used to measure the expression of 47 cytokines/chemokines in 69 seroconvertors from the CAPRISA 004 trial. Cox proportional hazards regression analyses were used to measure associations between cytokine expression and CD4 decline prior to antiretroviral therapy initiation. Linear regression models were used to assess whether pre-infection cytokine expression were predictors of disease progression outcomes including peak and set-point viral load and CD4:CD8 ratio at less and greater than180 days post infection. Several cytokines were associated with increased peak HIV viral load (including IL-16, SCGFß, MCP-3, IL-12p40, SCF, IFNα2 and IL-2). The strongest association with peak viral load was observed for SCGFß, which was also inversely associated with lowest CD4:CD8 ratio < 180 days post infection and faster CD4 decline below 500 cells/µl (adjusted HR 4.537, 95% CI 1.475-13.954; p = 0.008) in multivariable analysis adjusting for age, study site, contraception, baseline HSV-2 status and trial arm allocation. Our results show that pre-infection systemic immune responses could play a role in HIV disease progression, especially in the early stages of infection.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Quimiocinas/sangue , Progressão da Doença , Infecções por HIV/sangue , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Tenofovir/uso terapêutico , Adolescente , Adulto , Biomarcadores/sangue , Relação CD4-CD8 , Estudos de Coortes , Método Duplo-Cego , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Soropositividade para HIV , Humanos , Imunidade , Prognóstico , África do Sul/epidemiologia , Resultado do Tratamento , Carga Viral , Adulto Jovem
9.
Biomolecules ; 12(2)2022 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-35204801

RESUMO

Chemerin, a novel adipokine, is a potent chemoattractant molecule with antimicrobial properties, implicated in immune responses. Our aim was to investigate circulating chemerin and its kinetics, early in sepsis in critically ill patients and its association with severity and prognosis. Serum chemerin was determined in a cohort of 102 critically ill patients with sepsis during the first 48 h from sepsis onset and one week later, and in 102 age- and gender-matched healthy controls. Patients were followed for 28 days and their outcomes were recorded. Circulating chemerin was significantly higher in septic patients at onset compared to controls (342.3 ± 108.1 vs. 200.8 ± 40.1 µg/L, p < 0.001). Chemerin decreased significantly from sepsis onset to one week later (342.3 ± 108.1 vs. 308.2 ± 108.5 µg/L, p < 0.001), but remained higher than in controls. Chemerin was higher in patients presenting with septic shock than those with sepsis (sepsis onset: 403.2 ± 89.9 vs. 299.7 ± 99.5 µg/L, p < 0.001; one week after: 374.9 ± 95.3 vs. 261.6 ± 91.9 µg/L, p < 0.001), and in nonsurvivors than survivors (sepsis onset: 427.2 ± 96.7 vs. 306.9 ± 92.1 µg/L, p < 0.001; one week after: 414.1 ± 94.5 vs. 264.2 ± 79.9 µg/L, p < 0.001). Moreover, patients with septic shock and nonsurvivors, presented a significantly lower absolute and relative decrease in chemerin one week after sepsis onset compared to baseline (p < 0.001). Based on ROC curve analyses, the diagnostic performance of chemerin (AUC 0.78, 95% CI 0.69-0.87) was similar to C-reactive protein (CRP) (AUC 0.78, 95% CI 0.68-0.87) in discriminating sepsis severity. However, increased chemerin at sepsis onset and one week later was an independent predictor of 28-day mortality (sepsis onset: HR 3.58, 95% CI 1.48-8.65, p = 0.005; one week after: HR 10.01, 95% CI 4.32-23.20, p < 0.001). Finally, serum chemerin exhibited significant correlations with the severity scores, white blood cells, lactate, CRP and procalcitonin, as well as with biomarkers of glucose homeostasis, but not with cytokines and soluble urokinase-type plasminogen activator receptor (suPAR). Circulating chemerin is increased early in sepsis and its kinetics may have diagnostic and prognostic value in critically ill patients. Further studies are needed to shed light on the role of chemerin in sepsis.


Assuntos
Quimiocinas , Sepse , Choque Séptico , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Quimiocinas/sangue , Estado Terminal , Humanos , Prognóstico , Estudos Prospectivos , Sepse/sangue , Sepse/diagnóstico , Choque Séptico/sangue , Choque Séptico/diagnóstico
10.
Theranostics ; 12(1): 290-306, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34987646

RESUMO

Coronavirus disease 2019 (COVID19), caused by SARS-CoV-2, is a complex disease, with a variety of clinical manifestations ranging from asymptomatic infection or mild cold-like symptoms to more severe cases requiring hospitalization and critical care. The most severe presentations seem to be related with a delayed, deregulated immune response leading to exacerbated inflammation and organ damage with close similarities to sepsis. Methods: In order to improve the understanding on the relation between host immune response and disease course, we have studied the differences in the cellular (monocytes, CD8+ T and NK cells) and soluble (cytokines, chemokines and immunoregulatory ligands) immune response in blood between Healthy Donors (HD), COVID19 and a group of patients with non-COVID19 respiratory tract infections (NON-COV-RTI). In addition, the immune response profile has been analyzed in COVID19 patients according to disease severity. Results: In comparison to HDs and patients with NON-COV-RTI, COVID19 patients show a heterogeneous immune response with the presence of both activated and exhausted CD8+ T and NK cells characterised by the expression of the immune checkpoint LAG3 and the presence of the adaptive NK cell subset. An increased frequency of adaptive NK cells and a reduction of NK cells expressing the activating receptors NKp30 and NKp46 correlated with disease severity. Although both activated and exhausted NK cells expressing LAG3 were increased in moderate/severe cases, unsupervised cell clustering analyses revealed a more complex scenario with single NK cells expressing more than one immune checkpoint (PD1, TIM3 and/or LAG3). A general increased level of inflammatory cytokines and chemokines was found in COVID19 patients, some of which like IL18, IL1RA, IL36B and IL31, IL2, IFNα and TNFα, CXCL10, CCL2 and CCL8 were able to differentiate between COVID19 and NON-COV-RTI and correlated with bad prognosis (IL2, TNFα, IL1RA, CCL2, CXCL10 and CXCL9). Notably, we found that soluble NKG2D ligands from the MIC and ULBPs families were increased in COVID19 compared to NON-COV-RTI and correlated with disease severity. Conclusions: Our results provide a detailed comprehensive analysis of the presence of activated and exhausted CD8+T, NK and monocyte cell subsets as well as extracellular inflammatory factors beyond cytokines/chemokines, specifically associated to COVID19. Importantly, multivariate analysis including clinical, demographical and immunological experimental variables have allowed us to reveal specific immune signatures to i) differentiate COVID19 from other infections and ii) predict disease severity and the risk of death.


Assuntos
COVID-19/sangue , COVID-19/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Linfócitos T CD8-Positivos/virologia , COVID-19/mortalidade , Estudos de Casos e Controles , Quimiocinas/sangue , Citocinas/sangue , Feminino , Hospitalização , Humanos , Células Matadoras Naturais/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Monócitos/virologia , Estudos Prospectivos , Infecções Respiratórias/sangue , Infecções Respiratórias/imunologia , Índice de Gravidade de Doença
11.
Cytokine ; 150: 155790, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34991059

RESUMO

BACKGROUND: Several immune mediators (IM) including cytokines, chemokines, and their receptors have been suggested to play a role in COVID-19 pathophysiology and severity. AIM: To determine if early IM profiles are predictive of clinical outcome and which of the IMs tested possess the most clinical utility. METHODS: A custom bead-based multiplex assay was used to measure IM concentrations in a cohort of SARS-CoV-2 PCR positive patients (n = 326) with varying disease severities as determined by hospitalization status, length of hospital stay, and survival. Patient groups were compared, and clinical utility was assessed. Correlation plots were constructed to determine if significant relationships exist between the IMs in the setting of COVID-19. RESULTS: In PCR positive SARS-CoV-2 patients, IL-6 was the best predictor of the need for hospitalization and length of stay. Additionally, MCP-1 and sIL-2Rα were moderate predictors of the need for hospitalization. Hospitalized PCR positive SARS-CoV-2 patients displayed a notable correlation between sIL-2Rα and IL-18 (Spearman's ρ = 0.48, P=<0.0001). CONCLUSIONS: IM profiles between non-hospitalized and hospitalized patients were distinct. IL-6 was the best predictor of COVID-19 severity among all the IMs tested.


Assuntos
COVID-19/imunologia , Citocinas/fisiologia , Hospitalização , Receptores de Citocinas/fisiologia , SARS-CoV-2 , Adulto , Área Sob a Curva , Biomarcadores , Proteína C-Reativa/análise , COVID-19/fisiopatologia , COVID-19/terapia , Quimiocinas/sangue , Quimiocinas/fisiologia , Citocinas/sangue , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Mortalidade Hospitalar , Humanos , Interleucina-6/sangue , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Receptores de Quimiocinas/fisiologia , Respiração Artificial/estatística & dados numéricos , Índice de Gravidade de Doença , Resultado do Tratamento
12.
Cancer Epidemiol Biomarkers Prev ; 31(1): 236-241, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34697062

RESUMO

BACKGROUND: Previous prospective studies of associations between circulating inflammation-related molecules and pancreatic cancer risk have included limited numbers of markers. METHODS: We conducted a case-cohort study nested within the Japan Public Health Center-based Prospective Study Cohort II. We selected a random subcohort (n = 774) from a total of 23,335 participants aged 40 to 69 years who returned a questionnaire and provided blood samples at baseline. During the follow-up period from 1993 to 2010, we identified 111 newly diagnosed pancreatic cancer cases, including one case within the subcohort. Plasma concentrations of 62 inflammatory markers of chemokines, cytokines, and growth factors were measured by a Luminex fluorescent bead-based assay. Cox regression models were applied to estimate HR and 95% confidence intervals (CI) for pancreatic cancer risk for quartiles of marker levels adjusted for potential confounders. RESULTS: The HR (95% CI) for the highest versus the lowest category of C-C motif ligand chemokine 8/monocyte chemoattractant protein 2 (CCL8/MCP2) was 2.03 (1.05-3.93; P trend = 0.048). After we corrected for multiple comparisons, none of the examined biomarkers were associated with pancreatic cancer risk at P-value <0.05. CONCLUSIONS: We found no significant associations between 62 inflammatory markers and pancreatic cancer risk. IMPACT: The suggestive association with circulating levels of leukocyte recruiting cytokine CCL8/MCP2 may warrant further investigation.


Assuntos
Biomarcadores Tumorais/sangue , Inflamação/sangue , Neoplasias Pancreáticas/sangue , Adulto , Idoso , Quimiocinas/sangue , Citocinas/sangue , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
13.
Brain Dev ; 44(1): 30-35, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34332826

RESUMO

OBJECTIVE: Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS), the second most common encephalopathy syndrome in Japan, is most often associated with viral infection. Bacterial MERS has been rarely reported but is mostly associated with acute focal bacterial nephritis (AFBN) for an unknown reason. We examined cytokines and chemokines in four MERS patients with AFBN to determine if they play an important role in the pathogenesis. METHODS: We examined the clinical charts and MRI results in four MERS patients with AFBN, and measured 10 cytokines and chemokines in serum and cerebrospinal fluid in the acute phase. These were analyzed using the Mann-Whitney U test, compared with the control group (cases with a non-inflammatory neurological disease). Longitudinal changes in the serum cytokine and chemokine levels were evaluated in two patients. RESULTS: Hyponatremia was observed in all four patients with MERS associated with AFBN (128-134 mEq/L). CSF analysis revealed increased cytokines/chemokines associated with Th1 (CXCL10, TNF-α, IFN-γ), T reg (IL-10), Th17 (IL-6), and neutrophil (IL-8 and CXCL1). In serum, upregulation was observed in those associated with Th1 (CXCL10, TNF-α, IFN-γ), Th17 (IL-6), and inflammasome (IL-1ß). The increased serum cytokines/chemokines in the acute stage normalized within 2 weeks in patients 1 and 2, so examined, in accordance with their clinical improvement. CONCLUSION: Increased cytokines/chemokines and hyponatremia may be factors that explain why AFBN is likely to cause MERS.


Assuntos
Infecções Bacterianas/complicações , Citocinas , Encefalite/etiologia , Hiponatremia/complicações , Nefrite/complicações , Infecções Bacterianas/sangue , Infecções Bacterianas/líquido cefalorraquidiano , Infecções Bacterianas/imunologia , Quimiocinas/sangue , Quimiocinas/líquido cefalorraquidiano , Quimiocinas/imunologia , Pré-Escolar , Citocinas/sangue , Citocinas/líquido cefalorraquidiano , Citocinas/imunologia , Encefalite/sangue , Encefalite/líquido cefalorraquidiano , Encefalite/imunologia , Feminino , Humanos , Hiponatremia/sangue , Hiponatremia/líquido cefalorraquidiano , Hiponatremia/imunologia , Masculino , Nefrite/sangue , Nefrite/líquido cefalorraquidiano , Nefrite/imunologia
14.
Gene ; 807: 145888, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34371096

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is a glucose intolerance condition encounters for the first time in a fraction of pregnant women. The role of different host inflammatory molecules in GDM etiology has been deciphered. Chemerin is a chemoattractant protein primarily associated with the pathogenesis of type 2 diabetes, obesity, and metabolic syndrome. However, the association of chemerin and its genetic variants with the predisposition of GDM is not clear, and our present study is aimed to address the issue. MATERIALS AND METHODS: A total of 703 Chinese women comprising of GDM (n = 303), glucose tolerant pregnant women (n = 211), and non-pregnant glucose tolerant controls (n = 189) were recruited in the present investigation. GDM was diagnosed according to the World Health Organization recommendation for diagnosis of gestational diabetes during pregnancy. Plasma levels of chemerin were quantified by an Enzyme-linked Immunosorbent Assay (ELISA). Common variants in the chemerin gene (rs4721, rs17173617, rs7806429, and rs17173608) were genotyped by using TaqMan assay. RESULTS: Plasma chemerin level was found higher in subjects with GDM as compared to glucose tolerant pregnant and non-pregnant women. Further, a positive correlation between plasma chemerin and HOMA-IR index suggesting an essential role of chemerin in mediating insulin resistance. Variants of rs4721 and rs17173608 polymorphisms were associated with lower levels of plasma chemerin and low HOMA-IR index. Furthermore, mutants of rs4721 and rs17173608 polymorphisms were associated with protection against the development of GDM in the Chinese cohort. CONCLUSIONS: Plasma chemerin is elevated in GDM patients. Genetic variation in chemerin gene associated with lower plasma levels of chemerin, HOMA-IR index and protects against the development of GDM in Chinese.


Assuntos
Quimiocinas/genética , Quimiocinas/metabolismo , Diabetes Gestacional/genética , Adulto , Glicemia/genética , Quimiocinas/sangue , China , Estudos de Coortes , Diabetes Gestacional/metabolismo , Diabetes Gestacional/fisiopatologia , Testes Diagnósticos de Rotina/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Intolerância à Glucose/genética , Humanos , Insulina/metabolismo , Resistência à Insulina/genética , Resistência à Insulina/fisiologia , Síndrome Metabólica/genética , Obesidade/genética , Polimorfismo Genético/genética , Gravidez
15.
J Exp Med ; 219(1)2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34854884

RESUMO

We previously demonstrated that lifelong antibiotic (ABX) perturbations of the gut microbiome in male APPPS1-21 mice lead to reductions in amyloid ß (Aß) plaque pathology and altered phenotypes of plaque-associated microglia. Here, we show that a short, 7-d treatment of preweaned male mice with high-dose ABX is associated with reductions of Aß amyloidosis, plaque-localized microglia morphologies, and Aß-associated degenerative changes at 9 wk of age in male mice only. More importantly, fecal microbiota transplantation (FMT) from transgenic (Tg) or WT male donors into ABX-treated male mice completely restored Aß amyloidosis, plaque-localized microglia morphologies, and Aß-associated degenerative changes. Transcriptomic studies revealed significant differences between vehicle versus ABX-treated male mice and FMT from Tg mice into ABX-treated mice largely restored the transcriptome profiles to that of the Tg donor animals. Finally, colony-stimulating factor 1 receptor (CSF1R) inhibitor-mediated depletion of microglia in ABX-treated male mice failed to reduce cerebral Aß amyloidosis. Thus, microglia play a critical role in driving gut microbiome-mediated alterations of cerebral Aß deposition.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Amiloidose/metabolismo , Encéfalo/metabolismo , Microbioma Gastrointestinal/fisiologia , Microglia/metabolismo , Amiloidose/genética , Animais , Anticorpos/administração & dosagem , Encéfalo/efeitos dos fármacos , Quimiocinas/sangue , Quimiocinas/genética , Quimiocinas/metabolismo , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Transplante de Microbiota Fecal , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , RNA-Seq/métodos , Fatores Sexuais
16.
Cytokine ; 150: 155785, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34933240

RESUMO

SARS-CoV-2 and latent Mycobacterium tuberculosis infection are both highly co-prevalent in many parts of the globe. Whether exposure to SARS-CoV-2 influences the antigen specific immune responses in latent tuberculosis has not been investigated. We examined the baseline, mycobacterial antigen and mitogen induced cytokine and chemokine responses in latent tuberculosis (LTBI) individuals with or without SARS-CoV-2 seropositivity, LTBI negative individuals with SARS-CoV-2 seropositivity and healthy control (both LTBI and SARS-CoV-2 negative) individuals. Our results demonstrated that LTBI individuals with SARS-CoV-2 seropositivity (LTBI+/IgG +) were associated with increased levels of unstimulated and TB-antigen stimulated IFNγ, IL-2, TNFα, IL-17, IL-1ß, IL-6, IL-12, IL-4, CXCL1, CXCL9 and CXCL10 when compared to those without seropositivity (LTBI+/IgG-). In contrast, LTBI+/IgG+ individuals were associated with decreased levels of IL-5 and IL-10. No significant difference in the levels of cytokines/chemokines was observed upon mitogen stimulation between the groups. SARS-CoV-2 seropositivity was associated with enhanced unstimulated and TB-antigen stimulated but not mitogen stimulated production of cytokines and chemokines in LTBI+ compared to LTBI negative individuals. Finally, most of these significant differences were not observed when LTBI negative individuals with SARS-CoV-2 seropositivity and controls were examined. Our data clearly demonstrate that both baseline and TB - antigen induced cytokine responses are augmented in the presence of SARS-CoV-2 seropositivity, suggesting an augmenting effect of prior SARS-CoV-2 infection on the immune responses of LTBI individuals.


Assuntos
COVID-19/complicações , Citocinas/sangue , Tuberculose Latente/complicações , SARS-CoV-2/imunologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Antígenos de Bactérias/imunologia , COVID-19/imunologia , Quimiocinas/sangue , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunoglobulina G/sangue , Inflamação , Tuberculose Latente/sangue , Tuberculose Latente/imunologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fito-Hemaglutininas/farmacologia , Soroconversão
17.
Clin Immunol ; 234: 108912, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34968746

RESUMO

Despite high levels of MMR-II usage in the US, mumps outbreaks continue to occur. Evidence suggests that mumps vaccine-induced humoral immunity wanes over time. Relatively few studies have examined cell-mediated immunity or reported on sex-based differences. To better understand sex-based differences in the immune response to mumps vaccine, we measured neutralizing antibody titers and mumps-specific cytokine/chemokine responses in a cohort of 748 adolescents and young adults after two doses of MMR vaccine. We observed significantly higher neutralizing antibody titers in females than in males (120.8 IU/mL, 98.7 IU/mL, p = 0.038) but significantly higher secretion levels of MIP-1α, MIP-1ß, TNFα, IL-6, IFNγ, and IL-1ß in males compared to females. These data demonstrate that sex influences mumps-specific humoral and cell-mediated immune response outcomes, a phenomenon that should be considered during efforts to improve vaccines and prevent future outbreaks.


Assuntos
Anticorpos Antivirais/sangue , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Vírus da Caxumba/imunologia , Vacinação , Adolescente , Quimiocinas/sangue , Criança , Estudos de Coortes , Citocinas/sangue , Feminino , Humanos , Masculino , Caracteres Sexuais , Adulto Jovem
18.
Front Endocrinol (Lausanne) ; 13: 1076951, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36714603

RESUMO

Background: Polycystic ovary syndrome (PCOS) is one of the most common gynecological endocrine disorders. Apelin and chemerin are newly identified adipokines, which are higher in obesity and diabetes. Studies have found that the serum apelin and chemerin levels in patients with PCOS are significantly increased. However, other studies showed the opposite results. Therefore, the relationship between those two adipokines and PCOS is still controversial. Aim: This meta-analysis was conducted to statistically evaluate the apelin and chemerin levels of patients with PCOS. Methods: We searched the Web of Science, Embase, PubMed, and Google Scholar databases for potential studies. "Polycystic ovary syndrome" or "PCOS" in combination with the terms "apelin" or "chemerin" were used as keywords search titles or abstracts. The publication period examined was between 1990 and 2021. Standardized mean differences (SMD) with corresponding 95% confidence intervals (CIs) were determined as the results of the meta-analysis. Results: A total of 148 articles were initially retrieved, and 18 qualified articles were finally obtained through preliminary screening and quality evaluation. The publications together contain 1,265 cases and 894 controls. The results of the meta-analysis showed that the circulating chemerin levels in patients with PCOS were significantly higher than those in the controls (SMD: 0.79, 95% CI [0.36, 1.23]), and there was no significant difference in circulating apelin between patients with PCOS and controls (SMD: 0.57, 95% CI [-0.21, 1.35]). Conclusions: This meta-analysis is the first to evaluate circulating apelin and chemerin levels in patients with PCOS. Our findings suggest that circulating chemerin levels of patients with PCOS are significantly higher than those of healthy controls. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=218316, identifier CRD42020218316.


Assuntos
Apelina , Quimiocinas , Síndrome do Ovário Policístico , Feminino , Humanos , Adipocinas , Obesidade , Apelina/sangue , Quimiocinas/sangue
19.
Lipids Health Dis ; 20(1): 108, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544451

RESUMO

BACKGROUND: The current study was conducted to explore the effects of chemerin and homocysteine (Hcy) levels and their associations with the occurrence and development of ischemic cerebrovascular disease (ICVD). METHODS: There involved a total of 187 patients with ICVD and 190 healthy people for physical examination in Cangzhou Central hospital from January 2020 to April 2021. The participants enrolled were divided into four groups based on the digital subtraction angiography: mild stenosis group (64 cases, stenosis rate 30-49 %), moderate stenosis group (72 cases, stenosis rate 50-69 %), severe stenosis group (51 cases, stenosis rate 70-99 %) and control group (190 cases, in healthy condition). The laboratory indexes of ICVD group and control group were observed and the four groups were further compared. Pearson linear correlation was applied to analyze the link between chemerin and Hcy levels and the degree of cerebral vascular stenosis in ICVD patients, and multivariate logistic regression was used to analyze the influencing factors of ICVD. RESULTS: No significant difference was found in general information including age, gender, body mass index (BMI), heart rate, systolic blood pressure, diastolic blood pressure, smoking and drinking between the two groups (P > 0.05). Moreover, there was no significant difference in fasting blood glucose (FBG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels between the two groups (P > 0.05). However, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), chemerin and Hcy in ICVD group were significantly higher than those in control group (P < 0.05). When comparing the four groups, there was no significant difference in FBG and TC levels (P > 0.05). The levels of TG, LDL-C, chemerin and Hcy in mild, moderate and severe stenosis groups were higher than those in control group, the above levels in moderate and severe stenosis group were higher than those in mild stenosis group, and severe stenosis group higher than moderate stenosis group (P < 0.05). Chemerin and Hcy levels were positively correlated with the degree of cerebral vascular stenosis in ICVD patients (r = 0.612, 0.519, P < 0.001). ICVD was regarded as the dependent variable, and the abovementioned general data as well as significant laboratory indicators, including TG, LDL-C, chemerin and Hcy, as independent variables. The results of multivariate logistic regression analysis revealed that TG, LDL-C, chemerin and Hcy were independent influencing factors of ICVD. CONCLUSIONS: Chemerin and Hcy levels exerted a close link to the occurrence and development of ICVD as independent influencing factors.


Assuntos
Transtornos Cerebrovasculares/sangue , Quimiocinas/sangue , LDL-Colesterol/sangue , Estenose Coronária/sangue , Homocisteína/sangue , Isquemia/sangue , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/patologia , HDL-Colesterol/sangue , Estenose Coronária/diagnóstico , Estenose Coronária/patologia , Feminino , Humanos , Isquemia/diagnóstico , Isquemia/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Triglicerídeos/sangue
20.
Biomolecules ; 11(12)2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34944507

RESUMO

The potential involvement of neuropeptide Q (NPQ) and chemerin (CHEM) in metabolic disorders is yet to be fully elucidated. The aim of this study was to evaluate serum concentrations of NPQ and CHEM and to establish their relationship with cardiometabolic risk factors among individuals with metabolic syndrome. A total of 66 patients with metabolic syndrome (MetS) and 83 healthy volunteers (non-MetS) underwent biochemical, blood pressure, and anthropometric measurements. The concentration of NPQ in the MetS group was significantly lower (0.47 (0.34 ; 0.54) vs. 0.52 (0.43 ; 0.60) ng/mL, p = 0.015) than in non-MetS, while there were no differences in CHEM level. In the entire study population, we observed several negative correlations between NPQ concentration and waist-hip ratio (WHR), visceral adipose tissue, diastolic blood pressure (DBP), triglycerides (TG) along with a positive correlation with high-density lipoprotein (HDL), total muscle mass, and CHEM. Moreover, a negative correlation was observed in the MetS group between NPQ and glycemia. CHEM showed no significant correlations with cardiometabolic risk factors in the study population. In a multiple regression model, the total muscle mass proved to be an independent factor determining NPQ concentration in the population (p < 0.00000001, R2adj = 28.6%). NPQ seems to protect against metabolic disorders correlated with obesity. Thus, it is worth considering NPQ level as a candidate protective biomarker of metabolic syndrome complications.


Assuntos
Quimiocinas/sangue , Regulação para Baixo , Síndrome Metabólica/sangue , Hormônios Peptídicos/sangue , Adulto , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Fatores de Risco Cardiometabólico , Estudos de Casos e Controles , Feminino , Humanos , Gordura Intra-Abdominal/metabolismo , Masculino , Pessoa de Meia-Idade , Triglicerídeos/metabolismo , Relação Cintura-Quadril
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