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1.
Front Immunol ; 12: 716361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34491250

RESUMO

Background: COVID-19 pathology is associated with exuberant inflammation, vascular damage, and activation of coagulation. In addition, complement activation has been described and is linked to disease pathology. However, few studies have been conducted in cancer patients. Objective: This study examined complement activation in response to COVID-19 in the setting of cancer associated thromboinflammation. Methods: Markers of complement activation (C3a, C5a, sC5b-9) and complement inhibitors (Factor H, C1-Inhibitor) were evaluated in plasma of cancer patients with (n=43) and without (n=43) COVID-19 and stratified based on elevated plasma D-dimer levels (>1.0 µg/ml FEU). Markers of vascular endothelial cell dysfunction and platelet activation (ICAM-1, thrombomodulin, P-selectin) as well as systemic inflammation (pentraxin-3, serum amyloid A, soluble urokinase plasminogen activator receptor) were analyzed to further evaluate the inflammatory response. Results: Increases in circulating markers of endothelial cell dysfunction, platelet activation, and systemic inflammation were noted in cancer patients with COVID-19. In contrast, complement activation increased in cancer patients with COVID-19 and elevated D-dimers. This was accompanied by decreased C1-Inhibitor levels in patients with D-dimers > 5 ug/ml FEU. Conclusion: Complement activation in cancer patients with COVID-19 is significantly increased in the setting of thromboinflammation. These findings support a link between coagulation and complement cascades in the setting of inflammation.


Assuntos
COVID-19/imunologia , Ativação do Complemento/imunologia , Inflamação/imunologia , Neoplasias/imunologia , SARS-CoV-2/imunologia , Trombose/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/sangue , COVID-19/virologia , Inativadores do Complemento/sangue , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Ativação Plaquetária/imunologia , Estudos Retrospectivos , SARS-CoV-2/fisiologia , Trombose/sangue , Adulto Jovem
2.
J Gerontol A Biol Sci Med Sci ; 76(10): 1775-1783, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34396395

RESUMO

Aging and comorbidities make individuals at greatest risk of COVID-19 serious illness and mortality due to senescence-related events and deleterious inflammation. Long-living individuals (LLIs) are less susceptible to inflammation and develop more resiliency to COVID-19. As demonstrated, LLIs are characterized by high circulating levels of BPIFB4, a protein involved in homeostatic response to inflammatory stimuli. Also, LLIs show enrichment of homozygous genotype for the minor alleles of a 4 missense single-nucleotide polymorphism haplotype (longevity-associated variant [LAV]) in BPIFB4, able to counteract progression of diseases in animal models. Thus, the present study was designed to assess the presence and significance of BPIFB4 level in COVID-19 patients and the potential therapeutic use of LAV-BPIFB4 in fighting COVID-19. BPIFB4 plasma concentration was found significantly higher in LLIs compared to old healthy controls while it significantly decreased in 64 COVID-19 patients. Further, the drop in BPIFB4 values correlated with disease severity. Accordingly to the LAV-BPIFB4 immunomodulatory role, while lysates of SARS-CoV-2-infected cells induced an inflammatory response in healthy peripheral blood mononuclear cells in vitro, the co-treatment with recombinant protein (rh) LAV-BPIFB4 resulted in a protective and self-limiting reaction, culminating in the downregulation of CD69 activating-marker for T cells (both TCD4+ and TCD8+) and in MCP-1 reduction. On the contrary, rhLAV-BPIFB4 induced a rapid increase in IL-18 and IL-1b levels, shown largely protective during the early stages of the virus infection. This evidence, along with the ability of rhLAV-BPIFB4 to counteract the cytotoxicity induced by SARS-CoV-2 lysate in selected target cell lines, corroborates BPIFB4 prognostic value and open new therapeutic possibilities in more vulnerable people.


Assuntos
COVID-19 , Peptídeos e Proteínas de Sinalização Intercelular , Longevidade/imunologia , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/imunologia , Linhagem Celular , Citocinas/sangue , Citotoxicidade Imunológica/efeitos dos fármacos , Feminino , Humanos , Fatores Imunológicos/imunologia , Fatores Imunológicos/farmacologia , Inflamação/sangue , Inflamação/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Itália/epidemiologia , Masculino , Prognóstico , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença
3.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360768

RESUMO

Colorectal cancer (CRC) is the leading cause of cancer deaths around the world. It is necessary to identify patients with poor prognosis or with high risk for recurrence so that we can selectively perform intensive treatments such as preoperative and/or postoperative chemotherapy and extended surgery. The clinical usefulness of inflammation-related prognostic biomarkers available from routine blood examination has been reported in many types of cancer, e.g., neutrophil-lymphocyte ratio (NLR), lymphocyte-C-reactive protein ratio (LCR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and so on. Moreover, some scoring systems based on circulating blood cell counts and albumin concentration have been also reported to predict cancer patients' prognosis, such as the Glasgow prognostic score (GPS), systemic inflammation score (SIS), and prognostic nutritional index (PNI). The optimal biomarker and optimal cutoff value of the markers can be different depending on the cancer type. In this review, we summarize the prognostic impact of each inflammation-related marker in CRC.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Contagem de Leucócitos , Avaliação Nutricional , Valor Preditivo dos Testes , Prognóstico
4.
Front Immunol ; 12: 720363, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447386

RESUMO

Severe coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan dysfunction. It has been documented that severe COVID-19 is associated with higher levels of inflammatory mediators than a mild disease, and tracking these markers may allow early identification or even prediction of disease progression. It is well known that C-reactive protein (CRP) is the acute-phase protein and the active regulator of host innate immunity, which is highly predictive of the need for mechanical ventilation and may guide escalation of treatment of COVID-19-related uncontrolled inflammation. There are numerous causes of an elevated CRP, including acute and chronic responses, and these can be infectious or non-infectious in etiology. CRP are normally lacking in viral infections, while adaptive immunity appears to be essential for COVID-19 virus clearance, and the macrophage activation syndrome may explain the high serum CRP contents and contribute to the disease progression. Nevertheless, for the assessment of host inflammatory status and identification of viral infection in other pathologies, such as bacterial sepsis, the acute-phase proteins, including CRP and procalcitonin, can provide more important information for guiding clinical diagnosis and antibiotic therapy. This review is aimed to highlight the current and most recent studies with regard to the clinical significance of CRP in severe COVID-19 and other viral associated illnesses, including update advances on the implication of CRP and its form specifically on the pathogenesis of these diseases. The progressive understanding in these areas may be translated into promising measures to prevent severe outcomes and mitigate appropriate treatment modalities in critical COVID-19 and other viral infections.


Assuntos
Proteína C-Reativa/metabolismo , COVID-19/sangue , COVID-19/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Humanos , Inflamação/sangue , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/sangue , Influenza Humana/complicações , Acidente Vascular Cerebral/sangue , Viroses
5.
Nat Commun ; 12(1): 4677, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34326336

RESUMO

SARS-CoV-2 infection can affect all human beings, including pregnant women. Thus, understanding the immunological changes induced by the virus during pregnancy is nowadays of pivotal importance. Here, using peripheral blood from 14 pregnant women with asymptomatic or mild SARS-CoV-2 infection, we investigate cell proliferation and cytokine production, measure plasma levels of 62 cytokines, and perform a 38-parameter mass cytometry analysis. Our results show an increase in low density neutrophils but no lymphopenia or gross alterations of white blood cells, which display normal levels of differentiation, activation or exhaustion markers and show well preserved functionality. Meanwhile, the plasma levels of anti-inflammatory cytokines such as interleukin (IL)-1RA, IL-10 and IL-19 are increased, those of IL-17, PD-L1 and D-dimer are decreased, but IL-6 and other inflammatory molecules remain unchanged. Our profiling of antiviral immune responses may thus help develop therapeutic strategies to avoid virus-induced damages during pregnancy.


Assuntos
COVID-19/imunologia , Citocinas/sangue , Inflamação/imunologia , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Infecções Assintomáticas , Biomarcadores/sangue , COVID-19/sangue , COVID-19/virologia , Estudos de Casos e Controles , Estudos Transversais , Citocinas/imunologia , Feminino , Humanos , Inflamação/sangue , Inflamação/prevenção & controle , Inflamação/virologia , Pessoa de Meia-Idade , Gravidez , Complicações Infecciosas na Gravidez/sangue , SARS-CoV-2/isolamento & purificação , Adulto Jovem
6.
Am J Cardiol ; 155: 128-134, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34315570

RESUMO

Fontan palliation has improved survival for single ventricle patients, but long-term complications persist including cardiovascular dysfunction, neurohormonal abnormalities, and protein-losing enteropathy (PLE). Although chronic inflammation contributes to morbidity, an association between inflammation and vascular dysfunction has not been studied. We assessed inflammation and vascular function in 31 Fontan-palliated patients (52% male, median age 14.3 years), including 10 PLE+. Fontan circulation was associated with altered inflammatory cytokines (TNF-α: mean 2.5 ± 1.4 vs. 0.7 ± 0.2 pg/ml, p < 0.0001; sTNFR2: 371 ± 108 vs. 2694 ± 884 pg/ml, p < 0.0001) and vascular dysfunction [log-transformed reactive hyperemia index (lnRHI) 0.28 ± 0.19 vs. 0.47 ± 0.26, p < 0.01; augmentation index (AI) -2.9 ± 13.8 vs. -16.3 ± 12.0, p = 0.001; circulating endothelial progenitor cells (cEPCs) 5.0 ± 8.1 vs. 22.8 ± 15.9, p = 0.0002)]. Furthermore, PLE+ patients showed greater inflammation (IFN-γ 6.3 ± 2.2 vs. 11.5 ± 7.9 pg/ml, p = 0.01; sTNFR1: 1181 ± 420 vs. 771 ± 350 pg/ml, p = 0.01) and decreased arterial compliance (AI: 5.4 ± 17.1 vs. -6.8 ± 10.2, p = 0.02) than PLE- patients. Circulating EPCs, but not inflammatory cytokines, were inversely associated with arterial stiffness in Fontan patients. In conclusion, chronic inflammation and vascular dysfunction are observed after Fontan operation, with greater inflammation and arterial stiffness in Fontan patients with active PLE. However, there is no clear association between inflammatory cytokines and vascular dysfunction, suggesting these pathophysiologic processes are not mechanistically linked.


Assuntos
Biomarcadores/sangue , Técnica de Fontan/efeitos adversos , Cardiopatias Congênitas/cirurgia , Complicações Pós-Operatórias/sangue , Enteropatias Perdedoras de Proteínas/sangue , Doenças Vasculares/sangue , Resistência Vascular/fisiologia , Adolescente , Adulto , Criança , Feminino , Seguimentos , Cardiopatias Congênitas/sangue , Humanos , Inflamação/sangue , Inflamação/etiologia , Masculino , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Enteropatias Perdedoras de Proteínas/etiologia , Doenças Vasculares/etiologia , Doenças Vasculares/fisiopatologia , Adulto Jovem
7.
Clin Nutr ESPEN ; 44: 466-468, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34330507

RESUMO

BACKGROUND & AIMS: Systemic inflammation has been reported as a new predictor for COVID-19 outcomes. Thus, we hypothesized that ICU patients infected by COVID-19 had lower blood vitamin D levels and increased systemic inflammation. Therefore, this is the first Brazilian study to evaluate the vitamin D concentrations and NLR as a systemic inflammation in patients infected by COVID-19 admitted in ICU. METHODS: This cross-sectional study selected twenty-six patients from COVID-19 Data Sharing/FAPESP, Brazil. Twenty-five patients were enrolled from a single hospital and those with blood vitamin D and neutrophil and lymphocyte data were included and had all available data analyzed. Patients were divided in two groups: low vitamin D concentration when ≤20 ng/mL (low Vit D group, n = 8, 5M/3F, 62.7 ± 8.4 years old), and normal vitamin D when > 20 ng/mL (normal Vit D group, n = 17, 9M/8F, 74 ± 8.2 years old). Serum 25-hydroxy-vitamin D, C reactive protein (CRP), and count of neutrophils and lymphocytes concentrations were collected from COVID-19 Data Sharing/FAPESP. Statistical analyses were performed using the Prism version 5.0 and Student T test was applied to verify any difference between the groups. RESULTS: Low vitamin D group had 15.5 ± 3.3 ng/mL of 25OH Vit D concentrations and normal vitamin D group had 35.9 ± 8.8 ng/mL. Although no difference between groups for CRP concentrations (low Vit D: 4.5 ± 3.3 vs. normal Vit D: 4.2 ± 4.0 mg/dL, p = 0.45), we found higher neutrophil count and NLR values in the low Vit D group when compared to normal Vit D group (low Vit D: 6049.8 ± 3719.7 vs. normal Vit D: 3741.8 ± 1704.1 ng/mL, p = 0.02) and (low Vit D: 9.0 ± 8.6 vs. normal Vit D: 4.2 ± 4.0 ng/mL, p = 0.03), respectively. CONCLUSION: This data sharing-derived cases of COVID-19 in patients admitted at ICU showed that patients infected by COVID-19 had lower serum 25-hydroxy vitamin D and enhanced systemic inflammation when assessed by NLR values.


Assuntos
COVID-19/sangue , COVID-19/epidemiologia , Unidades de Terapia Intensiva , Neutrófilos/metabolismo , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/sangue , Brasil/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Humanos , Inflamação/sangue , Inflamação/epidemiologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2
8.
Life Sci Alliance ; 4(9)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34321327

RESUMO

The use of high-dose of intravenous immunoglobulins (IVIGs) as immunomodulators for the treatment of COVID-19-affected individuals has shown promising results. IVIG reduced inflammation in these patients, who progressively restored respiratory function. However, little is known about how they may modulate immune responses in COVID-19 individuals. Here, we have analyzed the levels of 41 inflammatory biomarkers in plasma samples obtained at day 0 (pretreatment initiation), 3, 7, and 14 from five hospitalized COVID-19 patients treated with a 5-d course of 400 mg/kg/d of IVIG. The plasmatic levels of several cytokines (Tumor Necrosis Factor, IL-10, IL-5, and IL-7), chemokines (macrophage inflammatory protein-1α), growth/tissue repairing factors (hepatic growth factor), complement activation (C5a), and intestinal damage such as Fatty acid-binding protein 2 and LPS-binding protein showed a progressive decreasing trend during the next 2 wk after treatment initiation. This trend was not observed in IVIG-untreated COVID-19 patients. Thus, the administration of high-dose IVIG to hospitalized COVID-19 patients may improve their clinical evolution by modulating their hyperinflammatory and immunosuppressive status.


Assuntos
COVID-19/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Administração Intravenosa , Adulto , Idoso , Biomarcadores/sangue , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Quimiocinas/sangue , Citocinas/sangue , Feminino , Humanos , Imunidade/imunologia , Imunoglobulinas/imunologia , Imunoglobulinas/uso terapêutico , Imunoglobulinas Intravenosas/imunologia , Inflamação/sangue , Inflamação/terapia , Inflamação/virologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação
9.
Nutrients ; 13(6)2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34203015

RESUMO

The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (rs = -0.495), PCT (rs = -0.413), IL-6 (rs = -0.429), IL-1ß (rs = -0.440) and IL-10 (rs = -0.461). Positive associations were found for CD8+ T cells (rs = 0.636), NK cells (rs = 0.772), total IgG (rs = 0.493) and PaO2/FiO2 ratios (rs = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.


Assuntos
COVID-19/tratamento farmacológico , Estado Terminal/terapia , Deficiências Nutricionais/tratamento farmacológico , Suplementos Nutricionais , Micronutrientes/uso terapêutico , Selênio/uso terapêutico , Zinco/uso terapêutico , Idoso , Proteína C-Reativa/metabolismo , COVID-19/sangue , COVID-19/imunologia , Deficiências Nutricionais/complicações , Humanos , Sistema Imunitário/efeitos dos fármacos , Inflamação/sangue , Inflamação/tratamento farmacológico , Unidades de Terapia Intensiva , Interleucinas/sangue , Masculino , Micronutrientes/sangue , Micronutrientes/deficiência , Pessoa de Meia-Idade , Oxigênio/metabolismo , Síndrome do Desconforto Respiratório/tratamento farmacológico , Estudos Retrospectivos , SARS-CoV-2 , Selênio/sangue , Selênio/deficiência , Selenoproteína P/sangue , Índice de Gravidade de Doença , Zinco/sangue , Zinco/deficiência
10.
PLoS One ; 16(7): e0254167, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34214123

RESUMO

Dexamethasone provides benefits in patients with coronavirus disease 2019 (COVID-19), although data regarding immunological profiles and viral clearance are limited. This study aimed to evaluate for differences in biomarkers among patients with severe COVID-19 who did and did not receive dexamethasone. We measured plasma biomarkers of lung epithelial/endothelial injury and inflammation in 31 patients with severe COVID-19 and in 13 controls. Changes in biomarkers and clinical parameters were compared during the 7-day period among COVID-19 patients, and also according to dexamethasone use. Thirty-two patients with severe COVID-19 who received mechanical ventilation (n = 6), high-flow nasal cannula (n = 11), and supplemental oxygen (n = 15) were analyzed. Relative to controls, patients with severe COVID-19 had significantly higher concentrations of biomarkers related to glycocalyx shedding (endocan and syndecan-1), endothelial injury (von Willebrand factor), and inflammation (soluble receptor for advanced glycation end-products [sRAGE] and interleukin-6). The 7-day decreases in biomarkers of endothelial injury (angiopoietin-2 [Ang-2] and intercellular adhesion molecule-1 [ICAM-1]) and sRAGE, but not in the biomarker of lung epithelial injury (surfactant protein D), were correlated with decreases in C-reactive protein and radiologic score at day 7. Twenty patients (63%) received dexamethasone, and the dexamethasone and non-dexamethasone groups differed in terms of disease severity. However, dexamethasone was associated marginally with increased SpO2/FiO2 and significantly with decreases in C-reactive protein and radiologic score after adjusting for baseline imbalances. Furthermore, the dexamethasone group exhibited a significant decrease in the concentrations of Ang-2, ICAM-1, soluble form of the Tie2 receptor (a biomarker of glycocalyx shedding), and sRAGE. Both groups exhibited a clinically insignificant increase in the cycle threshold value. Severe COVID-19 may be characterized by more severe endothelial injury and inflammation, and less severe lung epithelial injury. There is a possibility that dexamethasone improved severe COVID-19 and related endothelial injury without delaying viral clearance.


Assuntos
Anti-Inflamatórios/uso terapêutico , COVID-19/tratamento farmacológico , Dexametasona/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Inflamação/prevenção & controle , SARS-CoV-2 , Viremia/tratamento farmacológico , Adulto , Idoso , Anti-Inflamatórios/farmacologia , Biomarcadores , COVID-19/sangue , COVID-19/diagnóstico por imagem , Dexametasona/farmacologia , Endotélio Vascular/patologia , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Lesão Pulmonar/sangue , Lesão Pulmonar/diagnóstico por imagem , Lesão Pulmonar/etiologia , Masculino , Oxigênio/sangue , Projetos Piloto , Carga Viral , Viremia/sangue
11.
Anticancer Res ; 41(8): 4005-4011, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281865

RESUMO

BACKGROUND: This study evaluated the prognostic value of preoperative immunoinflammatory scores and 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) for patients undergoing salvage esophagectomy to identify suitable candidates for surgery. PATIENTS AND METHODS: Twenty-five patients undergoing salvage esophagectomy were included. The prognostic value of the preoperative C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and maximum standardized FDG uptake value (SUVmax) were investigated. RESULTS: Multivariate analysis demonstrated high CAR to be an independent prognostic factor for overall survival (p=0.013). CAR had no association with clinicopathological variables, whereas the SUVmax was significantly positively associated with tumor aggressiveness. Multivariate analysis using residual tumor and the combination of CAR and SUVmax revealed both residual tumor (p=0.009) and high CAR/high SUVmax (p=0.016) to be independent prognostic factors for overall survival. CONCLUSION: Preoperative evaluation of CAR as an immunoinflammatory indicator and SUVmax as a marker of tumor aggressiveness will be useful to identify suitable candidates for this high-risk surgery.


Assuntos
Proteína C-Reativa/análise , Neoplasias Esofágicas , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Albumina Sérica/análise , Idoso , Biomarcadores/sangue , Plaquetas , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Esofagectomia , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico por imagem , Inflamação/terapia , Estimativa de Kaplan-Meier , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Terapia de Salvação
12.
Nutrients ; 13(6)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201185

RESUMO

High-protein diets (HPDs) are widely accepted as a way to stimulate muscle protein synthesis when combined with resistance training (RT). However, the effects of HPDs on adipose tissue plasticity and local inflammation are yet to be determined. This study investigated the impact of HPDs on glucose control, adipocyte size, and epididymal adipose inflammatory biomarkers in resistance-trained rats. Eighteen Wistar rats were randomly assigned to four groups: normal-protein (NPD; 17% protein total dietary intake) and HPD (26.1% protein) without RT and NPD and HPD with RT. Trained groups received RT for 12 weeks with weights secured to their tails. Glucose and insulin tolerance tests, adipocyte size, and an array of cytokines were determined. While HPD without RT induced glucose intolerance, enlarged adipocytes, and increased TNF-α, MCP-1, and IL1-ß levels in epididymal adipose tissue (p < 0.05), RT diminished these deleterious effects, with the HPD + RT group displaying improved blood glucose control without inflammatory cytokine increases in epididymal adipose tissue (p < 0.05). Furthermore, RT increased glutathione expression independent of diet (p < 0.05). RT may offer protection against adipocyte hypertrophy, pro-inflammatory states, and glucose intolerance during HPDs. The results highlight the potential protective effects of RT to mitigate the maladaptive effects of HPDs.


Assuntos
Glicemia/metabolismo , Dieta Rica em Proteínas , Inflamação/sangue , Gordura Intra-Abdominal/patologia , Treinamento de Força , Adipócitos/patologia , Animais , Tamanho Celular , Dieta , Epididimo/patologia , Glutationa/metabolismo , Resistência à Insulina , Masculino , Tamanho do Órgão , Ratos Wistar , Ganho de Peso
13.
Nutrients ; 13(6)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201276

RESUMO

Depression and vitamin D deficiency are major public health problems. The existing literature indicates the complex relationship between depression and vitamin D. The purpose of this study was to examine whether this relationship is moderated or mediated by inflammation. A community sample (n = 7162) from the LIFE-Adult-Study was investigated, for whom depressive symptoms were assessed via the German version of CES-D scale and serum 25-hydroxyvitamin D (25(OH)D) levels and inflammatory markers (IL-6 and CRP levels, WBC count) were quantified. Mediation analyses were performed using Hayes' PROCESS macro and regression analyses were conducted to test moderation effects. There was a significant negative correlation between CES-D and 25(OH)D, and positive associations between inflammatory markers and CES-D scores. Only WBC partially mediated the association between 25(OH)D levels and depressive symptoms both in a simple mediation model (ab: -0.0042) and a model including covariates (ab: -0.0011). None of the inflammatory markers showed a moderation effect on the association between 25(OH)D levels and depressive symptoms. This present work highlighted the complex relationship between vitamin D, depressive symptoms and inflammation. Future studies are needed to examine the effect of vitamin D supplementation on inflammation and depressive symptomatology for causality assessment.


Assuntos
Depressão/sangue , Depressão/psicologia , Inflamação/sangue , Inflamação/psicologia , Vitamina D/sangue , Adulto , Idoso , Biomarcadores/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Análise de Regressão , Vitamina D/análogos & derivados , Adulto Jovem
14.
Nutrients ; 13(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209267

RESUMO

This study was conducted to investigate the ß-carotene status in osteoarthritis (OA) patients and examine its relationships with the risk of inflammation and metabolic syndrome. OA patients were stratified by obesity based on body fat percentage (obese OA, n = 44; non-obese OA, n = 56), and sixty-nine subjects without OA or obesity were assigned as a non-obese control group. ß-carotene, metabolic parameters, and inflammation status were assessed. Obese OA patients exhibited a significantly higher rate of metabolic syndrome (p = 0.02), abdominal obesity (p < 0.01), and lower ß-carotene status (p < 0.01) compared with non-obese OA and non-obese controls. After adjusting for potential confounders, ß-carotene status (≥0.8 µM) was significantly inversely correlated with the risk of metabolic syndrome (odds ratio = 0.27, p < 0.01), abdominal obesity (odds ratio = 0.33, p < 0.01), high blood pressure (odds ratio = 0.35, p < 0.01), hyperglycemia (odds ratio = 0.45, p < 0.05), and inflammation (odds ratio = 0.30, p = 0.01). Additionally, subjects who had a high ß-carotene status with a low proportion of metabolic syndrome when they had a low-grade inflammatory status (p < 0.01). Obese OA patients suffered from a higher prevalence of metabolic syndrome and lower ß-carotene status compared to the non-obese controls. A better ß-carotene status (≥0.8 µM) was inversely associated with the risk of metabolic syndrome and inflammation, so we suggest that ß-carotene status could be a predictor of the risk of metabolic syndrome and inflammation in patients with and without OA.


Assuntos
Inflamação/sangue , Inflamação/complicações , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Osteoartrite/sangue , Osteoartrite/complicações , beta Caroteno/sangue , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Nature ; 596(7872): 417-422, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34192737

RESUMO

Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.


Assuntos
Envelhecimento/imunologia , Vacinas contra COVID-19/imunologia , Imunidade , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Autoanticorpos/imunologia , Linfócitos B/citologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Vacinas contra COVID-19/administração & dosagem , Feminino , Pessoal de Saúde , Humanos , Imunidade/genética , Imunização Secundária , Imunoglobulina A/imunologia , Switching de Imunoglobulina , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Memória Imunológica/imunologia , Inflamação/sangue , Inflamação/imunologia , Interferon gama/imunologia , Interleucina-2/imunologia , Masculino , Pessoa de Meia-Idade , Hipermutação Somática de Imunoglobulina , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologia , Vacinação , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia
16.
Adv Sci (Weinh) ; 8(17): e2101222, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34180141

RESUMO

COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+ ) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.


Assuntos
COVID-19/metabolismo , Adulto , Idoso , Antioxidantes/metabolismo , COVID-19/sangue , Método Duplo-Cego , Feminino , Humanos , Inflamação/sangue , Inflamação/metabolismo , Masculino , Metaboloma/fisiologia , Pessoa de Meia-Idade , Proteínas/metabolismo , Proteoma/metabolismo , Adulto Jovem
17.
Medicine (Baltimore) ; 100(25): e26437, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160435

RESUMO

ABSTRACT: Recent studies have shown that some inflammatory markers are associated with the prognosis of solid tumors. This study aims to evaluate the prognosis of glioma patients with or without adjuvant treatment using the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR).All patients who were diagnosed with gliomas at the first and second affiliated hospital of Guangxi Medical University between 2011 and 2020 were included in this study. The optimal cutoff value of SII, NLR, and PLR was determined by X-tile software program. We stratified patients into several groups and evaluated the progression-free survival (PFS) and overall survival (OS) of SII, NLR, and PLR during the period of pre-surgical, con-chemoradiotherapy, and post-treatments. Multivariate Cox regression analyses were performed to detect the relationships between OS, PFS, and prognostic variables.A total of 67 gliomas patients were enrolled in the study. The cutoff values of SII, NLR, and PLR were 781.5 × 109/L, 2.9 × 109/L, and 123.2 × 109/L, respectively. Patients who are pre-SII < 781.5 × 109/L had better PFS (P = .027), but no difference in OS. In addition, patients who had low pre-NLR (<2.9 × 109/L) meant better OS and PFS. PLR after adjuvant treatments (post-PLR) was significantly higher than pre-PLR (P = .035). Multivariate analyses revealed that pre-SII, pre-NLR were independent prognostic factors for OS (pre-SII: HR 1.002, 95% CI: 1.000-1.005, P = .030 and pre-PLR: HR 0.983, 95% CI: 0.973-0.994, P = .001), while pre-PLR was an independent factor for PFS (HR 0.989, 95% CI: 0.979-1.000, P = .041).High pre-SII or high pre-NLR could be prognostic markers to identify glioma patients who had a poor prognosis.


Assuntos
Plaquetas/imunologia , Neoplasias Encefálicas/terapia , Glioma/terapia , Linfócitos/imunologia , Procedimentos Neurocirúrgicos , Neutrófilos/imunologia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/mortalidade , Quimiorradioterapia/métodos , Feminino , Glioma/sangue , Glioma/imunologia , Glioma/mortalidade , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Contagem de Plaquetas , Período Pré-Operatório , Prognóstico , Intervalo Livre de Progressão , Valores de Referência , Estudos Retrospectivos , Adulto Jovem
18.
Medicine (Baltimore) ; 100(25): e26506, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160470

RESUMO

ABSTRACT: Many clinical studies have demonstrated that the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and Onodera's prognostic nutritional index (OPNI) are visibly involved in the prognosis of a variety of tumors. In our research, we aim to determin the prognostic impact of NLR, PLR, and OPNI for hepatocellular carcinoma (HCC).Data of hepatocellular carcinoma patients undergoing treatment in Changzhi People's Hospital between 2011 and 2017 were reviewed. 270 patients with HCC were under inclusion criteria. The optimal cut-off points of OPNI, NLR and PLR were determined by using the X-tile program. The overall survival (OS) was analyzed by Kaplan-Meier method. Multivariate analysis was performed using Cox Proportional Hazard Regression model to determine independent prognostic indicators for HCC.As revealed by Univariate and multivariate analysis, OPNI, Treatment, PLR, and BCLC Stage can be used as independent prognostic indicators for HCC. Comparing the P values and hazard ratios, we found out that the OPNI has greatest influence on prognosis in these indexes. The appropriate cut-off points of NLR, PLR, and OPNI were 2.5, 133.3, and 39.5, respectively. High score OPNI group had a better OS. In the analysis between OPNI and clinicopathological characteristics, there were differences in treatment, postoperative therapy, AST, ALBI grade, NLR and PLR between the high OPNI group and the low OPNI group, while others did not.OPNI is a straightforward and effective independent prognostic indicator for HCC.


Assuntos
Plaquetas/imunologia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Linfócitos/imunologia , Neutrófilos/imunologia , Avaliação Nutricional , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Quimioterapia Adjuvante , Feminino , Hepatectomia , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Estimativa de Kaplan-Meier , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/terapia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Valores de Referência , Estudos Retrospectivos
19.
J Laryngol Otol ; 135(8): 723-728, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34184623

RESUMO

OBJECTIVE: To analyse the correlations between olfactory psychophysical scores and the serum levels of D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio in coronavirus disease 2019 patients. METHODS: Patients underwent psychophysical olfactory assessment with the Connecticut Chemosensory Clinical Research Center test, and determination of blood serum levels of the inflammatory markers D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio within 10 days of the clinical onset of coronavirus disease 2019 and 60 days after. RESULTS: Seventy-seven patients were included in this study. D-dimer, procalcitonin, ferritin and neutrophil-to-lymphocyte ratio correlated significantly with severe coronavirus disease 2019. No significant correlations were found between baseline and 60-day Connecticut Chemosensory Clinical Research Center test scores and the inflammatory markers assessed. CONCLUSION: Olfactory disturbances appear to have little prognostic value in predicting the severity of coronavirus disease 2019 compared to D-dimer, ferritin, procalcitonin and neutrophil-to-lymphocyte ratio. The lack of correlation between the severity and duration of olfactory disturbances and serum levels of inflammatory markers seems to further suggest that the pathogenetic mechanisms underlying the loss of smell in coronavirus disease 2019 patients are related to local rather than systemic inflammatory factors.


Assuntos
COVID-19/patologia , Transtornos do Olfato/etiologia , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , COVID-19/sangue , COVID-19/complicações , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Inflamação/sangue , L-Lactato Desidrogenase/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/sangue , Transtornos do Olfato/patologia , Pró-Calcitonina/sangue , Índice de Gravidade de Doença
20.
Br J Haematol ; 194(3): 518-529, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34114204

RESUMO

The COVID-19 pandemic has been the most significant health crisis in recent global history. Early studies from Wuhan highlighted COVID-19-associated coagulopathy and a significant association with mortality was soon recognised. As research continues across the world, more evidence is emerging of the cross-talk between the innate immune system, coagulation activation and inflammation. Immunothrombosis has been demonstrated to play a key role in the pathophysiology of severe COVID-19, with extracellular histones and neutrophil extracellular traps detected in the plasma and cardiopulmonary tissues of critically ill patients. Targeting the components of immunothrombosis is becoming an important factor in the treatment of patients with COVID-19 infection. Recent studies report outcomes of intermediate and therapeutic anticoagulation in hospitalised patients with varying severities of COVID-19 disease, including optimal dosing and associated bleeding risks. Immunomodulatory therapies, including corticosteroids and IL-6 receptor antagonists, have been demonstrated to significantly reduce mortality in COVID-19 patients. As the pandemic continues, more studies are required to understand the driving factors and upstream mechanisms for coagulopathy and immunothrombosis in COVID-19, and thus potentially develop more targeted therapies for SARS-CoV-2 infection, both in the acute phase and in those who develop longer-term symptom burden.


Assuntos
COVID-19/complicações , Trombose/etiologia , Animais , Coagulação Sanguínea , COVID-19/sangue , COVID-19/imunologia , COVID-19/terapia , Gerenciamento Clínico , Humanos , Morte Celular Imunogênica , Inflamação/sangue , Inflamação/etiologia , Inflamação/imunologia , Inflamação/terapia , SARS-CoV-2/imunologia , Trombose/sangue , Trombose/imunologia , Trombose/terapia
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