Introduction In this paper we present a case of monocytic sarcoma of the vertebral canal with a review of relevant literature references. According to the extensive morphological and immunohistochemical analyses, mono...Introduction In this paper we present a case of monocytic sarcoma of the vertebral canal with a review of relevant literature references. According to the extensive morphological and immunohistochemical analyses, monocytic sarcoma is one type of myeloid sarcoma, and can be diagnosed from extensive morphological and immunohistochemical analysis. Most cases of myeloid sarcomas are associated with acute, or chronic leukemia, or myelo-proliferative disorders, as well as monocytic sarcoma. Rarely, the tumors may be identified before the diagnosis of any hematological malignancy and most of them predict portend existing, or pending acute myeloid leukemia （AML）. Myeloid sarcomas may occur in almost every part of the bodyt, but spinal monocytic sarcomas are relatively uncommon.展开更多
Human Ehrlichiosis infrequently occurs and can be missed, but attention to history and a meticulous physical examination would raise the index for suspicion and is documented with proper investigations. We report the ...Human Ehrlichiosis infrequently occurs and can be missed, but attention to history and a meticulous physical examination would raise the index for suspicion and is documented with proper investigations. We report the first case of human monocytic Ehrlichiosis (HME) in a young female patient who lives in the Suburb city of Madaba, Jordan. She presented with fever, severe headache, skin rash, and confusion. She rapidly deteriorated and was admitted to our hospital. She had arrhythmias, convulsions, lapsed into a coma and respiratory failure and needed non-invasive ventilation. In addition to her clinical and epidemiological characteristics, the diagnosis was confirmed by the buffy coat. She had a swift response to oral doxycycline and was discharged home.展开更多
Background: Unique receptor involved in leukemogenesis is CD85k;an immuneglobulin receptor for immune tolerance, CD36 is glycoprotein mediates cellular adhesion and metastatic spread, CD14, CD15 considered common mono...Background: Unique receptor involved in leukemogenesis is CD85k;an immuneglobulin receptor for immune tolerance, CD36 is glycoprotein mediates cellular adhesion and metastatic spread, CD14, CD15 considered common monocytic markers. Aims: to investigate CD85k with monocytic lineage involved leukemia (MLIL) markers in leukemia pathogenesis and clinical presentation. Patients and Methods: 47 patients (32 diagnosed acute myeloid leukemia (AML);15 non-malignant hematological disease as a control), were included, aged from 2 to 80 years, all subjected to peripheral blood (P.Bl) and bone marrow (B.M) examination, immunophenotyping (IPT) using FASC Canto four color flow cytometer (FCM) Becton Dickenson (BD) USA, for CD13, CD33, MPO, HLA-DR, CD34, CD38, CD117, CD14, CD15 and CD36 the Mo Abs supplied by B.D Bioscience, and anti CD85k Mo Abs by Aveda de Coimbra Flamenco, reference No. 1399990130. Results: Frequency of CD85k is 19/32 (59.37%) of AML;14/14 (M4/M5) 100% positive CD85k, insignificant correlations of CD85k to sex, lymphadenopathy or organomegaly, platelets count and P.Bl blast (P > 0.05), significant to age 50,000 × 109/l, Hb 0.05). Conclusion: Although CD85k is MLIL associated marker, it is not correlated with other MLIL markers with frequency 100% in MLIL and 59.37% in AML, age predisposition is <35 years with no sex variation, significant correlation to progenitor and myeloid markers, it’s a crucial role in leukemogenesis biology, not in clinical presentations, considered good follow up predictor MLIL marker.展开更多
Background:The adhesion of monocytes to the endothelium following accumulation of low-density lipoprotein (LDL) in subendothelial spaces is an important step in the development of intimal hyperplasia in arterially imp...Background:The adhesion of monocytes to the endothelium following accumulation of low-density lipoprotein (LDL) in subendothelial spaces is an important step in the development of intimal hyperplasia in arterially implanted vein grafts and atherosclerosis in both animals and humans. However, it is not well known how serum factors affect the adhesion of monocytes. Methods: We have studied the effect of fetal calf serum (FCS), which we considered a source of LDL, on the adhesion of monocytes to endothelial cells (ECs) by using human monocytic THP-1 cells and both a monolayer of cultured bovine aortic endothelial cells (EC monoculture) and a co-culture with bovine aortic smooth muscle cells (EC-SMC co-culture). Results: It was found that the addition of FCS to the medium greatly affected the adhesion of THP-1 cells, and the higher the concentration of FCS in the medium, the greater the adhesion of THP-1 cells to endothelial cells. Adhesion of THP-1 cells to an EC-SMC co-culture was approximately twofold greater than that to an EC monoculture, and after adhering to endothelial cells, many THP-1 cells trans-migrated into the layer of smooth muscle cells. Conclusion: The results suggest that the elevation of the LDL (cholesterol) level in blood provides a favorable condition for the development of intimal hyperplasia and atherosclerosis by promoting the adhesion of monocytes to the endothelium and their subsequent migration into subendothelial spaces.展开更多
Objective: To identify the changes in the proteome of U937 cells infected with dengue virus(DENV).Methods: In this study, differentiated U937 cultures were infected with two DENV-2strains, one of which was associated ...Objective: To identify the changes in the proteome of U937 cells infected with dengue virus(DENV).Methods: In this study, differentiated U937 cultures were infected with two DENV-2strains, one of which was associated with dengue(DENV-2/NG) and the other one with severe dengue(DENV-2/16681), with the aim of determining the cellular proteomic profiles under different infection conditions. Cellular proteins were extracted and separated by two-dimensional electrophoresis, and those proteins with differential expression profiles were identified by mass spectrometry. The obtained results were correlated with cellular viability, the number of infectious viral particles, and the viral DNA/protein quantity.Results: In comparison with non-infected cultures, in the cells infected with the DENV-2/NG strain, nine proteins were expressed differentially(five were upregulated and four were downregulated); in those cultures infected with the DENV-2/16681 strain, six proteins were differentially expressed(two were downregulated and four were upregulated). The downregulated proteins included fatty acid-binding protein, heterogeneous nuclear ribonucleoprotein 1, protein disulfide isomerase, enolase 1, heat shock 70 k Da protein 9, phosphotyrosyl phosphatase, and annexin IV. The upregulated proteins included heat shock 90 k Da protein AA1, tubulin beta, enolase 1, pyruvate kinase,transaldolase and phospholipase C-alpha.Conclusions: Because the monocyte/macrophage lineage is critical for disease pathogenicity, additional studies on these proteins could provide a better understanding of the cellular response to DENV infection and could help identify new therapeutic targets against infection.展开更多
Periodontal diseases are chronic inflammation caused by particular types of bacteria and have been recognized as a cause of tooth loss in adults. These bacteria which invade periodontal tissue are phagocytosed mainly ...Periodontal diseases are chronic inflammation caused by particular types of bacteria and have been recognized as a cause of tooth loss in adults. These bacteria which invade periodontal tissue are phagocytosed mainly by monocytes and macrophages in this immune response, and will be presented to lymphocytes. Recently, therapies for regenerating periodontal tissues have been used extensively to treat periodontal disease, and in particular, enamel matrix derivative (EMD) is commonly used for such therapies in Japan. Amelogenin is a type of the extracellular matrix protein that accounts for 90% of the constituents of EMD. In this study, we carried out a detailed microarray analysis in order to evaluate a gene group involved in amelogenin stimuli in the human monocytic cell line U-937. Microarray analysis revealed that statistically significant changes were apparent in 273 genes (163 up-regulated and 110 down-regulated) subsequent to 4 h of amelogenin stimulation. The most highly enriched categories included “cell cycle”, “DNA replication”, and “DNA repair” in up-regulated annotation terms. On the other hand, “type I diabetes mellitus”, “allograft rejection”, and “graft versus host disease” were observed in down-regulated annotation terms. Specifically, the gene expression of major to compatibility complex (MHC) class I/II and CD80/86 was impaired in U937 cells after stimulation with amelogenin. In addition, the results of heat-map showed that the gene expression of inflammatory cytokine such as tumor necrosis factor (TFN), interleukin-18 (IL-18), and CXCL16 was markedly decreased after stimulation of monocytes with amelogenin. In conclusion, the findings of our study showed that by inducing monocyte growth through the suppression of the antigen-presenting ability of U937 cells, amelogenin may affect the immune responses of periodontal tissues originating from monocytes. Examining the effects of amelogenin on the transformation of macrophages differentiating from monocytes may establish a molecular basis for the anti-inflammatory effect of amelogenin in periodontal tissues.展开更多
Previously, we reported that M-CSF induced monocyte survival through the activation of Akt, p38MAPK and Erk1/2 kinases. Here, we found that Src family kinases were upstream of these kinases and played a central role i...Previously, we reported that M-CSF induced monocyte survival through the activation of Akt, p38MAPK and Erk1/2 kinases. Here, we found that Src family kinases were upstream of these kinases and played a central role in regulating M-CSF-induced monocyte survival. We observed that M-CSF promoted c-Src activation in monocytes and MDMs in a time-dependent manner. Src inhibitors reduced M-CSF-mediated phosphorylation of the M-CSF receptor (M-CSFR), Akt, Erk1/2, and p38 MAPK. We also observed that Src directly phosphorylated the M-CSFR. Notably, the inhibitors blocked phosphorylation of specific tyrosine residues within the M-CSFR. We further demonstrated that the Src inhibitor, PP2, attenuated M-CSF-induced NF-κB activation and M-CSF-induced monocyte survival. These findings indicated that Src family kinases mediate monocyte survival through the regulation of receptor phosphorylation and modulation of downstream signaling events. Thus, we predict that targeting Src family kinases may have therapeutic implication in inflammatory diseases.展开更多
Background and aims:Cancer cachexia is prevalent in various cancers and is associated with chemotherapy toxicity.However,limited data exist on the relationship between cachexia and immune-related adverse events(irAEs)...Background and aims:Cancer cachexia is prevalent in various cancers and is associated with chemotherapy toxicity.However,limited data exist on the relationship between cachexia and immune-related adverse events(irAEs).The aim of this study is to explore the correlation between cancer cachexia and irAEs and its possible mechanism.-Methods:A murine model of orthotopic hepatocellular carcinoma(HCC)with cachexia was developed to evaluate the impact of T-cell infiltration into multiple tumor-free organs on the occurrence of irAEs.Single-cell RNA sequencing of thymic stromal cells was performed.Additionally,patients with advanced cancers receiving anti-programmed cell death protein 1/ligand 1(PD-1/L1)antibody treatment were followed to investigate the relationship between cachexia and irAEs.Results:Inflammatory cell infiltration was observed in multiple tumor-free organs of cachexic HCC mice but not in non-cachexic controls.Immunofluorescence confirmed that the infiltrating cells included CD4^(+)and CD8^(+)T cells.Morphological assessment and hematoxylin-eosin staining revealed thymic atrophy in cachexic HCC mice.Single-cell RNA sequencing of thymic stromal cells showed a reduction in medullary thymic epithelial cells(mTECs)Ⅱ and Ⅲ in cachexic mice.Autoimmune regulator(Aire)downregulation was accompanied by decreased expression of tissue-restricted antigens in mTECs.T cells from cachexic HCC mice induced organ-specific inflammation and T-cell infiltration in multiple organs of tumor-free mice.Following anti-mouse PD-1 antibody treatment,the incidence of inflammation in multiple organs markedly increased in cachexic HCC mice and in tumor-free mice that had received T cells from the cachexic HCC mice.Flow cytometry and immunofluorescence analyses revealed enrichment of thymic monocytic myeloid-derived suppressor cells(M-MDSCs)in cachexic HCC mice.M-MDSCs infiltrated the thymus in cachexic mice with cancer,and they induced apoptosis of mTECs from tumor-free mice in vitro via nitric oxide production.Transfer of M-MDSCs led to inflammatory cell infiltration in multiple organs and thymic involution in tumor-free mice without affecting body weight.Sixty-four patients with advanced cancer receiving anti-PD-1/L1 therapy were enrolled.Patients who developed irAEs had higher levels of circulating M-MDSCs than those who did not.Moreover,patients with cachexia(body mass index(BMI)<20 kg/m^(2) or≥5% weight loss over the past 6 months)had elevated M-MDSC levels.Patients with both high M-MDSC levels and low BMI or weight loss≥5% experienced more irAEs(hazard ratio:2.333;95% confidence interval:1.231-4.423).Conclusions:M-MDSCs in cachexic mice induced mTEC apoptosis through nitric oxide production,impairing T-cell negative selection and promoting autoimmune T-cell infiltration into tumor-free organs.Cancer cachexia-related M-MDSCs may serve as predictive biomarkers for irAEs in patients with advanced cancer.展开更多
RNA-binding proteins(RBPs)are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes.The transcriptional regulatory ability of RBPs was indicated by the identificati...RNA-binding proteins(RBPs)are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes.The transcriptional regulatory ability of RBPs was indicated by the identification of chromatin-enriched RBPs(Che-RBPs).One of these proteins,KH-type splicing regulatory protein(KHSRP),is a multifunctional RBP that has been implicated in mRNA decay,alternative splicing,and miRNA biogenesis and plays an essential role in myeloid differentiation by facilitating the maturation of miR-129.In this study,we revealed that KHSRP regulates monocytic differentiation by regulating gene transcription and RNA splicing.KHSRP-occupied specific genomic sites in promoter and enhancer regions to regulate the expression of several hematopoietic genes through transcriptional activation and bound to pre-mRNA intronic regions to modulate alternative splicing during monocytic differentiation.Of note,KHSRP had co-regulatory effects at both the transcriptional and posttranscriptional levels on MOGOH and ADARB1.Taken together,our analyses revealed the dual DNA-and RNA-binding activities of KHSRP and have provided a paradigm to guide the analysis of other functional Che-RBPs in different biological systems.展开更多
Interleukin 34(IL-34)is a cytokine that shares the receptor with colony-stimulating factor 1(CSF-1).IL-34 is involved in a broad range of pathologic processes including cancer.We previously demonstrated that IL-34 pro...Interleukin 34(IL-34)is a cytokine that shares the receptor with colony-stimulating factor 1(CSF-1).IL-34 is involved in a broad range of pathologic processes including cancer.We previously demonstrated that IL-34 promoted the proliferation and colony formation of human acute monocytic leukemia(AMoL)cells.However,the mechanism has not been elucidated.Here,by analyzing the gene profiles of Molm13 and THP1 cells overexpressing IL-34(Molm13-IL-34 and THP1-IL-34),upregulation of the DNA damageinducible transcript 4(DDIT4)was detected in both series.Knockdown of DDIT4 effectively inhibited the proliferation,promoted apoptosis and colony formation in Molm13-IL-34 and THP1-IL-34 cells.Our results suggest that DDIT4 mediates the proliferationpromotive effect of IL-34 whereas does not mediate the promotive effect of IL-34 on colony formation in AMoL cells.展开更多
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
Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 tr...Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 trial)showed no additional advantage.The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment(TME)to aid in optimizing sequencing of combination therapies.Methods:The PD-RAD trial(ClinicalTrials.gov identifier:NCT03258788)aimed to enroll thirty NSCLC patients receiving radical-intent RT.Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry(mIHC)and high-dimensional mass cytometry(CyTOF),respectively.Results:Paired biopsies were collected from only three patients(Pts 1,3&4)and blood from four patients(Pts 1-4)before the study was closed early during the COVID-19 pandemic.Programmed Death-Ligand 1(PD-L1)expression in the TME was raised in Patient 1,who responded well to treatment,and unaltered in two patients with progressive disease.CyTOF analysis revealed elevated circulating classical monocytes,highest in the patient with a good response.Conclusions:This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint.The hypothesis-generating findings highlight PD-L1+macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response,but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.展开更多
Background:With a total of 1.46 million new cases and 396,792 deaths in 2022,prostate cancer is a major medical challenge around the world.Detecting and treating cancer at earlier,preferably localized stages can signi...Background:With a total of 1.46 million new cases and 396,792 deaths in 2022,prostate cancer is a major medical challenge around the world.Detecting and treating cancer at earlier,preferably localized stages can significantly increase survival rates.Here,a novel blood-based cancer screening as a pre-test in combination with targeted MRI imaging enabled the early diagnosis of prostate cancer.Case Description:We present the case of a 64-year-old man who participated in a prospective,interventional,multicenter cancer screening study where an immunological biopsy-based technique served as a part of a novel screening technique.This immunology technique represents a blood test exploiting two biomarkers,which may allow for the identification of individuals at an early stage of tumor development.Due to the elevated biomarker levels of Transketolase-like protein 1(TKTL1)and Apoptoic-associated cell population 10(Apo10),magnetic resonance imaging(MRI)was indicated for further clarification.A multiparametric MRI of the pelvis/prostate revealed an enlarged prostate gland and several suspicious lesions classified as Prostate Imaging Reporting and Data System(PI-RADS)4 and PI-RADS 5.In further assessments,both lesions were categorized as an acinar adenocarcinoma of the prostate(Gleason Score 6,International Society of Urological Pathology(ISUP)1,no perineural infiltration).After surgical resection,the tumor was classified histopathologically as an adenocarcinoma,pT2c pN0(0/7),L0,V0,Pn1,R0,Gleason score 7a,ISUP 2.Conclusions:The combination of the TKTL1/Apo10 blood test and subsequent imaging made it possible to detect a developing prostate carcinoma in a localized stage.All in all,this case report proves not just the ability but also the potential of the TKTL1/Apo10 blood test for early detection of(pre-)malignant lesions,which still present with a promising prospect for a cure.展开更多
Objective To investigate the expression of mRNA and proteins ofβ-catenin,TCF-4(ICAT)and Wnt signaling pathway-related genes in the monocytic differentiation of acute myeloid leukemia HL-60 cells induced by a new ster...Objective To investigate the expression of mRNA and proteins ofβ-catenin,TCF-4(ICAT)and Wnt signaling pathway-related genes in the monocytic differentiation of acute myeloid leukemia HL-60 cells induced by a new steroidal drug NSC67657.Methods Wright’s staining andα-NBE staining were used to observe the differentiation of HL-60 cells after 5 days of展开更多
Background:It has recently been recognized that serum vimentin is elevated in infectious diseases,and that vimentin plays a role in regulating neutrophils and macrophages associated inflammation.However,the mechanisms...Background:It has recently been recognized that serum vimentin is elevated in infectious diseases,and that vimentin plays a role in regulating neutrophils and macrophages associated inflammation.However,the mechanisms are unclear.This study was designed to explore the role of vimentin in regulating monocyte survival or apoptosis as well as inflammatory cytokine secretion in response to lipopolysaccharides(LPSs).Methods:A human monocytic leukemia cell line(THP-1)was transfected with vimentin-specific small interfering RNA(siRNA)or vimentin over-expressing plasmid.Apoptosis was assessed by TdT-mediated dUTP Nick-End Labeling(TUNEL)and DNA content assay.Immunoblotting was performed to detect apoptosis-associated proteins.Cytokines(interleukin[IL]-6,IL-10,and tumor necrosis factorα[TNF-α])were measured by enzyme-linked immuno sorbent assay.Two-way analysis of variance followed by Student's t test was used to compare means between different groups.Results:Suppression of vimentin in THP-1 cells resulted in increased apoptotic response in the presence of LPS,while overexpression of vimentin could prevent the cells from apoptosis in response to LPS.LPS alone or suppression of vimentin resulted in significant up-regulation of caspase-3(1.42±0.20 of LPS alone and 1.68±0.10 of vimentin suppression vs.control,t=5.21 and 10.28,respectively,P<0.05).In addition,pro-inflammatory cytokines(IL-6 and TNF-α)was significantly increased(IL-6:577.90±159.90 pg/day/105 cells vs.283.80±124.60 pg/day/105 cells of control,t=14.76,P<0.05;TNF-α:54.10±5.80 vs.17.10±0.10 pg/day/105 cells of control,t=6.71,P<0.05),while anti-inflammatory cytokine(IL-10)was significantly up-regulated in the THP-1 cells that over-expressed vimentin(140.9±17.2 pg/day/105 cells vs.undetectable in control cells).Contusions:In summary,the vimentin may regulate innate immunity through modulating monocytes viability as well as inflammatory response in sepsis through shifting the balance of pro-inflammatory and anti-inflammatory cytokines.展开更多
Dendritic cells （DCs） are professional antigen-presenting cells with the ability to induce primary T-cell responses. They are commonly produced by culturing monocytes in the presence of IL-4 and GM-CSF （cells produ...Dendritic cells （DCs） are professional antigen-presenting cells with the ability to induce primary T-cell responses. They are commonly produced by culturing monocytes in the presence of IL-4 and GM-CSF （cells produced in this manner are called conventional DCs）. Here we report the generation of two functionally distinct subsets of DCs derived from programmable cells of monocytic origin （PCMOs） in the presence of IL-3 or tumor necrosis factor alpha （TNF-e）. Monocytes were treated with macrophage colony-stimulating factor （M-CSF） and IL-3 for 6 days and then incubated with IL-4 and IL-3 （for IL-3 DCs） or with IL-4, GM-CSF and TNF-a （for TNF-a DCs） for 7 days. Monocytes were then loaded with tumor lysate （used as antigen）, and poly （I ： C） was added. The maturation factors TNF-e and monocyte conditioned medium （MCM） were added on days 4 and 5, respectively. The phenotypes of the DCs generated were characterized by flow cytometry, and the cells＇ phagocytic activities were measured using FITC-conjugated latex bead uptake. T-cell proliferation and cytokine release were assayed using MTT and commercially available ELISA kits, respectively. We found that either IL-3DCs or TNF-α DCs induce T-cell proliferation and cytokine secretion; the cytokine release pattern showed reduced IL-12/IL- 10 and IFN-γ/IL-4 ratios in both types of DCs and in DC-primed T-cell supernatant, respectively, which confirmed that the primed T cells were polarized toward aTh2-type immune response. We concluded that PCMOs are a new cell source that can develop into two functionally distinct DCs that both induce a Th2-type response in vitro. This modality can be used as a DC-based immunotherapy for autoimmune diseases.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
文摘Introduction In this paper we present a case of monocytic sarcoma of the vertebral canal with a review of relevant literature references. According to the extensive morphological and immunohistochemical analyses, monocytic sarcoma is one type of myeloid sarcoma, and can be diagnosed from extensive morphological and immunohistochemical analysis. Most cases of myeloid sarcomas are associated with acute, or chronic leukemia, or myelo-proliferative disorders, as well as monocytic sarcoma. Rarely, the tumors may be identified before the diagnosis of any hematological malignancy and most of them predict portend existing, or pending acute myeloid leukemia （AML）. Myeloid sarcomas may occur in almost every part of the bodyt, but spinal monocytic sarcomas are relatively uncommon.
文摘Human Ehrlichiosis infrequently occurs and can be missed, but attention to history and a meticulous physical examination would raise the index for suspicion and is documented with proper investigations. We report the first case of human monocytic Ehrlichiosis (HME) in a young female patient who lives in the Suburb city of Madaba, Jordan. She presented with fever, severe headache, skin rash, and confusion. She rapidly deteriorated and was admitted to our hospital. She had arrhythmias, convulsions, lapsed into a coma and respiratory failure and needed non-invasive ventilation. In addition to her clinical and epidemiological characteristics, the diagnosis was confirmed by the buffy coat. She had a swift response to oral doxycycline and was discharged home.
文摘Background: Unique receptor involved in leukemogenesis is CD85k;an immuneglobulin receptor for immune tolerance, CD36 is glycoprotein mediates cellular adhesion and metastatic spread, CD14, CD15 considered common monocytic markers. Aims: to investigate CD85k with monocytic lineage involved leukemia (MLIL) markers in leukemia pathogenesis and clinical presentation. Patients and Methods: 47 patients (32 diagnosed acute myeloid leukemia (AML);15 non-malignant hematological disease as a control), were included, aged from 2 to 80 years, all subjected to peripheral blood (P.Bl) and bone marrow (B.M) examination, immunophenotyping (IPT) using FASC Canto four color flow cytometer (FCM) Becton Dickenson (BD) USA, for CD13, CD33, MPO, HLA-DR, CD34, CD38, CD117, CD14, CD15 and CD36 the Mo Abs supplied by B.D Bioscience, and anti CD85k Mo Abs by Aveda de Coimbra Flamenco, reference No. 1399990130. Results: Frequency of CD85k is 19/32 (59.37%) of AML;14/14 (M4/M5) 100% positive CD85k, insignificant correlations of CD85k to sex, lymphadenopathy or organomegaly, platelets count and P.Bl blast (P > 0.05), significant to age 50,000 × 109/l, Hb 0.05). Conclusion: Although CD85k is MLIL associated marker, it is not correlated with other MLIL markers with frequency 100% in MLIL and 59.37% in AML, age predisposition is <35 years with no sex variation, significant correlation to progenitor and myeloid markers, it’s a crucial role in leukemogenesis biology, not in clinical presentations, considered good follow up predictor MLIL marker.
基金a Grant-in-Aid for Scientific Research onPriority Areas (No. 15086201) from the Ministry of Education, Culture, Sports, Science and Technology of Japanthe Health Bureauof Zhejiang Province (No. 2007B132), China
文摘Background:The adhesion of monocytes to the endothelium following accumulation of low-density lipoprotein (LDL) in subendothelial spaces is an important step in the development of intimal hyperplasia in arterially implanted vein grafts and atherosclerosis in both animals and humans. However, it is not well known how serum factors affect the adhesion of monocytes. Methods: We have studied the effect of fetal calf serum (FCS), which we considered a source of LDL, on the adhesion of monocytes to endothelial cells (ECs) by using human monocytic THP-1 cells and both a monolayer of cultured bovine aortic endothelial cells (EC monoculture) and a co-culture with bovine aortic smooth muscle cells (EC-SMC co-culture). Results: It was found that the addition of FCS to the medium greatly affected the adhesion of THP-1 cells, and the higher the concentration of FCS in the medium, the greater the adhesion of THP-1 cells to endothelial cells. Adhesion of THP-1 cells to an EC-SMC co-culture was approximately twofold greater than that to an EC monoculture, and after adhering to endothelial cells, many THP-1 cells trans-migrated into the layer of smooth muscle cells. Conclusion: The results suggest that the elevation of the LDL (cholesterol) level in blood provides a favorable condition for the development of intimal hyperplasia and atherosclerosis by promoting the adhesion of monocytes to the endothelium and their subsequent migration into subendothelial spaces.
基金Supported by the Administrative Department of Science,Technology,and Research-COLCIENCIAS(Projects 111549326092 and 111549326083)
文摘Objective: To identify the changes in the proteome of U937 cells infected with dengue virus(DENV).Methods: In this study, differentiated U937 cultures were infected with two DENV-2strains, one of which was associated with dengue(DENV-2/NG) and the other one with severe dengue(DENV-2/16681), with the aim of determining the cellular proteomic profiles under different infection conditions. Cellular proteins were extracted and separated by two-dimensional electrophoresis, and those proteins with differential expression profiles were identified by mass spectrometry. The obtained results were correlated with cellular viability, the number of infectious viral particles, and the viral DNA/protein quantity.Results: In comparison with non-infected cultures, in the cells infected with the DENV-2/NG strain, nine proteins were expressed differentially(five were upregulated and four were downregulated); in those cultures infected with the DENV-2/16681 strain, six proteins were differentially expressed(two were downregulated and four were upregulated). The downregulated proteins included fatty acid-binding protein, heterogeneous nuclear ribonucleoprotein 1, protein disulfide isomerase, enolase 1, heat shock 70 k Da protein 9, phosphotyrosyl phosphatase, and annexin IV. The upregulated proteins included heat shock 90 k Da protein AA1, tubulin beta, enolase 1, pyruvate kinase,transaldolase and phospholipase C-alpha.Conclusions: Because the monocyte/macrophage lineage is critical for disease pathogenicity, additional studies on these proteins could provide a better understanding of the cellular response to DENV infection and could help identify new therapeutic targets against infection.
文摘Periodontal diseases are chronic inflammation caused by particular types of bacteria and have been recognized as a cause of tooth loss in adults. These bacteria which invade periodontal tissue are phagocytosed mainly by monocytes and macrophages in this immune response, and will be presented to lymphocytes. Recently, therapies for regenerating periodontal tissues have been used extensively to treat periodontal disease, and in particular, enamel matrix derivative (EMD) is commonly used for such therapies in Japan. Amelogenin is a type of the extracellular matrix protein that accounts for 90% of the constituents of EMD. In this study, we carried out a detailed microarray analysis in order to evaluate a gene group involved in amelogenin stimuli in the human monocytic cell line U-937. Microarray analysis revealed that statistically significant changes were apparent in 273 genes (163 up-regulated and 110 down-regulated) subsequent to 4 h of amelogenin stimulation. The most highly enriched categories included “cell cycle”, “DNA replication”, and “DNA repair” in up-regulated annotation terms. On the other hand, “type I diabetes mellitus”, “allograft rejection”, and “graft versus host disease” were observed in down-regulated annotation terms. Specifically, the gene expression of major to compatibility complex (MHC) class I/II and CD80/86 was impaired in U937 cells after stimulation with amelogenin. In addition, the results of heat-map showed that the gene expression of inflammatory cytokine such as tumor necrosis factor (TFN), interleukin-18 (IL-18), and CXCL16 was markedly decreased after stimulation of monocytes with amelogenin. In conclusion, the findings of our study showed that by inducing monocyte growth through the suppression of the antigen-presenting ability of U937 cells, amelogenin may affect the immune responses of periodontal tissues originating from monocytes. Examining the effects of amelogenin on the transformation of macrophages differentiating from monocytes may establish a molecular basis for the anti-inflammatory effect of amelogenin in periodontal tissues.
文摘Previously, we reported that M-CSF induced monocyte survival through the activation of Akt, p38MAPK and Erk1/2 kinases. Here, we found that Src family kinases were upstream of these kinases and played a central role in regulating M-CSF-induced monocyte survival. We observed that M-CSF promoted c-Src activation in monocytes and MDMs in a time-dependent manner. Src inhibitors reduced M-CSF-mediated phosphorylation of the M-CSF receptor (M-CSFR), Akt, Erk1/2, and p38 MAPK. We also observed that Src directly phosphorylated the M-CSFR. Notably, the inhibitors blocked phosphorylation of specific tyrosine residues within the M-CSFR. We further demonstrated that the Src inhibitor, PP2, attenuated M-CSF-induced NF-κB activation and M-CSF-induced monocyte survival. These findings indicated that Src family kinases mediate monocyte survival through the regulation of receptor phosphorylation and modulation of downstream signaling events. Thus, we predict that targeting Src family kinases may have therapeutic implication in inflammatory diseases.
基金supported by the National Natural Science Foundation of China(No.82170749)the Guangdong Basic and Applied Basic Research Foundation(No.2022A1515010465 and 2022A1515012659)+1 种基金Guangzhou Science and Technology Program Key Projects(No.2023B01J1007)the Traditional Chinese Medicine Bureau of Guangdong Province,China(No.20241045).
文摘Background and aims:Cancer cachexia is prevalent in various cancers and is associated with chemotherapy toxicity.However,limited data exist on the relationship between cachexia and immune-related adverse events(irAEs).The aim of this study is to explore the correlation between cancer cachexia and irAEs and its possible mechanism.-Methods:A murine model of orthotopic hepatocellular carcinoma(HCC)with cachexia was developed to evaluate the impact of T-cell infiltration into multiple tumor-free organs on the occurrence of irAEs.Single-cell RNA sequencing of thymic stromal cells was performed.Additionally,patients with advanced cancers receiving anti-programmed cell death protein 1/ligand 1(PD-1/L1)antibody treatment were followed to investigate the relationship between cachexia and irAEs.Results:Inflammatory cell infiltration was observed in multiple tumor-free organs of cachexic HCC mice but not in non-cachexic controls.Immunofluorescence confirmed that the infiltrating cells included CD4^(+)and CD8^(+)T cells.Morphological assessment and hematoxylin-eosin staining revealed thymic atrophy in cachexic HCC mice.Single-cell RNA sequencing of thymic stromal cells showed a reduction in medullary thymic epithelial cells(mTECs)Ⅱ and Ⅲ in cachexic mice.Autoimmune regulator(Aire)downregulation was accompanied by decreased expression of tissue-restricted antigens in mTECs.T cells from cachexic HCC mice induced organ-specific inflammation and T-cell infiltration in multiple organs of tumor-free mice.Following anti-mouse PD-1 antibody treatment,the incidence of inflammation in multiple organs markedly increased in cachexic HCC mice and in tumor-free mice that had received T cells from the cachexic HCC mice.Flow cytometry and immunofluorescence analyses revealed enrichment of thymic monocytic myeloid-derived suppressor cells(M-MDSCs)in cachexic HCC mice.M-MDSCs infiltrated the thymus in cachexic mice with cancer,and they induced apoptosis of mTECs from tumor-free mice in vitro via nitric oxide production.Transfer of M-MDSCs led to inflammatory cell infiltration in multiple organs and thymic involution in tumor-free mice without affecting body weight.Sixty-four patients with advanced cancer receiving anti-PD-1/L1 therapy were enrolled.Patients who developed irAEs had higher levels of circulating M-MDSCs than those who did not.Moreover,patients with cachexia(body mass index(BMI)<20 kg/m^(2) or≥5% weight loss over the past 6 months)had elevated M-MDSC levels.Patients with both high M-MDSC levels and low BMI or weight loss≥5% experienced more irAEs(hazard ratio:2.333;95% confidence interval:1.231-4.423).Conclusions:M-MDSCs in cachexic mice induced mTEC apoptosis through nitric oxide production,impairing T-cell negative selection and promoting autoimmune T-cell infiltration into tumor-free organs.Cancer cachexia-related M-MDSCs may serve as predictive biomarkers for irAEs in patients with advanced cancer.
基金This work was supported by the National Key Research and Development Program of China(2019YFA0801800,2021YFA1102400,2019YFA0802600 and 2021YFA0805703)the National Natural Science Foundation of China(81530007,31900072,31725013,82022001,82122005,81970103 and 81970101)CAMS Innovation Fund for Medical Sciences[2021-I2M-1-019 and 2021-I2M-1-040].
文摘RNA-binding proteins(RBPs)are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes.The transcriptional regulatory ability of RBPs was indicated by the identification of chromatin-enriched RBPs(Che-RBPs).One of these proteins,KH-type splicing regulatory protein(KHSRP),is a multifunctional RBP that has been implicated in mRNA decay,alternative splicing,and miRNA biogenesis and plays an essential role in myeloid differentiation by facilitating the maturation of miR-129.In this study,we revealed that KHSRP regulates monocytic differentiation by regulating gene transcription and RNA splicing.KHSRP-occupied specific genomic sites in promoter and enhancer regions to regulate the expression of several hematopoietic genes through transcriptional activation and bound to pre-mRNA intronic regions to modulate alternative splicing during monocytic differentiation.Of note,KHSRP had co-regulatory effects at both the transcriptional and posttranscriptional levels on MOGOH and ADARB1.Taken together,our analyses revealed the dual DNA-and RNA-binding activities of KHSRP and have provided a paradigm to guide the analysis of other functional Che-RBPs in different biological systems.
基金This work was supported by grants 81770183 and 81970155 from the National Natural Science Foundation of China(NSFC)programs 2016-I2M-2-006 and 2017-I2M-1-015 from the CAMS Innovation Fund for Medical Sciences(CIFMS)+1 种基金State Key Laboratory of Experimental Hematology Research Grant(Z20-06)G.Z.is a recipient of the New Century Excellent Talents in University(NCET-08–0329).
文摘Interleukin 34(IL-34)is a cytokine that shares the receptor with colony-stimulating factor 1(CSF-1).IL-34 is involved in a broad range of pathologic processes including cancer.We previously demonstrated that IL-34 promoted the proliferation and colony formation of human acute monocytic leukemia(AMoL)cells.However,the mechanism has not been elucidated.Here,by analyzing the gene profiles of Molm13 and THP1 cells overexpressing IL-34(Molm13-IL-34 and THP1-IL-34),upregulation of the DNA damageinducible transcript 4(DDIT4)was detected in both series.Knockdown of DDIT4 effectively inhibited the proliferation,promoted apoptosis and colony formation in Molm13-IL-34 and THP1-IL-34 cells.Our results suggest that DDIT4 mediates the proliferationpromotive effect of IL-34 whereas does not mediate the promotive effect of IL-34 on colony formation in AMoL cells.
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the National Institute for Health and Care Research(NHR)Manchester Biomedical Research Centre(BRC)(NIHR203308,NIHR-BRC-1215-20007)Astra-Zeneca(ESR-14-10711)+2 种基金CRUK RadNet(C19941/A27801)TMI and CFF are the recipient of an NIHR Senior Investigator Award(NIHR205054 and NIHR205061)CTH is supported by the NIHR University College London Hospitals NHS Foundation Trust BRC,the City of London CRUK RadNet and the CRUK Lung Cancer Centre of Excellence.
文摘Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 trial)showed no additional advantage.The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment(TME)to aid in optimizing sequencing of combination therapies.Methods:The PD-RAD trial(ClinicalTrials.gov identifier:NCT03258788)aimed to enroll thirty NSCLC patients receiving radical-intent RT.Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry(mIHC)and high-dimensional mass cytometry(CyTOF),respectively.Results:Paired biopsies were collected from only three patients(Pts 1,3&4)and blood from four patients(Pts 1-4)before the study was closed early during the COVID-19 pandemic.Programmed Death-Ligand 1(PD-L1)expression in the TME was raised in Patient 1,who responded well to treatment,and unaltered in two patients with progressive disease.CyTOF analysis revealed elevated circulating classical monocytes,highest in the patient with a good response.Conclusions:This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint.The hypothesis-generating findings highlight PD-L1+macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response,but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.
基金This study was conducted and financed by the sponsor Zyagnum AG,https://www.zyagnum.com/Zyagnum AG has not received any grants,rather,this study was fully financed by Zyagnum AG.The authors S.B.and A.L.C.G.participated in the study as investigators.The University Hospital Hamburg-Eppendorf received reimbursement for the study from Zyagnum AG.
文摘Background:With a total of 1.46 million new cases and 396,792 deaths in 2022,prostate cancer is a major medical challenge around the world.Detecting and treating cancer at earlier,preferably localized stages can significantly increase survival rates.Here,a novel blood-based cancer screening as a pre-test in combination with targeted MRI imaging enabled the early diagnosis of prostate cancer.Case Description:We present the case of a 64-year-old man who participated in a prospective,interventional,multicenter cancer screening study where an immunological biopsy-based technique served as a part of a novel screening technique.This immunology technique represents a blood test exploiting two biomarkers,which may allow for the identification of individuals at an early stage of tumor development.Due to the elevated biomarker levels of Transketolase-like protein 1(TKTL1)and Apoptoic-associated cell population 10(Apo10),magnetic resonance imaging(MRI)was indicated for further clarification.A multiparametric MRI of the pelvis/prostate revealed an enlarged prostate gland and several suspicious lesions classified as Prostate Imaging Reporting and Data System(PI-RADS)4 and PI-RADS 5.In further assessments,both lesions were categorized as an acinar adenocarcinoma of the prostate(Gleason Score 6,International Society of Urological Pathology(ISUP)1,no perineural infiltration).After surgical resection,the tumor was classified histopathologically as an adenocarcinoma,pT2c pN0(0/7),L0,V0,Pn1,R0,Gleason score 7a,ISUP 2.Conclusions:The combination of the TKTL1/Apo10 blood test and subsequent imaging made it possible to detect a developing prostate carcinoma in a localized stage.All in all,this case report proves not just the ability but also the potential of the TKTL1/Apo10 blood test for early detection of(pre-)malignant lesions,which still present with a promising prospect for a cure.
文摘Objective To investigate the expression of mRNA and proteins ofβ-catenin,TCF-4(ICAT)and Wnt signaling pathway-related genes in the monocytic differentiation of acute myeloid leukemia HL-60 cells induced by a new steroidal drug NSC67657.Methods Wright’s staining andα-NBE staining were used to observe the differentiation of HL-60 cells after 5 days of
基金National Science Foundation for Young Scientists of China(No.81501707).
文摘Background:It has recently been recognized that serum vimentin is elevated in infectious diseases,and that vimentin plays a role in regulating neutrophils and macrophages associated inflammation.However,the mechanisms are unclear.This study was designed to explore the role of vimentin in regulating monocyte survival or apoptosis as well as inflammatory cytokine secretion in response to lipopolysaccharides(LPSs).Methods:A human monocytic leukemia cell line(THP-1)was transfected with vimentin-specific small interfering RNA(siRNA)or vimentin over-expressing plasmid.Apoptosis was assessed by TdT-mediated dUTP Nick-End Labeling(TUNEL)and DNA content assay.Immunoblotting was performed to detect apoptosis-associated proteins.Cytokines(interleukin[IL]-6,IL-10,and tumor necrosis factorα[TNF-α])were measured by enzyme-linked immuno sorbent assay.Two-way analysis of variance followed by Student's t test was used to compare means between different groups.Results:Suppression of vimentin in THP-1 cells resulted in increased apoptotic response in the presence of LPS,while overexpression of vimentin could prevent the cells from apoptosis in response to LPS.LPS alone or suppression of vimentin resulted in significant up-regulation of caspase-3(1.42±0.20 of LPS alone and 1.68±0.10 of vimentin suppression vs.control,t=5.21 and 10.28,respectively,P<0.05).In addition,pro-inflammatory cytokines(IL-6 and TNF-α)was significantly increased(IL-6:577.90±159.90 pg/day/105 cells vs.283.80±124.60 pg/day/105 cells of control,t=14.76,P<0.05;TNF-α:54.10±5.80 vs.17.10±0.10 pg/day/105 cells of control,t=6.71,P<0.05),while anti-inflammatory cytokine(IL-10)was significantly up-regulated in the THP-1 cells that over-expressed vimentin(140.9±17.2 pg/day/105 cells vs.undetectable in control cells).Contusions:In summary,the vimentin may regulate innate immunity through modulating monocytes viability as well as inflammatory response in sepsis through shifting the balance of pro-inflammatory and anti-inflammatory cytokines.
文摘Dendritic cells （DCs） are professional antigen-presenting cells with the ability to induce primary T-cell responses. They are commonly produced by culturing monocytes in the presence of IL-4 and GM-CSF （cells produced in this manner are called conventional DCs）. Here we report the generation of two functionally distinct subsets of DCs derived from programmable cells of monocytic origin （PCMOs） in the presence of IL-3 or tumor necrosis factor alpha （TNF-e）. Monocytes were treated with macrophage colony-stimulating factor （M-CSF） and IL-3 for 6 days and then incubated with IL-4 and IL-3 （for IL-3 DCs） or with IL-4, GM-CSF and TNF-a （for TNF-a DCs） for 7 days. Monocytes were then loaded with tumor lysate （used as antigen）, and poly （I ： C） was added. The maturation factors TNF-e and monocyte conditioned medium （MCM） were added on days 4 and 5, respectively. The phenotypes of the DCs generated were characterized by flow cytometry, and the cells＇ phagocytic activities were measured using FITC-conjugated latex bead uptake. T-cell proliferation and cytokine release were assayed using MTT and commercially available ELISA kits, respectively. We found that either IL-3DCs or TNF-α DCs induce T-cell proliferation and cytokine secretion; the cytokine release pattern showed reduced IL-12/IL- 10 and IFN-γ/IL-4 ratios in both types of DCs and in DC-primed T-cell supernatant, respectively, which confirmed that the primed T cells were polarized toward aTh2-type immune response. We concluded that PCMOs are a new cell source that can develop into two functionally distinct DCs that both induce a Th2-type response in vitro. This modality can be used as a DC-based immunotherapy for autoimmune diseases.
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.
