The establishment of drug-free feeding systems has been required for secure and healthy livestock production. Although functional feed materials containing microorganisms as alternatives to enhance intestinal immunity...The establishment of drug-free feeding systems has been required for secure and healthy livestock production. Although functional feed materials containing microorganisms as alternatives to enhance intestinal immunity are expected to be beneficial for reducing diarrhoea caused by pathogens in weaned piglets, the effects of such materials on porcine intestinal cells have not been investigated in detail. Therefore, this work evaluated the immunoregulatory functions of microbial feed materials in porcine intestinal immune and epithelial cells. Porcine immune cells isolated from Peyer’s patches and mesenteric lymph nodes were stimulated with six different feed materials containing microorganisms, and evaluated for lymphocyte mitogenicity and cytokine inductions. In addition, porcine intestinal epithelial cells were stimulated with the materials before treatment with heat-killed enterotoxigenic Escherichia coli (ETEC), and analyzed for the proinflammatory cytokine expressions. The material containing Bifidobacterium thermophilum significantly augmented lymphocytes’ mitogenicity and also induced a high expression of IL-2, IL-6 and IFN-γ in immune cells, and inhibited ETEC-induced overexpression of IL-6 and IL-8 via regulation of Toll-like receptor signaling. These results suggest that this feed material stimulates intestinal epithelial and immune cells to exert immunoregulation, suggesting that this feed is expected to contribute to promoting the health of piglets without using antimicrobial feed materials.展开更多
BACKGROUND The coronavirus disease 2019(COVID-19)caused by novel coronavirus 2019 in December 2019 has spread all around the globe and has caused a pandemic.There is still no current effective guidance on the clinical...BACKGROUND The coronavirus disease 2019(COVID-19)caused by novel coronavirus 2019 in December 2019 has spread all around the globe and has caused a pandemic.There is still no current effective guidance on the clinical management of COVID-19.Mesenchymal stem cell therapy has been shown to be one of the therapeutic approaches to alleviate pneumonia and symptoms through their immunomodulatory effect in COVID-19 patients.CASE SUMMARY We describe the first confirmed case of COVID-19 in Hangzhou to explore the role of human menstrual blood-derived stem cells(MenSCs)in the treatment of COVID-19.Moreover,we review the immunomodulation effect including nonspecific and specific immune functions of MenSCs for the therapy of COVID-19.CONCLUSION MenSCs can be helpful to find a promising therapeutic approach for COVID-19.展开更多
[Objectives]To study immunoregulatory effects of Nuhuang Fuzheng Granules on mice with Cytoxan-induced immunosuppression.[Methods]Kunming variety mice were randomly divided into the control group,model group,positive ...[Objectives]To study immunoregulatory effects of Nuhuang Fuzheng Granules on mice with Cytoxan-induced immunosuppression.[Methods]Kunming variety mice were randomly divided into the control group,model group,positive medicine group,and low,medium,and high dosage groups of Nuhuang Fuzheng Granules. Except the control group,the rest groups of mice were injected with Cytoxan at60 mg/kg to reproduce the immunosuppressive mice model,and were fed through stomach at 0. 5g/kg,1. 0 g/kg and 2. 0 g/kg Nuhuang Fuzheng Granules for seven days( twice a day); the positive control group was fed with Astragalus Polysacharin( 500 mg/L). The carbon clearance index,immune organ index,serum hemolysin were determined. IL-2,IFN-γ,and IL-4 levels in mouse serum were measured by ELISA. [Results] Nuhuang Fuzheng Granules could significantly incease the carbon granular expurgation index of mice with Cytoxan-induced immunosuppression,and the 2. 0 g/kg and 1. 0 g/kg dosage groups had better effect than 0. 5 g/kg dosage group( P < 0. 05); the spleen index of mice with Cytoxan-induced immunosuppression increased significantly and there was dose-effect relationship in a certain range of concentration; the thymus index and serum hemolysin HC_(50) were significantly higher than 0. 5 g/kg dosage group( P < 0. 05); IL-4 and IFN-γ in the serum was significantly higher than the model group( P < 0. 01),the increase of IL-2 was not significantly( P > 0. 05). [Conclusions] Nuhuang Fuzheng Granules can promote growth of immune organs and secretion of cytokines through improving the carbon granular expurgation ability of mice with Cytoxan-induced immunosuppression.展开更多
Antibacterial piezoelectric materials have broad application prospects in the medical field because of their broadspectrum antibacterial properties and no bacterial drug resistance.At present,one of the main problems ...Antibacterial piezoelectric materials have broad application prospects in the medical field because of their broadspectrum antibacterial properties and no bacterial drug resistance.At present,one of the main problems in the application of piezoelectric materials is the low electrocatalytic efficiency,which limits its application in anti-bacterial field.In this study,a piezoelectric antibacterial(PLGA/Zn-KNN)scaffold was fabricated by incorpo-rating zinc oxide(ZnO)into potassium-sodium niobate(KNN)and composited with a poly(lactic-co-glycolic acid)(PLGA)to achieve multicombination antibacterial for bone infection.The physicochemical properties of piezoelectric antibacterial scaffolds were analyzed.Bacterial,cell,and animal experiments were performed to characterize the antibacterial and infection treatment capabilities of piezoelectric scaffolds.The piezoelectric properties of the PLGA/Zn-KNN scaffold were enhanced by embedding ZnO particles into the KNN solid solution matrix.Furthermore,the piezoelectric scaffold released zinc ions,and electrical stimulation driven by ultrasound resulted in significant antibacterial effects through direct and immunoregulatory antibacterial pathways.Mechanistic investigation suggested that extracellular matrix ligands and complement and coagulation cascades may have a moderate effect on macrophage phagocytosis.This work highlights potential application methods for fabricating novel antibacterial hybrid piezoelectric scaffolds and engineering macrophages with immunoregu-latory antibacterial activity.展开更多
The aging microenvironment,as a key driver of tumorigenesis and progression,plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype(SASP).SASP co...The aging microenvironment,as a key driver of tumorigenesis and progression,plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype(SASP).SASP consists of a variety of interleukins,chemokines,proteases,and growth factors.It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms,thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment.Furthermore,these secreted factors activate key signaling pathways such as NF-κB,cGAS-STING,and mTOR,which regulate the expression of immune-related molecules(such as PDL1)and promote the recruitment of immunosuppressive cells,including regulatory T cells and myeloid-derived suppressor cells.This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment.Furthermore,the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms,including approaches to inhibit SASP secretion or eliminate senescent cells.Although these strategies have shown promise in certain tumor models,the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies.This highlights the need for further research into adaptive stratification and personalized treatment approaches.Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.展开更多
Cluster of differentiation 47(CD47)is a widely expressed transmembrane protein that serves as a critical immunoregulatory checkpoint in both homeostatic and pathological conditions of the digestive system.It interacts...Cluster of differentiation 47(CD47)is a widely expressed transmembrane protein that serves as a critical immunoregulatory checkpoint in both homeostatic and pathological conditions of the digestive system.It interacts with signal regulatory protein alpha to send a‘do not eat me’signal,thereby preventing phagocytosis and shaping immune responses.Beyond immunity,CD47 also influences cell death,growth and metabolism through interactions with integrins and thrombospondin-1.Recent studies implicate CD47 as a central nexus in the pathogenesis of diverse liver and gastrointestinal disorders,including metabolic dysfunction-associated steatotic liver disease,metabolic dysfunction-associated steatohepatitis,inflammatory bowel disease,liver ischaemia-reperfusion injury,drug-induced liver injury and gastrointestinal malignancies such as hepatocellular carcinoma,colorectal and pancreatic cancers.CD47 contributes to disease progression through immune modulation,endothelial dysfunction,fibrogenic activation and suppression of antitumour immunity.This review summarises current mechanistic insights into CD47 signalling across digestive diseases and highlights its emerging potential as a therapeutic target for immunometabolic and oncological interventions in gastroenterology and hepatology.展开更多
Objective： To investigate the anti-inflammatory and immunoregulatory effects of Yupingfeng , Powder and its components in rats. Methods： A rat chronic bronchitis （CB） model was developed using lipopolysaccharide ...Objective： To investigate the anti-inflammatory and immunoregulatory effects of Yupingfeng , Powder and its components in rats. Methods： A rat chronic bronchitis （CB） model was developed using lipopolysaccharide （LPS） combined with bacillus Calmette Guerin （BCG）. YPF, simple recipe Astragalus membranaceus （Fisch.） Bge （AM） and Astragalus membranaceus （Fisch.） Bge plus rhizome of Atractylodes macrocepha/a Koidz （AM＋RA） decoction were administered （intragastric administration, once a day for 21 days） to rats, to prevent and treat CB. Immunoregulatory and anti-inflammatory effects of YPF, AM and AM＋RA were tested by serum pharmacology in vitro on splenic lymphocytes of normal rats and alveolar macrophages of CB rats. Results： Inflammation in the pulmonary tissue and the bronchus of CB rats was significantly reduced in the YPF-treatment groups, AM and AM＋RA groups demonstrating the efficacy of YPF. Serum samples collected at different times from rats after administration of YPF, AM and AM＋RA demonstrated increased proliferation of splenic lymphocytes with area under the effect curve （AUE） of 552.6%, 336.3% and 452.0%, respectively. Treatment of alveolar macrophages with serum samples in YPF, AM or AM＋RA group inhibited interleukin-8 （IL-8） in the cell culture media, and the effect was much better in the YPF group compared with AM or AM＋RA group, with a higher maximal effect （Emax, P〈0.05） and larger AUE （P〈0.01 and P〈0.05）. Moreover, serum from rats treated with AM or AM＋RA had similar efficacy, while the efficiency was lower than that treated with YPF. Conclusion： YPF demonstrated anti-inflammatory and immunoregulatory effects in a rat model of CB, and time- dependent relationships were demonstrated in vitro.展开更多
Background This study was to evaluate whether anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro and prolong cardiac allograft...Background This study was to evaluate whether anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro and prolong cardiac allograft survival after adoptive transfer KH*2/5DMethods Anergic cells were induced in vitro by the addition of anti-CD154 and anti-CD80 monoclonal antibodies (mAbs) to primary MLR (mixed lymphocyte reaction) consisting of BALB/c as responder and C3H as stimulator Anergic cells were added to a newly formed MLR in assessing the regulatory capacity and antigen specificity of anergic cells The ability of anergic cells to respond to antigen and/or exogenous recombinant mouse interleukin-2 (rmIL-2) was tested For in vivo studies, anergic cells were intravenously injected into 3 0-Gy γ-irradiated BALB/c mice immediately after heterotopic abdominal cardiac transplantation To prolong allograft survival, recipient mice injected with anergic cells received rapamycin therapy (1 mg·day -1 ·kg -1 ) KH*2/5DResults Anergic cells strongly suppressed the proliferation of naǐve BALB/c splenocytes against the original (C3H) stimulator in a dose-dependent manner, but they failed to suppress the proliferation of naǐve BALB/c splenocytes against the third-party (C57BL/6J) stimulator The anergic state was reversed by both original (C3H) stimulator and additional exogenous IL-2 In in vivo studies, untreated irradiated BALB/c mice rejected C3H cardiac allografts with a mean survival time of (8 6±1 1) days, whereas those injected with the anergic cells rejected the allografts with a mean survival time of (11 8±1 9) days, which was slightly longer than that of the untreated mice The protocol based on anergic cells injection plus rapamycin therapy could prolong allograft survival significantly [(29 6±4 4) days] Conclusions Anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro , and prolong cardiac allograft survival after adoptive transfer in the presence of rapamycin therapy This procedure might be clinically useful for prolonging allograft survival if optimal protocols are developed展开更多
Objective:The objective of this study was to characterize the chemical compounds of a Hanshi-Yufei formulation(HSYF;a modified formulation of a traditional Chinese medicine used for treating COVID-19)to elucidate the ...Objective:The objective of this study was to characterize the chemical compounds of a Hanshi-Yufei formulation(HSYF;a modified formulation of a traditional Chinese medicine used for treating COVID-19)to elucidate the mechanism of action and to evaluate potential anti-inflammatory effects of HSYF.Materials and Methods:The chemical constituents of HSYF extract were characterized using UPLC-Q-TOF/MS.Subsequently,a set of TCM network pharmacology methods was applied to identify disease-associated genes and to predict target profiles and pharmacological actions associated with the constituents of HSYF.Then,the antiviral effects of HSYF on H1N1 were assessed in RAW264.7 cells using MTT assays.Expression levels of pro-inflammatory cytokines interleukin(IL)-6 and tumor necrosis factor(TNF)-αfollowing infection of RAW264.7 cells with H1N1 were measured using an enzyme-linked immune sorbent assay(ELISA),and expression levels of inflammatory-related factors were detected using western blotting.Results:In total,165 chemical constituents(including glycosides,tannins,volatile oils,amino acids,triterpenoids,polyphenols,phenylpropanoids,sesquiterpenes,alkaloids,and flavonoids,among others)were tentatively identified in HSYF.Network pharmacology demonstrated that HSYF can regulate immunomodulatory-and anti-inflammatory-related targets of multiple pathways through its active ingredients,suggesting potential anti-COVID-19 effects.Furthermore,cell viability assays and ELISA showed that HSYF significantly inhibited H1N1 replication in RAW64.7 cells and markedly reduced expression of pro-inflammatory cytokines TNF-αand IL-6 at the proteins level.Conclusions:The results of the present study help improve our understanding of the therapeutic effects of HSYF in COVID-19 treatment from multi-level perspectives.展开更多
α-Galactosylceramides, which can be recognized by natural killer T （NKT） cells, are now attracting more and more attention due to their therapeutic potential in cancer, infection and autoimmune diseases. Advances h...α-Galactosylceramides, which can be recognized by natural killer T （NKT） cells, are now attracting more and more attention due to their therapeutic potential in cancer, infection and autoimmune diseases. Advances have been achieved in discovering compounds with better activities and efforts have been made to understand the structure-activity relationships （SARs） of these NKT cell ligands. In this review, we discuss the structure modifications based on KRN7000, the principal glycolipid used in the study of NKT cell stimulation, and the SARs based on these modified structures.展开更多
The activation of heme oxygenase-1(HO-1) appears to be an endogenous defensive mechanism used by cells to reduce inflammation and tissue damage in a number of injury models. HO-1, a stress-responsive enzyme that catab...The activation of heme oxygenase-1(HO-1) appears to be an endogenous defensive mechanism used by cells to reduce inflammation and tissue damage in a number of injury models. HO-1, a stress-responsive enzyme that catabolizes heme into carbon monoxide(CO), biliverdin and iron, has previously been shown to protect grafts from ischemia/reperfusion and rejection.In addition, the products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin, have been shown to exert protective effects in the liver against a number of stimuli, as in chronic hepatitis C and in transplanted liver grafts. Furthermore, the induction of HO-1 expression can protect the liver against damage caused by a number of chemical compounds. More specifically, the CO derived from HO-1-mediated heme catabolism has been shown to be involved in the regulation of inflammation; furthermore, administration of low concentrations of exogenous CO has a protective effect against inflammation. Both murine and human HO-1 deficiencies have systemic manifestations associated with iron metabolism, such as hepatic overload(with signs of a chronic hepatitis) and iron deficiency anemia(with paradoxical increased levels of ferritin).Hypoxia induces HO-1 expression in multiple rodent,bovine and monkey cell lines, but interestingly, hypoxia represses expression of the human HO-1 gene in a variety of human cell types(endothelial cells, epithelial cells, T cells). These data suggest that HO-1 and CO are promising novel therapeutic molecules for patients with inflammatory diseases. In this review, we present what is currently known regarding the role of HO-1 in liver injuries and in particular, we focus on the implications of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against chemically induced injury.展开更多
Plant-based fermentations provide an untapped source for novel biotechnological applications.In this study,a probiotic named Lactobacillus fermentum 21828 was introduced to ferment Lentinus edodes.Polysaccharides were...Plant-based fermentations provide an untapped source for novel biotechnological applications.In this study,a probiotic named Lactobacillus fermentum 21828 was introduced to ferment Lentinus edodes.Polysaccharides were extracted from fermented and non-fermented L.edodes and purified via DEAE-52 and Sephadex G-100.The components designated F-LEP-2a and NF-LEP-2a were analyzed by FT-IR,HPGPC,HPAEC,SEM,GC-MS and NMR.The results revealed that probiotic fermentation increased the molecular weight from 1.16×10^(4) Da to 1.87×10^(4) Da and altered the proportions of glucose,galactose and mannose,in which glucose increased from 45.94%to 48.16%.Methylation analysis and NMR spectra indicated that F-LEP-2a and NF-LEP-2a had similar linkage patterns.Furthermore,their immunomodulatory activities were evaluated with immunosuppressive mice.NF-LEP and F-LEP improved immune organ indices,immunoglobulin(Ig G and Ig M)and cytokines concentrations;restored the antioxidation capacity of liver;and maintained the balance of gut microbiota.F-LEP displayed better moderating effects on the spleen index,immunoglobulin,cytokines and the diversity of gut microbiota than NF-LEP(200,400 mg/kg).Our study provides an efficient and environment-friendly way for the structural modification of polysaccharides,which helps to enhance their biological activity and promote their wide application in food,medicine and other fields.展开更多
A purified polysaccharide with a galactose backbone(SPR-1,Mw 3,622 Da)was isolated from processed Polygonati Rhizoma with black beans(PRWB)and characterized its chemical properties.The backbone of SPR-1 consisted of[(...A purified polysaccharide with a galactose backbone(SPR-1,Mw 3,622 Da)was isolated from processed Polygonati Rhizoma with black beans(PRWB)and characterized its chemical properties.The backbone of SPR-1 consisted of[(4)-b-D-Galp-(1]9/4,6)-b-D-Galp-(1/4)-a-D-GalpA-(1/4)-a-D-GalpA-(1/4)-aD-Glcp-(1/4,6)-a-D-Glcp-(1/4)-a/b-D-Glcp,with a branch chain of R1:b-D-Galp-(1/3)-b-D-Galp-(1/connected to the/4,6)-b-D-Galp-(1/via O-6,and a branch chain of R2:a-D-Glcp-(1/6)-a-D-Glcp-(1/connected to the/4,6)-a-D-Glcp-(1/via O-6.Immunomodulatory assays showed that the SPR-1 significantly activated macrophages,and increased secretion of NO and cytokines(i.e.,IL-1b and TNF-a),as well as promoted the phagocytic activities of cells.Furthermore,isothermal titration calorimetry(ITC)analysis and molecular docking results indicated high-affinity binding between SPR-1 and MD2 with the equilibrium dissociation constant(KD)of 18.8 mM.It was suggested that SPR-1 activated the immune response through Toll-like receptor 4(TLR4)signaling and downstream responses.Our research demonstrated that the SPR-1 has a promising candidate from PRWB for the TLR4 agonist to induce immune response,and also provided an easily accessible way that can be used for PR deep processing。展开更多
T regulatory cells (Tregs) play an important role in the induction and maintenance of immunological tolerance to self and alloantigens. Recent findings in experimental transplant models have demonstrated that Treg cou...T regulatory cells (Tregs) play an important role in the induction and maintenance of immunological tolerance to self and alloantigens. Recent findings in experimental transplant models have demonstrated that Treg could control and delay allograft rejection. Induction of immune tolerance decreases the risk of acute and chronic graft rejection after solid organ transplantation and can improve transplanted organ survival. Tregs are being tested in trials as a potential therapy in cell and solid organ transplantation. However, as we know, regulatory T cells (Tregs) are crucial for peripheral tolerance and are intimately involved in cancer. The influence of Tregs on cancer progression has been demonstrated in a large number of preclinical models and confirmed in several types of malignancies. Neoplastic processes trigger an increase of Treg numbers in draining lymph nodes, spleen, blood, and tumors, leading to the suppression of anti-tumor responses. In this review, we summarize some of the critical aspects of the immunoregulatory function of Treg cells in cancer and transplantation and discuss their potential research progress and challenge.展开更多
African swine fever(ASF),caused by the ASF virus(ASFV),is an acute,severe,and highly contagious infectious disease in domestic pigs and wild boars.Domestic pigs infected with a virulent ASFV strain can have morbidity ...African swine fever(ASF),caused by the ASF virus(ASFV),is an acute,severe,and highly contagious infectious disease in domestic pigs and wild boars.Domestic pigs infected with a virulent ASFV strain can have morbidity and mortality rates of up to 100%.The epidemic of ASF has caused serious economic losses to the global pig industry.Currently,there is no safe and efective vaccine or specifc drug for treating ASF.Therefore,ASFV still poses a great threat to pig factories.ASFV is a double-stranded DNA virus with a complex icosahedral multilayer structure.The ASFV genome contains 150-170 open reading frames(ORFs)that encode 150-200 proteins.Some ASFV-encoded proteins are involved in virus invasion,genome replication,DNA repair,and virion formation.Some ASFV proteins execute immunomodulatory functions by regulating the host antiviral innate immune response.Accumulating studies have shown that the immunomodulatory functions of ASFV genes are closely related to the virulence and pathogenicity of ASFV isolates.This review summarizes the research advances on ASFV immune evasion mechanisms in African swine fever patients and provides new insights for developing attenuated live vaccine candidates to prevent and control ASF.展开更多
Hericium erinaceus-derived peptides have been found to exhibit various bioactivities,including immunoregulatory properties.This study investigated the transport,absorption,and potential immunomodulatory activities of ...Hericium erinaceus-derived peptides have been found to exhibit various bioactivities,including immunoregulatory properties.This study investigated the transport,absorption,and potential immunomodulatory activities of a new peptide,Leu-Pro-Gly-Lys-Val-Ile-Ala-Ser(LPGKVIAS),derived from H.erinaceus.Transport and absorption of LPGKVIAS were analyzed by near-infrared fluorescence in vivo imaging in mice injected with a fluorescence probe-labeled LPGKVIAS.RNA sequencing was used to explore the immunological effects of the peptide on mouse splenocytes.Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that LPGKVAS upregulated differentially expressed genes involved in immune regulation.Notably,activation of the lysosome-phagosome pathway in splenocytes of mice treated with LPGKVIAS was identified as a crucial immune defense mechanism against pathogen infection.Furthermore,reverse transcription-polymerase chain reaction studies validated the gene expression data,supporting the potential application of the peptide LPGKVIAS as an immunomodulator.展开更多
Immune imbalance is a critical factor in the occurrence and progression of cancers because it disrupts the immune system's ability to detect and eliminate abnormal cells.Restoring immune balance and reactivating i...Immune imbalance is a critical factor in the occurrence and progression of cancers because it disrupts the immune system's ability to detect and eliminate abnormal cells.Restoring immune balance and reactivating immune cells remain major challenges in cancer immunotherapy.Current immunoregulatory strategies,such as immune checkpoint blockade,adoptive cell therapy,and therapeutic vaccines,aim to influence key immune cells,such as T cells,dendritic cells,and macrophages,to boost anticancer responses.However,conventional material design in immunotherapy usually emphasizes chemical composition and physical morphology,while neglecting the critical role of stereochemistry in immune cell recognition and activation.展开更多
Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance,preventing autoimmune responses,and minimizing tissue damage by regulating the duration and intensi...Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance,preventing autoimmune responses,and minimizing tissue damage by regulating the duration and intensity of the immune response.Furthermore,immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response.Based on substantial physiological analyses as well as preclinical and clinical studies,checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers.In the last few years,extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines(TCMs).The main advantage of TCMs and natural medicine is that they usually contain multiple active components,which can act on multiple targets at the same time,resulting in additive or synergistic effects.The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest.For example,Astragalus membranaceus polysaccharides can induce anti-PD-1 antibody responses in animals,and these antibodies can overcome the exhaustion of immune cells under tumor immune evasion.Furthermore,many other TCM molecules could also be novel and effective drug candidates for the treatment of cancers.Therefore,it is essential to assess the application of immune checkpoints in the development of new drugs and TCMs.In this review,we focus on research progress in the field of immune checkpoints based on three topics:(1)immune checkpoint targets and pathways,(2)development of novel immune checkpoint-based drugs,and(3)application of immune checkpoints in the development of TCMs.展开更多
文摘The establishment of drug-free feeding systems has been required for secure and healthy livestock production. Although functional feed materials containing microorganisms as alternatives to enhance intestinal immunity are expected to be beneficial for reducing diarrhoea caused by pathogens in weaned piglets, the effects of such materials on porcine intestinal cells have not been investigated in detail. Therefore, this work evaluated the immunoregulatory functions of microbial feed materials in porcine intestinal immune and epithelial cells. Porcine immune cells isolated from Peyer’s patches and mesenteric lymph nodes were stimulated with six different feed materials containing microorganisms, and evaluated for lymphocyte mitogenicity and cytokine inductions. In addition, porcine intestinal epithelial cells were stimulated with the materials before treatment with heat-killed enterotoxigenic Escherichia coli (ETEC), and analyzed for the proinflammatory cytokine expressions. The material containing Bifidobacterium thermophilum significantly augmented lymphocytes’ mitogenicity and also induced a high expression of IL-2, IL-6 and IFN-γ in immune cells, and inhibited ETEC-induced overexpression of IL-6 and IL-8 via regulation of Toll-like receptor signaling. These results suggest that this feed material stimulates intestinal epithelial and immune cells to exert immunoregulation, suggesting that this feed is expected to contribute to promoting the health of piglets without using antimicrobial feed materials.
基金Zhejiang Basic Public Welfare Research Program,No.LQ20H030012.
文摘BACKGROUND The coronavirus disease 2019(COVID-19)caused by novel coronavirus 2019 in December 2019 has spread all around the globe and has caused a pandemic.There is still no current effective guidance on the clinical management of COVID-19.Mesenchymal stem cell therapy has been shown to be one of the therapeutic approaches to alleviate pneumonia and symptoms through their immunomodulatory effect in COVID-19 patients.CASE SUMMARY We describe the first confirmed case of COVID-19 in Hangzhou to explore the role of human menstrual blood-derived stem cells(MenSCs)in the treatment of COVID-19.Moreover,we review the immunomodulation effect including nonspecific and specific immune functions of MenSCs for the therapy of COVID-19.CONCLUSION MenSCs can be helpful to find a promising therapeutic approach for COVID-19.
基金Supported by Fundamental Research Funds of Chongqing Municipality(16423)Chongqing Agricultural Science and Technology Achievements Transformation Fund Project(cst2014jcsf-nycgzha10002)
文摘[Objectives]To study immunoregulatory effects of Nuhuang Fuzheng Granules on mice with Cytoxan-induced immunosuppression.[Methods]Kunming variety mice were randomly divided into the control group,model group,positive medicine group,and low,medium,and high dosage groups of Nuhuang Fuzheng Granules. Except the control group,the rest groups of mice were injected with Cytoxan at60 mg/kg to reproduce the immunosuppressive mice model,and were fed through stomach at 0. 5g/kg,1. 0 g/kg and 2. 0 g/kg Nuhuang Fuzheng Granules for seven days( twice a day); the positive control group was fed with Astragalus Polysacharin( 500 mg/L). The carbon clearance index,immune organ index,serum hemolysin were determined. IL-2,IFN-γ,and IL-4 levels in mouse serum were measured by ELISA. [Results] Nuhuang Fuzheng Granules could significantly incease the carbon granular expurgation index of mice with Cytoxan-induced immunosuppression,and the 2. 0 g/kg and 1. 0 g/kg dosage groups had better effect than 0. 5 g/kg dosage group( P < 0. 05); the spleen index of mice with Cytoxan-induced immunosuppression increased significantly and there was dose-effect relationship in a certain range of concentration; the thymus index and serum hemolysin HC_(50) were significantly higher than 0. 5 g/kg dosage group( P < 0. 05); IL-4 and IFN-γ in the serum was significantly higher than the model group( P < 0. 01),the increase of IL-2 was not significantly( P > 0. 05). [Conclusions] Nuhuang Fuzheng Granules can promote growth of immune organs and secretion of cytokines through improving the carbon granular expurgation ability of mice with Cytoxan-induced immunosuppression.
基金supported by grants from the Key R&D Projects of the Science and Technology Development Plan of Jilin Province,China(20220204126YY)the Medical and Health Talent Special Project of Jilin Province,China(JLSWSRCZX2023-32)the Natural Science Foundation Discipline Layout Project of Jilin Province,China(20200201478JC).
文摘Antibacterial piezoelectric materials have broad application prospects in the medical field because of their broadspectrum antibacterial properties and no bacterial drug resistance.At present,one of the main problems in the application of piezoelectric materials is the low electrocatalytic efficiency,which limits its application in anti-bacterial field.In this study,a piezoelectric antibacterial(PLGA/Zn-KNN)scaffold was fabricated by incorpo-rating zinc oxide(ZnO)into potassium-sodium niobate(KNN)and composited with a poly(lactic-co-glycolic acid)(PLGA)to achieve multicombination antibacterial for bone infection.The physicochemical properties of piezoelectric antibacterial scaffolds were analyzed.Bacterial,cell,and animal experiments were performed to characterize the antibacterial and infection treatment capabilities of piezoelectric scaffolds.The piezoelectric properties of the PLGA/Zn-KNN scaffold were enhanced by embedding ZnO particles into the KNN solid solution matrix.Furthermore,the piezoelectric scaffold released zinc ions,and electrical stimulation driven by ultrasound resulted in significant antibacterial effects through direct and immunoregulatory antibacterial pathways.Mechanistic investigation suggested that extracellular matrix ligands and complement and coagulation cascades may have a moderate effect on macrophage phagocytosis.This work highlights potential application methods for fabricating novel antibacterial hybrid piezoelectric scaffolds and engineering macrophages with immunoregu-latory antibacterial activity.
基金supported by the National Natural Science Foundation of China(No.82430123)the Joint Fund for Innovative Development of Shandong Natural Science Foundation(No.ZR2023LZY006,China)+1 种基金the Taishan Scholar Foundation of Shandong Province(No.tstp20221166,China)the National Administration of Traditional Chinese Medicine Science and Technology Department Science and Technology Joint Construction Project(No.GZY-KJS-SD-2023-023,China).
文摘The aging microenvironment,as a key driver of tumorigenesis and progression,plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype(SASP).SASP consists of a variety of interleukins,chemokines,proteases,and growth factors.It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms,thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment.Furthermore,these secreted factors activate key signaling pathways such as NF-κB,cGAS-STING,and mTOR,which regulate the expression of immune-related molecules(such as PDL1)and promote the recruitment of immunosuppressive cells,including regulatory T cells and myeloid-derived suppressor cells.This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment.Furthermore,the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms,including approaches to inhibit SASP secretion or eliminate senescent cells.Although these strategies have shown promise in certain tumor models,the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies.This highlights the need for further research into adaptive stratification and personalized treatment approaches.Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.
基金supported by the Department of Veterans Affairs Merit Review Award(BX004252,to SW)the National Institutes of Health(NIH)Grant(DK131786,to SW)。
文摘Cluster of differentiation 47(CD47)is a widely expressed transmembrane protein that serves as a critical immunoregulatory checkpoint in both homeostatic and pathological conditions of the digestive system.It interacts with signal regulatory protein alpha to send a‘do not eat me’signal,thereby preventing phagocytosis and shaping immune responses.Beyond immunity,CD47 also influences cell death,growth and metabolism through interactions with integrins and thrombospondin-1.Recent studies implicate CD47 as a central nexus in the pathogenesis of diverse liver and gastrointestinal disorders,including metabolic dysfunction-associated steatotic liver disease,metabolic dysfunction-associated steatohepatitis,inflammatory bowel disease,liver ischaemia-reperfusion injury,drug-induced liver injury and gastrointestinal malignancies such as hepatocellular carcinoma,colorectal and pancreatic cancers.CD47 contributes to disease progression through immune modulation,endothelial dysfunction,fibrogenic activation and suppression of antitumour immunity.This review summarises current mechanistic insights into CD47 signalling across digestive diseases and highlights its emerging potential as a therapeutic target for immunometabolic and oncological interventions in gastroenterology and hepatology.
基金Supported by National Natural Science Foundation of China (No.30973917)Foundation of Provincial Key Laboratory of Anhui Medical University(No.SBSYS-0803)
文摘Objective： To investigate the anti-inflammatory and immunoregulatory effects of Yupingfeng , Powder and its components in rats. Methods： A rat chronic bronchitis （CB） model was developed using lipopolysaccharide （LPS） combined with bacillus Calmette Guerin （BCG）. YPF, simple recipe Astragalus membranaceus （Fisch.） Bge （AM） and Astragalus membranaceus （Fisch.） Bge plus rhizome of Atractylodes macrocepha/a Koidz （AM＋RA） decoction were administered （intragastric administration, once a day for 21 days） to rats, to prevent and treat CB. Immunoregulatory and anti-inflammatory effects of YPF, AM and AM＋RA were tested by serum pharmacology in vitro on splenic lymphocytes of normal rats and alveolar macrophages of CB rats. Results： Inflammation in the pulmonary tissue and the bronchus of CB rats was significantly reduced in the YPF-treatment groups, AM and AM＋RA groups demonstrating the efficacy of YPF. Serum samples collected at different times from rats after administration of YPF, AM and AM＋RA demonstrated increased proliferation of splenic lymphocytes with area under the effect curve （AUE） of 552.6%, 336.3% and 452.0%, respectively. Treatment of alveolar macrophages with serum samples in YPF, AM or AM＋RA group inhibited interleukin-8 （IL-8） in the cell culture media, and the effect was much better in the YPF group compared with AM or AM＋RA group, with a higher maximal effect （Emax, P〈0.05） and larger AUE （P〈0.01 and P〈0.05）. Moreover, serum from rats treated with AM or AM＋RA had similar efficacy, while the efficiency was lower than that treated with YPF. Conclusion： YPF demonstrated anti-inflammatory and immunoregulatory effects in a rat model of CB, and time- dependent relationships were demonstrated in vitro.
文摘Background This study was to evaluate whether anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro and prolong cardiac allograft survival after adoptive transfer KH*2/5DMethods Anergic cells were induced in vitro by the addition of anti-CD154 and anti-CD80 monoclonal antibodies (mAbs) to primary MLR (mixed lymphocyte reaction) consisting of BALB/c as responder and C3H as stimulator Anergic cells were added to a newly formed MLR in assessing the regulatory capacity and antigen specificity of anergic cells The ability of anergic cells to respond to antigen and/or exogenous recombinant mouse interleukin-2 (rmIL-2) was tested For in vivo studies, anergic cells were intravenously injected into 3 0-Gy γ-irradiated BALB/c mice immediately after heterotopic abdominal cardiac transplantation To prolong allograft survival, recipient mice injected with anergic cells received rapamycin therapy (1 mg·day -1 ·kg -1 ) KH*2/5DResults Anergic cells strongly suppressed the proliferation of naǐve BALB/c splenocytes against the original (C3H) stimulator in a dose-dependent manner, but they failed to suppress the proliferation of naǐve BALB/c splenocytes against the third-party (C57BL/6J) stimulator The anergic state was reversed by both original (C3H) stimulator and additional exogenous IL-2 In in vivo studies, untreated irradiated BALB/c mice rejected C3H cardiac allografts with a mean survival time of (8 6±1 1) days, whereas those injected with the anergic cells rejected the allografts with a mean survival time of (11 8±1 9) days, which was slightly longer than that of the untreated mice The protocol based on anergic cells injection plus rapamycin therapy could prolong allograft survival significantly [(29 6±4 4) days] Conclusions Anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro , and prolong cardiac allograft survival after adoptive transfer in the presence of rapamycin therapy This procedure might be clinically useful for prolonging allograft survival if optimal protocols are developed
基金supported by the National Key R&D Program of China(NO.2019YFC1711000)the National Natural Science Foundation of China(NO.81530095,81673591)+3 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(NO.XDA12020348)the National Standardization of Traditional Chinese Medicine Project(NO.ZYBZH K LN 01)the Science and Technology Commission Foundation of Shanghai(NO.15DZ0502800)the Projects of Research and Develop Plan in the Key Field of Guangdong(No 2020B1111110007)。
文摘Objective:The objective of this study was to characterize the chemical compounds of a Hanshi-Yufei formulation(HSYF;a modified formulation of a traditional Chinese medicine used for treating COVID-19)to elucidate the mechanism of action and to evaluate potential anti-inflammatory effects of HSYF.Materials and Methods:The chemical constituents of HSYF extract were characterized using UPLC-Q-TOF/MS.Subsequently,a set of TCM network pharmacology methods was applied to identify disease-associated genes and to predict target profiles and pharmacological actions associated with the constituents of HSYF.Then,the antiviral effects of HSYF on H1N1 were assessed in RAW264.7 cells using MTT assays.Expression levels of pro-inflammatory cytokines interleukin(IL)-6 and tumor necrosis factor(TNF)-αfollowing infection of RAW264.7 cells with H1N1 were measured using an enzyme-linked immune sorbent assay(ELISA),and expression levels of inflammatory-related factors were detected using western blotting.Results:In total,165 chemical constituents(including glycosides,tannins,volatile oils,amino acids,triterpenoids,polyphenols,phenylpropanoids,sesquiterpenes,alkaloids,and flavonoids,among others)were tentatively identified in HSYF.Network pharmacology demonstrated that HSYF can regulate immunomodulatory-and anti-inflammatory-related targets of multiple pathways through its active ingredients,suggesting potential anti-COVID-19 effects.Furthermore,cell viability assays and ELISA showed that HSYF significantly inhibited H1N1 replication in RAW64.7 cells and markedly reduced expression of pro-inflammatory cytokines TNF-αand IL-6 at the proteins level.Conclusions:The results of the present study help improve our understanding of the therapeutic effects of HSYF in COVID-19 treatment from multi-level perspectives.
基金National Natural Science Foundation of China (Grant No.90713010)"863"Program from the Ministry of Science and Technology of China (Grant No.2006AA09Z405).
文摘α-Galactosylceramides, which can be recognized by natural killer T （NKT） cells, are now attracting more and more attention due to their therapeutic potential in cancer, infection and autoimmune diseases. Advances have been achieved in discovering compounds with better activities and efforts have been made to understand the structure-activity relationships （SARs） of these NKT cell ligands. In this review, we discuss the structure modifications based on KRN7000, the principal glycolipid used in the study of NKT cell stimulation, and the SARs based on these modified structures.
基金Supported by Brazilian Foundation-FAPESP(Fundao deapoio à pesquisa do Estado de So Paulo),No.07/07139-3,10/02024-6 and CNPq
文摘The activation of heme oxygenase-1(HO-1) appears to be an endogenous defensive mechanism used by cells to reduce inflammation and tissue damage in a number of injury models. HO-1, a stress-responsive enzyme that catabolizes heme into carbon monoxide(CO), biliverdin and iron, has previously been shown to protect grafts from ischemia/reperfusion and rejection.In addition, the products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin, have been shown to exert protective effects in the liver against a number of stimuli, as in chronic hepatitis C and in transplanted liver grafts. Furthermore, the induction of HO-1 expression can protect the liver against damage caused by a number of chemical compounds. More specifically, the CO derived from HO-1-mediated heme catabolism has been shown to be involved in the regulation of inflammation; furthermore, administration of low concentrations of exogenous CO has a protective effect against inflammation. Both murine and human HO-1 deficiencies have systemic manifestations associated with iron metabolism, such as hepatic overload(with signs of a chronic hepatitis) and iron deficiency anemia(with paradoxical increased levels of ferritin).Hypoxia induces HO-1 expression in multiple rodent,bovine and monkey cell lines, but interestingly, hypoxia represses expression of the human HO-1 gene in a variety of human cell types(endothelial cells, epithelial cells, T cells). These data suggest that HO-1 and CO are promising novel therapeutic molecules for patients with inflammatory diseases. In this review, we present what is currently known regarding the role of HO-1 in liver injuries and in particular, we focus on the implications of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against chemically induced injury.
基金supported by grants from the National Key R&D Program of China(2019YFC1606701)。
文摘Plant-based fermentations provide an untapped source for novel biotechnological applications.In this study,a probiotic named Lactobacillus fermentum 21828 was introduced to ferment Lentinus edodes.Polysaccharides were extracted from fermented and non-fermented L.edodes and purified via DEAE-52 and Sephadex G-100.The components designated F-LEP-2a and NF-LEP-2a were analyzed by FT-IR,HPGPC,HPAEC,SEM,GC-MS and NMR.The results revealed that probiotic fermentation increased the molecular weight from 1.16×10^(4) Da to 1.87×10^(4) Da and altered the proportions of glucose,galactose and mannose,in which glucose increased from 45.94%to 48.16%.Methylation analysis and NMR spectra indicated that F-LEP-2a and NF-LEP-2a had similar linkage patterns.Furthermore,their immunomodulatory activities were evaluated with immunosuppressive mice.NF-LEP and F-LEP improved immune organ indices,immunoglobulin(Ig G and Ig M)and cytokines concentrations;restored the antioxidation capacity of liver;and maintained the balance of gut microbiota.F-LEP displayed better moderating effects on the spleen index,immunoglobulin,cytokines and the diversity of gut microbiota than NF-LEP(200,400 mg/kg).Our study provides an efficient and environment-friendly way for the structural modification of polysaccharides,which helps to enhance their biological activity and promote their wide application in food,medicine and other fields.
基金supported by Sichuan Provincial Regional Innovation Cooperation Project,China(Grant No.:2023YFQ0084)the Macao Science and Technology Development Fund(FDCT),China(Grant No.:0043/2021/AGJ).
文摘A purified polysaccharide with a galactose backbone(SPR-1,Mw 3,622 Da)was isolated from processed Polygonati Rhizoma with black beans(PRWB)and characterized its chemical properties.The backbone of SPR-1 consisted of[(4)-b-D-Galp-(1]9/4,6)-b-D-Galp-(1/4)-a-D-GalpA-(1/4)-a-D-GalpA-(1/4)-aD-Glcp-(1/4,6)-a-D-Glcp-(1/4)-a/b-D-Glcp,with a branch chain of R1:b-D-Galp-(1/3)-b-D-Galp-(1/connected to the/4,6)-b-D-Galp-(1/via O-6,and a branch chain of R2:a-D-Glcp-(1/6)-a-D-Glcp-(1/connected to the/4,6)-a-D-Glcp-(1/via O-6.Immunomodulatory assays showed that the SPR-1 significantly activated macrophages,and increased secretion of NO and cytokines(i.e.,IL-1b and TNF-a),as well as promoted the phagocytic activities of cells.Furthermore,isothermal titration calorimetry(ITC)analysis and molecular docking results indicated high-affinity binding between SPR-1 and MD2 with the equilibrium dissociation constant(KD)of 18.8 mM.It was suggested that SPR-1 activated the immune response through Toll-like receptor 4(TLR4)signaling and downstream responses.Our research demonstrated that the SPR-1 has a promising candidate from PRWB for the TLR4 agonist to induce immune response,and also provided an easily accessible way that can be used for PR deep processing。
文摘T regulatory cells (Tregs) play an important role in the induction and maintenance of immunological tolerance to self and alloantigens. Recent findings in experimental transplant models have demonstrated that Treg could control and delay allograft rejection. Induction of immune tolerance decreases the risk of acute and chronic graft rejection after solid organ transplantation and can improve transplanted organ survival. Tregs are being tested in trials as a potential therapy in cell and solid organ transplantation. However, as we know, regulatory T cells (Tregs) are crucial for peripheral tolerance and are intimately involved in cancer. The influence of Tregs on cancer progression has been demonstrated in a large number of preclinical models and confirmed in several types of malignancies. Neoplastic processes trigger an increase of Treg numbers in draining lymph nodes, spleen, blood, and tumors, leading to the suppression of anti-tumor responses. In this review, we summarize some of the critical aspects of the immunoregulatory function of Treg cells in cancer and transplantation and discuss their potential research progress and challenge.
基金supported by the National Key Research and Development Program of China(Grant No.2021YFD1800100)the National Natural Science Foundation of China(Grant Nos.32172874 and 31941002).
文摘African swine fever(ASF),caused by the ASF virus(ASFV),is an acute,severe,and highly contagious infectious disease in domestic pigs and wild boars.Domestic pigs infected with a virulent ASFV strain can have morbidity and mortality rates of up to 100%.The epidemic of ASF has caused serious economic losses to the global pig industry.Currently,there is no safe and efective vaccine or specifc drug for treating ASF.Therefore,ASFV still poses a great threat to pig factories.ASFV is a double-stranded DNA virus with a complex icosahedral multilayer structure.The ASFV genome contains 150-170 open reading frames(ORFs)that encode 150-200 proteins.Some ASFV-encoded proteins are involved in virus invasion,genome replication,DNA repair,and virion formation.Some ASFV proteins execute immunomodulatory functions by regulating the host antiviral innate immune response.Accumulating studies have shown that the immunomodulatory functions of ASFV genes are closely related to the virulence and pathogenicity of ASFV isolates.This review summarizes the research advances on ASFV immune evasion mechanisms in African swine fever patients and provides new insights for developing attenuated live vaccine candidates to prevent and control ASF.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),Chinathe National Natural Science Foundation of China(No.32101944)the National Natural Science Foundation of China(No.32072293).
文摘Hericium erinaceus-derived peptides have been found to exhibit various bioactivities,including immunoregulatory properties.This study investigated the transport,absorption,and potential immunomodulatory activities of a new peptide,Leu-Pro-Gly-Lys-Val-Ile-Ala-Ser(LPGKVIAS),derived from H.erinaceus.Transport and absorption of LPGKVIAS were analyzed by near-infrared fluorescence in vivo imaging in mice injected with a fluorescence probe-labeled LPGKVIAS.RNA sequencing was used to explore the immunological effects of the peptide on mouse splenocytes.Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that LPGKVAS upregulated differentially expressed genes involved in immune regulation.Notably,activation of the lysosome-phagosome pathway in splenocytes of mice treated with LPGKVIAS was identified as a crucial immune defense mechanism against pathogen infection.Furthermore,reverse transcription-polymerase chain reaction studies validated the gene expression data,supporting the potential application of the peptide LPGKVIAS as an immunomodulator.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.U23A20591,52273158,52273159,and W2421115)the Science and Technology Department Project of Jilin Province(Grant No.20250204068YY)the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.Y2023066).
文摘Immune imbalance is a critical factor in the occurrence and progression of cancers because it disrupts the immune system's ability to detect and eliminate abnormal cells.Restoring immune balance and reactivating immune cells remain major challenges in cancer immunotherapy.Current immunoregulatory strategies,such as immune checkpoint blockade,adoptive cell therapy,and therapeutic vaccines,aim to influence key immune cells,such as T cells,dendritic cells,and macrophages,to boost anticancer responses.However,conventional material design in immunotherapy usually emphasizes chemical composition and physical morphology,while neglecting the critical role of stereochemistry in immune cell recognition and activation.
基金partly supported by National Natural Science Foundation of China for Key Projects(No.81430096,China)National New Drug Innovation(No.2017ZX09301062,China)Tianjin Science and Technology Plan Project(No.19YFSLQY00110,China)。
文摘Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance,preventing autoimmune responses,and minimizing tissue damage by regulating the duration and intensity of the immune response.Furthermore,immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response.Based on substantial physiological analyses as well as preclinical and clinical studies,checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers.In the last few years,extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines(TCMs).The main advantage of TCMs and natural medicine is that they usually contain multiple active components,which can act on multiple targets at the same time,resulting in additive or synergistic effects.The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest.For example,Astragalus membranaceus polysaccharides can induce anti-PD-1 antibody responses in animals,and these antibodies can overcome the exhaustion of immune cells under tumor immune evasion.Furthermore,many other TCM molecules could also be novel and effective drug candidates for the treatment of cancers.Therefore,it is essential to assess the application of immune checkpoints in the development of new drugs and TCMs.In this review,we focus on research progress in the field of immune checkpoints based on three topics:(1)immune checkpoint targets and pathways,(2)development of novel immune checkpoint-based drugs,and(3)application of immune checkpoints in the development of TCMs.
