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Traditional Chinese medicine for the treatment of immune-related nephropathy:A review

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Acta Pharmaceutica Sinica B 2024年第1期14卷 38-66页

作者： Pu Jiang Changliang Yao De-an Guo School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China Shanghai Research Center for Modernization of Traditional Chinese Medicine National Engineering Research Center of TCM Standardization TechnologyShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China

Immune-related nephropathy(IRN)refers to immune-response-mediated glomerulonephritis and is the main cause of end-stage renal failure.The pathogenesis of IRN is not fully understood;therefore,treatment is challenging.Traditional Chinese medicines(TCMs)have potent clinical effects in the treatment of the IRN conditions immunoglobulin A nephropathy,lupus nephropathy,and diabetic nephropathy.The underlying mechanisms mainly include its inhibition of inflammation;improvements to renal interstitial fibrosis,oxidative stress,autophagy,apoptosis;and regulation of immunity.In this review,we summarize the clinical symptoms of the three IRN subtypes and the use of TCM prescriptions,herbs,and bioactive compounds in treating IRN,as well as the potential mechanisms,intending to provide a reference for the future study of TCM as IRN treatments.

关键词： IgA nephropathy Diabetic nephropathy Lupus nephritis Traditional Chinese medicine immunity Pathogenesis Mechanism Pathophysiology

New insights into the role of the immune inhibitory receptor VSTM1 in autoimmune disease

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Cellular & Molecular Immunology 2024年第1期21卷 95-96页

作者： Najun Miaol Jing Wang Center for Immune-related Diseases at Shanghai Institute of Immunology Rujin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Immune inhibitory receptors(IRs)are germline-encoded transmembrane receptors that function as negative regulators of immune cells and dampen the cellular response to keep the immune system in balance^([1]).There are more than 300 potential immune IRs encoded in the human genome^([2]).The most studied IRs in cancer immunity are programmed cell death protein 1,cytotoxic T lymphocyte protein 4 in T cells,and killer cell Ig-like IRs on NK cells^([3]).

关键词： immunity immune autoimmune

Heterocyclic Molecules Tethered Branched Polymers with Innate Immune Stimulating Activity

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CCS Chemistry 2024年第5期6卷 1278-1288页

作者： Jiayu Zhao Liping Liu Yibo Wang Zichao Huang Yu Zhang Ruirui Qiao Thomas P.Davis Zhaohui Tang Wantong Song Xuesi Chen Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022 School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026 Laboratory of Chemical Biology Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022 Jilin Biomedical Polymers Engineering Laboratory Changchun 130022 Australian Institute of Bioengineering and Nanotechnology The University of QueenslandBrisbaneQueensland 4072

We report herein an interesting finding that heterocyclic molecules tethered branched polymers exhibit innate immune stimulating activity.When we conjugated a series of five-,six-,or seven-membered heterocyclic molecules to branched polyethylenimine(bPEI),over 70%of them could induce the secretion of interferon-β(IFN-β)from murine dendritic and human leukemia monocytic(DC2.4 and THP-1)cells through activating the stimulator of interferon genes(STING)pathway.We further proved that this kind of innate stimulating activity was dependent on the macromolecular architecture as heterocyclic molecules tethered linear PEI(lPEI)or dendritic polyamidoamine(PAMAM)induced no or much less IFN-βsecretion.Furthermore,we prepared a series of poly-L-lysine(PLL)-derivatives with different branches to tether with heterocyclic molecules and proved that this kind of bPEI-like structure was important in en hancing the binding affinity with STING proteins and for exhibiting innate stimulating activity.

关键词： bioactive materials polymers heterocycles branched structure immunity

Development and validation of a prognostic immunoinflammatory index for patients with gastric cancer

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World Journal of Gastroenterology 2024年第24期30卷 3059-3075页

作者： Zhi-Chang Ba Xi-Qing Zhu Zhi-Guo Li Yuan-Zhou Li Department of Radiology Harbin Medical University Cancer HospitalHarbin 150081Heilongjiang ProvinceChina Department of Gastrointestinal Surgery Harbin Medical University Cancer HospitalHarbin 150081Heilongjiang ProvinceChina

BACKGROUND Studies have demonstrated the influence of immunity and inflammation on the development of tumors.Although single biomarkers of immunity and inflam-mation have been shown to be clinically predictive,the use of biomarkers integrating both to predict prognosis in patients with gastric cancer remains to be investigated.AIM To investigate the prognostic and clinical significance of inflammatory biomarkers and lymphocytes in patients undergoing surgical treatment for gastric cancer.METHODS Univariate COX regression analysis was performed to identify potential prognostic factors for patients with gastric cancer undergoing surgical treatment.Least absolute shrinkage and selection operator-COX(LASSO-COX)regression analysis was performed to integrate these factors and formulate a new prognostic immunoinflammatory index(PII).The correlation between PII and clinical charac-teristics was statistically analyzed.Nomograms incorporating the PII score were devised and validated based on the time-dependent area under the curve and decision curve analysis.RESULTS Patients exhibiting elevated neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and systemic immune inflammatory index displayed inferior progression-free survival(PFS)and overall survival(OS).Conversely,low levels of CD3(+),CD3(+)CD8(+),CD4(+)CD8(+),and CD3(+)CD16(+)CD56(+)T lymphocytes were associated with improved PFS and OS,while high CD19(+)T lymphocyte levels were linked to worse PFS and OS.The PII score demonstrated associations with tumor characteristics(primary tumor site and tumor size),establishing itself as an independent prognostic factor for both PFS and OS.Time-dependent area under the curve and decision curve analysis affirmed the effectiveness of the PII-based nomogram as a robust prognostic predictive model.CONCLUSION PII may be a reliable predictor of prognosis in patients with gastric cancer undergoing surgical treatment,and it offers insights into cancer-related immune-inflammatory responses,with potential significance in clinical

关键词： Gastric cancer immunity Inflammation Prognosis Nomogram

Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

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Neural Regeneration Research 2025年第3期20卷 763-778页

作者： Minghuang Gao Xinyue Wang Shijie Su Weicheng Feng Yaona Lai Kongli Huang Dandan Cao Qi Wang Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina Institute of Clinical Pharmacology Guangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina The Sixth Affiliated Hospital Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

关键词： central nervous system meningeal lymphatic vessels immunity myeloid cells lymphatic cells neurodegenerative disease

Meningeal lymphatic vasculature,a general target for glioblastoma therapy?

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Fundamental Research 2024年第2期4卷 267-269页

作者： Changping Zhou Han Xu Jincai Luo Laboratory of Vascular Biology Institute of Molecular MedicineCollege of Future TechnologyBeijing Key Laboratory of Cardiometabolic Molecular MedicinePeking UniversityBeijing 100871China

Glioblastoma(GBM)causes nearly universal mortality as a result of the failure of conventional therapies including surgical resection,targeted radiation therapy,and chemotherapy.An increasingly important treatment option is combining immunotherapy with other therapies in both preclinical and clinical studies.The central nervous system(CNS)has been historically considered an immune privileged area,but increasing evidence,including the recent rediscovery of meningeal lymphatic vessels(MLVs),has overturned this notion.MLVs are populated by multiple immune cells and connect the CNS to the periphery by draining cerebrospinal fluid with soluble CNS antigens and immune cells into cervical lymph nodes.In the past few years,more and more studies have indicated that MLVs are involved in the regulation of inflammation and the immune response in the pathogenesis of various CNS diseases including GBM.Here,we explore the critical interlinkages between MLVs and GBM therapies including chemotherapy,radiotherapy and immunotherapy,and propose the meningeal lymphatic vasculature as a general target for GBM therapy.

关键词： Meningeal lymphatic vessels Glioblastoma immunity Vascular endothelial growth factor C Immune modulation

部分ESCRT亚基通过调控STING的降解调节其活性

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Science Bulletin 2024年第8期69卷 1000-1005页

作者：赵远周晨暄田文敏陈杨赵冲冲栗妍王世宣荣岳光 School of Basic Medicine Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious DiseaseHuazhong University of Science and TechnologyWuhan 430030China Center for Precision Medicine Multi-Omics Research Peking University Health Science CenterPeking UniversityBeijing 100191China School of Basic Medical Sciences Peking University Health Science CenterPeking UniversityBeijing 100083China The State Key Laboratory of Membrane Biology Tsinghua University-Peking University Joint Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China The HIT Center for Life Sciences Harbin Institute of TechnologyHarbin 150080China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Cell Architecture Research Center Huazhong University of Science and TechnologyWuhan 430030China

Stimulator of interferon genes(STING),also known as MITA,ERIS,MPYS or TMEM173,is a key player in innate immunity,specifically in the typeⅠinterferon response[1-3].It is also involved in a range of non-canonical biological functions,including autophagy,cellular metabolism,translation,and DNA repair,and has implications in many diseases[4-9].After activation by its ligands,STING translocates from endoplasmic reticulum(ER),via ERGIC,Golgi apparatus and endosomes,finally to lysosomes for degradation[4-9].However,the mechanisms by which STING is delivered to lysosomes and whether this delivery process regulates STING activity remain elusive.

关键词： has finally immunity

Role of T Cells in Viral and Immune-mediated Myocarditis

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Cardiology Discovery 2024年第1期4卷 43-54页

作者： Chunyan Cheng Anna Baritussio Andrea Silvio Giordani Renzo Marcolongo Alida L.P.Caforio Sabino Iliceto Department of Cardiovascular Medicine Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhouGuangdong 510080China Cardiology Unit Department of Cardiac Thoracic Vascular Sciences and Public HealthUniversity of PadovaVia Giustiniani2Padova 35128Italy

Myocarditis is characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function with a heterogeneous etiology. Both viral- and myosin-induced myocarditis experimental models are used to mimic myocarditis in humans. Here, coxsackie virus B3-induced and non-virus-induced myocarditis models and data obtained in clinical studies were reviewed. Experimental murine myocarditis following immunization with α-myosin together with complete Freund adjuvant represents the classical immune-mediated model. T helper 1 (Th1) and Th2 pathways and important cytokines are involved in the autoimmunity of myocarditis, and the dynamic balance between Th17 and regulatory T cell seems to have an important role in the process of myocarditis. The purpose of this review is to summarize the existing understanding of the immunological mechanisms underlying myocarditis and exploring gaps in knowledge in both animal and human studies, since these mechanistic insights are a critical requirement for the development of novel therapeutic and vaccination strategies.

关键词： Myocarditis immunity T cells Animal models Clinical study

Impact of corticosteroids on initiation and half-year durability of humoral response in COVID-19 survivors

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 48-55页

作者： Yeming Wang Li Guo Guohui Fan Yang Han Qiao Zhang Lili Ren Hui Zhang Geng Wang Xueyang Zhang Tingxuan Huang Weiyang Wang Lan Chen Lixue Huang Xiaoying Gu Xinming Wang Jingchuan Zhong Ying Wang Hui Li Jiapei Yu Zhibo Liu Chaolin Huang Bin Cao Jianwei Wang National Center for Respiratory Medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesChina-Japan Friendship HospitalBeijing 100029China National Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 102629China Key Laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical SciencesBeijing 100029China School of Population Medicine and Public Health Chinese Academy of Medical Sciences&Peking Union Medical CollegeState Key Laboratory of Respiratory Health and MultimorbidityKey Laboratory of Pathogen Infection Prevention and Control(Peking Union Medical College)Ministry of EducationBeijing 100730China National Center for Respiratory Medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Clinical research and Data managementCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Jin Yin-tan Hospital WuhanHubei 430023China Department of Pulmonary and Critical Care Medicine West China HospitalSichuan UniversityChengduSichuan 610041China Department of Rheumatology and Clinical Immunology Chinese Academy of Medical Sciences&Peking Union Medical CollegeNational Clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID)Ministry of Science&TechnologyState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College Hospital(PUMCH)Key Laboratory of Rheumatology and Clinical ImmunologyMinistry of EducationBeijing 100730China Department of Pulmonary and Critical Care Medicine Center of Respiratory MedicineChina-Japan Friendship HospsitalInstitute of Respiratory MedicineChinese

Background:The impact of corticosteroids on humoral responses in coronavirus disease 2019(COVID-19)sur-vivors during the acute phase and subsequent 6-month period remains unknown.This study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection onset.Methods:We used kinetic antibody data from the lopinavir-ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020,which involved adults hospitalized with severe COVID-19(LOTUS,ChiCTR2000029308).Anti-body samples were collected from 192 patients during hospitalization,and kinetic antibodies were monitored at all available time points after recruitment.Additionally,plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up visit.The main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid group.Results:From illness onset to day 30,the median antibody titre areas under the receiver operating characteristic curve(AUCs)of nucleoprotein(N),spike protein(S),and receptor-binding domain(RBD)immunoglobulin G(IgG)were significantly lower in the corticosteroids group.The AUCs of N-,S-,and RBD-IgM as well as neutralizing antibodies(NAbs)were numerically lower in the corticosteroids group compared with the non-corticosteroid group.However,peak titres of N,S,RBD-IgM and-IgG and NAbs were not influenced by corticosteroids.During 6-month follow-up,we observed a delayed decline for most binding antibodies,except N-IgM(𝛽−0.05,95%CI[−0.10,0.00])in the corticosteroids group,though not reaching statistical significance.No significant difference was observed for NAbs.However,for the half-year seropositive rate,corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-,S-,and RBD-IgG or NAbs.Additionally,corticosteroids group showed a trend towards delayed viral clearance compared with the non-cort

关键词： COVID-19 Corticosteroid immunity Antibody Humoral response