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1.
J Immunol Res ; 2024: 6817965, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962578

RESUMO

Therapeutic vaccines based on monocyte-derived dendritic cells have been shown to be promising strategies and may act as complementary treatments for viral infections, cancers, and, more recently, autoimmune diseases. Alpha-type-1-polarized dendritic cells (aDC1s) have been shown to induce type-1 immunity with a high capacity to produce interleukin-12p70 (IL-12p70). In the clinical use of cell-based therapeutics, injectable solutions can affect the morphology, immunophenotypic profile, and viability of cells before delivery and their survival after injection. In this sense, preparing a cell suspension that maintains the quality of aDC1s is essential to ensure effective immunotherapy. In the present study, monocytes were differentiated into aDC1s in the presence of IL-4 and GM-CSF. On day 5, the cells were matured by the addition of a cytokine cocktail consisting of IFN-α, IFN-γ, IL-1ß, TNF-α, and Poly I:C. After 48 hr, mature aDC1s were harvested and suspended in two different solutions: normal saline and Ringer's lactate. The maintenance of cells in suspension was evaluated after 4, 6, and 8 hr of storage. Cell viability, immunophenotyping, and apoptosis analyses were performed by flow cytometry. Cellular morphology was observed by electron microscopy, and the production of IL-12p70 by aDC1s was evaluated by ELISA. Compared with normal saline, Ringer's lactate solution was more effective at maintaining DC viability for up to 8 hr of incubation at 4 or 22°C.


Assuntos
Diferenciação Celular , Sobrevivência Celular , Células Dendríticas , Imunoterapia , Interleucina-12 , Monócitos , Células Dendríticas/imunologia , Humanos , Monócitos/imunologia , Imunoterapia/métodos , Sobrevivência Celular/efeitos dos fármacos , Interleucina-12/metabolismo , Imunofenotipagem , Citocinas/metabolismo , Células Cultivadas , Apoptose , Injeções
2.
Front Immunol ; 15: 1425873, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38953025

RESUMO

Background: The immune system plays an important role in the development and treatment of thyroid cancer(THCA).However, the correlation between immune cells and THCA has not been systematically studied. Methods: This study used a two-sample Mendelian randomization (MR) study to determine the causal relationship between immune cell characteristics and THCA. Based on a large sample of publicly available genetic data, we explored the causal relationship between 731 immune cell characteristics and THCA risk. The 731 immunophenotypes were divided into 7 groups, including B cell panel(n=190),cDC panel(n=64),Maturation stages of T cell panel(n=79),Monocyte panel(n=43),Myeloid cell panel(n=64),TBNK panel(n=124),and Treg panel(n=167). The sensitivity of the results was analyzed, and heterogeneity and horizontal pleiotropy were excluded. Results: After FDR correction, the effect of immunophenotype on THCA was not statistically significant. It is worth mentioning, however, that there are some unadjusted low P-values phenotypes. The odds ratio (OR) of CD62L on monocyte on THCA risk was estimated to be 0.953 (95% CI=0.930~0.976, P=1.005×10-4),and which was estimated to be 0.975(95% CI=0.961-0.989, P=7.984×10-4) for Resting Treg%CD4 on THCA risk. Furthermore, THCA was associated with a reduced risk of 5 immunophenotype:CD25 on CD39+ CD4 on Treg (OR=0.871, 95% CI=0.812~0.935, P=1.274×10-4), activated Treg AC (OR=0.884, 95% CI=0.820~0.953, P=0.001), activated & resting Treg % CD4 Treg (OR=0.872, 95%CI=0.811~0.937,P=2.109×10-4),CD28- CD25++ CD8br AC(OR=0.867,95% CI=0.809~0.930,P=6.09×10-5),CD28-CD127-CD25++CD8brAC(OR=0.875,95%CI=0.814~0.942,P=3.619×10-4).THCA was associated with an increased risk of Secreting Treg % CD4 Treg (OR=1.143, 95% CI=1.064~1.229, P=2.779×10-4) and CD19 on IgD+ CD24+ (OR=1.118, 95% CI=1.041~1.120, P=0.002). Conclusions: These findings suggest the causal associations between immune cells and THCA by genetic means. Our results may have the potential to provide guidance for future clinical research.


Assuntos
Imunofenotipagem , Análise da Randomização Mendeliana , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Monócitos/imunologia
3.
BMC Cancer ; 24(1): 782, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951749

RESUMO

BACKGROUND AND AIMS: The cardiotoxicity related to 5-Fluorouracil (5-FU) in cancer patients has garnered widespread attention. The systemic immune-inflammation index (SII) has recently been identified as a novel predictive marker for the development of cardiovascular illnesses in individuals without pre-existing health conditions. However, it remains unclear whether the levels of SII are linked to cardiotoxicity related to 5-FU. This retrospective study aims to fill this knowledge gap by examining the correlation between SII and cardiotoxicity related to 5-FU in a colorectal cancer cohort. METHODS: The study comprised colorectal cancer patients who received 5-FU-based chemotherapy at the affiliated cancer hospital of Guizhou Medical University between January 1, 2018 and December 31, 2020. After adjustment for confounders and stratification by tertiles of the interactive factor, linear regression analyses, curve fitting and threshold effect analyses were conducted. RESULTS: Of the 754 patients included final analysis, approximately 21% (n = 156) of them ultimately experienced cardiotoxicity related to 5-FU. Monocytes (M) was found as an influential element in the interaction between SII and cardiotoxicity related to 5-FU. In the low tertile of M (T1: M ≤ 0.38 × 109/L), increasing log SII was positively correlated with cardiotoxicity related to 5-FU (Odds Ratio [OR], 8.04; 95% confidence interval [95%CI], 1.68 to 38.56). However, a curvilinear relationship between log SII and cardiotoxicity was observed in the middle tertile of M (T2: 0.38 < M ≤ 0.52 × 109/L). An increase in log SII above 1.37 was shown to be associated with a decreased risk of cardiotoxicity (OR, 0.14; 95%CI, 0.02 to 0.88), indicating a threshold effect. In the high tertile of M (T3: M > 0.52 × 109/L), there was a tendency towards a negative linear correlation between the log SII and cardiotoxicity was observed (OR, 0.85; 95%CI, 0.37 to 1.98). CONCLUSION: Our findings suggest that SII may serve as a potential biomarker for predicting cardiotoxicity related to 5-FU in colorectal cancer patients. SII is an independent risk factor for cardiotoxicity related to 5-FU with low monocytes levels (T1). Conversely, in the middle monocytes levels (T2), SII is a protective factor for cardiotoxicity related to 5-FU but with a threshold effect.


Assuntos
Cardiotoxicidade , Neoplasias Colorretais , Fluoruracila , Humanos , Fluoruracila/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Cardiotoxicidade/etiologia , Estudos Retrospectivos , Idoso , Inflamação , Antimetabólitos Antineoplásicos/efeitos adversos , Monócitos/imunologia , Monócitos/efeitos dos fármacos , Adulto
4.
Am J Reprod Immunol ; 92(1): e13891, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38958250

RESUMO

PROBLEM: The decidualization process conditions monocytes to the immunosuppressive and tolerogenic dendritic cell (DC)-10 profile, a DC subset with high IL-10 production. Since the implantation process implies an embryo-endometrium-immune crosstalk, here we focused on the ability of embryonic soluble factors to modify decidual DC conditioning accordingly with its quality. METHOD OF STUDY: Human endometrial stromal cell line (HESC) decidualized with medroxyprogesterone and dibutyryl-cAMP (Dec) was stimulated with human embryo-conditioned media (ECM), classified as normal (ND) or impaired developed (ID) for 48 h (n = 18/group). Monocytes isolated from six healthy women were differentiated to DCs with rhGM-CSF+rhIL-4 in the presence/absence of conditioned media (CM) from decidualized cells stimulated with ECM or nontreated. RESULTS: We found that decidualized cells stimulated with ECM sustain a myeloid regulatory cell profile on monocyte-derived culture with increased frequency of CD1a-CD14+ and CD83+CD86low cells. ND-Dec sustained the higher expression of the DC-10 markers, HLA-G and IL-10 whereas ID-Dec diminished IL-10 production (ID-Dec: 135 ± 37.4 vs. Dec: 223.3 ± 49.9 pg/mL, p < 0.05). The treatment with ECM-Dec sustained a higher IL-10 production and prevented the increase of CD83/CD86 after LPS challenge regardless of embryo quality. Notably, TNF-α production increased in ID-Dec cultures (ID-Dec: 475.1 ± 134.7 vs. Dec: 347.5 ± 98 pg/mL, p < 0.05). CONCLUSIONS: Although remaining in a tolerogenic profile compatible with DC-10, DCs can differentially respond to decidual secreted factors based on embryo quality, changing their secretome. These results suggest that in the presence of arrested embryo, DCs could differentially shape the immunological microenvironment, contributing to arrested embryo clearance during the menstrual phase.


Assuntos
Decídua , Células Dendríticas , Implantação do Embrião , Tolerância Imunológica , Humanos , Feminino , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/efeitos dos fármacos , Implantação do Embrião/imunologia , Decídua/imunologia , Decídua/citologia , Diferenciação Celular , Meios de Cultivo Condicionados , Interleucina-10/metabolismo , Adulto , Células Estromais/imunologia , Células Estromais/metabolismo , Células Cultivadas , Embrião de Mamíferos , Endométrio/imunologia , Endométrio/citologia , Linhagem Celular , Monócitos/imunologia , Gravidez
5.
Cancer Immunol Immunother ; 73(9): 166, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954042

RESUMO

BACKGROUND: Vulvar squamous cell carcinoma (VSCC) arises after an HPV infection or the mutation of p53 or other driver genes and is treated by mutilating surgery and/or (chemo) radiation, with limited success and high morbidity. In-depth information on the immunological make up of VSCC is pivotal to assess whether immunotherapy may form an alternative treatment. METHODS: A total of 104 patient samples, comprising healthy vulva (n = 27) and VSCC (n = 77), were analyzed. Multispectral immunofluorescence (15 markers) was used to study both the myeloid and lymphoid immune cell composition, and this was linked to differences in transcriptomics (NanoString nCounter, 1258 genes) and in survival (Kaplan-Meier analyses). RESULTS: Healthy vulva and VSCC are both well infiltrated but with different subpopulations of lymphoid and myeloid cells. In contrast to the lymphoid cell infiltrate, the density and composition of the myeloid cell infiltrate strongly differed per VSCC molecular subtype. A relative strong infiltration with epithelial monocytes (HLADR-CD11c-CD14+CD68-CD163-CD33-) was prognostic for improved survival, independent of T cell infiltration, disease stage or molecular subtype. A strong infiltration with T cells and/or monocytes was associated with drastic superior survival: 5-year survival > 90% when either one is high, versus 40% when both are low (p < 0.001). CONCLUSION: A hot myeloid and/or lymphoid infiltrate predicts excellent survival in VSCC. Based on the response of similarly high-infiltrated other tumor types, we have started to explore the potential of neoadjuvant checkpoint blockade in VSCC.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Escamosas , Monócitos , Neoplasias Vulvares , Humanos , Feminino , Neoplasias Vulvares/imunologia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/mortalidade , Neoplasias Vulvares/terapia , Prognóstico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Monócitos/imunologia , Pessoa de Meia-Idade , Idoso , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Adulto , Idoso de 80 Anos ou mais
6.
Sci Rep ; 14(1): 15255, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956252

RESUMO

The monocyte distribution width (MDW) has emerged as a promising biomarker for accurate and early identification of patients with potentially life-threatening infections. Here we tested the diagnostic performance of MDW in adult patients requiring hospital admission for community-acquired infections and sepsis, evaluated sources of heterogeneity in the estimates of diagnostic accuracy, and assessed the meaning of MDW in a patient population presenting to the emergency department (ED) for acute non-infectious conditions. 1925 consecutive patients were categorized into three groups: non-infection (n = 1507), infection (n = 316), and sepsis/septic shock (n = 102). Diagnostic performance for infection or sepsis of MDW alone or in combination with components of SOFA was tested using AUC of ROC curves, sensitivity, and specificity. The relationship between MDW and different pathogens as well as the impact of non-infectious conditions on MDW values were explored. For the prediction of infection, the AUC/ROC of MDW (0.84) was nearly overlapping that of procalcitonin (0.83), and C-reactive protein (0.89). Statistical optimal cut-off value for MDW was 21 for predicting infection (sensitivity 73%, specificity 82%) and 22 for predicting sepsis (sensitivity 79%, specificity 83%). The best threshold to rule out infection was MDW ≤ 17 (NPV 96.9, 95% CI 88.3-100.0), and ≤ 18 (NPV 99.5, 95% CI 98.3-100.0) to rule out sepsis. The combination of MDW with markers of organ dysfunction (creatinine, bilirubin, platelets) substantially improved the AUC (0.96 (95% CI 0.94-0.97); specificity and sensitivity of 88% and 94%, respectively). In conclusion, MDW has a good diagnostic performance in diagnosing infection and sepsis in patients presenting in ED. Its use as an infection marker even increases when combined with other markers of organ dysfunction. Understanding the impact of interactions of non-infectious conditions and comorbidities on MDW and its diagnostic accuracy requires further elucidation.


Assuntos
Biomarcadores , Serviço Hospitalar de Emergência , Monócitos , Sepse , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Sepse/diagnóstico , Sepse/sangue , Monócitos/metabolismo , Biomarcadores/sangue , Adulto , Curva ROC , Doença Aguda , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/diagnóstico , Sensibilidade e Especificidade
7.
Front Immunol ; 15: 1397475, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979407

RESUMO

Monocytes are pivotal immune cells in eliciting specific immune responses and can exert a significant impact on the progression, prognosis, and immunotherapy of intracranial aneurysms (IAs). The objective of this study was to identify monocyte/macrophage (Mo/MΦ)-associated gene signatures to elucidate their correlation with the pathogenesis and immune microenvironment of IAs, thereby offering potential avenues for targeted therapy against IAs. Single-cell RNA-sequencing (scRNA-seq) data of IAs were acquired from the Gene Expression Synthesis (GEO) database. The significant infiltration of monocyte subsets in the parietal tissue of IAs was identified using single-cell RNA sequencing and high-dimensional weighted gene co-expression network analysis (hdWGCNA). The integration of six machine learning algorithms identified four crucial genes linked to these Mo/MΦ. Subsequently, we developed a multilayer perceptron (MLP) neural model for the diagnosis of IAs (independent external test AUC=1.0, sensitivity =100%, specificity =100%). Furthermore, we employed the CIBERSORT method and MCP counter to establish the correlation between monocyte characteristics and immune cell infiltration as well as patient heterogeneity. Our findings offer valuable insights into the molecular characterization of monocyte infiltration in IAs, which plays a pivotal role in shaping the immune microenvironment of IAs. Recognizing this characterization is crucial for comprehending the limitations associated with targeted therapies for IAs. Ultimately, the results were verified by real-time fluorescence quantitative PCR and Immunohistochemistry.


Assuntos
Aneurisma Intracraniano , Aprendizado de Máquina , Macrófagos , Monócitos , Análise de Célula Única , Humanos , Aneurisma Intracraniano/genética , Aneurisma Intracraniano/imunologia , Análise de Célula Única/métodos , Monócitos/imunologia , Monócitos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Perfilação da Expressão Gênica , Transcriptoma , Microambiente Celular/imunologia , Microambiente Celular/genética , Masculino , Feminino , Redes Reguladoras de Genes , Biologia Computacional/métodos
8.
Front Immunol ; 15: 1423776, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979427

RESUMO

Introduction: The endocannabinoid system (ECS), named after the chemical compounds found in the cannabis plant, is a regulatory network of neurotransmitters, receptors, and enzymes that plays crucial roles in skin health and disease. Endogenous ligands of the ECS, called endocannabinoids, have proven to be important regulators of immune responses. One of the most prevalent endocannabinoids, arachidonoylethanolamide (also known as anandamide), is known for its anti-inflammatory effects. Langerhans cells (LCs) are the sole antigen-presenting cells present in the human epidermis. They serve as the first line of defense against pathogens and are essential for the skin's specific immune responses and play a critical role in maintaining tissue homeostasis; however, little is known about the effect of endocannabinoids on these cells. Our research aimed to provide the connection between monocyte-derived Langerhans cells (moLCs) and the ECS, shedding light on their collaborative roles in immune homeostasis and inflammation. Methods: Human monocytes were differentiated into moLCs using established protocols. Anandamide was applied during the differentiation process to test its effect on the viability, marker expression, and cytokine production of the cells, as well as in short term treatments for intracellular calcium measurement. TLR ligands applied after the differentiation protocol were used to activate moLCs. The impact of anandamide on the functionality of moLCs was further assessed using differential gene expression analysis of bulk RNA-Seq data, moLC-T cell cocultures, while ELISpot was employed to determine polarization of T cells activated in the aforementioned cocultures. Results: Anandamide did not significantly affect the viability of moLCs up to 10 µM. When applied during the differentiation process it had only a negligible effect on CD207 expression, the prototypic marker of LCs; however, there was an observed reduction in CD1a expression by moLCs. Anandamide had no significant effects on the maturation status of moLCs, nor did it affect the maturation induced by TLR3 and TLR7/8 agonists. MoLCs differentiated in the presence of anandamide did however show decreased production of CXCL8, IL-6, IL-10 and IL-12 cytokines induced by TLR3 and TLR7/8 activation. Anandamide-treated moLCs showed an increased capability to activate naïve T cells; however, not to the level seen with combined TLR agonism. RNA sequencing analysis of moLCs differentiated with anandamide showed modest changes compared to control cells but did reveal an inhibitory effect on oxidative phosphorylation specifically in activated moLCs. Anandamide also promoted the polarization of naïve T cells towards a Th1 phenotype. Discussion: Our results show that anandamide has nuanced effects on the differentiation, maturation, cytokine secretion, metabolism and function of activated moLCs. Among these changes the decrease in CD1a expression on moLCs holds promise to selectively dampen inflammation induced by CD1a restricted T cells, which have been implicated as drivers of inflammation in common inflammatory skin conditions such as psoriasis, atopic dermatitis and contact dermatitis.


Assuntos
Ácidos Araquidônicos , Endocanabinoides , Homeostase , Células de Langerhans , Monócitos , Alcamidas Poli-Insaturadas , Endocanabinoides/farmacologia , Endocanabinoides/metabolismo , Humanos , Alcamidas Poli-Insaturadas/farmacologia , Células de Langerhans/imunologia , Células de Langerhans/metabolismo , Células de Langerhans/efeitos dos fármacos , Ácidos Araquidônicos/farmacologia , Monócitos/imunologia , Monócitos/metabolismo , Monócitos/efeitos dos fármacos , Citocinas/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Células Cultivadas , Pele/imunologia , Pele/metabolismo , Inflamação/imunologia , Inflamação/metabolismo
9.
Front Immunol ; 15: 1415565, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38989285

RESUMO

How the microbiome regulates responses of systemic innate immune cells is unclear. In the present study, our purpose was to document a novel mechanism by which the microbiome mediates crosstalk with the systemic innate immune system. We have identified a family of microbiome Bacteroidota-derived lipopeptides-the serine-glycine (S/G) lipids, which are TLR2 ligands, access the systemic circulation, and regulate proinflammatory responses of splenic monocytes. To document the role of these lipids in regulating systemic immunity, we used oral gavage with an antibiotic to decrease the production of these lipids and administered exogenously purified lipids to increase the systemic level of these lipids. We found that decreasing systemic S/G lipids by decreasing microbiome Bacteroidota significantly enhanced splenic monocyte proinflammatory responses. Replenishing systemic levels of S/G lipids via exogenous administration returned splenic monocyte responses to control levels. Transcriptomic analysis demonstrated that S/G lipids regulate monocyte proinflammatory responses at the level of gene expression of a small set of upstream inhibitors of TLR and NF-κB pathways that include Trem2 and Irf4. Consistent with enhancement in proinflammatory cytokine responses, decreasing S/G lipids lowered gene expression of specific pathway inhibitors. Replenishing S/G lipids normalized gene expression of these inhibitors. In conclusion, our results suggest that microbiome-derived S/G lipids normally establish a level of buffered signaling activation necessary for well-regulated innate immune responses in systemic monocytes. By regulating gene expression of inflammatory pathway inhibitors such as Trem2, S/G lipids merit broader investigation into the potential dysfunction of other innate immune cells, such as microglia, in diseases such as Alzheimer's disease.


Assuntos
Monócitos , Transdução de Sinais , Monócitos/imunologia , Monócitos/metabolismo , Monócitos/efeitos dos fármacos , Animais , Camundongos , Microbiota/imunologia , Camundongos Endogâmicos C57BL , Imunidade Inata , Receptor 2 Toll-Like/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Lipopeptídeos/farmacologia , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , NF-kappa B/metabolismo , Inflamação/imunologia , Fatores Reguladores de Interferon/metabolismo , Fatores Reguladores de Interferon/genética , Masculino , Lipídeos , Baço/imunologia , Baço/metabolismo , Citocinas/metabolismo , Feminino
10.
J Matern Fetal Neonatal Med ; 37(1): 2371979, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38991941

RESUMO

OBJECTIVE: To evaluate neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-monocyte ratio (NMR), and other hemogram-derived inflammatory parameters measured in the early second trimester and their association with the risk of gestational diabetes mellitus (GDM). METHODS: This case-control study was conducted with 105 women with GDM and 205 healthy pregnant women, matched for maternal age at a 1:2 ratio with the cases at two regional maternity hospitals between January 2021 and August 2022. The inflammatory blood cell indices were tested in the early second trimester, and the patient's characteristics and the course of the pregnancy were analyzed. Logistic regression was used to determine the association between hematological parameters and the risk of GDM. Data were analyzed using SPSS, version 25.0 (SPSS, Chicago, IL). RESULTS: The final analysis included 310 pregnant women. The GDM group showed a higher pre-pregnancy BMI compared to the healthy controls (p < .01). There was no difference in NMR, PLR, and NLR between the groups (p = .63, .54, and .39, respectively). GDM was only positively associated with MLR (p = .02). After adjusting for potential confounding risk factors including maternal age, parity, and BMI, the multivariate regression analysis showed a higher level of MLR, with a cutoff point of 0.312, was independently associated with the risk of GDM (OR = 2.15, 95%CI 1.51-4.31, p = .03). However, ROC analysis showed that the AUC value of MLR was poor (0.670). CONCLUSIONS: We found that MLR, an inflammatory combined index derived from whole blood counts, may potentially serve as a predictor of GDM in the early second trimester.


Assuntos
Diabetes Gestacional , Monócitos , Segundo Trimestre da Gravidez , Humanos , Feminino , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Gravidez , Segundo Trimestre da Gravidez/sangue , Adulto , Estudos de Casos e Controles , Linfócitos , Contagem de Linfócitos , Valor Preditivo dos Testes
11.
Elife ; 122024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980302

RESUMO

Trained immunity is the long-term functional reprogramming of innate immune cells, which results in altered responses toward a secondary challenge. Despite indoxyl sulfate (IS) being a potent stimulus associated with chronic kidney disease (CKD)-related inflammation, its impact on trained immunity has not been explored. Here, we demonstrate that IS induces trained immunity in monocytes via epigenetic and metabolic reprogramming, resulting in augmented cytokine production. Mechanistically, the aryl hydrocarbon receptor (AhR) contributes to IS-trained immunity by enhancing the expression of arachidonic acid (AA) metabolism-related genes such as arachidonate 5-lipoxygenase (ALOX5) and ALOX5 activating protein (ALOX5AP). Inhibition of AhR during IS training suppresses the induction of IS-trained immunity. Monocytes from end-stage renal disease (ESRD) patients have increased ALOX5 expression and after 6 days training, they exhibit enhanced TNF-α and IL-6 production to lipopolysaccharide (LPS). Furthermore, healthy control-derived monocytes trained with uremic sera from ESRD patients exhibit increased production of TNF-α and IL-6. Consistently, IS-trained mice and their splenic myeloid cells had increased production of TNF-α after in vivo and ex vivo LPS stimulation compared to that of control mice. These results provide insight into the role of IS in the induction of trained immunity, which is critical during inflammatory immune responses in CKD patients.


Assuntos
Indicã , Falência Renal Crônica , Receptores de Hidrocarboneto Arílico , Animais , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Falência Renal Crônica/imunologia , Falência Renal Crônica/metabolismo , Humanos , Camundongos , Monócitos/imunologia , Monócitos/metabolismo , Monócitos/efeitos dos fármacos , Ácido Araquidônico/metabolismo , Masculino , Imunidade Inata/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Araquidonato 5-Lipoxigenase/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Imunidade Treinada
12.
PLoS One ; 19(7): e0306429, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38980867

RESUMO

Brucella abortus (Ba) is a pathogen that survives inside macrophages. Despite being its preferential niche, Ba infects other cells, as shown by the multiple signs and symptoms humans present. This pathogen can evade our immune system. Ba displays a mechanism of down-modulating MHC-I on monocytes/macrophages in the presence of IFN-γ (when Th1 response is triggered) without altering the total expression of MHC-I. The retained MHC-I proteins are located within the Golgi Apparatus (GA). The RNA of Ba is one of the PAMPs that trigger this phenomenon. However, we acknowledged whether this event could be triggered in other cells relevant during Ba infection. Here, we demonstrate that Ba RNA reduced the surface expression of MHC-I induced by IFN-γ in the human bronchial epithelium (Calu-6), the human alveolar epithelium (A-549) and the endothelial microvasculature (HMEC) cell lines. In Calu-6 and HMEC cells, Ba RNA induces the retention of MHC-I in the GA. This phenomenon was not observed in A-549 cells. We then evaluated the effect of Ba RNA on the secretion of IL-8, IL-6 and MCP-1, key cytokines in Ba infection. Contrary to our expectations, HMEC, Calu-6 and A-549 cells treated with Ba RNA had higher IL-8 and IL-6 levels compared to untreated cells. In addition, we showed that Ba RNA down-modulates the MHC-I surface expression induced by IFN-γ on human monocytes/macrophages via the pathway of the Epidermal Growth Factor Receptor (EGFR). So, cells were stimulated with an EGFR ligand-blocking antibody (Cetuximab) and Ba RNA. Neutralization of the EGFR to some extent reversed the down-modulation of MHC-I mediated by Ba RNA in HMEC and A-549 cells. In conclusion, this is the first study exploring a central immune evasion strategy, such as the downregulation of MHC-I surface expression, beyond monocytes and could shed light on how it persists effectively within the host, enduring unseen and escaping CD8+ T cell surveillance.


Assuntos
Brucella abortus , Células Endoteliais , Células Epiteliais , Antígenos de Histocompatibilidade Classe I , Interferon gama , Humanos , Interferon gama/metabolismo , Interferon gama/farmacologia , Células Endoteliais/metabolismo , Células Endoteliais/microbiologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Células Epiteliais/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe I/genética , RNA Bacteriano/genética , Linhagem Celular , Regulação para Baixo/efeitos dos fármacos , Receptores ErbB/metabolismo , Brucelose/imunologia , Brucelose/metabolismo , Brucelose/microbiologia , Brucelose/genética , Complexo de Golgi/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos/microbiologia , Monócitos/metabolismo , Monócitos/imunologia , Monócitos/efeitos dos fármacos
13.
PLoS One ; 19(7): e0306860, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38980876

RESUMO

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common health disorder of the male genitourinary system with a high prevalence, especially among middle-aged and older adults, which seriously affects men's quality of life. Inflammatory markers derived from complete blood cell count (CBC) have previously been considered a prognostic indicator for various diseases, but little is known about their relationship with BPH. This study evaluated the relationship between complete blood cell count (CBC)-derived inflammatory biomarkers and BPH. METHODS: Data for this cross-sectional study were gathered from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2008. Using multiple logistic regressions, the study examined the association between benign prostatic hyperplasia(BPH) and Inflammatory biomarkers derived from blood cell counts such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), Systemic Inflammatory Response Index (SIRI) and Systemic Immunoinflammatory Index (SII). RESULTS: 3,919 participants were included, with a median age of 61.00 (52.00-71.00) years old. Among them, 609 participants had benign prostatic hyperplasia, with a prevalence of 15.54%. Upon accounting for confounding factors, the study revealed a positive correlation between the plurality of BPH PLR and SII. However, MLR, NLR, and SIRI did not significantly correlate with the prevalence of BPH (p>0.05). In contrast to the lowest quartile, higher quartiles of PLR (OR = 1.93[1.38-2.69]) and SII (OR = 1.71[1.22-2.40]) were linked to an elevated risk of BPH. Interaction tests showed that age, body mass index, hypertension, diabetes, smoking, and drinking had no significant effect on this positive correlation (p for interaction>0.05). In addition, we found a roughly linear association between SII, PLR, and BPH using smoothed curve fitting. CONCLUSIONS: According to our research, high levels of PLR and SII are positively linked with an increased risk of BPH in middle-aged and elderly individuals in the United States. The results compensate for previous studies that still need to be validated with larger prospective cohorts.


Assuntos
Biomarcadores , Inquéritos Nutricionais , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/sangue , Hiperplasia Prostática/epidemiologia , Pessoa de Meia-Idade , Idoso , Biomarcadores/sangue , Estados Unidos/epidemiologia , Estudos Transversais , Contagem de Células Sanguíneas , Inflamação/sangue , Monócitos/metabolismo , Linfócitos , Neutrófilos , Prevalência
14.
Egypt J Immunol ; 31(3): 161-169, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38996074

RESUMO

Pregnancy results in an increase in immune cells, especially monocytes, which enhances the innate immune system. The increase of inflammatory cytokines in pregnant women's amniotic fluid, can cause uterine contraction, is linked to preterm labor. These inflammatory responses are controlled by Toll-like receptors (TLRs), which are largely expressed on neutrophils and monocytes. This study aimed to determine the role of neutrophils and monocyte subsets, as well as their expression of TLR-2 and TLR-4 in women with preterm and full-term delivery. The study involved a total of 74 women, comprising of 29 preterm labor, 25 full-term labor, and 20 non-pregnant women. The distribution of three monocyte subsets, namely (CD14++CD16-), (CD14+CD16+), and (CD14-/dim CD16++) was measured. Also, the expression of TLR2 and TLR4 in monocytes and neutrophils was analyzed using flow cytometry. Non-classical monocytes and intermediate monocytes were significantly higher in the preterm group than the control and full-term groups (p=0.041, p=0.043, and p=0.004, p= 0.049, respectively). Women in the preterm group showed significantly TLR2 expression on nonclassical monocytes compared to the control and full-term groups (p=0.002, and p=0.010, respectively). Also, preterm group expression of TLR4 was significantly higher in classical monocytes and nonclassical monocytes in comparison to the control group (p=0.019, and p≤0.0001, respectively). Besides, TLR4 expression was significantly up regulated in the preterm group compared to full-term in non-classical monocyte subset (p < 0.0001). Moreover, the expression of TLR-4 in neutrophils from the preterm group was statistically higher than expression from the full-term labor and control groups (p < .0001 for both). Such findings highlight the important role of monocyte subsets and neutrophils in activating the innate immune system and initiating strong pro-inflammatory responses that induce preterm labor. Additionally, TLR4 and TLR2 expressions on non-classical monocytes may be used as a marker to assess the probability of preterm labor.


Assuntos
Monócitos , Neutrófilos , Receptor 2 Toll-Like , Receptor 4 Toll-Like , Humanos , Feminino , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Gravidez , Neutrófilos/imunologia , Neutrófilos/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Adulto , Nascimento Prematuro/imunologia , Nascimento a Termo/imunologia , Trabalho de Parto Prematuro/imunologia , Trabalho de Parto Prematuro/metabolismo , Adulto Jovem , Receptores de Lipopolissacarídeos/metabolismo
15.
Front Immunol ; 15: 1426474, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947325

RESUMO

Background: Monocytes play a critical role in tumor initiation and progression, with their impact on prostate adenocarcinoma (PRAD) not yet fully understood. This study aimed to identify key monocyte-related genes and elucidate their mechanisms in PRAD. Method: Utilizing the TCGA-PRAD dataset, immune cell infiltration levels were assessed using CIBERSORT, and their correlation with patient prognosis was analyzed. The WGCNA method pinpointed 14 crucial monocyte-related genes. A diagnostic model focused on monocytes was developed using a combination of machine learning algorithms, while a prognostic model was created using the LASSO algorithm, both of which were validated. Random forest and gradient boosting machine singled out CCNA2 as the most significant gene related to prognosis in monocytes, with its function further investigated through gene enrichment analysis. Mendelian randomization analysis of the association of HLA-DR high-expressing monocytes with PRAD. Molecular docking was employed to assess the binding affinity of CCNA2 with targeted drugs for PRAD, and experimental validation confirmed the expression and prognostic value of CCNA2 in PRAD. Result: Based on the identification of 14 monocyte-related genes by WGCNA, we developed a diagnostic model for PRAD using a combination of multiple machine learning algorithms. Additionally, we constructed a prognostic model using the LASSO algorithm, both of which demonstrated excellent predictive capabilities. Analysis with random forest and gradient boosting machine algorithms further supported the potential prognostic value of CCNA2 in PRAD. Gene enrichment analysis revealed the association of CCNA2 with the regulation of cell cycle and cellular senescence in PRAD. Mendelian randomization analysis confirmed that monocytes expressing high levels of HLA-DR may promote PRAD. Molecular docking results suggested a strong affinity of CCNA2 for drugs targeting PRAD. Furthermore, immunohistochemistry experiments validated the upregulation of CCNA2 expression in PRAD and its correlation with patient prognosis. Conclusion: Our findings offer new insights into monocyte heterogeneity and its role in PRAD. Furthermore, CCNA2 holds potential as a novel targeted drug for PRAD.


Assuntos
Imunoterapia , Monócitos , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/terapia , Neoplasias da Próstata/diagnóstico , Monócitos/imunologia , Monócitos/metabolismo , Prognóstico , Imunoterapia/métodos , Biomarcadores Tumorais/genética , Aprendizado de Máquina , Simulação de Acoplamento Molecular , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica , Biologia Computacional/métodos , Multiômica
16.
Theranostics ; 14(9): 3486-3508, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948064

RESUMO

Rationale: Device implantation frequently triggers cardiac remodeling and fibrosis, with monocyte-driven inflammatory responses precipitating arrhythmias. This study investigates the role of m6A modification enzymes METTL3 and METTL14 in these responses and explores a novel therapeutic strategy targeting these modifications to mitigate cardiac remodeling and fibrosis. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from patients with ventricular septal defects (VSD) who developed conduction blocks post-occluder implantation. The expression of METTL3 and METTL14 in PBMCs was measured. METTL3 and METTL14 deficiencies were induced to evaluate their effect on angiotensin II (Ang II)-induced myocardial inflammation and fibrosis. m6A modifications were analyzed using methylated RNA immunoprecipitation followed by quantitative PCR. NF-κB pathway activity and levels of monocyte migration and fibrogenesis markers (CXCR2 and TGF-ß1) were assessed. An erythrocyte microvesicle-based nanomedicine delivery system was developed to target activated monocytes, utilizing the METTL3 inhibitor STM2457. Cardiac function was evaluated via echocardiography. Results: Significant upregulation of METTL3 and METTL14 was observed in PBMCs from patients with VSD occluder implantation-associated persistent conduction block. Deficiencies in METTL3 and METTL14 significantly reduced Ang II-induced myocardial inflammation and fibrosis by decreasing m6A modification on MyD88 and TGF-ß1 mRNAs. This disruption reduced NF-κB pathway activation, lowered CXCR2 and TGF-ß1 levels, attenuated monocyte migration and fibrogenesis, and alleviated cardiac remodeling. The erythrocyte microvesicle-based nanomedicine delivery system effectively targeted inflamed cardiac tissue, reducing inflammation and fibrosis and improving cardiac function. Conclusion: Inhibiting METTL3 and METTL14 in monocytes disrupts the NF-κB feedback loop, decreases monocyte migration and fibrogenesis, and improves cardiac function. Targeting m6A modifications of monocytes with STM2457, delivered via erythrocyte microvesicles, reduces inflammation and fibrosis, offering a promising therapeutic strategy for cardiac remodeling associated with device implantation.


Assuntos
Fibrose , Metiltransferases , Monócitos , NF-kappa B , Humanos , Metiltransferases/metabolismo , Metiltransferases/genética , Monócitos/metabolismo , Masculino , Animais , NF-kappa B/metabolismo , Eritrócitos/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Feminino , Metilação , Camundongos , Fator de Crescimento Transformador beta1/metabolismo , Micropartículas Derivadas de Células/metabolismo , Leucócitos Mononucleares/metabolismo , Angiotensina II/metabolismo , Receptores de Interleucina-8B/metabolismo , Receptores de Interleucina-8B/genética , Remodelação Ventricular , Miocárdio/metabolismo , Miocárdio/patologia , Nanomedicina/métodos
17.
J Immunother Cancer ; 12(7)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38964786

RESUMO

BACKGROUND: Esophageal cancer (ESCA) is a form of malignant tumor associated with chronic inflammation and immune dysregulation. However, the specific immune status and key mechanisms of immune regulation in this disease require further exploration. METHODS: To investigate the features of the human ESCA tumor immune microenvironment and its possible regulation, we performed mass cytometry by time of flight, single-cell RNA sequencing, multicolor fluorescence staining of tissue, and flow cytometry analyses on tumor and paracancerous tissue from treatment-naïve patients. RESULTS: We depicted the immune landscape of the ESCA and revealed that CD8+ (tissue-resident memory CD8+ T cells (CD8+ TRMs) were closely related to disease progression. We also revealed the heterogeneity of CD8+ TRMs in the ESCA tumor microenvironment (TME), which was associated with their differentiation and function. Moreover, the subset of CD8+ TRMs in tumor (called tTRMs) that expressed high levels of granzyme B and immune checkpoints was markedly decreased in the TME of advanced ESCA. We showed that tTRMs are tumor effector cells preactivated in the TME. We then demonstrated that conventional dendritic cells (cDC2s) derived from intermediate monocytes (iMos) are essential for maintaining the proliferation of CD8+ TRMs in the TME. Our preliminary study showed that hypoxia can promote the apoptosis of iMos and impede the maturation of cDC2s, which in turn reduces the proliferative capacity of CD8+ TRMs, thereby contributing to the progression of cancer. CONCLUSIONS: Our study revealed the essential antitumor roles of CD8+ TRMs and preliminarily explored the regulation of the iMo/cDC2/CD8+ TRM immune axis in the human ESCA TME.


Assuntos
Linfócitos T CD8-Positivos , Células Dendríticas , Neoplasias Esofágicas , Microambiente Tumoral , Humanos , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/patologia , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Monócitos/imunologia , Monócitos/metabolismo , Masculino , Feminino , Proteína Quinase CDC2/metabolismo
18.
Medicine (Baltimore) ; 103(27): e38826, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968486

RESUMO

Using the novel inflammatory biomarker lymphocyte-to-monocyte ratio (LMR), this work aimed to look into any potential connections between LMR and prostate cancer (PCa). A cross-sectional research investigation was conducted on 7706 male participants involved in the National Health and Nutrition Examination Survey from 2001 to 2010. Multivariate logistic regression modeling investigated the relationship between LMR levels and PCa risk. Furthermore, threshold analysis, subgroup analysis, interaction testing, and smoothed curve fitting were carried out. A significant negative correlation was seen between LMR and PCa risk (OR = 0.79, 95% CI: 0.65-0.97, P = .0002), even after controlling for potential confounding factors. A significant nonlinear negative correlation with a threshold effect and a breakpoint of 4.86 was found by smooth curve fitting between LMR and PCa. Subgroup analysis revealed a significant interaction (P for interaction = 0.0448) between the negative correlation between PCa and LMR about hypertension. Moreover, additional stratified smoothed curve fitting demonstrated a statistically significant inverse relationship between PCa risk and LMR. According to our findings, there is a substantial inverse relationship between PCa risk and LMR level. The inflammatory response-related index is quick, easy to use, and offers some clinical references. However, more extensive prospective investigations are required to confirm the involvement of LMR levels in PCa.


Assuntos
Linfócitos , Monócitos , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/diagnóstico , Estudos Transversais , Pessoa de Meia-Idade , Idoso , Inquéritos Nutricionais , Contagem de Linfócitos , Fatores de Risco , Adulto , Contagem de Leucócitos , Modelos Logísticos
19.
Sci Rep ; 14(1): 15736, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977751

RESUMO

Benign Prostatic Hyperplasia (BPH) is a complex condition leading to Lower Urinary Tract Symptoms in aging men, characterized by cellular proliferation, smooth muscle dysfunction, inflammation, and fibrosis. While BPH is known to involve heightened macrophage infiltration, the specific contribution of infiltrating monocytes/macrophages to the disease mechanism remains uncertain. This research explores the impact of reducing circulating monocytes and subsequently limiting their tissue infiltration by using Ccr2 knockout (Ccr2-KO) mice. Ccr2-KO and wild type mice were implanted with testosterone and estradiol (T + E2, 25 mg + 2.5 mg) pellets. Urinary function was assessed via weekly void spot assays over 12 weeks, and prostatic macrophage levels were visualized and quantified in tissue sections using an F4/80 antibody. Additionally, Ki-67 staining was used to evaluate cell proliferation, and picrosirius red staining to assess collagen accumulation. Increased voiding frequency which developed in T + E2 mice, was significantly ameliorated in Ccr2-KO mice, however, both Ccr2-KO and wild type (WT) mice showed increased bladder weights after three month, representing a hypertrophic response to bladder outlet obstruction. T + E2 substantially increased the density of macrophages in WT but not Ccr2-KO mouse prostate. Proliferation rate, as indicated by Ki-67 positivity, was elevated in the vental and anterior prostate lobes but was only marginally reduced in Ccr2-KO mice. Most importantly, a significant prostatic collagen accumulation was observed in WT mice that was markedly reduced by Ccr2 deficiency post T + E2 treatment. The absence of Ccr2 mitigates urinary dysfunction and alters prostatic macrophage levels and collagen accumulation in steroid hormone imbalance. These findings suggest a crucial role for monocyte infiltration, giving rise to macrophages or other cell derivatives, to drive fibrosis.


Assuntos
Estradiol , Fibrose , Macrófagos , Camundongos Knockout , Monócitos , Próstata , Receptores CCR2 , Testosterona , Animais , Masculino , Receptores CCR2/metabolismo , Macrófagos/metabolismo , Camundongos , Monócitos/metabolismo , Próstata/metabolismo , Próstata/patologia , Testosterona/metabolismo , Estradiol/metabolismo , Estradiol/farmacologia , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Proliferação de Células , Camundongos Endogâmicos C57BL
20.
Sci Rep ; 14(1): 15663, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977917

RESUMO

Mycobacterium avium complex pulmonary disease (MAC-PD) has a heterogeneous clinical course. However, immune profiles associated with MAC-PD clinical course are limited. We performed single-cell RNA sequencing of peripheral blood mononuclear cells from 21 MAC-PD patients divided into three clinical courses: group A, spontaneous culture conversion; group B, stable disease without antibiotic treatment; and group C, progressive disease with antibiotic treatment. A lower proportion of NK cells and higher proportion of monocytes were noted in group C compared to combined groups A and B. The proportion of classical monocytes was higher in group C compared to groups A and B, while the proportion of non-classical monocytes decreased. EGR1, HSPA1A, HSPA1B, and CD83 were up-regulated in spontaneous culture conversion group A compared to progressive disease group C. Up-regulation of MYOM2 and LILRA4 and down-regulation of MT-ATP8, CD83, and CCL3L1 was found in progressive disease group C. PCBP1, FOS, RGCC, S100B, G0S2, AREG, and LYN were highly expressed in favorable treatment response compared to unfavorable response. Our findings may offer a comprehensive understanding of the host immune profiles that influence a particular MAC-PD clinical course and could suggest an immunological mechanism associated with the disease progression of MAC-PD.


Assuntos
Complexo Mycobacterium avium , Infecção por Mycobacterium avium-intracellulare , Transcriptoma , Humanos , Masculino , Feminino , Infecção por Mycobacterium avium-intracellulare/microbiologia , Idoso , Complexo Mycobacterium avium/genética , Pessoa de Meia-Idade , Análise de Célula Única/métodos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/microbiologia , Pneumopatias/microbiologia , Pneumopatias/genética , Perfilação da Expressão Gênica , Progressão da Doença , Monócitos/metabolismo , Monócitos/imunologia
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