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The role of inflammasomes in human diseases and their potential as therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 479-508页

作者： Jing Yao Keenan Sterling Zhe Wang Yun Zhang Weihong Song The National Clinical Research Center for Geriatric disease Xuanwu HospitalCapital Medical UniversityBeijing 100053China Townsend Family laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Key laboratory of Neurodegenerative diseases Ministry of EducationBeijingP.R.China Zhejiang Clinical Research Center for Mental Disorders Key Laboratory of Alzheimer’s Disease of Zhejiang ProvinceSchool of Mental Health and The Affiliated Kangning HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325000China Oujiang laboratory(Zhejiang lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325000China

Inflammasomes are large protein complexes that play a major role in sensing inflammatory signals and triggering the innate immune *** inflammasome complex has three major components:an upstream sensor molecule that is connected to a downstream effector protein such as caspase-1 through the adapter protein *** formation typically occurs in response to infectious agents or cellular *** active inflammasome then triggers caspase-1 activation,followed by the secretion of pro-inflammatory cytokines and pyroptotic cell *** inflammasome activation and activity contribute to the development of diabetes,cancer,and several cardiovascular and neurodegenerative *** a result,recent research has increasingly focused on investigating the mechanisms that regulate inflammasome assembly and activation,as well as the potential of targeting inflammasomes to treat various *** clinical trials are currently underway to evaluate the therapeutic potential of several distinct inflammasome-targeting ***,understanding how different inflammasomes contribute to disease pathology may have significant implications for developing novel therapeutic *** this article,we provide a summary of the biological and pathological roles of inflammasomes in health and *** also highlight key evidence that suggests targeting inflammasomes could be a novel strategy for developing new disease-modifying therapies that may be effective in several conditions.

关键词： inflam therapeutic potential

Size-dependent macrophage-targeting of mannose-modified rosiglitazone liposomes to alleviate inflammatory bowel disease

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Chinese Chemical Letters 2024年第1期35卷 385-391页

作者： Erjin Wang Run Han Mingyue Wu Yuan He Yaxin Cheng Jiahong Lu Ying Zheng State Key laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Department of Pharmacy Xuzhou Medical UniversityXuzhou 221004China Faculty of Health Sciences University of MacaoMacao 999078China Guangdong-Hong Kong-Macao Joint lab on Chinese Medicine and Immune disease Research University of MacaoMacao 999078China

inflammatory bowel disease (IBD) is a refractory chronic intestinal inflammatory disease caused by a malfunction of immune system. As the key immune cells in the intestine, macrophages play an important role in maintaining intestinal homeostasis and tissue repair of the IBD. Pharmacological modulation of macrophage function exhibits the promising therapeutic effect for IBD. In this study, mannose-modified liposomes (MAN-LPs) are prepared for macrophage targeting to improve therapeutic efficiency. Rosiglitazone (ROSI) as an agonist of peroxisome proliferators-activated receptor γ (PPAR-γ) is used as the model drug to fabricate different sized liposomes. The impacts of mannose modification and particle size for macrophage targeting are investigated in cells, zebrafish, and mouse models and the therapeutic effects of the MAN-LPs are evaluated on dextran sulfate sodium (DSS)-induced IBD mouse. Compared to unmodified liposome, MAN-LPs display higher uptake by RAW 264.7 cells and better co-localization with macrophage in zebrafish model. Furthermore, MAN-LPs could effectively accumulate in the inflammatory intestinal sites in IBD mouse model. Most importantly, the targeting ability of MAN-LPs is obviously enhanced with the increasing of particle size, whereas the largest MAN-LPs particles achieve the best anti-inflammatory effect in cells, and a higher therapeutic efficiency in IBD mouse model. Therefore, mannose-modified liposome is a promising strategy for macrophage-targeting in IBD treatment. Particle size of MAN-LPs will affect macrophage targeting ability, as well as the therapeutic effect in-vivo.

关键词： Macrophage targeting Liposome Mannose Particle size inflammatory bowel disease

Oncostatin M:a love-hate relationship in neuroinflammation

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Neural Regeneration Research 2024年第12期19卷 2571-2572页

作者： Doryssa Hermans Niels Hellings Bieke Broux University MS Center Campus DiepenbeekDiepenbeekBelgium Neuro-Immune Connections and Repair lab Department of Immunology and InfectionBiomedical Research InstituteHasselt UniversityDiepenbeekBelgium

Oncostatin M and multiple sclerosis:Every 5minutes,someone in the world is diagnosed with multiple sclerosis(MS),a chronic inflammatory and degenerative disease of the central nervous system(CNS).MS appears in unpredictable episodes of symptoms,which are highly patient-dependent,but often include visual impairment,muscle weakness/spasms,fatigue,cognitive difficulties,and *** sexual dysfunction.

关键词： visual bladder someone

Heat-killed Lactobacillus paracasei JY56 can relieve ovalbumin-induced food allergy via regulating immuno-inflammatory responses and gut microbiota

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Food Science and Human Wellness 2024年

作者： Miao Zheng Ming Ma Ruxue Fang Yilin Sun Xinyan Yang Chaoxin Man Qianyu Zhao Yujun Jiang Key lab of Dairy Science Ministry of Education College of Food Science Northeast Agricultural University

Food allergy (FA) is an aberrant immune response triggered by the ingestion of a food antigen. Ovalbumin (OVA)-sensitized and challenged BALB/c mice were orally administered heat-killed (HK)-L. paracasei JY56. In this work， HK-L. paracasei JY56 alleviated the FA-induced decrease in body weight and rectal temperature and reduced the allergy score. Serum analysis showed that HK-L. paracasei JY56 reduced the levels of specific antibodies (OVA-sIgE and OVA-sIgG) and allergic mediators (histamine and mast cell protease) in FA mice. In addition， HK-L. paracasei JY56 also could alleviate OVA-induced FA by suppressing Th2 and Th17-type immune responses， which was evidenced by the regulation of splenic lymphocyte subpopulations and associated cytokine secretion. Moreover， jejunal histological analysis and intestinal barrier function related gene expression measurement were performed to verify the intestinal barrier repair of HK-L. paracasei JY56. Meanwhile， the TLR4/NF-κB inflammatory pathway activation was inhibited by HK-L. paracasei JY56 at gene and protein levels. Finally， HK-L. paracasei JY56 was performed to modulate the gut microbiota structure and increase the levels of short-chain fatty acids. In conclusion， HK-L. paracasei JY56 could alleviate OVA-induced FA in multiple ways， and this study provides a theoretical basis for the application of inactivated probiotics in functional foods for FA.

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Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair

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Chinese Journal of Integrative Medicine 2024年第3期30卷 243-250页

作者： XU Han XU Si-cong LI Li-yan WU Yu-huang TAN Yin-feng CHEN Long LIU Pei LIANG Chang-fu HE Xiao-ning LI Yong-hui Hainan Provincial Key lab of Research&Development on Tropic Herbs Hainan Medical UniversityHaikou571199China Department of Stomatology the Second Affiliated Hospital of Hainan Medical UniversityHaikou571199China

Objective:To investigate the effects of Danmu Extract Syrup(DMS) on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice and explore the ***:Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table(n=12),including control(normal saline),LPS(5 mg/kg),LPS+DMS 2.5 mL/kg,LPS+DMS 5 mL/kg,LPS+DMS 10 mL/kg,and LPS+Dexamethasone(DXM,5 mg/kg) *** pretreatment with DMS and DXM,the ALI mice model was induced by LPS,and the bronchoalveolar lavage fluid(BALF) were collected to determine protein concentration,cell counts and inflammatory *** lung tissues of mice were stained with hematoxylin-eosin,and the wet/dry weight ratio(W/D) of lung tissue was *** levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-1βin BALF of mice were detected by enzyme linked immunosorbent *** expression levels of Claudin-5,vascular endothelial(VE)-cadherin,vascular endothelial growth factor(VEGF),phospho-protein kinase B(p-Akt) and Akt were detected by Western blot ***:DMS pre-treatment significantly ameliorated lung histopathological *** with the LPS group,the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment(P<0.05 or P<0.01).The number of cells in BALF and myeloperoxidase(MPO) activity decreased significantly after DMS pretreatment(P<0.05 or P<0.01).DMS pre-treatment decreased the levels of TNF-α,IL-6 and IL-1β(P<0.01).Meanwhile,DMS activated the phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) pathway and reversed the expressions of Claudin-5,VE-cadherin and VEGF(P<0.01).Conclusions:DMS attenuated LPS-induced ALI in mice through repairing endothelial *** might be a potential therapeutic drug for LPS-induced lung injury.

关键词： Danmu Extract Syrup acute lung injury inflammatory factors vascular endothelial growth factor phosphoinositide 3-kinase/protein kinase B Chinese medicine Nauclea officinalis

Mogroside IIE,an in vivo metabolite of sweet agent,alleviates acute lung injury via Pla2g2a-EGFR inhibition

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Food Science and Human Wellness 2024年第1期13卷 299-312页

作者： Weichao Lü Guoqing Ren Kuniyoshi Shimizu Renshi Li Chaofeng Zhang State Key laboratory of Natural Medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 211198China Sino-Jan Joint lab of Natural Health Products Research School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 211198China Faculty of Agriculture Kyushu UniversityFukuoka 819-0395Japan

In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious *** IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia *** study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury(ALI).A lipopolysaccharide(LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting,co-immunoprecipitation,and quantitative real time-PCR *** results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA(Pla2g2a)-epidermal growth factor receptor(EGFR).The interaction of Pla2g2a and EGFR was identified by *** addition,M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and m TOR via the inhibition of ***2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury,which may represent a promising strategy to treat ALI.

关键词： Mogroside IIE Acute lung injury Secreted phospholipase A2 type IIA(Pla2g2a) Epidermal growth factor receptor(EGFR)

Foeniculum vulgare *** lipopolysaccharide-induced microglia activation and ameliorates neuroinflammation-mediated behavioral deficits in mice

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Asian Pacific Journal of Tropical Biomedicine 2024年第1期14卷 28-39页

作者： Sushruta Koppula Ramesh Alluri Spandana Rajendra Kopalli College of Biomedical and Health Sciences Konkuk UniversityChungju-SiChungcheongbuk Do27478Republic of Korea Cognitive Science Research Initiative lab Department of PharmacologyVishnu Institute of Pharmaceutical Education and ResearchNarsapurTelangana502313India Department of Bioscience and Biotechnology Sejong UniversityGwangjin-guSeoul 05006Republic of Korea

Objective:To investigate the effect of Foeniculum vulgare extract against lipopolysaccharide(LPS)-induced microglial activation in vitro as well as cognitive behavioral deficits in ***:LPS-activated BV-2 cell viability was measured using MTT assay and reactive oxygen species(ROS)was studied using DCF-DA *** antioxidative enzymes and pro-inflammatory mediators were analyzed using respective ELISA kits and Western *** in vivo testing,LPS(1 mg/kg,i.p.)was given daily for five days in male Swiss albino mice to produce chronic *** and behavioral tests were performed using open-field,passive avoidance,and rotarod experiments in LPS-induced ***:Foeniculum vulgare extract(25,50 and 100μg/mL)significantly attenuated the LPS-activated increase in nitric oxide(NO),ROS,cyclooxygenase-2,inducible NO synthase,IL-6,and TNF-alpha(Pinflammatory responses in BV-2 microglial cells and improve cognitive and locomotor performance in LPS-administered mice.

关键词： Foeniculum vulgare Microglia Lipopolysaccharide Antioxidant Neuroinflammation MAPK signaling Cognition

Pneumocystis jiroveci pneumonia after total hip arthroplasty in a dermatomyositis patient:A case report

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World Journal of Clinical Cases 2022年第10期10卷 3313-3320页

作者： Mao Hong Zi-Yu Zhang Xiao-Wei Sun Wei-Guo Wang Qi-Dong Zhang Wan-Shou Guo Beijing University of Chinese Medicine Beijing 100029China Department of Orthopaedic Surgery Beijing Key Lab Immune-Mediated Inflammatory DiseasesChina-Japan Friendship HospitalBeijing 100029China Graduate School of Peking Union Medical College Chinese Academy of Medical SciencesBeijing 100029China

BACKGROUND Pneumocystis jiroveci pneumonia(PJP)is a serious opportunistic infection that occurs mostly in patients with immunodeficiency and long-term immunosuppressive *** non-human immunodeficiency virus-infected patients,the most important risk factor for PJP is the use of glucocorticoids in combination with other immunosuppressive *** management of glucocorticoids during the perioperative period in patients with dermatomyositis requires special *** SUMMARY We report a case of PJP in the perioperative period.A 61-year-old woman with a history of anti-melanoma differentiation-associated gene 5(MDA5)-positive dermatomyositis and interstitial pneumonia was administered with long-term oral methylprednisolone and *** patient underwent right total hip arthroplasty in the orthopaedic department for bilateral osteonecrosis of the femoral *** was given intravenous drip hydrocortisone before anesthesia and on the first day after surgery and resumed oral methylprednisolone on the second postoperative *** the fifth day after surgery,the patient suddenly developed *** computed tomography scan showed diffuse grid shadows and ground glass shadows in both *** chain reaction testing of bronchoalveolar lavage fluid was positive for Pneumocystis *** patient was eventually diagnosed with PJP and was administered with oral *** the 6-mo review,there was no recurrence or *** Continued perioperative glucocorticoid use in patients with anti-MDA5-positive dermatomyositis may increase the risk of PJP.

关键词： Pneumocystis jiroveci pneumonia Glucocorticoids Perioperative period Dermatomyositis Hypothalamic-pituitary-adrenal axis Case report

Protective Effect of Tangshen Formula on Interstitial Cells of Cajal in Colon of Diabetic Rats

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Chinese Journal of Integrative Medicine 2022年第1期28卷 43-51页

作者： CHEN Peng-min ZHAO Jing-bo YANG Xin LI Jing ZHANG Hao-jun ZHANG Hui-cun ZHANG Yu-ting LI Ping Beijing Key lab Immune-Mediated inflammatory diseases Institute of Clinical Medical SciencesChina-Japan Friendship HospitalBeijing(100029)China Department of Clinical Medicine Aarhus UniversityAarhus(8200)Denmark Department of Combination of Traditional Chinese and Western Medicine Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing(100010)China

Objective:To explore the effect of Tangshen Formula(TSF),a Chinese herbal medicine,on interstitial cells of Cajal(ICC)in the colon of diabetic ***:Fifty-four male Wistar rats were randomly divided into normal control(NC,n=14)and high-fat diet(HFD)groups(n=40).After 6 weeks,the rats in the HFD group were injected intraperitoneally streptozotocin once(30 mg/kg).Thirty rats with fasting blood glucose higher than 11.7 mmol/L were randomly divided into diabetes(DM)and TSF groups,15 rats in each *** in the NC and DM groups were intragastrically administered with saline,and those in the TSF group were given with TSF(2.4 g/kg)once daily for 20 *** levels of Bax,Bcl-2,and caspase-3 in colonic smooth muscle layer were measured by Western blotting and immunohistochemical *** number of ICC was determined by immunohistochemical *** was used for analyzing the ratio of classically activated macrophages(M1)and alternatively activated macrophages(M2)to total *** microscopy was used to observe the epithelial ultrastructure and ***:TSF appeared to partially prevented loss of ICC in DM rats(P<0.05).Compared with the NC group,expression levels of Bcl-2,Bax,caspase-3,and TNF-αas well as the ratio of M1 to total macrophages increased in DM rats(all P<0.05),and the ratio of M2 to total macrophages decreased(P<0.05 or P<0.01).Compared with the DM group,TSF decreased the expression levels of abovementioned proteins and restore M2 to total macrophages ratio(P<0.05 or P<0.01).TSF appeared to attenuate the ultrastructural changes of epithelia and improve the tight and desmosome junctions between epithelia reduced in the DM ***:Reduced number of ICC in DM rats may be associated with damage of the intestinal *** protective effects of TSF on ICC may be through repair of the epithelial junctions,which attenuates inflammation and inflammation-initiated apoptosis in colon of DM rats.

关键词： diabetes interstitial cells of Cajal tight junction intestinal epithelia macrophage Tangshen Formula