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Herb pair of Huangqi-Danggui exerts anti-tumor immunity to breast cancer by upregulating PIK3R1 被引量:2
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作者 Hai-Xin Liu Li Lian +5 位作者 Li-Li Hou Cai-Xia Liu Jin-Hong Ren Yuan-Biao Qiao Shi-Yuan Wen Qing-Shan Li 《Animal Models and Experimental Medicine》 CAS CSCD 2024年第3期234-258,共25页
Background:According to traditional Chinese medicine(TCM),drugs supplementing the vital energy,Qi,can eliminate tumors by restoring host immunity.The objective of this study is to investigate the underlying immune mec... Background:According to traditional Chinese medicine(TCM),drugs supplementing the vital energy,Qi,can eliminate tumors by restoring host immunity.The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs,specifically the paired use of Huangqi and Danggui.Methods:Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs.Using the MTT assay and a transplanted tumor mice model,the anti-tumor effects of combination TCMs were investigated in vitro and in vivo.High content analysis and flow cytometry were then used to evaluate cellular immunity,followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms.Finally,the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments.Results:There is an optimal combination of Huangqi and Danggui that,administered as an aqueous extract,can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo.Based on network pharmacology analysis,PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui.Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract(quercetin,jaranol,isorhamnetin,kaempferol,calycosin,and suchilactone)that bind to PIK3R1.Jaranol is the most important component against breast cancer.The suchilactone/jaranol combination and,especially,the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract.Conclusions:The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone. 展开更多
关键词 ANTI-TUMOR Danggui Huangqi immunity
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The role of innate immunity in diabetic nephropathy and their therapeutic consequences 被引量:2
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作者 Min Yang Chun Zhang 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2024年第1期39-51,共13页
Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of prot... Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of proteins in the urine are typical aspects of DN, ultimately resulting in renal failure. Mounting evidence suggests that immunological and inflammatory factors are crucial for the development of DN. Therefore, the activation of innate immunity by resident renal and immune cells is critical for initiating and perpetuating inflammation. Toll-like receptors (TLRs) are an important group of receptors that identify patterns and activate immune responses and inflammation. Meanwhile, inflammatory responses in the liver, pancreatic islets, and kidneys involve inflammasomes and chemokines that generate pro-inflammatory cytokines. Moreover, the activation of the complement cascade can be triggered by glycated proteins. This review highlights recent findings elucidating how the innate immune system contributes to tissue fibrosis and organ dysfunction, ultimately leading to renal failure. This review also discusses innovative approaches that can be utilized to modulate the innate immune responses in DN for therapeutic purposes. 展开更多
关键词 Innate immunity Diabetic nephropathy INFLAMMATION Toll-like receptor INFLAMMASOMES
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m^(1)A inhibition fuels oncolytic virus-elicited antitumor immunity via downregulating MYC/PD-L1 signaling 被引量:1
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作者 Shujin Li Tian Feng +7 位作者 Yuantong Liu Qichao Yang An Song Shuo Wang Jun Xie Junjie Zhang Bifeng Yuan Zhijun Sun 《International Journal of Oral Science》 SCIE CAS CSCD 2024年第3期486-498,共13页
N^(1)-methyladenosine(m^(1)A)RNA methylation is critical for regulating mRNA translation;however,its role in the development,progression,and immunotherapy response of head and neck squamous cell carcinoma(HNSCC)remain... N^(1)-methyladenosine(m^(1)A)RNA methylation is critical for regulating mRNA translation;however,its role in the development,progression,and immunotherapy response of head and neck squamous cell carcinoma(HNSCC)remains largely unknown.Using Tgfbr1 and Pten conditional knockout(2cKO)mice,we found the neoplastic transformation of oral mucosa was accompanied by increased m^(1)A modification levels.Analysis of m^(1)A-associated genes identified TRMT61A as a key m^(1)A writer linked to cancer progression and poor prognosis.Mechanistically,TRMT61A-mediated tRNA-m^(1)A modification promotes MYC protein synthesis,upregulating programmed death-ligand 1(PD-L1)expression.Moreover,m^(1)A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus(oHSV),contributing to reactive PD-L1 upregulation.Therapeutic m^(1)A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth,representing a promising strategy to alleviate resistance.These findings indicate that m^(1)A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression,providing a mutually reinforcing combination immunotherapy approach. 展开更多
关键词 immunity SUSTAINED representing
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Impact of exercise on markers of B cell-related immunity:A systematic review
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作者 David Walzik Sergen Belen +7 位作者 Karen Wilisch Marie Kupjetz Silvana Kirschke Tobias Esser Niklas Joisten Alexander Schenk Sebastian Proschinger Philipp Zimmer 《Journal of Sport and Health Science》 SCIE CAS CSCD 2024年第3期339-352,I0002,共15页
Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins.Exercise alters B cell counts and immunoglobulin l... Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins.Exercise alters B cell counts and immunoglobulin levels,but evidence-based conclusions on potential benefits for adaptive immunity are lacking.This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells,immunoglobulins,and markers of secretory immunity in human biofluids.Methods:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,MEDLINE,Web of Science,and Embase were searched on March 8,2023.Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions,immunoglobulin levels,salivary flow rate,or secretory immunoglobulin A secretion rate were included.Quality and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in Exercise.Study characteristics,outcome measures,and statistically significant changes were summarized tabularly.Results:Of the 67 eligible studies,22 applied acute exercise and 45 applied exercise training.All included outcomes revealed significant alterations over time in acute exercise and exercise training context,but only a few investigations showed significant differences compared to control conditions.Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training.Conclusion:B cell-related outcomes are altered by acute exercise and exercise training,but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities.Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity. 展开更多
关键词 ANTIBODY B-LYMPHOCYTE EXERCISE Humoral immunity Immune system
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The life-history trait trade-offs mediated by reproduction and immunity in the brown planthopper,Nilaparvata lugens Stål
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作者 Dan Sun Hongfeng Wang +4 位作者 Jiahui Zeng Qiuchen Xu Mingyun Wang Xiaoping Yu Xuping Shentu 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2024年第6期2018-2032,共15页
Reproduction and immune defense are costly functions,and they are expected to tradeoff with each other to drive evolution.The brown planthopper(BPH),Nilaparvata lugens Stål(Hemiptera,Delphacidae),is a global supe... Reproduction and immune defense are costly functions,and they are expected to tradeoff with each other to drive evolution.The brown planthopper(BPH),Nilaparvata lugens Stål(Hemiptera,Delphacidae),is a global superpest that mostly damages rice crops.Yeast-like symbionts(YLS)exist in the abdominal fat body tissue and are tightly associated with the development,growth,and reproduction of BPH.Our previous research demonstrated that mating behavior promotes the release of YLS from the fat body into the hemolymph in the BPH,thereby triggering an immune response.Additionally,the fitness costs related to life-history traits of BPH(such as survival rate)have a strong dependence on the relative abundance of YLS.However,the possible relationship between reproduction and the immune response in BPH has not been identified.In this study,an omics-based approach was used to analyze the transcriptome of fat body tissues in mated and unmated BPH at 72 h post-eclosion,from which two antimicrobial peptide genes,NlDefensin A(NlDfA)and NlDefensin B(NlDfB),were selected since they were highly expressed in mated BPH.Subsequently,the full-length cDNA sequences of the NlDfA and NlDfB genes were cloned and analyzed.qPCR results showed up-regulation of the NlDfA and NlDfB genes in mated BPH when compared to unmated BPH.Spatial-temporal expression analysis indicated that the NlDfA and NlDfB genes were expressed in all tissues and developmental stages,and they were most highly expressed in the fat body at 24 h post-eclosion.Moreover,the symbionts in BPH were significantly inhibited by the in vitro expression of the NlDfA and NlDfB proteins.Furthermore,RNA interference(RNAi)-mediated suppression of NlDfA and NlDfB dramatically increased the relative abundance of YLS in the fat body,while YLS in the hemolymph decreased significantly.These BPHs also displayed some fitness disadvantages in survival,fecundity,hatchability,and possibly the vertical transmission of YLS from hemolymph to egg.Our results indicated that mating could heighten the immunity of BPH by upregulating the expression of the NlDfA and NlDfB genes,which protect the host from pathogen challenges during reproduction.However,the reduced content of YLS may act as a fitness disadvantage in dictating the life-history traits of BPH.This work has significant theoretical and practical implications for the precise green control technology that involves crucial gene targeting,as well as for the“endosymbionts for pest control”strategy in insects. 展开更多
关键词 Nilaparvata lugens REPRODUCTION immune defense trade-off
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Pharmacological Investigation on the Qi-Invigorating Action of Schisandrin B: Effects on Mitochondrial ATP Generation in Multiple Tissues and Innate/Adaptive Immunity in Mice
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作者 Hoi Yan Leung Suen Chit Sze Kam Ming Ko 《Chinese Medicine》 CAS 2024年第2期15-26,共12页
Schisandrae Fructus, containing schisandrin B (Sch B) as its main active component, is recognized in traditional Chinese medicine (TCM) for its Qi-invigorating properties in the five visceral organs. Our laboratory ha... Schisandrae Fructus, containing schisandrin B (Sch B) as its main active component, is recognized in traditional Chinese medicine (TCM) for its Qi-invigorating properties in the five visceral organs. Our laboratory has shown that the Qi-invigorating action of Chinese tonifying herbs is linked to increased mitochondrial ATP generation and an enhancement in mitochondrial glutathione redox status. To explore whether Sch B can exert Qi-invigorating actions across various tissues, we investigated the effects of Sch B treatment on mitochondrial ATP generation and glutathione redox status in multiple mouse tissues ex vivo. In line with TCM theory, which posits that Zheng Qi generation relies on the Qi function of the visceral organs, we also examined Sch B’s impact on natural killer cell activity and antigen-induced splenocyte proliferation, both serving as indirect measures of Zheng Qi. Our findings revealed that Sch B treatment consistently enhanced mitochondrial ATP generation and improved mitochondrial glutathione redox status in mouse tissues. This boost in mitochondrial function was associated with stimulated innate and adaptive immune responses, marked by increased natural killer cell activity and antigen-induced T/B cell proliferation, potentially through the increased generation of Zheng Qi. 展开更多
关键词 Zheng Qi Schisandrin B MITOCHONDRIA ATP Generation Glutathione Redox Innate immunity Adaptive immunity Natural Killer Cell Activity Splenocyte Proliferation
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Effects of antioxidant‑rich Lactiplantibacillus plantarum inoculated alfalfa silage on rumen fermentation, antioxidant and immunity status, and mammary gland gene expression in dairy goats
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作者 Yixin Zhang Samaila Usman +4 位作者 Qiang Li Fuhou Li Xia Zhang Luiz Gustavo Nussio Xusheng Guo 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2024年第3期1227-1240,共14页
Background Milk synthesis in lactating animals demands high energy metabolism,which results in an increased production of reactive oxygen metabolites(ROM)causing an imbalance between oxidants and antioxidants thereby ... Background Milk synthesis in lactating animals demands high energy metabolism,which results in an increased production of reactive oxygen metabolites(ROM)causing an imbalance between oxidants and antioxidants thereby inducing oxidative stress(OS)on the animals.To mitigate OS and postpartum disorders in dairy goats and gain insight into the impact of dietary choices on redox status during lactation,a feeding trial was conducted using alfalfa silage inoculated with a high-antioxidant strain of Lactiplantibacillus plantarum.Methods Twenty-four Guanzhong dairy goats(38.1±1.20 kg)were randomly assigned to two dietary treatments:one containing silage inoculated with L.plantarum MTD/1(RSMTD-1),and the other containing silage inoculated with high antioxidant activity L.plantarum 24-7(ES24-7).Results ES24-7-inoculated silage exhibited better fermentation quality and antioxidant activity compared to RSMTD-1.The ES24-7 diet elevated the total antioxidant capacity(T-AOC),superoxide dismutase(SOD),glutathione peroxi-dase(GSH-Px),and catalase(CAT)activities in milk,serum,and feces of lactating goats(with the exception of T-AOC in milk).Additionally,the diet containing ES24-7 inoculated silage enhanced casein yield,milk free fatty acid(FFA)content,and vitamin A level in the goats’milk.Furthermore,an increase of immunoglobulin(Ig)A,IgG,IgM,inter-leukin(IL)-4,and IL-10 concentrations were observed,coupled with a reduction in IL-1β,IL-2,IL-6,interferon(IFN)-γ,and tumor necrosis factor(TNF)-αconcentrations in the serum of lactating goats fed ES24-7.Higher concentrations of total volatile fatty acid(VFA),acetate,and propionate were observed in the rumen fluid of dairy goats fed ES24-7 inoculated silage.Moreover,the diet containing ES24-7 inoculated silage significantly upregulated the expression of nuclear factor erythroid 2 like 2(NFE2L2),beta-carotene oxygenase 1(BCO1),SOD1,SOD2,SOD3,GPX2,CAT,glu-tathione-disulfide reductase(GSR),and heme oxygenase 1(HMOX1)genes in the mammary gland,while decreased the levels of NADPH oxidase 4(NOX4),TNF,and interferon gamma(IFNG).Conclusions These findings indicated that feeding L.plantarum 24-7 inoculated alfalfa silage not only improved rumen fermentation and milk quality in lactating dairy goats but also boosted their immunity and antioxidant status by modulating the expression of several genes related to antioxidant and inflammation in the mammary gland. 展开更多
关键词 Alfalfa silage Antioxidant activity Gene expression Goats immunity LACTATION
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A novel chorismate mutase effector secreted from root-knot nematode Meloidogyne enterolobii manipulates plant immunity to promote parasitism
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作者 Tuizi Feng Yuan Chen +4 位作者 Zhourong Li Ji Pei Deliang Peng Huan Peng Haibo Long 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2024年第12期4107-4119,共13页
Meloidogyne spp.is an economically important plant-parasitic nematode distributed worldwide.To fight with host immune system for successful parasitism,plant parasitic nematodes secrete effectors to promote infection.I... Meloidogyne spp.is an economically important plant-parasitic nematode distributed worldwide.To fight with host immune system for successful parasitism,plant parasitic nematodes secrete effectors to promote infection.In this study,we identified one chorismate mutase(CM)effector from M.enterolobii,named Me-CM.Spatial and temporal expression assays exhibited Me-cm is expressed in esophageal glands and up-regulated at parasitic-stage juveniles.Me-CM affects the pathogenicity of M.enterolobii based on the reduced infection rate,number of galls,egg masses,eggs per mass and multiplication rate collected from RNA silencing experiments.We showed that Me-CM localized in the cytoplasm and nucleus of plant cells and decreased the expression level of the marker gene PR1 of salicylic acid(SA)pathway.Besides,constitutive expression of Me-cm in Arabidopsis thaliana significantly reduced salicylic acid concentration.These results suggested that M.enterolobii may secrete effector Me-CM to fight with plantimmunesystemsvia regulating SA signaling pathway when interacting with host plants,ultimately facilitating parasitism. 展开更多
关键词 Meloidogyne enterolobii EFFECTOR chorismate mutase salicylic acid plant immunity
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Does Herd Immunity Reduce the Risk of Contracting COVID-19?
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作者 Emma Li 《Journal of Biosciences and Medicines》 2024年第9期21-27,共7页
Herd immunity is often considered a measure to protect a whole community or population from disease if the vaccination threshold is met. Using the demographic and COVID-19 infection data from the state of Pennsylvania... Herd immunity is often considered a measure to protect a whole community or population from disease if the vaccination threshold is met. Using the demographic and COVID-19 infection data from the state of Pennsylvania, United States, the study aimed to determine if herd immunity by vaccination is an effective way to reduce the spread of the COVID-19 virus. The Pennsylvania counties were split into two groups based on qualification of herd immunity: counties that met the COVID-19 herd immunization rate of 70% and counties that did not. The ANOVA test was used to analyze the difference between the groups with and without herd immunity by the COVID-19 vaccine. The results demonstrated that there was no significant statistical difference between counties that did achieve and those that did not achieve the herd immunity threshold for the COVID-19 vaccine. On the other hand, it was observed that there had been a significant decrease in positive cases between 2020 and 2023. This decline can be attributed to the overall protection by the vaccination and adaptability to the disease, not specifically due to herd immunity alone. Ultimately, these outcomes suggest that herd immunity cannot reduce the risk of contracting COVID-19. Increased efforts to get vaccinated should be implemented to protect the general community and a wider scope of age. 展开更多
关键词 COVID-19 Herd immunity VACCINE
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A novel ABA structural analogues enhanced plant resistance by inducing the plant immunity and inactivating ABA signaling pathway 被引量:1
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作者 Yanke Jiang Yingzhe Yue +6 位作者 Zhaoxu Wang Chongchong Lu Zhizheng Wang Ziyi Yin Yang Li Ge-Fei Hao Xinhua Ding 《Advanced Agrochem》 2024年第1期64-73,共10页
Abscisic acid(ABA)is a phytohormone that not only important for plant growth,but also mediating the stress response.The roles of ABA in plant immunity are especially multifaceted.Recently,the ABA functional analogues ... Abscisic acid(ABA)is a phytohormone that not only important for plant growth,but also mediating the stress response.The roles of ABA in plant immunity are especially multifaceted.Recently,the ABA functional analogues are of great significance to promote its application.Here,we reported an ABA functional analogue named 167A.167A inhibits plant growth and seeds germinating of Arabidopsis.Meanwhile,the 167A enhanced the plant immunity,which is opposite of ABA.We further investigated the PTI-response after 167A treatment,and the results show that the ROS burst,callose deposition accumulate with 167A treatment.Moreover,167A also influence the degree of stomal closed.RNA-seq assays show that the 167A down-regulated the ABA associated genes and upregulated the JA/SA/ET associated genes.Through genetic analysis,the 167A modulating the plant resistance through the PYR/PYL Receptors.Together,these results demonstrate that a novel ABA analogue 167A positive regulated plant immunity and has great potential for agricultural applications. 展开更多
关键词 Abscisic acid Structural analogues Plant immunity PYR1/PYL receptors
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Harnessing immunity:Immunomodulatory therapies in COVID-19
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作者 Tsvetelina Velikova Hristo Valkov +3 位作者 Anita Aleksandrova Monika Peshevska-Sekulovska Metodija Sekulovski Russka Shumnalieva 《World Journal of Virology》 2024年第2期34-47,共14页
An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,decipherin... An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators. 展开更多
关键词 IMMUNOMODULATION COVID-19 SARS-CoV-2 IMMUNOTHERAPY Antiviral immune response Cytokine storm Adaptive immunity Therapeutic strategies Immune modulators Viral infection Host immune response
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Targeting the chromatin structural changes of antitumor immunity
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作者 Nian-nian Li Deng-xing Lun +22 位作者 Ningning Gong Gang Meng Xin-ying Du He Wang Xiangxiang Bao Xin-yang Li Ji-wu Song Kewei Hu Lala Li Si-ying Li Wenbo Liu Wanping Zhu Yunlong Zhang Jikai Li Ting Yao Leming Mou Xiaoqing Han Furong Hao Yongcheng Hu Lin Liu Hongguang Zhu Yuyun Wu Bin Liu 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2024年第4期460-482,共23页
Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor imm... Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology. 展开更多
关键词 Antitumor immunity Chromatin structural Cancer epigenetics DNA methylation Histone modification CHEMOTHERAPY
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The Magnaporthe oryzae effector Avr-PikD suppresses rice immunity by inhibiting an LSD1-like transcriptional activator
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作者 Jiayuan Guo Yiling Wu +8 位作者 Jianqiang Huang Kaihui Yu Meilian Chen Yijuan Han Zhenhui Zhong Guodong Lu Yonghe Hong Zonghua Wang Xiaofeng Chen 《The Crop Journal》 SCIE CSCD 2024年第2期482-492,共11页
Avirulence effectors(Avrs),encoded by plant pathogens,can be recognized by plants harboring the corresponding resistance proteins,thereby initiating effector-triggered immunity(ETI).In susceptible plants,however,Avrs ... Avirulence effectors(Avrs),encoded by plant pathogens,can be recognized by plants harboring the corresponding resistance proteins,thereby initiating effector-triggered immunity(ETI).In susceptible plants,however,Avrs can function as effectors,facilitating infection via effector-triggered susceptibility(ETS).Mechanisms of Avr-mediated ETS remain largely unexplored.Here we report that the Magnaporthe oryzae effector Avr-PikD enters rice cells via the canonical cytoplasmic secretion pathway and suppresses rice basal defense.Avr-PikD interacts with an LSD1-like transcriptional activator AKIP30 of rice,and AKIP30 is also a positive regulator of rice immunity,whereas Avr-PikD impedes its nuclear localization and suppresses its transcriptional activity.In summary,M.oryzae delivers Avr-PikD into rice cells to facilitate ETS by inhibiting AKIP30-mediated transcriptional regulation of immune response against M.oryzae. 展开更多
关键词 Magnaporthe oryzae Avirulence effector Avr-PikD Effector-triggered susceptibility Rice immunity Transcriptional activator
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CNGC20 plays dual roles in regulating plant growth and immunity in Brassica napus
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作者 Yingying Tan Guowei Huang +3 位作者 Haiyan Fan Tao Wua Zhilin Guan Kede Liu 《The Crop Journal》 SCIE CSCD 2024年第6期1533-1546,共14页
Inflorescence architecture is determined by inflorescence length,branch angles and the density of siliques,which affects planting density,lodging resistance and mechanical operation in rapeseed.However,the molecular m... Inflorescence architecture is determined by inflorescence length,branch angles and the density of siliques,which affects planting density,lodging resistance and mechanical operation in rapeseed.However,the molecular mechanisms controlling inflorescence architecture are poorly understood,restricting the progress of breeding varieties with ideal plant architecture in oilseed rape.In this study,we have identified and characterized a rapeseed inflorescence development mutant,reduced inflorescence length(ril),which exhibits determinate and shortened inflorescences,reduced plant height,compact branches,and increased silique density.Through BSA-seq and map-based cloning,we find that RIL encodes a cyclic nucleotide-gated channel 20(BnaA01.CNGC20).A substitution of proline at the 304th position to leucine(P304L)was identified in the conserved transmembrane domain of BnaA01.CNGC20.This P304L substitution neither affects the subcellular localization and self-assembly of BnaA01.CNGC20,nor disrupts the interactions with BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1(BAK1),which interacts with CNGC20 and phosphorylates it to regulate Ca^(2+)channel stability.However,the P304L substitution increases channel activity and Ca^(2+)influx,which in turn induces immune responses such as cell death,H2O2 accumulation,upregulation of pathogenesis-related genes,and pattern-triggered immunity.The enhanced immunity improves the resistance to Leptosphaeria biglobosa and Sclerotinia sclerotiorum.Transcriptome analysis further revealed that CNGC20 plays dual roles in regulating plant growth and immunity via the brassinosteroid and auxin signaling pathways.The findings in this study provide deeper insights into the intricate relationship between cytosolic Ca^(2+)level and plant development and immunity,as well as the trade-off between immunity and the performance of yield-related traits in the heterozygous plants(+/ril),which may serve as a guide for balancing yield and disease resistance in oilseed rape breeding. 展开更多
关键词 Brassica napus L. Plant architecture Inflorescence development CNGC20 Plant immunity
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Tumor-infiltrating T-Lymphocyte immunity-related immune tolerance and anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy for advanced hepatocellular carcinoma
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作者 Lingzhen Hu Zongren Wang +3 位作者 Yang Liao Xiaomeng Jiang Huojun Lian Zhuoying Lin 《Oncology and Translational Medicine》 CAS 2024年第4期162-170,共9页
Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes ... Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC. 展开更多
关键词 Anti–PD-1/PD-L1 treatment Combination therapy Hepatocellular carcinoma Immune tolerance Tumor-infiltrating T lymphocyte immunity
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OsbZIP53 Negatively Regulates Immunity Response by Involving in Reactive Oxygen Species and Salicylic Acid Metabolism in Rice
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作者 WU Lijuan HAN Cong +5 位作者 WANG Huimei HE Yuchang LIN Hai WANG Lei CHEN Chen E Zhiguo 《Rice science》 SCIE CSCD 2024年第2期190-202,I0022-I0028,共20页
The basic region/leucine zipper(bZIP)transcription factors play important roles in plant development and responses to abiotic and biotic stresses.OsbZIP53 regulates resistance to Magnaporthe oryzae in rice by analyzin... The basic region/leucine zipper(bZIP)transcription factors play important roles in plant development and responses to abiotic and biotic stresses.OsbZIP53 regulates resistance to Magnaporthe oryzae in rice by analyzing APIP5-RNAi transgenic plants.To further investigate the biological functions of OsbZIP53,we generated osbzip53 mutants using CRISPR/Cas9 editing and also constructed OsbZIP53 over-expression transgenic plants.Comprehensive analysis of phenotypical,physiological,and transcriptional data showed that knocking-out OsbZIP53 not only improved disease resistance by inducing a hypersensitivity response in plants,but also regulated the immune response through the salicylic acid pathway.Specifically,disrupting OsbZIP53 increased H2O2 accumulation by promoting reactive oxygen species generation through up-regulation of several respiratory burst oxidase homologs(Osrboh genes)and weakened H2O2 degradation by directly targeting OsMYBS1.In addition,the growth of osbzip53 mutants was seriously impaired,while OsbZIP53 over-expression lines displayed a similar phenotype to the wild type,suggesting that OsbZIP53 has a balancing effect on rice immune response and growth. 展开更多
关键词 OsbZIP53 hypersensitive response reactive oxygen species metabolism rice immunity salicylic acid transcription factor
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Impact of nutritional support on immunity,nutrition,inflammation,and outcomes in elderly gastric cancer patients after surgery
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作者 Xiao-Wan Chen Xiao-Chun Guo Fen Cheng 《World Journal of Gastrointestinal Surgery》 SCIE 2024年第7期2175-2182,共8页
BACKGROUND Postoperative rehabilitation of elderly patients with gastric cancer has always been the focus of clinical attention.Whether the intervention by a full-course nutritional support team can have a positive im... BACKGROUND Postoperative rehabilitation of elderly patients with gastric cancer has always been the focus of clinical attention.Whether the intervention by a full-course nutritional support team can have a positive impact on the postoperative immune function,nutritional status,inflammatory response,and clinical outcomes of this special population has not yet been fully verified.AIM To evaluate the impact of full-course nutritional support on postoperative comprehensive symptoms in elderly patients with gastric cancer.METHODS This is a retrospective study,including 60 elderly gastric cancer patients aged 70 years and above,divided into a nutritional support group and a control group.The nutritional support group received full postoperative nutritional support,including individualized meal formulation,and intravenous and parenteral nutrition supplementation,and was regularly evaluated and adjusted by a professional nutrition team.The control group received routine postoperative care.RESULTS After intervention,the proportion of CD4+lymphocytes(25.3%±3.1%vs 21.8%±2.9%,P<0.05)and the level of immunoglobulin G(12.5 G/L±2.3 G/L vs 10.2 G/L±1.8 G/L,P<0.01)were significantly higher in the nutritional support group than in the control group;the changes in body weight(-0.5 kg±0.8 kg vs-1.8 kg±0.9 kg,P<0.05)and body mass index(-0.2±0.3 vs-0.7±0.4,P<0.05)were less significant in the nutritional support group than in the control group;and the level of C-reactive protein(1.2 mg/L±0.4 mg/L vs 2.5 mg/L±0.6 mg/L,P<0.01)and WBC count(7.2×10^(9)/L±1.5×10^(9)/L vs 9.8×10^(9)/L±2.0×10^(9)/L,P<0.01)were significantly lower in the nutritional support group than in the control group.In addition,patients in the nutritional support group had a shorter hospital stay(10.3 d±2.1 d vs 14.8 d±3.6 d,P<0.05)and lower incidence of infection(15%vs 35%,P<0.05)in those of the control group.CONCLUSION The intervention by the nutritional support team has a positive impact on postoperative immune function,nutritional status,inflammatory response,and clinical outcomes in elderly patients with gastric cancer. 展开更多
关键词 Elderly gastric cancer POSTOPERATIVE Nutritional support Immune function Inflammatory response Clinical outcome
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TIR domain protein-mediated phase separation activates plant immunity
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作者 Hadiatullah Hadiatullah Lei Li +1 位作者 Zhiyuan Hao Zhiguang Yuchi 《Advanced Agrochem》 2024年第3期183-184,共2页
We spotlight recent findings from a Nature paper unveiling captivating insights into how substrates such as NADþand ATP stimulate the condensation of TIR domain proteins.This process culminates in the formation o... We spotlight recent findings from a Nature paper unveiling captivating insights into how substrates such as NADþand ATP stimulate the condensation of TIR domain proteins.This process culminates in the formation of a quaternary structural pattern akin to the catalytic arrangement observed in conventional TNL proteins.Consequently,this mechanism enables the production of pivotal signaling molecules crucial for fortifying plant immunity.Expanding on these revelations,we propose the prospect of creating modulatory compounds capable of initiating the phase separation of TIR domain proteins as an innovative approach to enhance plant immunity against pathogenic challenges. 展开更多
关键词 TIR domain protein Phase separation Plant immunity
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苦马豆素对家兔脾脏免疫功能及代谢的影响
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作者 赵金香 陶大勇 +3 位作者 杜国丰 张家鸣 沈佳宜 矫继峰 《动物医学进展》 北大核心 2025年第1期74-80,共7页
为了探讨苦马豆素通过消化系统对家兔脾脏免疫功能和代谢的影响,将体重为(1.9±0.12)kg的24只家兔随机分成对照组与试验组,每组雌、雄各半。试验组家兔饲喂含有小花棘豆的自制颗粒饲料,饲喂苦马豆素剂量为2 mg/(kg·d),对照组... 为了探讨苦马豆素通过消化系统对家兔脾脏免疫功能和代谢的影响,将体重为(1.9±0.12)kg的24只家兔随机分成对照组与试验组,每组雌、雄各半。试验组家兔饲喂含有小花棘豆的自制颗粒饲料,饲喂苦马豆素剂量为2 mg/(kg·d),对照组家兔饲喂自制颗粒饲料中不含小花棘豆。所有家兔单笼饲养,自由饮水,每天观测并记录家兔的健康状态。在试验的第60天,采取所有家兔脾脏,对脾脏进行基于iTRAQ的定量蛋白质组学分析、生物信息学分析及关键蛋白质的Western blot验证。结果显示,所有试验组家兔均呈现明显的中毒现象。与对照组相比,共鉴定出315个与新陈代谢(81%)及免疫相关(15%)的差异表达蛋白质(>1.5倍或<1/1.5倍)。而且,苦马豆素中毒家兔脾脏细胞分解代谢处于激活状态,但其免疫反应处于抑制状态。说明苦马豆素抑制了家兔脾脏的免疫功能,激活了脾脏组织的分解代谢。 展开更多
关键词 苦马豆素 小花棘豆 脾脏 同位素标记的相对和绝对定量技术 蛋白质组 免疫 家兔
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不同细胞来源外泌体miRNAs在胃癌进展及诊断和预后中的作用
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作者 王磊 王白燕 +3 位作者 周春光 任晓云 代月优 冯书营 《中国组织工程研究》 CAS 北大核心 2025年第25期5434-5442,共9页
背景:肿瘤微环境可通过多种途径参与胃癌的发生发展并促进胃癌化疗耐药,其中外泌体miRNAs介导的肿瘤微环境串话可诱导基质重编程,参与肿瘤异质性,并形成有利于肿瘤增殖、迁移、侵袭、免疫逃逸和化疗耐药的微环境。目的:对近年来外泌体mi... 背景:肿瘤微环境可通过多种途径参与胃癌的发生发展并促进胃癌化疗耐药,其中外泌体miRNAs介导的肿瘤微环境串话可诱导基质重编程,参与肿瘤异质性,并形成有利于肿瘤增殖、迁移、侵袭、免疫逃逸和化疗耐药的微环境。目的:对近年来外泌体miRNAs在胃癌微环境中的作用机制及其在胃癌诊断及预后评估中的应用进展作一综述。方法:以“Exosomal miRNAs,gastric cancer,angiogenesis,apoptosis,proliferation,migration,autophagy,invasion,immune response,chemotherapy resistance,biomarker”为英文检索词和“外泌体miRNAs,胃癌”为中文检索词分别检索PubMed及中国知网数据库。检索时限为2017-2024年。通过阅读文题及摘要进行初步筛选,排除研究内容相关性差及内容重复的文献,最终纳入77篇文献进行归纳探讨。结果与结论:①外泌体作为细胞间信息交流的重要载体,可携带miRNA等多种信息物质,通过激活靶细胞上的细胞表面受体、与受体细胞质膜融合及内吞作用3种途径实现细胞间信号传递。②外泌体miRNAs通过调节胃癌细胞增殖、凋亡、自噬、血管形成、侵袭转移、免疫应答以及耐药性的形成等多种途径,进而在胃癌进展中发挥着重要作用。③miRNA与靶mRNA相互作用及其调控网络广泛存在于肿瘤发生和人类癌症发展中,不同类型外泌体miRNAs对调控胃癌细胞凋亡具有不同的作用,鉴别不同外泌体miRNAs对胃癌细胞凋亡相关蛋白及通路的影响,合理运用其诱导剂或抑制剂可对胃癌细胞凋亡水平进行调控。④不同细胞来源的外泌体miRNAs通过将M1极化型巨噬细胞诱导为M2型,在肿瘤微环境的建立、血管生成、免疫应答及化疗耐药中扮演重要角色。⑤外泌体miRNAs广泛稳定存在于血液及其他体液中,其在胃癌患者中的差异性表达可作为胃癌患者诊断、预后及治疗依据。目前作为生物标志物研究较多的外泌体miRNAs包括miR-379-5p,miR-590-5p,miR-29s和miR-21等,其中miR-590-5p灵敏度与特异性分别为63.7%和86%,其表达水平与胃癌患者总体生存率、浸润深度密切相关。⑥设计外泌体miRNAs模拟物或抑制物,并利用纳米递送载体(如外泌体、脂质体)将其靶向递送至肿瘤部位以恢复miRNAs正常水平,可能是治疗胃癌的一种新策略。⑦虽然外泌体miRNAs在胃癌患者诊疗中具有很大的应用前景,但仍存在一些问题亟待解决,例如外泌体miRNAs的潜在靶点及作用机制尚未完全探讨,其有效性及安全性有待进一步确认;而且外泌体的提取及纯化缺乏标准化规模化制备流程等。 展开更多
关键词 胃癌 肿瘤微环境 外泌体miRNAs 血管生成 免疫应答 自噬 耐药 诊疗 预后 生物标记物
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