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Chinese Chemical Letters 2023年第1期34卷 225-229页

作者： Kosheli Thapa Magar George Frimpong Boafo Makhloufi Zoulikha Xiaohong Jiang Xiaotong Li Qingqing Xiao Xuyang Xing Xiaochun Wang Lifang Fan Zhenfeng Wu Wei He School of Pharmacy China Pharmaceutical UniversityNanjing 211198China Jiangsu Aosaikang Pharmaceutical Co. Ltd.Nanjing 211112China Key Laboratory of Modern Preparation of TCM Ministry of EducationJiangxi University of Chinese MedicineNanchang 330004China

macrophages play a crucial role in initiating,maintaining,and resolving inflammation through the phenotypic shift,inducing or inhibiting the production of inflammatory cytokines.Therefore,macrophages are potential targets for treating inflammatory diseases.Andrographolide(AND)is a potent anti-inflammatory drug that can reduce pro-inflammatory cytokines and suppress NF-κB/MAPK pathway in activated macrophages.Although AND has many medicinal properties,its lower water solubility and first-pass effect in the liver have hindered its clinical application.In this context,by using a metal phenolic network as a stabilizer,we designed and prepared highly stabilized AND nanocrystals(AND-MPN Ns)with high drug loading capacity to facilitate the clinical application of AND.Our findings showed that AND-MPN Ns could be used to enhance the anti-inflammation in-vitro via macrophage polarization,reducing proinflammatory cytokines IL-6 and TNF-α,and suppressing the NF-κB signaling pathway activation.The results demonstrated the potential of AND-MPN Ns to combat inflammatory diseases effectively.

关键词： Inflammation macrophages Andrographolide Metal phenolic network Nanocrystals

Tumor-associated macrophages (TAMs) as biomarkers for gastric cancer:A review

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Chronic Diseases and Translational Medicine 2018年第3期4卷 156-163页

作者： Meri R.Raiha Pauli A.Puolakkainen Department of Surgery Helsinki University Hospital and University of HelsinkiHelsinki 00014Finland

Gastric adenocarcinoma is one of the most common types of cancer worldwide, with an incidence of a million new cases annually. In addition to having a high mortality rate due to often delayed detection and its poor response to cancer therapy, it also spreads aggressively. Inflammation has been shown to play a role in carcinogenesis. Consequently, macrophages are important in phagocytosis, antigen presenting and producing cytokines and growth factors. As a response to microenvironmental signals, they may polarize into tumor resisting M1 or tumor promoting M2 macrophages. Recently, studies have indicated that M2-type macrophage resembling tumor-associated macrophages (TAMs) might be used as an independent prognostic factor for gastric cancer. This review will discuss the possible use of TAMs as prognostic tools for gastric cancer and whether they are suitable for use in clinical environment.

关键词： Gastric cancer Tumor-associated macrophages Biomarkers Prognosis Diagnosis

Flavonoids from Scutellaria barbata inhibit activation of tumor-associated macrophages by blocking the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB signaling pathway

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Journal of Traditional Chinese Medicine 2019年第2期39卷 160-165页

作者： Bao Xiaoxia Li Liuye Xue Xiaoou Department of Gynecology Dongzhimen Hospital Beijing University of Chinese Medicine

OBJECTIVE: To determine the efficacy of Scutellaria barbata flavonoids and polysaccharides on Ishikawa endometrial carcinoma cells co-cultured with U937 macrophages.METHODS: The presence of CD163 and CD206 was determined by flow cytometry. Thiazolyl Blue Tetrazolium Bromide assays were used to assess the proliferation effect of tumor-associated macrophages(TAMs) on Ishikawa cells. The secretion of interleukin(IL)-10 in the co-culture conditioned media was examined using an enzyme-linked immunosorbent assay. The protein expression levels of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88) and nuclear factor(NF)-κB p65 were detected by Western blot. The mRNA expression levels of TLR4 and MyD88 were analyzed by real-time polymerase chain reaction(PCR). The expression levels of IL-12, IL-1β and tumor necrosis factor-α(TNF-α) were evaluated with real-time PCR.RESULTS: Compared with the U937 control group,the expression levels of CD163 and CD206 in the TAM group were higher(P < 0.05). TAMs co-cultured with Ishikawa cells for 24 or 48 h showed higher proliferation rates(P < 0.05). The expression levels of IL-12 decreased than compared with those in the U937 untreated group(P <0.05) and those of the Scutellaria barbata flavonoids group(P < 0.05). The expression levels of CD206, CD163, IL-10, IL-1β and TNF-α, NF-κB p65 and TLR4/MyD88 in the TAMs control group were greater than those in the U937 untreated group(P < 0.05) and those of the Scutellaria barbata flavonoids group(P < 0.05).CONCLUSION: Scutellaria barbata flavonoids may inhibit TAM activation by blocking the TLR4/MyD88/NF-κB signaling pathway.

关键词： Endometrial neoplasms Scutellaria baicalensis Flavonoids Toll-like receptor 4 Myeloid differentiation factor 88 macrophages

C-X3-C motif chemokine ligand 1/receptor 1 regulates the M1 polarization and chemotaxis of macrophages after hypoxia/reoxygenation injury

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Chronic Diseases and Translational Medicine 2021年第4期7卷 254-265页

作者： Shuiming Guo Lei Dong Junhua Li Yuetao Chen Ying Yao Rui Zeng Nelli Shushakova Hermann Haller Gang Xu Song Rong Department of Nephrology Division of Internal MedicineTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Department of Respiratory Division of Internal MedicineTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Department of Nephrology Hannover Medical SchoolHannover 30625Germany

Background:macrophages play an important role in renal ischemia reperfusion injury,but the functional changes of macrophages under hypoxia/reoxygenation and the related mechanism are unclear and need to be further clarified.Methods:The effects of hypoxia/reoxygenation on functional characteristics of RAW264.7 macrophages were analyzed through the protein expression detection of pro-inflammatory factors TNF-αand CD80,anti-inflammatory factors ARG-1 and CD206.The functional implications of C-X3-C motif chemokine receptor 1(CX3CR1)down-regulation in hypoxic macrophages were explored using small interfering RNA technology.Significance was assessed by the parametrict-test or nonparametric Mann-Whitney test for two group comparisons,and a one-way ANOVA or the Kruskal-Wallis test for multiple group comparisons.Results:Hypoxia/reoxygenation significantly increased the protein expression of M1-related pro-inflammatory factors TNF-α,CD80 and chemokine C-X3-C motif chemokine ligand 1(CX3CL1)/CX3CR1 and inhibited the protein expression of M2-related anti-inflammatory factors ARG-1 and CD206 in a time-dependent manner in RAW264.7 cells.However,the silencing of CX3CR1 in RAW264.7 cells using specific CX3CR1-siRNA,significantly attenuated the increase in protein expression of TNF-α(Pmacrophages compared with the control group,and CX3CR1-siRNA had an inhibitory role(40%and 20%reduction,respectively).For elucidating the mechanism,we showed that the phosphorylation levels of ERK(P<0.01)and the p65 subunit of NF-κB(P<0.01)of the RAW264.7 cells in the hypoxic/reoxygenation group were significantly increased,which could be attenuated by down-regulation of CX3CR1 expression(P<0.01,both).ERK inhibitors also significantly blocked the effects of hypoxic/reoxygenation on the

关键词： macrophages Hypoxia/Reoxygenation C-X3-C motif chemokine ligand 1/receptor 1 Phenotypic polarization

Young Yum pill inhibits inflammatory mediators and nuclear factor-kappa B signaling in lipopolysaccharide-stimulated RAW 264.7 macrophages

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Journal of Traditional Chinese Medicine 2019年第5期39卷 624-631页

作者： Yin Chengle Muhammad Jahangir Hossen Anfernee Kai-Wing Tse Su Tao Fu Xiuqiong Li Ting Guo Hui Zhu Peili Li Junkui Chou Jiyao Wang Yaping Yu Zhiling Centre for Cancer and Inflammation Research School of Chinese Medicine Hong Kong Baptist UniversityHong KongChina Research and Development Centre for Natural Health Products Hong Kong Baptist University Shenzhen Research Institute and Continuing EducationShenzhen 518057China Centre for Cancer and Inflammation Research School of Chinese MedicineHong Kong Baptist University Hong KongChina

OBJECTIVE: To investigate the effect of Young Yum pill (YYP) on inflammatory mediators in cultured RAW 264.7 cells and elucidate the nuclear factor- kappa B (NF-κB)-related mechanism behind the action. METHODS: YYP was extracted with 95% ethanol Lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages were used to evaluate the effect of YYP on inflammatory mediators. Production of nitric oxide (NO) and prostaglandin E2 (PGE2) were measured by Griess test and enzyme-linked immunosorbent assay, respectively. The levels of genes and proteins involved in the generation of inflammatory mediators were examined using real-time polymerase chain reaction and Western blotting, respectively. RESULTS: YYP dose-dependently suppressed LPS-induced production of NO, PGE2 and tumor necrosis factor-α(TNF-α), and elevation of mRNA and protein levels of inducible NO synthase and cyclooxygenase- 2 in RAW 264.7 macrophages. These observations were associated with decreased NF-κB p65 phosphorylation and nuclear localization, enhanced Akt (protein kinase B) phosphorylation, as well as reduced inhibitor of κB (IκB)α degradation and IκB kinase α/β phosphorylation. CONCLUSION: The present study demonstrated an inhibitory effect of YYP on the NF-κB-regulated inflammatory mediators NO, PGE2 and TNF-α in LPS-stimulated RAW 264.7 macrophages, providing a pharmacological basis for the use of YYP in treating inflammatory disorders.

关键词： Inflammation NF-kappa B Lipopolysaccharides RAW 264.7 cells macrophages Young Yum pill

Lipid-based nanoparticles for cancer immunotherapy

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Medical Review

Medical Review 2023年第3期3卷 230-269页

作者： Shumin Fan Huize Han Zhicheng Yan Yao Lu Bing He Qiang Zhang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijingChina Ningbo Institute of Marine Medicine Peking UniversityNingbo 315832Zhejiang ProvinceChina

As the fourth most important cancer management strategy except surgery, chemotherapy and radiotherapy, cancer immunotherapy has been confirmed to elicitdurable antitumor effects in the clinic by leveraging thepatient’s own immune system to eradicate the cancer cells.However, the limited population of patients who benefitfrom the current immunotherapies and the immune relatedadverse events hinder its development. The immunosuppressive microenvironment is the main cause of the failure,which leads to cancer immune evasion and immunity cycleblockade. Encouragingly, nanotechnology has been engineered to enhance the efficacy and reduce off-target toxicityof their therapeutic cargos by spatiotemporally controllingthe biodistribution and release kinetics. Among them, lipid-based nanoparticles are the first nanomedicines to makeclinical translation, which are now established platforms fordiverse areas. In this perspective, we discuss the availablelipid-based nanoparticles in research and market here, thendescribe their application in cancer immunotherapy, withspecial emphasis on the T cells-activated and macrophagestargeted delivery system. Through perpetuating each step ofcancer immunity cycle, lipid-based nanoparticles can reduceimmunosuppression and promote drug delivery to triggerrobust antitumor response.

关键词： cancer immunity cycle cancer immunotherapy lipid-based nanoparticles macrophages T cells

Hepatitis B Virus X Protein Up-regulates TNF-α and IL-1β Secretion of macrophages

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Chinese Journal of Cancer Research 2007年第3期19卷 206-209页

作者：陈春莲吴移谋王静朱翠明刘安元尹卫国万艳平 Institute of Pathogenic Biology University of South China

Objective： To provide the experimental basis for further studying the molecular transformation mechanism of Hepatitis B virus （HBV） X protein （HBx） on hepatocellular carcinoma. Methods： Reconstructed plasmid pcDNA3.1（＋）-HBx was transfected into THP-1 macrophages. Expression of HBx was assayed in macrophages lysate by Western-blotting, and TNF-α and IL-1β contents were detected respectively by ELISA. All the data were analyzed by SPSS13.0. Results： In THP-lmacrophages, the pcDNA3.1（＋）-HBx plasmid expressed HBx with a molecular weight of about 17 KDa demonstrated by Western-blotting. The secreted TNF-α and IL-1β from macrophages were determined by ELISA, the results from analysis of all groups showed as following： control group was different from LPS group and pcDNA3.1（＋） group （P〈0.01）, and so was pcDNA3.1（＋）-HBx group; but there was no obvious difference between pcDNA3.1（＋） group and LPS group （P〉0.05）, all of which indicated that transient overexpression of HBx enhanced LPS-induced production of TNF-α and IL-1β by macrophages. Conclusion： Transient overexpression of HBx up-regulates LPS-induced TNF-t~ and IL-113 secretion of macrophages.

关键词： HBV X protein macrophages TNF-α IL-1β

macrophages in Ischemic Heart Failure:Yesterday,Today,and Tomorrow

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Cardiology Discovery 2021年第2期1卷 128-134页

作者： Demin Liu Wenjun Yan Jingwen Huang Jianli Zhao Houston Kilby Theodore AChristopher Bernard Lopez Ling Tao Xinliang Ma Guoqiang Gu Yajing Wang Department of Cardiology The Second Hospital of Hebei Medical UniversityShijiazhuang 050000China Xijing Hospital Fourth Military Medical UniversityXi’an 710032China Department of Medicine and Department of Emergency Medicine Thomas Jefferson UniversityPhiladelphiaPennsylvania 19107USA.

With continually improving reperfusion strategies and patient care,the overall mortality of acute myocardial infarction(AMI)has been significantly reduced during the past two decades.However,this success is a double-edged sword,as many patients surviving an AMI will progress towards ischemic heart failure(HF)over time.The pathologic causes of ischemic HF are undoubtedly multifactorial.However,the inflammatory response is considered one of the most important causes of pathological remodeling because it spans the whole process of HF development.The macrophage-mediated inflammatory response was once considered a purely harmful factor leading to pathological remodeling and HF.However,growing evidence demonstrates that multiple subgroups of macrophage exist and contribute differently to ischemic HF development.Understanding macrophage populations and how they contribute to post-MI remodeling and consequent ischemic HF is,therefore,critical to understanding and treating the disease.This review focuses on different macrophage populations that regulate post-MI cardiac injury and how immunoregulation therapy may benefit patients with ischemic HF.

关键词： Acute myocardial infarction Heart failure Immunoregulation therapy Inflammation macrophages

Are M1 and M2 macrophages Effectual Players in Pathological Conditions?

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Proceedings of Anticancer Research 2022年第3期6卷 34-41页

作者： Elham Abdollahi Nafiseh Saghafi Maliheh Hasanzade Department of Gynecology and Obstetrics Mashhad University of Medical SciencesMashhadIran Immunology Research Center Inflammation and Inflammatory Disease Research CentreMashhad University of Medical SciencesMashhadIran

Pathologic inflammatory conditions are frequently correlated with dynamic alterations through macrophage activation,with classically activated Ml cells associated with promoting and sustaining inflammation and M2 cells implicated in resolving or smoldering chronic inflammation.Inflammation is a common feature of various chronic diseases,and it has direct involvement in the emergence and progression of these conditions.macrophages participate in an autoregulatory loop characterizing inflammatory process,as they produce a wide range of biologically active mediators that exert either deleterious or beneficial effects during inflammation.Therefore,balancing the ratio of M1/M2 macrophages can help to ameliorate the inflammatory landscape of pathological conditions.This review will explore the role of macrophage polarization in distant pathological inflammatory conditions,such as cancer,autoimmunity,renal inflammation,stroke,and atherosclerosis,while sharing macrophage-driven pathogenesis.

关键词： M1 M2 macrophages Inflammation Polarization

Glycolysis and acute lung injury:A review

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Asian Pacific Journal of Tropical Medicine 2023年第11期16卷 490-497页

作者： Yang Yi Jun Chen Nan Li Yue Huang Jichao Peng Xiaoran Liu College of Emergency Trauma Hainan Medical UniversityHaikouChina Key Laboratory of Hainan Trauma and Disaster Rescue the First Affiliated Hospital of Hainan Medical UniversityHaikouChina Key Laboratory of Emergency and Trauma Ministry of Education Hainan Medical UniversityHaikouChina Danzhou People’s Hospital DanzhouChina

Acute lung injury is featured as diffuse pulmonary edema and persistent hypoxemia caused by lung or systemic injury.It is believed that these pathological changes are associated with damage to the alveolar epithelium and vascular endothelium,recruitment of inflammatory cells,and inflammatory factor storms.In recent years,the metabolic reprogramming of lung parenchymal cells and immune cells,particularly alterations in glycolysis,has been found to occur in acute lung injury.Inhibition of glycolysis can reduce the severity of acute lung injury.Thus,this review focuses on the interconnection between acute lung injury and glycolysis and the mechanisms of interaction,which may bring hope for the treatment of acute lung injury.

关键词： Acute lung injury Glycolysis Hypoxia-inducible factor 1 Endothelium macrophages