Background:The nuclear receptor coactivator(NCOA)family,including NCOA1,NCOA2,and NCOA3,is critical in regulating gene expression through interactions with nuclear receptors and other transcription factors.These coact...Background:The nuclear receptor coactivator(NCOA)family,including NCOA1,NCOA2,and NCOA3,is critical in regulating gene expression through interactions with nuclear receptors and other transcription factors.These coactivators are implicated in various cancers,but their comprehensive roles across different cancer types remain poorly understood.Methods:We performed a pan-cancer bioinformatics analysis using data from The Cancer Genome Atlas and the Genotype-Tissue Expression project.We assessed the differential expression,copy number variations,mutations,methylation status,tumor mutation burden,microsatellite instability,and immune cell infiltration associated with NCOA family members across various cancers.Differential expression analysis was conducted using the DESeq2 package.Methylation data were analyzed using the ChAMP package,and immune cell infiltration was estimated using the CIBERSORT algorithm.Results:NCOA1 and NCOA2 were predominantly downregulated in multiple cancers,suggesting potential tumor suppressor roles,whereas NCOA3 was largely upregulated,indicating a consistent oncogenic function.These expression patterns significantly correlated with patient prognosis.Frequent copy number variations,particularly gains,and high mutation rates were observed in NCOA2.NCOA3 demonstrated consistent hypomethylation in tumors,which was associated with increased gene expression.Significant correlations were found between NCOA expression and tumor mutation burden,microsatellite instability,and immune cell infiltration,indicating their involvement in genomic instability and immune modulation.Conclusion:This comprehensive analysis reveals significant alterations in the expression,genomic,and epigenetic profiles of NCOA family members across various cancers.The findings highlight the multifaceted roles of NCOA1,NCOA2,and NCOA3 in tumorigenesis and their potential as biomarkers and therapeutic targets.Future research should focus on elucidating the mechanisms underlying the associations between NCOA expression,genomic alterations,and immune modulation to develop targeted cancer therapies.展开更多
The emergence of SARS-CoV-2 variants and drug-resistant mutants emphasizes the urgent need to develop novel antiviral agents.In the present study,we examined the therapeutic effect of the Chinese medicinal herb,Scutel...The emergence of SARS-CoV-2 variants and drug-resistant mutants emphasizes the urgent need to develop novel antiviral agents.In the present study,we examined the therapeutic effect of the Chinese medicinal herb,Scutellaria barbata D.Don(SBD),against SARS-CoV-2 infection both in vitro and in vivo.Using a viral replicon particle(VRP)-based mouse model of SARS-CoV-2 infection,our study revealed that SBD extracts can reduce viral load in mouse lungs and alleviate the viral induced pneumonia.In vitro antiviral determination further validated the direct acting antiviral efficacy of SBD extracts against SARS-CoV-2 replication.Mechanistic studies demonstrated that SBD can act against SARS-CoV2 replication by targeting both 3-chymotrypsin-like and papain-like cysteine proteases,via a combination of multiple active constituents.Moreover,SBD can modulate the host inflammation response in a bi-directional manner,which also contribute to the mitigation of viral induced acute lung injury.In summary,our study provides SBD as a promising therapeutic agent to combat SARS-CoV-2 infections that merit further development.展开更多
Enteral nutrition has been strongly recommended by major scientific societies for the nutritional management of patients with acute pancreatitis.Providing severe acute pancreatitis patients with enteral nutrition with...Enteral nutrition has been strongly recommended by major scientific societies for the nutritional management of patients with acute pancreatitis.Providing severe acute pancreatitis patients with enteral nutrition within the first 24-48 h of hospital admission can help improve outcomes compared to parenteral nutrition and no feeding.New research is focusing in on when and what to feed to best improve outcomes for acute pancreatitis patients.Early enteral nutrition have the potential to modulate the immune responses.Despite this consistent evidence of early enteral nutrition in patients with acute pancreatitis,clinical practice continues to vary due to individual clinician preference.Achieving the immune modulating effects of enteral nutrition heavily depend on proper placement of the feeding tube and managing any tube feeding associated complications.The current article reviews the immune modulating effects of enteral nutrition and pro-and prebiotics and suggests some practical tools that help improve the patient adherence and tolerance to the tube feeding.Proper selection of the type of the tube,close monitoring of the tube for its placement,patency and securing its proper placement and routine checking the gastric residual volume could all help improve the outcome.Using peptide-based and high medium chaintriglycerides feeding formulas help improving feeding tolerance.展开更多
Diabetic wounds present multiple functional impairments,including neurovascular dysregulation,oxidative imbalance,and immune dysfunction,making wound healing particularly challenging,while traditional therapeutical st...Diabetic wounds present multiple functional impairments,including neurovascular dysregulation,oxidative imbalance,and immune dysfunction,making wound healing particularly challenging,while traditional therapeutical strategies fail to address these complex issues effectively.Herein,we propose a strategy utilizing duallayer microneedles to deliver therapeutic gases by modulating neurovascular coupling and immune functions for diabetic wound treatment.The microneedle can respond to reactive oxygen species(ROS)in the diabetic microenvironment and subsequently generate oxygen(O_(2))and nitric oxide(NO).These gases comprehensively promote neuro-vascular regeneration,reduce oxidative stress levels,and attenuate inflammation.In vivo studies demonstrate that the microneedle can accelerate diabetic wound healing by modulating neurovascular regeneration and inflammatory processes.Transcriptomic analyses further validate the involvement of related advantageous signaling pathways.The potential mechanism involves the activation of the PI3K-AKT-mTOR pathway to facilitate autophagy,ultimately accelerating the healing process.Thus,our multifunctional duallayer microneedles provide an effective strategy for treating diabetic wounds.展开更多
Dear Editor,Esophageal cancer is the seventh most common malignant tumor in China and has the third highest fatality rate worldwide(Siegel et al.,2022).The most common type in China is esophageal squamous cell carcino...Dear Editor,Esophageal cancer is the seventh most common malignant tumor in China and has the third highest fatality rate worldwide(Siegel et al.,2022).The most common type in China is esophageal squamous cell carcinoma(ESCC),which has shown a promising response to immune checkpoint inhibitors(Doki et al.,2022;Sun et al.,2021).However,challenges remain in effectively using immunotherapy due to varying patient responses and difficulties in identifying suitable candidates.展开更多
The concept of neuroimmune interactions has shown significant advancements over the years. Modern research has revealed many areas of connection between fields, which were previously viewed as distinct disciplines. Fo...The concept of neuroimmune interactions has shown significant advancements over the years. Modern research has revealed many areas of connection between fields, which were previously viewed as distinct disciplines. For example, the nervous system can sense changes in the external environment and convey these changes through molecules and mediators with receptors in the immune system to modulate immune responses. Neuromediators can act on different receptors in the same group of cells, producing antipodal effects. Identification of the anti-inflammatory role of glucocorticoids highlighted that the body functions properly in an integrated manner. These interactions and crosstalk are not unidirectional, as the immune system can also influence various aspects of the nervous system, such as synaptic plasticity and fever. Strict integration of neuro-immuno-endocrine circuits is indispensable for homeostasis. Understanding these circuits and molecules can lead to advances in the understanding of various immune diseases, which will offer promising therapeutic options.展开更多
BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related morbidity and mor-tality globally.Exosomal microRNAs(miRNAs)are known to modulate tumor progression by influencing immune responses and vascular dy...BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related morbidity and mor-tality globally.Exosomal microRNAs(miRNAs)are known to modulate tumor progression by influencing immune responses and vascular dynamics.However,the roles of specific exosomal miRNAs,such as miR-425-5p and miR-135b-3p,in CRC remain unclear.AIM To explore the specific roles and underlying mechanisms of exosomal miR-425-5p and miR-135b-3p in CRC progression.METHODS Differentially expressed miRNAs were identified through microarray analysis of exosomes isolated from CRC tissues and adjacent normal mucosa.Functional roles of miR-425-5p and miR-135b-3p were evaluated in vitro using macrophage polarization,T cell differentiation,and vascular permeability assays,as well as in vivo tumor formation and metastasis experiments in nude mice.Validation expe-riments were performed using CRC cell lines(HCT116 and SW620).RESULTS Exosomal miR-425-5p and miR-135b-3p were significantly upregulated in CRC compared to normal tissues.Functional studies revealed that miR-425-5p promo-tes macrophage M2-like polarization and suppresses T cell proinflammatory responses,while miR-135b-3p enhances vascular permeability and angiogenesis.Inhibition of these miRNAs in CRC cell-derived exosomes significantly supp-ressed tumor growth and metastasis in nude mice,reprogramming the tumor microenvironment toward reduced angiogenesis and enhanced immune acti-vation.Combined inhibition of both miRNAs resulted in the most pronounced effects.CONCLUSION Exosomal miR-425-5p and miR-135b-3p drive CRC progression by promoting immune suppression and vascular permeability.Their inhibition offers a promising strategy for modulating the tumor microenvironment and limiting CRC metastasis.展开更多
A recent study published in the World Journal of Gastroenterology,suggests that transplanting the gut microbiota from healthy donors can alleviate the pathological processes linked to inflammatory bowel disease(IBD),p...A recent study published in the World Journal of Gastroenterology,suggests that transplanting the gut microbiota from healthy donors can alleviate the pathological processes linked to inflammatory bowel disease(IBD),particularly Crohn's disease.In addition,that paper illustrates the effect of changes in the gut microbiota on IBD and points out that altered mesenteric adipose tissue caused by the gut microbiota and creeping fat lead to increased inflammation,which exacerbates IBD.Moreover,recent research has shown that the interaction between Helicobacter pylori(H.pylori)and the gut microbiota is mediated through immune mechanisms,resulting in a synergistic impact on IBD.Therefore,in this manuscript,we will focus on the role of the gut microbiota and H.pylori in the immune response to IBD,as well as the possible impact of H.pylori on the gut microbiota.We will also explore their individual and synergistic immune effects on IBD and look at future therapeutic perspectives for IBD.展开更多
Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have con...Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have contrib-uted to the emergence and spread of antimicrobial resistance.Novel antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being investigated.Lactoferrin has shown promising results against porcine enterotoxigenic E.coli strains,both in vitro and in vivo.Results We investigated the influence of bovine lactoferrin(bLF)on the microbiome of healthy and infected weaned piglets.Additionally,we assessed whether bLF influenced the immune responses upon Shiga toxin-producing E.coli(STEC)infection.Therefore,2 in vivo trials were conducted:a microbiome trial and a challenge infection trial,using an F18+STEC strain.BLF did not affect theα-andβ-diversity.However,bLF groups showed a higher relative abundance(RA)for the Actinobacteria phylum and the Bifidobacterium genus in the ileal mucosa.When analysing the immune response upon infection,the STEC group exhibited a significant increase in F18-specific IgG serum levels,whereas this response was absent in the bLF group.Conclusion Taken together,the oral administration of bLF did not have a notable impact on theα-andβ-diversity of the gut microbiome in weaned piglets.Nevertheless,it did increase the RA of the Actinobacteria phylum and Bifi-dobacterium genus,which have previously been shown to play an important role in maintaining gut homeostasis.Furthermore,bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.展开更多
Objectives:The phytochemical investigation of traditional herbal medicines holds significant promise for modern drug discovery,particularly in cancer therapy.This study aimed to evaluate the cytotoxicity,apoptosis ind...Objectives:The phytochemical investigation of traditional herbal medicines holds significant promise for modern drug discovery,particularly in cancer therapy.This study aimed to evaluate the cytotoxicity,apoptosis induction,and immune-modulatory activities of extracts from three herbal medicines with historical use in traditional medicine—Acanthopanax sessiliflorus,Phragmites communis,and Pinus densiflora,as well as their combined extract(GMAS 01/COM),on human lung cancer cells(A549)and normal cell lines,including murine macrophages(RAW 264.7)and human keratinocytes(HaCaT).Methods:Plant extracts were prepared using aqueous extraction,sonication,and rotary evaporation.The total phenolic and flavonoid contents were quantified using the Folin-Ciocalteu and AlCl3 colorimetric methods,respectively.Antioxidant potential was evaluated via 2,2-Diphenyl-1-picrylhydrazyl(DPPH)scavenging and reducing power assays.Cytotoxicity was assessed using an MTT assay,while reactive oxygen species(ROS)generation was quantified using a 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA)assay.Anticancer properties,including colony formation inhibition and migration suppression,were examined using colony formation and wound healing assays.The expression of apoptotic and inflammatory mediators was analysed through qPCR.Results:GMAS 01 selectively induced apoptosis in A549 cells without cytotoxic effects on RAW264.7 and HaCaT cells.Mechanistically,it elevated intracellular ROS and activated the intrinsic mitochondrial apoptotic pathway,evidenced by p53 upregulation,increased Bax,and decreased Bcl-2 expression.GMAS 01 also significantly inhibited colony formation and migration in A549 cells.In RAW264.7 cells,it reduced nitric oxide(NO)production and downregulated iNOS,COX-2,IL-6,and IL-8,indicating strong immunomodulatory activity.Conclusion:GMAS 01 exhibits potent antioxidant,anti-inflammatory,and anticancer effects,likely mediated through ROS-induced mitochondrial apoptosis.However,mechanistic interpretations are limited by the absence of protein-level validation and pathway inhibition studies.Upcoming studies should aim to verify the underlying mechanisms and evaluate their potential for real-world application.展开更多
Gastric cancer(GC)remains one of the leading causes of cancer-related morbidity and mortality globally.Although significant progress has been made in treatment options,the survival rates for GC patients continue to be...Gastric cancer(GC)remains one of the leading causes of cancer-related morbidity and mortality globally.Although significant progress has been made in treatment options,the survival rates for GC patients continue to be low.This is primarily attributed to the intricate and insufficiently understood mechanisms of disease progression,as well as the considerable challenges associated with tumor hetero-geneity.The recent study by Tang et al provides a detailed single-cell RNA se-quencing analysis of GC across different stages,revealing dynamic changes in the tumor microenvironment and key immune responses.We aim to offer a compre-hensive interpretation of the study’s findings and propose several innovative directions for future academic research in gastric cancer.These include exploring advanced multi-omics approaches,leveraging spatial transcriptomics,integrating artificial intelligence for clinical applications,and developing novel immuno-therapy strategies.We further emphasize the importance of personalized medi-cine,early detection,and novel drug discovery techniques in improving GC treatment outcomes.展开更多
Vitamin D,beyond its classical role in calcium homeostasis,has emerged as a key regulator of immune function and epithelial barrier integrity.Its deficiency during early childhood—a critical period for immune maturat...Vitamin D,beyond its classical role in calcium homeostasis,has emerged as a key regulator of immune function and epithelial barrier integrity.Its deficiency during early childhood—a critical period for immune maturation—has been increasingly implicated in the development of atopic diseases.While extensively studied in asthma,its role in non-respiratory allergic conditions such as atopic dermatitis(AD)and allergic rhinitis(AR)remains comparatively underexplored.This minireview synthesizes current mechanistic and clinical evidence on vitamin D in pediatric AD and AR.In AD,vitamin D promotes epidermal barrier function through upregulation of filaggrin and ceramide synthesis,and enhances antimicrobial defense via induction of antimicrobial peptides.Observational studies consistently report lower serum 25-hydroxyvitamin D in affected children,particularly those with allergic sensitization.Select randomized controlled trials suggest clinical improvement with supplementation,especially at doses>2000 IU/day in deficient individuals.In AR,epidemiological data indicate stronger inverse associations with seasonal(pollen-induced)disease.Proposed mechanisms include modulation of dendritic cells,regulatory T cells,T helper 2 cytokines,and mucosal barrier integrity.The shared immunopathogenesis of AD and AR underscores vitamin D’s relevance.Although promising,clinical evidence remains heterogeneous.Future research should prioritize phenotype-stratified trials to clarify optimal dosing,timing,and individual response determinants,including genetics and microbiome composition.展开更多
The gut microbiome plays a pivotal role in immune homeostasis and systemic inflammatory regulation,both of which are critically involved in the pathogenesis and progression of pediatric leukemias.Recent evidence revea...The gut microbiome plays a pivotal role in immune homeostasis and systemic inflammatory regulation,both of which are critically involved in the pathogenesis and progression of pediatric leukemias.Recent evidence reveals that children with leukemia often exhibit distinct gut microbiome profiles at diagnosis,marked by reduced microbial diversity and the enrichment of pro-inflammatory taxa such as Enterococcus and Streptococcus.This microbial dysbiosis may promote leukemogenesis by disrupting immune regulation and driving chronic inflammation.Chemotherapy significantly alters the gut microbiome,inducing dysbiosis characterized by a loss of beneficial commensals and the dominance of pathobionts.Specific microbial signatures,such as the enrichment of Bacteroides,correlate with reduced inflammation and improved prognosis,underscoring the gut microbiome's prognostic value.Emerging therapies,including dietary adjustments,probiotics,and fecal gut microbiome transplantation,aim to restore microbial balance and reduce treatment-related complications.Moreover,gut microbiome profiling shows potential for identifying biomarkers linked to leukemia predisposition,paving the way for early diagnosis and tailored preventive strategies.This mini-review explores recent advancements in understanding the influence of the gut microbiome on pediatric leukemias,emphasizing its role as both a therapeutic target and a prognostic biomarker.Integrating gut microbiome research into clinical practice may help optimize treatment outcomes and improve quality of life for children with leukemia.展开更多
Organ transplantation has long been recognized as an effective treatment for endstage organ failure,metabolic diseases,and malignant tumors.However,graft rejection caused by major histocompatibility complex mismatch r...Organ transplantation has long been recognized as an effective treatment for endstage organ failure,metabolic diseases,and malignant tumors.However,graft rejection caused by major histocompatibility complex mismatch remains a significant challenge.While modern immunosuppressants have made significant strides in reducing the incidence and risk of rejection,they have not been able to eliminate it completely.The intricate mechanisms underlying transplant rejection have been the subject of intense investigation by transplant immunologists.Among these factors,autophagy has emerged as a key player.Autophagy is an evolutionarily conserved mechanism in eukaryotic cells that mediates autophagocytosis and cellular protection.This process is regulated by autophagy-related genes and their encoded protein families,which maintain the material and energetic balance within cells.Additionally,autophagy has been reported to play crucial roles in the development,maturation,differentiation,and responses of immune cells.In the complex immune environment following transplantation,the role and mechanisms of autophagy are gradually being revealed.In this review,we aim to explore the current understanding of the role of autophagy in solid organ rejection after transplantation.Furthermore,we delve into the therapeutic advancements achieved by targeting autophagy involved in the rejection process.展开更多
Background Preclinical studies demonstrate that exercise reduces tumor incidence and growth.Rapid release of extracellular vesicles(EVs)during exercise suggests their potential role as mediators of exercise-induced sy...Background Preclinical studies demonstrate that exercise reduces tumor incidence and growth.Rapid release of extracellular vesicles(EVs)during exercise suggests their potential role as mediators of exercise-induced systemic effects and physiological adaptation.This study investigated the impact of exercise-induced plasma EVs on tumor growth and immune tumor microenvironment in murine models of triple-negative breast cancer(TNBC):EO771(a C57BL/6-derived TNBC cell line)and 4T1(a BALB/c-derived TNBC cell line).Methods Size exclusion chromatography was used to isolate exercise-induced EVs from plasma of healthy female mice(BALB/c and C56BL/6,n=30 per strain)that underwent ten 30-min moderate-intensity treadmill running sessions over 2 weeks.Nanoparticle tracking analysis,Western blot,and electron microscopy confirmed the presence of EVs in the samples.Tumor-bearing mice(n=72 per strain)were administered with exercise-induced EVs before or/and after tumor implantation.Local and systemic immune responses were assessed using flow cytometry,enzyme-linked immunosorbent assay(ELISA),and quantitative polymerase chain reaction(qPCR).Results Administration of exercise-induced EVs,particularly before tumor implantation,significantly suppressed tumor growth and reduced tumor burden in both TNBC models.In EO771,endpoint tumor volumes were 278–330 mm^(3)in treated groups compared to 799 mm^(3)in untreated(p<0.0001),while in 4T1,treated groups showed volumes of 287–564 mm^(3)vs.696 mm^(3)in untreated(p=0.0002).Notable differences in tumor-infiltrating lymphoid and myeloid cell subpopulations indicated immunomodulatory effects of exercise-induced EVs,particularly in the 4T1 model,where their continuous administration significantly increased intratumoral cluster of differentiation 8(CD8)T lymphocyte proportion(5.77%vs.0.90%in untreated,p<0.0001).Similarly,in the EO771 model,exercise-induced EVs administered before tumor implantation led to a marked rise in intratumoral CD8 T lymphocytes(2.24%vs.1.08%in untreated,p=0.0181).Conclusion Our findings indicate that exercise-induced EV treatment elicits a pro-inflammatory antitumor immune response,suggesting a shift of immunologically cold TNBC tumors towards a more inflamed phenotype associated with better outcomes.Our study supports the further investigation of EVs as modulators of antitumor immunity and their potential utility in enhancing the efficacy of immunotherapy.展开更多
Objectives:Despite the considerable regenerative capacity exhibited by adipose-derived mesenchymal stem cells(ASCs),their genetic and molecular mechanisms remain incompletely understood.Methods:In this study,we analyz...Objectives:Despite the considerable regenerative capacity exhibited by adipose-derived mesenchymal stem cells(ASCs),their genetic and molecular mechanisms remain incompletely understood.Methods:In this study,we analyzed the global gene expression profile of adipose-derived mesenchymal stem cells(ASCs)using microarray analysis and compared it with stromal vascular fraction(SVF)cells.Results:Microarray analysis revealed that ASCs express elevated levels of genes related to the extracellular matrix(ECM;extracellular matrix)and collagen,which are critical components of tissue remodeling and wound healing.Additionally,genes associated with cell growth,differentiation,motility,and plasticity were highly expressed.When compared to stromal vascular fraction(SVF)cells,ASCs demonstrated enrichment of genes involved in anti-inflammatory responses,immune modulation,tissue repair,cell adhesion,and migration processes.Gene Set Enrichment Analysis(GSEA;Gene Set Enrichment Analysis)showed activation of pathways related to angiogenesis,such as vascular endothelial growth factor(VEGF),Integrin,Wnt signaling pathways,transforming growth factor-beta(TGF-β),extracellular matrix(ECM),and matrix metalloproteinase(MMP),highlighting the significant angiogenic potential of ASCs.Gene Ontology(GO;Gene Ontology)analysis further linked ASCs to biological processes associated with the regulation of cell proliferation and muscle cell differentiation.Conclusion:These findings collectively underscore the suitability of adipose-derived mesenchymal stem cells(ASCs)as a promising candidate for regenerative medicine,particularly in applications involving tissue repair,immune modulation,and promotion of angiogenesis.展开更多
Two hundred and forty specific pathogen free leghorn chickens were randomly divided into four groups and reared in isolated pens. The tested chickens were negative to infectious bursal disease virus （IBDV） at 25 d o...Two hundred and forty specific pathogen free leghorn chickens were randomly divided into four groups and reared in isolated pens. The tested chickens were negative to infectious bursal disease virus （IBDV） at 25 d old. Group 1 was treated with saline, whereas Groups 2, 3, and 4 were inoculated with 0.3 mL IBDV suspension intranasally the next day. Groups 3 and 4 were also administered with Astragalus polysaccharides （APS） intramuscularly twice daily at 5 or 10 mg kg-1 BW, respectively, until 31 d old. The erythrocyte-C3b receptor rosette rate （E-C3bRR） and the erythrocyte-C3b immune complex rosette rate （E-ICRR） were measured at 25, 29, 32, 35, and 38 d old. The results showed that IBDV significantly reduced E-C3bRR and E-ICRR when compared with the control group （P 〈 0.05）, while simultaneous administration of APS with 1BDV maintained E-C3bRR at similar levels to the control group （P 〉 0.05） and increased E-ICRR when compared with the control group and the group non-treated with APS （P 〈 0.05）. APS treatment reduced the morbidity and mortality of chickens inoculated with IBDV （P 〈 0.05）. The results suggest that APS may enhance the immune adherence of chickens erythrocytes by affecting the activity and/or the number of complement receptors on the erythrocyte membrane. These findings can be beneficial in providing an understanding of the basic mechanisms required for the rational application of APS in modern medicine.展开更多
AIM： To investigate cytokine production and cell surface phenotypes of dendritic cells （DC） in the presence of epithelial cells stimulated by probiotics.METHODS： Mouse DC were cultured alone or together with mouse...AIM： To investigate cytokine production and cell surface phenotypes of dendritic cells （DC） in the presence of epithelial cells stimulated by probiotics.METHODS： Mouse DC were cultured alone or together with mouse epithelial cell monolayers in normal or in- verted systems and were stimulated with heat-killed probiotic bacteria, Bifidobacterium lactis ADO 11 （BL）, Bifidobacterium bilfidum BGN4 （BB）, Lactobacillus casei IBS041 （LC）, and Lactobacillus acidophilus AD031 （LA）, for 12 h. Cytokine levels in the culture supernatants were determined by enzyme-linked immunosorbent as say and phenotypic analysis of DC was investigated by flow cytometry.RESULTS： BB and LC in singlecultured DC increased the expression of I-Ad, CD86 and CD40 （I-Ad, 18.51 vs 30.88, 46.11, CD86, 62.74 vs 92.7, 104.12; CD40, 0.67 vs 6.39, 3.37, P 〈 0.05）. All of the experimental probiot-ics increased the production of inflammatory cytokines, interleukin （IL）-6 and tumor necrosis factor （TNF）-α. However, in the normal coculture systems, LC and LA decreased the expression of I-A^α （39.46 vs 30.32, 33.26, P 〈 0.05）, and none of the experimental probiotics increased the levels of IL-6 or TNF-α. In the inverted coculture systems, LC decreased the expression of CD40 （1.36 vs -2.27, P 〈 0.05）, and all of the experimental probiotics decreased the levels of IL-6. In addition, BL increased the production of IL-10 （103.8 vs 166.0, P 〈 0.05） and LC and LA increased transforming growth factor-13 secretion （235.9 vs 618.9, 607.6, P 〈 0.05）.CONCLUSION： These results suggest that specific pro- biotic strains exert differential immune modulation mediated by the interaction of dendritic cells and epithelial cells in the homeostasis of gastrointestinal tract.展开更多
In the immune oncology era,the clinical efficacy of immune checkpoint inhibitors(ICIs)against most solid cancers is well known.In hepatocellular carcinoma,the recent success of combination therapy with targeting agent...In the immune oncology era,the clinical efficacy of immune checkpoint inhibitors(ICIs)against most solid cancers is well known.In hepatocellular carcinoma,the recent success of combination therapy with targeting agents has accelerated the search for novel combination strategies.Radiotherapy(RT),an attractive modality,can be combined with ICIs,which act as strong modulators of the tumor immune microenvironment.Herein,we discuss immune modulation caused by radiation and the current trials of RT-ICI combination treatment as well as future perspectives.展开更多
Objective: To study mechanisms by which human gliomas may escape immune surveillance Methods: The effect of supernatant (SN) obtained from cultured media of malignant glioma cell lines on the proliferation of phyto...Objective: To study mechanisms by which human gliomas may escape immune surveillance Methods: The effect of supernatant (SN) obtained from cultured media of malignant glioma cell lines on the proliferation of phytohemagglutinin p stimulated peripheral blood lymphocytes (PBLs) from healthy subjects and patients with gliomas was examined by MTT assay The immunosuppressive factor which might be existed in the SN was identified by neutralization method with specific antibodies and Northern blot hybridization of glioma cells In addition, the cellular immunity of patients with gliomas and relevant hormone and catecholamine were determined Results: It was found that the malignant glioma cells could release an immunosuppressive factor in an autocrine fashion which was further identified as the transforming growth factor β 2 (TGF β 2) It was also demonstrated that the plasma levels of norepinephrine in glioma patients were significantly reduced and correlated well with the suppression of the patients' own cellular immunity Conclusions: Two distinct mechanisms by which human gliomas may evade immune surveillance: 1 The secretion of an immunosuppressive factor which was identified as TGF β 2; 2 The dysfunction of Neuro Immune modulation in the presence of cerebral gliomas展开更多
基金supported by grants from the Tianjin Health Technology Project(Grant No.2022QN106).
文摘Background:The nuclear receptor coactivator(NCOA)family,including NCOA1,NCOA2,and NCOA3,is critical in regulating gene expression through interactions with nuclear receptors and other transcription factors.These coactivators are implicated in various cancers,but their comprehensive roles across different cancer types remain poorly understood.Methods:We performed a pan-cancer bioinformatics analysis using data from The Cancer Genome Atlas and the Genotype-Tissue Expression project.We assessed the differential expression,copy number variations,mutations,methylation status,tumor mutation burden,microsatellite instability,and immune cell infiltration associated with NCOA family members across various cancers.Differential expression analysis was conducted using the DESeq2 package.Methylation data were analyzed using the ChAMP package,and immune cell infiltration was estimated using the CIBERSORT algorithm.Results:NCOA1 and NCOA2 were predominantly downregulated in multiple cancers,suggesting potential tumor suppressor roles,whereas NCOA3 was largely upregulated,indicating a consistent oncogenic function.These expression patterns significantly correlated with patient prognosis.Frequent copy number variations,particularly gains,and high mutation rates were observed in NCOA2.NCOA3 demonstrated consistent hypomethylation in tumors,which was associated with increased gene expression.Significant correlations were found between NCOA expression and tumor mutation burden,microsatellite instability,and immune cell infiltration,indicating their involvement in genomic instability and immune modulation.Conclusion:This comprehensive analysis reveals significant alterations in the expression,genomic,and epigenetic profiles of NCOA family members across various cancers.The findings highlight the multifaceted roles of NCOA1,NCOA2,and NCOA3 in tumorigenesis and their potential as biomarkers and therapeutic targets.Future research should focus on elucidating the mechanisms underlying the associations between NCOA expression,genomic alterations,and immune modulation to develop targeted cancer therapies.
基金supported by the National Natural Science Foundation of China(82274204 and 82104134)the Natural Science Foundation of Shandong Province,China(ZR2024QH110)+1 种基金the Major Basic Program of Shandong Natural Science Foundation,China(ZR2021ZD17)the Project of Youth Innovation Team of Shandong Province(2022KJ254).
文摘The emergence of SARS-CoV-2 variants and drug-resistant mutants emphasizes the urgent need to develop novel antiviral agents.In the present study,we examined the therapeutic effect of the Chinese medicinal herb,Scutellaria barbata D.Don(SBD),against SARS-CoV-2 infection both in vitro and in vivo.Using a viral replicon particle(VRP)-based mouse model of SARS-CoV-2 infection,our study revealed that SBD extracts can reduce viral load in mouse lungs and alleviate the viral induced pneumonia.In vitro antiviral determination further validated the direct acting antiviral efficacy of SBD extracts against SARS-CoV-2 replication.Mechanistic studies demonstrated that SBD can act against SARS-CoV2 replication by targeting both 3-chymotrypsin-like and papain-like cysteine proteases,via a combination of multiple active constituents.Moreover,SBD can modulate the host inflammation response in a bi-directional manner,which also contribute to the mitigation of viral induced acute lung injury.In summary,our study provides SBD as a promising therapeutic agent to combat SARS-CoV-2 infections that merit further development.
文摘Enteral nutrition has been strongly recommended by major scientific societies for the nutritional management of patients with acute pancreatitis.Providing severe acute pancreatitis patients with enteral nutrition within the first 24-48 h of hospital admission can help improve outcomes compared to parenteral nutrition and no feeding.New research is focusing in on when and what to feed to best improve outcomes for acute pancreatitis patients.Early enteral nutrition have the potential to modulate the immune responses.Despite this consistent evidence of early enteral nutrition in patients with acute pancreatitis,clinical practice continues to vary due to individual clinician preference.Achieving the immune modulating effects of enteral nutrition heavily depend on proper placement of the feeding tube and managing any tube feeding associated complications.The current article reviews the immune modulating effects of enteral nutrition and pro-and prebiotics and suggests some practical tools that help improve the patient adherence and tolerance to the tube feeding.Proper selection of the type of the tube,close monitoring of the tube for its placement,patency and securing its proper placement and routine checking the gastric residual volume could all help improve the outcome.Using peptide-based and high medium chaintriglycerides feeding formulas help improving feeding tolerance.
基金supported by grants from the National Natural Science Foundation of China(52372272,32201109,82072440)Zhongnan Hospital of Wuhan University,Excellent Doctor Fund Project(ZNYB2022015)+1 种基金Natural Science Foundation of Hubei Province(2024AFD167)the Basic and Applied Basic Research Foundation of Guangdong Province(2022B1515120052,2021A1515110557)。
文摘Diabetic wounds present multiple functional impairments,including neurovascular dysregulation,oxidative imbalance,and immune dysfunction,making wound healing particularly challenging,while traditional therapeutical strategies fail to address these complex issues effectively.Herein,we propose a strategy utilizing duallayer microneedles to deliver therapeutic gases by modulating neurovascular coupling and immune functions for diabetic wound treatment.The microneedle can respond to reactive oxygen species(ROS)in the diabetic microenvironment and subsequently generate oxygen(O_(2))and nitric oxide(NO).These gases comprehensively promote neuro-vascular regeneration,reduce oxidative stress levels,and attenuate inflammation.In vivo studies demonstrate that the microneedle can accelerate diabetic wound healing by modulating neurovascular regeneration and inflammatory processes.Transcriptomic analyses further validate the involvement of related advantageous signaling pathways.The potential mechanism involves the activation of the PI3K-AKT-mTOR pathway to facilitate autophagy,ultimately accelerating the healing process.Thus,our multifunctional duallayer microneedles provide an effective strategy for treating diabetic wounds.
基金supported by the Natural Science Foundation of China(Grant No.82373072)awarded to Z.N.the Key Project of Hebei Province Natural Science Precision Medicine Joint Fund(H2022201067)awarded to Z.N.the Natural Science Foundation of Hebei Province(Grant No.H2024206159)awarded to J.Z.
文摘Dear Editor,Esophageal cancer is the seventh most common malignant tumor in China and has the third highest fatality rate worldwide(Siegel et al.,2022).The most common type in China is esophageal squamous cell carcinoma(ESCC),which has shown a promising response to immune checkpoint inhibitors(Doki et al.,2022;Sun et al.,2021).However,challenges remain in effectively using immunotherapy due to varying patient responses and difficulties in identifying suitable candidates.
文摘The concept of neuroimmune interactions has shown significant advancements over the years. Modern research has revealed many areas of connection between fields, which were previously viewed as distinct disciplines. For example, the nervous system can sense changes in the external environment and convey these changes through molecules and mediators with receptors in the immune system to modulate immune responses. Neuromediators can act on different receptors in the same group of cells, producing antipodal effects. Identification of the anti-inflammatory role of glucocorticoids highlighted that the body functions properly in an integrated manner. These interactions and crosstalk are not unidirectional, as the immune system can also influence various aspects of the nervous system, such as synaptic plasticity and fever. Strict integration of neuro-immuno-endocrine circuits is indispensable for homeostasis. Understanding these circuits and molecules can lead to advances in the understanding of various immune diseases, which will offer promising therapeutic options.
文摘BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related morbidity and mor-tality globally.Exosomal microRNAs(miRNAs)are known to modulate tumor progression by influencing immune responses and vascular dynamics.However,the roles of specific exosomal miRNAs,such as miR-425-5p and miR-135b-3p,in CRC remain unclear.AIM To explore the specific roles and underlying mechanisms of exosomal miR-425-5p and miR-135b-3p in CRC progression.METHODS Differentially expressed miRNAs were identified through microarray analysis of exosomes isolated from CRC tissues and adjacent normal mucosa.Functional roles of miR-425-5p and miR-135b-3p were evaluated in vitro using macrophage polarization,T cell differentiation,and vascular permeability assays,as well as in vivo tumor formation and metastasis experiments in nude mice.Validation expe-riments were performed using CRC cell lines(HCT116 and SW620).RESULTS Exosomal miR-425-5p and miR-135b-3p were significantly upregulated in CRC compared to normal tissues.Functional studies revealed that miR-425-5p promo-tes macrophage M2-like polarization and suppresses T cell proinflammatory responses,while miR-135b-3p enhances vascular permeability and angiogenesis.Inhibition of these miRNAs in CRC cell-derived exosomes significantly supp-ressed tumor growth and metastasis in nude mice,reprogramming the tumor microenvironment toward reduced angiogenesis and enhanced immune acti-vation.Combined inhibition of both miRNAs resulted in the most pronounced effects.CONCLUSION Exosomal miR-425-5p and miR-135b-3p drive CRC progression by promoting immune suppression and vascular permeability.Their inhibition offers a promising strategy for modulating the tumor microenvironment and limiting CRC metastasis.
文摘A recent study published in the World Journal of Gastroenterology,suggests that transplanting the gut microbiota from healthy donors can alleviate the pathological processes linked to inflammatory bowel disease(IBD),particularly Crohn's disease.In addition,that paper illustrates the effect of changes in the gut microbiota on IBD and points out that altered mesenteric adipose tissue caused by the gut microbiota and creeping fat lead to increased inflammation,which exacerbates IBD.Moreover,recent research has shown that the interaction between Helicobacter pylori(H.pylori)and the gut microbiota is mediated through immune mechanisms,resulting in a synergistic impact on IBD.Therefore,in this manuscript,we will focus on the role of the gut microbiota and H.pylori in the immune response to IBD,as well as the possible impact of H.pylori on the gut microbiota.We will also explore their individual and synergistic immune effects on IBD and look at future therapeutic perspectives for IBD.
基金The research that yielded these results,was funded by the Belgian Federal Public Service of Health,Food Chain Safety and Environment through the contract RF 17/6314 LactoPigHealthMatthias Dierick is supported by the Flemish fund for scientific research(FWO3S036319).
文摘Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have contrib-uted to the emergence and spread of antimicrobial resistance.Novel antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being investigated.Lactoferrin has shown promising results against porcine enterotoxigenic E.coli strains,both in vitro and in vivo.Results We investigated the influence of bovine lactoferrin(bLF)on the microbiome of healthy and infected weaned piglets.Additionally,we assessed whether bLF influenced the immune responses upon Shiga toxin-producing E.coli(STEC)infection.Therefore,2 in vivo trials were conducted:a microbiome trial and a challenge infection trial,using an F18+STEC strain.BLF did not affect theα-andβ-diversity.However,bLF groups showed a higher relative abundance(RA)for the Actinobacteria phylum and the Bifidobacterium genus in the ileal mucosa.When analysing the immune response upon infection,the STEC group exhibited a significant increase in F18-specific IgG serum levels,whereas this response was absent in the bLF group.Conclusion Taken together,the oral administration of bLF did not have a notable impact on theα-andβ-diversity of the gut microbiome in weaned piglets.Nevertheless,it did increase the RA of the Actinobacteria phylum and Bifi-dobacterium genus,which have previously been shown to play an important role in maintaining gut homeostasis.Furthermore,bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.
文摘Objectives:The phytochemical investigation of traditional herbal medicines holds significant promise for modern drug discovery,particularly in cancer therapy.This study aimed to evaluate the cytotoxicity,apoptosis induction,and immune-modulatory activities of extracts from three herbal medicines with historical use in traditional medicine—Acanthopanax sessiliflorus,Phragmites communis,and Pinus densiflora,as well as their combined extract(GMAS 01/COM),on human lung cancer cells(A549)and normal cell lines,including murine macrophages(RAW 264.7)and human keratinocytes(HaCaT).Methods:Plant extracts were prepared using aqueous extraction,sonication,and rotary evaporation.The total phenolic and flavonoid contents were quantified using the Folin-Ciocalteu and AlCl3 colorimetric methods,respectively.Antioxidant potential was evaluated via 2,2-Diphenyl-1-picrylhydrazyl(DPPH)scavenging and reducing power assays.Cytotoxicity was assessed using an MTT assay,while reactive oxygen species(ROS)generation was quantified using a 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA)assay.Anticancer properties,including colony formation inhibition and migration suppression,were examined using colony formation and wound healing assays.The expression of apoptotic and inflammatory mediators was analysed through qPCR.Results:GMAS 01 selectively induced apoptosis in A549 cells without cytotoxic effects on RAW264.7 and HaCaT cells.Mechanistically,it elevated intracellular ROS and activated the intrinsic mitochondrial apoptotic pathway,evidenced by p53 upregulation,increased Bax,and decreased Bcl-2 expression.GMAS 01 also significantly inhibited colony formation and migration in A549 cells.In RAW264.7 cells,it reduced nitric oxide(NO)production and downregulated iNOS,COX-2,IL-6,and IL-8,indicating strong immunomodulatory activity.Conclusion:GMAS 01 exhibits potent antioxidant,anti-inflammatory,and anticancer effects,likely mediated through ROS-induced mitochondrial apoptosis.However,mechanistic interpretations are limited by the absence of protein-level validation and pathway inhibition studies.Upcoming studies should aim to verify the underlying mechanisms and evaluate their potential for real-world application.
基金Supported by Scientific Research Project of Putian University,No.2022059Special Project for Outstanding Young Talents of Putian University,No.2024072Natural Science Foundation of Fujian Province,No.2023J01160.
文摘Gastric cancer(GC)remains one of the leading causes of cancer-related morbidity and mortality globally.Although significant progress has been made in treatment options,the survival rates for GC patients continue to be low.This is primarily attributed to the intricate and insufficiently understood mechanisms of disease progression,as well as the considerable challenges associated with tumor hetero-geneity.The recent study by Tang et al provides a detailed single-cell RNA se-quencing analysis of GC across different stages,revealing dynamic changes in the tumor microenvironment and key immune responses.We aim to offer a compre-hensive interpretation of the study’s findings and propose several innovative directions for future academic research in gastric cancer.These include exploring advanced multi-omics approaches,leveraging spatial transcriptomics,integrating artificial intelligence for clinical applications,and developing novel immuno-therapy strategies.We further emphasize the importance of personalized medi-cine,early detection,and novel drug discovery techniques in improving GC treatment outcomes.
文摘Vitamin D,beyond its classical role in calcium homeostasis,has emerged as a key regulator of immune function and epithelial barrier integrity.Its deficiency during early childhood—a critical period for immune maturation—has been increasingly implicated in the development of atopic diseases.While extensively studied in asthma,its role in non-respiratory allergic conditions such as atopic dermatitis(AD)and allergic rhinitis(AR)remains comparatively underexplored.This minireview synthesizes current mechanistic and clinical evidence on vitamin D in pediatric AD and AR.In AD,vitamin D promotes epidermal barrier function through upregulation of filaggrin and ceramide synthesis,and enhances antimicrobial defense via induction of antimicrobial peptides.Observational studies consistently report lower serum 25-hydroxyvitamin D in affected children,particularly those with allergic sensitization.Select randomized controlled trials suggest clinical improvement with supplementation,especially at doses>2000 IU/day in deficient individuals.In AR,epidemiological data indicate stronger inverse associations with seasonal(pollen-induced)disease.Proposed mechanisms include modulation of dendritic cells,regulatory T cells,T helper 2 cytokines,and mucosal barrier integrity.The shared immunopathogenesis of AD and AR underscores vitamin D’s relevance.Although promising,clinical evidence remains heterogeneous.Future research should prioritize phenotype-stratified trials to clarify optimal dosing,timing,and individual response determinants,including genetics and microbiome composition.
文摘The gut microbiome plays a pivotal role in immune homeostasis and systemic inflammatory regulation,both of which are critically involved in the pathogenesis and progression of pediatric leukemias.Recent evidence reveals that children with leukemia often exhibit distinct gut microbiome profiles at diagnosis,marked by reduced microbial diversity and the enrichment of pro-inflammatory taxa such as Enterococcus and Streptococcus.This microbial dysbiosis may promote leukemogenesis by disrupting immune regulation and driving chronic inflammation.Chemotherapy significantly alters the gut microbiome,inducing dysbiosis characterized by a loss of beneficial commensals and the dominance of pathobionts.Specific microbial signatures,such as the enrichment of Bacteroides,correlate with reduced inflammation and improved prognosis,underscoring the gut microbiome's prognostic value.Emerging therapies,including dietary adjustments,probiotics,and fecal gut microbiome transplantation,aim to restore microbial balance and reduce treatment-related complications.Moreover,gut microbiome profiling shows potential for identifying biomarkers linked to leukemia predisposition,paving the way for early diagnosis and tailored preventive strategies.This mini-review explores recent advancements in understanding the influence of the gut microbiome on pediatric leukemias,emphasizing its role as both a therapeutic target and a prognostic biomarker.Integrating gut microbiome research into clinical practice may help optimize treatment outcomes and improve quality of life for children with leukemia.
基金Supported by the National Natural Science Foundation of China,No.82100691China Postdoctoral Science Foundation,No.2021M693631.
文摘Organ transplantation has long been recognized as an effective treatment for endstage organ failure,metabolic diseases,and malignant tumors.However,graft rejection caused by major histocompatibility complex mismatch remains a significant challenge.While modern immunosuppressants have made significant strides in reducing the incidence and risk of rejection,they have not been able to eliminate it completely.The intricate mechanisms underlying transplant rejection have been the subject of intense investigation by transplant immunologists.Among these factors,autophagy has emerged as a key player.Autophagy is an evolutionarily conserved mechanism in eukaryotic cells that mediates autophagocytosis and cellular protection.This process is regulated by autophagy-related genes and their encoded protein families,which maintain the material and energetic balance within cells.Additionally,autophagy has been reported to play crucial roles in the development,maturation,differentiation,and responses of immune cells.In the complex immune environment following transplantation,the role and mechanisms of autophagy are gradually being revealed.In this review,we aim to explore the current understanding of the role of autophagy in solid organ rejection after transplantation.Furthermore,we delve into the therapeutic advancements achieved by targeting autophagy involved in the rejection process.
基金funded by the Europe Economic Area(EEA)and Norway Grants 2014-2021,Grant No.EEA-RESEARCH-164 for AM,ALl,and ALi.
文摘Background Preclinical studies demonstrate that exercise reduces tumor incidence and growth.Rapid release of extracellular vesicles(EVs)during exercise suggests their potential role as mediators of exercise-induced systemic effects and physiological adaptation.This study investigated the impact of exercise-induced plasma EVs on tumor growth and immune tumor microenvironment in murine models of triple-negative breast cancer(TNBC):EO771(a C57BL/6-derived TNBC cell line)and 4T1(a BALB/c-derived TNBC cell line).Methods Size exclusion chromatography was used to isolate exercise-induced EVs from plasma of healthy female mice(BALB/c and C56BL/6,n=30 per strain)that underwent ten 30-min moderate-intensity treadmill running sessions over 2 weeks.Nanoparticle tracking analysis,Western blot,and electron microscopy confirmed the presence of EVs in the samples.Tumor-bearing mice(n=72 per strain)were administered with exercise-induced EVs before or/and after tumor implantation.Local and systemic immune responses were assessed using flow cytometry,enzyme-linked immunosorbent assay(ELISA),and quantitative polymerase chain reaction(qPCR).Results Administration of exercise-induced EVs,particularly before tumor implantation,significantly suppressed tumor growth and reduced tumor burden in both TNBC models.In EO771,endpoint tumor volumes were 278–330 mm^(3)in treated groups compared to 799 mm^(3)in untreated(p<0.0001),while in 4T1,treated groups showed volumes of 287–564 mm^(3)vs.696 mm^(3)in untreated(p=0.0002).Notable differences in tumor-infiltrating lymphoid and myeloid cell subpopulations indicated immunomodulatory effects of exercise-induced EVs,particularly in the 4T1 model,where their continuous administration significantly increased intratumoral cluster of differentiation 8(CD8)T lymphocyte proportion(5.77%vs.0.90%in untreated,p<0.0001).Similarly,in the EO771 model,exercise-induced EVs administered before tumor implantation led to a marked rise in intratumoral CD8 T lymphocytes(2.24%vs.1.08%in untreated,p=0.0181).Conclusion Our findings indicate that exercise-induced EV treatment elicits a pro-inflammatory antitumor immune response,suggesting a shift of immunologically cold TNBC tumors towards a more inflamed phenotype associated with better outcomes.Our study supports the further investigation of EVs as modulators of antitumor immunity and their potential utility in enhancing the efficacy of immunotherapy.
基金supported through National Research Foundation(NRF)of Korea grants funded by the Korean Government(No.NRF-2022R1F1A1064405)the research fund of Catholic Kwandong University and Catholic Kwandong University International St.Mary’s Hospital for S.-W Kim.
文摘Objectives:Despite the considerable regenerative capacity exhibited by adipose-derived mesenchymal stem cells(ASCs),their genetic and molecular mechanisms remain incompletely understood.Methods:In this study,we analyzed the global gene expression profile of adipose-derived mesenchymal stem cells(ASCs)using microarray analysis and compared it with stromal vascular fraction(SVF)cells.Results:Microarray analysis revealed that ASCs express elevated levels of genes related to the extracellular matrix(ECM;extracellular matrix)and collagen,which are critical components of tissue remodeling and wound healing.Additionally,genes associated with cell growth,differentiation,motility,and plasticity were highly expressed.When compared to stromal vascular fraction(SVF)cells,ASCs demonstrated enrichment of genes involved in anti-inflammatory responses,immune modulation,tissue repair,cell adhesion,and migration processes.Gene Set Enrichment Analysis(GSEA;Gene Set Enrichment Analysis)showed activation of pathways related to angiogenesis,such as vascular endothelial growth factor(VEGF),Integrin,Wnt signaling pathways,transforming growth factor-beta(TGF-β),extracellular matrix(ECM),and matrix metalloproteinase(MMP),highlighting the significant angiogenic potential of ASCs.Gene Ontology(GO;Gene Ontology)analysis further linked ASCs to biological processes associated with the regulation of cell proliferation and muscle cell differentiation.Conclusion:These findings collectively underscore the suitability of adipose-derived mesenchymal stem cells(ASCs)as a promising candidate for regenerative medicine,particularly in applications involving tissue repair,immune modulation,and promotion of angiogenesis.
文摘Two hundred and forty specific pathogen free leghorn chickens were randomly divided into four groups and reared in isolated pens. The tested chickens were negative to infectious bursal disease virus （IBDV） at 25 d old. Group 1 was treated with saline, whereas Groups 2, 3, and 4 were inoculated with 0.3 mL IBDV suspension intranasally the next day. Groups 3 and 4 were also administered with Astragalus polysaccharides （APS） intramuscularly twice daily at 5 or 10 mg kg-1 BW, respectively, until 31 d old. The erythrocyte-C3b receptor rosette rate （E-C3bRR） and the erythrocyte-C3b immune complex rosette rate （E-ICRR） were measured at 25, 29, 32, 35, and 38 d old. The results showed that IBDV significantly reduced E-C3bRR and E-ICRR when compared with the control group （P 〈 0.05）, while simultaneous administration of APS with 1BDV maintained E-C3bRR at similar levels to the control group （P 〉 0.05） and increased E-ICRR when compared with the control group and the group non-treated with APS （P 〈 0.05）. APS treatment reduced the morbidity and mortality of chickens inoculated with IBDV （P 〈 0.05）. The results suggest that APS may enhance the immune adherence of chickens erythrocytes by affecting the activity and/or the number of complement receptors on the erythrocyte membrane. These findings can be beneficial in providing an understanding of the basic mechanisms required for the rational application of APS in modern medicine.
基金Supported by The Small and Medium Business Administration,No. S1072365the Next-Generation BioGreen 21 Program,No. PJ008005,Rural Development Administration,South Korea
文摘AIM： To investigate cytokine production and cell surface phenotypes of dendritic cells （DC） in the presence of epithelial cells stimulated by probiotics.METHODS： Mouse DC were cultured alone or together with mouse epithelial cell monolayers in normal or in- verted systems and were stimulated with heat-killed probiotic bacteria, Bifidobacterium lactis ADO 11 （BL）, Bifidobacterium bilfidum BGN4 （BB）, Lactobacillus casei IBS041 （LC）, and Lactobacillus acidophilus AD031 （LA）, for 12 h. Cytokine levels in the culture supernatants were determined by enzyme-linked immunosorbent as say and phenotypic analysis of DC was investigated by flow cytometry.RESULTS： BB and LC in singlecultured DC increased the expression of I-Ad, CD86 and CD40 （I-Ad, 18.51 vs 30.88, 46.11, CD86, 62.74 vs 92.7, 104.12; CD40, 0.67 vs 6.39, 3.37, P 〈 0.05）. All of the experimental probiot-ics increased the production of inflammatory cytokines, interleukin （IL）-6 and tumor necrosis factor （TNF）-α. However, in the normal coculture systems, LC and LA decreased the expression of I-A^α （39.46 vs 30.32, 33.26, P 〈 0.05）, and none of the experimental probiotics increased the levels of IL-6 or TNF-α. In the inverted coculture systems, LC decreased the expression of CD40 （1.36 vs -2.27, P 〈 0.05）, and all of the experimental probiotics decreased the levels of IL-6. In addition, BL increased the production of IL-10 （103.8 vs 166.0, P 〈 0.05） and LC and LA increased transforming growth factor-13 secretion （235.9 vs 618.9, 607.6, P 〈 0.05）.CONCLUSION： These results suggest that specific pro- biotic strains exert differential immune modulation mediated by the interaction of dendritic cells and epithelial cells in the homeostasis of gastrointestinal tract.
文摘In the immune oncology era,the clinical efficacy of immune checkpoint inhibitors(ICIs)against most solid cancers is well known.In hepatocellular carcinoma,the recent success of combination therapy with targeting agents has accelerated the search for novel combination strategies.Radiotherapy(RT),an attractive modality,can be combined with ICIs,which act as strong modulators of the tumor immune microenvironment.Herein,we discuss immune modulation caused by radiation and the current trials of RT-ICI combination treatment as well as future perspectives.
文摘Objective: To study mechanisms by which human gliomas may escape immune surveillance Methods: The effect of supernatant (SN) obtained from cultured media of malignant glioma cell lines on the proliferation of phytohemagglutinin p stimulated peripheral blood lymphocytes (PBLs) from healthy subjects and patients with gliomas was examined by MTT assay The immunosuppressive factor which might be existed in the SN was identified by neutralization method with specific antibodies and Northern blot hybridization of glioma cells In addition, the cellular immunity of patients with gliomas and relevant hormone and catecholamine were determined Results: It was found that the malignant glioma cells could release an immunosuppressive factor in an autocrine fashion which was further identified as the transforming growth factor β 2 (TGF β 2) It was also demonstrated that the plasma levels of norepinephrine in glioma patients were significantly reduced and correlated well with the suppression of the patients' own cellular immunity Conclusions: Two distinct mechanisms by which human gliomas may evade immune surveillance: 1 The secretion of an immunosuppressive factor which was identified as TGF β 2; 2 The dysfunction of Neuro Immune modulation in the presence of cerebral gliomas
