RESUMO
Silver nanoparticles (AgNPs) are a potential antiviral agent due to their ability to disrupt the viral particle or alter the virus metabolism inside the host cell. In vitro, AgNPs exhibit antiviral activity against the most common human respiratory viruses. However, their capacity to modulate immune responses during respiratory viral infections has yet to be explored. This study demonstrates that administering AgNPs directly into the lungs prior to infection can reduce viral loads and therefore virus-induced cytokines in mice infected with influenza virus or murine pneumonia virus. The prophylactic effect was diminished in mice with depleted lymphoid cells. We showed that AgNPs-treatment resulted in the recruitment and activation of lymphocytes in the lungs, particularly natural killer (NK) cells. Mechanistically, AgNPs enhanced the ability of alveolar macrophages to promote both NK cell migration and IFN-γ production. By contrast, following infection, in mice treated with AgNPs, NK cells exhibited decreased activation, indicating that these nanoparticles can regulate the potentially deleterious activation of these cells. Overall, the data suggest that AgNPs may possess prophylactic antiviral properties by recruiting and controlling the activation of lymphoid cells through interaction with alveolar macrophages.
Assuntos
Células Matadoras Naturais , Pulmão , Nanopartículas Metálicas , Infecções por Orthomyxoviridae , Prata , Animais , Prata/química , Prata/farmacologia , Nanopartículas Metálicas/química , Pulmão/virologia , Pulmão/patologia , Pulmão/efeitos dos fármacos , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/virologia , Camundongos , Células Matadoras Naturais/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/virologia , Camundongos Endogâmicos C57BL , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Antivirais/farmacologia , Antivirais/uso terapêutico , Feminino , Ativação Linfocitária/efeitos dos fármacosRESUMO
OBJECTIVE: The aim of this study was to investigate the role of systemic immune-inflammation index, neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, and platelet-lymphocyte ratios calculated in the first trimester as inflammatory markers in predicting gestational diabetes mellitus diagnosis. METHODS: This study was conducted retrospectively at a tertiary center between January 2020 and June 2023. A total of 111 pregnant women with gestational diabetes and 378 pregnant women in the control group were included in the study. Systemic immune-inflammation index, neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, and platelet-lymphocyte ratios values were compared between the gestational diabetes mellitus group patients and the healthy group. Receiver operating characteristic analysis curve was used for predicting gestational diabetes mellitus using systemic immune-inflammation index and lymphocyte-monocyte ratio. RESULTS: In pregnant women in the first trimester, systemic immune-inflammation index and lymphocyte-monocyte ratio values based on routine complete blood count parameters were found to be statistically significantly higher in gestational diabetes mellitus patients compared to healthy patients, while neutrophil-lymphocyte ratio and platelet-lymphocyte ratios values were found to be similar (p=0.033, p=0.005, p=0.211, and p=0.989). For predicting gestational diabetes mellitus, a cut-off value of 655.75 for systemic immune-inflammation index resulted in 80.2% sensitivity and 34.4% specificity, and a cut-off value of 3.62 for lymphocyte-monocyte ratio resulted in 56.8% sensitivity and 63.2% specificity, indicating good discriminatory ability. CONCLUSION: We believe that systemic immune-inflammation index and lymphocyte-monocyte ratio values measured in the first-trimester complete blood count parameters are effective in predicting gestational diabetes mellitus but are not effective in determining insulin requirement.
Assuntos
Biomarcadores , Diabetes Gestacional , Neutrófilos , Primeiro Trimestre da Gravidez , Curva ROC , Humanos , Diabetes Gestacional/sangue , Diabetes Gestacional/imunologia , Diabetes Gestacional/diagnóstico , Feminino , Gravidez , Primeiro Trimestre da Gravidez/sangue , Primeiro Trimestre da Gravidez/imunologia , Estudos Retrospectivos , Adulto , Biomarcadores/sangue , Inflamação/sangue , Inflamação/imunologia , Linfócitos/imunologia , Valor Preditivo dos Testes , Monócitos/imunologia , Estudos de Casos e Controles , Contagem de Plaquetas , Contagem de Linfócitos , Sensibilidade e EspecificidadeRESUMO
Background and purpose:
Mechanical thrombectomy is the most important treatment modality in acute stroke; despite successful thrombectomy, good functional outcome is not achieved in a significant proportion of patients. This study examined the effect of neutrophil lymphocyte ratio (NLR) values at admission on functional outcomes in successfully recanalized patients.
. Methods:Patients who underwent mechanical thrombectomy due to anterior system major vessel occlusion were retrospectively analyzed and compared with the admission NLR values and 3-month clinical modified Rankin Scale (mRS) scores of successfully recanalized patients.
. Results:Of a total of 126 patients who underwent thrombectomy within the specified period, 97 patients with successful recanalization were included in the study. The overall successful recanalization rate was calculated as 77%. The mean NLR of patients with mRS ≤2 (n=65) was found to be significantly lower than patients with mRS≥3 (n=32) (p<0.001). A weak and significant correlation was found between National Institutes of Health Stroke Scale (NIHSS) value and NLR (r= 0.315, p=.002).
. Conclusion:NLR value has been found to be associated with futile recanalization in mechanical thrombectomy patients. Therefore, we think that suppression of inflammation before thrombectomy will increase the chance of successful thrombectomy.
.Assuntos
Linfócitos , Neutrófilos , Acidente Vascular Cerebral , Trombectomia , Humanos , Acidente Vascular Cerebral/cirurgia , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Inflamação , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to evaluate the potential of immunonutritional markers, specifically the hemoglobin, albumin, lymphocyte, and platelet (HALP) score and the prognostic nutritional index (PNI), in predicting late-onset fetal growth restriction (LO-FGR) during the first trimester. MATERIALS AND METHODS: This retrospective study was conducted at a tertiary care center between October 2022 and August 2023. The study included a total of 213 singleton pregnancies, with 99 women in the LO-FGR group and 114 in the healthy control group, matched by maternal age and gestational age at delivery. All blood samples were collected between 11 and 14 weeks of gestation (during the first-trimester screening test). We analyzed first-trimester laboratory parameters, specifically focusing on hemoglobin levels, white blood cells (WBCs), lymphocytes, platelets, and albumin levels. Afterwards, we calculated the HALP score and PNI, and then compared the values of both groups. RESULTS: Both HALP score (3.58 ± 1.31 vs. 4.19 ± 1.8, p = 0.012) and PNI (36.75 ± 2.9 vs. 39.37 ± 3.96, p < 0.001) were significantly lower in the FGR group than in the control group. The HALP score cut-off value of < 3.43 in predicting FGR had a sensitivity of 62.3% and specificity of 54.5% (AUC = 0.600, 95% CI: 0.528-0.672, p = 0.012). The PNI cut-off value of < 37.9 in predicting FGR had a sensitivity of 65.8% and specificity of 62.9% (AUC = 0.707, 95% CI: 0.632-0.778, p < 0.001). While the HALP score was not a significant predictor of composite adverse neonatal outcomes in the FGR group, PNI showed a cut-off value of < 37.7 with a sensitivity of 60.9% and specificity of 59.7% (AUC = 0.657, 95% CI: 0.581-0.733, p < 0.001). CONCLUSION: The HALP score and PNI are valuable prognostic tools for predicting the risk of FGR in the first trimester. Low PNI values are also associated with composite adverse neonatal outcomes in pregnancies complicated by FGR.
Assuntos
Retardo do Crescimento Fetal , Hemoglobinas , Avaliação Nutricional , Estado Nutricional , Primeiro Trimestre da Gravidez , Humanos , Feminino , Gravidez , Primeiro Trimestre da Gravidez/sangue , Estudos Retrospectivos , Retardo do Crescimento Fetal/sangue , Retardo do Crescimento Fetal/diagnóstico , Adulto , Prognóstico , Hemoglobinas/análise , Linfócitos , Albumina Sérica/análise , Biomarcadores/sangue , Plaquetas , Valor Preditivo dos Testes , Contagem de Plaquetas , Estudos de Casos e Controles , Inflamação/sangue , Contagem de LinfócitosRESUMO
Ankylosing spondylitis (AS) as a autoimmune disease involves inflammatory responses in the development of the disease, often causing changes in the neutrophil to lymphocyte ratio (NLR). In the past few decades, research on the relationship between NLR and AS has generally shown an upward trend. This study adopts the bibliometrics method to analyze the development trend, frontier, and hotspots of global research in this field in the past 2 decades. By searching for publications in the SCI-Expanded edition of the Web of Science Core Collection, the information of literature published between 2000 and 2023 is recorded. Based on the VOSviewer, CiteSpace and Excel, bibliometric analysis, and visualization analysis are conducted on the overall distribution of annual output, leading countries, active institutions, journals, authors, co-cited references, and keywords. Through retrieving and screening, a total of 1654 papers are obtained for analysis. In the past 2 decades, the number of publications related to this field has shown an increasing trend. The United States has the highest Hirsch index (H-index) and publication volume. The most productive institution is Harvard University, while the H-index of the University of Milan in Italy is far ahead. Frontiers in Immunology is the institution with the highest output. The H-index of the Annals of the Rheumatic holds the top position. This study has uncovered the main emphasis on NLR in AS research and has provided clarification regarding the value of NLR as a biomarker for immune inflammatory response in the diagnosis and prognosis of AS.
Assuntos
Bibliometria , Linfócitos , Neutrófilos , Espondilite Anquilosante , Espondilite Anquilosante/sangue , Humanos , Linfócitos/imunologiaRESUMO
Background: The chronic inflammatory immune response is a significant factor in the pathogenesis of benign gynecological diseases. The systemic immunoinflammatory index (SII) and the platelet-to-lymphocyte ratio (PLR) are commonly available biomarkers of inflammation. However, evidence of the relationship between SII and PLR in patients with adenomyosis is limited. This study aimed to investigate the relationship between SII and PLR in patients with adenomyosis. Methods: This cross-sectional study included 483 patients with adenomyosis who were first diagnosed at our institution between January 2019 and December 2021. Basic patient clinical information and inflammatory factors were collected for univariate analysis, smoothed curve fitting, and multivariate segmented linear regression. Results: The results of the univariate analysis showed a significant positive correlation between PLR levels and SII (P < 0.001). In addition, a nonlinear relationship between PLR and SII was tested using a smoothed curve fit after adjusting for potential confounders. Multiple segmented linear regression models showed a significant relationship between SII and PLR in both SII < 1,326.47 (ß 0.14, 95% CI: 0.12, 0.16; P < 0.0001) and >1,326.47 (ß 0.02, 95% CI: -0.01, 0.05; P = 0.2461). Conclusions: In conclusion, this study showed a nonlinear relationship between SII and PLR in patients with uterine adenomyosis. An increase in serum PLR levels correlates with an increase in SII before SII levels reach an inflection point.
Assuntos
Adenomiose , Plaquetas , Linfócitos , Humanos , Adenomiose/sangue , Feminino , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Inflamação/sangue , Modelos Lineares , Biomarcadores/sangue , Contagem de PlaquetasRESUMO
This study aims to evaluate the neutrophil-to-lymphocyte ratio (NLR) as a predictive biomarker for cardiovascular mortality among cancer patients, utilizing data from the National Health and Nutrition Examination Survey (NHANES). From the NHANES dataset (2007-2018), we analyzed 4974 cancer survivors, investigating the prognostic significance of NLR for all-cause, cardiovascular, and cancer-specific mortality. Survival outcomes were analyzed using Cox regression and Kaplan-Meier methods. Optimal NLR cutoffs were identified as 2.61 for differentiating the higher NLR group from lower NLR group. Elevated NLR levels significantly correlated with increased all-cause mortality (HR 1.11, 95% CI 1.07-1.14, P < 0.001) and cardiovascular mortality (HR 1.14, 95% CI 1.08-1.21, P < 0.001) in adjusted models. Subgroup analyses revealed that age, sex, smoking status, and hypertension significantly influence NLR's association with cardiovascular mortality. Specific cancers including breast, prostate, non-melanoma skin, colon and melanoma experience increased all-cause and cardiovascular mortality in the higher NLR group compared to lower NLR group. Elevated NLR is a significant predictor of increased mortality in cancer patients, particularly for cardiovascular outcomes. These findings support that NLR acts as a pivotal prognostic tool with significant implications for clinical practice in the realm of cardio-oncology.
Assuntos
Sobreviventes de Câncer , Doenças Cardiovasculares , Linfócitos , Neoplasias , Neutrófilos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Sobreviventes de Câncer/estatística & dados numéricos , Idoso , Prognóstico , Neoplasias/mortalidade , Neoplasias/sangue , Neoplasias/complicações , Adulto , Contagem de Linfócitos , Inquéritos Nutricionais , Estimativa de Kaplan-Meier , Contagem de LeucócitosRESUMO
BACKGROUND: While COVID-19 has been controlled and deaths have decreased, the long-term consequences of COVID-19 remain a challenge we face today. This study was conducted to determine the relationship between the apoptosis of lymphocyte cells with DNA damage and oxidative stress and the therapeutic and clinical outcomes of elderly patients with COVID-19. METHODS: This study was conducted from April 2020 to May 2021 (the period of severe attacks of the epidemic peak of COVID-19) and September 2022 (the post-COVID-19 period). The study groups included elderly patients with COVID-19 hospitalized in the ICU and normal wards of the hospital as well as elderly patients with influenza. A polymerase chain reaction was used to check the validity of the studied diseases. The Annexin V/Propidium Iodide method was used to evaluate the level of apoptosis. Genotoxic effects and DNA damage were assessed by the comet assay method. Total antioxidant status (TAS), total oxidant status (TOS), and myeloperoxidase activity (MPO) were measured by photometric methods. RESULTS: The highest level of apoptosis in peripheral blood lymphocytes and the highest level of DNA damage were observed at both times in the intubated-ICU and non-intubated-ICU groups. In all groups, there was a significant increase in peripheral blood lymphocyte apoptosis levels and DNA damage levels compared to the healthy control group (p < 0.01). The level of apoptosis and DNA damage decreased significantly in the post-COVID-19 period (p < 0.01). In the investigation of oxidative stress biomarkers, the oxidative stress index, including TOS and MPO levels, increased in patients (p < 0.01), and the TAS level decreased (p < 0.01). CONCLUSION: It shows that the apoptosis of lymphocyte cells, DNA damage, and oxidative stress can be effective in prognostic decisions and is a suitable predictor for diagnosing the condition of patients with viral infections such as COVID-19 and influenza.
Assuntos
Apoptose , COVID-19 , Dano ao DNA , Linfócitos , Estresse Oxidativo , SARS-CoV-2 , Humanos , COVID-19/patologia , COVID-19/terapia , Idoso , Masculino , Feminino , Idoso de 80 Anos ou mais , Antioxidantes/metabolismoRESUMO
Introduction: Group 3 innate lymphoid cells (ILC3s) are enriched in the intestinal mucosa and play important roles in host defense against infection and inflammatory diseases. Sirtuin 6 (SIRT6) is a nicotinamide adenine dinucleotide (NAD+)- dependent deacetylase and has been shown to control intestinal epithelial cell differentiation and survival. However, the role of SIRT6 in ILC3s remains unknown. Methods: To investigate the role of SIRT6 in gut ILC3s, we generated SIRT6 conditional knockout mice by crossing Rorccre and Sirt6flox/flox mice. Cell number and cytokine production was examined using flow cytometry. Citrobacter rodentium infection and dextran sodium sulfate-induced colitis models were used to determine the role of SIRT6 in gut defense. RT-qPCR, flow cytometry and immunohistochemistry were used to assess the intestinal inflammatory responses. Results: Here we show that SIRT6 inhibits IL-22 expression in intestinal ILC3s in a cell-intrinsic manner. Deletion of SIRT6 in ILC3s does not affect the cell numbers of total ILC3s and subsets, but results in increased IL-22 production. Furthermore, ablation of SIRT6 in ILC3s protects mice against Citrobacter rodentium infection and dextran sodium sulfate-induced colitis. Our results suggest that SIRT6 may play a role in ILC3 function by regulating gut immune responses against bacterial infection and inflammation. Discussion: Our finding provided insight into the relation of epigenetic regulators with IL-22 production and supplied a new perspective for a potential strategy against inflammatory bowel disease.
Assuntos
Citrobacter rodentium , Colite , Infecções por Enterobacteriaceae , Imunidade Inata , Interleucina 22 , Interleucinas , Linfócitos , Camundongos Knockout , Sirtuínas , Animais , Camundongos , Linfócitos/imunologia , Linfócitos/metabolismo , Interleucinas/metabolismo , Interleucinas/imunologia , Interleucinas/genética , Sirtuínas/genética , Sirtuínas/metabolismo , Colite/imunologia , Colite/induzido quimicamente , Citrobacter rodentium/imunologia , Infecções por Enterobacteriaceae/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Camundongos Endogâmicos C57BL , Sulfato de Dextrana , Modelos Animais de DoençasRESUMO
Sarcoidosis is a multiorgan granulomatous disease that lacks diagnostic biomarkers and targeted treatments. Using blood and skin from patients with sarcoid and non-sarcoid skin granulomas, we discovered that skin granulomas from different diseases exhibit unique immune cell recruitment and molecular signatures. Sarcoid skin granulomas were specifically enriched for type 1 innate lymphoid cells (ILC1s) and B cells and exhibited molecular programs associated with formation of mature tertiary lymphoid structures (TLSs), including increased CXCL12/CXCR4 signaling. Lung sarcoidosis granulomas also displayed similar immune cell recruitment. Thus, granuloma formation was not a generic molecular response. In addition to tissue-specific effects, patients with sarcoidosis exhibited an 8-fold increase in circulating ILC1s, which correlated with treatment status. Multiple immune cell types induced CXCL12/CXCR4 signaling in sarcoidosis, including Th1 T cells, macrophages, and ILCs. Mechanistically, CXCR4 inhibition reduced sarcoidosis-activated immune cell migration, and targeting CXCR4 or total ILCs attenuated granuloma formation in a noninfectious mouse model. Taken together, our results show that ILC1s are a tissue and circulating biomarker that distinguishes sarcoidosis from other skin granulomatous diseases. Repurposing existing CXCR4 inhibitors may offer a new targeted treatment for this devastating disease.
Assuntos
Granuloma , Imunidade Inata , Receptores CXCR4 , Sarcoidose , Receptores CXCR4/imunologia , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Animais , Humanos , Camundongos , Sarcoidose/imunologia , Sarcoidose/patologia , Granuloma/imunologia , Granuloma/patologia , Dermatopatias/imunologia , Dermatopatias/patologia , Feminino , Quimiocina CXCL12/imunologia , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Linfócitos/imunologia , Linfócitos/patologia , Masculino , Pele/imunologia , Pele/patologia , Transdução de Sinais/imunologiaRESUMO
Haemocytes play a crucial role in the invertebrate's immune system. In our lab, five subpopulations of shrimp haemocytes were identified in the past: hyalinocytes, granulocytes, semi-granulocytes and two subpopulations of non-phagocytic cells. In the latter two subpopulations, their characteristics such as having small cytoplasmic rims and not adhering to plastic cell-culture plates are very similar to those of mammalian lymphocytes. Therefore, they were designated lymphocyte-like haemocytes. Although little is known about their function, we hypothesize, based on their morphology, that they may have a cytotoxic activity like natural killer cells, with the ability to recognize and kill target cells. In our study, K562 cells and Sf9 cells were used as xenogenous target cells to detect the cytotoxic activity of the shrimp non-adherent lymphocyte-like haemocytes. Non-adherent haemocytes were collected and mixed with K562 cells and Sf9 cells at a 5:1 ratio and the binding activity was examined under a microscope. The binding rate of non-adherent haemocytes to K562 cells and Sf9 cells reached 6.6 % and 2.4 % after 240 min of culture, respectively. Then, the killing activity of non-adherent haemocytes was detected by an EMA staining (fluorescence microscopy), which showed 3.75 % dead K562 cells and 1.025 % dead Sf9 cells, and by Sytox® blue staining (flow cytometry), which showed 4.97 % of dead K562 cells. Next, a killing assay was developed to visualize the killing activity of shrimp non-adherent haemocytes. Non-adherent haemocytes were pre-labeled in blue (CellTracker blue) and K562/Sf9 cells in green (CFSE); dead cells were differentially stained red with ethidium bromide. The cytotoxic activity increased and reached a level of 2.59 % in K562 cells and 0.925 % in Sf9 cells at 120 min after co-culture. Furthermore, in the co-cultures of non-adherent haemocytes with K562 cells and Sf9 cells, upregulation of the gene and protein expression of the cytotoxic molecules torso-like protein and granzyme B was observed by RT-qPCR at 240 min and western blotting at 180 min. Additionally, non-adherent haemocytes were co-cultured with WSSV-inoculated shrimp ovary and lymphoid organ cells to detect the cytotoxicity to homogenous target cells. The binding activity started at 60 min in both the ovary and lymphoid organ cultures and reached at 240 min 50.62 % and 40.7 %, respectively. The killing activity was detected by EMA staining and the percentage of dead ovary and lymphoid organ cells increased respectively from 10.84 % to 6.89 % at 0 min to 13.09 % and 8.37 % at 240 min. In conclusion, we demonstrated the existence of cytotoxic activity of shrimp lymphocyte-like haemocytes against xenogenous cells from mammals and insects and against WSSV-infected homogenous shrimp cells.
Assuntos
Hemócitos , Penaeidae , Animais , Hemócitos/imunologia , Penaeidae/imunologia , Células K562 , Linfócitos/imunologia , Humanos , Vírus da Síndrome da Mancha Branca 1/fisiologiaRESUMO
BACKGROUND: This study aims to investigate preoperative prognostic factors available for intrahepatic cholangiocarcinoma (ICC) patients and propose a new preoperative prognostic scoring system for ICC that combines CA19-9 and neutrophil/lymphocyte ratio (NLR). METHODS: In this retrospective analysis, 1728 patients diagnosed with ICC and undergoing curative liver resections were studied. This study employed univariate and multivariate Cox regression to find factors affecting recurrence and overall survival (OS), and furthermore assessed how preoperative models influenced tumor traits and postoperative recurrence. RESULTS: The results of the multivariate Cox regression analysis indicated that two preoperative variables, NLR and Ca19-9, were independent risk factors affecting postoperative recurrence and OS in ICC patients. Based on this data, assigning a score of 0 (NLR ≤ 2.4 and Ca19-9 ≤ 37U/ml) or 1 (NLR > 2.4 and Ca19-9 > 37U/ml) to these two factors, a preoperative prognostic score was derived. According to the scoring model, patients were divided into three groups: 0 points (low-risk group), 1 point (intermediate-risk group), and 2 points (high-risk group). The 5-year recurrence and OS rates for the three groups were 56.6%, 68.2%, 77.8%, and 56.8%, 40.6%, 27.6%, respectively, with all P values < 0.001. Furthermore, high-risk group patients were more prone to early recurrence (early recurrence rates for high-, intermediate-, and low-risk groups were 56.8%, 51.5%, and 37.1%, respectively, P < 0.001) and extrahepatic metastasis (extrahepatic metastasis rates for high-, intermediate-, and low-risk groups were 31.7%, 26.4%, and 15.4%, respectively, P < 0.001). In terms of tumor characteristics, high-risk group patients had larger tumor diameters and were more likely to experience microvascular invasion, lymph node metastasis, and perineural invasion. CONCLUSIONS: The predictive capacity of postoperative recurrence and OS rates in ICC patients is effectively captured by the preoperative scoring system incorporating NLR and CA19-9 levels.
Assuntos
Neoplasias dos Ductos Biliares , Antígeno CA-19-9 , Colangiocarcinoma , Hepatectomia , Linfócitos , Recidiva Local de Neoplasia , Neutrófilos , Humanos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/sangue , Colangiocarcinoma/patologia , Colangiocarcinoma/mortalidade , Masculino , Feminino , Neutrófilos/patologia , Pessoa de Meia-Idade , Prognóstico , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/sangue , Neoplasias dos Ductos Biliares/mortalidade , Estudos Retrospectivos , Linfócitos/patologia , Antígeno CA-19-9/sangue , Idoso , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Adulto , Período Pré-Operatório , Contagem de Linfócitos , Fatores de RiscoRESUMO
Innate lymphoid cells (ILCs) are critical in maintaining tissue homeostasis, and during infection and inflammation. Here we identify, by using combinatorial reporter mice, a rare ILC progenitor (ILCP) population, resident to the small intestinal lamina propria (siLP) in adult mice. Transfer of siLP-ILCP into recipients generates group 1 ILCs (including ILC1 and NK cells), ILC2s and ILC3s within the intestinal microenvironment, but almost exclusively group 1 ILCs in the liver, lung and spleen. Single cell gene expression analysis and high dimensional spectral cytometry analysis of the siLP-ILCPs and ILC progeny indicate that the phenotype of the group 1 ILC progeny is also influenced by the tissue microenvironment. Thus, a local pool of siLP-ILCP can contribute to pan-ILC generation in the intestinal microenvironment but has more restricted potential in other tissues, with a greater propensity than bone marrow-derived ILCPs to favour ILC1 and ILC3 production. Therefore, ILCP potential is influenced by both tissue of origin and the microenvironment during development. This may provide additional flexibility during the tuning of immune reactions.
Assuntos
Imunidade Inata , Mucosa Intestinal , Células Progenitoras Linfoides , Camundongos Endogâmicos C57BL , Animais , Camundongos , Mucosa Intestinal/imunologia , Mucosa Intestinal/citologia , Células Progenitoras Linfoides/citologia , Células Progenitoras Linfoides/metabolismo , Células Progenitoras Linfoides/imunologia , Microambiente Celular/imunologia , Linfócitos/imunologia , Intestino Delgado/imunologia , Intestino Delgado/citologia , Feminino , MasculinoRESUMO
Introduction: Platelets (PLT) and host systemic inflammatory response (SIR) are known to be effective in the aggregation of cancer cells and the formation of metastasis. There are studies pointing out to the prognostic efficacy of lymphocyte-monocyte ratio (LMR) showing SIR activation and mean platelet volume (MPV) values indicating platelet activation in various cancer types. We predict that easy-to-access hemogram parameters such as MPV, MPV/PLT, and LMR can be guiding in the clinical follow-up period of patients with epidermal growth factor receptor (EGFR) positive mutation and who received EGFR, tyrosine kinase inhibitor (TKI) in the first-line treatment in predicting the progression of the disease, predicting the survival time of the patients, and evaluating the response to treatment. Materials and Methods: The study is retrospective and included patients with stage III and stage IV pulmonary adenocarcinoma with positive EGFR mutations and for whom TKI was used in the first-line treatment between January 2011 and January 2021. MPV, MPV/PLT, and LMR values of the patients were calculated before treatment. Age, sex, comorbidity, smoking history, TNM stage, metastasis localizations, EGFR mutation types, TKI treatments used in first-line treatment, and MPV, MPV/PLT, and LMR values at the 1st month of treatment were recorded. With Kaplan-Meier, six-month, one-year, three-year, and five-year survival rates, average life expectancy, and 95% confidence intervals for these periods were calculated. Variables that may affect progression and overall survival (OS) were determined by performing univariate and multivariate Cox regression analysis. Result: One hundred and two patients were included in the study. The mean age of the patients was 64.30 ± 12.6 years. Eighty-four patients were in stage IV at the time of diagnosis. The expected mean progression-free survival (PFS) period of the cases was found to be 13.3 months. The mean life expectancy of the cases was found to be 35.1 months. Web-based Cutoff Finder algorithm written in the R program (http://molpath.charite.de/cutoff) was used to determine the ideal cut points for MPV, MPV/PLT, and LMR. The cut-off values were found to be 7.55 fL for MPV, 0.251 for MPV/PLT, and 2.615 for LMR, respectively. In univariate Cox regression analysis, LMR level lower than 2.615 increased the rate of progression 1.747 times (95% confidence interval: 1.129-2.705) and the death rate 2.056 times (95% confidence interval: 1.217-3.475) (p= 0.012, p= 0.007). The mean PFS LMR cut-off value was 10.3 months, and 15.3 months, and mean OS durations were 25.1 months and 40.8 months for the groups with low and high cut-off values respectively (p= 0.011, p= 0.006 log-rank test). According to the results of multivariate Cox regression analysis, MPV/PLT < 0.251, smoking, presence of pleural and adrenal metastases, and gefitinib treatment were independent factors in determining PFS. The independent factors determining OS in multivariate Cox regression analysis were being male, platelet increase, MPV > 7.55, gefitinib treatment, and smoking. Conclusions: MPV, MPV/PLT, and LMR are potential biomarkers that can be used for the clinical follow-up of lung ADC patients receiving EGFR-TKI treatment.
Assuntos
Adenocarcinoma de Pulmão , Receptores ErbB , Neoplasias Pulmonares , Volume Plaquetário Médio , Inibidores de Proteínas Quinases , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/sangue , Adenocarcinoma de Pulmão/patologia , Idoso , Inibidores de Proteínas Quinases/uso terapêutico , Prognóstico , Mutação , Monócitos , Plaquetas , LinfócitosRESUMO
OBJECTIVE: To investigate markers of systemic inflammation and the effect of thyroid dysfunction on these parameters in patients with Hashimoto's thyroiditis (HT). METHODS: Patients with HT and volunteer healthy individuals admitted to the general surgery outpatient clinic between January 2020 and June 2023 were enrolled into the study. Patients with HT were divided into euthyroid, hypothyroid, and hyperthyroid subgroups. All participant data were retrospectively extracted from the hospital database. RESULTS: A total of 268 patients (euthyroid, n = 131; hypothyroid, n = 83; and hyperthyroid, n = 54) and 124 controls were included. The platelet-to-lymphocyte ratio was lower in the euthyroid group versus control group, and the neutrophil-to-lymphocyte ratio was lower in controls than the three patient subgroups. Euthyroid and hypothyroid patients with HT exhibited a higher systemic inflammation index than the control group. The pan-immune inflammation index was lower in controls than in euthyroid, hypothyroid, and hyperthyroid patients with HT. In patients with HT, inflammation markers did not significantly differ between subgroups. CONCLUSIONS: Markers of systemic inflammation provide meaningful and reliable information in patients with HT, but do not differentiate between euthyroid, hypothyroid, or hyperthyroid patients.
Assuntos
Biomarcadores , Doença de Hashimoto , Inflamação , Humanos , Doença de Hashimoto/sangue , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/imunologia , Feminino , Masculino , Adulto , Biomarcadores/sangue , Inflamação/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos de Casos e Controles , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Neutrófilos/patologia , Linfócitos , Hipertireoidismo/sangue , Hipertireoidismo/diagnóstico , Plaquetas/patologia , Plaquetas/metabolismoRESUMO
Objective: To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system. Methods: This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis. Results: The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×109/L, 1.41×109/L, and 355×109/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS (P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival (P<0.05), but not progression-free survival (P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%-75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion: This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.
Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Estudos Retrospectivos , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neutrófilos , Plaquetas , Contagem de Células Sanguíneas , LinfócitosRESUMO
OBJECTIVE: Congenital nasolacrimal duct obstruction (CNLDO) is a common lacrimal system anomaly in newborns and infants. We aimed to evaluate the role of inflammation in the pathogenesis of persistent CNLDO and its potential use in diagnosis and follow up, focusing on novel inflammatory biomarkers: Systemic Immune-Inflammation Index (SII), Neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR), Red cell distribution width (RDW), and Mean platelet volume (MPV). METHODS: A retrospective case-control study involving 76 CNLDO patients and 47 age-matched healthy controls was conducted. Complete blood count parameters were analyzed to calculate SII, NLR, PLR, RDW, and MPV. Receiver Operating Characteristic (ROC) analysis determined the diagnostic efficacy of these markers. RESULTS: SII, RDW, and neutrophil count were significantly elevated in the CNLDO group (p < 0.05). An elevated SII (cutoff > 200.9) demonstrated a sensitivity of 63.2% and a specificity of 63.8%. ROC analysis (AUC = 61.7%, p = 0.029) indicated that SII is a more significant marker for diagnosing CNLDO compared to NLR and PLR. CONCLUSION: Elevated SII, indicative of systemic inflammation may serve as a significant biomarker in the diagnosis of CNLDO that does not resolve spontaneously and requires probing. SII > 200.9 acts as a threshold that aids in the diagnosis of persistent CNLDO. Being a valuable biomarker, SII can be used in monitoring patients with CNLDO and in identifying those who will require advanced treatment like probing. Prospective studies are essential to validate these findings.
Assuntos
Biomarcadores , Inflamação , Obstrução dos Ductos Lacrimais , Ducto Nasolacrimal , Curva ROC , Humanos , Estudos Retrospectivos , Masculino , Feminino , Obstrução dos Ductos Lacrimais/diagnóstico , Ducto Nasolacrimal/patologia , Biomarcadores/sangue , Estudos de Casos e Controles , Inflamação/diagnóstico , Inflamação/sangue , Lactente , Neutrófilos , Linfócitos , Recém-NascidoRESUMO
In most multicellular organisms, cells within an individual have essentially identical genomes. This principle underlies the ability to reprogram fibroblasts into induced pluripotent stem cells using defined transcription factors, clone a frog by transferring a nucleus from a tadpole somatic cell into an enucleated egg, and form totipotent callus cells by wounding plants. However, an exception to this one-body-one-genome principle exists in our blood cells. In developing lymphocytes in vertebrates, a process termed V(D)J recombination shuffles the antigen-binding regions of immunoglobulins and T-cell receptors.
Assuntos
Recombinação V(D)J , Animais , Linfócitos/metabolismo , Linfócitos/fisiologiaRESUMO
OBJECTIVE: We conducted this study to summarize the results of studies reporting the role of NLR (neutrophil to lymphocyte ratio) in PSCC (penile squamous cell carcinoma). METHODS: This meta-analysis was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria. A systematic search was conducted on PubMed, Scopus, and web of science up to March 10, 2023. Fourteen studies were included in the review. The NOS (Newcastle-Ottawa Scale) was used to determine the quality of the included studies. This meta-analysis was conducted on the studies reporting the relationship between NLR and survival using HR (hazard ratio) and 95% CI (confidence interval). RESULTS: There was a significant association between NLR levels and the prognosis, nodal stage, and anatomical tumor stage of PSCC patients. In the meta-analysis of the association of NLR with survival, NLR level was significantly associated with lower cancer-specific survival (HR = 3.51, 95% CI = 2.07-5.98, p < 0.001) and lower disease-free survival (HR = 2.88, 95% CI = 1.60-5.20, p < 0.001). However, NLR was found to have no association with the stage, grade, location, and size of the tumor. CONCLUSION: NLR has a significant diagnostic and prognostic value in PSCC.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Penianas , Humanos , Neoplasias Penianas/sangue , Neoplasias Penianas/patologia , Neoplasias Penianas/mortalidade , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Masculino , Prognóstico , Neutrófilos , Linfócitos/patologia , Contagem de Linfócitos , Contagem de Leucócitos , Taxa de SobrevidaRESUMO
OBJECTIVE: The relationship between lymphocyte-associated inflammatory indices and portal vein thrombosis (PVT) following splenectomy combined with esophagogastric devascularization (SED) is currently unclear. This study aims to investigate the association between these inflammatory indices and PVT, and to develop a nomogram based on these indices to predict the risk of PVT after SED, providing an early warning tool for clinical practice. METHODS: We conducted a retrospective analysis of clinical data from 131 cirrhotic patients who underwent SED at Lanzhou University's Second Hospital between January 2014 and January 2024. Independent risk factors for PVT were identified through univariate and multivariate logistic regression analyses, and the best variables were selected using the Akaike Information Criterion (AIC) to construct the nomogram. The model's predictive performance was assessed through receiver operating characteristic (ROC), calibration, decision, and clinical impact curves, with bootstrap resampling used for internal validation. RESULTS: The final model incorporated five variables: splenic vein diameter (SVD), D-Dimer, platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and red cell distribution width-to-lymphocyte ratio (RLR), achieving an area under the curve (AUC) of 0.807, demonstrating high predictive accuracy. Calibration and decision curves demonstrated good calibration and significant clinical benefits. The model exhibited good stability through internal validation. CONCLUSION: The nomogram model based on lymphocyte-associated inflammatory indices effectively predicts the risk of portal vein thrombosis after SED, demonstrating high accuracy and clinical utility. Further validation in larger, multicenter studies is needed.