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1.
Medicine (Baltimore) ; 99(27): e20888, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629679

RESUMO

This study aims to identify prognostic value of neutrophil-to-lymphocyte ratio (NLR) in early miscarriages. A total of 260 pregnant women with vaginal spotting were recruited from the Department of Obstetrics and Gynecology of the Kyung Hee Medical Center from January 1, 2011, and December 31, 2018. Venous samples were obtained from the women for measurements of platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and NLR. All the patients were in < 14 gestational weeks of their pregnancy. Eighty-four patients were excluded because of incomplete data, loss of follow-up, and serious medical diseases. We enrolled 176 women for analysis and divided them into two groups. Group 1 included 104 women with threatened abortion; and group 2, 72 women with missed abortion. A significant difference in NLR was found between the groups (p = 0.001; P < .01). The multivariate analysis also revealed that NLR was the only prognostic factor of early miscarriage (odd ratio [OR], 0.732; 95% confidence interval [CI], 0.612-0.881, P = .001). The area under the Receiver-operating characteristic of NLR for distinguishing between the missed and threatened abortion groups was 0.792, and the best cutoff value was 5.72 (P < .05).


Assuntos
Aborto Espontâneo/sangue , Linfócitos/metabolismo , Neutrófilos/metabolismo , Adulto , Plaquetas/metabolismo , Feminino , Humanos , Monócitos/metabolismo , Gravidez , Prognóstico , Estudos Retrospectivos
2.
Cell Host Microbe ; 28(1): 9-11, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32645355

RESUMO

Plasmacytoid DCs (pDCs) are typically thought to be key in antiviral defense. In this issue of Cell Host & Microbe, Guo, Kasahara et al. (2020) reveal a critical role for pDCs in antifungal immunity. Aspergillus-infected monocyte-derived DCs and neutrophils recruit pDCs, which promote neutrophil fungicidal activity.


Assuntos
Aspergilose , Monócitos , Antifúngicos , Células Dendríticas , Humanos , Imunidade Inata , Neutrófilos , Receptores CXCR3
3.
Medicine (Baltimore) ; 99(22): e20346, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481414

RESUMO

The immune system plays a fundamental role in the response to neoadjuvant chemotherapy (NAC) of locally advanced breast cancer (LABC) patients. Patients with pathological complete response (pCR) after NAC have a higher survival rate. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are peripheral blood indicators of inflammatory response. This investigates the correlation between NLR, PLR, LMR, and other clinicopathological features of breast cancer patients before receiving NAC and pCR.Data of LABC patients who underwent NAC between 2009 and 2018 were retrospectively reviewed. Each patient's peripheral complete blood count was recorded before starting NAC. The cut-off values for neutrophils, lymphocytes, monocytes, and platelets in the peripheral blood and NLR, PLR, and LMR were determined by receiver operating characteristic curve analyses.The records of 131 patients were analyzed and divided into two groups, pCR (+ve) and pCR (-ve), and their clinicopathological features and laboratory findings were compared. pCR was achieved in 23.6% of patients. The cut-off values of neutrophils, lymphocytes, monocytes, and platelets at the time of diagnosis and NLR, PLR, and LMR were, respectively, 4150 µL, 2000 µL, 635 µL, 271 × 10 µL, 1.95, 119, and 3.35. The pCR rate was higher in patients with low neutrophil count, low NLR, and high lymphocyte count (P = .002, <.001, and .040, respectively).As per the findings of multivariate logistic regression analysis, the independent predictive factors of pCR were clinical tumor size T1 and T2, grade 3, ER negativity, and low NLR (P = .015, .001, .020, .022, and .001, respectively).While NLR was found to be an independent predictive factor of pCR in LABC patients receiving NAC, a similar result was not observed for PLR and LMR. NLR can be a useful biomarker for predicting the response of patients receiving NAC.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Mediadores da Inflamação/sangue , Adulto , Idoso , Biomarcadores Tumorais , Plaquetas/metabolismo , Quimioterapia Adjuvante , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Linfócitos/metabolismo , Pessoa de Meia-Idade , Monócitos/metabolismo , Neutrófilos/metabolismo , Estudos Retrospectivos , Análise de Sobrevida
5.
Sci Immunol ; 5(48)2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503877

RESUMO

Patients with severe COVID-19 have a hyperinflammatory immune response suggestive of macrophage activation. Bruton tyrosine kinase (BTK) regulates macrophage signaling and activation. Acalabrutinib, a selective BTK inhibitor, was administered off-label to 19 patients hospitalized with severe COVID-19 (11 on supplemental oxygen; 8 on mechanical ventilation), 18 of whom had increasing oxygen requirements at baseline. Over a 10-14 day treatment course, acalabrutinib improved oxygenation in a majority of patients, often within 1-3 days, and had no discernable toxicity. Measures of inflammation - C-reactive protein and IL-6 - normalized quickly in most patients, as did lymphopenia, in correlation with improved oxygenation. At the end of acalabrutinib treatment, 8/11 (72.7%) patients in the supplemental oxygen cohort had been discharged on room air, and 4/8 (50%) patients in the mechanical ventilation cohort had been successfully extubated, with 2/8 (25%) discharged on room air. Ex vivo analysis revealed significantly elevated BTK activity, as evidenced by autophosphorylation, and increased IL-6 production in blood monocytes from patients with severe COVID-19 compared with blood monocytes from healthy volunteers. These results suggest that targeting excessive host inflammation with a BTK inhibitor is a therapeutic strategy in severe COVID-19 and has led to a confirmatory international prospective randomized controlled clinical trial.


Assuntos
Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Tirosina Quinase da Agamaglobulinemia/metabolismo , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/virologia , Estado Terminal , Feminino , Seguimentos , Humanos , Inflamação/tratamento farmacológico , Inflamação/virologia , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Pandemias , Pneumonia Viral/virologia , Estudos Prospectivos , Respiração Artificial , Resultado do Tratamento
6.
Anticancer Res ; 40(6): 3371-3377, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487633

RESUMO

BACKGROUND/AIM: Several indicators of systemic inflammation have been reported to predict the outcomes of patients with malignant tumors but have not been fully investigated. The aim of this study was to evaluate whether the preoperative lymphocyte-to-monocyte ratio (LMR) can predict the outcomes of patients with pancreatic head cancer. PATIENTS AND METHODS: We studied 32 patients who underwent curative surgery for pancreatic head cancer in our hospital between 2006 and 2016. Patients were classified into high and low groups according to their LMR. RESULTS: The low LMR group had a significantly lower survival rate than the high LMR group (p=0.0313). A multivariate analysis showed that the pretreatment LMR (p=0.01) was an independent risk factor for cancer-related death. The LMR was correlated with obstructive jaundice (p=0.001). CONCLUSION: Preoperative LMR is a significant predictor of the outcome after pancreaticoduodenectomy in patients with pancreatic head cancer.


Assuntos
Icterícia Obstrutiva/etiologia , Linfócitos/metabolismo , Monócitos/metabolismo , Neoplasias Pancreáticas/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Icterícia Obstrutiva/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
7.
Cell Host Microbe ; 27(5): 683-684, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32407702

RESUMO

The phagosomal pathogen Leishmania appears unaffected by deliberate changes in the early Th1/Th2 balance. In this issue, Carneiro et al. explain these paradoxical results by showing that manipulations affecting IFN-γ-mediated phagocyte activation are counteracted by effects on IFN-γ-dependent recruitment of CCR2+ monocytes permissive to parasite growth.


Assuntos
Leishmaniose , Monócitos , Humanos , Interferon gama , Fagossomos , Pele
8.
Medicine (Baltimore) ; 99(18): e18755, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358341

RESUMO

Many inflammation indicators have been reported to be related with patient outcomes in various cancers. Previous studies have evaluated the combination of platelet (PLT) and lymphocyte to monocyte ratio (COP-LMR) as a systemic inflammatory marker for prognostication in lung cancer, yet its prognostic role among breast cancer patients remains unclear.In the present study, a total of 409 breast cancer patients with surgical resection were retrospectively investigated. The receiver operating characteristic (ROC) curve was used to choose the optimal cut-off value of PLT and lymphocyte to monocyte ratio (LMR). Patients were classified into 3 groups according to the score of COP-LMR, and its relationship with various clinicopathological factors and breast cancer prognosis were further evaluated.The ROC curve analysis showed that COP-LMR had a higher area under the ROC curve for the prediction of 5-year disease-free survival and overall survival than PLT or LMR alone. Multivariable analysis showed that an elevated COP-LMR was an independent predictor of poor disease-free survival (P = .032) and overall survival (P = .005). Subgroup analysis revealed that COP-LMR was still significantly associated with prognosis in both luminal A and luminal B subtypes.Preoperative COP-LMR is a potential prognostic factor in breast cancer patients who underwent surgery.


Assuntos
Neoplasias da Mama/mortalidade , Contagem de Leucócitos/estatística & dados numéricos , Linfócitos , Monócitos , Contagem de Plaquetas/estatística & dados numéricos , Adulto , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos
9.
Ann Hematol ; 99(7): 1531-1542, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32430703

RESUMO

In haemophilia, thrombin generation and fibrin deposition upon vascular injury critically depend on the tissue factor (TF)-driven coagulation pathway. TF expression by monocytes/macrophages and circulating microvesicles contributes to haemostasis, thrombosis and inflammation. Inflammation is a hallmark of blood-induced joint disease. The aim of this study is to correlate TF production by whole-blood monocytes with inflammatory markers and clinical parameters in patients with moderate-to-severe haemophilia A or B (n = 43) in comparison to healthy males (n = 23). Monocyte TF antigen and microvesicle-associated TF procoagulant activity (MV TF PCA) were measured immediately after blood draw (baseline) and following incubation of whole blood with buffer or lipopolysaccharide (LPS) using two-colour flow cytometry and chromogenic FXa generation assay, respectively. Patients with HIV or uncontrolled HBV/HCV infections were excluded. TF was hardly detectable and not different in baseline and buffer-treaded samples from both groups. Stimulation with LPS, however, induced monocyte TF production, with increased TF-specific mean fluorescence intensity (P = 0.08) and MV TF PCA (P < 0.05) in patients compared to controls. Patients also had elevated hs-CRP and IL-6 serum levels (P < 0.001), which correlated with LPS-induced TF parameters. Further exploratory analyses revealed that the presence of systemic (low-grade) inflammation and boosted LPS-induced monocyte TF production were mainly restricted to patients with clinically controlled HBV and/or HCV infection (n = 16), who were older and also had a significantly worse orthopaedic joint score than patients with no history of viral hepatitis (P < 0.01). Our study delineates a previously unrecognised link between systemic inflammation and inducible monocyte TF production in patients with haemophilia A or B.


Assuntos
Hemofilia A/metabolismo , Lipopolissacarídeos/farmacologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Tromboplastina/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Hemofilia A/patologia , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Via Secretória/efeitos dos fármacos , Índice de Gravidade de Doença , Adulto Jovem
10.
Wiad Lek ; 73(5): 983-987, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32386381

RESUMO

OBJECTIVE: The aim: To establish changes in hematological parameters of endogenous intoxication, nonspecific reactivity, activity of inflammation in HIV-infected persons, to improve verification of the clinical stage of the disease. PATIENTS AND METHODS: Materials and methods: Anamnestic, clinical, laboratory data. The statistical processing was performed in the Microsoft Office Excel 2010 and IBM SPSS Statistic 23 computer software, variational statistics processing (Student's t-criteria). RESULTS: Results: 51 HIV-infected were examined (main group) and 44 clinically anamnestic healthy blood donors (comparison group). The study included 46 patients (5 were withdrawn due to failure to meet criteria - severe septic condition). All patients were divided into three groups: A1 - all patients, 46 persons, men 76.0%, women - 24.0%; A2 - 11 people with I-III stages of HIV infection, men 72,7%, women - 27,3%; A3 - 35 HIV infected with stage IV disease, men 76.0%, women - 24.0%. All patients had an increase in intoxication indices and sex-dependent changes. Nonspecific reactivity indices in group A1 were above the norm, independent of gender except the index of neutrophils and lymphocyte (NLR). Below the norm is the immunoreactivity index (IR), the lymphocyte-monocyte ratio index (LMR), the lymphocyte index (Ilymph), the index of allergization (IA). Indices of nonspecific reactivity of A2 patients exceeded the norm and were independent of sex, with the exception of IR, Ilymph, IA, which were reduced. Non-specific reactivity indices are increased in HIV-infected group A3. Below the norm were IR, LMR, Ilymph, IA. Analyzing the activity indexes of inflammation, it became clear that the Krebs index (KI) was increased in all groups of patients; lymphocyte-granulocyte index (ILG) in groups A1 and A3 is less than normal, unlike patients in group A2, where it remained within the normal range. The leukocyte ratio and erythrocyte sedimentation rate (ILESR) in A1 and A3 have increased rates, unlike in A2, where the index is smaller. CONCLUSION: Conclusions: Men are predominantly HIV positive. The systemic immune response is more pronounced in women. There is a progressive impairment of immunological reactivity, indicating an immunodeficiency of the cell type with a decrease in nonspecific anti-infective protection. Patients with stage IV of HIV infection have moderate and severe inflammatory reactions, impaired reactivity, and are more pronounced in women.


Assuntos
Infecções por HIV , Feminino , Humanos , Inflamação , Leucócitos , Masculino , Monócitos , Neutrófilos
11.
Science ; 368(6495): 1122-1127, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32381589

RESUMO

Immunological memory specific to previously encountered antigens is a cardinal feature of adaptive lymphoid cells. However, it is unknown whether innate myeloid cells retain memory of prior antigenic stimulation and respond to it more vigorously on subsequent encounters. In this work, we show that murine monocytes and macrophages acquire memory specific to major histocompatibility complex I (MHC-I) antigens, and we identify A-type paired immunoglobulin-like receptors (PIR-As) as the MHC-I receptors necessary for the memory response. We demonstrate that deleting PIR-A in the recipient or blocking PIR-A binding to donor MHC-I molecules blocks memory and attenuates kidney and heart allograft rejection. Thus, innate myeloid cells acquire alloantigen-specific memory that can be targeted to improve transplant outcomes.


Assuntos
Rejeição de Enxerto/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Imunidade Inata , Memória Imunológica , Macrófagos/imunologia , Monócitos/imunologia , Receptores Imunológicos/fisiologia , Animais , Deleção de Genes , Rejeição de Enxerto/genética , Transplante de Coração , Transplante de Rim , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Mutantes , Receptores Imunológicos/genética
12.
Nat Rev Immunol ; 20(6): 355-362, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376901

RESUMO

The COVID-19 pandemic caused by infection with SARS-CoV-2 has led to more than 200,000 deaths worldwide. Several studies have now established that the hyperinflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. Macrophages are a population of innate immune cells that sense and respond to microbial threats by producing inflammatory molecules that eliminate pathogens and promote tissue repair. However, a dysregulated macrophage response can be damaging to the host, as is seen in the macrophage activation syndrome induced by severe infections, including in infections with the related virus SARS-CoV. Here we describe the potentially pathological roles of macrophages during SARS-CoV-2 infection and discuss ongoing and prospective therapeutic strategies to modulate macrophage activation in patients with COVID-19.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Inflamação/etiologia , Macrófagos/imunologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Animais , Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Humanos , Inflamação/patologia , Ativação de Macrófagos/efeitos dos fármacos , Monócitos/imunologia , Pandemias , Pneumonia Viral/patologia
14.
Medicine (Baltimore) ; 99(19): e20190, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384513

RESUMO

Diabetic nephropathy (DN) is serious threat to human health. Therefore, early prediction of its occurrence is important. This study aimed to assess the predictive significance of monocyte-lymphocyte ratio (MLR) for DN.A total of 301 patients with type 2 diabetes (T2D), including 212 T2D patients without diabetic-related complications and 99 DN patients, were enrolled. Peripheral white blood cells were measured before treatment to calculate MLR, and the risk factors and predictive significance for T2D and DN were assessed.T2D patients without diabetic-related complications had higher MLR than control patients (P < .01). However, MLR was significantly higher in DN patients than in T2D patients without diabetic-related complications (P < .001). According to MLR quartiles, higher MLR in DN patients was correlated with higher serum creatinine, estimated glomerular filtration rate, and urinary albumin excretion (UAE) levels (P < .01 or P < .001). Furthermore, MLR was positively correlated with UAE level (R = 0.5973; P < .01) and an independent predictor for DN (odds ratio: 7.667; 95% confidence interval [CI]: 3.689-21.312; P < .001). The area under the receiver-operating characteristic (ROC) curve for MLR was 0.874 (95%CI: 0.830-0.918, P < .001). When the optimal cutoff value was 0.23, the sensitivity and specificity of MLR for DN prediction were 0.85 and 0.74, respectively.The present findings suggest that MLR is a powerful independent predictor for DN.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Linfócitos/citologia , Monócitos/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Curva ROC , Fatores de Risco
15.
BMC Bioinformatics ; 21(1): 214, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32456667

RESUMO

BACKGROUND: Mounting evidence suggests several diseases and biological processes target transcription termination to misregulate gene expression. Disruption of transcription termination leads to readthrough transcription past the 3' end of genes, which can result in novel transcripts, changes in epigenetic states and altered 3D genome structure. RESULTS: We developed Automatic Readthrough Transcription Detection (ARTDeco), a tool to detect and analyze multiple features of readthrough transcription from RNA-seq and other next-generation sequencing (NGS) assays that profile transcriptional activity. ARTDeco robustly quantifies the global severity of readthrough phenotypes, and reliably identifies individual genes that fail to terminate (readthrough genes), are aberrantly transcribed due to upstream termination failure (read-in genes), and novel transcripts created as a result of readthrough (downstream of gene or DoG transcripts). We used ARTDeco to characterize readthrough transcription observed during influenza A virus (IAV) infection, validating its specificity and sensitivity by comparing its performance in samples infected with a mutant virus that fails to block transcription termination. We verify ARTDeco's ability to detect readthrough as well as identify read-in genes from different experimental assays across multiple experimental systems with known defects in transcriptional termination, and show how these results can be leveraged to improve the interpretation of gene expression and downstream analysis. Applying ARTDeco to a gene expression data set from IAV-infected monocytes from different donors, we find strong evidence that read-in gene-associated expression quantitative trait loci (eQTLs) likely regulate genes upstream of read-in genes. This indicates that taking readthrough transcription into account is important for the interpretation of eQTLs in systems where transcription termination is blocked. CONCLUSIONS: ARTDeco aids researchers investigating readthrough transcription in a variety of systems and contexts.


Assuntos
Software , Transcrição Genética , Regulação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Vírus da Influenza A/fisiologia , Monócitos/metabolismo , Monócitos/virologia , Locos de Características Quantitativas , RNA-Seq , Terminação da Transcrição Genética
16.
Mult Scler Relat Disord ; 43: 102174, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32464584

RESUMO

BACKGROUND: SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS. OBJECTIVE: To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis. OBSERVATIONS: Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm and vascular pathology appears to contribute to the damage in ARDS. IMPLICATIONS: In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.


Assuntos
Betacoronavirus/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Imunossupressores/uso terapêutico , Linfopenia/imunologia , Esclerose Múltipla/terapia , Pneumonia Viral/imunologia , Alemtuzumab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Antivirais/imunologia , Cladribina/uso terapêutico , Crotonatos/uso terapêutico , Desprescrições , Fumarato de Dimetilo/uso terapêutico , Cloridrato de Fingolimode/uso terapêutico , Acetato de Glatiramer/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Evasão da Resposta Imune/imunologia , Imunidade Inata/imunologia , Fatores Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Macrófagos/imunologia , Monócitos/imunologia , Natalizumab/uso terapêutico , Pandemias , Síndrome do Desconforto Respiratório do Adulto/imunologia , Toluidinas/uso terapêutico
17.
PLoS One ; 15(5): e0227932, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469873

RESUMO

BACKGROUND AND OBJECTIVE: For many pathological states, microparticles are supposed to be one of the causes of hypercoagulation. Although there are some indirect data about microparticles participation in coagulation activation and propagation, the integral hemostasis test Thrombodynamics allows to measure micropaticles participation in these two coagulation phases directly. Demonstrates microparticles participation in coagulation activation by influence on the appearance of coagulation centres in the plasma volume and the rate of clot growth from the surface with immobilized tissue factor.Methods: Microparticles were obtained from platelets and erythrocytes by stimulation with thrombin receptor-activating peptide (SFLLRN) and calcium ionophore (A23187), respectively, from monocytes, endothelial HUVEC culture and monocytic THP cell culture by stimulation with lipopolysaccharides. Microparticles were counted by flow cytometry and titrated in microparticle-depleted normal plasma in the Thrombodynamics test. RESULTS: Monocyte microparticles induced the appearance of clotting centres through the TF pathway at concentrations approximately 100-fold lower than platelet and erythrocyte microparticles, which activated plasma by the contact pathway. For endothelial microparticles, both activation pathways were essential, and their activity was intermediate. Monocyte microparticles induced plasma clotting by the appearance of hundreds of clots with an extremely slow growth rate, while erythrocyte microparticles induced the appearance of a few clots with a growth rate similar to that from surface covered with high-density tissue factor. Patterns of clotting induced by platelet and endothelial microparticles were intermediate. Platelet, erythrocyte and endothelial microparticles impacts on the rate of clot growth from the surface with tissue factor did not differ significantly within the 0-200·103/ul range of microparticles concentrations. However, at concentrations greater than 500·103/ul, erythrocyte microparticles increased the stationary clot growth rate to significantly higher levels than do platelet microparticles or artificial phospholipid vesicles consisting of phosphatidylcholine and phosphatidylserine. CONCLUSION: Microparticles of different origins demonstrated qualitatively different characteristics related to coagulation activation and propagation.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Micropartículas Derivadas de Células/efeitos dos fármacos , Trombina/metabolismo , Trombose/sangue , Plaquetas/efeitos dos fármacos , Calcimicina/farmacologia , Cálcio/metabolismo , Micropartículas Derivadas de Células/metabolismo , Células Endoteliais/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Citometria de Fluxo , Células Endoteliais da Veia Umbilical Humana , Humanos , Monócitos/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Trombose/tratamento farmacológico , Trombose/patologia
18.
PLoS Pathog ; 16(5): e1008553, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32453761

RESUMO

IRGM and its mouse orthologue Irgm1 are dynamin-like proteins that regulate vesicular remodeling, intracellular microbial killing, and pathogen immunity. IRGM dysfunction is linked to inflammatory bowel disease (IBD), and while it is thought that defective intracellular killing of microbes underscores IBD susceptibility, studies have yet to address how IRGM/Irgm1 regulates immunity to microbes relevant to intestinal inflammation. Here we find that loss of Irgm1 confers marked susceptibility to Citrobacter rodentium, a noninvasive intestinal pathogen that models inflammatory responses to intestinal bacteria. Irgm1-deficient mice fail to control C. rodentium outgrowth in the intestine, leading to systemic pathogen spread and host mortality. Surprisingly, susceptibility due to loss of Irgm1 function was not linked to defective intracellular killing of C. rodentium or exaggerated inflammation, but was instead linked to failure to remodel specific colon lamina propria (C-LP) myeloid cells that expand in response to C. rodentium infection and are essential for C. rodentium immunity. Defective immune remodeling was most striking in C-LP monocytes, which were successfully recruited to the infected C-LP, but subsequently underwent apoptosis. Apoptotic susceptibility was induced by C. rodentium infection and was specific to this setting of pathogen infection, and was not apparent in other settings of intestinal inflammation. These studies reveal a novel role for Irgm1 in host defense and suggest that deficiencies in survival and remodeling of C-LP myeloid cells that control inflammatory intestinal bacteria may underpin IBD pathogenesis linked to IRGM dysfunction.


Assuntos
Citrobacter rodentium/imunologia , Colo/imunologia , Infecções por Enterobacteriaceae/imunologia , Proteínas de Ligação ao GTP/deficiência , Doenças Inflamatórias Intestinais/imunologia , Monócitos/imunologia , Animais , Colo/microbiologia , Colo/patologia , Infecções por Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/patologia , Proteínas de Ligação ao GTP/imunologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Camundongos , Camundongos Knockout , Monócitos/microbiologia , Monócitos/patologia , Membrana Mucosa/imunologia , Membrana Mucosa/microbiologia , Membrana Mucosa/patologia
19.
Clin Chim Acta ; 508: 98-102, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32405079

RESUMO

BACKGROUND: Novel coronavirus infectious disease (COVID-19) has been spreading worldwide, and tracking laboratory indexes during the diagnosis and treatment of patients with severe COVID-19 can provide a reference for patients in other countries and regions. METHODS: We closely tracked the epidemiological history, diagnosis and treatment process, as well as dynamic changes in routine blood indicators, of a severe COVID-19 patient who was hospitalized for 26 days. RESULTS: Our study found that the patient's condition worsened in the first week after admission, white blood cells (WBCs), neutrophils, lymphocytes, monocytes, eosinophils, red blood cells (RBCs), hemoglobin, neutrophil lymphocyte ratio (NLR), platelets (PLT) and platelet lymphocyte ratio (PLR) decreased. On the 7th day of admission, the levels of these cells decreased to their lowest values, though the red blood cell distribution width (RDW) and C-reactive protein (CRP) level remained at high values. From 8 to 14 days of admission, the patient's condition improved, hypoxemia was corrected, and mechanical ventilation was discontinued. The number of WBCs, neutrophils, monocytes, eosinophils and lymphocytes increased gradually, and the erythrocyte parameters stopped declining and stabilized in a certain range; CRP decreased rapidly. On the 20th day of admission, the nucleic acid test was negative, WBC, neutrophil, CRP, NLR and PLR decreased gradually, and monocyte, lymphocyte, and eosinophil counts increased. Although RBCs and hemoglobin (Hb) levels continued to decrease, RDW gradually increased, indicating the recovery of hematopoiesis. In addition, it should be noted that monocytes and eosinophils were at extremely low levels within 10 days after admission; the recovery time of eosinophils was approximately 12 days after admission, which was earlier than other parameters, which might be of great value in judging the progress of the disease. CONCLUSIONS: Dynamic changes in routine blood parameters might be helpful for the prognosis of COVID-19 patients and evaluation of the treatment effect.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Antibacterianos/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Biomarcadores/sangue , Plaquetas/efeitos dos fármacos , Plaquetas/patologia , Plaquetas/virologia , Proteína C-Reativa/metabolismo , Contagem de Células , Convalescença , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Eritrócitos/efeitos dos fármacos , Eritrócitos/patologia , Eritrócitos/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/patologia , Monócitos/virologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Neutrófilos/virologia , Oseltamivir/uso terapêutico , Pandemias , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Prognóstico , Respiração Artificial , Índice de Gravidade de Doença
20.
Clin Chim Acta ; 508: 122-129, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32417210

RESUMO

BACKGROUND: The underlying changes of peripheral blood inflammatory cells (PBICs) in COVID-19 patients are little known. Moreover, the risk factors for the underlying changes of PBICs and their predicting role in severe COVID-19 patients remain uncertain. MATERIAL AND METHODS: This retrospective study including two cohorts: the main cohort enrolling 45 patients of severe type serving as study group, and the secondary cohort enrolling 12 patients of no-severe type serving as control group. The PBICs analysis was based on blood routine and lymphocyte subsets. The inflammatory cell levels were compared among patients according to clinical classifications, disease-associated phases, as well as one-month outcomes. RESULTS: Compared with patients of non-severe type, the patients of severe type suffered from significantly decreased counts of lymphocytes, eosinophils, basophils, but increased counts of neutrophils. These PBICs alterations got improved in recovery phase, but persisted or got worse in aggravated phase. Compared with patients in discharged group, the patients in un-discharged/died group suffered from decreased counts of total T lymphocytes, CD4 + T lymphocytes, CD8 + T lymphocytes, as well as NK cells at 2 weeks after treatment. Clinical classification-critically severe was the independently risk factor for lymphopenia (OR = 7.701, 95%CI:1.265-46.893, P = 0.027), eosinopenia (OR = 5.595, 95%CI:1.008-31.054, P = 0.049), and worse one-month outcome (OR = 8.984; 95%CI:1.021-79.061, P = 0.048). CONCLUSION: Lymphopenia and eosinopenia may serve as predictors of disease severity and disease progression in COVID-19 patients, and enhancing the cellular immunity may contribute to COVID-19 treatment. Thus, PBICs might become a sentinel of COVID-19, and it deserves attention during COVID-19 treatment.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Eosinófilos/patologia , Subpopulações de Linfócitos/patologia , Linfopenia/diagnóstico , Pneumonia Viral/diagnóstico , Idoso , Biomarcadores/sangue , Contagem de Células , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Progressão da Doença , Eosinófilos/virologia , Feminino , Humanos , Células Matadoras Naturais/patologia , Células Matadoras Naturais/virologia , Subpopulações de Linfócitos/virologia , Linfopenia/sangue , Linfopenia/fisiopatologia , Linfopenia/virologia , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Monócitos/virologia , Neutrófilos/patologia , Neutrófilos/virologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida
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