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Nano Research 2024年第3期17卷 1818-1826页

作者： Kun Chen Shengqiu Liu Yujun Wei South China Advanced Institute for Soft Matter Science and Technology School of Emergent Soft MatterSouth China University of TechnologyGuangzhou 510641China Guangdong Provincial Key Laboratory of Technique and Equipment for Macromolecular Advanced Manufacturing South China University of TechnologyGuangzhou 510641China Guangdong Provincial Key Laboratory of Functional and Intelligent Hybrid Materials and Devices South China University of TechnologyGuangzhou 510641China

Obesity is closely related with insulin resistance and chronic ***,we report that unsaturated lipid-modified polyoxovanadates(ULPOVs)can restrict weight gain of diet-induced obese mice and improve their glycemic control and obesity-associated *** administration of the sub-nanosized ULPOVs at a low dosage for 7 weeks reduces the body weight and almost normalizes the blood glucose levels of obese mice fed on a high-fat *** treatment increases the activity of the nuclear receptor peroxisome proliferator-activated receptorγ(PPARγ)and reduces intestinal caloric intake,which may be the main reason for blood sugar and body weight *** addition to insulin-sensitizing,PPARγactivation induced by ULPOV treatment in obese mice with atopic dermatitis(AD)promotes the type 2 T helper(TH_(2))cell selective responses and therapeutic effects on immune dysregulation caused by *** data suggest sub-nanosized polyoxovanadate clusters as a class of potential candidates to relieve symptoms accompanied by diet-induced obesity.

关键词： polyoxovanadates lipid modification glucose homeostasis obesity inflammatory disease peroxisome proliferator-activated receptorγ(PPARγ)

Interleukin-6 as a Therapeutic Target on inflammatory disease and Castleman's disease

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Interleukin-6 as a Therapeutic Target on inflammatory diseas...

Self-therapeutic metal-based nanoparticles for treating inflammatory diseases

第十一届全国免疫学学术大会

作者： Wang Yue Yu Bo Logistics College of Chinese People’s Armed Police Forces

Objective: Human Interleukin-6(IL-6) is a cytokine produced by many cell types, including stromal cells, hematopoietic cells, epithelial cells, or muscle cells, that has pleiotropic effects. IL-6 acts through a hexametric receptor, which contains the ligand-binding IL-6 receptor α chain and the common cytokine receptor signal-transducing subunit gp130. The binding of IL-6 to gp130 activates multiple signal transduction pathways such as JAK/STATs, MEK/ERK and PI3K/Akt pathways. Methods: Anti-IL-6 therapy reduces inflammation, hepatic acute phase proteins, and anemia and has antiangiogenic effects. Castleman disease is a lymphoproliferative disease characterized by benign hyperplastic lymph nodes, follicular hyperplasia with polyclonal plasmablastic proliferation and capillary proliferation associated with vascular hyperplasia and high IL-6 activity, mainly due to viral IL-6. Results: Blocking IL-6 has demonstrated therapeutic efficacy with drug registration in Castleman disease and inflammatory disease such as rheumatoid arthritis or Crohn disease without major toxicity. Interestingly, the inhibition of C-reactive protein(CRP) production is a trustworthy surrogate marker of anti-IL-6 therapy efficacy. Clinically registered IL-6 inhibitors include siltuximab, an anti-IL-6 m Ab, and tocilizumab, an anti-IL-6 receptor m Ab. Sirukumab, a humanized antiIL-6 m Ab, has been assayed in healthy subjects to determine PK/PD and safety. Sant7, a potent antagonist of the IL-6 receptor, was engineered through targeted amino acid substitutions in key residues of the human IL-6 molecule. Conclusion: Anti-IL-6 theraprutics are able to neutralize IL-6 production in vivo and are safe and useful in inflammatory disease and Castleman disease.

关键词： IL-6 inflammatory disease Castleman disease

来源： cnki会议评论

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Acta Pharmaceutica Sinica B 2023年第5期13卷 1847-1865页

作者： Ruifang Han Yu Xiao Qianqian Bai Chung Hang Jonathan Choi Department of Biomedical Engineering the Chinese University of Hong KongShatinNew TerritoriesHong Kong SARChina

inflammatory diseases are key contributors to high mortality globally and adversely affect the quality of *** treatments include corticosteroids or nonsteroidal anti-inflammatories that may cause systemic toxicity and biologics that may increase the risk of *** nanoparticles that bear not only the drug payload but also targeting ligands for delivery to inflammation sites at lowered systemic toxicity are established in the nanomedicine field,but their relatively large size often leads to systemic ***-based nanoparticles with intrinsic anti-inflammatory properties represent attractive *** are not only designed to be compact for crossing biological barriers(with the nanoparticle serving as a dual carrier and drug),but also support label-free tracking of their interactions with *** review commences with an outline of the common inflammatory diseases,inflammatory pathways involved,and conventional drug-loaded nanoparticles for ***,the review features the emerging applications of self-therapeutic metal-based nanoparticles(e.g.,gold,coper oxide,platinum,ceria,and zinc oxide)for managing inflammatory diseases in animals over the past three years,focusing on therapeutic outcomes and anti-inflammatory *** review concludes with an outlook on the biodistribution,long-term toxicity,and clinical translation of self-therapeutic metalbased nanoparticles.

关键词： Metal-based nanoparticles inflammatory disease Self-therapeutic Nanomedicine Delivery Gold nanoparticles Clinical translation Reactive oxygen species

Latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases

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Genes & diseases 2022年第5期9卷 1194-1207页

作者： XiaoYi He Stephanie Tan Zhong Shao Xiao Wang Department of Neurology Affiliated Zhongshan Hospital of Dalian UniversityDalianLiaoning 116001PR China The Third Hospital of Fushun FushunLiaoning 113004PR China Stanley Manne Children’s Research Institute Ann&Robert H.Lurie Children’s Hospital of ChicagoChicagoIL 60611USA Department of Pediatrics Feinberg School of MedicineNorthwestern UniversityChicagoIL 60611USA

Macrophages are dominant innate immune *** demonstrate remarkable het-erogeneity and plasticity that are essential for homeostasis and host *** heterogeneity of tissue macrophages is shaped by the ontogeny,tissue factors,and environmental signals,a pattern in a tissue-associated latitudinal *** the same time,macrophages have long been considered as mainly plastic *** cells respond to stimulation quickly and in a stimulus-specific way by utilizing a longitudinal cascaded activation,including coordination of signal trans-ducer,epigenetic elements,and transcription factors,conclusively determine the macrophage phenotypes and *** the development of cutting-edge technologies,such as fate-mapping,single-cell transcriptomics,ipsc platform,nanotherapeutic materials,etc.,our under-standing of macrophage biology and the roles in the pathogenesis of diseases is much *** review summarizes recent progress on the latitudinal and longitudinal regulation of tissue macrophages in inflammatory *** latitudinal regulation covers the tissue macrophage or-igins,tissue factors,and environmental signals,reflecting the macrophage *** lon-gitudinal regulation focuses on how multiple factors shape the phenotypes and functions of macrophage subsets to gain plasticity in inflammatory diseases(i.e.,inflammatory bowel disease).In addition,how to target macrophages as a potential therapeutic approach and cutting edge-technologies for tissue macrophage study are also discussed in this review.

关键词： Epigenetic regulation inflammatory disease microRNA Macrophage origin Macrophage polarization Single-cell RNA-sequencing Tissue macrophage

The Effect of FOXP3^(+) Regulatory T Cells on Infectious and inflammatory diseases

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Infectious Microbes & diseases 2021年第4期3卷 187-197页

作者： Yakun Bai Fang Gao Dan Li Suyuan Ji Shuijun Zhang Wenzhi Guo Bin Li Zhengzhou Engineering Laboratory of Organ Transplantation Technique and Application ZhengzhouHenanChina Henan Engineering Technology Research Center of Organ Transplantation ZhengzhouHenanChina Department of Hepatobiliary and Pancreatic Surgery the First Affiliated Hospital of ZhengzhouZhengzhouHenanChina Shanghai Institute of Immunology Department of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghaiChina Binzhou People’s Hospital Health Management Center BinzhouShandongChina.

CD4^(+)CD25^(+)FOXP3^(+)regulatory T cells(Tregs)contribute to the maintenance of immune homeostasis and tolerance in the *** expression levels and functional stability of FOXP3 control the function and plasticity of *** critically impact infectious diseases,especially by regulating the threshold of immune responses to pathogenic *** functional regulatory mechanism and cell-specific surface markers of Tregs in different tissues and inflammatory microenvironments have been investigated in depth,which can provide novel ideas and strategies for immunotherapies targeting infectious diseases.

关键词： FOXP3 infection inflammatory disease regulatory T cells

Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases

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Journal of Pharmaceutical Analysis 2023年第6期13卷 545-562页

作者： Jiuping Zeng Mingxing Li Qianyun Zhao Meijuan Chen Long Zhao Shulin Wei Huan Yang Yueshui Zhao Anqi Wang Jing Shen Fukuan Du Yu Chen Shuai Deng Fang Wang Zhuo Zhang Zhi Li Tiangang Wang Shengpeng Wang Zhangang Xiao Xu Wu Laboratory of Molecular Pharmacology Department of PharmacologySchool of PharmacySouthwest Medical UniversityLuzhouSichuan646000China Cell Therapy&Cell Drugs of Luzhou Key Laboratory LuzhouSichuan646000China South Sichuan Institute of Translational Medicine LuzhouSichuan646000China Department of Spleen and Stomach diseases The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical UniversityLuzhouSichuan646000China School of Medicine Chengdu UniversityChengdu610106China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao999078China Department of Oncology The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan646000China

As a ligand-dependent transcription factor,retinoid-associated orphan receptor gt(RORγt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune *** emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 *** RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric-or allosteric-binding sites in the ligand-binding *** of small-molecule inhibitors have entered clinical ***,in current review,the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was ***,the recently developed RORγt inhibitors were summarized,with an emphasis on their optimization from lead compounds,efficacy,toxicity,mechanisms of action,and clinical *** limitations of current development in this area were also discussed to facilitate future research.

关键词： T helper 17 RORγt Small-molecule inhibitor inflammatory disease Autoimmune disease

Extracellular vesicle activities regulating macrophage- and tissue-mediated injury and repair responses

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Acta Pharmaceutica Sinica B 2021年第6期11卷 1493-1512页

作者： Qian Hu Christopher J.Lyon Jesse K.Fletcher Wenfu Tang Meihua Wan Tony Y.Hu Department of Integrated Traditional Chinese and Western Medicine West China HospitalSichuan UniversityChengdu 610041China Center of Cellular and Molecular Diagnosis Tulane University School of MedicineNew OrleansLA 70112USA Department of Biochemistry&Molecular Biology Tulane University School of MedicineNew OrleansLA 70112USA

Macrophages are typically identified as classically activated(M1) macrophages and alternatively activated(M2) macrophages,which respectively exhibit pro-and anti-inflammatory phenotypes,and the balance between these two subtypes plays a critical role in the regulation of tissue inflammation,injury,and repair *** studies indicate that tissue cells and macrophages interact via the release of small extracellular vesicles(EVs) in processes where EVs released by stressed tissue cells can promote the activation and polarization of adjacent macrophages which can in turn release EVs and factors that can promote cell stress and tissue inflammation and injury and vice *** review discusses the roles of such EVs in resulating such interactions to influence tissue inflammation and injury in a number of acute and chronic inflammatory disease conditions,and the potential applications,advantage and concerns for using EV-based therapeutic approaches to treat such conditions,including their potential role of drug carriers for the treatment of infectious diseases.

关键词： Extracellular vesicles Macrophage Tissue injury inflammatory disease Interaction loop Stem cell Sepsis Targeted therapy

Periodontal disease and risk of benign prostate hyperplasia: a cross-sectional study

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Military Medical Research 2020年第2期7卷 157-165页

作者： Lan Wu Bing-Hui Li Yun-Yun Wang Chao-Yang Wang Hao Zi Hong Weng Qiao Huang You-Jia Zhu Xian-Tao Zeng Center for Evidence-Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China department of Stomatology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Evidence-Based Medicine Institute of Evidence-Based Medicine and Knowledge TranslationHenan UniversityKaifeng 475000China Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China

Background:Both periodontal disease and benign prostatic hyperplasia are age-related diseases that affect millions of people ***,this study aimed to investigate the association between periodontal disease and the risk of benign prostatic ***:A total of 4930 participants were selected from an available health examination that was carried out in 2017,only males were considered for further *** eligible males were divided into benign prostatic hyperplasia and normal groups,the benign prostatic hyperplasia group was then divided into prostate volume≤60 g and>60 g subgroups;all their periodontal status was extracted and then into normal(CPI score of 0),periodontal disease(CPI score between 1 and 4),and periodontitis(CPI score between 3 and 4)*** correlation between periodontal disease and benign prostatic hyperplasia was investigated using logistic regression analyses and greedy matching case-control *** analysis based on prostate volume was also *** analyses were conducted with SAS 9.4 ***:A total of 2171 males were selected for this *** presence of periodontal disease significantly increased the risk of benign prostatic hyperplasia by 1.68 times(OR=1.68,95%CI:1.26–2.24),and individuals with periodontitis showed a higher risk(OR=4.18,95%CI:2.75–6.35).In addition,among matched cases and controls,this association remained robust(periodontal disease:OR=1.85,95%CI:1.30–2.64;periodontitis:OR=4.83,95%CI:2.57–9.07).Subgroup analysis revealed that periodontal disease significantly increased benign prostate hyperplasia risk as well(for prostate volume≤60 g:OR=1.64,95%CI:1.22–2.20;for volume>60 g:OR=2.17,95%CI:1.04–4.53),and there was a higher risk in the group with a prostate volume greater than 60 ***:Periodontal disease is significantly and positively associated with an increased risk of benign prostatic *** validation studies should be performed to explore the re

关键词： Benign prostate hyperplasia Periodontal disease Periodontitis Risk factor inflammatory disease

Pathologically triggered in situ aggregation of nanoparticles for inflammation-targeting amplification and therapeutic potentiation

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Acta Pharmaceutica Sinica B 2023年第1期13卷 390-409页

作者： Qiang Nie Chenwen Li Yu Wang Yi Hu Wendan Pu Qixiong Zhang Jiajun Cai Yongyao Lin Gang Li Chenping Wang Lanlan Li Yin Dou Jianxiang Zhang Department of Pharmaceutics College of PharmacyThird Military Medical University(Army Medical University)Chongqing 400038China Department of Radiology Chongqing University Cancer Hospital&Chongqing Cancer Institute&Chongqing Cancer HospitalChongqing 400030China State Key Lab of Trauma Burn and Combined InjuryInstitute of Combined InjuryThird Military Medical University(Army Medical University)Chongqing 400038China

Uncontrolled and persistent inflammation is closely related to numerous acute and chronic ***,effective targeting delivery systems remain to be developed for precision therapy of inflammatory *** we report a novel strategy for engineering inflammationaccumulation nanoparticles via phenolic *** phenol-functionalized nanoparticles were first developed,which can undergo in situ aggregation upon triggering by the inflammatory/oxidative *** compound-decorated poly(lactide-co-glycolide)nanoparticles,in particular tyramine(Tyr)-coated nanoparticles,showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis,acute liver injury,and acute lung injury,mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen *** combining a cyclodextrin-derived bioactive material with Tyr decoration,a multifunctional nanotherapy(TTN)was further developed,which displayed enhanced cellular uptake,antiinflammatory activities,and inflammatory tissue accumulation,thereby affording amplified therapeutic effects in mice with colitis or acute liver ***,TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration,leading to considerably potentiated in vivo *** studies also revealed good safety of orally delivered ***,Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.

关键词： inflammatory disease Reactive oxygen species Myeloperoxidase Targeted therapy Nanoparticles Surface engineering Triggerable aggregation Nanotherapy

Interplay between intestinal alkaline phosphatase, diet, gut microbes and immunity

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World Journal of Gastroenterology 2014年第42期20卷 15650-15656页

作者： Mehrbod Estaki Daniella DeCoffe Deanna L Gibson Department of Biology University of British Columbia Okanagan

Intestinal alkaline phosphatase (IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP’s role in the intestine is to dephosphorylate toxic microbial ligands such as lipopolysaccharides, unmethylated cytosine-guanosine dinucleotides and flagellin as well as extracellular nucleotides such as uridine diphosphate. IAP’s ability to detoxify these ligands is essential in protecting the host from sepsis during acute inflammation and chronic inflammatory conditions such as inflammatory bowel disease. Also important in these complications is IAP’s ability to regulate the microbial ecosystem by forming a complex relationship between microbiota, diet and the intestinal mucosal surface. Evidence reveals that diet alters IAP expression and activity and this in turn can influence the gut microbiota and homeostasis. IAP’s ability to maintain a healthy gastrointestinal tract has accelerated research on its potential use as a therapeutic agent against a multitude of diseases. Exogenous IAP has been shown to have beneficial effects when administered during ulcerative colitis, coronary bypass surgery and sepsis. There are currently a handful of human clinical trials underway investigating the effects of exogenous IAP during sepsis, rheumatoid arthritis and heart surgery. In light of these findings IAP has been marked as a novel agent to help treat a variety of other inflammatory and infectious diseases. The purpose of this review is to highlight the essential characteristics of IAP in protection and maintenance of intestinal homeostasis while addressing the intricate interplay between IAP, diet, microbiota and the intestinal epithelium.

关键词： Intestinal alkaline phosphatase Inflammation Infection Lipopolysaccharides inflammatory disease Intestinal microbiota Diet