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
Cell membrane-derived nanovesicles(CMNVs)are nanoscale lipid bilayer structures obtained from cellular membranes that serve as biomimetic drug delivery platforms,offering immune evasion,targeting,and surface functiona...Cell membrane-derived nanovesicles(CMNVs)are nanoscale lipid bilayer structures obtained from cellular membranes that serve as biomimetic drug delivery platforms,offering immune evasion,targeting,and surface functionalization capabilities.While most CMNVs originate from mammalian cells,Toxoplasma gondii(T.gondii),a genetically tractable protozoan with a structurally distinct membrane,offers a high-yield and underexplored source for producing T.gondii-derived CMNVs(TgCMNVs).These vesicles are obtained from the parasite’s plasma membrane and inner membrane complex and retain unique features including abundant GPI-anchored SRS proteins,phosphatidylthreonine-rich lipids,and an editable genome,enabling versatile engineering via genetic and chemical strategies.We review methods for TgCMNV fabrication,purification,and functionalization,and evaluate their potential in immunomodulation,attenuation of tissue injury,cancer immunotherapy,and self-adjuvanting vaccine design.By combining intrinsic immune engagement with programmable surface architec-ture,TgCMNVs could serve as a complementary and adaptable platform alongside established CMNV systems.Finally,we discuss key translational considerations,including scalable production,immunogenicity control,regulatory compliance,and stability testing,which will be essential for assessing the feasibility of TgCMNVs in clinical applications.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
Metal-based antimicrobial materials have been extensively studied and applied over decades.While these materials are notably characterized by their superior antibacterial performance and low propensity to induce drug ...Metal-based antimicrobial materials have been extensively studied and applied over decades.While these materials are notably characterized by their superior antibacterial performance and low propensity to induce drug resistance,critical limitations such as inherent cytotoxicity,poor solubility,and instability in aqueous solution remain significant challenges requiring systematic optimization.In this study,we synthesized water-soluble molecular iron-oxo clusters(MIC)with excellent biosafety and stability of aqueous solution.Our findings demonstrate that MIC exhibits marked therapeutic efficacy in cecal ligation and puncture induced sepsis models,a critical validation given sepsis'etiology as a life-threatening infection mediated systemic inflammatory syndrome.MIC combats bacteria by enhancing humoral immune responsiveness.MIC significantly improved the survival rate,reduced bacterial burden,stabilized body temperature,and modulated cytokine profiles in mice with sepsis.Further investigations revealed that MIC promotes B cells proliferation and oxidative phosphorylation,and mitigates mitochondrial damage and apoptosis in B cells,suggesting its role in modulating cellular metabolism.RNA sequencing analysis demonstrated that MIC exerts its effects by influencing key pathways involved in humoral immunity,inflammatory responses,and metabolic adaptation.These findings establish MIC as a novel therapeutic agent for regulating immune responses in sepsis,providing innovative strategies to improve recovery from this life-threatening condition.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
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
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
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
Blinding diseases such as photoreceptor degenerations are debilitating conditions that severely impair daily lives of affected patients.This group of diseases are amenable to photoreceptor replacement therapies and re...Blinding diseases such as photoreceptor degenerations are debilitating conditions that severely impair daily lives of affected patients.This group of diseases are amenable to photoreceptor replacement therapies and recent transplantation studies provided proof-of-principle for functional recovery at the retinal and behavioral level,though the actual mechanism of repair still needs further investigations.The immune system responds in several ways upon photoreceptor engraftment,resulting in T-cell and macrophage infiltrations and,consequently,decrease in graft survival.Most studies on the role of the immune system suggest a detrimental effect in a therapeutic setting.Conversely,the opposite idea wherein the immune system can be activated towards a protective state was also explored in other experimental paradigms.Here,Neves and colleagues explored the potential of cross-species studies and,to a certain extent,the concept of a protective immune system in retinal degeneration and therapy.Mesencephalic astrocyte-derived neurotrophic factor(MANF)was identified in this study as a novel factor that,by modulating the immune system,can slow down photoreceptor degeneration and improve transplantation outcome.展开更多
Flap ischemia-reperfusion(I/R)injury triggers intense inflammatory responses and oxidative stress following blood flow restoration,often resulting in tissue dysfunction.Currently,no effective and widely recognized tre...Flap ischemia-reperfusion(I/R)injury triggers intense inflammatory responses and oxidative stress following blood flow restoration,often resulting in tissue dysfunction.Currently,no effective and widely recognized treatment strategies are available in clinical practice.During flap I/R injury,macrophages,T cells,and neu-trophils form a complex regulatory network that jointly participates in inflammatory responses,immune mod-ulation,and tissue repair.Achieving a dynamic balance among these three cell types is critical for flap survival and healing.In this study,a novel Cu-DHM NP metal-polyphenol nanozyme that effectively amplifies immune modulation in a cascade manner,inhibits apoptosis,and treats flap I/R injury was developed.Leveraging their excellent antioxidant properties and SOD-like and CAT-like enzyme activities,Cu-DHM NPs eliminate ROS,alleviate intracellular oxidative stress,protect mitochondrial function,and reduce apoptosis.Moreover,Cu-DHM NPs can regulate the immune microenvironment,cascade and amplify the immunomodulatory effect between macrophages and Naive CD4^(+)T cells,increase the proportions of M2 macrophages and Treg cells,and alleviate inflammation.In animal experiments,Cu-DHM NPs downregulated several pathways associated with inflam-mation and cell death.Cu-DHM NPs inhibited apoptosis,reduced neutrophil infiltration,alleviated inflamma-tion,enhanced angiogenesis,and ultimately improved flap survival rates.This novel metal-polyphenol nanozyme offers a new strategy for treating flap I/R injury by increasing immune modulation and inhibiting apoptosis.展开更多
Inflammatory responses are essential in eliminating harmful substrates from damaged tissue and inducing recovery.Several cytokines participate in and facilitate this response. Certain cytokines such as interleukin(IL...Inflammatory responses are essential in eliminating harmful substrates from damaged tissue and inducing recovery.Several cytokines participate in and facilitate this response. Certain cytokines such as interleukin(IL)-1β and IL-18 are initially produced in precursor form in response to toll-like receptor(TLR) ligands and undergo maturation by inflammasomes, which are cytosolic multi-protein complexes containing nucleotide-binding oligomerization domain(NOD)-containing protein 2-like receptors(NLRs). Immune modulators targeting inflammasomes have been investigated to control inflammatory diseases such as metabolic syndrome. However, most immune modulators possessing anti-inflammasome properties attenuate production of other cytokines, which are essential for host defense. In this review, we analyzed the effect of anti-inflammasome agents on the production of cytokines which are not regulated by inflammasome and involving in initial immune responses. As a result, the infiammasome inhibitors are put into three categories: non-effector, stimulator, or inhibitor of cytokine production. Even the stimulator of cytokine production ameliorated symptoms resulting from inflammasome activation in mouse models. Thus, we suggest ideal immune modulators targeting inflammasomes in order to enhance cytokine production while inhibiting cytokine maturation.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
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.
基金supported in part by grants from the National Natural Science Foundation of China(82470719)High-level Medical Team Project in Baoan,Shenzhen(202401).
文摘Cell membrane-derived nanovesicles(CMNVs)are nanoscale lipid bilayer structures obtained from cellular membranes that serve as biomimetic drug delivery platforms,offering immune evasion,targeting,and surface functionalization capabilities.While most CMNVs originate from mammalian cells,Toxoplasma gondii(T.gondii),a genetically tractable protozoan with a structurally distinct membrane,offers a high-yield and underexplored source for producing T.gondii-derived CMNVs(TgCMNVs).These vesicles are obtained from the parasite’s plasma membrane and inner membrane complex and retain unique features including abundant GPI-anchored SRS proteins,phosphatidylthreonine-rich lipids,and an editable genome,enabling versatile engineering via genetic and chemical strategies.We review methods for TgCMNV fabrication,purification,and functionalization,and evaluate their potential in immunomodulation,attenuation of tissue injury,cancer immunotherapy,and self-adjuvanting vaccine design.By combining intrinsic immune engagement with programmable surface architec-ture,TgCMNVs could serve as a complementary and adaptable platform alongside established CMNV systems.Finally,we discuss key translational considerations,including scalable production,immunogenicity control,regulatory compliance,and stability testing,which will be essential for assessing the feasibility of TgCMNVs in clinical applications.
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.
基金the generous supported by the National Key R&D Program of China(No.2023YFC2413100)the National Natural Science Foundation of China(Nos.22322102,21871042 and 21471028)+1 种基金the Fundamental Research Funds for the Central Universities-Excellent Youth Team Program(No.2412023YQ001)the Natural Science Foundation of Jilin Province(Nos.YDZJ202401550ZYTS,20200201083JC)。
文摘Metal-based antimicrobial materials have been extensively studied and applied over decades.While these materials are notably characterized by their superior antibacterial performance and low propensity to induce drug resistance,critical limitations such as inherent cytotoxicity,poor solubility,and instability in aqueous solution remain significant challenges requiring systematic optimization.In this study,we synthesized water-soluble molecular iron-oxo clusters(MIC)with excellent biosafety and stability of aqueous solution.Our findings demonstrate that MIC exhibits marked therapeutic efficacy in cecal ligation and puncture induced sepsis models,a critical validation given sepsis'etiology as a life-threatening infection mediated systemic inflammatory syndrome.MIC combats bacteria by enhancing humoral immune responsiveness.MIC significantly improved the survival rate,reduced bacterial burden,stabilized body temperature,and modulated cytokine profiles in mice with sepsis.Further investigations revealed that MIC promotes B cells proliferation and oxidative phosphorylation,and mitigates mitochondrial damage and apoptosis in B cells,suggesting its role in modulating cellular metabolism.RNA sequencing analysis demonstrated that MIC exerts its effects by influencing key pathways involved in humoral immunity,inflammatory responses,and metabolic adaptation.These findings establish MIC as a novel therapeutic agent for regulating immune responses in sepsis,providing innovative strategies to improve recovery from this life-threatening condition.
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.
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
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Blinding diseases such as photoreceptor degenerations are debilitating conditions that severely impair daily lives of affected patients.This group of diseases are amenable to photoreceptor replacement therapies and recent transplantation studies provided proof-of-principle for functional recovery at the retinal and behavioral level,though the actual mechanism of repair still needs further investigations.The immune system responds in several ways upon photoreceptor engraftment,resulting in T-cell and macrophage infiltrations and,consequently,decrease in graft survival.Most studies on the role of the immune system suggest a detrimental effect in a therapeutic setting.Conversely,the opposite idea wherein the immune system can be activated towards a protective state was also explored in other experimental paradigms.Here,Neves and colleagues explored the potential of cross-species studies and,to a certain extent,the concept of a protective immune system in retinal degeneration and therapy.Mesencephalic astrocyte-derived neurotrophic factor(MANF)was identified in this study as a novel factor that,by modulating the immune system,can slow down photoreceptor degeneration and improve transplantation outcome.
基金supported by the National Natural Science Foundation of China(82172204,82372552,82372517)the Anhui Provincial Natural Science Foundation(2408085Y016)+1 种基金the Anhui Key Research and Development Plan(202104j07020027)the Excellent Youth of Natural Science Research Projects in Anhui Province Universities(2023AH030060).
文摘Flap ischemia-reperfusion(I/R)injury triggers intense inflammatory responses and oxidative stress following blood flow restoration,often resulting in tissue dysfunction.Currently,no effective and widely recognized treatment strategies are available in clinical practice.During flap I/R injury,macrophages,T cells,and neu-trophils form a complex regulatory network that jointly participates in inflammatory responses,immune mod-ulation,and tissue repair.Achieving a dynamic balance among these three cell types is critical for flap survival and healing.In this study,a novel Cu-DHM NP metal-polyphenol nanozyme that effectively amplifies immune modulation in a cascade manner,inhibits apoptosis,and treats flap I/R injury was developed.Leveraging their excellent antioxidant properties and SOD-like and CAT-like enzyme activities,Cu-DHM NPs eliminate ROS,alleviate intracellular oxidative stress,protect mitochondrial function,and reduce apoptosis.Moreover,Cu-DHM NPs can regulate the immune microenvironment,cascade and amplify the immunomodulatory effect between macrophages and Naive CD4^(+)T cells,increase the proportions of M2 macrophages and Treg cells,and alleviate inflammation.In animal experiments,Cu-DHM NPs downregulated several pathways associated with inflam-mation and cell death.Cu-DHM NPs inhibited apoptosis,reduced neutrophil infiltration,alleviated inflamma-tion,enhanced angiogenesis,and ultimately improved flap survival rates.This novel metal-polyphenol nanozyme offers a new strategy for treating flap I/R injury by increasing immune modulation and inhibiting apoptosis.
基金supported by 2015 Research Grant from Kangwon National University(No.520150280)
文摘Inflammatory responses are essential in eliminating harmful substrates from damaged tissue and inducing recovery.Several cytokines participate in and facilitate this response. Certain cytokines such as interleukin(IL)-1β and IL-18 are initially produced in precursor form in response to toll-like receptor(TLR) ligands and undergo maturation by inflammasomes, which are cytosolic multi-protein complexes containing nucleotide-binding oligomerization domain(NOD)-containing protein 2-like receptors(NLRs). Immune modulators targeting inflammasomes have been investigated to control inflammatory diseases such as metabolic syndrome. However, most immune modulators possessing anti-inflammasome properties attenuate production of other cytokines, which are essential for host defense. In this review, we analyzed the effect of anti-inflammasome agents on the production of cytokines which are not regulated by inflammasome and involving in initial immune responses. As a result, the infiammasome inhibitors are put into three categories: non-effector, stimulator, or inhibitor of cytokine production. Even the stimulator of cytokine production ameliorated symptoms resulting from inflammasome activation in mouse models. Thus, we suggest ideal immune modulators targeting inflammasomes in order to enhance cytokine production while inhibiting cytokine maturation.
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.
