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
Typhonium flagelliforme(TF)is a Southeast Asian medicinal plant traditionally used for cancer,respiratory disorders,gastrointestinal complaints,wound healing,inflammation,and general health.Contemporary studies valida...Typhonium flagelliforme(TF)is a Southeast Asian medicinal plant traditionally used for cancer,respiratory disorders,gastrointestinal complaints,wound healing,inflammation,and general health.Contemporary studies validate these uses,showing potent anticancer,immunomodulatory,anti-inflammatory,gastroprotective,antibacterial,antioxidant,and wound-healing activities.Ethanol,dichloromethane,methanol,and ethyl acetate extracts exhibit strong cytotoxicity against breast(MCF-7,T47D),lung(NCI-H23),colon(WiDr),and leukemia(CEM-ss,WEHI-3)cells via apoptosis,telomerase inhibition,HER2/neu and BCL-2 suppression,and antiangiogenesis.Notably,2-octenoic acid and 2-hexenoic acid show exceptional activity(IC₅₀=2.66 and 3.10μg/mL)against MCF-7 cells.TF also restores lymphocyte proliferation,enhances macrophage activity,increases both CD4+and CD8+T-cell levels,and modulates cytokines(TNF-α,IL-1α,IL-10).Gastroprotective,anti-ulcer,antibacterial,antioxidant,and wound-healing effects further support traditional claims.Key phytochemicals include flavonoids(isovitexin,kaempferol,vitexin),phenolics(vanillin,4-hydroxybenzaldehyde),phytosterols(β-sitosterol,campesterol,stigmasterol,daucosterol),chlorophyll derivatives(pheophorbides),and long-chain fatty acids(linoleic,linolenic,oleic,stearic).These findings highlight TF as a source of multifunctional bioactive compounds,warranting further pharmacokinetic,safety,and clinical evaluation for evidence-based therapeutic development.展开更多
Mesenchymal stem cells(MSCs) are widely utilized in disease treatment and regenerative medicine due to their potent immunomodulatory properties and capacity for tissue repair.However, limitations—including insufficie...Mesenchymal stem cells(MSCs) are widely utilized in disease treatment and regenerative medicine due to their potent immunomodulatory properties and capacity for tissue repair.However, limitations—including insufficient migratory capacity, suboptimal survival, proliferation, differentiation potential, and variable immunomodulatory responses—significantly hinder their clinical translation and therapeutic impact. Natural products have been shown to enhance MSC homing, stress resilience, immune regulation, and lineage-specific differentiation through multi-target mechanisms, thereby emerging as promising, safe, and practical strategies to improve the in vivo performance of MSC-based therapies. This review examines the key translational challenges associated with MSCs, elucidates the mechanistic basis by which natural products regulate the in vivo fate of MSCs, and explores the potential of integrating natural product adjuvants with MSC therapy for enhanced clinical outcomes.展开更多
The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR...The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR.However,their clinical translation is hindered by their inherently low immunogenicity,often requiring potent adjuvants and advanced delivery systems.Biomembrane nanostructures(e.g.,liposomes,exosomes,and cell membrane-derived nanostructures),characterized by superior biocompatibility,intrinsic targeting ability,and immune-modulating properties,could serve as versatile platforms that potentiate vaccine efficacy by increasing antigen stability,enabling codelivery of immunostimulants,and facilitating targeted delivery to lymphoid tissues/antigen-presenting cells.This intrinsic immunomodulation promotes robust humoral and cellular immune responses to combat bacteria.This review critically reviews(1)key biomembrane nanostructure classes for bacterial protein antigens,(2)design strategies leveraging biomembrane nanostructures to enhance humoral and cellular immune responses,(3)preclinical efficacy against diverse pathogens,and(4)translational challenges and prospects.Biomembrane nanostructure-driven approaches represent a paradigm shift in the development of next-generation bacterial protein vaccines against resistant infections.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
Cancer vaccines are a notable area of immunotherapy due to their capacity to elicit specific antitumor immune responses and to create immune memory.However,they encounter challenges in clinical practice due to several...Cancer vaccines are a notable area of immunotherapy due to their capacity to elicit specific antitumor immune responses and to create immune memory.However,they encounter challenges in clinical practice due to several bottlenecks,including tumor heterogeneity,low immunogenicity,immunosuppressive tumor environment,and delivery obstacles,which collectively impact their clinical effectiveness.In this study,we developed nanocomposites containing positively charged melittin(MEL)and negatively charged photosensitizer indocyanine green(ICG),embedded in dissolving microneedles(MEL/ICG-HA@DMNs).This approach allows precise drug delivery by creating microchannels that bypass the stratum corneum barrier,targeting superficial lesions directly.Our results demonstrated that the complexation of MEL and ICG significantly reduced the hemolytic activity of MEL while maintaining its ability to disrupt cell membranes.After loading MEL/ICG-HA into the microneedle,MEL/ICG-HA@DMNs not only effectively concentrated the drug at the tumor site,inducing localized hyperthermia and successfully ablating the tumor,but also formed an in situ whole-cell vaccine containing a rich source of tumor-associated antigens.Moreover,the system promoted dendritic cell maturation and increased the M1/M2 macrophage ratio,enhancing the immune response.By overcoming the limitations of traditional cancer vaccines,this system ensures precise drug delivery and robust immune activation.This innovative approach holds the potential to revolutionize cancer treatment,offering a new paradigm in precision oncology.展开更多
Diabetes,a metabolic disease stemming from impaired or defective insulin secretion,ranks among the most severe chronic illnesses globally.While several approved drugs exist for its treatment,they often come with multi...Diabetes,a metabolic disease stemming from impaired or defective insulin secretion,ranks among the most severe chronic illnesses globally.While several approved drugs exist for its treatment,they often come with multiple side effects.Therefore,there is a pressing need for safe and effective anti-diabetic medications.Traditional Chinese medicine has recognized Lycium barbarum(LB;goji berry)plant,commonly known as“wolfberry fruit”in China,for over 2,000 years.Natural compounds derived from LB show promise in reducing diabetes levels.Although research on the impact of LB on diabetes is still limited,our review aims to explore the potential of LB in reducing the risk of diabetes and examine the underlying mechanisms involved.LB can modulate diabetes through various pathways,such as inhibitingα-amylase andα-glucosidase activities,promotingβ-cell proliferation,stimulating insulin secretion,inhibiting glucagon secretion,improving insulin resistance and glucose tolerance,and enhancing antioxidant and anti-inflammatory activities.Additionally,LB improves gut flora and immunomodulation,further aiding diabetes management.These findings highlight the potential clinical utility of LB in managing diabetes and its complications within the framework of evidence-based modern medicine.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
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
Anemoside B4(AB4),a triterpenoidal saponin derived from Pulsatilla chinensis,has garnered considerable attention for its potent anti-inflammatory and immunomodulatory activities,culminating in its approval for clinica...Anemoside B4(AB4),a triterpenoidal saponin derived from Pulsatilla chinensis,has garnered considerable attention for its potent anti-inflammatory and immunomodulatory activities,culminating in its approval for clinical trials by the Center for Drug Evaluation,National Medical Products Administration,for the treatment of mild to moderate ulcerative colitis.Despite this,AB4’s therapeutic potential remained underexplored until the development of its injection formulation.This review discusses the scientific rationale and theoretical framework behind AB4’s development,offering a new paradigm and innovative research strategy for discovering lead compounds or drug candidates from natural medicines.In-depth investigations into AB4’s cellular targets,biochemical pathways,and administration routes have provided valuable insights into its druggability evaluation and clinical potential.The high water solubility of AB4,attributable to its multiple sugar units,imposes limitations on its bioavailability and pharmacokinetic profiles.To address this,structural modification via chemical methods and enzymatic hydrolysis have been employed,resulting in derivatives with reduced molecular weight,improved bioavailability,enhanced pharmacological activity,and greater clinical potential.These advances lay a solid foundation for the continued development of AB4 and its derivatives as promising therapeutic agents.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
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
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
Mesenchymal stem or stromal cells(MSCs)are among the most extensively studied cell populations in regenerative medicine due to their multipotent differentiation potential,secretion of trophic factors,and immunomodulat...Mesenchymal stem or stromal cells(MSCs)are among the most extensively studied cell populations in regenerative medicine due to their multipotent differentiation potential,secretion of trophic factors,and immunomodulatory effects.Over the past two decades,preclinical studies have demonstrated encouraging results across musculoskeletal,cardiovascular,neurological,and immunemediated disorders.However,the translation of MSCs from the laboratory to routine clinical practice remains hindered by unresolved scientific,technical,and regulatory challenges.This review provides a critical appraisal of these hurdles,organized across three major stages of translation:In vitro research,in vivo animal studies,and clinical application.In vitro issues include the heterogeneity of isolation techniques,replicative senescence during expansion,genetic and epigenetic instability,and the need for xeno-free,standardized culture platforms.In vivo challenges arise from poor cell survival,low engraftment rates,off-target migration,and microenvironmental influences that shape therapeutic outcomes.Clinical translation introduces additional complexity,including inter-patient variability,large-scale manufacturing difficulties,stringent regulatory compliance,high production costs,and the absence of harmonized potency assays.Solutions under exploration include the use of automated bioreactors,biomimetic scaffolds,hypoxic preconditioning,extracellular vesicle-based therapies,and international standardization efforts.Addressing these hurdles through multidisciplinary collaboration is essential for MSC-based therapies to become reliable,safe,and accessible regenerative treatments.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the Ministry of Higher Education(MOHE),Malaysia,for funding this research through grant no.IF070-2020the Science and Technology Research Partnership for Sustainable Development(SATREPS)program,administered by the Japan Agency for Medical Research and Development(AMED)and the Japan International Cooperation Agency(JICA).
文摘Typhonium flagelliforme(TF)is a Southeast Asian medicinal plant traditionally used for cancer,respiratory disorders,gastrointestinal complaints,wound healing,inflammation,and general health.Contemporary studies validate these uses,showing potent anticancer,immunomodulatory,anti-inflammatory,gastroprotective,antibacterial,antioxidant,and wound-healing activities.Ethanol,dichloromethane,methanol,and ethyl acetate extracts exhibit strong cytotoxicity against breast(MCF-7,T47D),lung(NCI-H23),colon(WiDr),and leukemia(CEM-ss,WEHI-3)cells via apoptosis,telomerase inhibition,HER2/neu and BCL-2 suppression,and antiangiogenesis.Notably,2-octenoic acid and 2-hexenoic acid show exceptional activity(IC₅₀=2.66 and 3.10μg/mL)against MCF-7 cells.TF also restores lymphocyte proliferation,enhances macrophage activity,increases both CD4+and CD8+T-cell levels,and modulates cytokines(TNF-α,IL-1α,IL-10).Gastroprotective,anti-ulcer,antibacterial,antioxidant,and wound-healing effects further support traditional claims.Key phytochemicals include flavonoids(isovitexin,kaempferol,vitexin),phenolics(vanillin,4-hydroxybenzaldehyde),phytosterols(β-sitosterol,campesterol,stigmasterol,daucosterol),chlorophyll derivatives(pheophorbides),and long-chain fatty acids(linoleic,linolenic,oleic,stearic).These findings highlight TF as a source of multifunctional bioactive compounds,warranting further pharmacokinetic,safety,and clinical evaluation for evidence-based therapeutic development.
基金supported by the Leading Technology Foundation Research Project of Jiangsu Province (No. BK20232035)the Key Project of Basic Research Program of Jiangsu Province(No. BK20243061)+1 种基金the Project of State Key Laboratory of Natural Medicines,China Pharmaceutical University (No.SKLNMZZ202302)the Haihe Laboratory of Cell Ecosystem Innovation Fund (No. 22HHXBSS00005)。
文摘Mesenchymal stem cells(MSCs) are widely utilized in disease treatment and regenerative medicine due to their potent immunomodulatory properties and capacity for tissue repair.However, limitations—including insufficient migratory capacity, suboptimal survival, proliferation, differentiation potential, and variable immunomodulatory responses—significantly hinder their clinical translation and therapeutic impact. Natural products have been shown to enhance MSC homing, stress resilience, immune regulation, and lineage-specific differentiation through multi-target mechanisms, thereby emerging as promising, safe, and practical strategies to improve the in vivo performance of MSC-based therapies. This review examines the key translational challenges associated with MSCs, elucidates the mechanistic basis by which natural products regulate the in vivo fate of MSCs, and explores the potential of integrating natural product adjuvants with MSC therapy for enhanced clinical outcomes.
基金the National Natural Science Foundation of China(82573571)the Shanghai 2025 Basic Research Plan Natural Science Foundation(25ZR1401393)the First Batch of Open Topics of the Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices(2025QN13)。
文摘The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR.However,their clinical translation is hindered by their inherently low immunogenicity,often requiring potent adjuvants and advanced delivery systems.Biomembrane nanostructures(e.g.,liposomes,exosomes,and cell membrane-derived nanostructures),characterized by superior biocompatibility,intrinsic targeting ability,and immune-modulating properties,could serve as versatile platforms that potentiate vaccine efficacy by increasing antigen stability,enabling codelivery of immunostimulants,and facilitating targeted delivery to lymphoid tissues/antigen-presenting cells.This intrinsic immunomodulation promotes robust humoral and cellular immune responses to combat bacteria.This review critically reviews(1)key biomembrane nanostructure classes for bacterial protein antigens,(2)design strategies leveraging biomembrane nanostructures to enhance humoral and cellular immune responses,(3)preclinical efficacy against diverse pathogens,and(4)translational challenges and prospects.Biomembrane nanostructure-driven approaches represent a paradigm shift in the development of next-generation bacterial protein vaccines against resistant infections.
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 Natural Science Foundation of China(Nos.82173747,82373803)the Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province(No.2021TQ060944)。
文摘Cancer vaccines are a notable area of immunotherapy due to their capacity to elicit specific antitumor immune responses and to create immune memory.However,they encounter challenges in clinical practice due to several bottlenecks,including tumor heterogeneity,low immunogenicity,immunosuppressive tumor environment,and delivery obstacles,which collectively impact their clinical effectiveness.In this study,we developed nanocomposites containing positively charged melittin(MEL)and negatively charged photosensitizer indocyanine green(ICG),embedded in dissolving microneedles(MEL/ICG-HA@DMNs).This approach allows precise drug delivery by creating microchannels that bypass the stratum corneum barrier,targeting superficial lesions directly.Our results demonstrated that the complexation of MEL and ICG significantly reduced the hemolytic activity of MEL while maintaining its ability to disrupt cell membranes.After loading MEL/ICG-HA into the microneedle,MEL/ICG-HA@DMNs not only effectively concentrated the drug at the tumor site,inducing localized hyperthermia and successfully ablating the tumor,but also formed an in situ whole-cell vaccine containing a rich source of tumor-associated antigens.Moreover,the system promoted dendritic cell maturation and increased the M1/M2 macrophage ratio,enhancing the immune response.By overcoming the limitations of traditional cancer vaccines,this system ensures precise drug delivery and robust immune activation.This innovative approach holds the potential to revolutionize cancer treatment,offering a new paradigm in precision oncology.
基金supported by the Kunlun Mountain Scholar Project of Qinghai Province,China(Project No.:2021-13).
文摘Diabetes,a metabolic disease stemming from impaired or defective insulin secretion,ranks among the most severe chronic illnesses globally.While several approved drugs exist for its treatment,they often come with multiple side effects.Therefore,there is a pressing need for safe and effective anti-diabetic medications.Traditional Chinese medicine has recognized Lycium barbarum(LB;goji berry)plant,commonly known as“wolfberry fruit”in China,for over 2,000 years.Natural compounds derived from LB show promise in reducing diabetes levels.Although research on the impact of LB on diabetes is still limited,our review aims to explore the potential of LB in reducing the risk of diabetes and examine the underlying mechanisms involved.LB can modulate diabetes through various pathways,such as inhibitingα-amylase andα-glucosidase activities,promotingβ-cell proliferation,stimulating insulin secretion,inhibiting glucagon secretion,improving insulin resistance and glucose tolerance,and enhancing antioxidant and anti-inflammatory activities.Additionally,LB improves gut flora and immunomodulation,further aiding diabetes management.These findings highlight the potential clinical utility of LB in managing diabetes and its complications within the framework of evidence-based modern medicine.
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 National Natural Science Foundation of China(82341087,82073912,and 81903896)a project funded by Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions.
文摘Anemoside B4(AB4),a triterpenoidal saponin derived from Pulsatilla chinensis,has garnered considerable attention for its potent anti-inflammatory and immunomodulatory activities,culminating in its approval for clinical trials by the Center for Drug Evaluation,National Medical Products Administration,for the treatment of mild to moderate ulcerative colitis.Despite this,AB4’s therapeutic potential remained underexplored until the development of its injection formulation.This review discusses the scientific rationale and theoretical framework behind AB4’s development,offering a new paradigm and innovative research strategy for discovering lead compounds or drug candidates from natural medicines.In-depth investigations into AB4’s cellular targets,biochemical pathways,and administration routes have provided valuable insights into its druggability evaluation and clinical potential.The high water solubility of AB4,attributable to its multiple sugar units,imposes limitations on its bioavailability and pharmacokinetic profiles.To address this,structural modification via chemical methods and enzymatic hydrolysis have been employed,resulting in derivatives with reduced molecular weight,improved bioavailability,enhanced pharmacological activity,and greater clinical potential.These advances lay a solid foundation for the continued development of AB4 and its derivatives as promising therapeutic agents.
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.
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.
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.
文摘Mesenchymal stem or stromal cells(MSCs)are among the most extensively studied cell populations in regenerative medicine due to their multipotent differentiation potential,secretion of trophic factors,and immunomodulatory effects.Over the past two decades,preclinical studies have demonstrated encouraging results across musculoskeletal,cardiovascular,neurological,and immunemediated disorders.However,the translation of MSCs from the laboratory to routine clinical practice remains hindered by unresolved scientific,technical,and regulatory challenges.This review provides a critical appraisal of these hurdles,organized across three major stages of translation:In vitro research,in vivo animal studies,and clinical application.In vitro issues include the heterogeneity of isolation techniques,replicative senescence during expansion,genetic and epigenetic instability,and the need for xeno-free,standardized culture platforms.In vivo challenges arise from poor cell survival,low engraftment rates,off-target migration,and microenvironmental influences that shape therapeutic outcomes.Clinical translation introduces additional complexity,including inter-patient variability,large-scale manufacturing difficulties,stringent regulatory compliance,high production costs,and the absence of harmonized potency assays.Solutions under exploration include the use of automated bioreactors,biomimetic scaffolds,hypoxic preconditioning,extracellular vesicle-based therapies,and international standardization efforts.Addressing these hurdles through multidisciplinary collaboration is essential for MSC-based therapies to become reliable,safe,and accessible regenerative treatments.
