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
The article is devoted to the study of the immunomodulating activity of rectal suppositories with an extract of licorice root and essential oils of chamomile and tea tree. Taking into account that medicine is intended...The article is devoted to the study of the immunomodulating activity of rectal suppositories with an extract of licorice root and essential oils of chamomile and tea tree. Taking into account that medicine is intended and prescribed for children, all the experiments were performed on immature nonlinear one-month rats with weight of 60.0-80.0 g. As a result, it was found out that rectal insertion of suppositories with an extract of licorice root causes an increase in the phagocytic function of neutrophils and increases the quantity of antibodies in the spleen and titers of hemagglutinins and hemolysins in serum, that indicating on the activation of nonspecific and humoral immunity of immature animals. Moreover, the prospects of possible application of suppositories with an extract of licorice root are showed for prevention and treatment of various immunodependent diseases, viral in particular.展开更多
Several novel C-pseudonucleosides containing thiazolidin-4-one and phenyl connected by acetamide bond were rationally designed and easily synthesized at room temperature by using the unprotected sugar aldehyde as the ...Several novel C-pseudonucleosides containing thiazolidin-4-one and phenyl connected by acetamide bond were rationally designed and easily synthesized at room temperature by using the unprotected sugar aldehyde as the starting material. The effects of the compounds on Con A-induced T cell proliferation were evaluated at five concentrations of 5, 10, 25, 50, and 100 mmol/L Interestingly,compounds 7a and 8a（n = 2, R = H） exhibited immunostimulating activities, while compounds 5a, 6a（n = 1, R = H） and 7b, 8b（n = 2, R = CH3） showed immunosuppressive activities. Another two compounds 5 b and 6b（n = 1, R = CH3） had no immunomodulating activities. These initial biological results suggested that subtle structural changes to the phenyl and acetamide bond of C-pseudonucleosides could have a significant effect on T cell proliferation bias, although it was difficult to formulate a rigorous structureactivity relationship based on the observed activities.展开更多
Using<sup>125</sup>I-UDR labelled K562 cells as target cells, we assay the natural killer cell （NK） activity in peripheral blood mononuclear cells （PBMCs） from 36 cases of various types of viral hepati...Using<sup>125</sup>I-UDR labelled K562 cells as target cells, we assay the natural killer cell （NK） activity in peripheral blood mononuclear cells （PBMCs） from 36 cases of various types of viral hepatitis B （HB）, together with 33 healthy adults as controls. At same time the NK activity was detected when PBMCs were pretreated with recombinant IL-2 （rIL-2） in 19 patients with various types of HB and 14 normal controls. We also determined the IL-2 activity produced by PBMCs in 26 HB patients and 14 normal controls. The following results were obtained: （1） The NK activity was markedly elevated in early acute hepatitis B （AH） （P【0.01）; significantly decreased in chronic active hepatitis （CAH）, chronic persistent hepatitis （CPH） and fulminant hepatitis （FH） （P【0.01）, while that of convalescents with AH was within normal range 35.85±12.52%. （2） The early rise of NK activity in acute infection and the decline in convalescence and also the parallel change in SGPT level in 3 AH cases were observed. （3） The amount of IL-2 produced by PBMCs in HB patients was lower than that of normal controls （P【0.01 ）. （4）There was no correlation between the change of IL-2 activity and NK activity in HB patients （r=0.15; P】O.05）. （5） The NK activity of most normal subjects were enhanced when the PBMCs were pretreated with rIL-2 but the latter was still within the normal ranges. These results suggest that the mechanism of the effect of IL-2 in modulating the NK activity of HB patients is very complicated. IL-2 not only directly enhances the low NK activity of HB patients, but also depresses the high NK activity. This immunomodulating effect may be influenced by serum inhibitory facts as well as the amount and the combining ability of IL-2 receptor or on NK cell surface.展开更多
Cancer,ranging from early stages to metastatic spread,is one of the leading causes of death globally.Current treatment options,including chemotherapy,radiotherapy,and targeted drugs,have limitations substantial advers...Cancer,ranging from early stages to metastatic spread,is one of the leading causes of death globally.Current treatment options,including chemotherapy,radiotherapy,and targeted drugs,have limitations substantial adverse effects,the development of drug resistance,and high cost.To address these challenges,numerous studies have focused on repurposing existing drugs for anticancer therapy,with clotrimazole(CLZ)emerging as a promising candidate due to its notable anticancer activity.CLZ was first developed as an antifungal agent.Recently,significant anticancer effects have been observed making it a suitable candidate for drug repurposing.Compared with other azole-based antifungals,CLZ has shown distinct therapeutic effects on cancer cells via several pathways.Its ability to disrupt glycolysis by inhibiting phosphofructokinase(PFK)and hexokinase(HK)distinguishes it from other azoles.Furthermore,CLZ obstructs calcium homeostasis and critical survival pathways,such as extracellular signal-regulated kinase(ERK)-p65,phosphatidylinositol 3-kinase(PI3K),and mitochondrial apoptotic pathways,inhibiting tumor growth,inducing apoptosis,and attenuating metastasis.This review summarizes the potential of CLZ repurposing for cancer therapy,emphasizing its well-established safety profile and cost-effectiveness while addressing unmet clinical needs in current cancer treatment.It briefly examines in vitro and in vivo assessments to understand the mechanisms and effects of CLZ on various cancer types.Furthermore,novel strategies such as nanoformulations and combination therapies with existing chemotherapeutic drugs have been highlighted to improve therapeutic outcomes.Preclinical studies have provided promising evidence for the efficacy of CLZ in different cancers,showing tumor regression and improved responses to conventional chemotherapy or targeted therapies.Given its evident preclinical results and diverse mechanisms of action,CLZ may be considered an antineoplastic agent.Further clinical research is required to fully elucidate its anticancer potential,potentially positing it as a valuable addition to currently available cancer treatments.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
The stimulator of interferon genes(STING),as a critical innate immune sensor,has been widely and continually explored in immune-related disease treatment.As lipid bilayer-closed particles derived from cells,extracellu...The stimulator of interferon genes(STING),as a critical innate immune sensor,has been widely and continually explored in immune-related disease treatment.As lipid bilayer-closed particles derived from cells,extracellular vesicles(EVs)inherently function in target-guided intercellular communication.To incorporate the native merits of EVs into STING pathways,i.e.,engineered EV@STING,poor bioavailability and off-target issues that STING activators possess could be significantly overcome.In this review,emerged STING activators such as nitrogen-containing heterocyclic structures and the universal STING activation strategy(uniSTING)are firstly summarized.Diverse EVs sources from mesenchymal stem cells(MSCs)and innate and adaptive immune cells may evoke distinct regulatory results.Concurrently,how the EVs contents including double-stranded DNA(dsDNA),microRNA(miRNA),cyclic GMP-AMP synthase(cGAS)and 2′3′-cyclic GMP-AMP(2′3′-cGAMP)proteins participate in the regulation of STING activation are widely studied.After mastering the two pivotal aspects of EV@STING,their immunomodulatory roles including in pathogen infection,inflammatory diseases,and cancer therapy are comprehensively summed up and discussed.Finally,in cancer study field,therapeutic challenges and clinical translational opportunities of EV@STING are thoroughly evaluated.展开更多
The pathophysiology of many ailments,including neurological,gastrointestinal,and metabolic disorders,is well known to be influenced by intestinal dysbiosis.Clinical research has provided evidence suggesting a strong c...The pathophysiology of many ailments,including neurological,gastrointestinal,and metabolic disorders,is well known to be influenced by intestinal dysbiosis.Clinical research has provided evidence suggesting a strong correlation between dysbiosis of the gut microbiome and colorectal cancer(CRC)development.The active reprogramming of metabolic pathways to boost glycolysis,fatty acid production,lipogenesis,and glutaminolysis constitutes a major metabolic shift in cancer development,including CRC.The complex combination of different factors leads to CRC,making it an environmental disease.These factors include food and lifestyle choices,genetics and family history,age,underlying intestinal diseases,and dysbiosis of the gut microbiota.One of the primary risk factors for carcinoma development is diet,which impacts an individual’s gut microbiome.In addition to impacting CRC formation,the gut microbiome also has immunomodulatory effects,including various immunological interactions and the underlying mechanisms governing them.Microbial interactions in CRC have been extensively studied,yet numerous unresolved queries exist on how gut bacteria can influence treatment.Microbiome-driven immunotherapies,focusing on probiotics,prebiotics,and synbiotics,represent a promising therapeutic avenue.However,large-scale treatment utilization in CRC patients is limited by several issues,including variations in the microbial makeup of each patient’s gut and a lack of established methods.The study highlights the impact of several risk factors,including dysbiosis of the gut microbiome and different approaches to halting and treating CRC progression with a focus on diet changes and modulation of the gut flora.Given the foregoing,we propose that if research gaps are addressed and immunotherapy is paired with microbial interventions,microbiota-based therapeutics could potentially impede the growth of tumors and treat CRC.展开更多
Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms...Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms are often overlooked.Recent evidence suggests that monocyte phenotypic plasticity plays a central role in PAD development,affecting atherogenesis,plaque progression,ischemia-reperfusion injury,and chronic ischemic remodeling.This narrative review aims to summarize the latest advances(2023-2025)in understanding monocyte diversity,functional states,and their changes throughout different stages of PAD.We discuss both established and emerging biomarkers,such as circulating monocyte subset proportions,functional assays,immune checkpoint expression,and multi-omics signatures,highlighting their potential for prognosis and the challenges in translating them to clinical practice.We also present a stage-specific approach to mapping out potential therapies,linking monocyte phenotypes to molecular targets and possible interventions.Additionally,we address regulatory,economic,and implementation considerations for applying these findings in a clinical setting.The goal of this review is to facilitate the development of targeted immunomodulatory strategies to improve limb and cardiovascular outcomes in PAD by combining mechanistic understanding with therapeutic innovation.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
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
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
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The article is devoted to the study of the immunomodulating activity of rectal suppositories with an extract of licorice root and essential oils of chamomile and tea tree. Taking into account that medicine is intended and prescribed for children, all the experiments were performed on immature nonlinear one-month rats with weight of 60.0-80.0 g. As a result, it was found out that rectal insertion of suppositories with an extract of licorice root causes an increase in the phagocytic function of neutrophils and increases the quantity of antibodies in the spleen and titers of hemagglutinins and hemolysins in serum, that indicating on the activation of nonspecific and humoral immunity of immature animals. Moreover, the prospects of possible application of suppositories with an extract of licorice root are showed for prevention and treatment of various immunodependent diseases, viral in particular.
基金supports from the National Natural Science Foundation of China (Nos. 20972039, 21372060)Research Fund for the Doctoral Program of Higher Education of China (No. 20121301110004)+2 种基金Hebei Province Natural Science Fund for Distinguished Young Scholars (No. B2015201005)the Medicinal Joint Funds of the Natural Science Foundation of Hebei and Shijiazhuang Pharmaceutical Group Foundation (No. B2011201169)the Natural Science Foundations of Education Department of Hebei (No. ZH2011110)
文摘Several novel C-pseudonucleosides containing thiazolidin-4-one and phenyl connected by acetamide bond were rationally designed and easily synthesized at room temperature by using the unprotected sugar aldehyde as the starting material. The effects of the compounds on Con A-induced T cell proliferation were evaluated at five concentrations of 5, 10, 25, 50, and 100 mmol/L Interestingly,compounds 7a and 8a（n = 2, R = H） exhibited immunostimulating activities, while compounds 5a, 6a（n = 1, R = H） and 7b, 8b（n = 2, R = CH3） showed immunosuppressive activities. Another two compounds 5 b and 6b（n = 1, R = CH3） had no immunomodulating activities. These initial biological results suggested that subtle structural changes to the phenyl and acetamide bond of C-pseudonucleosides could have a significant effect on T cell proliferation bias, although it was difficult to formulate a rigorous structureactivity relationship based on the observed activities.
文摘Using<sup>125</sup>I-UDR labelled K562 cells as target cells, we assay the natural killer cell （NK） activity in peripheral blood mononuclear cells （PBMCs） from 36 cases of various types of viral hepatitis B （HB）, together with 33 healthy adults as controls. At same time the NK activity was detected when PBMCs were pretreated with recombinant IL-2 （rIL-2） in 19 patients with various types of HB and 14 normal controls. We also determined the IL-2 activity produced by PBMCs in 26 HB patients and 14 normal controls. The following results were obtained: （1） The NK activity was markedly elevated in early acute hepatitis B （AH） （P【0.01）; significantly decreased in chronic active hepatitis （CAH）, chronic persistent hepatitis （CPH） and fulminant hepatitis （FH） （P【0.01）, while that of convalescents with AH was within normal range 35.85±12.52%. （2） The early rise of NK activity in acute infection and the decline in convalescence and also the parallel change in SGPT level in 3 AH cases were observed. （3） The amount of IL-2 produced by PBMCs in HB patients was lower than that of normal controls （P【0.01 ）. （4）There was no correlation between the change of IL-2 activity and NK activity in HB patients （r=0.15; P】O.05）. （5） The NK activity of most normal subjects were enhanced when the PBMCs were pretreated with rIL-2 but the latter was still within the normal ranges. These results suggest that the mechanism of the effect of IL-2 in modulating the NK activity of HB patients is very complicated. IL-2 not only directly enhances the low NK activity of HB patients, but also depresses the high NK activity. This immunomodulating effect may be influenced by serum inhibitory facts as well as the amount and the combining ability of IL-2 receptor or on NK cell surface.
文摘Cancer,ranging from early stages to metastatic spread,is one of the leading causes of death globally.Current treatment options,including chemotherapy,radiotherapy,and targeted drugs,have limitations substantial adverse effects,the development of drug resistance,and high cost.To address these challenges,numerous studies have focused on repurposing existing drugs for anticancer therapy,with clotrimazole(CLZ)emerging as a promising candidate due to its notable anticancer activity.CLZ was first developed as an antifungal agent.Recently,significant anticancer effects have been observed making it a suitable candidate for drug repurposing.Compared with other azole-based antifungals,CLZ has shown distinct therapeutic effects on cancer cells via several pathways.Its ability to disrupt glycolysis by inhibiting phosphofructokinase(PFK)and hexokinase(HK)distinguishes it from other azoles.Furthermore,CLZ obstructs calcium homeostasis and critical survival pathways,such as extracellular signal-regulated kinase(ERK)-p65,phosphatidylinositol 3-kinase(PI3K),and mitochondrial apoptotic pathways,inhibiting tumor growth,inducing apoptosis,and attenuating metastasis.This review summarizes the potential of CLZ repurposing for cancer therapy,emphasizing its well-established safety profile and cost-effectiveness while addressing unmet clinical needs in current cancer treatment.It briefly examines in vitro and in vivo assessments to understand the mechanisms and effects of CLZ on various cancer types.Furthermore,novel strategies such as nanoformulations and combination therapies with existing chemotherapeutic drugs have been highlighted to improve therapeutic outcomes.Preclinical studies have provided promising evidence for the efficacy of CLZ in different cancers,showing tumor regression and improved responses to conventional chemotherapy or targeted therapies.Given its evident preclinical results and diverse mechanisms of action,CLZ may be considered an antineoplastic agent.Further clinical research is required to fully elucidate its anticancer potential,potentially positing it as a valuable addition to currently available cancer treatments.
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 National Natural Science Foundation of China(NSFC,Nos.32222090,32101069 and 32171318)Faculty of Health Sciences,University of Macao,the Multi-Year Research Grant(MYRG)of University of Macao and the University of Macao Development Foundation(UMDF)(Nos.MYRG2022-00011-FHS and MYRG-GRG2023-00013-FHS-UMDF)+2 种基金the Science and Technology Development Fund,Macao SAR(Nos.0002/2021/AKP,0133/2022/A3,0009/2022/AKP,and 0006/2023/ITP1)Ministry of Education Frontiers Science Centre for Precision Oncology,University of Macao(No.SP2023-00001-FSCPO)Guangdong Provincial Applied Science and Technology Research and Development Program(No.2024A1515011140).
文摘The stimulator of interferon genes(STING),as a critical innate immune sensor,has been widely and continually explored in immune-related disease treatment.As lipid bilayer-closed particles derived from cells,extracellular vesicles(EVs)inherently function in target-guided intercellular communication.To incorporate the native merits of EVs into STING pathways,i.e.,engineered EV@STING,poor bioavailability and off-target issues that STING activators possess could be significantly overcome.In this review,emerged STING activators such as nitrogen-containing heterocyclic structures and the universal STING activation strategy(uniSTING)are firstly summarized.Diverse EVs sources from mesenchymal stem cells(MSCs)and innate and adaptive immune cells may evoke distinct regulatory results.Concurrently,how the EVs contents including double-stranded DNA(dsDNA),microRNA(miRNA),cyclic GMP-AMP synthase(cGAS)and 2′3′-cyclic GMP-AMP(2′3′-cGAMP)proteins participate in the regulation of STING activation are widely studied.After mastering the two pivotal aspects of EV@STING,their immunomodulatory roles including in pathogen infection,inflammatory diseases,and cancer therapy are comprehensively summed up and discussed.Finally,in cancer study field,therapeutic challenges and clinical translational opportunities of EV@STING are thoroughly evaluated.
文摘The pathophysiology of many ailments,including neurological,gastrointestinal,and metabolic disorders,is well known to be influenced by intestinal dysbiosis.Clinical research has provided evidence suggesting a strong correlation between dysbiosis of the gut microbiome and colorectal cancer(CRC)development.The active reprogramming of metabolic pathways to boost glycolysis,fatty acid production,lipogenesis,and glutaminolysis constitutes a major metabolic shift in cancer development,including CRC.The complex combination of different factors leads to CRC,making it an environmental disease.These factors include food and lifestyle choices,genetics and family history,age,underlying intestinal diseases,and dysbiosis of the gut microbiota.One of the primary risk factors for carcinoma development is diet,which impacts an individual’s gut microbiome.In addition to impacting CRC formation,the gut microbiome also has immunomodulatory effects,including various immunological interactions and the underlying mechanisms governing them.Microbial interactions in CRC have been extensively studied,yet numerous unresolved queries exist on how gut bacteria can influence treatment.Microbiome-driven immunotherapies,focusing on probiotics,prebiotics,and synbiotics,represent a promising therapeutic avenue.However,large-scale treatment utilization in CRC patients is limited by several issues,including variations in the microbial makeup of each patient’s gut and a lack of established methods.The study highlights the impact of several risk factors,including dysbiosis of the gut microbiome and different approaches to halting and treating CRC progression with a focus on diet changes and modulation of the gut flora.Given the foregoing,we propose that if research gaps are addressed and immunotherapy is paired with microbial interventions,microbiota-based therapeutics could potentially impede the growth of tumors and treat CRC.
文摘Peripheral artery disease(PAD)remains a significant global health issue,with current treatments primarily focused on relieving symptoms and addressingmacrovascular issues.However,critical immunoinflammatory mechanisms are often overlooked.Recent evidence suggests that monocyte phenotypic plasticity plays a central role in PAD development,affecting atherogenesis,plaque progression,ischemia-reperfusion injury,and chronic ischemic remodeling.This narrative review aims to summarize the latest advances(2023-2025)in understanding monocyte diversity,functional states,and their changes throughout different stages of PAD.We discuss both established and emerging biomarkers,such as circulating monocyte subset proportions,functional assays,immune checkpoint expression,and multi-omics signatures,highlighting their potential for prognosis and the challenges in translating them to clinical practice.We also present a stage-specific approach to mapping out potential therapies,linking monocyte phenotypes to molecular targets and possible interventions.Additionally,we address regulatory,economic,and implementation considerations for applying these findings in a clinical setting.The goal of this review is to facilitate the development of targeted immunomodulatory strategies to improve limb and cardiovascular outcomes in PAD by combining mechanistic understanding with therapeutic innovation.
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.
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.
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.
