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Immunologic tumor microenvironment modulators for turning cold tumors hot

Cancer Communications 2024年第5期44卷 521-553页

作者： Gholam-Reza Khosravi Samaneh Mostafavi Sanaz Bastan Narges Ebrahimi Roya Safari Gharibvand Nahid Eskandari department of Medical immunology School of MedicineIsfahan University of Medical SciencesIsfahanIran department of immunology Faculty of Medical SciencesTarbiat Modares UniversityTehranIran department of immunology School of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran

Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within the tumor microenvironment(TME).Hot tumors,characterized by heightened immune activity and responsiveness to immune checkpoint inhibitors(ICIs),stand in stark contrast to cold tumors,which lack immune infiltration and remain resistant to *** overcome immune evasion mechanisms employed by tumor cells,novel immunologic modulators have emerged,particularly ICIs targeting cytotoxic T-lymphocyte-associated protein 4(CTLA-4)and programmed cell death protein 1/programmed death-ligand 1(PD-1/PD-L1).These agents disrupt inhibitory signals and reactivate the immune system,transforming cold tumors into hot ones and promoting effective antitumor ***,challenges persist,including primary resistance to immunotherapy,autoimmune side effects,and tumor response *** these challenges requires innovative strategies,deeper mechanistic insights,and a combination of immune interventions to enhance the effectiveness of *** the landscape of cancer medicine,where immune cold tumors represent a formidable hurdle,understanding the TME and harnessing its potential to reprogram the immune response is *** review sheds light on current advancements and future directions in the quest for more effective and safer cancer treatment strategies,offering hope for patients with immune-resistant tumors.

关键词： cold tumor hot tumor immunologic modulator immunotherapy therapeutic strategy tumor microenvironment

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Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

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Cellular & Molecular immunology 2024年第4期21卷 393-408页

作者： Sujin Lee Yeunjung Ko Hyun Woo Lee Won Joon Oh Hun Gi Hong Dinuka Ariyaratne Se Jin Im Tae Jin Kim department of immunology Graduate School of Basic Medical ScienceSungkyunkwan University School of MedicineSuwon16419Republic of Korea department of immunology and Molecular medicine Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka Present address:immunology and Microbiology Graduate Program Baylor College of MedicineHoustonTX77030USA

Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous ***,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression ***80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B ***,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after *** of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine ***80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant ***80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B *** transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B *** summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

关键词： Marginal Zone B Cell CD80 Autoreactivity Radioresistance

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PD-1^(+)and TIM-3^(+)T cells widely express commonγ-chain cytokine receptors in multiple myeloma patients,and IL-2,IL-7,IL-15 stimulation up-regulates PD-1 and TIM-3 on T cells

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Oncology Research 2024年第10期32卷 1575-1587页

作者： EGOR V.BATOROV ALISA D.INESHINA TATIANA A.ARISTOVA VERA V.DENISOVA SVETLANA A.SIZIKOVA DARIA S.BATOROVA GALINA Y.USHAKOVA EKATERINA Y.SHEVELA ELENA R.CHERNYKH Laboratory of Cellular Immunotherapy Research Institute of Fundamental and Clinical ImmunologyNovosibirsk630099Russia V.Zelman Institute of medicine and Psychology Novosibirsk National Research State UniversityNovosibirsk630090Russia department of Hematology and Bone Marrow Transplantation Research Institute of Fundamental and Clinical ImmunologyNovosibirsk630099Russia

Background:Immune checkpoint ligand-receptor interactions appear to be associated with multiple myeloma(MM)***,previous studies showed the possibility of PD-1 and TIM-3 expression on T cells upon stimulation with commonγ-chain family cytokines in vitro and during homeostatic *** aim of the present work was to study the impact of homeostatic proliferation on the expansion of certain T cell subsets upregulating PD-1 and TIM-3 checkpoint ***:The expression of CD25,CD122,CD127 commonγ-chain cytokine receptors,phosphorylated signal transducer and activator of transcription-5(pSTAT5)and eomesodermin(EOMES)was comparatively assessed with flow cytometry in PD-1-and TIM-3-negative and positive T cells before the conditioning and during the first post-transplant month in peripheral blood samples of MM ***:Substantial proportions of PD-1-and TIM-3-positive T lymphocytes expressed commonγ-chain cytokine receptors and *** of cytokine receptor expressing cells were significantly higher within TIM-3+T cells compared to PD-1+TIM-3−*** proportions of both PD-1-/TIM-3-negative and positive CD8+T cells express EOMES,while only moderate frequencies of CD4+PD-1+/TIM-3+T cells up-regulate this transcription ***,the surface presence of CD25 and intranuclear expression of EOMES in CD4+T cells were mutually exclusive regardless of PD-1 and TIM-3 *** stimulation with commonγ-chain cytokines up-regulates PD-1 and TIM-3 during the proliferation of initially PD-1/TIM-3-negative T cells but fails to expand initially PD-1+and TIM-3+T cell subsets in ***:Both PD-1 and TIM-3 expressing T cells appear to be able to respond to homeostatic cytokine *** in commonγ-chain cytokine receptor expression between PD-1+and TIM-3+T cells may reflect functional dissimilarity of these cell *** blockade appears to alleviate lymphopenia-induced prolif

关键词： Autologous hematopoietic stem cell transplantation(AHSCT) CD25 CD122 Eomesodermin(EOMES) Homeostatic proliferation

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MCP-1 and IL-4 encapsulated hydrogel particles with macrophages enrichment and polarization capabilities for systemic lupus erythematosus treatment

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Nano Research 2024年第9期17卷 8316-8324页

作者： Shengjie Zhu Danqing Huang Qichen Luan Yang Li Jingjing Gan Yuanjin Zhao Lingyun Sun department of Rheumatology and immunology Nanjing Drum Tower HospitalClinical Medical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing 210096China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China

Macrophages play a pivotal role in systemic lupus erythematosus(SLE)*** have been made to develop multifunctional drug delivery systems capable of directing macrophage ***,we present a novel hyaluronic acid methacrylate(HAMA)hydrogel microparticle encapsulating multiple cytokines for SLE remission though enhancing macrophage *** HAMA microparticles loaded with monocyte chemotactic protein-1(MCP-1)and interleukin-4(IL-4)were fabricated by using a microfluidic *** released MCP-1 facilitates the aggregation of inflammatory macrophages,after which IL-4 induces the macrophage phenotype shift from inflammatory M1 to immune-protective M2,thus restoring immune *** have demonstrated in MRL/lpr mice that the hydrogel microparticles could improve their efficacy of intraperitoneal drug delivery,modulate immune function,and attenuate the disease *** results suggest that our proposed microparticles delivery platform has potential clinical value for treating autoimmune diseases.

关键词： microfluidics M2 polarization hydrogel drug delivery systemic lupus erythematosus(SLE)

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Traditional Chinese medicine Integrated Responsive Microneedles for Systemic Sclerosis Treatment

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Research 2024年第1期2023卷 139-147页

作者： Xi Luan Xiaoxuan Zhang Min Nie Yuanjin Zhao department of Rheumatology and immunology Nanjing Drum Tower HospitalSchool of PharmacyClinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China

Traditional Chinese medicine,such as Tripterygium wilfordii and Paeonia lactiflora,has potential values in treating systemic sclerosis(SSc)and other autoimmune diseases,while their toxic side effect elimination and precise tropical drug delivery are still ***,we present multiple traditional Chinese medicine integrated photoresponsive black phosphorus(BP)microneedles(MNs)with the desired features for the SSc *** employing a template-assisted layer-by-layer curing method,such MNs with triptolide(TP)/paeoniflorin(Pae)needle tips and BP-hydrogel needle bottoms could be well *** combined administration of TP and Pae can not only provide anti-inflammatory,detoxification,and immunomodulatory effects to treat skin lesions in the early stage of SSc but also remarkably reduce the toxicity of single drug ***,the additive BPs possess good biocompatibility and near-infrared(NIR)responsiveness,imparting the MN photothermal-controlled drug release *** on these features,we have demonstrated that the traditional Chinese medicine integrated responsive MNs could effectively improve skin fibrosis and telangiectasia,reduce collagen deposition,and reduce epidermal thickness in the SSc mouse *** results indicated that the proposed Chinese medicine integrated responsive MNs had enormous potential in clinical therapy of SSc and other diseases.

关键词： needle precise template

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Enterogenic Stenotrophomonas maltophilia migrates to the mammary gland to induce mastitis by activating the calcium-ROS-AMPK-mTOR-autophagy pathway

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Journal of Animal Science and Biotechnology 2024年第1期15卷 236-252页

作者： Zhaoqi He Caijun Zhao Yuhong He Zhuoyu Liu Guyue Fan Kun Zhu Yiqi Wang Naisheng Zhang Yunhe Fu Xiaoyu Hu department of clinical Veterinary medicine College of Veterinary MedicineJilin UniversityChangchun 130062Jilin ProvinceChina

Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food *** previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in‘gastroenterogenic mastitis'.However,the mechanism has not been fully ***,we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows,and the abundance of Stenotrophomonas maltophilia(***)was significantly increased in both the rumen and milk ***,we hypothesized that‘gastroenterogenic mastitis'can be induced by the migration of endogenous gut bacteria to the mammary ***,this study investigated the mechanism by which enterogenic *** induces *** First,*** was labelled with superfolder GFP and administered to mice via *** results showed that treatment with *** promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier,leading to intestinal inflammation and intestinal ***,tracking of ingested *** revealed that *** could migrate from the gut to the mammary gland and induce ***,mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with ***,using mouse mammary epithelial cells(MMECs),we verified that *** induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy *** In conclusion,the results showed that enterogenic *** could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce *** the gut-mammary gland axis may also be an effective method to treat mastitis.

关键词： Calcium-ROS-AMPK-mTOR-autophagy pathway Gut-mammary axis Mastitis S.maltophilia

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SARS-CoV-2 and innate immunity:the good,the bad,and the"goldilocks"

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Cellular & Molecular immunology 2024年第2期21卷 171-183页

作者： Benjamin L.Sievers Mark T.K.Cheng Kata Csiba Bo Meng Ravindra K.Gupta department of medicine University of CambridgeCambridgeUK Cambridge Institute of Therapeutic immunology&Infectious Disease(CITID) Department of MedicineUniversity of CambridgeCambridgeUk

An ancient conflict between hosts and pathogens has driven the innate and adaptive arms of *** about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that can be leveraged *** humoral response to SARS-CoV-2 infection has been the focus of intense research,and the role of the innate immune system has received significantly less ***,we review current knowledge of the innate immune response to SARS-CoV-2 infection and the various means SARS-CoV-2 employs to evade innate defense *** also consider the role of innate immunity in SARS-CoV-2 vaccines and in the phenomenon of long COVID.

关键词： SARS-CoV-2 Innate immune response Interferon Cytokines Inflammation Antiviral targets

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Therapeutic Role of Chinese medicine Targeting Nrf2/HO-1 Signaling Pathway in Myocardial Ischemia/Reperfusion Injury

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Chinese Journal of Integrative medicine 2024年第10期30卷 949-960页

作者： LIU Chang-xing GUO Xin-yi ZHOU Ya-bin WANG He First clinical Medical School Heilongjiang University of Chinese Medicine clinical Medical School Chengdu University of Traditional Chinese Medicine department of Cardiology the First Affiliated Hospital of Heilongjiang University of Chinese Medicine

Acute myocardial infarction(AMI), characterized by high incidence and mortality rates, poses a significant public health threat. Reperfusion therapy, though the preferred treatment for AMI, often exacerbates cardiac damage, leading to myocardial ischemia/reperfusion injury(MI/RI). Consequently, the development of strategies to reduce MI/RI is an urgent priority in cardiovascular therapy. Chinese medicine, recognized for its multi-component, multi-pathway, and multi-target capabilities, provides a novel approach for alleviating MI/RI. A key area of interest is the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway. This pathway is instrumental in regulating inflammatory responses, oxidative stress, apoptosis, endoplasmic reticulum stress, and ferroptosis in MI/RI. This paper presents a comprehensive overview of the Nrf2/HO-1 signaling pathway's structure and its influence on MI/RI. Additionally, it reviews the latest research on leveraging Chinese medicine to modulate the Nrf2/HO-1 pathway in MI/RI treatment.

关键词： Chinese medicine mechanisms myocardial ischemia/reperfusion injury nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway

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ROS-induced metabolic reprogramming to one-carbon metabolism and S-adenosylmethionine-mediated epigenetic modification in IL-10-producing B cells for the resolution of pneumonia

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Cellular & Molecular immunology 2024年第2期21卷 203-204页

作者： Sujin Lee Tae Jin Kim department of immunology Sungkyunkwan University School of MedicineSuwon16419Republic of Korea

B cells have an essential immunoregulatory function,which is mediated by the secretion of IL-10 and TGFβand interaction with activated CD4^(+)T *** antibody-independent function of B cells contributes to ameliorating autoimmune diseases or infection-induced tissue *** this Cellular and Molecular immunology issue,Fu et *** that regulatory B(Breg)cells play a critical role in resolving Pseudomonas aeruginosa-induced pneumonia[1].

关键词： metabolism pneumonia immunology

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Emerging role of galectin 3 in neuroinflammation and neurodegeneration

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Neural Regeneration Research 2024年第9期19卷 2004-2009页

作者： Brian M.Lozinski Khanh Ta Yifei Dong department of clinical Neuroscience University of CalgaryCalgaryABCanada Deparment of Biochemistry Microbiology&ImmunologyUniversity of SaskatchewanSaskatoonSKCanada

Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological ***,the mechanisms modulating these processes in different diseases remain incompletely *** in single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 that is associated with neuroinflammation and neurodegeneration in the central nervous system(CNS).Lgals3 encodes galectin-3(Gal3),aβ-galactoside and glycan binding glycoprotein that is frequently upregulated by reactive microglia/macrophages in the CNS during various neurological *** Gal3 has previously been associated with non-CNS inflammatory and fibrotic diseases,recent studies highlight Gal3 as a prominent regulator of inflammation and neuroaxonal damage in the CNS during diseases such as multiple sclerosis,Alzheimer’s disease,and Parkinson’s *** this review,we summarize the pleiotropic functions of Gal3 and discuss evidence that demonstrates its detrimental role in neuroinflammation and neurodegeneration during different neurological *** also consider the challenges of translating preclinical observations into targeting Gal3 in the human CNS.

关键词： Alzheimer’s disease Galectin 3 microglia multiple sclerosis neurodegeneration neuroinflammation Parkinson’s disease therapeutics

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