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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(1): 127-132, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35048612

RESUMO

Objective: To establish a 14-color flow cytometry protocol for the examination of leukocyte subsets in human peripheral blood. Methods: We used cell membrane surface antibodies CD45, CD3, CD4, CD8, CD19, CD56, CD16, CD14, CD25, CD127, HLA-DR, CD123, CD11c and nucleus staining dye DAPI to establish a 14-color flow cytometry assay to determine the major cell subsets in human peripheral blood. We collected peripheral blood specimens from healthy volunteers to test for antibody titers and optimal photomultiplier tube (PMT) voltage, and to conduct single-color staining and fluorescence minus one control staining. After determining the test method and test conditions, the peripheral blood samples of 18 healthy volunteers were analyzed. Results: According to the cell classification and staining index, optimal antibody mass concentrations selected were as follows: CD25 and CD127 at 8.0 µg/mL, CD45, CD3, CD14 and CD123 at 4.0 µg/mL, CD8, CD19, CD56, CD16, HLA-DR and CD11c at 2.0 µg/mL, CD4 at 1.0 µg/mL and DAPI at 0.1 µg/mL. The detection voltages for CD45, CD3, CD4, CD8, CD19, CD56, CD16, CD14, CD25, CD127, HLA-DR, CD123, CD11c and DAPI were 450 V, 410 V, 400 V, 550 V, 405 V, 500 V, 520 V, 550 V, 550 V, 400 V, 450 V, 400 V, 580 V, and 300 V, respectively. The appropriate fluorescence compensation was determined by single-color staining and fluorescence minus one controls. The 14-color flow cytometry panel was established to analyze the main subsets of leukocytes in human peripheral blood, and peripheral blood samples from 18 healthy adults were examined, obtaining the percentages of each subset of peripheral blood leukocytes and the immunophenotypes of the main subsets. Conclusion: We established a 14-color panel for determining leukocyte subsets in human peripheral blood by flow cytometry, which produced stable and reliable results and was easy to operate.


Assuntos
Leucócitos , Subpopulações de Linfócitos , Contagem de Células , Citometria de Fluxo , Humanos , Imunofenotipagem
2.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166288, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34628032

RESUMO

GPR65 (TDAG8) is a proton-sensing G protein-coupled receptor predominantly expressed in immune cells. Genome-wide association studies (GWAS) have identified GPR65 gene polymorphisms as an emerging risk factor for the development of inflammatory bowel disease (IBD). Patients with IBD have an elevated risk of developing colorectal cancer when compared to the general population. To study the role of GPR65 in intestinal inflammation and colitis-associated colorectal cancer (CAC), colitis and CAC were induced in GPR65 knockout (KO) and wild-type (WT) mice using dextran sulfate sodium (DSS) and azoxymethane (AOM)/DSS, respectively. Disease severity parameters such as fecal score, colon shortening, histopathology, and mesenteric lymph node enlargement were aggravated in GPR65 KO mice compared to WT mice treated with DSS. Elevated leukocyte infiltration and fibrosis were observed in the inflamed colon of GPR65 KO when compared to WT mice which may represent a cellular mechanism for the observed exacerbation of intestinal inflammation. In line with high expression of GPR65 in infiltrated leukocytes, GPR65 gene expression was increased in inflamed intestinal tissue samples of IBD patients compared to normal intestinal tissues. Moreover, colitis-associated colorectal cancer development was higher in GPR65 KO mice than WT mice when treated with AOM/DSS. Altogether, our data demonstrate that GPR65 suppresses intestinal inflammation and colitis-associated tumor development in murine colitis and CAC models, suggesting potentiation of GPR65 with agonists may have an anti-inflammatory therapeutic effect in IBD and reduce the risk of developing colitis-associated colorectal cancer.


Assuntos
Neoplasias Associadas a Colite/genética , Colite/genética , Inflamação/genética , Doenças Inflamatórias Intestinais/genética , Animais , Azoximetano/toxicidade , Colite/induzido quimicamente , Colite/patologia , Neoplasias Associadas a Colite/induzido quimicamente , Neoplasias Associadas a Colite/patologia , Colo/efeitos dos fármacos , Colo/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Fibrose/genética , Fibrose/patologia , Regulação da Expressão Gênica/genética , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Doenças Inflamatórias Intestinais/patologia , Leucócitos/patologia , Camundongos , Camundongos Knockout , Receptores Acoplados a Proteínas G/genética , Índice de Gravidade de Doença
3.
J Nurs Care Qual ; 37(1): 42-46, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34224533

RESUMO

BACKGROUND: In 2019, an increase in clotted platelet filter occurrences was noted with the implementation of new leukocyte reduction filters through a volumetric pump. LOCAL PROBLEM: Occluded platelet filters contribute to delays in platelet transfusions, additional nursing workflows, and potential wastage of platelets, leading to staff and patient dissatisfaction. METHODS: Direct observation of nursing practice with priming platelet filters identified opportunities for improvement. Education was designed incorporating manufacturer recommendations with results of the observations. Nursing education was disseminated through small group sessions, one-to-one teaching, tip sheets, and an e-learning video. RESULTS: Nursing education interventions resulted in a 170% reduction in the reported monthly filter occlusion rate. CONCLUSION: Engagement of nurses in quality improvement processes and collaboration across departments led to a sustained decrease in the clotted platelet filters.


Assuntos
Leucócitos , Transfusão de Plaquetas , Humanos
4.
Eur J Endocrinol ; 186(2): 297-308, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-34914631

RESUMO

Objective: Cushing's syndrome represents a state of excessive glucocorticoids related to glucocorticoid treatments or to endogenous hypercortisolism. Cushing's syndrome is associated with high morbidity, with significant inter-individual variability. Likewise, adrenal insufficiency is a life-threatening condition of cortisol deprivation. Currently, hormone assays contribute to identify Cushing's syndrome or adrenal insufficiency. However, no biomarker directly quantifies the biological glucocorticoid action. The aim of this study was to identify such markers. Design: We evaluated whole blood DNA methylome in 94 samples obtained from patients with different glucocorticoid states (Cushing's syndrome, eucortisolism, adrenal insufficiency). We used an independent cohort of 91 samples for validation. Methods: Leukocyte DNA was obtained from whole blood samples. Methylome was determined using the Illumina methylation chip array (~850 000 CpG sites). Both unsupervised (principal component analysis) and supervised (Limma) methods were used to explore methylome profiles. A Lasso-penalized regression was used to select optimal discriminating features. Results: Whole blood methylation profile was able to discriminate samples by their glucocorticoid status: glucocorticoid excess was associated with DNA hypomethylation, recovering within months after Cushing's syndrome correction. In Cushing's syndrome, an enrichment in hypomethylated CpG sites was observed in the region of FKBP5 gene locus. A methylation predictor of glucocorticoid excess was built on a training cohort and validated on two independent cohorts. Potential CpG sites associated with the risk for specific complications, such as glucocorticoid-related hypertension or osteoporosis, were identified, needing now to be confirmed on independent cohorts. Conclusions: Whole blood DNA methylome is dynamically impacted by glucocorticoids. This biomarker could contribute to better assessment of glucocorticoid action beyond hormone assays.


Assuntos
Síndrome de Cushing/genética , Metilação de DNA/genética , DNA/sangue , Epigenoma/genética , Glucocorticoides/sangue , Glucocorticoides/genética , Adolescente , Insuficiência Adrenal/sangue , Insuficiência Adrenal/genética , Adulto , Idoso , Biomarcadores/sangue , Ilhas de CpG/genética , Síndrome de Cushing/sangue , Feminino , Humanos , Hidrocortisona/análise , Hidrocortisona/sangue , Hidrocortisona/urina , Leucócitos/química , Masculino , Pessoa de Meia-Idade , Saliva/química , Proteínas de Ligação a Tacrolimo/genética
5.
Virology ; 566: 122-135, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34906793

RESUMO

Mouse hepatitis virus (MHV; m-ß-CoV) serves as a useful model for studying the cellular factors involved in neuroinflammation. To understand the role of matrix metalloproteinases (MMPs) in neuroinflammation, brain tissues from m-ß-CoV-infected mice were harvested at different days post-infection (d.p.i) and investigated for Mmp expression by RT-qPCR. Mmp-2, -3, -8, -12 showed significant mRNA upregulation peaking with viral replication between 5 and 6 d.p.i. Elevated levels of MMP regulator TIMP-1 are suggestive of a TIMP-1 mediated host antiviral response. Biological network assessment suggested a direct involvement of MMP-3, -8, -14 in facilitating peripheral leukocyte infiltrations. Flow cytometry confirmed the increased presence of NK cells, CD4+ and CD8+ T cells, neutrophils, and MHCII expressing cells in the m-ß-CoV infected mice brain. Our study revealed that m-ß-CoV upregulated Park7, RelA, Nrf2, and Hmox1 transcripts involved in ROS production and antioxidant pathways, describing the possible nexus between oxidative pathways, MMPs, and TIMP in m-ß-CoV-induced neuroinflammation.


Assuntos
Encéfalo/metabolismo , Infecções por Coronavirus/metabolismo , Leucócitos/metabolismo , Metaloproteinases da Matriz/metabolismo , Vírus da Hepatite Murina/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Animais , Encéfalo/virologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vírus da Hepatite Murina/imunologia , /virologia , Oxirredução , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima
7.
Wiad Lek ; 74(10 pt 1): 2417-2422, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34896997

RESUMO

OBJECTIVE: The aim: To find an association of COVID-19 on different types of leukocytes either count increasing or decreasing. PATIENTS AND METHODS: Materials and methods: A cross sectional study conducted from October /2020 to January /2021. Eighty patients out of 170 were enrolled in this study, who were attended a private clinic for clinical investigation and a private laboratory for laboratory diagnosis of COVID-19 who were divided into two groups, asymptomatic or mild (group 1), and moderate or severe (group 2). Five milliliter of blood samples were collected from patients with COVD-19 by venipuncture using a syringe for evaluation of different cells. RESULTS: Results: The current study revealed a significant difference in white blood cells count, neutrophils count, monocytes count, basophils count, and neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio between group 1 and group 2. While lymphocytes, and eosinophil showed no significant difference. CONCLUSION: Conclusion: The current study concluded that COVID-19 may affect the count of some leukocytes in patient with severe infection.


Assuntos
COVID-19 , Estudos Transversais , Humanos , Contagem de Leucócitos , Leucócitos , SARS-CoV-2
8.
Cells ; 10(12)2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34943888

RESUMO

Cystic fibrosis in characterized by pulmonary bacterial colonization and hyperinflammation. Lymphocytes, monocytes/macrophages, neutrophils, and dendritic cells of patients with CF express functional CFTR and are directly affected by altered CFTR expression/function, impairing their ability to resolve infections and inflammation. However, the mechanism behind and the contribution of leukocytes in the pathogenesis of CF are still poorly characterized. The recent clinical introduction of specific CFTR modulators added an important tool not only for the clinical management of the disease but also to the investigation of the pathophysiological mechanisms related to CFTR dysfunction and dysregulated immunity. These drugs treat the basic defect in cystic fibrosis (CF) by increasing CFTR function with improvement of lung function and quality of life, and may improve clinical outcomes also by correcting the dysregulated immune function that characterizes CF. Measure of CFTR function, protein expression profiling and several omics methods were used to identify molecular changes in freshly isolated leukocytes of CF patients, highlighting two roles of leukocytes in CF: one more generally related to the mechanism(s) causing immune dysregulation in CF and unresolved inflammation, and another more applicative role, which identifies in myeloid cells, an important tool predictive of the therapeutic response of CF patients. In this review we will summarize available data on CFTR expression and function in leukocyte populations and will discuss potential clinical applications based on available data.


Assuntos
Fibrose Cística/patologia , Leucócitos/patologia , Animais , Ensaios Clínicos como Assunto , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Humanos , Modelos Biológicos
9.
Cells ; 10(12)2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34943894

RESUMO

The recent (re)discovery of the meningeal lymphatic system has opened new theories as to how immune cells traffic and interact with the central nervous system (CNS). While evidence is accumulating on the contribution of the meningeal lymphatic system in both homeostatic and disease conditions, a lot remains unknown about the mechanisms that allow for interaction between the meningeal lymphatic system and immune cells. In this review, we synthesize the knowledge about the lymphatic immune interaction in the CNS and highlight the important questions that remain to be answered.


Assuntos
Vasos Linfáticos/imunologia , Meninges/imunologia , Animais , Movimento Celular , Homeostase , Humanos , Leucócitos/citologia , Fenótipo
10.
Viruses ; 13(12)2021 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-34960752

RESUMO

Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we conducted in vitro assessment of whether convalescent serum enhanced SARS-CoV-2 infection or induced excessive immune responses in immune cells. Our data revealed that SARS-CoV-2 infection of primary B cells, macrophages and monocytes, which express variable levels of FcγR, could be enhanced by convalescent serum from COVID-19 patients. We also determined the factors associated with ADE, and found which showed a time-dependent but not viral-dose dependent manner. Furthermore, the ADE effect is not associated with the neutralizing titer or RBD antibody level when testing serum samples collected from different patients. However, it is higher in a medium level than low or high dilutions in a given sample that showed ADE effect, which is similar to dengue. Finally, we demonstrated more viral genes or dysregulated host immune gene expression under ADE conditions compared to the no-serum infection group. Collectively, our study provides insight into the understanding of an association of high viral antibody titer and severe lung pathology in severe patients with COVID-19.


Assuntos
Anticorpos Facilitadores/imunologia , Leucócitos/virologia , SARS-CoV-2/patogenicidade , COVID-19/imunologia , Células Cultivadas , Perfilação da Expressão Gênica , Humanos , Soros Imunes/imunologia , Leucócitos/metabolismo , Receptores de IgG/metabolismo , Replicação Viral/imunologia
11.
Biomed Res Int ; 2021: 1401945, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917680

RESUMO

Objective: Mangifera indica Linn, Bridelia ferruginea Benth, and Alstonia boonei De Wild are three plants commonly used in the traditional treatment of urinary tract infections in Benin. This study sets out to assess the cytotoxic and teratogenic effects of extracts of these plants on Artemia salina larvae and hen embryos. Methods and Results: The aqueous and ethanolic extracts were obtained by maceration of the powders in solvents. Larval cytotoxicity was performed on Artemia salina larvae. The teratogenic effect of these plants was evaluated on chick embryos at 100 mg/kg and 300 mg/kg. The extracts were injected on the 7th and 14th days of incubation. The quality of the hatched chicks was evaluated by the Tona score followed by the hematological and the biochemical parameter assays. The extracts did not show cytotoxicity on the larvae. The eggs treated with plant extracts at 300 mg/kg significantly lowered the hatchability rate, except for the Mangifera indica Linn. The chicks obtained were all at the very good quality. Then, no significant variation was observed between hematological parameters except white blood cells. For the biochemical parameters, only ASAT showed some significant variations for a few extracts. It would be important to assess the genotoxicity of the plant extracts to determine more broader toxicity. These data justify the use of these medicinal plants in traditional Beninese medicine and constitute in fact a source of production of anti-infectious drugs.


Assuntos
Larva/efeitos dos fármacos , Medicina Tradicional/efeitos adversos , Plantas Medicinais/efeitos adversos , Plantas Medicinais/química , Teratogênese/efeitos dos fármacos , Infecções Urinárias/tratamento farmacológico , Animais , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/farmacologia , Benin , Embrião de Galinha , Galinhas , Leucócitos/efeitos dos fármacos , Mangifera/química , Testes de Mutagenicidade/métodos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/farmacologia
12.
Cells ; 10(12)2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34943947

RESUMO

Intravital microscopy and other direct-imaging techniques have allowed for a characterisation of leukocyte migration that has revolutionised the field of immunology, resulting in an unprecedented understanding of the mechanisms of immune response and adaptive immunity. However, there is an assumption within the field that modern imaging techniques permit imaging parameters where the resulting cell track accurately captures a cell's motion. This notion is almost entirely untested, and the relationship between what could be observed at a given scale and the underlying cell behaviour is undefined. Insufficient spatial and temporal resolutions within migration assays can result in misrepresentation of important physiologic processes or cause subtle changes in critical cell behaviour to be missed. In this review, we contextualise how scale can affect the perceived migratory behaviour of cells, summarise the limited approaches to mitigate this effect, and establish the need for a widely implemented framework to account for scale and correct observations of cell motion. We then extend the concept of scale to new approaches that seek to bridge the current "black box" between single-cell behaviour and systemic response.


Assuntos
Movimento Celular/fisiologia , Rastreamento de Células/tendências , Leucócitos/fisiologia , Imagem Molecular/tendências , Imunidade Adaptativa/genética , Movimento Celular/genética , Humanos , Imunidade/genética , Leucócitos/ultraestrutura
13.
Viruses ; 13(12)2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34960790

RESUMO

Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.


Assuntos
Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/mortalidade , Leucócitos/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Índice de Gravidade de Doença , Receptor Gatilho 1 Expresso em Células Mieloides/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Feminino , Humanos , Inflamação , Interleucina-10/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Estudos Prospectivos , SARS-CoV-2 , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Adulto Jovem
14.
Anal Chem ; 93(51): 17076-17085, 2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-34913344

RESUMO

There is an unmet clinical need to extract living circulating tumor cells (CTCs) for functional studies and in vitro expansion to enable drug testing and predict responses to therapy in metastatic cancer. Here, we present a novel two-step acoustophoresis (A2) method for isolation of unfixed, viable cancer cells from red blood cell (RBC) lysed whole blood. The A2 method uses an initial acoustofluidic preseparation step to separate cells based on their acoustic mobility. This acoustofluidic step enriches viable cancer cells in a central outlet, but a significant number of white blood cells (WBCs) remain in the central outlet fraction due to overlapping acoustophysical properties of these viable cells. A subsequent purging step was employed to remove contaminating WBCs through negative selection acoustophoresis with anti-CD45-functionalized negative acoustic contrast particles. We processed 1 mL samples of 1:1 diluted RBC lysed whole blood mixed with 10 000 DU145 cells through the A2 method. Additional experiments were performed using 1000 DU145 cells spiked into 1.5 × 106 WBCs in 1 mL of buffer to further elucidate the dynamic range of the method. Using samples with 10 000 DU145 cells, we obtained 459 ± 188-fold depletion of WBC and 42% recovery of viable cancer cells. Based on spiked samples with 1000 DU145 cells, our cancer cell recovery was 28% with 247 ± 156-fold WBC depletion corresponding to a depletion efficacy of ≥99.5%. The novel A2 method provides extensive elimination of WBCs combined with the gentle recovery of viable cancer cells suitable for downstream functional analyses and in vitro culture.


Assuntos
Células Neoplásicas Circulantes , Acústica , Separação Celular , Humanos , Contagem de Leucócitos , Leucócitos
15.
Cells ; 10(12)2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34944002

RESUMO

Cell-based cancer immunotherapy has revolutionized the treatment of hematological malignancies. Specifically, autologous chimeric antigen receptor-engineered T (CAR-T) cell therapies have received approvals for treating leukemias, lymphomas, and multiple myeloma following unprecedented clinical response rates. A critical barrier to the widespread usage of current CAR-T cell products is their autologous nature, which renders these cellular products patient-selective, costly, and challenging to manufacture. Allogeneic cell products can be scalable and readily administrable but face critical concerns of graft-versus-host disease (GvHD), a life-threatening adverse event in which therapeutic cells attack host tissues, and allorejection, in which host immune cells eliminate therapeutic cells, thereby limiting their antitumor efficacy. In this review, we discuss recent advances in developing stem cell-engineered allogeneic cell therapies that aim to overcome the limitations of current autologous and allogeneic cell therapies, with a special focus on stem cell-engineered conventional αß T cells, unconventional T (iNKT, MAIT, and γδ T) cells, and natural killer (NK) cells.


Assuntos
Imunoterapia , Leucócitos/citologia , Neoplasias/imunologia , Neoplasias/terapia , Células-Tronco/citologia , Células Alógenas/citologia , Animais , Engenharia Celular , Humanos
16.
Front Immunol ; 12: 774776, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917088

RESUMO

Both RNA N6-methyladenosine (m6A) modification of SARS-CoV-2 and immune characteristics of the human body have been reported to play an important role in COVID-19, but how the m6A methylation modification of leukocytes responds to the virus infection remains unknown. Based on the RNA-seq of 126 samples from the GEO database, we disclosed that there is a remarkably higher m6A modification level of blood leukocytes in patients with COVID-19 compared to patients without COVID-19, and this difference was related to CD4+ T cells. Two clusters were identified by unsupervised clustering, m6A cluster A characterized by T cell activation had a higher prognosis than m6A cluster B. Elevated metabolism level, blockage of the immune checkpoint, and lower level of m6A score were observed in m6A cluster B. A protective model was constructed based on nine selected genes and it exhibited an excellent predictive value in COVID-19. Further analysis revealed that the protective score was positively correlated to HFD45 and ventilator-free days, while negatively correlated to SOFA score, APACHE-II score, and crp. Our works systematically depicted a complicated correlation between m6A methylation modification and host lymphocytes in patients infected with SARS-CoV-2 and provided a well-performing model to predict the patients' outcomes.


Assuntos
Adenosina/análogos & derivados , COVID-19/imunologia , COVID-19/virologia , Interações Hospedeiro-Patógeno/imunologia , Leucócitos/imunologia , RNA Viral/genética , SARS-CoV-2/fisiologia , Adenosina/metabolismo , Análise por Conglomerados , Biologia Computacional/métodos , Suscetibilidade a Doenças/imunologia , Perfilação da Expressão Gênica , Humanos , Leucócitos/metabolismo , RNA Viral/metabolismo , Curva ROC
17.
Int J Mol Sci ; 22(24)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34948112

RESUMO

The human host immune responses to parasitic infections are complex. They can be categorized into four immunological pathways mounted against four types of parasitic infections. For intracellular protozoa, the eradicable host immunological pathway is TH1 immunity involving macrophages (M1), interferon gamma (IFNγ) CD4 T cells, innate lymphoid cells 1 (NKp44+ ILC1), CD8 T cells (Effector-Memory4, EM4), invariant natural killer T cells 1 (iNKT1) cells, and immunoglobulin G3 (IgG3) B cells. For intracellular protozoa, the tolerable host immunological pathway is TH1-like immunity involving macrophages (M2), interferon gamma (IFNγ)/TGFß CD4 T cells, innate lymphoid cells 1 (NKp44- ILC1), CD8 T cells (EM3), invariant natural killer T 1 (iNKT1) cells, and immunoglobulin A1 (IgA1) B cells. For free-living extracellular protozoa, the eradicable host immunological pathway is TH22 immunity involving neutrophils (N1), interleukin-22 CD4 T cells, innate lymphoid cells 3 (NCR+ ILC3), iNKT17 cells, and IgG2 B cells. For free-living extracellular protozoa, the tolerable host immunological pathway is TH17 immunity involving neutrophils (N2), interleukin-17 CD4 T cells, innate lymphoid cells 3 (NCR- ILC3), iNKT17 cells, and IgA2 B cells. For endoparasites (helminths), the eradicable host immunological pathway is TH2a immunity with inflammatory eosinophils (iEOS), interleukin-5/interleukin-4 CD4 T cells, interleukin-25 induced inflammatory innate lymphoid cells 2 (iILC2), tryptase-positive mast cells (MCt), iNKT2 cells, and IgG4 B cells. For ectoparasites (parasitic insects and arachnids), the eradicable host immunological pathway is TH2b immunity with inflammatory basophils, chymase- and tryptase-positive mast cells (MCct), interleukin-3/interleukin-4 CD4 T cells, interleukin-33 induced nature innate lymphoid cells 2 (nILC2), iNKT2 cells, and immunoglobulin E (IgE) B cells. The tolerable host immunity against ectoparasites and endoparasites is TH9 immunity with regulatory eosinophils, regulatory basophils, interleukin-9 mast cells (MMC9), thymic stromal lymphopoietin induced innate lymphoid cells 2, interleukin-9 CD4 T cells, iNKT2 cells, and IgA2 B cells. In addition, specific transcription factors important for specific immune responses were listed. This JAK/STAT signaling is key to controlling or inducing different immunological pathways. In sum, Tfh is related to STAT5ß, and BCL6 expression. Treg is related to STAT5α, STAT5ß, and FOXP3. TH1 immunity is related to STAT1α, STAT4, and T-bet. TH2a immunity is related to STAT6, STAT1α, GATA1, and GATA3. TH2b immunity is related to STAT6, STAT3, GATA2, and GATA3. TH22 immunity is associated with both STAT3α and AHR. THαß immunity is related to STAT1α, STAT1ß, STAT2, STAT3ß, and ISGF. TH1-like immunity is related to STAT1α, STAT4, STAT5α, and STAT5ß. TH9 immunity is related to STAT6, STAT5α, STAT5ß, and PU.1. TH17 immunity is related to STAT3α, STAT5α, STAT5ß, and RORG. TH3 immunity is related to STAT1α, STAT1ß, STAT2, STAT3ß, STAT5α, STAT5ß, and ISGF. This categorization provides a complete framework of immunological pathways against four types of parasitic infections. This framework as well as relevant JAK/STAT signaling can provide useful knowledge to control allergic hypersensitivities and parasitic infections via development of vaccines or drugs in the near future.


Assuntos
Citocinas/imunologia , Imunidade Inata , Leucócitos/imunologia , Doenças Parasitárias/imunologia , Humanos
18.
Biochemistry (Mosc) ; 86(11): 1489-1501, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34906042

RESUMO

Bronchial asthma is a heterogeneous chronic inflammatory disease of airways. The studies of molecular and cellular mechanisms of bronchial asthma have established that a wide range of immune (T and B cells, eosinophils, neutrophils, macrophages, etc.) and structural (epithelial and endothelial) cells are involved in its pathogenesis. These cells are activated in response to external stimuli (bacteria, viruses, allergens, and other pollutants) and produce pro-inflammatory factors (cytokines, chemokines, metalloproteinases, etc.), which ultimately leads to the initiation of pathological processes in the lungs. Genes encoding transcription factors of the STAT family (signal transducer and activator of transcription), that includes seven representatives, are involved in the cell activation. Recent studies have shown that the transcription factor STAT3 plays an important role in the activation of the abovementioned cells, thus contributing to the development of asthma. In animal studies, selective inhibition of STAT3 significantly reduces the severity of lung inflammation, which indicates its potential as a therapeutic target. In this review, we describe the mechanisms of STAT3 activation and its role in polarization of Th2/Th17 cells and M2 macrophages, as well as in the dysfunction of endothelial cells, which ultimately leads to development of bronchial asthma symptoms, such as infiltration of neutrophils and eosinophils into the lungs, bronchial hyperreactivity, and the respiratory tract remodeling.


Assuntos
Asma/imunologia , Leucócitos/imunologia , Pulmão/imunologia , Fator de Transcrição STAT3/imunologia , Animais , Asma/patologia , Humanos , Leucócitos/patologia , Pulmão/patologia
19.
Proc Natl Acad Sci U S A ; 118(51)2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34911767

RESUMO

Human phagocytes have key functions in the resolution of inflammation. Here, we assessed the role of the proposed 4S,5S-epoxy-resolvin intermediate in the biosynthesis of both resolvin D3 and resolvin D4. We found that human neutrophils converted this synthetic intermediate to resolvin D3 and resolvin D4. M2 macrophages transformed this labile epoxide intermediate to resolvin D4 and a previously unknown cysteinyl-resolvin isomer without appreciable amounts of resolvin D3. M2 macrophages play critical roles in the resolution of inflammation and in wound healing. Human M2 macrophages also converted leukotriene A4 to lipoxins. The cysteinyl-resolvin isomer significantly accelerated tissue regeneration of surgically injured planaria. In a model of human granuloma formation, the cysteinyl-resolvin isomer significantly inhibited granuloma development by human peripheral blood leukocytes. Together, these results provide evidence for a human cell type-specific role of 4S,5S-epoxy-resolvin in the biosynthesis of resolvin D3 by neutrophils, resolvin D4 by both M2 macrophages and neutrophils, and a unique cysteinyl-resolvin isomer produced by M2 macrophages that carries potent biological activities in granuloma formation and tissue regeneration.


Assuntos
Ácidos Graxos Insaturados/metabolismo , Leucócitos/metabolismo , Macrófagos/metabolismo , Células Cultivadas , Granuloma , Humanos
20.
BMC Bioinformatics ; 22(Suppl 5): 94, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34749635

RESUMO

BACKGROUND: Differentiating and counting various types of white blood cells (WBC) in bone marrow smears allows the detection of infection, anemia, and leukemia or analysis of a process of treatment. However, manually locating, identifying, and counting the different classes of WBC is time-consuming and fatiguing. Classification and counting accuracy depends on the capability and experience of operators. RESULTS: This paper uses a deep learning method to count cells in color bone marrow microscopic images automatically. The proposed method uses a Faster RCNN and a Feature Pyramid Network to construct a system that deals with various illumination levels and accounts for color components' stability. The dataset of The Second Affiliated Hospital of Zhejiang University is used to train and test. CONCLUSIONS: The experiments test the effectiveness of the proposed white blood cell classification system using a total of 609 white blood cell images with a resolution of 2560 × 1920. The highest overall correct recognition rate could reach 98.8% accuracy. The experimental results show that the proposed system is comparable to some state-of-art systems. A user interface allows pathologists to operate the system easily.


Assuntos
Aprendizado Profundo , Leucemia , Medula Óssea , Humanos , Processamento de Imagem Assistida por Computador , Leucócitos
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