Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20.655
Filtrar
2.
Nat Commun ; 11(1): 4718, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948777

RESUMO

Disturbances in glucose homeostasis and low-grade chronic inflammation culminate into metabolic syndrome that increase the risk for the development of type 2 diabetes mellitus (T2DM). The recently discovered group 2 innate lymphoid cells (ILC2s) are capable of secreting copious amounts of type 2 cytokines to modulate metabolic homeostasis in adipose tissue. In this study, we have established that expression of Death Receptor 3 (DR3), a member of the TNF superfamily, on visceral adipose tissue (VAT)-derived murine and peripheral blood human ILC2s is inducible by IL-33. We demonstrate that DR3 engages the canonical and/or non-canonical NF-κB pathways, and thus stimulates naïve and co-stimulates IL-33-activated ILC2s. Importantly, DR3 engagement on ILC2s significantly ameliorates glucose tolerance, protects against insulin-resistance onset and remarkably reverses already established insulin-resistance. Taken together, these results convey the potent role of DR3 as an ILC2 regulator and introduce DR3 agonistic treatment as a novel therapeutic avenue for treating T2DM.


Assuntos
Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Linfócitos/metabolismo , Membro 25 de Receptores de Fatores de Necrose Tumoral/metabolismo , Adipócitos/metabolismo , Adolescente , Adulto , Idoso , Animais , Citocinas/metabolismo , Proteínas de Ligação a DNA/genética , Feminino , Glucose/metabolismo , Homeostase , Humanos , Imunidade Inata , Resistência à Insulina , Interleucina-33/metabolismo , Gordura Intra-Abdominal/metabolismo , Masculino , Síndrome Metabólica/complicações , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Membro 25 de Receptores de Fatores de Necrose Tumoral/uso terapêutico , Adulto Jovem
3.
Medicine (Baltimore) ; 99(33): e21550, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872002

RESUMO

To study the relationship between neutrophil to lymphocyte ratio (NLR) and exercise tolerance of patients with chronic obstructive pulmonary disease (COPD).235 patients with COPD were selected as the study subjects. Complete blood count, C reactive protein (CRP), pulmonary function tests, the 6-minute walk distance (6MWD), Modified Medical Respiratory Council, the COPD assessment test, and clinical COPD questionnaire were tested. Heart rate, oxygen saturation, and Borg scale were tested before or after 6MWD test.By the median of NLR, the subjects were divided into 2 groups, NLR ≥4.5 group and NLR <4.5 group. The white blood cell count (WBC), CRP and deoxygenation saturation in the NLR ≥4.5 group were higher than those in the NLR <4.5 group, while the age, body mass index (BMI), 6MWD, and heart rate variation were lower than those in the NLR <4.5 group. CRP, WBC, and deoxygenation saturation had positive effects on NLR, BMI, 6MWT, and heart rate variation had negative effects on NLR. The Pearson correlation analysis showed NLR was positively correlated with WBC, CRP, BMI index, 6MWT, and deoxygenation saturation, while it was negatively correlated with BMI and heart rate variation.NLR might associate with exercise tolerance and cardiorespiratory reserve of COPD patients, and could be used as an indicator of muscle function in COPD patients.


Assuntos
Tolerância ao Exercício , Linfócitos/metabolismo , Neutrófilos/metabolismo , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Inquéritos e Questionários , Teste de Caminhada
4.
Nat Commun ; 11(1): 4786, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963227

RESUMO

Evidence points to an indispensable function of macrophages in tissue regeneration, yet the underlying molecular mechanisms remain elusive. Here we demonstrate a protective function for the IL-33-ST2 axis in bronchial epithelial repair, and implicate ST2 in myeloid cell differentiation. ST2 deficiency in mice leads to reduced lung myeloid cell infiltration, abnormal alternatively activated macrophage (AAM) function, and impaired epithelial repair post naphthalene-induced injury. Reconstitution of wild type (WT) AAMs to ST2-deficient mice completely restores bronchial re-epithelialization. Central to this mechanism is the direct effect of IL-33-ST2 signaling on monocyte/macrophage differentiation, self-renewal and repairing ability, as evidenced by the downregulation of key pathways regulating myeloid cell cycle, maturation and regenerative function of the epithelial niche in ST2-/- mice. Thus, the IL-33-ST2 axis controls epithelial niche regeneration by activating a large multi-cellular circuit, including monocyte differentiation into competent repairing AAMs, as well as group-2 innate lymphoid cell (ILC2)-mediated AAM activation.


Assuntos
Bronquíolos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Epiteliais/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , Interleucina-33/farmacologia , Animais , Bronquíolos/lesões , Bronquíolos/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Células Epiteliais/patologia , Feminino , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Pulmão/patologia , Ativação Linfocitária , Linfócitos/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais
5.
Front Immunol ; 11: 1337, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733448

RESUMO

Autophagy is a cellular recycling system found in almost all types of eukaryotic organisms. The system is made up of a variety of proteins which function to deliver intracellular cargo to lysosomes for formation of autophagosomes in which the contents are degraded. The maintenance of cellular homeostasis is key in the survival and function of a variety of human cell populations. The interconnection between metabolism and autophagy is extensive, therefore it has a role in a variety of different cell functions. The disruption or dysfunction of autophagy in these cell types have been implicated in the development of a variety of inflammatory diseases including asthma. The role of autophagy in non-immune and immune cells both lead to the pathogenesis of lung inflammation. Autophagy in pulmonary non-immune cells leads to tissue remodeling which can develop into chronic asthma cases with long term effects. The role autophagy in the lymphoid and myeloid lineages in the pathology of asthma differ in their functions. Impaired autophagy in lymphoid populations have been shown, in general, to decrease inflammation in both asthma and inflammatory disease models. Many lymphoid cells rely on autophagy for effector function and maintained inflammation. In stark contrast, autophagy deficient antigen presenting cells have been shown to have an activated inflammasome. This is largely characterized by a TH17 response that is accompanied with a much worse prognosis including granulocyte mediated inflammation and steroid resistance. The cell specificity associated with changes in autophagic flux complicates its targeting for amelioration of asthmatic symptoms. Differing asthmatic phenotypes between TH2 and TH17 mediated disease may require different autophagic modulations. Therefore, treatments call for a more cell specific and personalized approach when looking at chronic asthma cases. Viral-induced lung inflammation, such as that caused by SARS-CoV-2, also may involve autophagic modulation leading to inflammation mediated by lung resident cells. In this review, we will be discussing the role of autophagy in non-immune cells, myeloid cells, and lymphoid cells for their implications into lung inflammation and asthma. Finally, we will discuss autophagy's role viral pathogenesis, immunometabolism, and asthma with insights into autophagic modulators for amelioration of lung inflammation.


Assuntos
Asma/complicações , Asma/patologia , Autofagia/imunologia , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Animais , Asma/imunologia , Autofagossomos/metabolismo , Autofagia/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Células Dendríticas/metabolismo , Humanos , Linfócitos/metabolismo , Lisossomos/metabolismo , Células Mieloides/metabolismo , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Mucosa Respiratória/metabolismo , Transdução de Sinais/imunologia
6.
PLoS One ; 15(8): e0236805, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790689

RESUMO

OBJECTIVE: To predict spontaneous preterm birth among pregnant women in an African American population using first trimester peripheral blood maternal immune cell microRNA. STUDY DESIGN: This was a retrospective nested case-control study in pregnant patients enrolled between March 2006 and October 2016. For initial study inclusion, samples were selected that met the following criteria: 1) singleton pregnancy; 2) maternal body mass index (BMI) <30 kg/m2; 3) blood sample drawn between 6 weeks to 12 weeks 6 days gestation; 4) live born neonate with no detectable birth defects. Using these entry criteria, 486 samples were selected for study inclusion. After sample quality was confirmed, 139 term deliveries (38-42 weeks) and 18 spontaneous preterm deliveries (<35 weeks) were selected for analysis. Samples were divided into training and validation sets. Real time reverse transcription quantitative polymerase chain reaction (rt-qPCR) was performed on each sample for 45 microRNAs. MicroRNA Risk Scores were calculated on the training set and area-under-the-curve receiver-operating-characteristic (AUC-ROC) curves were derived from the validation set. RESULTS: The AUC-ROC for the validation set delivering preterm was 0.80 (95% CI: 0.69 to 0.88; p = 0.0001), sensitivity 0.89, specificity of 0.71 and a mean gestational age of 10.0 ±1.8 weeks (range: 6.6-12.9 weeks). When the validation population was divided by gestational age at the time of venipuncture into early first trimester (mean 8.4 ±1.0 weeks; range 6.6-9.7 weeks) and late first trimester (mean 11.5±0.8 weeks; range 10.0-12.9 weeks), the AUC-ROC scores for early and late first trimester were 0.79 (95% CI: 0.63 to 0.91) and 0.81 (95% CI: 0.66 to 0.92), respectively. CONCLUSION: Quantification of first trimester peripheral blood MicroRNA identifies risk of spontaneous preterm birth in samples obtained early and late first trimester of pregnancy in an African American population.


Assuntos
MicroRNAs/sangue , Nascimento Prematuro/epidemiologia , Adulto , Área Sob a Curva , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Linfócitos/citologia , Linfócitos/metabolismo , Gravidez , Primeiro Trimestre da Gravidez , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
7.
Nat Commun ; 11(1): 3998, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778730

RESUMO

Allergic asthma is a leading chronic disease associated with airway hyperreactivity (AHR). Type-2 innate lymphoid cells (ILC2s) are a potent source of T-helper 2 (Th2) cytokines that promote AHR and lung inflammation. As the programmed cell death protein-1 (PD-1) inhibitory axis regulates a variety of immune responses, here we investigate PD-1 function in pulmonary ILC2s during IL-33-induced airway inflammation. PD-1 limits the viability of ILC2s and downregulates their effector functions. Additionally, PD-1 deficiency shifts ILC2 metabolism toward glycolysis, glutaminolysis and methionine catabolism. PD-1 thus acts as a metabolic checkpoint in ILC2s, affecting cellular activation and proliferation. As the blockade of PD-1 exacerbates AHR, we also develop a human PD-1 agonist and show that it can ameliorate AHR and suppresses lung inflammation in a humanized mouse model. Together, these results highlight the importance of PD-1 agonistic treatment in allergic asthma and underscore its therapeutic potential.


Assuntos
Asma/imunologia , Asma/metabolismo , Imunidade Inata/imunologia , Linfócitos/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Animais , Citocinas/metabolismo , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Humanos , Inflamação/imunologia , Subunidade gama Comum de Receptores de Interleucina/genética , Interleucina-33/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Receptor de Morte Celular Programada 1/genética , Células Th2/metabolismo , Transcriptoma
8.
Nat Commun ; 11(1): 4076, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796851

RESUMO

Group 3 innate lymphoid cells (ILC3) are an important regulator for immunity, inflammation and tissue homeostasis in the intestine, but how ILC3 activation is regulated remains elusive. Here we identify a new circular RNA (circRNA) circKcnt2 that is induced in ILC3s during intestinal inflammation. Deletion of circKcnt2 causes gut ILC3 activation and severe colitis in mice. Mechanistically, circKcnt2, as a nuclear circRNA, recruits the nucleosome remodeling deacetylase (NuRD) complex onto Batf promoter to inhibit Batf expression; this in turn suppresses Il17 expression and thereby ILC3 inactivation to promote innate colitis resolution. Furthermore, Mbd3-/-Rag1-/- and circKcnt2-/-Rag1-/- mice develop severe innate colitis following dextran sodium sulfate (DSS) treatments, while simultaneous deletion of Batf promotes colitis resolution. In summary, our data support a function of the circRNA circKcnt2 in regulating ILC3 inactivation and resolution of innate colitis.


Assuntos
Colite/imunologia , Colite/metabolismo , Linfócitos/metabolismo , Canais de Potássio Ativados por Sódio/metabolismo , RNA Circular/metabolismo , Animais , Colite/patologia , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Feminino , Proteínas de Homeodomínio/genética , Homeostase , Humanos , Imunidade Inata , Inflamação/imunologia , Inflamação/patologia , Intestinos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout , Canais de Potássio Ativados por Sódio/genética , RNA Circular/genética , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Fatores de Transcrição/genética
9.
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
10.
Ann Surg ; 272(2): 342-351, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32675548

RESUMO

BACKGROUND: Systemic inflammation via host-tumor interactions is currently recognized as a hallmark of cancer. The aim of this study was to evaluate the prognostic value of various combinations of inflammatory factors using preoperative blood, and to assess the clinical significance of our newly developed inflammatory score in colorectal cancer (CRC) patients. METHOD: In total 477 CRC patients from the discovery and validation cohorts were enrolled in this study. We assessed the predictive impact for recurrence using a combination of nine inflammatory markers in the discovery set, and focused on lymphocyte-C-reactive protein ratio (LCR) to elucidate its prognostic and predictive value for peri-operative risk in both cohorts. RESULTS: A combination of lymphocytic count along with C-reactive protein levels demonstrated the highest correlation with recurrence compared with other parameters in CRC patients. Lower levels of preoperative LCR significantly correlated with undifferentiated histology, advanced T stage, presence of lymph node metastasis, distant metastasis, and advanced stage classification. Decreased preoperative LCR (using an optimal cut-off threshold of 6000) was an independent prognostic factor for both disease-free survival and overall survival, and emerged as an independent risk factor for postoperative complications and surgical-site infections in CRC patients. Finally, we assessed the clinical feasibility of LCR in an independent validation cohort, and confirmed that decreased preoperative LCR was an independent prognostic factor for both disease-free survival and overall survival, and was an independent predictor for postoperative complications and surgical-site infections in CRC patients. CONCLUSION: Preoperative LCR is a useful marker for perioperative and postoperative management of CRC patients.


Assuntos
Biomarcadores Tumorais/sangue , Proteína C-Reativa/metabolismo , Neoplasias Colorretais/sangue , Neoplasias Colorretais/cirurgia , Linfócitos/metabolismo , Adulto , Idoso , Estudos de Coortes , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
12.
DNA Cell Biol ; 39(9): 1573-1582, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32678986

RESUMO

Many immune cells participate in the pathogenesis of ulcerative colitis (UC), and fatty acid metabolism (FAM) is reported to supporting their cell-specific functions and proliferation, but the underlying mechanism is unclear. This study aimed to investigate the relationship between FAM and inflammation in colon tissues and identify potential therapeutic targets for regulating immune response. A total of 870 different expression genes (DEGs), 304 immunity-related DEGs, and 11 FAM-related DEGs were obtained, gene ontology analysis results showed that immune DEGs were significantly enriched in neutrophil migration, positive regulation of T cell activation. Fifteen types of immune cells were identified in inflamed colon tissues. Five FAM-related DEGs (ACOX1, ACSL4, ELOVL5, FADS2, and SCD) were highly correlated with immunity-related DEGs, and ACSL4, ELOVL5, and FADS2 were significantly upregulated in immune cells, while SCD is downregulated. Five FAM-related DEGs were highly correlated with immune cells. The study promotes the understanding of the pathogenesis of FAM in UC immune cells.


Assuntos
Colite Ulcerativa/genética , Ácidos Graxos/metabolismo , Redes Reguladoras de Genes , Transcriptoma , Acil-CoA Oxidase/genética , Acil-CoA Oxidase/metabolismo , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo , Colite Ulcerativa/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Elongases de Ácidos Graxos/genética , Elongases de Ácidos Graxos/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Linfócitos/metabolismo , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo
13.
Ann Hematol ; 99(10): 2231-2242, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32621182

RESUMO

Long non-coding RNAs (lncRNAs) have an established role in cell biology. Among their functions is the regulation of hematopoiesis. They characterize the different stages of hematopoiesis in a more lineage-restricted expression pattern than coding mRNAs. They affect hematopoietic stem cell renewal, proliferation, and differentiation of committed progenitors by interacting with master regulators transcription factors. Among these transcription factors, MYC has a prominent role. Similar to MYC's transcriptional activation/amplification of protein coding genes, MYC also regulates lncRNAs' expression profile, while it is also regulated by lncRNAs. Both myeloid and lymphoid malignancies are prone to the association of MYC with lncRNAs. Such interaction inhibits apoptosis, enhances cell proliferation, deregulates metabolism, and promotes genomic instability and resistance to treatment. In this review, we discuss the recent findings that encompass the crosstalk between lncRNAs and describe the pathways that very probably have a pathogenetic role in both acute and chronic hematologic malignancies.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Hematológicas/genética , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas c-myc/fisiologia , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Autorrenovação Celular/genética , Genes myc , Hematopoese/genética , Humanos , Leucemia/genética , Linfócitos/metabolismo , Linfócitos/patologia , Linfoma/genética , Mieloma Múltiplo/genética , Células Mieloides/metabolismo , Células Mieloides/patologia , Nicho de Células-Tronco
14.
PLoS One ; 15(7): e0236744, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730309

RESUMO

Repeated exposures to environmental allergens in susceptible individuals drive the development of type 2 inflammatory conditions such as asthma, which have been traditionally considered to be mainly mediated by Th2 cells. However, emerging evidence suggest that a new innate cell type, group 2 innate lymphoid cells (ILC2), plays a central role in initiating and amplifying a type 2 response, even in the absence of adaptive immunity. At present, the regulatory mechanisms for controlling ILC2 activation remain poorly understood. Here we report that respiratory delivery of immunogenic extracellular RNA (exRNAs) derived from RNA- and DNA-virus infected cells, was able to activate a protective response against acute type 2 lung immunopathology and airway hyperresponsiveness (AHR) induced by IL-33 and a fungal allergen, A. flavus, in mice. Mechanistically, we found that the innate immune responses triggered by exRNAs had a potent suppressive effect in vivo on the proliferation and function of ILC2 without the involvement of adaptive immunity. We further provided the loss-of-function genetic evidence that the TLR3- and MAVS-mediated signaling axis is essential for the inhibitory effects of exRNAs in mouse lungs. Thus, our results indicate that the host detection of extracellular immunostimulatory RNAs generated during respiratory viral infections have an important function in the regulation of ILC2-driven acute lung inflammation.


Assuntos
Armadilhas Extracelulares/imunologia , Imunidade Inata/imunologia , Linfócitos/imunologia , Pneumonia/imunologia , RNA/imunologia , Hipersensibilidade Respiratória/imunologia , Imunidade Adaptativa , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas Adaptadoras de Transporte Vesicular/fisiologia , Alérgenos/imunologia , Alérgenos/metabolismo , Animais , Citocinas/metabolismo , Armadilhas Extracelulares/metabolismo , Interleucina-33/imunologia , Interleucina-33/metabolismo , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/metabolismo , Pneumonia/patologia , RNA/metabolismo , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia , Transdução de Sinais , Células Th2/imunologia , Células Th2/metabolismo , Receptor 3 Toll-Like/fisiologia
15.
Drug Discov Ther ; 14(3): 117-121, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32595179

RESUMO

The advent of immune checkpoint inhibitors such as anti-PD-1 antibodies had a striking impact on the treatment for advanced malignant melanoma. However, less than half of the patients benefited from those antibodies, and biomarkers that could sensitively differentiate responders from non-responders are urgently needed. Herein, we explored such biomarkers by retrospectively analyzing clinical data from patients with advanced malignant melanoma treated with nivolumab and pembrolizumab. We found that anti-PD-1 antibody was especially effective for those with metastasis only to soft tissues. Although no significant difference was found in the baseline value of relative neutrophil count (RNC), relative lymphocyte count (RLC), neutrophil to lymphocyte ratio (NLR), and relative eosinophil count (REC) between responders and non-responders, responders after anti-PD-1 therapy revealed the increase of lymphocytes and eosinophils and the decrease of neutrophils within the first 6 weeks of the treatment. We also calculated the change of RNC and RLC 3 weeks and 6 weeks after the initiation of the therapy and designated as NΔ3-LΔ3 and NΔ6-LΔ6 respectively. NΔ3-LΔ3 was significantly decreased in responders, which suggest that the neutrophil decrease and lymphocyte increase after as early as 3 weeks of anti-PD-1 therapy might be a useful clinical indicator. In addition, the difference of NΔ6-LΔ6 between responders and non-responders was even more robust. These data suggest that change of RNC, RLC, and REC together with the combination of NΔ3-LΔ3 and NΔ6-LΔ6 might be a useful tool for early and sensitive biomarkers for anti-PD-1 therapy.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Melanoma/tratamento farmacológico , Nivolumabe/administração & dosagem , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Autoanticorpos/sangue , Autoanticorpos/efeitos dos fármacos , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Melanoma/sangue , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Receptor de Morte Celular Programada 1/sangue , Estudos Retrospectivos , Neoplasias Cutâneas/sangue , Resultado do Tratamento
16.
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
17.
Medicine (Baltimore) ; 99(23): e20629, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502042

RESUMO

BACKGROUND: Incarcerated groin hernia (IGH) is a common surgical emergency. However, there are few accurate and applicable predictors for differentiating patients with strangulated groin hernia from those with IGH. In this study, we aimed to identify the independent risk factors for bowel resection in patients with IGH. METHODS: We retrospectively collected 323 patients who underwent emergency hernia repair surgery for IGH between January 2010 and October 2019. The patients were categorized into those who received bowel resection and those who did not require bowel resection. The receiver-operating characteristic curve was used to identify the best cutoff values for continuous variables. Following this, univariate and multivariate analyses were performed to identify potential risk factors for bowel resection in these patients. RESULTS: Univariate analysis identified 6 variables that were significantly associated with bowel resection among patients with IGH. On multivariate analysis, neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR] = 3.362, 95% confidence interval [CI] 1.705-6.628, P = .000) and bowel obstruction (OR = 3.191, 95% CI 1.873-5.437, P = 0.000) were identified as independent risk factors for bowel resection among patients with IGH. CONCLUSION: In this study, an elevated NLR and those with bowel obstruction are associated with an increased risk of bowel resection among patients with IGH. Based on our findings, surgeons should prioritize prompt emergency surgical repair for patients who present with elevated NLR and bowel obstruction concurrent with IGH.


Assuntos
Hérnia Inguinal/cirurgia , Herniorrafia/efeitos adversos , Obstrução Intestinal/cirurgia , Estudos de Casos e Controles , Emergências , Feminino , Hérnia Inguinal/complicações , Herniorrafia/métodos , Humanos , Obstrução Intestinal/etiologia , Linfócitos/metabolismo , Masculino , Neutrófilos/metabolismo , Estudos Retrospectivos , Fatores de Risco
18.
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
19.
Drug Discov Ther ; 14(3): 143-144, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32581194

RESUMO

In the midst of a pandemic, finding effective treatments for coronavirus disease 2019 (COVID-19) is the urgent issue. In "chronic inflammatory diseases", the overexpression of delayed rectifier K+-channels (Kv1.3) in leukocytes is responsible for the overactivation of cellular immunity and the subsequent cytokine storm. In our previous basic studies, drugs including chloroquine and azithromycin strongly suppressed the channel activity and pro-inflammatory cytokine production from lymphocytes. These findings suggest a novel pharmacological mechanism by which chloroquine, with or without azithromycin, is effective for severe cases of COVID-19, in which the overactivation of cellular immunity and the subsequent cytokine storm are responsible for the pathogenesis.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Citocinas/antagonistas & inibidores , Sistemas de Liberação de Medicamentos/métodos , Canal de Potássio Kv1.3/antagonistas & inibidores , Linfócitos/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Azitromicina/administração & dosagem , Cloroquina/administração & dosagem , Infecções por Coronavirus/metabolismo , Citocinas/metabolismo , Sistemas de Liberação de Medicamentos/tendências , Humanos , Canal de Potássio Kv1.3/metabolismo , Linfócitos/metabolismo , Pandemias , Pneumonia Viral/metabolismo , Índice de Gravidade de Doença
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA