As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to pr...As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to predict the risk of obesity-associated cardiac dysfunction.By retrospectively analyzing the clinical characteristics of 5648 cardiac disease patients,we found that both the plasma level of high-density lipoprotein cholesterol(HDLC)and the blood monocyte count were significantly associated with impairment of the left ventricular ejection fraction(LVEF).Univariate and multivariate regression analyses revealed that the monocyte to HDL-C ratio(MHR)was a more powerful predictor of the risk of LVEF decline than either HDL-C or monocyte alone.Mediation analysis further revealed a mediating effect of a high MHR on the decline in obesity-associated cardiac systolic function.Collectively,our results demonstrate a superior role of MHR in predicting the risk of an obesityassociated decline in cardiac systolic function among routine metabolic/inflammatory markers.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
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
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 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
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
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
[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: In order to detect the role of monocytes inHSV-2 infection, we studied the effect of herpes sim-plex Virus-2 infection on the production of tumor ne-crosis factor (TNF-σ), interleukin-6 (IL-6) secretedby m...Objective: In order to detect the role of monocytes inHSV-2 infection, we studied the effect of herpes sim-plex Virus-2 infection on the production of tumor ne-crosis factor (TNF-σ), interleukin-6 (IL-6) secretedby monocytes. Methods: Monocytes were infected by HSV-2 (333Strain). Culture supernatants were collected at 1, 3,5, 7 days post-infection. The levels of TNF-α, IL-6were measured by enzyme-linked immunosorbent as-say (ELISA). Results: The levels of TNF-α secretion by mono-cytes significantly decreased on first day post-infection. The levels of IL-6 significantly decreasedon first and third days post-infection, and then gradu-ally increased to the control on seventh day post-infection. Conclusions: TNF-α and IL-6 production by mono-cytes was inhibited during HSV-2 infection. The pro-duction of cytokines may play an important role inherpes simplex viurs-2 pathogenicity and immunity.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
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
Alzheimer＇s disease（AD） is a neurodegenerative disease characterized by extracellular amyloid beta（Aβ） deposition and intracellular neurofibrillary tangle formation.Monocyte is part of the innate immune system a...Alzheimer＇s disease（AD） is a neurodegenerative disease characterized by extracellular amyloid beta（Aβ） deposition and intracellular neurofibrillary tangle formation.Monocyte is part of the innate immune system and can effectively remove dead cells and debris.It has been suggested that Aβ can recruit monocytes into brain in AD mice,resulting in restriction of cerebral amyloidosis.However,monocyte may act as a double-edged sword,either beneficial（e.g.,clearance of Aβ） or detrimental（e.g.,secretion of neurotoxic factors）.In addition,recent studies indicate that in AD patients,Aβ phagocytosis by monocytes is ineffective.The present review mainly summarized the current knowledge on monocytes and their potential roles in AD.展开更多
Acute pancreatitis(AP) is an inflammatory condition of the pancreas caused by an imbalance in factors involved in maintaining cellular homeostasis.Earliest events in AP occur within acinar cells accompanied by other p...Acute pancreatitis(AP) is an inflammatory condition of the pancreas caused by an imbalance in factors involved in maintaining cellular homeostasis.Earliest events in AP occur within acinar cells accompanied by other principal contributors to the inflammatory response i.e.the endothelial cells,immunocytes(granulocytes,monocytes/macrophages,lymphocytes) and neutrophils.Monocytes/macrophages are important inflammatory mediators,involved in the pathophysiology of AP,known to reside in the peritoneal cavity(in the vicinity of the pancreas) and in peripancreatic tissue.Recent studies suggested that impaired clearance of injured acini by macrophages is associated with an altered cytokine reaction which may constitute a basis for progression of AP.This review focuses on the role of monocytes/macrophages in progression of AP and discusses f indings on the inflammatory process involved.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
Background:As a surrogate marker of systemic inflammation,the lymphocyte-to-monocyte ratio(LMR) is an independent prognostic factor for various malignancies.This study investigated the prognostic significance of the p...Background:As a surrogate marker of systemic inflammation,the lymphocyte-to-monocyte ratio(LMR) is an independent prognostic factor for various malignancies.This study investigated the prognostic significance of the pre-chemotherapy LMR in patients with previously untreated metastatic colorectal cancer(mCRC) receiving chemotherapy.Methods:The present study included newly diagnosed mCRC patients treated between January 2005 and December 2013 with FOLFOX chemotherapy,specifically oxaliplatin 180 mg/m^2 on day 1,with leucovorin 400 mg/m^2administered as a 2-hour infusion before the administration of 5-fluorouracil 400 mg/m^2 as an intravenous bolus injection,and 5-fluorouracil 2400 mg/m^2 as a 46-h infusion immediately after 5-fluorouracil bolus injection.The LMR was calculated as the absolute count of lymphocytes divided by the absolute count of monocytes.COX proportional hazards analysis was performed to evaluate the association of LMR with survival outcomes.Results:A total of 488 patients were included.Patients with high pre-chemotherapy LMR experienced significant improvements in progression-free survival(PFS,9.2 vs.7.6 months,P < 0.001) and overall survival(OS,19.4 vs.16.6 months,P < 0.001) compared with patients with low pre-chemotherapy LMR.Subsequent COX multivariate analysis showed that high pre-chemotherapy LMR(>3.11) was an independent favorable prognostic factor for PFS and OS.Additionally,patients whose LMR remained high(high-high subgroup),increased(low-high subgroup),or decreased(high-low subgroup) following chemotherapy showed better results in terms of PFS and OS than patients whose LMR remained low(low-low subgroup) after chemotherapy.Conclusions:For patients with previously untreated mCRC receiving FOLFOX chemotherapy,an elevated pre-chemotherapy LMR is an independent favorable prognostic factor for PFS and OS,and changes in the LMR before and after chemotherapy seem to predict the benefit of chemotherapy.展开更多
Macrophages exist in most tissues and play a variety of functions in vertebrates.Teleost fish species are found in most aquatic environments throughout the world and are quite diverse for a group of vertebrate animals...Macrophages exist in most tissues and play a variety of functions in vertebrates.Teleost fish species are found in most aquatic environments throughout the world and are quite diverse for a group of vertebrate animals.Due to whole genome duplication and en vironme ntal adaptati on,teleost monocytes/macrophages possess a variety of different functions and modulations compared with those of mammals.A deeper understanding of teleost monocytes/macrophages in the immune system will not only help develop teleost-specific methods of disease prevention but will also help improve our understanding of the various immune mechanisms in mammals.In this review,we summarize the differences in polarizati on and phagocytosis of teleost and mammalian macrophages to improve our understanding of the various immune mechanisms in vertebrates.展开更多
AIM:To measure the prognostic significance of absolute monocyte count/absolute lymphocyte count prognostic score(AMLPS) in patients with gastric cancer.METHODS:We retrospectively examined the combination of absolute m...AIM:To measure the prognostic significance of absolute monocyte count/absolute lymphocyte count prognostic score(AMLPS) in patients with gastric cancer.METHODS:We retrospectively examined the combination of absolute monocyte count(AMC) and absolute lymphocyte count(ALC) as prognostic variables in a cohort of 299 gastric cancer patients who underwent surgical resection between 2006 and 2013 and were followed at a single institution.Both AMC and ALC were dichotomized into two groups using cut-off points determined by receiving operator characteristic curve analysis.An AMLPS was generated,which stratified patients into three risk groups:low risk(both low AMC and high ALC),intermediate risk(either high AMC or low ALC),and high risk(both high AMC and low ALC).The primary objective of the study was to validate the impact of AMLPS on both disease-free survival(DFS) and overall survival(OS),and the second objective was to assess the AMLPS as an independent prognostic factor for survival in comparison with known prognostic factors.RESULTS:Using data from the entire cohort,the most discriminative cut-off values of AMC and ALC selected on the receiver operating characteristic curve were 672.4/μL and 1734/μL for DFS and OS.AMLPS risk groups included 158(52.8%) patients in the lowrisk,128(42.8%) in the intermediate-risk,and 13(4.3%) in the high-risk group.With a median followup of 37.2 mo(range:1.7-91.4 mo),five-year DFS rates in the low-,intermediate-,and high-risk groups were 83.4%,78.7%,and 19.8%,respectively.And fiveyear OS rates in the low-,intermediate-,and high-risk groups were 89.3%,81.1%,and 14.4%,respectively.On multivariate analysis performed with patient- and tumor-related factors,we identified AMLPS,age,and pathologic tumor-node-metastasis stage as the most valuable prognostic factors impacting DFS and OS.CONCLUSION:AMLPS identified patients with a poor DFS and OS,and it was independent of age,pathologic stage,and various inflammatory markers.展开更多
BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death.However,the role of hepatocyte pyroptosis and its me...BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death.However,the role of hepatocyte pyroptosis and its mechanisms of expanding inflammatory responses in ALF are unclear.AIM To investigate the role and mechanisms of GSDMD-mediated hepatocyte pyroptosis through in vitro and in vivo experiments.METHODS The expression of pyroptosis pathway-associated proteins in liver tissues from ALF patients and a hepatocyte injury model was examined by Western blot.GSDMD short hairpin RNA(shRNA)was used to investigate the effects of downregulation of GSDMD on monocyte chemotactic protein 1(MCP1)and its receptor CC chemokine receptor-2(CCR2)in vitro.For in vivo experiments,we used GSDMD knockout mice to investigate the role and mechanism of GSDMD in a D-galactose/lipopolysaccharide(D-Galn/LPS)-induced ALF mouse model.RESULTS The levels of pyroptosis pathway-associated proteins in liver tissue from ALF patients and a hepatocyte injury model increased significantly.The level of GSDMD-N protein increased most obviously(P<0.001).In vitro,downregulation of GSDMD by shRNA decreased the cell inhibition rate and the levels of MCP1/CCR2 proteins(P<0.01).In vivo,GSDMD knockout dramatically eliminated inflammatory damage in the liver and improved the survival of DGaln/LPS-induced ALF mice(P<0.001).Unlike the mechanism of immune cell pyroptosis that involves releasing interleukin(IL)-1βand IL-18,GSDMDmediated hepatocyte pyroptosis recruited macrophages via MCP1/CCR2 to aggravate hepatocyte death.However,this pathological process was inhibited after knocking down GSDMD.CONCLUSION GSDMD-mediated hepatocyte pyroptosis plays an important role in the pathogenesis of ALF,recruiting macrophages to release inflammatory mediators by upregulating MCP1/CCR2 and leading to expansion of the inflammatory responses.GSDMD knockout can reduce hepatocyte death and inflammatory responses,thus alleviating ALF.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82430018 to Q.C.,82270361 and 82570402 to H.Z.)the Nanjing Medical University Undergraduate Innovation and Entrepreneurship Training Program Fund(Grant No.202410312138Y to C.Z.)the Basic Sciences of Jiangsu Higher Education Institutions(Grant No.22KJA310002 to H.Z.)。
文摘As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to predict the risk of obesity-associated cardiac dysfunction.By retrospectively analyzing the clinical characteristics of 5648 cardiac disease patients,we found that both the plasma level of high-density lipoprotein cholesterol(HDLC)and the blood monocyte count were significantly associated with impairment of the left ventricular ejection fraction(LVEF).Univariate and multivariate regression analyses revealed that the monocyte to HDL-C ratio(MHR)was a more powerful predictor of the risk of LVEF decline than either HDL-C or monocyte alone.Mediation analysis further revealed a mediating effect of a high MHR on the decline in obesity-associated cardiac systolic function.Collectively,our results demonstrate a superior role of MHR in predicting the risk of an obesityassociated decline in cardiac systolic function among routine metabolic/inflammatory markers.
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 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 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.
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.
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.
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: In order to detect the role of monocytes inHSV-2 infection, we studied the effect of herpes sim-plex Virus-2 infection on the production of tumor ne-crosis factor (TNF-σ), interleukin-6 (IL-6) secretedby monocytes. Methods: Monocytes were infected by HSV-2 (333Strain). Culture supernatants were collected at 1, 3,5, 7 days post-infection. The levels of TNF-α, IL-6were measured by enzyme-linked immunosorbent as-say (ELISA). Results: The levels of TNF-α secretion by mono-cytes significantly decreased on first day post-infection. The levels of IL-6 significantly decreasedon first and third days post-infection, and then gradu-ally increased to the control on seventh day post-infection. Conclusions: TNF-α and IL-6 production by mono-cytes was inhibited during HSV-2 infection. The pro-duction of cytokines may play an important role inherpes simplex viurs-2 pathogenicity and immunity.
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.
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Alzheimer＇s disease（AD） is a neurodegenerative disease characterized by extracellular amyloid beta（Aβ） deposition and intracellular neurofibrillary tangle formation.Monocyte is part of the innate immune system and can effectively remove dead cells and debris.It has been suggested that Aβ can recruit monocytes into brain in AD mice,resulting in restriction of cerebral amyloidosis.However,monocyte may act as a double-edged sword,either beneficial（e.g.,clearance of Aβ） or detrimental（e.g.,secretion of neurotoxic factors）.In addition,recent studies indicate that in AD patients,Aβ phagocytosis by monocytes is ineffective.The present review mainly summarized the current knowledge on monocytes and their potential roles in AD.
文摘Acute pancreatitis(AP) is an inflammatory condition of the pancreas caused by an imbalance in factors involved in maintaining cellular homeostasis.Earliest events in AP occur within acinar cells accompanied by other principal contributors to the inflammatory response i.e.the endothelial cells,immunocytes(granulocytes,monocytes/macrophages,lymphocytes) and neutrophils.Monocytes/macrophages are important inflammatory mediators,involved in the pathophysiology of AP,known to reside in the peritoneal cavity(in the vicinity of the pancreas) and in peripancreatic tissue.Recent studies suggested that impaired clearance of injured acini by macrophages is associated with an altered cytokine reaction which may constitute a basis for progression of AP.This review focuses on the role of monocytes/macrophages in progression of AP and discusses f indings on the inflammatory process involved.
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Background:As a surrogate marker of systemic inflammation,the lymphocyte-to-monocyte ratio(LMR) is an independent prognostic factor for various malignancies.This study investigated the prognostic significance of the pre-chemotherapy LMR in patients with previously untreated metastatic colorectal cancer(mCRC) receiving chemotherapy.Methods:The present study included newly diagnosed mCRC patients treated between January 2005 and December 2013 with FOLFOX chemotherapy,specifically oxaliplatin 180 mg/m^2 on day 1,with leucovorin 400 mg/m^2administered as a 2-hour infusion before the administration of 5-fluorouracil 400 mg/m^2 as an intravenous bolus injection,and 5-fluorouracil 2400 mg/m^2 as a 46-h infusion immediately after 5-fluorouracil bolus injection.The LMR was calculated as the absolute count of lymphocytes divided by the absolute count of monocytes.COX proportional hazards analysis was performed to evaluate the association of LMR with survival outcomes.Results:A total of 488 patients were included.Patients with high pre-chemotherapy LMR experienced significant improvements in progression-free survival(PFS,9.2 vs.7.6 months,P < 0.001) and overall survival(OS,19.4 vs.16.6 months,P < 0.001) compared with patients with low pre-chemotherapy LMR.Subsequent COX multivariate analysis showed that high pre-chemotherapy LMR(>3.11) was an independent favorable prognostic factor for PFS and OS.Additionally,patients whose LMR remained high(high-high subgroup),increased(low-high subgroup),or decreased(high-low subgroup) following chemotherapy showed better results in terms of PFS and OS than patients whose LMR remained low(low-low subgroup) after chemotherapy.Conclusions:For patients with previously untreated mCRC receiving FOLFOX chemotherapy,an elevated pre-chemotherapy LMR is an independent favorable prognostic factor for PFS and OS,and changes in the LMR before and after chemotherapy seem to predict the benefit of chemotherapy.
基金supported by the National Natural Science Foundation of China(31772876,41776151)Natural Science Foundation of Zhejiang Province(LZ18C190001,LR18C040001)+1 种基金Scientific Innovation Team Project of Ningbo(2015C110018)K.C.Wong Magna Fund in Ningbo University
文摘Macrophages exist in most tissues and play a variety of functions in vertebrates.Teleost fish species are found in most aquatic environments throughout the world and are quite diverse for a group of vertebrate animals.Due to whole genome duplication and en vironme ntal adaptati on,teleost monocytes/macrophages possess a variety of different functions and modulations compared with those of mammals.A deeper understanding of teleost monocytes/macrophages in the immune system will not only help develop teleost-specific methods of disease prevention but will also help improve our understanding of the various immune mechanisms in mammals.In this review,we summarize the differences in polarizati on and phagocytosis of teleost and mammalian macrophages to improve our understanding of the various immune mechanisms in vertebrates.
基金Supported by Kyung Hee University in 2006,No.KHU-20061216
文摘AIM:To measure the prognostic significance of absolute monocyte count/absolute lymphocyte count prognostic score(AMLPS) in patients with gastric cancer.METHODS:We retrospectively examined the combination of absolute monocyte count(AMC) and absolute lymphocyte count(ALC) as prognostic variables in a cohort of 299 gastric cancer patients who underwent surgical resection between 2006 and 2013 and were followed at a single institution.Both AMC and ALC were dichotomized into two groups using cut-off points determined by receiving operator characteristic curve analysis.An AMLPS was generated,which stratified patients into three risk groups:low risk(both low AMC and high ALC),intermediate risk(either high AMC or low ALC),and high risk(both high AMC and low ALC).The primary objective of the study was to validate the impact of AMLPS on both disease-free survival(DFS) and overall survival(OS),and the second objective was to assess the AMLPS as an independent prognostic factor for survival in comparison with known prognostic factors.RESULTS:Using data from the entire cohort,the most discriminative cut-off values of AMC and ALC selected on the receiver operating characteristic curve were 672.4/μL and 1734/μL for DFS and OS.AMLPS risk groups included 158(52.8%) patients in the lowrisk,128(42.8%) in the intermediate-risk,and 13(4.3%) in the high-risk group.With a median followup of 37.2 mo(range:1.7-91.4 mo),five-year DFS rates in the low-,intermediate-,and high-risk groups were 83.4%,78.7%,and 19.8%,respectively.And fiveyear OS rates in the low-,intermediate-,and high-risk groups were 89.3%,81.1%,and 14.4%,respectively.On multivariate analysis performed with patient- and tumor-related factors,we identified AMLPS,age,and pathologic tumor-node-metastasis stage as the most valuable prognostic factors impacting DFS and OS.CONCLUSION:AMLPS identified patients with a poor DFS and OS,and it was independent of age,pathologic stage,and various inflammatory markers.
基金Supported by the National Natural Science Foundation of China,No.81570543 and No.81560104
文摘BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death.However,the role of hepatocyte pyroptosis and its mechanisms of expanding inflammatory responses in ALF are unclear.AIM To investigate the role and mechanisms of GSDMD-mediated hepatocyte pyroptosis through in vitro and in vivo experiments.METHODS The expression of pyroptosis pathway-associated proteins in liver tissues from ALF patients and a hepatocyte injury model was examined by Western blot.GSDMD short hairpin RNA(shRNA)was used to investigate the effects of downregulation of GSDMD on monocyte chemotactic protein 1(MCP1)and its receptor CC chemokine receptor-2(CCR2)in vitro.For in vivo experiments,we used GSDMD knockout mice to investigate the role and mechanism of GSDMD in a D-galactose/lipopolysaccharide(D-Galn/LPS)-induced ALF mouse model.RESULTS The levels of pyroptosis pathway-associated proteins in liver tissue from ALF patients and a hepatocyte injury model increased significantly.The level of GSDMD-N protein increased most obviously(P<0.001).In vitro,downregulation of GSDMD by shRNA decreased the cell inhibition rate and the levels of MCP1/CCR2 proteins(P<0.01).In vivo,GSDMD knockout dramatically eliminated inflammatory damage in the liver and improved the survival of DGaln/LPS-induced ALF mice(P<0.001).Unlike the mechanism of immune cell pyroptosis that involves releasing interleukin(IL)-1βand IL-18,GSDMDmediated hepatocyte pyroptosis recruited macrophages via MCP1/CCR2 to aggravate hepatocyte death.However,this pathological process was inhibited after knocking down GSDMD.CONCLUSION GSDMD-mediated hepatocyte pyroptosis plays an important role in the pathogenesis of ALF,recruiting macrophages to release inflammatory mediators by upregulating MCP1/CCR2 and leading to expansion of the inflammatory responses.GSDMD knockout can reduce hepatocyte death and inflammatory responses,thus alleviating ALF.
