Objective: Human embryonic stem cells (hESCs) have recently been reported as an unlimited source of mesenchymal stem cells (MSCs).The present study not only provides an identical and clinically compliant MSC source de...Objective: Human embryonic stem cells (hESCs) have recently been reported as an unlimited source of mesenchymal stem cells (MSCs).The present study not only provides an identical and clinically compliant MSC source derived from hESCs (hESC-MSCs),but also describes the immunomodulative effects of hESC-MSCs in vitro and in vivo for a carbon tetrachloride (CCl4)-induced liver inflammation model.Methods: Undifferentiated hESCs were treated with Rho-associated kinase (ROCK) inhibitor and induced to fibroblast-looking cells.These cells were tested for their surface markers and multilineage differentiation capability.Further more,we analyzed their immune characteristics by mixed lymphocyte reactions (MLRs) and animal experiments.Results: hESC-MSCs show a homogenous fibroblastic morphology that resembles bone marrow-derived MSCs (BM-MSCs).The cell markers and differentiation potential of hESC-MSCs are also similar to those of BM-MSCs.Unlike their original cells,hESC-MSCs possess poor immunogenicity and can survive and be engrafted into a xenogenic immunocompetent environment.Conclusions: The hESC-MSCs demonstrate strong inhibitory effects on lymphocyte proliferation in vitro and anti-inflammatory infiltration properties in vivo.This study offers information essential to the applications of hESC-MSC-based therapies and evidence for the therapeutic mechanisms of action.展开更多
BACKGROUND Mesenchymal stem cells,found in various tissues,possess significant healing and immunomodulatory properties,influencing macrophage polarization,which is essential for wound repair.However,chronic wounds pre...BACKGROUND Mesenchymal stem cells,found in various tissues,possess significant healing and immunomodulatory properties,influencing macrophage polarization,which is essential for wound repair.However,chronic wounds present significant therapeutic challenges,requiring novel strategies to improve healing outcomes.AIM To investigate the potential of fetal dermal mesenchymal stem cells(FDMSCs)in enhancing wound healing through modulation of macrophage polarization,specifically by promoting the M2 phenotype to address inflammatory responses in chronic wounds.METHODS FDMSCs were isolated from BalB/C mice and co-cultured with RAW264.7 macrophages to assess their effects on macrophage polarization.Flow cytometry,quantitative reverse transcriptase polymerase chain reaction,and histological analyses were employed to evaluate shifts in macrophage phenotype and wound healing in a mouse model.Statistical analysis was performed using GraphPad Prism.RESULTS FDMSCs induced macrophage polarization from the M1 to M2 phenotype,as demonstrated by a reduction in proinflammatory markers(inducible nitric oxide synthase,interleukin-6)and an increase in anti-inflammatory markers[mannose receptor(CD206),arginase-1]in co-cultured RAW264.7 macrophages.These shifts were confirmed by flow cytometry.In an acute skin wound model,FDMSC-treated mice exhibited faster wound healing,enhanced collagen deposition,and improved vascular regeneration compared to controls.Significantly higher expression of arginase-1 further indicated an enriched M2 macrophage environment.CONCLUSION FDMSCs effectively modulate macrophage polarization from M1 to M2,reduce inflammation,and enhance tissue repair,demonstrating their potential as an immunomodulatory strategy in wound healing.These findings highlight the promising therapeutic application of FDMSCs in managing chronic wounds.展开更多
Background Broiler chickens are most vulnerable immediately after hatching due to their immature immune systems,making them susceptible to infectious diseases.The yolk plays an important role in early immune defence b...Background Broiler chickens are most vulnerable immediately after hatching due to their immature immune systems,making them susceptible to infectious diseases.The yolk plays an important role in early immune defence by showing relevant antioxidant and passive immunity capabilities during broiler embryonic development.The immunomodulatory effects of phytogenic compound carvacrol have been widely reported.After in ovo delivery in the amniotic fluid during embryonic development carvacrol is known to migrate to the yolk sac.However,it is unknown whether carvacrol in the yolk could enhance defence responsiveness in the yolk sac.Therefore,the aim of this study was to improve early immune function in chicken embryos,and it was hypothesized that in ovo delivery of carvacrol would result in immunomodulatory effects in the yolk sac,potentially improving post-hatch resilience.Methods On embryonic day(E)17.5,either a saline(control)or carvacrol solution was injected into the amniotic fluid.Yolk sac tissue samples were collected at E19.5,and transcriptomic analyses using RNA sequencing were performed,following functional enrichment analyses comparing the control(saline)and carvacrol-injected groups.Results The results showed that 268 genes were upregulated and 174 downregulated in the carvacrol group compared to the control(P<0.05;logFC<-0.5 or log FC>0.5).Functional analyses of these differentially expressed genes,using KEGG,REACTOME,and Gene Ontology databases,showed enrichment of several immune-related pathways.This included the pathways‘Antimicrobial peptides’(P=0.001)and‘Chemoattractant activity’(P=0.004),amongst others.Moreover,the‘NOD-like receptor signaling’pathway was enriched(P=0.002).Antimicrobial peptides are part of the innate immune defence and are amongst the molecules produced after the nucleotide oligomeriza-tion domain(NOD)-like receptor pathway activation.While these responses may be associated with an inflammatory reaction to an exogenous threat,they could also indicate that in ovo delivery of carvacrol could prepare the newly hatched chick against bacterial pathogens by potentially promoting antimicrobial peptide production through acti-vation of NOD-like receptor signaling in the yolk sac.Conclusion In conclusion,these findings suggest that in ovo delivery of carvacrol has the potential to enhance anti-pathogenic and pro-inflammatory responses in the yolk sac via upregulation of antimicrobial peptides,and NOD-like receptor pathways.展开更多
Severe tissue defects present formidable challenges to human health,persisting as major contributors to mortality rates.The complex pathological microenvironment,particularly the disrupted immune landscape within thes...Severe tissue defects present formidable challenges to human health,persisting as major contributors to mortality rates.The complex pathological microenvironment,particularly the disrupted immune landscape within these defects,poses substantial hurdles to existing tissue regeneration strategies.However,the emergence of nanobiotechnology has opened a new direction in immunomodulatory nanomedicine,providing encouraging prospects for tissue regeneration and restoration.This review aims to gather recent advances in immunomodulatory nanomedicine to foster tissue regeneration.We begin by elucidating the distinctive features of the local immune microenvironment within defective tissues and its crucial role in tissue regeneration.Subsequently,we explore the design and functional properties of immunomodulatory nanosystems.Finally,we address the challenges and prospects of clinical translation in nanomedicine development,aiming to propose a potent approach to enhance tissue regeneration through synergistic immune modulation and nanomedicine integration.展开更多
Humans and other vertebrates are safeguarded from invading pathogenic microbes by the immune system.Black seed,scientifically known as Nigella sativa,has garnered attention for its potential immunomodulatory effects i...Humans and other vertebrates are safeguarded from invading pathogenic microbes by the immune system.Black seed,scientifically known as Nigella sativa,has garnered attention for its potential immunomodulatory effects in both clinical and preclinical studies.This comprehensive review aims to consolidate and analyze the existing body of evidence surrounding the immunological impact of black seeds.In this review,we analyze the immunomodulatory potentials of black seeds(N.sativa).For the purpose of finding pertinent publications,the literatures was searched in web-based databases,including Web of Science,Medline/PMC/PubMed,Embase,EBSCO,Google Scholar,Science Direct,and reference lists.Several clinical,in vivo,and in vitro studies have demonstrated that supplementation with black seeds(N.sativa)has potential immunomodulatory activity.Black seeds(N.sativa)may influence immune responses through a variety of mechanisms.By synthesizing and critically assessing the current state of knowledge on the immunomodulatory effects of black seeds,this review aims to provide valuable insights into the potential therapeutic uses and future research directions for harnessing the immunological benefits of this natural remedy.展开更多
The remodeling of macrophages mediated by biomaterials is an important step in osseointegration.The biointerfacial characteristics shaped by implants and the bioenergetic state derived from macrophages are considered ...The remodeling of macrophages mediated by biomaterials is an important step in osseointegration.The biointerfacial characteristics shaped by implants and the bioenergetic state derived from macrophages are considered the key to macrophage reprogramming.In this study,the integrated Ti/Zn composites with optimized morphology and bioactive phase were prepared by friction stir processing,which could meet the multi-biofunctional requirements in the application of narrow-diameter implants.The severe plastic deformation and the hindrance of Zn particles to grain growth promote grain refinement,resulting in enhanced mechanical properties.The cell interfacial adhesion mediated by the grain boundary collaborated the energy metabolism reprogramming induced by the released Zn ion,promoting jointly anti-inflammatory cascade in macrophages and favorable osteogenesis in bone marrow mesenchymal stem cells(BMSCs).This study provides a new simultaneous approach of morphology and composition modification for titanium implants,and reveals the important role of grain size and bioactive element in the reversion of macrophage fate as well.展开更多
The treatment of prolonged inflammation and cartilage damage due to osteoarthritis(OA)is a major clinical challenge.We developed a comprehensive cartilage repair therapy using a dual drug-loaded nanocomposite hydrogel...The treatment of prolonged inflammation and cartilage damage due to osteoarthritis(OA)is a major clinical challenge.We developed a comprehensive cartilage repair therapy using a dual drug-loaded nanocomposite hydrogel that leveraged the spatiotemporal immunomodulatory effects of a naturally degradable protein-based nanocomposite hydrogel.The hydrogel acted as a scaffold that created a favorable microenvironment for cartilage regeneration.The hydrogel recruited macrophages and human mesenchymal stem cells(hMSCs),which supported the growth and adhesion of osteoblasts,and degraded to provide nutrition.Silk protein nanoparticles were chemically cross-linked with kartogenin,and humanlike collagen was physically cross-linked with dexamethasone through hydrogen bonding.In the early stages of cartilage repair,a large quantity of dexamethasone was released.The dexamethasone acted as an anti-inflammatory agent and a spatiotemporal modulator of the polarization of M1 macrophages into M2 macrophages.In the middle and late stages of cartilage repair,kartogenin underwent sustained release from the hydrogel,inducing the differentiation of hMSCs into chondrocytes and maintaining chondrocyte stability.Therefore,kartogenin and dexamethasone acted synergistically to induce cartilage repair.In conclusion,we developed an integrated therapeutic system by constructing a cartilage regeneration microenvironment and inducing synergistic drug-based cartilage regeneration.The therapeutic system demonstrated satisfactory efficacy for repairing cartilage damage in rabbits.展开更多
Type 2 diabetes mellitus(T2DM)is a metabolic disorder marked by chronic hyperglycemia and low-grade inflammation,contributing to various complications.Natural agents with immunomodulatory and antioxidant properties ha...Type 2 diabetes mellitus(T2DM)is a metabolic disorder marked by chronic hyperglycemia and low-grade inflammation,contributing to various complications.Natural agents with immunomodulatory and antioxidant properties have gained attention as adjunct therapies.To review the effects of Allium sativum on inflammatory pathways and metabolic alterations associated with T2DM.A narrative review was performed using PubMed/MEDLINE,EMBASE,and Scielo databases.The search included terms such as“allium sativum”,“inflammation",“oxidative stress”,and“diabetes mellitus”.Studies in English and Spanish-ranging from clinical trials to meta-analyses-were selected based on relevance.Bioactive compounds such as allicin,S-allyl cysteine,and diallyl disulfide exhibit anti-inflammatory,antioxidant,hypoglycemic,and lipid-lowering actions.Preclinical studies show improved glucose metabolism,insulin sensitivity,and organ function.Moreover,clinical evidence supports reductions in fasting glucose,hemoglobin A1c,blood pressure,and oxidative stress,with good safety profiles.Allium sativum appears to be a promising adjuvant in T2DM management,offering metabolic and anti-inflammatory benefits.Nonetheless,further high-quality clinical trials are needed to confirm its long-term efficacy and standardize its therapeutic use.展开更多
In adaptive immunity,antigens are presented to T cells,which then become effector T cells(CD4+)or cytotoxic T cells(CD8+).These are called adaptive immune T cells.Cancer immunotherapy based on anti-programmed death re...In adaptive immunity,antigens are presented to T cells,which then become effector T cells(CD4+)or cytotoxic T cells(CD8+).These are called adaptive immune T cells.Cancer immunotherapy based on anti-programmed death receptor-1(PD-1)/programmed cell death 1 ligand 1(PD-L1)antibodies is a new way to treat cancer.Chinese herbal medicines are often used with cancer treatments in clinical practice.Recent studies have shown that Chinese herbal medicines affect the immune system and have an effect on PD-1/PD-L1.Baicalin,the main ingredient of Scutellaria baicalensis,can stop Tregs from working,increase the number of CD8+T cells in the tumour microenvironment and avoid PD-1 resistance.Solamargine has anti-cancer activity in a variety of tumours,including stopping tumour growth,stopping PD-L1 expression and blocking immune escape in combination with Immune checkpoint inhibitors.Taraxasterol,found in dandelion,can regulate anti-tumour T cells.It affects CD4+T cells by inhibiting STAT3.Platycodonis Radix can reduce the expression of PD-1 on the surface of CD8+T cells and increase their ability to kill tumour cells.Licorice compounds can regulate the cell cycle and PD-L1 expression,which can lead to tumour cell cycle blockade and increase the level of PD-L1 expression,thereby exerting anti-tumour effects.Marsdenia tenacissima extracts weakened the immunosuppressive effect of IL-10,improved T-cell function,stopped tumour cells escaping the immune system and reduced TGF-β1 and PD-L1.Strobilanthes crispus F3 extract increases lymphocyte infiltration,improves T-cell-mediated cytotoxicity,modulates immune cell expression,stops tumour-associated macrophage activity and slows tumour progression.The last five years of research on herbs with purgative and detoxifying effects were reviewed.This review will investigate how herbs can affect adaptive immune T cells in the immune system to improve cancer treatment.展开更多
Neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease,are characterized by the progressive loss of neuronal function and structure,leading to severe morbidity and morta...Neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease,are characterized by the progressive loss of neuronal function and structure,leading to severe morbidity and mortality.Current therapeutic approaches are ineffective at stopping or reversing disease progression.Stem cell therapy has emerged as a promising candidate in research and treatment.Mesenchymal stem cells(MSCs)are considered ideal candidates for regenerative medicine because of their high proliferation rate and multi-differentiation potential.MSCs can differentiate into neurons and glial cells,modulate immune responses,and reduce inflammation,and their exosomes can promote neural repair and regulate neuronal function;thus,MSCs offer unique advantages for treating neurodegenerative diseases.However,challenges remain in optimizing cell delivery methods,ensuring the long-term survival and integration of transplanted cells,and fully understanding their therapeutic effects.This article primarily outlines the functions of MSCs in neurodegenerative diseases,with the intention that further research will fully harness their potential and translate these findings into clinical applications,offering new hope for patients suffering from neurodegenerative diseases.展开更多
Food allergy(FA) is an aberrant immune response triggered by the ingestion of a food antigen.Ovalbumin(OVA)-sensitized and challenged BALB/c mice were orally administered heat-killed(HK)-Lactobacillus paracasei JY56.I...Food allergy(FA) is an aberrant immune response triggered by the ingestion of a food antigen.Ovalbumin(OVA)-sensitized and challenged BALB/c mice were orally administered heat-killed(HK)-Lactobacillus paracasei JY56.In this work,HK-L.paracasei JY56 alleviated the FA-induced decrease in body weight and rectal temperature and reduced the allergy score.Serum analysis showed that HK-L.paracasei JY56 reduced the levels of specific antibodies(OVA-specific Immunoglobulin E(sIgE) and OVA-specific Immunoglobulin G(sIgG)) and allergic mediators(histamine and mast cell protease) in FA mice.In addition,HK-L.paracasei JY56 also could alleviate OVA-induced FA by suppressing T helper(Th)2 and Th17-type immune responses,which was evidenced by the regulation of splenic lymphocyte subpopulations and associated cytokine secretion.Moreover,jejunal histological analysis and intestinal barrier function related gene expression measurement were performed to verify the intestinal barrier repair of HK-L.paracasei JY56.Meanwhile,the TLR4/NF-κB inflammatory pathway activation was inhibited by HK-L.paracasei JY56 at gene and protein levels.Finally,HK-L.paracasei JY56 was performed to modulate the gut microbiota structure and increase the levels of short-chain fatty acids.In conclusion,HK-L.paracasei JY56 could alleviate OVA-induced FA in multiple ways,and this study provides a theoretical basis for the application of inactivated probiotics in functional foods for FA.展开更多
Mesenchymal stem cell(MSC)-derived extracellular vesicles(MSC-EVs)represent the next generation of biomedical applications,offering advantages over MSCs such as higher stability and lower immunogenicity.As cell-free n...Mesenchymal stem cell(MSC)-derived extracellular vesicles(MSC-EVs)represent the next generation of biomedical applications,offering advantages over MSCs such as higher stability and lower immunogenicity.As cell-free nanoparticles MSC-EVs have demonstrated both efficacy and safety in the treatment of a range of diseases.This article discussed the applications of MSC-EVs in hair regene-ration,immunomodulation,and the treatment of acute kidney injury.MSC-EVs promote hair regeneration by enhancing dermal papilla cell proliferation and migration.They also modulate immune responses and mitigate inflammation through immune-related signaling pathways.Additionally,MSC-EVs contribute to improved renal function by modulating multiple signaling pathways.Despite these promising applications challenges remain in the clinical translation of MSC-EVs.Overcoming these challenges requires extensive research to fully optimize the therapeutic potential of MSC-EVs and advance their translation into clinical practice.展开更多
Korla fragrant pears are one of the“famous,excellent,and special”fruits in Xinjiang.They belong to the white pear variety in the genus Pyrus of the Rosaceae family.With a long-standing planting history and strong re...Korla fragrant pears are one of the“famous,excellent,and special”fruits in Xinjiang.They belong to the white pear variety in the genus Pyrus of the Rosaceae family.With a long-standing planting history and strong regional characteristics,they are mainly produced in southern Xinjiang.Due to unique natural conditions such as large temperature differences between day and night and sufficient sunlight,Korla fragrant pears have a crispy texture,a sweet but not cloying taste,and their flesh is delicate and juicy,with excellent quality.Korla fragrant pears contain a variety of bioactive substances,mainly including polysaccharides,polyphenolic compounds,flavonoid compounds,triterpenoids,and sterols.They have medical effects such as“moistening the lungs,calming the heart,reducing phlegm,anti-inflammation,relieving cough,and resolving carbuncle toxins”.Uyghur and Mongolian medicine often use them as a good dietary therapy product.Based on recent literature reports,this paper reviews the main chemical constituents and pharmacological effects of Korla fragrant pears,aiming to provide references for the research and utilization of the deep processing of Korla fragrant pears.展开更多
The neem flower(Azadirachta indica),a well-known element of Ayurvedic medicine,has attracted considerable interest due to its abundance of bioactive compounds.This systematic review examines its pharmacological and im...The neem flower(Azadirachta indica),a well-known element of Ayurvedic medicine,has attracted considerable interest due to its abundance of bioactive compounds.This systematic review examines its pharmacological and immunomodulatory properties in detail,emphasizing its potential role in contemporary healthcare.Neem flowers are rich in various bioactive components,such as flavonoids,terpenoids,and glycosides,known for their antioxidant,anti-inflammatory,antimicrobial,and anticancer properties.Recent studies indicate that extracts from neem flowers can influence immune system activity by boosting both innate and adaptive immune functions while reducing excessive inflammation.These properties suggest that neem flowers could serve as valuable therapeutic agents for treating immune-related disorders.Additionally,neem flowers have demonstrated promise in addressing conditions such as diabetes,cardiovascular issues,and microbial infections through their ability to regulate metabolic functions and inhibit the growth of harmful pathogens.Preclinical research highlights their protective effects against oxidative damage and their capacity to induce apoptosis in cancer cells.However,challenges such as the lack of standardized extraction processes and limited clinical research hinder broader utilization.This review emphasizes the need for more robust studies to fully harness the pharmacological potential of neem flowers and facilitate their incorporation into evidence-based medicinal properties.展开更多
Kawasaki disease(KD)is an acute,self-limited systemic vasculitis that primarily affects children.Treating nonresponding KD with intravenous immunoglobulin(IVIG)presents numerous challenges.This article comprehensively...Kawasaki disease(KD)is an acute,self-limited systemic vasculitis that primarily affects children.Treating nonresponding KD with intravenous immunoglobulin(IVIG)presents numerous challenges.This article comprehensively reviews the basic theory,clinical manifestations and diagnosis,treatment strategies,disputes and challenges,historical evolution and current situation,and future research directions of immunoglobulin unresponsive KD.In terms of basic theory,the epidemiological characteristics of KD,the mechanism of IVIG action,and the pathophysiological mechanism of the nonresponsive type are elaborated.In the clinical manifestation and diagnosis section,symptoms,diagnostic criteria,and imaging applications are analyzed.The treatment strategy encompasses drug,nondrug and individualized therapy.Controversies and challenges focus on diagnostic difficulties,treatment disputes,and long-term prognosis research.The historical evolution and current situation review the changes in treatment strategies and the current state of affairs.Future research directions anticipate the role of new therapeutic drug research and development,breakthroughs in basic research,and international cooperation,aiming to provide a comprehensive reference for research and clinical practice in this field.展开更多
This article systematically reviews the application of biomimetic nanotechnology in targeted therapy for triple-negative breast cancer(TNBC).TNBC poses significant challenges for conventional treatments due to the lac...This article systematically reviews the application of biomimetic nanotechnology in targeted therapy for triple-negative breast cancer(TNBC).TNBC poses significant challenges for conventional treatments due to the lack of defined therapeutic targets,chemotherapy resistance,and a complex immunosuppressive microenvironment.Biomimetic nanotechnology,by mimicking the functional properties of biological structures(e.g.,cell membranes,exosomes),has significantly enhanced drug delivery efficiency,targeting precision,and anti-tumor immune responses.This review focuses on the design strategies of biomimetic nanocarriers(including cell membrane-coated nanoparticles,engineered exosomes,and biomimetic synthetic materials)and their innovative applications in TNBC therapy:(1)Targeted delivery systems that overcome tumor barriers and reduce systemic toxicity;(2)Photothermal therapy combined with immunomodulation for precise treatment and immune activation;(3)Tumor microenvironment regulation(e.g.,vascular normalization,pH neutralization,immunosuppression reversal).Studies demonstrate that biomimetic nanotechnology significantly improves TNBC treatment efficacy through multimodal synergistic mechanisms(e.g.,chemo-photothermal-immunotherapy).However,challenges such as scalable production,long-term safety,and personalized adaptation remain for clinical translation.Future research should integrate artificial intelligence for optimized design and dynamic imaging technologies to advance biomimetic nanomedicines toward clinical applications.展开更多
Chronic hepatitis B virus(HBV)infection affects approximately 254 million individuals globally,contributing to significant morbidity and mortality due to HBV-related liver failure and cirrhosis,which result in million...Chronic hepatitis B virus(HBV)infection affects approximately 254 million individuals globally,contributing to significant morbidity and mortality due to HBV-related liver failure and cirrhosis,which result in millions of fatalities each year.Although approved antiviral nucleos(t)ide analogues can effectively suppress HBV replication,their ability to reduce hepatitis B surface antigen(HBsAg)levels in plasma remains limited.The clinical application of the immunomodulator interferon-alpha is restricted by concerns regarding its safety and the severity of associated adverse reactions,rendering long-term administration challenging.Therefore,current drug development efforts for chronic hepatitis B aim to achieve a functional cure,which is defined as HBsAg serological clearance and sustained suppression of HBV DNA.This review discusses recent advancements in novel direct-acting therapeutic strategies for the treatment of chronic hepatitis B by focusing on the progresses in HBV entry inhibitors,monoclonal antibodies,RNA interferences,and other agents that directly target the virus.Furthermore,we discuss the development of immunomodulatory therapies,including TLR-7/8 agonists,immune checkpoint inhibitors,and therapeutic vaccines.In the end,we conclude by highlighting the importance of the rational combination-strategy design to improve the functional cure rate of HBV.展开更多
Objective:To investigate the mechanism by which moxibustion regulates the expression of inflammatory cytokines in ulcerative colitis(UC)rats through the P2X7 receptor(P2X7R)/nuclear factor-kappa B(NF-κB)pathway.Metho...Objective:To investigate the mechanism by which moxibustion regulates the expression of inflammatory cytokines in ulcerative colitis(UC)rats through the P2X7 receptor(P2X7R)/nuclear factor-kappa B(NF-κB)pathway.Methods:UC was induced using dextran sulfate sodium(DSS)in both wild-type(WT)and P2X7R knockout(KO)mice.General health conditions,pathological changes,and periodic acid-Schiff(PAS)staining of the colonic tissues were analyzed.Immunohistochemistry was used to detect NF-κB p65 protein expression in colonic tissues.Male Sprague-Dawley(SD)rats were randomly assigned to four groups:normal,model,normal+herb-partitioned moxibustion,and model+herb-partitioned moxibustion.UC was induced in rats by cyclic DSS administration.Rats in the herb-partitioned moxibustion group received moxibustion at the bilateral Tianshu(ST25)and Qihai(RN6)acupoints.The effects of herb-partitioned moxibustion were evaluated regarding general health conditions and histopathological alterations in colon tissue.The protein expression of P2X7R and NF-κB p65 in colonic tissues was determined by immunohistochemistry,whereas interleukin(IL)-10 mRNA levels were quantified using real-time quantitative polymerase chain reaction(RT-qPCR).Furthermore,enzyme-linked immunosorbent assay(ELISA)was used to measure serum concentrations of tumor necrosis factor-alpha(TNF-α)and IL-6.Results:Colonic epithelial damage and inflammatory cell infiltration were significantly reduced in P2X7R KO mice compared to WT mice,along with reduced expression of NF-κB p65 protein in colonic tissues(P<0.05).Moxibustion improves histopathological damage,goblet cell number,and intestinal mucus secretion in rats with UC.Compared to the normal group,the model group exhibited increased histopathological scores,serum TNF-α,and IL-6 levels,as well as elevated P2X7R and NF-κB p65 protein expression in colonic tissues(P<0.05).In comparison to the model group,the model+herb-partitioned moxibustion group demonstrated significantly lower histopathological scores,reduced serum TNF-αand IL-6 levels,and decreased P2X7R and NF-κB p65 protein expression(P<0.05).Conclusions:Moxibustion at“Tianshu”and“Qihai”acupoints may inhibit the levels of IL-6 and TNF-αinflammatory factors and reduce inflammation in the UC colonic mucosa by regulating the P2X7R/NF-κB p65 pathway in UC colonic tissues.展开更多
Autoimmune diseases are complex clinical conditions that present significant therapeutic challenges due to their intricate immunological mechanisms.Conventional treatment strategies,such as immunosuppressive drugs and...Autoimmune diseases are complex clinical conditions that present significant therapeutic challenges due to their intricate immunological mechanisms.Conventional treatment strategies,such as immunosuppressive drugs and anti-inflammatory therapies,often demonstrate limited efficacy and are associated with considerable side effects.Recently,mesenchymal stem cells(MSCs)have attracted growing interest as a promising therapeutic approach,owing to their immunomodulatory properties and ability to promote tissue repair.However,the direct application of MSCs faces several limitations,including the risk of immunogenicity and difficulties in large-scale production.In this context MSC-derived exosomes(MSC-Exos),nano-sized extracellular vesicles secreted by MSCs,have emerged as a compelling alternative to cell-based therapies.Enriched with proteins,lipids,and nucleic acids,these exosomes exhibit potent anti-inflammatory and immunomodulatory effects.Their primary mechanisms of action include enhancing the population of regulatory T cells,modulating macrophage polarization,and suppressing proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α.The therapeutic potential of MSC-Exos extends beyond individual conditions,encompassing a wide range of autoimmune diseases.For instance in Behçet’s disease,they have been shown to regulate vasculitis and inflammatory processes by inhibiting proinflammatory cytokines and promoting endothelial cell regeneration.Moreover,MSC-Exos have demonstrated promising immunomodulatory effects in other autoimmune diseases,including systemic lupus erythematosus,rheumatoid arthritis,and multiple sclerosis.Through mechanisms such as inflammation suppression,vascular repair,and the restoration of immune homeostasis,MSC-Exos represent a versatile and innovative approach to autoimmune disease therapy.This review explored the molecular and therapeutic effects of MSCs and MSC-Exos in autoimmune diseases,with particular emphasis on their clinical potential in Behçet’s disease,systemic lupus erythematosus,rheumatoid arthritis,and multiple sclerosis.展开更多
Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a com...Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.展开更多
基金Project (No.2007CB947804) supported by the National Basic Research Program (973) of China
文摘Objective: Human embryonic stem cells (hESCs) have recently been reported as an unlimited source of mesenchymal stem cells (MSCs).The present study not only provides an identical and clinically compliant MSC source derived from hESCs (hESC-MSCs),but also describes the immunomodulative effects of hESC-MSCs in vitro and in vivo for a carbon tetrachloride (CCl4)-induced liver inflammation model.Methods: Undifferentiated hESCs were treated with Rho-associated kinase (ROCK) inhibitor and induced to fibroblast-looking cells.These cells were tested for their surface markers and multilineage differentiation capability.Further more,we analyzed their immune characteristics by mixed lymphocyte reactions (MLRs) and animal experiments.Results: hESC-MSCs show a homogenous fibroblastic morphology that resembles bone marrow-derived MSCs (BM-MSCs).The cell markers and differentiation potential of hESC-MSCs are also similar to those of BM-MSCs.Unlike their original cells,hESC-MSCs possess poor immunogenicity and can survive and be engrafted into a xenogenic immunocompetent environment.Conclusions: The hESC-MSCs demonstrate strong inhibitory effects on lymphocyte proliferation in vitro and anti-inflammatory infiltration properties in vivo.This study offers information essential to the applications of hESC-MSC-based therapies and evidence for the therapeutic mechanisms of action.
基金National Natural Science Foundation of China,No.81873934and Jinan Science and Technology Planning Project,No.202225065.
文摘BACKGROUND Mesenchymal stem cells,found in various tissues,possess significant healing and immunomodulatory properties,influencing macrophage polarization,which is essential for wound repair.However,chronic wounds present significant therapeutic challenges,requiring novel strategies to improve healing outcomes.AIM To investigate the potential of fetal dermal mesenchymal stem cells(FDMSCs)in enhancing wound healing through modulation of macrophage polarization,specifically by promoting the M2 phenotype to address inflammatory responses in chronic wounds.METHODS FDMSCs were isolated from BalB/C mice and co-cultured with RAW264.7 macrophages to assess their effects on macrophage polarization.Flow cytometry,quantitative reverse transcriptase polymerase chain reaction,and histological analyses were employed to evaluate shifts in macrophage phenotype and wound healing in a mouse model.Statistical analysis was performed using GraphPad Prism.RESULTS FDMSCs induced macrophage polarization from the M1 to M2 phenotype,as demonstrated by a reduction in proinflammatory markers(inducible nitric oxide synthase,interleukin-6)and an increase in anti-inflammatory markers[mannose receptor(CD206),arginase-1]in co-cultured RAW264.7 macrophages.These shifts were confirmed by flow cytometry.In an acute skin wound model,FDMSC-treated mice exhibited faster wound healing,enhanced collagen deposition,and improved vascular regeneration compared to controls.Significantly higher expression of arginase-1 further indicated an enriched M2 macrophage environment.CONCLUSION FDMSCs effectively modulate macrophage polarization from M1 to M2,reduce inflammation,and enhance tissue repair,demonstrating their potential as an immunomodulatory strategy in wound healing.These findings highlight the promising therapeutic application of FDMSCs in managing chronic wounds.
基金support by AgriFutures Australia’s Chicken Meat Program[grant number PRJ-011584]is gratefully acknowledged.
文摘Background Broiler chickens are most vulnerable immediately after hatching due to their immature immune systems,making them susceptible to infectious diseases.The yolk plays an important role in early immune defence by showing relevant antioxidant and passive immunity capabilities during broiler embryonic development.The immunomodulatory effects of phytogenic compound carvacrol have been widely reported.After in ovo delivery in the amniotic fluid during embryonic development carvacrol is known to migrate to the yolk sac.However,it is unknown whether carvacrol in the yolk could enhance defence responsiveness in the yolk sac.Therefore,the aim of this study was to improve early immune function in chicken embryos,and it was hypothesized that in ovo delivery of carvacrol would result in immunomodulatory effects in the yolk sac,potentially improving post-hatch resilience.Methods On embryonic day(E)17.5,either a saline(control)or carvacrol solution was injected into the amniotic fluid.Yolk sac tissue samples were collected at E19.5,and transcriptomic analyses using RNA sequencing were performed,following functional enrichment analyses comparing the control(saline)and carvacrol-injected groups.Results The results showed that 268 genes were upregulated and 174 downregulated in the carvacrol group compared to the control(P<0.05;logFC<-0.5 or log FC>0.5).Functional analyses of these differentially expressed genes,using KEGG,REACTOME,and Gene Ontology databases,showed enrichment of several immune-related pathways.This included the pathways‘Antimicrobial peptides’(P=0.001)and‘Chemoattractant activity’(P=0.004),amongst others.Moreover,the‘NOD-like receptor signaling’pathway was enriched(P=0.002).Antimicrobial peptides are part of the innate immune defence and are amongst the molecules produced after the nucleotide oligomeriza-tion domain(NOD)-like receptor pathway activation.While these responses may be associated with an inflammatory reaction to an exogenous threat,they could also indicate that in ovo delivery of carvacrol could prepare the newly hatched chick against bacterial pathogens by potentially promoting antimicrobial peptide production through acti-vation of NOD-like receptor signaling in the yolk sac.Conclusion In conclusion,these findings suggest that in ovo delivery of carvacrol has the potential to enhance anti-pathogenic and pro-inflammatory responses in the yolk sac via upregulation of antimicrobial peptides,and NOD-like receptor pathways.
基金supported by the National Science Foundation of China(82202714).
文摘Severe tissue defects present formidable challenges to human health,persisting as major contributors to mortality rates.The complex pathological microenvironment,particularly the disrupted immune landscape within these defects,poses substantial hurdles to existing tissue regeneration strategies.However,the emergence of nanobiotechnology has opened a new direction in immunomodulatory nanomedicine,providing encouraging prospects for tissue regeneration and restoration.This review aims to gather recent advances in immunomodulatory nanomedicine to foster tissue regeneration.We begin by elucidating the distinctive features of the local immune microenvironment within defective tissues and its crucial role in tissue regeneration.Subsequently,we explore the design and functional properties of immunomodulatory nanosystems.Finally,we address the challenges and prospects of clinical translation in nanomedicine development,aiming to propose a potent approach to enhance tissue regeneration through synergistic immune modulation and nanomedicine integration.
文摘Humans and other vertebrates are safeguarded from invading pathogenic microbes by the immune system.Black seed,scientifically known as Nigella sativa,has garnered attention for its potential immunomodulatory effects in both clinical and preclinical studies.This comprehensive review aims to consolidate and analyze the existing body of evidence surrounding the immunological impact of black seeds.In this review,we analyze the immunomodulatory potentials of black seeds(N.sativa).For the purpose of finding pertinent publications,the literatures was searched in web-based databases,including Web of Science,Medline/PMC/PubMed,Embase,EBSCO,Google Scholar,Science Direct,and reference lists.Several clinical,in vivo,and in vitro studies have demonstrated that supplementation with black seeds(N.sativa)has potential immunomodulatory activity.Black seeds(N.sativa)may influence immune responses through a variety of mechanisms.By synthesizing and critically assessing the current state of knowledge on the immunomodulatory effects of black seeds,this review aims to provide valuable insights into the potential therapeutic uses and future research directions for harnessing the immunological benefits of this natural remedy.
基金the National Natural Science Foundation of China(Nos.31971246&52274387)the Fundamental Research Funds for the Central Universities(No.YG2023QNA21)the Shanghai Science and Technology Commission(No.20S31900100)for their financial and project support.
文摘The remodeling of macrophages mediated by biomaterials is an important step in osseointegration.The biointerfacial characteristics shaped by implants and the bioenergetic state derived from macrophages are considered the key to macrophage reprogramming.In this study,the integrated Ti/Zn composites with optimized morphology and bioactive phase were prepared by friction stir processing,which could meet the multi-biofunctional requirements in the application of narrow-diameter implants.The severe plastic deformation and the hindrance of Zn particles to grain growth promote grain refinement,resulting in enhanced mechanical properties.The cell interfacial adhesion mediated by the grain boundary collaborated the energy metabolism reprogramming induced by the released Zn ion,promoting jointly anti-inflammatory cascade in macrophages and favorable osteogenesis in bone marrow mesenchymal stem cells(BMSCs).This study provides a new simultaneous approach of morphology and composition modification for titanium implants,and reveals the important role of grain size and bioactive element in the reversion of macrophage fate as well.
基金supported by the National Key Research and Development Program of China(2019YFA0905200).
文摘The treatment of prolonged inflammation and cartilage damage due to osteoarthritis(OA)is a major clinical challenge.We developed a comprehensive cartilage repair therapy using a dual drug-loaded nanocomposite hydrogel that leveraged the spatiotemporal immunomodulatory effects of a naturally degradable protein-based nanocomposite hydrogel.The hydrogel acted as a scaffold that created a favorable microenvironment for cartilage regeneration.The hydrogel recruited macrophages and human mesenchymal stem cells(hMSCs),which supported the growth and adhesion of osteoblasts,and degraded to provide nutrition.Silk protein nanoparticles were chemically cross-linked with kartogenin,and humanlike collagen was physically cross-linked with dexamethasone through hydrogen bonding.In the early stages of cartilage repair,a large quantity of dexamethasone was released.The dexamethasone acted as an anti-inflammatory agent and a spatiotemporal modulator of the polarization of M1 macrophages into M2 macrophages.In the middle and late stages of cartilage repair,kartogenin underwent sustained release from the hydrogel,inducing the differentiation of hMSCs into chondrocytes and maintaining chondrocyte stability.Therefore,kartogenin and dexamethasone acted synergistically to induce cartilage repair.In conclusion,we developed an integrated therapeutic system by constructing a cartilage regeneration microenvironment and inducing synergistic drug-based cartilage regeneration.The therapeutic system demonstrated satisfactory efficacy for repairing cartilage damage in rabbits.
文摘Type 2 diabetes mellitus(T2DM)is a metabolic disorder marked by chronic hyperglycemia and low-grade inflammation,contributing to various complications.Natural agents with immunomodulatory and antioxidant properties have gained attention as adjunct therapies.To review the effects of Allium sativum on inflammatory pathways and metabolic alterations associated with T2DM.A narrative review was performed using PubMed/MEDLINE,EMBASE,and Scielo databases.The search included terms such as“allium sativum”,“inflammation",“oxidative stress”,and“diabetes mellitus”.Studies in English and Spanish-ranging from clinical trials to meta-analyses-were selected based on relevance.Bioactive compounds such as allicin,S-allyl cysteine,and diallyl disulfide exhibit anti-inflammatory,antioxidant,hypoglycemic,and lipid-lowering actions.Preclinical studies show improved glucose metabolism,insulin sensitivity,and organ function.Moreover,clinical evidence supports reductions in fasting glucose,hemoglobin A1c,blood pressure,and oxidative stress,with good safety profiles.Allium sativum appears to be a promising adjuvant in T2DM management,offering metabolic and anti-inflammatory benefits.Nonetheless,further high-quality clinical trials are needed to confirm its long-term efficacy and standardize its therapeutic use.
文摘In adaptive immunity,antigens are presented to T cells,which then become effector T cells(CD4+)or cytotoxic T cells(CD8+).These are called adaptive immune T cells.Cancer immunotherapy based on anti-programmed death receptor-1(PD-1)/programmed cell death 1 ligand 1(PD-L1)antibodies is a new way to treat cancer.Chinese herbal medicines are often used with cancer treatments in clinical practice.Recent studies have shown that Chinese herbal medicines affect the immune system and have an effect on PD-1/PD-L1.Baicalin,the main ingredient of Scutellaria baicalensis,can stop Tregs from working,increase the number of CD8+T cells in the tumour microenvironment and avoid PD-1 resistance.Solamargine has anti-cancer activity in a variety of tumours,including stopping tumour growth,stopping PD-L1 expression and blocking immune escape in combination with Immune checkpoint inhibitors.Taraxasterol,found in dandelion,can regulate anti-tumour T cells.It affects CD4+T cells by inhibiting STAT3.Platycodonis Radix can reduce the expression of PD-1 on the surface of CD8+T cells and increase their ability to kill tumour cells.Licorice compounds can regulate the cell cycle and PD-L1 expression,which can lead to tumour cell cycle blockade and increase the level of PD-L1 expression,thereby exerting anti-tumour effects.Marsdenia tenacissima extracts weakened the immunosuppressive effect of IL-10,improved T-cell function,stopped tumour cells escaping the immune system and reduced TGF-β1 and PD-L1.Strobilanthes crispus F3 extract increases lymphocyte infiltration,improves T-cell-mediated cytotoxicity,modulates immune cell expression,stops tumour-associated macrophage activity and slows tumour progression.The last five years of research on herbs with purgative and detoxifying effects were reviewed.This review will investigate how herbs can affect adaptive immune T cells in the immune system to improve cancer treatment.
基金Supported by Natural Science Foundation of Henan Province,No.242300421199 and No.252300421395Henan Province Joint Fund for Science and Technology Research and Development,No.235101610002+1 种基金Key Technologies R&D Program of Henan Province,No.242102310134Henan Province Foundation for University Key Teacher,No.2024GGJS088.
文摘Neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease,are characterized by the progressive loss of neuronal function and structure,leading to severe morbidity and mortality.Current therapeutic approaches are ineffective at stopping or reversing disease progression.Stem cell therapy has emerged as a promising candidate in research and treatment.Mesenchymal stem cells(MSCs)are considered ideal candidates for regenerative medicine because of their high proliferation rate and multi-differentiation potential.MSCs can differentiate into neurons and glial cells,modulate immune responses,and reduce inflammation,and their exosomes can promote neural repair and regulate neuronal function;thus,MSCs offer unique advantages for treating neurodegenerative diseases.However,challenges remain in optimizing cell delivery methods,ensuring the long-term survival and integration of transplanted cells,and fully understanding their therapeutic effects.This article primarily outlines the functions of MSCs in neurodegenerative diseases,with the intention that further research will fully harness their potential and translate these findings into clinical applications,offering new hope for patients suffering from neurodegenerative diseases.
基金supported by the Natural Science Foundation of Heilongjiang Province of China (LH2023C033)。
文摘Food allergy(FA) is an aberrant immune response triggered by the ingestion of a food antigen.Ovalbumin(OVA)-sensitized and challenged BALB/c mice were orally administered heat-killed(HK)-Lactobacillus paracasei JY56.In this work,HK-L.paracasei JY56 alleviated the FA-induced decrease in body weight and rectal temperature and reduced the allergy score.Serum analysis showed that HK-L.paracasei JY56 reduced the levels of specific antibodies(OVA-specific Immunoglobulin E(sIgE) and OVA-specific Immunoglobulin G(sIgG)) and allergic mediators(histamine and mast cell protease) in FA mice.In addition,HK-L.paracasei JY56 also could alleviate OVA-induced FA by suppressing T helper(Th)2 and Th17-type immune responses,which was evidenced by the regulation of splenic lymphocyte subpopulations and associated cytokine secretion.Moreover,jejunal histological analysis and intestinal barrier function related gene expression measurement were performed to verify the intestinal barrier repair of HK-L.paracasei JY56.Meanwhile,the TLR4/NF-κB inflammatory pathway activation was inhibited by HK-L.paracasei JY56 at gene and protein levels.Finally,HK-L.paracasei JY56 was performed to modulate the gut microbiota structure and increase the levels of short-chain fatty acids.In conclusion,HK-L.paracasei JY56 could alleviate OVA-induced FA in multiple ways,and this study provides a theoretical basis for the application of inactivated probiotics in functional foods for FA.
文摘Mesenchymal stem cell(MSC)-derived extracellular vesicles(MSC-EVs)represent the next generation of biomedical applications,offering advantages over MSCs such as higher stability and lower immunogenicity.As cell-free nanoparticles MSC-EVs have demonstrated both efficacy and safety in the treatment of a range of diseases.This article discussed the applications of MSC-EVs in hair regene-ration,immunomodulation,and the treatment of acute kidney injury.MSC-EVs promote hair regeneration by enhancing dermal papilla cell proliferation and migration.They also modulate immune responses and mitigate inflammation through immune-related signaling pathways.Additionally,MSC-EVs contribute to improved renal function by modulating multiple signaling pathways.Despite these promising applications challenges remain in the clinical translation of MSC-EVs.Overcoming these challenges requires extensive research to fully optimize the therapeutic potential of MSC-EVs and advance their translation into clinical practice.
基金Science and Technology Achievements Transformation Project of the Autonomous Prefecture(Project No.:202401)National College Students'Innovation and Entrepreneurship Training Program(Project Title:"Li Zhiyun·Ku Li Chun"-Pioneer in Promoting National Geographic Brand,Project Number:202513561005).
文摘Korla fragrant pears are one of the“famous,excellent,and special”fruits in Xinjiang.They belong to the white pear variety in the genus Pyrus of the Rosaceae family.With a long-standing planting history and strong regional characteristics,they are mainly produced in southern Xinjiang.Due to unique natural conditions such as large temperature differences between day and night and sufficient sunlight,Korla fragrant pears have a crispy texture,a sweet but not cloying taste,and their flesh is delicate and juicy,with excellent quality.Korla fragrant pears contain a variety of bioactive substances,mainly including polysaccharides,polyphenolic compounds,flavonoid compounds,triterpenoids,and sterols.They have medical effects such as“moistening the lungs,calming the heart,reducing phlegm,anti-inflammation,relieving cough,and resolving carbuncle toxins”.Uyghur and Mongolian medicine often use them as a good dietary therapy product.Based on recent literature reports,this paper reviews the main chemical constituents and pharmacological effects of Korla fragrant pears,aiming to provide references for the research and utilization of the deep processing of Korla fragrant pears.
文摘The neem flower(Azadirachta indica),a well-known element of Ayurvedic medicine,has attracted considerable interest due to its abundance of bioactive compounds.This systematic review examines its pharmacological and immunomodulatory properties in detail,emphasizing its potential role in contemporary healthcare.Neem flowers are rich in various bioactive components,such as flavonoids,terpenoids,and glycosides,known for their antioxidant,anti-inflammatory,antimicrobial,and anticancer properties.Recent studies indicate that extracts from neem flowers can influence immune system activity by boosting both innate and adaptive immune functions while reducing excessive inflammation.These properties suggest that neem flowers could serve as valuable therapeutic agents for treating immune-related disorders.Additionally,neem flowers have demonstrated promise in addressing conditions such as diabetes,cardiovascular issues,and microbial infections through their ability to regulate metabolic functions and inhibit the growth of harmful pathogens.Preclinical research highlights their protective effects against oxidative damage and their capacity to induce apoptosis in cancer cells.However,challenges such as the lack of standardized extraction processes and limited clinical research hinder broader utilization.This review emphasizes the need for more robust studies to fully harness the pharmacological potential of neem flowers and facilitate their incorporation into evidence-based medicinal properties.
文摘Kawasaki disease(KD)is an acute,self-limited systemic vasculitis that primarily affects children.Treating nonresponding KD with intravenous immunoglobulin(IVIG)presents numerous challenges.This article comprehensively reviews the basic theory,clinical manifestations and diagnosis,treatment strategies,disputes and challenges,historical evolution and current situation,and future research directions of immunoglobulin unresponsive KD.In terms of basic theory,the epidemiological characteristics of KD,the mechanism of IVIG action,and the pathophysiological mechanism of the nonresponsive type are elaborated.In the clinical manifestation and diagnosis section,symptoms,diagnostic criteria,and imaging applications are analyzed.The treatment strategy encompasses drug,nondrug and individualized therapy.Controversies and challenges focus on diagnostic difficulties,treatment disputes,and long-term prognosis research.The historical evolution and current situation review the changes in treatment strategies and the current state of affairs.Future research directions anticipate the role of new therapeutic drug research and development,breakthroughs in basic research,and international cooperation,aiming to provide a comprehensive reference for research and clinical practice in this field.
文摘This article systematically reviews the application of biomimetic nanotechnology in targeted therapy for triple-negative breast cancer(TNBC).TNBC poses significant challenges for conventional treatments due to the lack of defined therapeutic targets,chemotherapy resistance,and a complex immunosuppressive microenvironment.Biomimetic nanotechnology,by mimicking the functional properties of biological structures(e.g.,cell membranes,exosomes),has significantly enhanced drug delivery efficiency,targeting precision,and anti-tumor immune responses.This review focuses on the design strategies of biomimetic nanocarriers(including cell membrane-coated nanoparticles,engineered exosomes,and biomimetic synthetic materials)and their innovative applications in TNBC therapy:(1)Targeted delivery systems that overcome tumor barriers and reduce systemic toxicity;(2)Photothermal therapy combined with immunomodulation for precise treatment and immune activation;(3)Tumor microenvironment regulation(e.g.,vascular normalization,pH neutralization,immunosuppression reversal).Studies demonstrate that biomimetic nanotechnology significantly improves TNBC treatment efficacy through multimodal synergistic mechanisms(e.g.,chemo-photothermal-immunotherapy).However,challenges such as scalable production,long-term safety,and personalized adaptation remain for clinical translation.Future research should integrate artificial intelligence for optimized design and dynamic imaging technologies to advance biomimetic nanomedicines toward clinical applications.
文摘Chronic hepatitis B virus(HBV)infection affects approximately 254 million individuals globally,contributing to significant morbidity and mortality due to HBV-related liver failure and cirrhosis,which result in millions of fatalities each year.Although approved antiviral nucleos(t)ide analogues can effectively suppress HBV replication,their ability to reduce hepatitis B surface antigen(HBsAg)levels in plasma remains limited.The clinical application of the immunomodulator interferon-alpha is restricted by concerns regarding its safety and the severity of associated adverse reactions,rendering long-term administration challenging.Therefore,current drug development efforts for chronic hepatitis B aim to achieve a functional cure,which is defined as HBsAg serological clearance and sustained suppression of HBV DNA.This review discusses recent advancements in novel direct-acting therapeutic strategies for the treatment of chronic hepatitis B by focusing on the progresses in HBV entry inhibitors,monoclonal antibodies,RNA interferences,and other agents that directly target the virus.Furthermore,we discuss the development of immunomodulatory therapies,including TLR-7/8 agonists,immune checkpoint inhibitors,and therapeutic vaccines.In the end,we conclude by highlighting the importance of the rational combination-strategy design to improve the functional cure rate of HBV.
基金funded by the National Natural Science Foundation of China(82174501,82105012,82205293,82205262)Shanghai Municipal Natural Science Foundation(22ZR1458400)+2 种基金Shanghai Talent Development Fund Project(2021058)Shanghai University of Traditional Chinese Medicine Science and Technology Development Project(23KFL111)State Administration of Traditional Chinese Medicine high-level key discipline construction project(zyyzdxk-2023068)。
文摘Objective:To investigate the mechanism by which moxibustion regulates the expression of inflammatory cytokines in ulcerative colitis(UC)rats through the P2X7 receptor(P2X7R)/nuclear factor-kappa B(NF-κB)pathway.Methods:UC was induced using dextran sulfate sodium(DSS)in both wild-type(WT)and P2X7R knockout(KO)mice.General health conditions,pathological changes,and periodic acid-Schiff(PAS)staining of the colonic tissues were analyzed.Immunohistochemistry was used to detect NF-κB p65 protein expression in colonic tissues.Male Sprague-Dawley(SD)rats were randomly assigned to four groups:normal,model,normal+herb-partitioned moxibustion,and model+herb-partitioned moxibustion.UC was induced in rats by cyclic DSS administration.Rats in the herb-partitioned moxibustion group received moxibustion at the bilateral Tianshu(ST25)and Qihai(RN6)acupoints.The effects of herb-partitioned moxibustion were evaluated regarding general health conditions and histopathological alterations in colon tissue.The protein expression of P2X7R and NF-κB p65 in colonic tissues was determined by immunohistochemistry,whereas interleukin(IL)-10 mRNA levels were quantified using real-time quantitative polymerase chain reaction(RT-qPCR).Furthermore,enzyme-linked immunosorbent assay(ELISA)was used to measure serum concentrations of tumor necrosis factor-alpha(TNF-α)and IL-6.Results:Colonic epithelial damage and inflammatory cell infiltration were significantly reduced in P2X7R KO mice compared to WT mice,along with reduced expression of NF-κB p65 protein in colonic tissues(P<0.05).Moxibustion improves histopathological damage,goblet cell number,and intestinal mucus secretion in rats with UC.Compared to the normal group,the model group exhibited increased histopathological scores,serum TNF-α,and IL-6 levels,as well as elevated P2X7R and NF-κB p65 protein expression in colonic tissues(P<0.05).In comparison to the model group,the model+herb-partitioned moxibustion group demonstrated significantly lower histopathological scores,reduced serum TNF-αand IL-6 levels,and decreased P2X7R and NF-κB p65 protein expression(P<0.05).Conclusions:Moxibustion at“Tianshu”and“Qihai”acupoints may inhibit the levels of IL-6 and TNF-αinflammatory factors and reduce inflammation in the UC colonic mucosa by regulating the P2X7R/NF-κB p65 pathway in UC colonic tissues.
文摘Autoimmune diseases are complex clinical conditions that present significant therapeutic challenges due to their intricate immunological mechanisms.Conventional treatment strategies,such as immunosuppressive drugs and anti-inflammatory therapies,often demonstrate limited efficacy and are associated with considerable side effects.Recently,mesenchymal stem cells(MSCs)have attracted growing interest as a promising therapeutic approach,owing to their immunomodulatory properties and ability to promote tissue repair.However,the direct application of MSCs faces several limitations,including the risk of immunogenicity and difficulties in large-scale production.In this context MSC-derived exosomes(MSC-Exos),nano-sized extracellular vesicles secreted by MSCs,have emerged as a compelling alternative to cell-based therapies.Enriched with proteins,lipids,and nucleic acids,these exosomes exhibit potent anti-inflammatory and immunomodulatory effects.Their primary mechanisms of action include enhancing the population of regulatory T cells,modulating macrophage polarization,and suppressing proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α.The therapeutic potential of MSC-Exos extends beyond individual conditions,encompassing a wide range of autoimmune diseases.For instance in Behçet’s disease,they have been shown to regulate vasculitis and inflammatory processes by inhibiting proinflammatory cytokines and promoting endothelial cell regeneration.Moreover,MSC-Exos have demonstrated promising immunomodulatory effects in other autoimmune diseases,including systemic lupus erythematosus,rheumatoid arthritis,and multiple sclerosis.Through mechanisms such as inflammation suppression,vascular repair,and the restoration of immune homeostasis,MSC-Exos represent a versatile and innovative approach to autoimmune disease therapy.This review explored the molecular and therapeutic effects of MSCs and MSC-Exos in autoimmune diseases,with particular emphasis on their clinical potential in Behçet’s disease,systemic lupus erythematosus,rheumatoid arthritis,and multiple sclerosis.
文摘Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.
