Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment o...Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.展开更多
Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple rol...Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.展开更多
BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents.This mental health condition can have severe consequences,including academic failure,social withdrawal,an...BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents.This mental health condition can have severe consequences,including academic failure,social withdrawal,and suicidal behavior.Given the increasing rate of depression in this age group,understanding the underlying biological mechanisms is essential for early detection and intervention.Recent studies have suggested that immune markers play a role in the pathophysiology of depression,prompting further investigation of their potential association with depressive symptoms in adolescents.AIM To investigate the relationship between immune markers(monocytes,lymphocytes,and direct bilirubin)and the incidence and severity of depression among adolescents.METHODS This cross-sectional study recruited 145 adolescent patients with depression[male(M)/female(F)=38/107]from Jiangbin Hospital in Guangxi,Zhuang and 163 healthy controls(M/F=77/86)from routine health check-ups.Blood samples were collected after an overnight fast.Depression severity was measured using the Zung Self-Rating Depression Scale.The inclusion criteria were age 12-24 years,diagnosis of depressive disorder(ICD-10),and no recent antidepressant use.The exclusion criteria included psychiatric comorbidities and serious somatic diseases.Key statistical methods included group comparisons and correlation analyses.RESULTS There was a higher prevalence of females in the depression group(P<0.001).Significant age differences were observed between the groups(Z=9.43,P<0.001).The depression group had higher monocyte(Z=3.43,P<0.001)and lymphocyte(t=2.29,P<0.05)counts,and higher serum direct bilirubin levels(Z=4.72,P<0.001).Monocyte count varied significantly according to depression severity,with lower counts in the mild group(Z=-2.90,P<0.05).A negative correlation between age and lymphocyte counts was observed(ρ=-0.22,P<0.01).Logistic regression analysis showed that serum direct bilirubin levels significantly predicted depression.CONCLUSION The potential role of elevated levels of immune markers in the early detection of depression in adolescents has been highlighted.Therefore,it is necessary to explore further the relationships between these immune markers and depression.展开更多
Background:Atherosclerosis(AS)is a chronic progressive inflammatory disease,and plaque stability plays a critical role in preventing acute events.Tanyu Tongzhi formula(TTF),a traditional Chinese medicine,has potential...Background:Atherosclerosis(AS)is a chronic progressive inflammatory disease,and plaque stability plays a critical role in preventing acute events.Tanyu Tongzhi formula(TTF),a traditional Chinese medicine,has potential therapeutic effects on AS.Methods:We used an AS animal model to examine the effects of TTF on atherosclerotic plaque vulnerability and CD40^(+)monocyte differentiation.AS plaque area,collagen content,and lipid area were assessed using histological staining.AS plaque-related biomarkers(monocyte chemoattractant protein 1(MCP-1),monocyte plus macrophage(MOMA-2),von Willebrand factor(vWF),CD31,and alpha-smooth muscle actin(α-SMA))were detected using immunohistochemistry.Inflammatory cytokines were determined using enzyme-linked immunosorbent assay.CD40 mRNA expression was detected by real-time quantitative PCR.CD40^(+)monocyte differentiation was evaluated by flow cytometry analysis in ApoE-/-mice and peripheral blood mononuclear cells(PBMCs).AMPK/NF-κB signaling pathways-related protein expression was investigated through western blotting.Results:TTF treatment reduced AS plaque area,collagen content,and lipid area in AS model mice.Levels of MCP-1,MOMA-2,vWF,and CD31 were decreased,whileα-SMA level was increased by TTF in model mice.TTF reduced inflammatory cytokines levels,including tumor necrosis factor receptor-α(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and interleukin-6(IL-6).TTF inhibited CD40^(+)monocyte differentiation and decreased the number of CD40^(+)/CD40-and Ly6C^(+)/Ly6C-cells and M1/M2 ratio in AS model mice and human PBMCs.Additionally,TTF modulated the AMPK/NF-κB signaling pathway in human PBMCs.Conclusion:TTF attenuates atherosclerotic plaque vulnerability by inhibiting CD40^(+)monocyte differentiation,possibly through the regulation of the AMPK/NF-κB signaling pathway.These findings suggest that TTF could be a potential therapeutic agent for preventing plaque rupture and subsequent cardiovascular events in patients with AS.展开更多
Background:SARS-CoV-2,first identified in late 2019,has given rise to numerous variants of concern(VOCs),posing a significant threat to human health.The emer-gence of Omicron BA.1.1 towards the end of 2021 led to a pa...Background:SARS-CoV-2,first identified in late 2019,has given rise to numerous variants of concern(VOCs),posing a significant threat to human health.The emer-gence of Omicron BA.1.1 towards the end of 2021 led to a pandemic in early 2022.At present,the lethal mouse model for the study of SARS-CoV-2 needs supplementation,and the alterations in neutrophils and monocytes caused by different strains remain to be elucidated.Methods:Human ACE2 transgenic mice were inoculated with the SARS-CoV-2 proto-type and Omicron BA.1,respectively.The pathogenicity of the two strains was evalu-ated by observing clinical symptoms,viral load and pathology.Complete blood count,immunohistochemistry and flow cytometry were performed to detect the alterations of neutrophils and monocytes caused by the two strains.Results:Our findings revealed that Omicron BA.1 exhibited significantly lower vir-ulence compared to the SARS-CoV-2 prototype in the mouse model.Additionally,we observed a significant increase in the proportion of neutrophils late in infection with the SARS-CoV-2 prototype and Omicron BA.1.We found that the proportion of monocytes increased at first and then decreased.The trends in the changes in the proportions of neutrophils and monocytes induced by the two strains were similar.Conclusion:Our study provides valuable insights into the utility of mouse models for simulating the severe disease of SARS-CoV-2 prototype infection and the milder manifestation associated with Omicron BA.1.SARS-CoV-2 prototype and Omicron BA.1 resulted in similar trends in the changes in neutrophils and monocytes.展开更多
BACKGROUND Deficient efferocytosis(i.e.,phagocytic clearance of apoptotic cells)by macrophages has been frequently reported in experimental models of type 2 diabetes(T2D).AIM To translate these findings to humans by t...BACKGROUND Deficient efferocytosis(i.e.,phagocytic clearance of apoptotic cells)by macrophages has been frequently reported in experimental models of type 2 diabetes(T2D).AIM To translate these findings to humans by testing whether the efferocytosis capacity of blood monocytes and monocyte-derived macrophages is impaired in T2D patients.METHODS Overall,30 patients with poorly controlled T2D[glycosylated hemoglobin(HbA1c)≥8.0%]and 30 age-and sex-matched control subjects were enrolled in the study.The efferocytosis capacities of peripheral blood monocytes and monocyte-derived macrophages were assessed by flow cytometry and immunostaining.Macrophage membrane CD14 expression was examined by flow cytometry.Metabolic factors such as 25(OH)D and immune factors such as interleukin-1βwere also measured.RESULTS The mean monocyte efferocytosis index in the diabetes group was significantly lower than that in the control group.Notably,efferocytosis remained impaired after monocytes differentiated into macrophages.Additionally,the percentages of classical monocytes(CD14^(++)CD16-monocytes)and CD14^(+)macrophages were significantly lower in the diabetes group.Multivariate linear regression analysis in diabetes patients demonstrated that the monocyte efferocytosis index was independently associated with the HbA1c level,and that the macrophage efferocytosis index was significantly associated with the percentage of CD14^(+)macrophages.CONCLUSION Impaired efferocytosis was observed in T2D patients,with poor glycemic control affecting both blood monocytes and monocyte-derived macrophages.The efferocytosis index was negatively associated with metrics of glycemic control,and glucotoxicity may impact efferocytosis through reducing CD14 expression on both monocytes and macrophages.展开更多
Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underp...Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.展开更多
Background With the continuous exploration of cardiovascular diseases,research has found that inflammatory reactions play an important role in the pathogenesis of cardiovascular diseases.In recent years,the ratio of m...Background With the continuous exploration of cardiovascular diseases,research has found that inflammatory reactions play an important role in the pathogenesis of cardiovascular diseases.In recent years,the ratio of monocyte to lymphocyte counts(MLR)has attracted widespread attention as a novel inflammatory marker.Therefore,this article will focus on the value of MLR in terms of prevalence risk,severity and prognosis in common cardiovascular diseases.[S Chin J Cardiol 2024;25(3):200-206]展开更多
BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.Howeve...BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.However,conventional diagnostic methods such as electrocardiography,echocardiography,and cardiac biomarkers have certain limitations,such as low sensitivity,specificity,availability,and cost-effectiveness.Therefore,there is a need for simple,noninvasive,and reliable biomarkers to diagnose CHD and HF.AIM To investigate serum cystatin C(Cys-C),monocyte/high-density lipoprotein cholesterol ratio(MHR),and uric acid(UA)diagnostic values for CHD and HF.METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023.The patients were divided into CHD(n=20),HF(n=20),CHD+HF(n=20),and control groups(n=20).The serum levels of Cys-C,MHR,and UA were measured using immunonephelometry and an enzymatic method,respectively,and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Serum levels of Cys-C,MHR,and UA were significantly higher in the CHD,HF,and CHD+HF groups than those in the control group.The serum levels of Cys-C,MHR,and UA were significantly higher in the CHD+HF group than those in the CHD or HF group.The ROC curve analysis showed that serum Cys-C,MHR,and UA had good diagnostic performance for CHD and HF,with areas under the curve ranging from 0.78 to 0.93.The optimal cutoff values of serum Cys-C,MHR,and UA for diagnosing CHD,HF,and CHD+HF were 1.2 mg/L,0.9×10^(9),and 389μmol/L;1.4 mg/L,1.0×10^(9),and 449μmol/L;and 1.6 mg/L,1.1×10^(9),and 508μmol/L,respectively.CONCLUSION Serum Cys-C,MHR,and UA are useful biomarkers for diagnosing CHD and HF,and CHD+HF.These can provide information for decision-making and risk stratification in patients with CHD and HF.展开更多
Pulmonary macrophages,such as tissue-resident alveolar and interstitial macrophages and recruited monocyte-derived macrophages,are the major macrophages present in the lungs during homeostasis and diseased conditions....Pulmonary macrophages,such as tissue-resident alveolar and interstitial macrophages and recruited monocyte-derived macrophages,are the major macrophages present in the lungs during homeostasis and diseased conditions.While tissue-resident macrophages act as sentinels of the alveolar space and play an important role in maintaining homeostasis and immune regulation,recruited macrophages accumulate in the respiratory tract after acute viral infections.Despite sharing similar anatomical niches,these macrophages are distinct in terms of their origins,surface marker expression,and transcriptional profiles,which impart macrophages with distinguished characteristics in physi-ological and pathophysiological conditions.In this review,we summarize the current view on these macrophage populations,their shared functions,and what makes them distinct from each other in the context of homeostasis andrespiratoryviral infections.展开更多
AIM:To evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio(MHR)and the disease activity of thyroid-associated ophthalmopathy(TAO).METHODS:A total of 87 patients were classified int...AIM:To evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio(MHR)and the disease activity of thyroid-associated ophthalmopathy(TAO).METHODS:A total of 87 patients were classified into two groups based on clinical activity score(CAS)scoring criteria:high CAS group(n=62,the CAS score was≥3);low CAS group(n=25,the CAS score was<3).In addition,a group of healthy people(n=114)were included to compared the MHR.Proptosis,MHR,average signal intensity ratio(SIR),average lacrimal gland(LG)-SIR,average extraocular muscles(EOM)area from 87 patients with TAO were calculated in magnetic resonance imaging(MRI),and compared between these two groups.Correlation testing was utilized to evaluate the association of parameters among the clinical variables.RESULTS:Patients in high CAS group had a higher proptosis(P=0.041)and MHR(P=0.048).Compared to the healthy group,the MHR in the TAO group was higher(P=0.001).Correlation testing declared that CAS score was strongly associated with proptosis and average SIR,and MHR was positively associated with CAS score,average SIR,and average LG-SIR.The area under the receiver operating characteristic curve(AUC)of MHR was 0.6755.CONCLUSION:MHR,a novel inflammatory biomarker,has a significant association with CAS score and MRI imaging(average SIR and LG-SIR)and it can be a new promising predictor during the active phase of TAO.展开更多
BACKGROUND The lymphocyte to monocyte ratio(LMR)is considered a marker of systemic inflammation in cardiovascular disease and acts as predictor of mortality in coronary artery disease.AIM To investigate the predictive...BACKGROUND The lymphocyte to monocyte ratio(LMR)is considered a marker of systemic inflammation in cardiovascular disease and acts as predictor of mortality in coronary artery disease.AIM To investigate the predictive role of LMR in diabetic coronary artery disease patients.METHODS This cross-sectional study was conducted at tertiary care super-specialty hospital at New Delhi,India.A total of 200 angiography-proven coronary artery disease(CAD)patients were enrolled and grouped into two categories:Group I[CAD patients with type 2 diabetes mellitus(T2DM)and glycated hemoglobin(HbA1c)levels≥6.5%],and Group II(CAD patients without T2DM and HbA1c levels<6.5%).Serum lipoproteins,HbA1c,and complete blood count of enrolled patients were analyzed using fully automatic analyzers.RESULTS The logistic regression analysis showed an odds ratio of 1.48(95%CI:1.28-1.72,P<0.05)for diabetic coronary artery disease patients(Group I)in unadjusted model.After adjusting for age,gender,diet,smoking,and hypertension history,the odds ratio increased to 1.49(95%CI:1.29-1.74,P<0.01)in close association with LMR.Further adjustment for high cholesterol and triglycerides yielded the same odds ratio of 1.49(95%CI:1.27-1.75,P<0.01).Receiver operating characteristic curve analysis revealed 74%sensitivity,64%specificity,and 0.74 area under the curve(95%CI:0.67-0.80,P<0.001),suggesting moderate predictive accuracy for diabetic CAD patients.CONCLUSION LMR showed positive association with diabetic coronary artery disease,with moderate predictive accuracy.These findings have implications for improving CAD management in diabetics,necessitating further research and targeted interventions.展开更多
Objective: To investigate the value of peripheral blood helper T cell 17 cell level and monocyte/lymphocyte ratio to predict the prognosis of colorectal cancer patients. Methods: 74 colorectal cancer patients who atte...Objective: To investigate the value of peripheral blood helper T cell 17 cell level and monocyte/lymphocyte ratio to predict the prognosis of colorectal cancer patients. Methods: 74 colorectal cancer patients who attended Hospital 960 from January 2021 to January 2022 were retrospectively analyzed. Clinical data of the patients were collected, including gender, age, and histologic type. Immunohistochemical indexes such as Th17 cell level and monocyte/ lymphocyte ratio in the peripheral blood of patients were also collected. The prognosis of patients after treatment, as well as peripheral blood Th17 and MLR levels, were observed and analyzed. Results: After follow-up after treatment, in the final 74 patients, the prognosis was good in 32 patients, accounting for 43.24%, and the prognosis was bad in 42 patients, accounting for 56.76%. There were no significant differences between the average age and tumor diameters of the good prognosis and poor prognosis groups (P > 0.05). However, the TNM staging, intervention taken, differentiation degree, presence of distant metastasis, presence of lymph node metastasis, Th17 level, and MLR level are significantly different between the two groups (P < 0.05). Conclusion: Peripheral blood Th17 and MLR have predictive value for the prognosis of colorectal cancer patients, and high levels of peripheral blood Th17 and MLR imply poor prognosis. The detection of peripheral blood Th17 and MLR levels is simple and convenient and can be used as indicators to provide a reference for the prognostic assessment of colorectal cancer patients.展开更多
BACKGROUND Colorectal cancer is the third most common malignancy worldwide.Therefore,it is critically important to identify new useful markers that can be easily obtained in routine practice.Inflammation is a crucial ...BACKGROUND Colorectal cancer is the third most common malignancy worldwide.Therefore,it is critically important to identify new useful markers that can be easily obtained in routine practice.Inflammation is a crucial issue in the pathogenesis and development of cancer.AIM To evaluate the prognostic value of absolute monocyte count,monocyte to lymphocyte ratio(MLR),the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio(NLR-PLR),and combined platelet and neutrophilto-lymphocyte ratio(PLT-NLR)in peripheral blood samples of patients with colorectal cancer undergoing surgery.METHODS We conducted a retrospective study of 160 patients with colorectal cancer who underwent surgery,and 42 healthy controls.The status of absolute monocyte count,MLR,NLR-PLR and PLT-NLR was calculated on the basis of blood samples obtained before and after surgery.Haematologic factors were examined in correlation with the type of tumour growth,tumour size,histological type,percentage of mucinous component,grade of malignancy,Tumour-Node-Metastasis stage,venous,lymphatic and perineural invasion of cancer cells,status of lymph node invasion and the presence of cancer cell deposits.The Kaplan-Meier method and the long-rank test were used to compare survival curves.To determine independent prognostic factors,univariate and multivariate Cox proportional hazards regression models were applied.RESULTS The PLT-NLR status was correlated with tumour size and the presence of perineural invasion(P=0.015;P=-0.174,P=0.037).Moreover,high NLR-PLR and PLR-NLR ratios in the blood samples obtained after surgery were positively associated with histological type of cancer and percentage of the mucinous component(NLR-PLR:P=0.002;P=0.009;PLR-NLR status:P=0.002;P=0.007).The analysis of 5-year disease-free survival showed that the MLR of whole blood obtained after surgery[HR=2.903,95%CI:(1.368-6.158),P=0.005]and the status of lymph node metastasis[HR=0.813,95%CI:(0.653-1.013),P=0.050]were independent prognostic factors in colorectal cancer patients.CONCLUSION The postoperative MLR in whole blood samples can be used as an independent prognostic factor in patients diagnosed with colorectal cancer.展开更多
Acute liver failure (ALF) is a devastating clinical syndrome characterised by progressive encephalopathy, coagulopathy, and circulatory dysfunction, which commonly leads to multiorgan failure and death. Central to the...Acute liver failure (ALF) is a devastating clinical syndrome characterised by progressive encephalopathy, coagulopathy, and circulatory dysfunction, which commonly leads to multiorgan failure and death. Central to the pathogenesis of ALF is activation of the immune system with mobilisation of cellular effectors and massive production of cytokines. As key components of the innate immune system, monocytes and macrophages are postulated to play a central role in the initiation, progression and resolution of ALF. ALF in humans follows a rapidly progressive clinical course that poses inherent difficulties in delineating the role of these pivotal immune cells. Therefore, a number of experimental models have been used to study the pathogenesis of ALF. Here we consider the evidence from experimental and human studies of ALF on the role of monocytes and macrophages in acute hepatic injury and the ensuing extrahepatic manifestations, including functional monocyte deactivation and multiple organ failure.展开更多
Monocyte chemoattractant protein-1(MCP-1), a potent chemoattractant, is thought to play an important role in migration of monocytes into atherosclerotic lesions. The present study was designed to investigate the capac...Monocyte chemoattractant protein-1(MCP-1), a potent chemoattractant, is thought to play an important role in migration of monocytes into atherosclerotic lesions. The present study was designed to investigate the capacity of human peripheral blood monocytes to express MCP-1 and effects of native very low density lipoprotein (VLDL) and oxidized VLDL(OX-VLDL) on the expression. The total RNA was extracted from cultured monocytes, which were exposed to VLDL and OX-VLDL, and the media conditioned by monocytes were collected. MCP-1 mRNA expression was examined by Northern blot analysis. MCP-1 protein in conditioned media was determined by using sandwich ELISA. The results showed that monocytes can express MCP-1 after a 24 h incubation at 37℃,and the expression was markedly increased by a exposure to OX-VLDL, whereas the expression was slightly increased when exposed to VLDL. It suggests that the capacity of monocytes to produce MCP-1 that recruits and activates circulating monocytes may be of considerable importance in atherogenesis, and oxidation of VLDL enhances its potential to promote atherogenesis.展开更多
[Objective] This study aimed to establish an in vitro culture model for porcine peripheral blood monocyte-derived dendritic cells (MoDCs). [Method] Fresh peripheral blood mononuclear cells (PBMCs) were separated f...[Objective] This study aimed to establish an in vitro culture model for porcine peripheral blood monocyte-derived dendritic cells (MoDCs). [Method] Fresh peripheral blood mononuclear cells (PBMCs) were separated from pig, and precursor dendritic cells were obtained by adherence method. The dendritic cells were treated by recombinant porcine granulocyte-monocyte colony stimulating factor (rpGM-CSF) and recombinant porcine interleukin-4 (rplL-4) together, and lipopolysaccharide (LPS) respectively. The cells in different time periods were collected. The morphology of the collected cells was observed by scanning electron microscopy; the expression of surface molecules and phagocytic ability to FITC-dextran were detected by flow cy- tometry; and the stimulating ability for allogeneic T cells was detected by mixed lymphocyte reaction. [Result] The DCs suffering maturation induction in vitro showed typical dendritic morphology; compared with those of DCs untreated by LPS, the cell surface expression of CDla, CD80, CD86, SLAII and CD172a of DCs treated by LPS was significantly increased, the phagocytic ability was reduced slightly, and the stimulating ability for allogeneic T cells was enhanced to some extent. [Conclusion] An in vitro culture method was successfully established for porcine MoDCs in this study, laying a foundation for further study on the role of porcine MoDCs in immunoregulation and anti-virus infection.展开更多
Aim This study was to evaluate the effect of arsenic trioxide (As2O3) on the transgenic TNF-α promoter activity in cultured vascular smooth muscle cells (VSMCs) and THP-1 monocytes. Methods Human TNF-α promoter ...Aim This study was to evaluate the effect of arsenic trioxide (As2O3) on the transgenic TNF-α promoter activity in cultured vascular smooth muscle cells (VSMCs) and THP-1 monocytes. Methods Human TNF-α promoter was constructed by reporter gene system and was transiently transfected into VSMCs and THP-1 in vitro. The promoter activity was tested by luciferase activity with or without LPS and Ang Ⅱ stimulation, before and after different dosage of As2O3 treatment. Results 1. TNF-α promoter effectively expressed in VSMCs and THP-1 compared with CMV promoter (58.3% and 80.9%, respectively). Both LPS and Ang Ⅱ significantly up-regulated TNF-α promoter activity (P〈0.05). 2. As2O3 significantly inhibited, both intact and LPS/Ang Ⅱ stimulated promoter activity, in a dose dependent manner (P〈0.05), and in both cell type. Conclusion These results manifested that, the inhibition effect of As2O3 on the activity of human TNF-α promoter indicated its potential inhibition on pro-inflammatory cytokine genes expression at transcriptional level and its potential anti-inflammatory property in the cardiovascular system.展开更多
Objective: To study the role of monocytes in the pathogenesis of genital herpes. Methods: TNF- α and IL-6 levels in 27 cases of genital herpes were detected by enzyme linked immunosorbant assay (ELISA). HLA class Ⅱ ...Objective: To study the role of monocytes in the pathogenesis of genital herpes. Methods: TNF- α and IL-6 levels in 27 cases of genital herpes were detected by enzyme linked immunosorbant assay (ELISA). HLA class Ⅱ antigen expression on monocytes were detected by an alkaline phosphatase anti-alkaline phosphatase method. Results: Compared with normal controls, levels of TNF- a and IL - 6 secreted by monocytes responding to LPS mitogen in vitro were significantly decreased [(3.13 ± 0.44ng/ml) vs (4.68 ± 0.54ng/ml), P<0.05 and (3.32 ± 1.06ng/ml) vs (6.46 ± 1.94ng/ ml), P<0.05, respectively]. HLA class Ⅱ antigen expression on monocytes in the genital herpes group was also significantly decreased [HLA-DR (67.48% ± 1.51%) vs (81.03% ± 1.32%), P<0.01 and HLA-DQ (29.54% ± 1.15%) vs (37.63% ± 1.79%), P <0.01 respectively]. Conclusion: These findings suggest that the decreased monocyte function may contribute to the pathogenesis of genital herpes. Augmenting or inducing monocyte function may be important in the prevention, treatment, and reduction of genital herpes cases.展开更多
Objectives: In order to investigate the role of mono-cytes and human leukocyte antigen (HLA) class II an-tigen in herpes simplex virus-2 (HSV-2) infection, westudied the effect of HSV-2 infection in vitro on theexpres...Objectives: In order to investigate the role of mono-cytes and human leukocyte antigen (HLA) class II an-tigen in herpes simplex virus-2 (HSV-2) infection, westudied the effect of HSV-2 infection in vitro on theexpression of HLA class II antigen on monocytes.Methods: Monocytes were infected with HSV-2(Strain 333). Culture cells were collected 1, 3, 5 and 7days after infection. The levels of expression of HLAclass II antigen were measured by using alkaline phos-phatase antialkaline phosphatase method (APAAP).Results: The levels of the expression of HLA class IIantigen on monocytes significantly decreased on thefirst day of post-infection, and then gradually returnedto levels found in the controls by the 7th day post-infection.Conclusion: HLA class II antigen expression onmonocytes was inhibited with HSV-2 infection, whichmight be one means of virus escape at an early phase.The expression of HLA class II antigen may play animportant role in herpes simplex viurs-2 pathogenic-ity and immunity.展开更多
基金supported by the China Scholarship Council(to YW)the Swedish Research Council,No.2018-02601(to MS)+7 种基金the Alzheimer Foundation,No.AF-980695(to MS)the Stockholm County Council,No.RS2020-0731(to MS)the Foundation of Old Servants(to MS)the Gun and Bertil Stohne Foundation(to MS)the?hlén Foundation,No.233055(to MS)The Swedish Fund for Research without Animal Experiments(to MS)the Swedish Dementia Foundation(to MS)the Brain foundation,No.FO2022-0131(to MS)。
文摘Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.
基金supported by the National Natural Science Foundation of China,Nos.82060219,82271234the Natural Science Foundation of Jiangxi Province,Nos.20212ACB216009,20212BAB216048+1 种基金Jiangxi Province Thousands of Plans,No.jxsq2019201023Youth Team Project of the Second Affiliated Hospital of Nanchang University,No.2019YNTD12003(all to FH)。
文摘Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.
基金Supported by the Medical Discipline Construction Project of Pudong Health Committee of Shanghai,No.PWZzb2022-09Nanning City Science Research and Technology Development Program,No.ZC20233017and Guangxi Medical and Health Appropriate Technology Development and Promotion Project,No.S2021061.
文摘BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents.This mental health condition can have severe consequences,including academic failure,social withdrawal,and suicidal behavior.Given the increasing rate of depression in this age group,understanding the underlying biological mechanisms is essential for early detection and intervention.Recent studies have suggested that immune markers play a role in the pathophysiology of depression,prompting further investigation of their potential association with depressive symptoms in adolescents.AIM To investigate the relationship between immune markers(monocytes,lymphocytes,and direct bilirubin)and the incidence and severity of depression among adolescents.METHODS This cross-sectional study recruited 145 adolescent patients with depression[male(M)/female(F)=38/107]from Jiangbin Hospital in Guangxi,Zhuang and 163 healthy controls(M/F=77/86)from routine health check-ups.Blood samples were collected after an overnight fast.Depression severity was measured using the Zung Self-Rating Depression Scale.The inclusion criteria were age 12-24 years,diagnosis of depressive disorder(ICD-10),and no recent antidepressant use.The exclusion criteria included psychiatric comorbidities and serious somatic diseases.Key statistical methods included group comparisons and correlation analyses.RESULTS There was a higher prevalence of females in the depression group(P<0.001).Significant age differences were observed between the groups(Z=9.43,P<0.001).The depression group had higher monocyte(Z=3.43,P<0.001)and lymphocyte(t=2.29,P<0.05)counts,and higher serum direct bilirubin levels(Z=4.72,P<0.001).Monocyte count varied significantly according to depression severity,with lower counts in the mild group(Z=-2.90,P<0.05).A negative correlation between age and lymphocyte counts was observed(ρ=-0.22,P<0.01).Logistic regression analysis showed that serum direct bilirubin levels significantly predicted depression.CONCLUSION The potential role of elevated levels of immune markers in the early detection of depression in adolescents has been highlighted.Therefore,it is necessary to explore further the relationships between these immune markers and depression.
基金Natural Science Foundation of Zhejiang Province(grant number LY20H290005)Key Research and Development Program of Zhejiang Province(grant number 2020C03119)+2 种基金National Natural Science Foundation of China(grant numbers 81673706,81973579,82174150)Science and Technology Program of Zhejiang Traditional Chinese Medicine(grant number 2018ZY005)TCM science and Technology Foundation Project of Zhejiang Province(grant number 2023ZL411).
文摘Background:Atherosclerosis(AS)is a chronic progressive inflammatory disease,and plaque stability plays a critical role in preventing acute events.Tanyu Tongzhi formula(TTF),a traditional Chinese medicine,has potential therapeutic effects on AS.Methods:We used an AS animal model to examine the effects of TTF on atherosclerotic plaque vulnerability and CD40^(+)monocyte differentiation.AS plaque area,collagen content,and lipid area were assessed using histological staining.AS plaque-related biomarkers(monocyte chemoattractant protein 1(MCP-1),monocyte plus macrophage(MOMA-2),von Willebrand factor(vWF),CD31,and alpha-smooth muscle actin(α-SMA))were detected using immunohistochemistry.Inflammatory cytokines were determined using enzyme-linked immunosorbent assay.CD40 mRNA expression was detected by real-time quantitative PCR.CD40^(+)monocyte differentiation was evaluated by flow cytometry analysis in ApoE-/-mice and peripheral blood mononuclear cells(PBMCs).AMPK/NF-κB signaling pathways-related protein expression was investigated through western blotting.Results:TTF treatment reduced AS plaque area,collagen content,and lipid area in AS model mice.Levels of MCP-1,MOMA-2,vWF,and CD31 were decreased,whileα-SMA level was increased by TTF in model mice.TTF reduced inflammatory cytokines levels,including tumor necrosis factor receptor-α(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and interleukin-6(IL-6).TTF inhibited CD40^(+)monocyte differentiation and decreased the number of CD40^(+)/CD40-and Ly6C^(+)/Ly6C-cells and M1/M2 ratio in AS model mice and human PBMCs.Additionally,TTF modulated the AMPK/NF-κB signaling pathway in human PBMCs.Conclusion:TTF attenuates atherosclerotic plaque vulnerability by inhibiting CD40^(+)monocyte differentiation,possibly through the regulation of the AMPK/NF-κB signaling pathway.These findings suggest that TTF could be a potential therapeutic agent for preventing plaque rupture and subsequent cardiovascular events in patients with AS.
基金supported by Beijing Natural Science Foundation(Grant No.Z210014)National Natural Science Foundation of China(Grant No.32070543)+1 种基金National Key Research and Development Project of China(Grant No.2022YFC2303404)CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.2022-12M-CoV19-002)
文摘Background:SARS-CoV-2,first identified in late 2019,has given rise to numerous variants of concern(VOCs),posing a significant threat to human health.The emer-gence of Omicron BA.1.1 towards the end of 2021 led to a pandemic in early 2022.At present,the lethal mouse model for the study of SARS-CoV-2 needs supplementation,and the alterations in neutrophils and monocytes caused by different strains remain to be elucidated.Methods:Human ACE2 transgenic mice were inoculated with the SARS-CoV-2 proto-type and Omicron BA.1,respectively.The pathogenicity of the two strains was evalu-ated by observing clinical symptoms,viral load and pathology.Complete blood count,immunohistochemistry and flow cytometry were performed to detect the alterations of neutrophils and monocytes caused by the two strains.Results:Our findings revealed that Omicron BA.1 exhibited significantly lower vir-ulence compared to the SARS-CoV-2 prototype in the mouse model.Additionally,we observed a significant increase in the proportion of neutrophils late in infection with the SARS-CoV-2 prototype and Omicron BA.1.We found that the proportion of monocytes increased at first and then decreased.The trends in the changes in the proportions of neutrophils and monocytes induced by the two strains were similar.Conclusion:Our study provides valuable insights into the utility of mouse models for simulating the severe disease of SARS-CoV-2 prototype infection and the milder manifestation associated with Omicron BA.1.SARS-CoV-2 prototype and Omicron BA.1 resulted in similar trends in the changes in neutrophils and monocytes.
基金Supported by National Natural Science Foundation of China,No.81970669,No.82170835,and No.82100848Shanghai Municipal Health Commission,No.202240107,and No.20234Y0040China Endocrine Metabolism Research Program of Excellence,No.2023-N-03-05。
文摘BACKGROUND Deficient efferocytosis(i.e.,phagocytic clearance of apoptotic cells)by macrophages has been frequently reported in experimental models of type 2 diabetes(T2D).AIM To translate these findings to humans by testing whether the efferocytosis capacity of blood monocytes and monocyte-derived macrophages is impaired in T2D patients.METHODS Overall,30 patients with poorly controlled T2D[glycosylated hemoglobin(HbA1c)≥8.0%]and 30 age-and sex-matched control subjects were enrolled in the study.The efferocytosis capacities of peripheral blood monocytes and monocyte-derived macrophages were assessed by flow cytometry and immunostaining.Macrophage membrane CD14 expression was examined by flow cytometry.Metabolic factors such as 25(OH)D and immune factors such as interleukin-1βwere also measured.RESULTS The mean monocyte efferocytosis index in the diabetes group was significantly lower than that in the control group.Notably,efferocytosis remained impaired after monocytes differentiated into macrophages.Additionally,the percentages of classical monocytes(CD14^(++)CD16-monocytes)and CD14^(+)macrophages were significantly lower in the diabetes group.Multivariate linear regression analysis in diabetes patients demonstrated that the monocyte efferocytosis index was independently associated with the HbA1c level,and that the macrophage efferocytosis index was significantly associated with the percentage of CD14^(+)macrophages.CONCLUSION Impaired efferocytosis was observed in T2D patients,with poor glycemic control affecting both blood monocytes and monocyte-derived macrophages.The efferocytosis index was negatively associated with metrics of glycemic control,and glucotoxicity may impact efferocytosis through reducing CD14 expression on both monocytes and macrophages.
文摘Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.
文摘Background With the continuous exploration of cardiovascular diseases,research has found that inflammatory reactions play an important role in the pathogenesis of cardiovascular diseases.In recent years,the ratio of monocyte to lymphocyte counts(MLR)has attracted widespread attention as a novel inflammatory marker.Therefore,this article will focus on the value of MLR in terms of prevalence risk,severity and prognosis in common cardiovascular diseases.[S Chin J Cardiol 2024;25(3):200-206]
文摘BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.However,conventional diagnostic methods such as electrocardiography,echocardiography,and cardiac biomarkers have certain limitations,such as low sensitivity,specificity,availability,and cost-effectiveness.Therefore,there is a need for simple,noninvasive,and reliable biomarkers to diagnose CHD and HF.AIM To investigate serum cystatin C(Cys-C),monocyte/high-density lipoprotein cholesterol ratio(MHR),and uric acid(UA)diagnostic values for CHD and HF.METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023.The patients were divided into CHD(n=20),HF(n=20),CHD+HF(n=20),and control groups(n=20).The serum levels of Cys-C,MHR,and UA were measured using immunonephelometry and an enzymatic method,respectively,and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Serum levels of Cys-C,MHR,and UA were significantly higher in the CHD,HF,and CHD+HF groups than those in the control group.The serum levels of Cys-C,MHR,and UA were significantly higher in the CHD+HF group than those in the CHD or HF group.The ROC curve analysis showed that serum Cys-C,MHR,and UA had good diagnostic performance for CHD and HF,with areas under the curve ranging from 0.78 to 0.93.The optimal cutoff values of serum Cys-C,MHR,and UA for diagnosing CHD,HF,and CHD+HF were 1.2 mg/L,0.9×10^(9),and 389μmol/L;1.4 mg/L,1.0×10^(9),and 449μmol/L;and 1.6 mg/L,1.1×10^(9),and 508μmol/L,respectively.CONCLUSION Serum Cys-C,MHR,and UA are useful biomarkers for diagnosing CHD and HF,and CHD+HF.These can provide information for decision-making and risk stratification in patients with CHD and HF.
基金supported by US National Institutes of Health grants Al147394,AG069264,Al112844,HL170961 and Al154598 to J.S.
文摘Pulmonary macrophages,such as tissue-resident alveolar and interstitial macrophages and recruited monocyte-derived macrophages,are the major macrophages present in the lungs during homeostasis and diseased conditions.While tissue-resident macrophages act as sentinels of the alveolar space and play an important role in maintaining homeostasis and immune regulation,recruited macrophages accumulate in the respiratory tract after acute viral infections.Despite sharing similar anatomical niches,these macrophages are distinct in terms of their origins,surface marker expression,and transcriptional profiles,which impart macrophages with distinguished characteristics in physi-ological and pathophysiological conditions.In this review,we summarize the current view on these macrophage populations,their shared functions,and what makes them distinct from each other in the context of homeostasis andrespiratoryviral infections.
基金Supported by the Special Fund for Clinical Research of Nanjing Drum Tower Hospital(No.2023-LCYJPY-37).
文摘AIM:To evaluate the relationship between monocyte to high-density lipoprotein cholesterol ratio(MHR)and the disease activity of thyroid-associated ophthalmopathy(TAO).METHODS:A total of 87 patients were classified into two groups based on clinical activity score(CAS)scoring criteria:high CAS group(n=62,the CAS score was≥3);low CAS group(n=25,the CAS score was<3).In addition,a group of healthy people(n=114)were included to compared the MHR.Proptosis,MHR,average signal intensity ratio(SIR),average lacrimal gland(LG)-SIR,average extraocular muscles(EOM)area from 87 patients with TAO were calculated in magnetic resonance imaging(MRI),and compared between these two groups.Correlation testing was utilized to evaluate the association of parameters among the clinical variables.RESULTS:Patients in high CAS group had a higher proptosis(P=0.041)and MHR(P=0.048).Compared to the healthy group,the MHR in the TAO group was higher(P=0.001).Correlation testing declared that CAS score was strongly associated with proptosis and average SIR,and MHR was positively associated with CAS score,average SIR,and average LG-SIR.The area under the receiver operating characteristic curve(AUC)of MHR was 0.6755.CONCLUSION:MHR,a novel inflammatory biomarker,has a significant association with CAS score and MRI imaging(average SIR and LG-SIR)and it can be a new promising predictor during the active phase of TAO.
文摘BACKGROUND The lymphocyte to monocyte ratio(LMR)is considered a marker of systemic inflammation in cardiovascular disease and acts as predictor of mortality in coronary artery disease.AIM To investigate the predictive role of LMR in diabetic coronary artery disease patients.METHODS This cross-sectional study was conducted at tertiary care super-specialty hospital at New Delhi,India.A total of 200 angiography-proven coronary artery disease(CAD)patients were enrolled and grouped into two categories:Group I[CAD patients with type 2 diabetes mellitus(T2DM)and glycated hemoglobin(HbA1c)levels≥6.5%],and Group II(CAD patients without T2DM and HbA1c levels<6.5%).Serum lipoproteins,HbA1c,and complete blood count of enrolled patients were analyzed using fully automatic analyzers.RESULTS The logistic regression analysis showed an odds ratio of 1.48(95%CI:1.28-1.72,P<0.05)for diabetic coronary artery disease patients(Group I)in unadjusted model.After adjusting for age,gender,diet,smoking,and hypertension history,the odds ratio increased to 1.49(95%CI:1.29-1.74,P<0.01)in close association with LMR.Further adjustment for high cholesterol and triglycerides yielded the same odds ratio of 1.49(95%CI:1.27-1.75,P<0.01).Receiver operating characteristic curve analysis revealed 74%sensitivity,64%specificity,and 0.74 area under the curve(95%CI:0.67-0.80,P<0.001),suggesting moderate predictive accuracy for diabetic CAD patients.CONCLUSION LMR showed positive association with diabetic coronary artery disease,with moderate predictive accuracy.These findings have implications for improving CAD management in diabetics,necessitating further research and targeted interventions.
文摘Objective: To investigate the value of peripheral blood helper T cell 17 cell level and monocyte/lymphocyte ratio to predict the prognosis of colorectal cancer patients. Methods: 74 colorectal cancer patients who attended Hospital 960 from January 2021 to January 2022 were retrospectively analyzed. Clinical data of the patients were collected, including gender, age, and histologic type. Immunohistochemical indexes such as Th17 cell level and monocyte/ lymphocyte ratio in the peripheral blood of patients were also collected. The prognosis of patients after treatment, as well as peripheral blood Th17 and MLR levels, were observed and analyzed. Results: After follow-up after treatment, in the final 74 patients, the prognosis was good in 32 patients, accounting for 43.24%, and the prognosis was bad in 42 patients, accounting for 56.76%. There were no significant differences between the average age and tumor diameters of the good prognosis and poor prognosis groups (P > 0.05). However, the TNM staging, intervention taken, differentiation degree, presence of distant metastasis, presence of lymph node metastasis, Th17 level, and MLR level are significantly different between the two groups (P < 0.05). Conclusion: Peripheral blood Th17 and MLR have predictive value for the prognosis of colorectal cancer patients, and high levels of peripheral blood Th17 and MLR imply poor prognosis. The detection of peripheral blood Th17 and MLR levels is simple and convenient and can be used as indicators to provide a reference for the prognostic assessment of colorectal cancer patients.
文摘BACKGROUND Colorectal cancer is the third most common malignancy worldwide.Therefore,it is critically important to identify new useful markers that can be easily obtained in routine practice.Inflammation is a crucial issue in the pathogenesis and development of cancer.AIM To evaluate the prognostic value of absolute monocyte count,monocyte to lymphocyte ratio(MLR),the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio(NLR-PLR),and combined platelet and neutrophilto-lymphocyte ratio(PLT-NLR)in peripheral blood samples of patients with colorectal cancer undergoing surgery.METHODS We conducted a retrospective study of 160 patients with colorectal cancer who underwent surgery,and 42 healthy controls.The status of absolute monocyte count,MLR,NLR-PLR and PLT-NLR was calculated on the basis of blood samples obtained before and after surgery.Haematologic factors were examined in correlation with the type of tumour growth,tumour size,histological type,percentage of mucinous component,grade of malignancy,Tumour-Node-Metastasis stage,venous,lymphatic and perineural invasion of cancer cells,status of lymph node invasion and the presence of cancer cell deposits.The Kaplan-Meier method and the long-rank test were used to compare survival curves.To determine independent prognostic factors,univariate and multivariate Cox proportional hazards regression models were applied.RESULTS The PLT-NLR status was correlated with tumour size and the presence of perineural invasion(P=0.015;P=-0.174,P=0.037).Moreover,high NLR-PLR and PLR-NLR ratios in the blood samples obtained after surgery were positively associated with histological type of cancer and percentage of the mucinous component(NLR-PLR:P=0.002;P=0.009;PLR-NLR status:P=0.002;P=0.007).The analysis of 5-year disease-free survival showed that the MLR of whole blood obtained after surgery[HR=2.903,95%CI:(1.368-6.158),P=0.005]and the status of lymph node metastasis[HR=0.813,95%CI:(0.653-1.013),P=0.050]were independent prognostic factors in colorectal cancer patients.CONCLUSION The postoperative MLR in whole blood samples can be used as an independent prognostic factor in patients diagnosed with colorectal cancer.
文摘Acute liver failure (ALF) is a devastating clinical syndrome characterised by progressive encephalopathy, coagulopathy, and circulatory dysfunction, which commonly leads to multiorgan failure and death. Central to the pathogenesis of ALF is activation of the immune system with mobilisation of cellular effectors and massive production of cytokines. As key components of the innate immune system, monocytes and macrophages are postulated to play a central role in the initiation, progression and resolution of ALF. ALF in humans follows a rapidly progressive clinical course that poses inherent difficulties in delineating the role of these pivotal immune cells. Therefore, a number of experimental models have been used to study the pathogenesis of ALF. Here we consider the evidence from experimental and human studies of ALF on the role of monocytes and macrophages in acute hepatic injury and the ensuing extrahepatic manifestations, including functional monocyte deactivation and multiple organ failure.
文摘Monocyte chemoattractant protein-1(MCP-1), a potent chemoattractant, is thought to play an important role in migration of monocytes into atherosclerotic lesions. The present study was designed to investigate the capacity of human peripheral blood monocytes to express MCP-1 and effects of native very low density lipoprotein (VLDL) and oxidized VLDL(OX-VLDL) on the expression. The total RNA was extracted from cultured monocytes, which were exposed to VLDL and OX-VLDL, and the media conditioned by monocytes were collected. MCP-1 mRNA expression was examined by Northern blot analysis. MCP-1 protein in conditioned media was determined by using sandwich ELISA. The results showed that monocytes can express MCP-1 after a 24 h incubation at 37℃,and the expression was markedly increased by a exposure to OX-VLDL, whereas the expression was slightly increased when exposed to VLDL. It suggests that the capacity of monocytes to produce MCP-1 that recruits and activates circulating monocytes may be of considerable importance in atherogenesis, and oxidation of VLDL enhances its potential to promote atherogenesis.
基金Supported by Fundamental and Advanced Research Projects of Henan Province(152300410076,2015-2017)Key Science and Technology Program of Henan Province(152102110048,2015-2017)~~
文摘[Objective] This study aimed to establish an in vitro culture model for porcine peripheral blood monocyte-derived dendritic cells (MoDCs). [Method] Fresh peripheral blood mononuclear cells (PBMCs) were separated from pig, and precursor dendritic cells were obtained by adherence method. The dendritic cells were treated by recombinant porcine granulocyte-monocyte colony stimulating factor (rpGM-CSF) and recombinant porcine interleukin-4 (rplL-4) together, and lipopolysaccharide (LPS) respectively. The cells in different time periods were collected. The morphology of the collected cells was observed by scanning electron microscopy; the expression of surface molecules and phagocytic ability to FITC-dextran were detected by flow cy- tometry; and the stimulating ability for allogeneic T cells was detected by mixed lymphocyte reaction. [Result] The DCs suffering maturation induction in vitro showed typical dendritic morphology; compared with those of DCs untreated by LPS, the cell surface expression of CDla, CD80, CD86, SLAII and CD172a of DCs treated by LPS was significantly increased, the phagocytic ability was reduced slightly, and the stimulating ability for allogeneic T cells was enhanced to some extent. [Conclusion] An in vitro culture method was successfully established for porcine MoDCs in this study, laying a foundation for further study on the role of porcine MoDCs in immunoregulation and anti-virus infection.
基金National Natural Science Foundation of China(No.30170368)
文摘Aim This study was to evaluate the effect of arsenic trioxide (As2O3) on the transgenic TNF-α promoter activity in cultured vascular smooth muscle cells (VSMCs) and THP-1 monocytes. Methods Human TNF-α promoter was constructed by reporter gene system and was transiently transfected into VSMCs and THP-1 in vitro. The promoter activity was tested by luciferase activity with or without LPS and Ang Ⅱ stimulation, before and after different dosage of As2O3 treatment. Results 1. TNF-α promoter effectively expressed in VSMCs and THP-1 compared with CMV promoter (58.3% and 80.9%, respectively). Both LPS and Ang Ⅱ significantly up-regulated TNF-α promoter activity (P〈0.05). 2. As2O3 significantly inhibited, both intact and LPS/Ang Ⅱ stimulated promoter activity, in a dose dependent manner (P〈0.05), and in both cell type. Conclusion These results manifested that, the inhibition effect of As2O3 on the activity of human TNF-α promoter indicated its potential inhibition on pro-inflammatory cytokine genes expression at transcriptional level and its potential anti-inflammatory property in the cardiovascular system.
文摘Objective: To study the role of monocytes in the pathogenesis of genital herpes. Methods: TNF- α and IL-6 levels in 27 cases of genital herpes were detected by enzyme linked immunosorbant assay (ELISA). HLA class Ⅱ antigen expression on monocytes were detected by an alkaline phosphatase anti-alkaline phosphatase method. Results: Compared with normal controls, levels of TNF- a and IL - 6 secreted by monocytes responding to LPS mitogen in vitro were significantly decreased [(3.13 ± 0.44ng/ml) vs (4.68 ± 0.54ng/ml), P<0.05 and (3.32 ± 1.06ng/ml) vs (6.46 ± 1.94ng/ ml), P<0.05, respectively]. HLA class Ⅱ antigen expression on monocytes in the genital herpes group was also significantly decreased [HLA-DR (67.48% ± 1.51%) vs (81.03% ± 1.32%), P<0.01 and HLA-DQ (29.54% ± 1.15%) vs (37.63% ± 1.79%), P <0.01 respectively]. Conclusion: These findings suggest that the decreased monocyte function may contribute to the pathogenesis of genital herpes. Augmenting or inducing monocyte function may be important in the prevention, treatment, and reduction of genital herpes cases.
文摘Objectives: In order to investigate the role of mono-cytes and human leukocyte antigen (HLA) class II an-tigen in herpes simplex virus-2 (HSV-2) infection, westudied the effect of HSV-2 infection in vitro on theexpression of HLA class II antigen on monocytes.Methods: Monocytes were infected with HSV-2(Strain 333). Culture cells were collected 1, 3, 5 and 7days after infection. The levels of expression of HLAclass II antigen were measured by using alkaline phos-phatase antialkaline phosphatase method (APAAP).Results: The levels of the expression of HLA class IIantigen on monocytes significantly decreased on thefirst day of post-infection, and then gradually returnedto levels found in the controls by the 7th day post-infection.Conclusion: HLA class II antigen expression onmonocytes was inhibited with HSV-2 infection, whichmight be one means of virus escape at an early phase.The expression of HLA class II antigen may play animportant role in herpes simplex viurs-2 pathogenic-ity and immunity.