To the Editor,We have read the article by Gener-Ricos et al.titled"NPM1-mutated myeloid neoplasms are a unique entity not defined by bone marrow blast percentage",published in Cancer[1].This retrospective,cr...To the Editor,We have read the article by Gener-Ricos et al.titled"NPM1-mutated myeloid neoplasms are a unique entity not defined by bone marrow blast percentage",published in Cancer[1].This retrospective,cross-sectional pilot study provides valuable insights into the clinicopathological features and treatment outcomes of patients with NPM1-mutated myeloid neoplasms(MNs)with less than 20%bone marrow blasts[1].展开更多
Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,ven...Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,venetoclax plus azacitidine(VEN-AZA)or intensive chemotherapy(IC)]on post-transplant outcomes remains inconclusive.This multicenter,retrospective study compared the post-transplant outcomes between patients receiving VEN-AZA and those receiving IC before allo-HSCT.Methods:This study was based on the transplant database of TROPHY group.Consecutive adverse-risk AML patients receiving allo-HSCT from January 2021 to June 2023 were screened in five Chinese transplant centers.Patients were categorized into VEN-AZA group if they received venetoclax combined with azacitidine as first-line therapy followed by allo-HSCT.Patients who received first-line therapy consisting of a mainstay treatment of cytarabine and anthracycline followed by allo-HSCT were categorized into IC group.Results:In the total cohort,the 3-year probabilities of overall survival,leukemia-free survival,and event-free survival were better in the IC group than VEN-AZA group,particularly for patients with ASXL1 mutations or SF3B1 mutations.However,the survival of the VEN-AZA group was not superior to that of IC group in patients aged≥55 years or those with the hematopoietic cell transplantation-comorbidity index scores≥1 before allo-HSCT.After propensity score matching(median age:VEN-AZA group:57 years;IC group:55 years),only the probability of overall survival for the IC group was better than that of VEN-AZA group(93.6%vs.78.0%,P=0.034)at the 1-year follow-up;however,all of the other clinical outcomes were comparable between the VEN-AZA and IC groups.The TP53 mutation was independently associated with post-transplant relapse and survival.Conclusions:Our results suggest that IC remains the cornerstone of therapy,whereas VEN-AZA may also be used in younger patients and medically fit patients with adverse-risk AML who are receiving allo-HSCT in CR1.展开更多
Intracerebral hemorrhage(ICH)is a common severe emergency in neurosurgery,causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically,especially...Intracerebral hemorrhage(ICH)is a common severe emergency in neurosurgery,causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically,especially among patients with poor functional outcomes.ICH is often accompanied by decreased consciousness and limb dysfunction.This seriously affects patients’ability to live independently.Although rapid advances in neurosurgery have greatly improved patient survival,there remains insufficient evidence that surgical treatment significantly improves long-term outcomes.With in-depth pathophysiological studies after ICH,increasing evidence has shown that secondary injury after ICH is related to long-term prognosis and that the key to secondary injury is various immune-mediated neuroinflammatory reactions after ICH.In basic and clinical studies of various systemic inflammatory diseases,triggering receptor expressed on myeloid cells 1/2(TREM-1/2),and the TREM receptor family is closely related to the inflammatory response.Various inflammatory diseases can be upregulated and downregulated through receptor intervention.How the TREM receptor functions after ICH,the types of results from intervention,and whether the outcomes can improve secondary brain injury and the long-term prognosis of patients are unknown.An analysis of relevant research results from basic and clinical trials revealed that the inhibition of TREM-1 and the activation of TREM-2 can alleviate the neuroinflammatory immune response,significantly improve the long-term prognosis of neurological function in patients with cerebral hemorrhage,and thus improve the ability of patients to live independently.展开更多
A series of cyclopropane-1,1-diamide derivatives containing imidazo[1,2-a]pyridine were synthesized.The inhibitory effects of these compounds on FLT3-ITD kinase and their anti-proliferative activities against two acut...A series of cyclopropane-1,1-diamide derivatives containing imidazo[1,2-a]pyridine were synthesized.The inhibitory effects of these compounds on FLT3-ITD kinase and their anti-proliferative activities against two acute myeloid leukemia cell lines expressing FLT3-ITD were evaluated.With focused on the different substitutions of imidazo[1,2-a]pyridine,a preliminary exploration of the structure-activity relationship was conducted for 22 compounds.The results revealed that most compounds exhibited certain inhibitory effects on FLT3-ITD kinase with IC_(50) values below 0.5μmol·L^(-1).Among them,N-(4-fluorophenyl)-N-(4-(7-((2-morpholinoethyl)carbamoyl)imidazo[1,2-a]pyridine-3-carbonyl)phenyl)cyclopropane-1,1-dicarboxamide(12a)demonstrated the most potent FLT3-ITD kinase inhibitory activity and the strongest anti-proliferative effect on the MV4-11 and MOLM-13 cell lines expressing FLT3-ITD with IC50 values of 0.06 and 0.2μmol·L^(-1),respectively.Moreover,compound 12a did not exhibit anti-proliferative activity against cell lines without FLT3 mutations,such as THP-1,HCT-116,A549,HepG2,K562,and MCF-7,and it displayed non-cytotoxicity towards normal human renal tubular epithelial cells(HK-2),human liver progenitor cells(HepaRG),and HEK293(human embryonic kidney cells).Although 12a exhibits inferior inhibitory activity against FLT3-ITD kinase and anti-tumor cell proliferation compared to C abozantinib in this study,it can provide a reference for further research into FLT3-ITD inhibitors.展开更多
Venetoclax(Vene),a BCL-2 inhibitor,is widely used as a chemotherapeutic drug in acute myeloid leukemia(AML).However,its treatment specificity for leukemia cells is limited,often leading to side effects and treatment r...Venetoclax(Vene),a BCL-2 inhibitor,is widely used as a chemotherapeutic drug in acute myeloid leukemia(AML).However,its treatment specificity for leukemia cells is limited,often leading to side effects and treatment resistance.In this study,we utilized L-phenylalanine as an efficient nanocarrier to enhance the delivery of Vene,forming the complex Vene@8P6.This complex was then applied to AML mouse models and human AML cell lines.The in vitro analysis showed that THP-1 and HL60 cells rapidly absorbed the Vene@8P6 nanoparticles.This absorption resulted in severe DNA damage,increased reactive oxygen species(ROS)production,elevated apoptosis rates,and decreased cell proliferation compared to the administration of Vene alone.In vivo studies demonstrated that Vene@8P6 more efficiently targeted leukemia cells than normal hematopoietic cells within the bone marrow and other major organs in AML mice,as evidenced by bioluminescence imaging and flow cytometry analysis.Furthermore,Vene@8P6 treatment resulted in reduced drug side effects and improved therapeutic efficacy in AML mice.Overall,Vene@8P6 represents a novel and efficient therapeutic agent for AML,offering enhanced leukemia target specificity,reduced side effects,and improved treatment outcomes.展开更多
Liver fibrosis,a hallmark pathological endpoint of chronic aging-related liver diseases,remains a clinical challenge with limited therapeutic options.In healthy liver,myeloid cells constitute<5%of total hepatic imm...Liver fibrosis,a hallmark pathological endpoint of chronic aging-related liver diseases,remains a clinical challenge with limited therapeutic options.In healthy liver,myeloid cells constitute<5%of total hepatic immune cells,primarily comprising tissue-resident Kupffer cells.However,during aging or chronic injury,bone marrow-derived myeloid cell recruitment increases by two-to threefold in murine fibrotic models,reaching 15%-20% of intrahepatic immune populations.These infiltrating myeloid subsets exhibit functional plasticity,dynamically differentiating into pro-inflammatory mac-rophages or fibrosis-promoting Kupffer-like cells,contingent upon chemokine gradi-ents(e.g.,CCL2/CCR2 axis)and damage-associated molecular patterns(DAMPs).This review systematically examines the regulatory mechanisms of myeloid cells in liver fibrogenesis,with particular emphasis on their developmental origins,hepatic recruit-ment dynamics,functional heterogeneity,and pathogenic contributions to fibrosis.Furthermore,signaling pathways involving myeloid cells in liver fibrosis and therapeu-tic approaches modulating their differentiation and recruitment are discussed in this review.展开更多
Objective:To evaluate the immune function and safety of Venetoclax combined with Azacitidine in the treatment of elderly patients with acute myeloid leukemia(AML).Methods:Sixty-eight elderly AML patients who visited t...Objective:To evaluate the immune function and safety of Venetoclax combined with Azacitidine in the treatment of elderly patients with acute myeloid leukemia(AML).Methods:Sixty-eight elderly AML patients who visited the hospital from January 2021 to December 2024 were selected as samples and randomly divided into two groups.Group A was treated with Venetoclax and Azacitidine,while Group B was treated with Azacitidine alone.Immune indicators,inflammatory factors,tumor markers,and adverse reactions were compared between the two groups.Results:The levels of CD3+,CD4+,and CD8+in Group A were higher than those in Group B(P<0.05).The tumor necrosis factor-α(TNF-α)level in Group A was lower than that in Group B,while the interferon-γ(IFN-γ)level was higher(P<0.05).The levels of cyclooxygenase-2(COX-2),lactate dehydrogenase(LDH),and vascular endothelial growth factor(VEGF)in Group A were lower than those in Group B(P<0.05).The adverse reaction rate in Group A was lower than that in Group B(P<0.05).Conclusion:The combination of Venetoclax and Azacitidine in the treatment of elderly AML patients can improve immune function,inhibit inflammation,delay disease progression,and is safe and efficient.展开更多
The clinical efficacy of immunotherapy in acute myeloid leukemia(AML)remains significantly limited by early relapse and treatment-associated toxicities.This review examines recent advances in antibody-and cell-based i...The clinical efficacy of immunotherapy in acute myeloid leukemia(AML)remains significantly limited by early relapse and treatment-associated toxicities.This review examines recent advances in antibody-and cell-based immunotherapies for AML,focusing on established targets(CD33,CD123,and CLL1)as well as emerging targets(including CD7,CD70,CD38,and FLT3).Therapeutic modalities discussed include immunoconjugates,bispecific T-cell engagers and chimeric antigen receptor T(CAR-T)cells.Furthermore,we summarize the current challenges impeding the success of immunotherapy in AML and propose strategies to enhance its efficacy.These include combination therapies,structural optimization of CAR constructs,functional enhancement of CAR-T cells,identification of novel targets,and the development of next-generation cellular therapies.Collectively,these approaches aim to offer new insights for improving immunotherapeutic outcomes in AML.展开更多
BACKGROUND Acute myeloid leukemia(AML)is a complicated disease with uncontrolled hematopoietic precursor proliferation induced by various genetic alterations.Runt-related transcription factor-1(RUNX1)is commonly disru...BACKGROUND Acute myeloid leukemia(AML)is a complicated disease with uncontrolled hematopoietic precursor proliferation induced by various genetic alterations.Runt-related transcription factor-1(RUNX1)is commonly disrupted by chromosomal translocations in hematological malignancies.AIM To characterize RUNX1 gene rearrangements and copy number variations in newly diagnosed adult AML patients,with an emphasis on the impact of clinical and laboratory features on the outcome.METHODS Fluorescence in situ hybridization was used to test RUNX1 gene alterations in 77 newly diagnosed adult AML cases.NPM1,FLT3/ITD,FLT3/TKD,and KIT mutations were tested by PCR.Prognostic clinical and laboratory findings were studied in relation to RUNX1 alterations.RESULTS RUNX1 abnormalities were detected by fluorescence in situ hybridization in 41.6%of patients:20.8%had translocations,22.1%had amplification,and 5.2%had deletion.Translocations prevailed in AML-M2(P=0.019)with a positive expression of myeloperoxidase(P=0.031),whereas deletions dominated in M4 and M5 subtypes(P=0.008)with a positive association with CD64 expression(P=0.05).The modal chromosomal number was higher in cases having amplifications(P=0.007)and lower in those with deletions(P=0.008).RUNX1 abnormalities were associated with complex karyotypes(P<0.001)and were mutually exclusive of NPM1 mutations.After 44 months of follow-up,RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.CONCLUSION RUNX1 abnormalities were mutually exclusive of NPM1 mutations.RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.展开更多
Background:Acute Myeloid Leukemia(AML)is a highly aggressive clonal hematological malignancy with limited treatment options.This study aimed to evaluate the therapeutic potential of nigericin,a polyether ionophore der...Background:Acute Myeloid Leukemia(AML)is a highly aggressive clonal hematological malignancy with limited treatment options.This study aimed to evaluate the therapeutic potential of nigericin,a polyether ionophore derived from Streptomyces DASNCL-29,as a mitochondrial-targeted agent for AML treatment.Methods:Nigericin was isolated from Streptomyces DASNCL-29 and characterized via chromatography and NMR.Its cytotoxicity was tested in MOLM13(sensitive and venetoclax-resistant)and HL60(sensitive and cytarabine-resistant)cells using the MTT assay.Mitochondrial dysfunction was assessed by measuring reactive oxygen species(ROS),mitochondrial membrane potential(Δψm),and mitochondrial mass.Apoptosis was evaluated with Annexin V/PI assays and immunoblotting,while proteomic analysis was conducted using Liquid Chromatography-Tandem Mass Spectrometry(LC-MS/MS)to identify differentially regulated proteins.Results:Nigericin demonstrated potent cytotoxicity with IC50 values of 57.02 nM in MOLM13-sensitive,35.29 nM in MOLM13-resistant,20.49 nM in HL60-sensitive,and 1.197 nM in HL60-cytarabine-resistant cells.Apoptosis was confirmed by Annexin V/PI staining and caspase-3/PARP cleavage,along with MCL-1 downregulation.Mitochondrial dysfunction was evident from increased ROS,reducedΔψm,and decreased mitochondrial mass.Proteomic profiling identified 264 dysregulated proteins,including a 3.8-fold upregulation of Succinate Dehydrogenase[Ubiquinone]Flavoprotein Subunit A(SDHA).Conclusion:Nigericin induces apoptosis in AML cells by disrupting mitochondrial function and enhancing oxidative stress.Its nanomolar potency highlights the need for further mechanistic studies and in vivo evaluations to explore its potential in AML treatment.展开更多
BACKGROUND The prognosis for acute myeloid leukemia(AML)remains poor,underscoring the need for a deeper understanding of its underlying molecular mechanisms.AIM To assess the significance of SOX11 gene expression in t...BACKGROUND The prognosis for acute myeloid leukemia(AML)remains poor,underscoring the need for a deeper understanding of its underlying molecular mechanisms.AIM To assess the significance of SOX11 gene expression in the clinical features,response to treatment,and survival outcomes of adult patients with AML.METHODS This retrospective study enrolled 102 adults with AML.SOX11 gene expression in bone marrow samples was measured using real-time PCR.Data were correlated to the patients’clinical features,response to treatment,and survival rates.RESULTS Increased SOX11 expression was significantly associated with the presence of the FLT3-ITD mutation(P<0.001),the FAB-M2 subtype(P=0.008),and cytogenetic abnormalities(P=0.011).However,no significant association was found between SOX11 expression and other clinical laboratory parameters,complete remission,disease-free survival,or overall survival.CONCLUSION SOX11 expression may serve as a marker to identify specific subsets of AML patients who could benefit from intensive targeted chemotherapy.展开更多
Myristica is a classic traditional Chinese medicine widely used for leukemia treatment.However,its main active ingredients and underlying mechanisms of action remain poorly understood.In this study,we comprehensively ...Myristica is a classic traditional Chinese medicine widely used for leukemia treatment.However,its main active ingredients and underlying mechanisms of action remain poorly understood.In this study,we comprehensively investigated the mechanisms by which Myristica exerted effects on radiation-induced myeloid leukemia(RIML)using molecular docking and network pharmacology.The active ingredients in Myristica were further identified via TCMSP database,potential Myristica-related targets were extracted from GEO,GeneCards,OMIM,and DisGeNET databases,a protein-protein interaction(PPI)network was constructed to screen key targets(followed by GO and KEGG enrichment analyses),and finally the binding affinity between active compounds and key targets was verified.The screening results identified 9 active substances,including Kudos,isoguaiacin,galbacin,and others.Topological analysis of the PPI network revealed that PARP1,ESR1,MTOR,MDM2,HIF1A,and ALB were key targets.GO enrichment analysis showed that these targets were mainly involved in biological processes such as DNA repair,cell cycle regulation,apoptosis,and oxidative stress response.KEGG pathway enrichment analysis indicated that Myristica might exert anti-leukemia effects by regulating signaling pathways such as PI3K-Akt,mTOR,and HIF-1.展开更多
Non-alcoholic fatty liver disease(NAFLD)is a progressive disease.Without effective interventions,NAFLD can gradually develop to non-alcoholic steatohepatitis,fatty liver fibrosis,liver cirrhosis and even hepatocellula...Non-alcoholic fatty liver disease(NAFLD)is a progressive disease.Without effective interventions,NAFLD can gradually develop to non-alcoholic steatohepatitis,fatty liver fibrosis,liver cirrhosis and even hepatocellular carcinoma.It is still to investigate the precise molecular mechanism behind the pathophysiology of NAFLD.Triggering receptor expressed on myeloid cells 2(TREM2)can sense tissue injury and mediate immune remodeling,thereby inducing phagocytosis,lipid metabolism,and metabolic transfer,promoting cell survival and combating inflammatory activation.NAFLD might develop as a result of TREM2's regulatory role.We here briefly summarize the biological characteristics of TREM2 and its functions in the disease progression of NAFLD.Moreover,we propose to broaden the therapeutic strategy for NAFLD by targeting TREM2.展开更多
Acute myeloid leukemia(AML)is a heterogeneous malignancy with heterogeneity,and 35%-45%of patients are refractory to first-line treatment[e.g.,standard chemotherapy and hematopoietic stem cell transplantation(HSCT)]or...Acute myeloid leukemia(AML)is a heterogeneous malignancy with heterogeneity,and 35%-45%of patients are refractory to first-line treatment[e.g.,standard chemotherapy and hematopoietic stem cell transplantation(HSCT)]or relapse after treatment.Patients with refractory/relapsed(R/R)AML have a dismal prognosis and are ralely cured with conventional treatment(1),indicating the need for new therapeutic strategies to improve outcomes.展开更多
Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underp...Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.展开更多
Background:The role of 1,25-dihydroxyvitamin D3(1,25-(OH)_(2)D_(3))in cancer prevention and treatment is an emerging topic of interest.However,its effects on the stemness of acute myeloid leukemia(AML)cells are poorly...Background:The role of 1,25-dihydroxyvitamin D3(1,25-(OH)_(2)D_(3))in cancer prevention and treatment is an emerging topic of interest.However,its effects on the stemness of acute myeloid leukemia(AML)cells are poorly understood.Methods:The proliferation and differentiation of AML cells(HL60 and NB4)were investigated by the CCK-8 assay,immunocytochemical staining,and flow cytometry.The abilities of HL60 and NB4 cells to form spheres were examined by the cell sphere formation assay.In addition,the levels of stemness-associated markers(SOX2,Nanog,OCT4,and c-Myc)in HL60 and NB4 cells were measured by western blotting and quantitative real-time polymerase chain reaction.Moreover,we obtainedβ-catenin-interacting protein 1(ICAT)-knockout and ICAT-overexpressing HL-60 cells using gene editing and lentiviral infection techniques and investigated the role of ICAT in modulating the stemness-inhibiting effects of 1,25-(OH)_(2)D_(3)using the aforementioned experimental methods.Finally,we validated our findings in vivo using NOD/SCID mice.Results:1,25-(OH)_(2)D_(3)inhibited the proliferation and stemness of AML cells(HL60 and NB4)and induced their differentiation into monocytes.Additionally,the knockdown of ICAT in HL60 cells attenuated the inhibitory effects of 1,25-(OH)_(2)D_(3)on proliferation and stemness and suppressed the expression of stemness markers.Conversely,overexpression of ICAT enhanced the aforementioned inhibitory effects of 1,25-(OH)_(2)D_(3).Consistently,in NOD/SCID mice,1,25-(OH)_(2)D_(3)suppressed tumor formation by HL-60 cells,and the effects of ICAT knockdown or overexpression on 1,25-(OH)_(2)D_(3) aligned with the in vitro findings.Conclusion:1,25-(OH)_(2)D_(3)inhibits AML cell stemness,possibly through modulation of the ICAT-mediated Wnt/β-catenin signaling pathway.展开更多
BACKGROUND Myeloid sarcoma(MS),also referred to as granulocytic sarcoma or chloroma,is a rare type of extramedullary malignant tumor.MS comprises primitive granulocytic precursor cells that play a key role in the earl...BACKGROUND Myeloid sarcoma(MS),also referred to as granulocytic sarcoma or chloroma,is a rare type of extramedullary malignant tumor.MS comprises primitive granulocytic precursor cells that play a key role in the early stages of white blood cell development.Notably,the occurrence of this tumor in the gingiva is rare.CASE SUMMARY The present study reported the case of MS with gingival swelling in the maxillary region,with aleukemic presentation in a 32-year-old male patient.Following two courses of chemotherapy,computed tomography of the region demonstrated complete clearance of the tumor.At the 12-month follow-up appointment,the patient was in a stable condition with the absence of progression.The etiology,clinical features,diagnosis,and relevant treatment of MS are discussed in the present study.CONCLUSION Diagnosis of MS may be confirmed following histological and immunohistochemical examinations.展开更多
Myeloid sarcoma(MS)is a rare neoplasm characterized by the proliferation of immature myeloid precursor cells outside the bone marrow.The pathogenesis of MS is complex and not completely understood.Moreover,it develops...Myeloid sarcoma(MS)is a rare neoplasm characterized by the proliferation of immature myeloid precursor cells outside the bone marrow.The pathogenesis of MS is complex and not completely understood.Moreover,it develops in any extramedullary site of the body.In this editorial,we discuss the article published by Li et al,which presents a clinical case involving a 32-year-old man who exhibited gingival inflammation in the maxillary region.It was initially diagnosed as periodontal disease.However,clinical evaluation revealed a firm,grayishwhite mass which underscored the need for comprehensive diagnostics to distinguish MS from other oral conditions.This article emphasizes the different clinical presentations of similar case studies in the literature,and highlights the difficulty in diagnosing oral MS due to its rarity and variability in clinical manifestation.The treatment of MS depends on the clinical presentation,tumor location,and the patient's response to conventional therapies.The various therapeutic options currently available are analyzed and discussed.Early intervention and multidisciplinary management are crucial for improving treatment outcomes.Increased awareness and education about the various clinical presentations of MS lead to earlier diagnosis and timely treatment,thereby enhancing patients'survival and quality of life.Continued research is essential for optimizing therapeutic strategies and addressing the challenges presented by this rare neoplasm.展开更多
OBJECTIVE:To investigate the effect of Taohong Siwu decoction(桃红四物汤,TSD)on atherosclerosis in rats as well as investigate the underlying mechanism based on molecular docking.METHODS:Sixty healthy male Sprague-Daw...OBJECTIVE:To investigate the effect of Taohong Siwu decoction(桃红四物汤,TSD)on atherosclerosis in rats as well as investigate the underlying mechanism based on molecular docking.METHODS:Sixty healthy male Sprague-Dawley rats were randomly divided into 6 groups with 10 rats in each group:control group,model group,atorvastatin group(AT,2.0 mg/kg),and TSD groups(20,10,5 g/kg)after 7 d of acclimation.The model of atherosclerosis was successfully established except the control group by high fat diet(HFD)and vitamin D2.Biochemical analyzers were used to detect the levels of triglyceride(TG),total cholestero(TC),low density lipoprotein-cholesterol(LDLC)and high density lipid-cholesterol(HDL-C)in blood lipid.The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1β)were determined by enzyme-linked immunosorbent assay.Sudan IV staining and Hematoxylin and eosin staining(HE staining)were performed to observe the pathological changes in aortic tissue.Molecular docking technology was used to predict the best matching between the main components of TSD and the target proteins.The expression of target proteins was further detected by quantitative real time polymerase chain reaction(q RTPCR)and Western blot analysis.RESULTS:The results showed that TSD restricted atherosclerosis development and decreased the inflammatory cytokines in plasma.Molecular docking results predicted that the main components of TSD showed a strong binding ability with toll-like receptor(TLR4),myeloid differentiation primary response protein 88(My D88),and nuclear factor kappa-B(NF-κB).The results of q RT-PCR and Western blot analysis showed that the m RNA and protein expressions of TLR4,My D88 and NF-κB p65 in the aorta were reduced in atorvastatin group and TSD group.CONCLUSIONS:TSD can ameliorate atherosclerosis in rats,and the underlying mechanism is supposed be related to the suppression of inflammatory response by regulating TLR4/My D88/NF-κB signal pathway.展开更多
OBJECTIVE: To explore whether moxibustion exerts therapeutic effects on rheumatoid arthritis(RA) by regulating the expression of T-cell immunoglobulin and mucin-containing protein-3(TIM-3) and subsequently modulating ...OBJECTIVE: To explore whether moxibustion exerts therapeutic effects on rheumatoid arthritis(RA) by regulating the expression of T-cell immunoglobulin and mucin-containing protein-3(TIM-3) and subsequently modulating the macrophage M1 polarization toll-like receptor 4(TLR4)-myeloid differentiation factor 88(My D88)-nuclear factor kappa B(NF-κB) signaling pathway. METHODS: We utilized moxibustion treatment in RA rat models using the Zusanli(ST36) and Shenshu(BL23) acupoints. Hematoxylin and eosin(HE) staining was used to observe the pathological changes of the synovial tissue under a section light microscope, and pathological scoring was performed according to the grading standard of the degree of synovial tissue disease. Enzyme-linked immunosorbent assay(ELISA) was applied to verify the efficacy of moxibustion in reducing inflammation. Quantitative real-time polymerase chain reaction(q RTPCR) was used to detect the expression of the TIM-3/TLR4-My D88-NF-κB signaling pathway-related molecules, and Western blot was used to detect the contents of synovial NF-κB. RESULTS: We established the Freund's complete adjuvant(FCA)-induced RA model in rats. The expression level of M1 polarization signaling pathway TLR4-My D88-NF-κB and the inflammatory factors interleukin-12(IL-12), tumor necrosis factor alpha(TNF-α), and tumor necrosis factor beta(TNF-β) were significantly increased in the RA model. After moxibustion treatment, the expression level of TLR4-My D88-NF-κB was significantly decreased, and the inflammatory factors IL-12, TNF-α, and TNF-β were decreased, but the expression level was significantly increased in the RA model. When TIM-3 expression was inhibited, the expression level of TLR4-My D88-NF-κB, and the inflammatory factors IL-12, TNF-α, and TNF-β were not suppressed, even after moxibustion treatment. CONCLUSIONS: Moxibustion regulates the key target TIM-3 by acting on the Zusanli(ST36) and Shenshu(BL23) points, thereby inhibiting the M1 polarization of macrophages;that is, it inhibits the TLR4-My D88-NF-κB signaling pathway, and finally achieves alleviation of pathological changes and anti-inflammatory effects.展开更多
文摘To the Editor,We have read the article by Gener-Ricos et al.titled"NPM1-mutated myeloid neoplasms are a unique entity not defined by bone marrow blast percentage",published in Cancer[1].This retrospective,cross-sectional pilot study provides valuable insights into the clinicopathological features and treatment outcomes of patients with NPM1-mutated myeloid neoplasms(MNs)with less than 20%bone marrow blasts[1].
基金supported by the Beijing Natural Science Foundation(No.Z230016)the National Key Research and Development Program of China(No.2022YFC 2502606)+4 种基金the Major Program of the National Natural Science Foundation of China(No.82293630)the Peking University Medicine Fund for the World’s Leading Discipline or Discipline Cluster Development(No.71003Y3035)the Plan Project of Tongzhou Municipal Science and Technology(No.KJ2024CX045)the National Natural Science Foundation of China(No.82170208)the Fundamental Research Funds for the Central Universities。
文摘Objective:Adverse-risk acute myeloid leukemia(AML)patients should receive allogeneic hematopoietic stem cell transplantation(allo-HSCT)at first complete remission(CR1).However,the influence of prior therapies[i.e.,venetoclax plus azacitidine(VEN-AZA)or intensive chemotherapy(IC)]on post-transplant outcomes remains inconclusive.This multicenter,retrospective study compared the post-transplant outcomes between patients receiving VEN-AZA and those receiving IC before allo-HSCT.Methods:This study was based on the transplant database of TROPHY group.Consecutive adverse-risk AML patients receiving allo-HSCT from January 2021 to June 2023 were screened in five Chinese transplant centers.Patients were categorized into VEN-AZA group if they received venetoclax combined with azacitidine as first-line therapy followed by allo-HSCT.Patients who received first-line therapy consisting of a mainstay treatment of cytarabine and anthracycline followed by allo-HSCT were categorized into IC group.Results:In the total cohort,the 3-year probabilities of overall survival,leukemia-free survival,and event-free survival were better in the IC group than VEN-AZA group,particularly for patients with ASXL1 mutations or SF3B1 mutations.However,the survival of the VEN-AZA group was not superior to that of IC group in patients aged≥55 years or those with the hematopoietic cell transplantation-comorbidity index scores≥1 before allo-HSCT.After propensity score matching(median age:VEN-AZA group:57 years;IC group:55 years),only the probability of overall survival for the IC group was better than that of VEN-AZA group(93.6%vs.78.0%,P=0.034)at the 1-year follow-up;however,all of the other clinical outcomes were comparable between the VEN-AZA and IC groups.The TP53 mutation was independently associated with post-transplant relapse and survival.Conclusions:Our results suggest that IC remains the cornerstone of therapy,whereas VEN-AZA may also be used in younger patients and medically fit patients with adverse-risk AML who are receiving allo-HSCT in CR1.
基金Supported by Shanxi Provincial Key Research and Development Plan Project,No.2020ZDLSF01-02Doctor Foundation of the Second Affiliated Hospital of Xi’an Medical University,No.X2Y-R11.
文摘Intracerebral hemorrhage(ICH)is a common severe emergency in neurosurgery,causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically,especially among patients with poor functional outcomes.ICH is often accompanied by decreased consciousness and limb dysfunction.This seriously affects patients’ability to live independently.Although rapid advances in neurosurgery have greatly improved patient survival,there remains insufficient evidence that surgical treatment significantly improves long-term outcomes.With in-depth pathophysiological studies after ICH,increasing evidence has shown that secondary injury after ICH is related to long-term prognosis and that the key to secondary injury is various immune-mediated neuroinflammatory reactions after ICH.In basic and clinical studies of various systemic inflammatory diseases,triggering receptor expressed on myeloid cells 1/2(TREM-1/2),and the TREM receptor family is closely related to the inflammatory response.Various inflammatory diseases can be upregulated and downregulated through receptor intervention.How the TREM receptor functions after ICH,the types of results from intervention,and whether the outcomes can improve secondary brain injury and the long-term prognosis of patients are unknown.An analysis of relevant research results from basic and clinical trials revealed that the inhibition of TREM-1 and the activation of TREM-2 can alleviate the neuroinflammatory immune response,significantly improve the long-term prognosis of neurological function in patients with cerebral hemorrhage,and thus improve the ability of patients to live independently.
文摘A series of cyclopropane-1,1-diamide derivatives containing imidazo[1,2-a]pyridine were synthesized.The inhibitory effects of these compounds on FLT3-ITD kinase and their anti-proliferative activities against two acute myeloid leukemia cell lines expressing FLT3-ITD were evaluated.With focused on the different substitutions of imidazo[1,2-a]pyridine,a preliminary exploration of the structure-activity relationship was conducted for 22 compounds.The results revealed that most compounds exhibited certain inhibitory effects on FLT3-ITD kinase with IC_(50) values below 0.5μmol·L^(-1).Among them,N-(4-fluorophenyl)-N-(4-(7-((2-morpholinoethyl)carbamoyl)imidazo[1,2-a]pyridine-3-carbonyl)phenyl)cyclopropane-1,1-dicarboxamide(12a)demonstrated the most potent FLT3-ITD kinase inhibitory activity and the strongest anti-proliferative effect on the MV4-11 and MOLM-13 cell lines expressing FLT3-ITD with IC50 values of 0.06 and 0.2μmol·L^(-1),respectively.Moreover,compound 12a did not exhibit anti-proliferative activity against cell lines without FLT3 mutations,such as THP-1,HCT-116,A549,HepG2,K562,and MCF-7,and it displayed non-cytotoxicity towards normal human renal tubular epithelial cells(HK-2),human liver progenitor cells(HepaRG),and HEK293(human embryonic kidney cells).Although 12a exhibits inferior inhibitory activity against FLT3-ITD kinase and anti-tumor cell proliferation compared to C abozantinib in this study,it can provide a reference for further research into FLT3-ITD inhibitors.
基金the National Natural Science Foundation of China(No.52173150 to J.Wu)the National Natural Science Foundation of China(No.82370164 to C.Chen)+5 种基金Guangzhou Science and Technology Program City-University Joint Funding Project(No.2023A03J0001 to J.Wu)the Affiliated Qingyuan Hospital of Guangzhou Medical University Open Project Fund(No.202301–211 to J.Wu)Sanming Project of Medicine in Shenzhen(No.SZSM201911004 to D.Lin and M.Zhao)National Natural Science Foundation of China(No.92268205 to D.Lin)Doctoral Scientific Research Foundation of Changzhi Medical College,China(to Z.Zhao)Post-doctoral Science Foundation(No.2022M723670 to L.Wang)。
文摘Venetoclax(Vene),a BCL-2 inhibitor,is widely used as a chemotherapeutic drug in acute myeloid leukemia(AML).However,its treatment specificity for leukemia cells is limited,often leading to side effects and treatment resistance.In this study,we utilized L-phenylalanine as an efficient nanocarrier to enhance the delivery of Vene,forming the complex Vene@8P6.This complex was then applied to AML mouse models and human AML cell lines.The in vitro analysis showed that THP-1 and HL60 cells rapidly absorbed the Vene@8P6 nanoparticles.This absorption resulted in severe DNA damage,increased reactive oxygen species(ROS)production,elevated apoptosis rates,and decreased cell proliferation compared to the administration of Vene alone.In vivo studies demonstrated that Vene@8P6 more efficiently targeted leukemia cells than normal hematopoietic cells within the bone marrow and other major organs in AML mice,as evidenced by bioluminescence imaging and flow cytometry analysis.Furthermore,Vene@8P6 treatment resulted in reduced drug side effects and improved therapeutic efficacy in AML mice.Overall,Vene@8P6 represents a novel and efficient therapeutic agent for AML,offering enhanced leukemia target specificity,reduced side effects,and improved treatment outcomes.
基金National Key Research and Development Program of China,Grant/Award Number:2021YFA0804903National Natural Science Foundation of China,Grant/Award Number:882171545 and 91949125The Start-up Fund for Distinguished Research Fellows,the International Institute of Health Medicine,Zhejiang University,Grant/Award Number:Q22005。
文摘Liver fibrosis,a hallmark pathological endpoint of chronic aging-related liver diseases,remains a clinical challenge with limited therapeutic options.In healthy liver,myeloid cells constitute<5%of total hepatic immune cells,primarily comprising tissue-resident Kupffer cells.However,during aging or chronic injury,bone marrow-derived myeloid cell recruitment increases by two-to threefold in murine fibrotic models,reaching 15%-20% of intrahepatic immune populations.These infiltrating myeloid subsets exhibit functional plasticity,dynamically differentiating into pro-inflammatory mac-rophages or fibrosis-promoting Kupffer-like cells,contingent upon chemokine gradi-ents(e.g.,CCL2/CCR2 axis)and damage-associated molecular patterns(DAMPs).This review systematically examines the regulatory mechanisms of myeloid cells in liver fibrogenesis,with particular emphasis on their developmental origins,hepatic recruit-ment dynamics,functional heterogeneity,and pathogenic contributions to fibrosis.Furthermore,signaling pathways involving myeloid cells in liver fibrosis and therapeu-tic approaches modulating their differentiation and recruitment are discussed in this review.
文摘Objective:To evaluate the immune function and safety of Venetoclax combined with Azacitidine in the treatment of elderly patients with acute myeloid leukemia(AML).Methods:Sixty-eight elderly AML patients who visited the hospital from January 2021 to December 2024 were selected as samples and randomly divided into two groups.Group A was treated with Venetoclax and Azacitidine,while Group B was treated with Azacitidine alone.Immune indicators,inflammatory factors,tumor markers,and adverse reactions were compared between the two groups.Results:The levels of CD3+,CD4+,and CD8+in Group A were higher than those in Group B(P<0.05).The tumor necrosis factor-α(TNF-α)level in Group A was lower than that in Group B,while the interferon-γ(IFN-γ)level was higher(P<0.05).The levels of cyclooxygenase-2(COX-2),lactate dehydrogenase(LDH),and vascular endothelial growth factor(VEGF)in Group A were lower than those in Group B(P<0.05).The adverse reaction rate in Group A was lower than that in Group B(P<0.05).Conclusion:The combination of Venetoclax and Azacitidine in the treatment of elderly AML patients can improve immune function,inhibit inflammation,delay disease progression,and is safe and efficient.
基金supported by grants from the National High Technology Research and Development Program of China(No.2021YFA1101500)the National Natural Science Foundation of China(No.81873427 and No.82070217)the Research and Innovation Team Project for Scientific Breakthroughs at Shanxi Bethune Hospital(No.2024ZHANCHI12)。
文摘The clinical efficacy of immunotherapy in acute myeloid leukemia(AML)remains significantly limited by early relapse and treatment-associated toxicities.This review examines recent advances in antibody-and cell-based immunotherapies for AML,focusing on established targets(CD33,CD123,and CLL1)as well as emerging targets(including CD7,CD70,CD38,and FLT3).Therapeutic modalities discussed include immunoconjugates,bispecific T-cell engagers and chimeric antigen receptor T(CAR-T)cells.Furthermore,we summarize the current challenges impeding the success of immunotherapy in AML and propose strategies to enhance its efficacy.These include combination therapies,structural optimization of CAR constructs,functional enhancement of CAR-T cells,identification of novel targets,and the development of next-generation cellular therapies.Collectively,these approaches aim to offer new insights for improving immunotherapeutic outcomes in AML.
文摘BACKGROUND Acute myeloid leukemia(AML)is a complicated disease with uncontrolled hematopoietic precursor proliferation induced by various genetic alterations.Runt-related transcription factor-1(RUNX1)is commonly disrupted by chromosomal translocations in hematological malignancies.AIM To characterize RUNX1 gene rearrangements and copy number variations in newly diagnosed adult AML patients,with an emphasis on the impact of clinical and laboratory features on the outcome.METHODS Fluorescence in situ hybridization was used to test RUNX1 gene alterations in 77 newly diagnosed adult AML cases.NPM1,FLT3/ITD,FLT3/TKD,and KIT mutations were tested by PCR.Prognostic clinical and laboratory findings were studied in relation to RUNX1 alterations.RESULTS RUNX1 abnormalities were detected by fluorescence in situ hybridization in 41.6%of patients:20.8%had translocations,22.1%had amplification,and 5.2%had deletion.Translocations prevailed in AML-M2(P=0.019)with a positive expression of myeloperoxidase(P=0.031),whereas deletions dominated in M4 and M5 subtypes(P=0.008)with a positive association with CD64 expression(P=0.05).The modal chromosomal number was higher in cases having amplifications(P=0.007)and lower in those with deletions(P=0.008).RUNX1 abnormalities were associated with complex karyotypes(P<0.001)and were mutually exclusive of NPM1 mutations.After 44 months of follow-up,RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.CONCLUSION RUNX1 abnormalities were mutually exclusive of NPM1 mutations.RUNX1 abnormalities affected neither patients’response to treatment nor overall survival.
文摘Background:Acute Myeloid Leukemia(AML)is a highly aggressive clonal hematological malignancy with limited treatment options.This study aimed to evaluate the therapeutic potential of nigericin,a polyether ionophore derived from Streptomyces DASNCL-29,as a mitochondrial-targeted agent for AML treatment.Methods:Nigericin was isolated from Streptomyces DASNCL-29 and characterized via chromatography and NMR.Its cytotoxicity was tested in MOLM13(sensitive and venetoclax-resistant)and HL60(sensitive and cytarabine-resistant)cells using the MTT assay.Mitochondrial dysfunction was assessed by measuring reactive oxygen species(ROS),mitochondrial membrane potential(Δψm),and mitochondrial mass.Apoptosis was evaluated with Annexin V/PI assays and immunoblotting,while proteomic analysis was conducted using Liquid Chromatography-Tandem Mass Spectrometry(LC-MS/MS)to identify differentially regulated proteins.Results:Nigericin demonstrated potent cytotoxicity with IC50 values of 57.02 nM in MOLM13-sensitive,35.29 nM in MOLM13-resistant,20.49 nM in HL60-sensitive,and 1.197 nM in HL60-cytarabine-resistant cells.Apoptosis was confirmed by Annexin V/PI staining and caspase-3/PARP cleavage,along with MCL-1 downregulation.Mitochondrial dysfunction was evident from increased ROS,reducedΔψm,and decreased mitochondrial mass.Proteomic profiling identified 264 dysregulated proteins,including a 3.8-fold upregulation of Succinate Dehydrogenase[Ubiquinone]Flavoprotein Subunit A(SDHA).Conclusion:Nigericin induces apoptosis in AML cells by disrupting mitochondrial function and enhancing oxidative stress.Its nanomolar potency highlights the need for further mechanistic studies and in vivo evaluations to explore its potential in AML treatment.
文摘BACKGROUND The prognosis for acute myeloid leukemia(AML)remains poor,underscoring the need for a deeper understanding of its underlying molecular mechanisms.AIM To assess the significance of SOX11 gene expression in the clinical features,response to treatment,and survival outcomes of adult patients with AML.METHODS This retrospective study enrolled 102 adults with AML.SOX11 gene expression in bone marrow samples was measured using real-time PCR.Data were correlated to the patients’clinical features,response to treatment,and survival rates.RESULTS Increased SOX11 expression was significantly associated with the presence of the FLT3-ITD mutation(P<0.001),the FAB-M2 subtype(P=0.008),and cytogenetic abnormalities(P=0.011).However,no significant association was found between SOX11 expression and other clinical laboratory parameters,complete remission,disease-free survival,or overall survival.CONCLUSION SOX11 expression may serve as a marker to identify specific subsets of AML patients who could benefit from intensive targeted chemotherapy.
基金National Natural Science Foundation of China (82104246)Postdoctoral Fellowship Program of CPSF (GZB20230996)+2 种基金Natural Science Basic Research Program of Shaanxi (2025JC-YBMS-917)Research Foundation of Air Force Medical University (2024JC054)Xijing Innovation Research Institute Joint Fund Project (LHJJ2023-YX16)。
文摘Myristica is a classic traditional Chinese medicine widely used for leukemia treatment.However,its main active ingredients and underlying mechanisms of action remain poorly understood.In this study,we comprehensively investigated the mechanisms by which Myristica exerted effects on radiation-induced myeloid leukemia(RIML)using molecular docking and network pharmacology.The active ingredients in Myristica were further identified via TCMSP database,potential Myristica-related targets were extracted from GEO,GeneCards,OMIM,and DisGeNET databases,a protein-protein interaction(PPI)network was constructed to screen key targets(followed by GO and KEGG enrichment analyses),and finally the binding affinity between active compounds and key targets was verified.The screening results identified 9 active substances,including Kudos,isoguaiacin,galbacin,and others.Topological analysis of the PPI network revealed that PARP1,ESR1,MTOR,MDM2,HIF1A,and ALB were key targets.GO enrichment analysis showed that these targets were mainly involved in biological processes such as DNA repair,cell cycle regulation,apoptosis,and oxidative stress response.KEGG pathway enrichment analysis indicated that Myristica might exert anti-leukemia effects by regulating signaling pathways such as PI3K-Akt,mTOR,and HIF-1.
基金Supported by Henan Province's"Double First-Class"Creation of Scientific Research in Traditional Chinese Medicine,No.HSRPDFCTCM-2023-7-23 and No.STG-ZYX02-202117National Traditional Chinese Medicine Clinical Research Base Scientific Research Special Project,No.2022JDZX098 and No.2022JDZX114+1 种基金National Natural Science Foundation of China,No.82205086The 9th China Association for Science and Technology Young Talent Support Project,No.2023QNRC001.
文摘Non-alcoholic fatty liver disease(NAFLD)is a progressive disease.Without effective interventions,NAFLD can gradually develop to non-alcoholic steatohepatitis,fatty liver fibrosis,liver cirrhosis and even hepatocellular carcinoma.It is still to investigate the precise molecular mechanism behind the pathophysiology of NAFLD.Triggering receptor expressed on myeloid cells 2(TREM2)can sense tissue injury and mediate immune remodeling,thereby inducing phagocytosis,lipid metabolism,and metabolic transfer,promoting cell survival and combating inflammatory activation.NAFLD might develop as a result of TREM2's regulatory role.We here briefly summarize the biological characteristics of TREM2 and its functions in the disease progression of NAFLD.Moreover,we propose to broaden the therapeutic strategy for NAFLD by targeting TREM2.
基金supported by the National Major Scientific and Technological Projects(No.2023ZD0501201)the Science and Technology Planning Project of Guangdong Province(No.2024A0505090015)+2 种基金the Clinical Research Project of Nanfang Hospital,Southern Medical University(No.2023CR007)the Science and Technology Project of Ganzhou City(No.GZ2024YLJ033)the National Natural Science Foundation of China(No.82170215)。
文摘Acute myeloid leukemia(AML)is a heterogeneous malignancy with heterogeneity,and 35%-45%of patients are refractory to first-line treatment[e.g.,standard chemotherapy and hematopoietic stem cell transplantation(HSCT)]or relapse after treatment.Patients with refractory/relapsed(R/R)AML have a dismal prognosis and are ralely cured with conventional treatment(1),indicating the need for new therapeutic strategies to improve outcomes.
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 the Guangdong Basic and Applied Basic Research Foundation(2022B1515230007).
文摘Background:The role of 1,25-dihydroxyvitamin D3(1,25-(OH)_(2)D_(3))in cancer prevention and treatment is an emerging topic of interest.However,its effects on the stemness of acute myeloid leukemia(AML)cells are poorly understood.Methods:The proliferation and differentiation of AML cells(HL60 and NB4)were investigated by the CCK-8 assay,immunocytochemical staining,and flow cytometry.The abilities of HL60 and NB4 cells to form spheres were examined by the cell sphere formation assay.In addition,the levels of stemness-associated markers(SOX2,Nanog,OCT4,and c-Myc)in HL60 and NB4 cells were measured by western blotting and quantitative real-time polymerase chain reaction.Moreover,we obtainedβ-catenin-interacting protein 1(ICAT)-knockout and ICAT-overexpressing HL-60 cells using gene editing and lentiviral infection techniques and investigated the role of ICAT in modulating the stemness-inhibiting effects of 1,25-(OH)_(2)D_(3)using the aforementioned experimental methods.Finally,we validated our findings in vivo using NOD/SCID mice.Results:1,25-(OH)_(2)D_(3)inhibited the proliferation and stemness of AML cells(HL60 and NB4)and induced their differentiation into monocytes.Additionally,the knockdown of ICAT in HL60 cells attenuated the inhibitory effects of 1,25-(OH)_(2)D_(3)on proliferation and stemness and suppressed the expression of stemness markers.Conversely,overexpression of ICAT enhanced the aforementioned inhibitory effects of 1,25-(OH)_(2)D_(3).Consistently,in NOD/SCID mice,1,25-(OH)_(2)D_(3)suppressed tumor formation by HL-60 cells,and the effects of ICAT knockdown or overexpression on 1,25-(OH)_(2)D_(3) aligned with the in vitro findings.Conclusion:1,25-(OH)_(2)D_(3)inhibits AML cell stemness,possibly through modulation of the ICAT-mediated Wnt/β-catenin signaling pathway.
基金The Natural Science Foundation of Shandong Province,No.ZR2019MH003.
文摘BACKGROUND Myeloid sarcoma(MS),also referred to as granulocytic sarcoma or chloroma,is a rare type of extramedullary malignant tumor.MS comprises primitive granulocytic precursor cells that play a key role in the early stages of white blood cell development.Notably,the occurrence of this tumor in the gingiva is rare.CASE SUMMARY The present study reported the case of MS with gingival swelling in the maxillary region,with aleukemic presentation in a 32-year-old male patient.Following two courses of chemotherapy,computed tomography of the region demonstrated complete clearance of the tumor.At the 12-month follow-up appointment,the patient was in a stable condition with the absence of progression.The etiology,clinical features,diagnosis,and relevant treatment of MS are discussed in the present study.CONCLUSION Diagnosis of MS may be confirmed following histological and immunohistochemical examinations.
文摘Myeloid sarcoma(MS)is a rare neoplasm characterized by the proliferation of immature myeloid precursor cells outside the bone marrow.The pathogenesis of MS is complex and not completely understood.Moreover,it develops in any extramedullary site of the body.In this editorial,we discuss the article published by Li et al,which presents a clinical case involving a 32-year-old man who exhibited gingival inflammation in the maxillary region.It was initially diagnosed as periodontal disease.However,clinical evaluation revealed a firm,grayishwhite mass which underscored the need for comprehensive diagnostics to distinguish MS from other oral conditions.This article emphasizes the different clinical presentations of similar case studies in the literature,and highlights the difficulty in diagnosing oral MS due to its rarity and variability in clinical manifestation.The treatment of MS depends on the clinical presentation,tumor location,and the patient's response to conventional therapies.The various therapeutic options currently available are analyzed and discussed.Early intervention and multidisciplinary management are crucial for improving treatment outcomes.Increased awareness and education about the various clinical presentations of MS lead to earlier diagnosis and timely treatment,thereby enhancing patients'survival and quality of life.Continued research is essential for optimizing therapeutic strategies and addressing the challenges presented by this rare neoplasm.
基金Supported by the National Natural Science Foundation of China:Investigating the Mechanism of Total Saponins in Treating Gouty Arthritis Based on Toll-like Receptor/Myeloid Differentiation Factor 88/Nuclear Factor-Kappa B Signal Pathway and Nacht Leucine-Rich Repeat Protein 3-Inflammasome(No.81573670)Study on the Material Basis and Pathway of Taohong Siwu Decoction in Regulating the Release of Platelet Alpha Granules in Postpartum Blood Stasis(No.81473387)+2 种基金Study on the Regulatory Mechanism of Taohong Siwu Decoction on Experimental Cerebral Ischemia Angiogenesis Based on the Messenger Effect of Platelet Microparticles(No.81503291)Investigating the Material Basis and Molecular Mechanism of Taohong Siwu Decoction Against Vascular Dementia Based on Microdialysis Technology and NOD-Like Receptor Protein 3 Inflammasome Vascular Endothelial Cell Interaction(No.81903953)the Anhui Province Key Research and Development Program:Research on the Development and Preparation of Taohong Siwu Granules(No.1704a0802141)。
文摘OBJECTIVE:To investigate the effect of Taohong Siwu decoction(桃红四物汤,TSD)on atherosclerosis in rats as well as investigate the underlying mechanism based on molecular docking.METHODS:Sixty healthy male Sprague-Dawley rats were randomly divided into 6 groups with 10 rats in each group:control group,model group,atorvastatin group(AT,2.0 mg/kg),and TSD groups(20,10,5 g/kg)after 7 d of acclimation.The model of atherosclerosis was successfully established except the control group by high fat diet(HFD)and vitamin D2.Biochemical analyzers were used to detect the levels of triglyceride(TG),total cholestero(TC),low density lipoprotein-cholesterol(LDLC)and high density lipid-cholesterol(HDL-C)in blood lipid.The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1β)were determined by enzyme-linked immunosorbent assay.Sudan IV staining and Hematoxylin and eosin staining(HE staining)were performed to observe the pathological changes in aortic tissue.Molecular docking technology was used to predict the best matching between the main components of TSD and the target proteins.The expression of target proteins was further detected by quantitative real time polymerase chain reaction(q RTPCR)and Western blot analysis.RESULTS:The results showed that TSD restricted atherosclerosis development and decreased the inflammatory cytokines in plasma.Molecular docking results predicted that the main components of TSD showed a strong binding ability with toll-like receptor(TLR4),myeloid differentiation primary response protein 88(My D88),and nuclear factor kappa-B(NF-κB).The results of q RT-PCR and Western blot analysis showed that the m RNA and protein expressions of TLR4,My D88 and NF-κB p65 in the aorta were reduced in atorvastatin group and TSD group.CONCLUSIONS:TSD can ameliorate atherosclerosis in rats,and the underlying mechanism is supposed be related to the suppression of inflammatory response by regulating TLR4/My D88/NF-κB signal pathway.
基金the National Natural Science Foundation of China:Study on Immunoregulatory Mechanism of Moxibustion"Regulating Weiqi"to Regulate the Intrasynovial Environment Steady State in Rheumatoid Arthritis Model Rats based on the Skin-resident Memory T cells-Growth Arrest-specific 6/Mer Tyrosine Kinase (No. 82374587)the National Natural Science Foundation of China:Study on the Immune Mechanisms of Macrophage M1/M2 Polarization in the Treatment of Rheumatoid Arthritis by Moxibustion"Strengthening Body Resistance and Eliminating Evil"(No. 81973959)+1 种基金the National Key R&D Program of China:Research on the Functional Characteristics of"Special Effects"and"Common Effects"of Acupoints (No. 2019YFC1709001)Science and Technology Innovation Seedling Project of Sichuan Province:based on Macrophage M1 Polarization Signaling Pathway Toll-like receptor 4/Myeloid differentiation factor 88/Nuclear factor kappa B and its Regulatory Molecule T-cell Immunoglobulin and Mucin-containing Protein-3 Exploring the Effect Mechanism of Moxibustion on Experimental Rheumatoid Arthritis Model (No. 2022037)。
文摘OBJECTIVE: To explore whether moxibustion exerts therapeutic effects on rheumatoid arthritis(RA) by regulating the expression of T-cell immunoglobulin and mucin-containing protein-3(TIM-3) and subsequently modulating the macrophage M1 polarization toll-like receptor 4(TLR4)-myeloid differentiation factor 88(My D88)-nuclear factor kappa B(NF-κB) signaling pathway. METHODS: We utilized moxibustion treatment in RA rat models using the Zusanli(ST36) and Shenshu(BL23) acupoints. Hematoxylin and eosin(HE) staining was used to observe the pathological changes of the synovial tissue under a section light microscope, and pathological scoring was performed according to the grading standard of the degree of synovial tissue disease. Enzyme-linked immunosorbent assay(ELISA) was applied to verify the efficacy of moxibustion in reducing inflammation. Quantitative real-time polymerase chain reaction(q RTPCR) was used to detect the expression of the TIM-3/TLR4-My D88-NF-κB signaling pathway-related molecules, and Western blot was used to detect the contents of synovial NF-κB. RESULTS: We established the Freund's complete adjuvant(FCA)-induced RA model in rats. The expression level of M1 polarization signaling pathway TLR4-My D88-NF-κB and the inflammatory factors interleukin-12(IL-12), tumor necrosis factor alpha(TNF-α), and tumor necrosis factor beta(TNF-β) were significantly increased in the RA model. After moxibustion treatment, the expression level of TLR4-My D88-NF-κB was significantly decreased, and the inflammatory factors IL-12, TNF-α, and TNF-β were decreased, but the expression level was significantly increased in the RA model. When TIM-3 expression was inhibited, the expression level of TLR4-My D88-NF-κB, and the inflammatory factors IL-12, TNF-α, and TNF-β were not suppressed, even after moxibustion treatment. CONCLUSIONS: Moxibustion regulates the key target TIM-3 by acting on the Zusanli(ST36) and Shenshu(BL23) points, thereby inhibiting the M1 polarization of macrophages;that is, it inhibits the TLR4-My D88-NF-κB signaling pathway, and finally achieves alleviation of pathological changes and anti-inflammatory effects.
