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Journal of Traditional Chinese Medicine 2023年第3期43卷 494-500页

作者： SUN Mengzhu ZHANG Yujie SONG Yafang GUO Jing WANG Yuhang XIN Chen GU Dongmei SUN Jianhua PEI Lixia Department of acupuncture Affiliated Hospital of Nanjing University of Chinese MeidicneNanjing 210023China Department of acupuncture Jiangsu Province Hospital of Chinese MedicineNanjing 210029China

OBJECTIVE:To evaluate the effects and related mechanisms of electroacupuncture(EA)on irritable bowel syndrome(IBS).METHODS:Male C57BL/6 mice were randomly allocated into normal,model,and EA groups.Experimental IBS mice models were established by exposure to water avoidance stress(WAS).Mice in the EA group were treated with EA at bilateral Tianshu(ST 25)and Zusanli(ST 36)for 7 consecutive days,15 min each day.Abdominal withdrawal reflex(AWR)tests and intestinal motility tests were performed to evaluate visceral sensitivity and intestinal motility of mice.Expression levels of tight junction proteins(TJPs)and inflammatory cytokines in colon tissues were determined through immunofluorescence,real-time polymerase chain reactions(PCR)and Western blot assays.RESULTS:EA alleviated visceral hypersensitivity and intestinal hypermotility in WAS-induced IBS mice.Moreover,EA promoted the expression of zonula occludens(ZO)-1,claudin-1,and occludin while suppressing the expression of interleukin(IL)-8,interferon(IFN)-γ,and tumor necrosis factor(TNF)-αin water avoidance stress(WAS)-induced irritable bowel syndrome(IBS)mice.CONCLUSION:EA alleviated WAS-induced IBS in mice by promoting intestinal barrier functions and suppressing the expression of inflammatory cytokines.

关键词： electroacupuncture irritable bowel syndrome intestinal barrier function tight junction proteins inflammatory cytokines

DNA Damage-driven inflammatory cytokines:Reprogramming of Tumor Immune Microenvironment and Application of Oncotherapy

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当代医学科学（英文） 2024年第2期44卷 261-272页

作者： Meng-jie WANG Yu XIA Qing-lei GAO Department of Obstetrics and Gynecology National Clinical Research Center for Obstetrics and GynecologyTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Key Laboratory of Cancer Invasion and Metastasis(Ministry of Education) Hubei Key Laboratory of Tumor Invasion and MetastasisTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

DNA damage occurs across tumorigenesis and tumor development.Tumor intrinsic DNA damage can not only increase the risk of mutations responsible for tumor generation but also initiate a cellular stress response to orchestrate the tumor immune microenvironment(TIME)and dominate tumor progression.Accumulating evidence documents that multiple signaling pathways,including cyclic GMP-AMP synthase-stimulator of interferon genes(cGAS-STING)and ataxia telangiectasia-mutated protein/ataxia telangiectasia and Rad3-related protein(ATM/ATR),are activated downstream of DNA damage and they are associated with the secretion of diverse cytokines.These cytokines possess multifaced functions in the anti-tumor immune response.Thus,it is necessary to deeply interpret the complex TIME reshaped by damaged DNA and tumor-derived cytokines,critical for the development of effective tumor therapies.This manuscript comprehensively reviews the relationship between the DNA damage response and related cytokines in tumors and depicts the dual immunoregulatory roles of these cytokines.We also summarize clinical trials targeting signaling pathways and cytokines associated with DNA damage andprovide future perspectives on emerging technologies.

关键词： DNA damage tumor immune microenvironment inflammatory cytokines cancer therapy

The combination of ciprofloxacin and indomethacin suppresses the level of inflammatory cytokines secreted by macrophages in vitro

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Chinese Journal of Traumatology 2022年第6期25卷 379-388页

作者： Ke Liu Jing Yu Yu Xia Lei-Ting Zhang Sui-Yan Li Jun Yan School of Life Science and Engineering Southwest Jiaotong UniversityChengdu 610031China State Key Laboratory of Trauma Burns and Combined InjuryResearch Institute of SurgeryDaping HospitalArmy Medical University(Third Military Medical University)Chongqing 400042China

Purpose:The combined use of antibiotics and anti-inflammatory medicine to manage bacterial endotoxin-induced inflammation following injuries or diseases is increasing.The cytokine level produced by macrophages plays an important role in this treatment course.Ciprofloxacin and indomethacin,two typical representatives of antibiotics and anti-inflammatory medicine,are cost-effective and has been reported to show satisfactory effect.The current study aims to investigate the effect of ciprofloxacin along with indomethacin on the secretion of inflammatory cytokines by macrophagesin vitro.Methods:Primary murine peritoneal macrophages and RAW 264.7 cells were administrated with lipopolysaccharide(LPS)for 24 h.The related optimal dose and time point of ciprofloxacin or indomethacin in response to macrophage inflammatory response inflammation were determined via macrophage secretion induced by LPS.Then,the effects of ciprofloxacin and indomethacin on the secretory functions and viability of various macrophages were determined by enzyme-linked immunosorbent assay and flow cytometry analysis,especially for the levels of interleukin(IL)-1β,IL-6,IL-10,and tumor necrosis factor(TNF)-α.The optimal dose and time course of ciprofloxacin affecting macrophage inflammatory response were determined by testing the maximum inhibitory effect of the drugs on pro-inflammatory factors at each concentration or time point.Results:According to the levels of cytokines secreted by various macrophages(1.2×10^(6) cells/well)after administration of 1μg/mL LPS,the optimal dose and usage timing for ciprofloxacin alone were 80μg/mL and 24 h,respectively,and the optimal dose for indomethacin alone was 10μg/mL.Compared with the LPS-stimulated group,the combination of ciprofloxacin and indomethacin reduced the levels of IL-1β(pinflammatory factor levels in the combination group compared with those in which only ciprofloxacin or indomethacin was

关键词： Ciprofloxacin Indomethacin inflammatory cytokines In vitro Macrophages

Nε-carboxymethyl-lysine and inflammatory cytokines,markers and mediators of coronary artery disease progression in diabetes

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World Journal of Diabetes 2024年第4期15卷 575-578页

作者： Sonia Eiras Translational Cardiology Health Research InstituteUniversity Hospital of Santiago de CompostelaSantiago de Compostela 15706Spain

This editorial refers to the article“Comparative analysis of Nε-carboxymethyllysine and inflammatory markers in diabetic and non-diabetic coronary artery disease patients”,published in the recent issue of the World Journal of Diabetes 2023 is based on glucose metabolism,advanced glycation end products(AGEs),inflammation and adiposity on diabetes and coronary artery disease(CAD).This study has included CAD patients who were stratified according to glycosylated hemoglobin higher than 6.5 and sex-matched.A higher prevalence of hypertension,dyslipidemia,and non-vegetarian diet were found in the diabetic group.These risk factors might influence body weight and adiposity and explain the increment of the left atrium.Although this data was not supported by the study.The diet can also explain the non-enzymatic reactions on lipids,proteins,or nucleic acids and consequently an increment of AGEs.These molecules can emit fluorescence.However,one of the non-fluorescent and most abundant AGEs is Nε-carboxymethyl-lysine(CML).Its association with coronary artery stenosis and severity in the diabetic group might suggest its role as a player in CAD progression.Thus,CML,after binding with its receptor(RAGE),can induce calcification cascade through reactive oxygen species and mitogen-activated protein kinase.Moreover,this interaction AGE-RAGE can cause activation of the transcription nuclear factor-kb and induce inflammatory cytokines.It might explain the relationship between CML and pro-inflammatory cytokines in diabetic and CAD patients.Although this is a population from one center,the determination of CML and inflammatory cytokines might improve the diagnosis of severe and progressive CAD.Future and comparative studies among glycosylated hemoglobin,CML,and other AGE levels according to diagnosis and prognosis value might modify the clinical practice.Although these molecules are irreversible,they can act through a specific receptor inducing a signal transduction that might be modulated by inhibitors,antibodies,or siRNA.Further mech

关键词： Nε-carboxymethyl-lysine inflammatory cytokines Adiposity Diabetes Coronary artery disease

HMGB1 Inhibitor Effectively Alleviates Psoriasis-Like Lesions and inflammatory cytokines in K14-VEGF Transgenic Mice

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International Journal of Dermatology and Venereology 2023年第1期6卷 9-14页

作者： Li-Xin Fu Bin Yin Na Cao Sha Qin Xiao-Yu Lei Tao Chen Zai-Pei Guo Department of Dermatovenereology Chengdu Second People’s HospitalChengduSichuan 610041China Department of Dermatovenereology Chengdu Qingbaijiang Distinct People’s HospitalChengduSichuan 610300China Department of Dermatovenereology West China Hospital of Sichuan UniversityChengduSichuan 610041China

Objective:Anti-high-mobility group box 1(HMGB1)is involved in the pathogenesis of many inflammatory and autoimmune diseases,including psoriasis.The present study aimed to investigate the therapeutic effects of HMGB1 monoclonal antibody(mAb)in keratin 14(K14)-vascular endothelial growth factor(VEGF)transgenic homozygous mice.Methods:Twelve VEGF transgenic mice were randomly divided into two groups of six mice each:the anti-HMGB1 mAb group and the immune complex(IC)mAb group.The mice underwent intraperitoneal injection of anti-HMGB1 mAb or IC mAb once every 2 days for a total of three treatments.Compare the lesions on the ears of the mice and evaluate the severity of the lesions using the baseline and clinical scores on the last day of treatment.The changes in psoriasis-like lesions,cellular infiltration of T cells,dendritic cells,and neutrophils were detected by hematoxylin-eosin staining and immunohistochemistry.The mRNA expression of the inflammatory cytokines,including interleukin(IL)-6,tumor necrosis factor-α,interferon-γ,and IL-17 in the lesions were assessed by real-time quantitative polymerase chain reaction.The number ofγδT cells in the lesions of two groups were detected by flow cytometry.Thet test was used to compare their differences.Results:The anti-HMGB1 mAb effectively ameliorated the clinical skin lesions.The clinical scores in the anti-HMGB1 mAb group were lower than those in the IC mAb group(6.00±0.52vs.10.83±0.48,P<0.001).Histopathologic changes and improvements in the K14-VEGF transgenic homozygous mice were evident after three treatments.The scores of mice in the anti-HMGB1 mAb group were significantly lower than those in the IC mAb group(3.25±0.71vs.6.95±0.83,P=0.0033).The average epidermal thickness in the anti-HMGB1 mAb group was reduced by about 45%when compared with that in the IC mAb group(32.15±7.08vs.64.69±7.93,P=0.0054).Moreover,anti-HMGB1 mAb also decreased the number of infiltrating CD3+T cells,myeloperoxidase-positive neutrophils,and CD11c+dendritic cells.The ratio of ear skinγδT ce

关键词： high-mobility group box 1 inflammatory cytokines K14-VEGF transgenic mouse psoriasis

Mutual Effect between Neuropeptides and inflammatory cytokines in Neurogenic SMSCs of Human Temporomandibular Joint

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2014年第4期34卷 602-607页

作者：刘志明彭友俭龙星李健柯金房维 Renmin Hospital of Wuhan University Key Laboratory of Oral Biomedicine Ministry of Education School & Hospital of Stomatology Wuhan University Department of Oral and Maxillofacial Surgery Hospital of Stomatology Wuhan University

In temporomandibular disorders（TMD）, pain takes place when neuropeptides stimulate synovial tissue to produce several cytokines such as interleukin（IL）-1β, IL-6 and tumor necrosis factor（TNF）-α, which activate neurons and glia of synovial membrane at the bilaminar regions of temporomandibular joint（TMJ）. It has been reported that, after neurogenic differentiation, the synovial mesenchymal stem cells（SMSCs）, deriving from TMJ, possess the same cytological features as the neuronal cells. This study examined the ability of substance P（SP） and calcitonin gene-related peptide（CGRP） to stimulate SMSCs and neurogenic SMSCs secreting inflammatory cytokines during TMD, evaluated the mutual effects of inflammatory cytokines and neuropeptides and tested the analgesic effect of hyaluronic acid（HA）. The levels of IL-1β, IL-6 and TNF-α in SMSCs and neurogenic SMSCs in the presence of neuropeptides were measured by ELISA. SP and CGRP produced by SMSCs and neurogenic SMSCs were determined by RT-PCR and Western blotting. The results showed that the expression of SP and CGRP was significantly enhanced in the neurogenic SMSCs in response to IL-1β, IL-6 and TNF-α, and the effect was remarkably inhibited by HA. IL-1β, IL-6 and TNF-α, in return, could be enhanced in the neurogenic SMSCs upon stimulation by SP and CGRP. Neuropeptides and inflammatory cytokines might work mutually on the TMD pain. The HA-mediated analgesic effect may be implicated in the inhibition of SP and CGRP expression in neurogenic SMSCs.

关键词： hyaluronic acid inflammatory cytokines substance P calcitonin gene-related peptide neurogenesis temporomandibular disorders

Effect of antimicrobial agents on the toll-like receptors and inflammatory cytokines in liver tissue of the alcohol-induced liver disease in rats with Vibrio vulnificus sepsis

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Chinese Medical Journal 2009年第16期122卷 1910-1916页

作者： LU Zhong-qiu LI Meng-fang QIU Qiao-meng LIANG Huang ZHOU Tie-li HONG Guang-liang WU Bin Department of Emergency First Affiliated Hospital of Wenzhou Medical College. Wenzhou Zhejiang 325000 China

Background Septicemia and inflammation-mediated septic shock caused by Vibrio vulnificus （VV） is strongly associated with chronic liver disease. This study examined the effects of antimicrobial therapy on expression of hepatic toll-like receptors and inflammatory cytokines in rats with alcohol-induced liver disease complicated by VV sepsis. Methods Male Sprague-Dawley rats were assigned to the following treatment groups： normal control （N）, alcoholic liver disease control （A）, antimicrobial-treated alcoholic liver disease control （AA）, alcoholic liver disease with VV sepsis （AV）, and antimicrobial-treated alcoholic liver disease with VV sepsis （AVA）. Alcohol-induced liver disease was observed in all groups except N. Expression of mRNAs encoding hepatic toll-like receptors 2 and 4, myeloid differentiation protein-2, tumor necrosis factor-α （TNF-α）, interleukin （IL）-1β, IL-6 and IL-10 was determined by RT-PCR. Results mRNAs encoding toll-like receptors 2 and 4 and myeloid differentiation protein-2 were significantly up-regulated in group AV as compared to control groups at 2-24 hours of sepsis; peak expression occurred at 12 hours. These mRNAs were also up-regulated in group AVA but to lesser degrees than in group AV at comparable time post-infection, mRNAs encoding TNF-α, IL-1β and IL-6 were significantly elevated in group AV as a function of infection. In group AVA as compared to AV, expression of TNF-α and IL-1β mRNAs was lower at 12-24 hours post-infection and expression of IL-6 mRNA was lower at 24 hours post-infection. Compared with control groups, IL-10 mRNA expression in group AV was markedly higher at 12-24 hours of sepsis. Expression of IL-10 mRNA was lower in group AVA as compared to AV at 24 hours of sepsis. Conclusions Antimicrobial therapy reduces expression of toll-like receptors and cytokines in rats with alcohol-induced liver disease complicated by VV sepsis. Monitoring hepatic toll-like receptor and cytokine expression during antibiotic therapy may be valuable for determining the course of VV seps

关键词： Vibrio vulnificus sepsis toll-like receptors inflammatory cytokines cefoperazone sodium levofloxacin

Triptolide Inhibits Expression of inflammatory cytokines and Proliferation of Fibroblast-like Synoviocytes Induced by IL-6/sIL-6R-Mediated JAK2/STAT3 Signaling Pathway

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Current Medical Science 2021年第1期41卷 133-139页

作者： Jian-jing LIN Ke TAO Nan GAO Hui ZENG De-li WANG Jun YANG Jian WENG National&Local Joint Engineering Research Center of Orthopaedic Biomaterials Department of Bone and Joint SurgeryPeking University Shenzhen HospitalShenzhen518000China Arthritis Clinical and Research Center Peking University People’s HospitalBeijing100044China Department of Rheumatism and Immunology Peking University Shenzhen HospitalShenzhen518000China Department of Radiology Peking University Shenzhen HospitalShenzhen518000China

Triptolide,a component of the Chinese herb Tripterygium wilfordii Hook F,has been proved to be effective in the treatment of rheumatoid arthritis(RA).However,its underlying mechanisms on RA have not yet been well established.We observed the inhibitory effect of triptolide on the expression of inflammatory cytokines and proliferation of fibroblast-like synoviocytes(FLS)induced by the complex of interleukin-6(IL-6)and the soluble form of the IL-6 receptor(sIL-6R).Furthermore,to clarify the underlying mechanisms,we treated FLS with the Janus-activated kinase 2(JAK2)inhibitor/signal transducer and activator of transcription 3(STAT3)activation blocker AZD1480.In this study,immunohistochemical staining was used to identify vimentin(+)and CD68(−)in FLS.The FLS proliferation was measured by cell proliferation assay,and the cell cycles were analyzed by flow cytometry.Furthermore,ELISA was used to detect the expression of the inflammatory factors in culture solution.The expression levels of p-JAK2,JAK2,p-STAT3 and STAT3 were investigated through Western blotting analysis.The results showed that IL-6/sIL-6R significantly increased the cell proliferation and expression of inflammatory cytokines,including IL-6,interleukin-1β(IL-1β)and vascular endothelial growth factor(VEGF).Triptolide or AZD1480 inhibited the cell proliferation and inflammatory cytokine expression in IL-6/sIL-6R-stimulated FLS by suppressing JAK2/STAT3.The study suggested that the physiological effects of triptolide on RA were due to its contribution to the inhibition of the inflammatory cytokine expression and FLS proliferation by suppressing the JAK2/STAT3 signaling pathway.It may provide an innovative insight into the effect of triptolide in preventing RA pathogenesis.

关键词： triptolide inflammatory cytokines proliferation fibroblast-like synoviocytes JAK2/STAT3

Association of Gut microbiota with Short-Chain Fatty Acids and inflammatory cytokines in Diabetic Cognitive Impairment Patients

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Association of Gut microbiota with Short-Chain Fatty Acids a...

Serum level changes of inflammatory cytokines in patients with moderate to severe acne vulgaris treated with dual-wavelength laser

中国营养学会第十五届全国营养科学大会

作者： Yage Du Ying Song Yanhui Lu Peking University

Emerging evidences suggest that gut microbiota, short-chain fatty acids(SCFAs), and inflammatory cytokines play important roles in the pathogenesis of diabetic cognitive impairment(DCI). However, fecal microbiome in Chinese patients with DCI remains unclear. Herein, we explore how the gut microbiota, plasma SCFAs and inflammatory cytokines differs in DCI patients compared to type 2 diabetes mellitus(T2 DM) patients. Methods A case-control study of 30 DCI patients and 30 T2 DM controls was conducted in the rural of Tianjin, China. Demographic information, blood samples, and fecal samples were collected. The fecal microbiome, SCFAs, and inflammatory cytokines were analyzed using 16 S ribosomal RNA(rRNA) gene sequencing, gas chromatography-mass spectrometry(GC-MS) and Luminex immunofluorescence assays, respectively. The association of gut microbiota with DCI clinical characteristics, SCFAs, and inflammatory cytokines were analyzed. Results At the genus level, DCI patients had a decreased abundance of Escherichia and Akkermansia. Moreover, acetic acid, propionic acid, isobutyric acid, and butyric acid concentrations were significantly reduced in DCI patients compared with T2 DM controls. The plasma TNF-α and IL-8 concentrations were significantly increased in DCI participants. The plasma acetic acid, propionic acid, butyric acid, and isovaleric acid concentration were negatively associated with TNF-α, and acetic acid and butyric acid were negatively associated with IL-8. Furthermore, the genera Alloprevotella was negatively associated with butyric acid, Holdemanella was negatively associated with propanoic acid and isobutyric acid, and Fusobacterium was negatively associated with propanoic acid. The genera Clostridium XlVb was negatively associated with TNF-α, while Shuttleworthia was positively associated with TNF-α, and the genera Prevotella was negatively associated with IL-6. Conclusion In the present study we evaluated the abundance of certain gut microbiota in DCI in China population, but also reveal their asso

关键词： diabetic cognitive impairment gut microbiota 16S rRNA gene short-chain fatty acids inflammatory cytokines

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Chinese Journal Of Plastic and Reconstructive Surgery 2023年第2期5卷 47-52页

作者： Yang Liu Qilin Sun Hui Xu Gang Ma Pinru Wu Department of Dermatology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Department of Laser and Aesthetic Medicine Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China

Background:Acne vulgaris(AV)is a common inflammatory skin disease.Although various mechanisms have been indicated in the etiopathogenesis of AV,the exact pathophysiology remains unknown.Various lasers have been used to treat AV;however,the serum level changes of inflammatory cytokines after laser therapy have not been elucidated.We aimed to investigate the relationship between inflammatory changes and remission on the opposite side in patients with moderate to severe AV after treating half of the face with 595-and 1064-nm dualwavelength laser.Methods:In total,18 patients(9 male and 9 female)between 16 and 35 years of age with moderate to severe AV were evaluated in the study.Disease severity was classified according to the Pillsbury grading system of acne.Patients were randomized to receive a series of two treatment sessions at intervals of 2 weeks and followed up at 2 weeks after the final treatment.A 3 mL blood sample was drawn from every subject each time,and serum levels of inflammatory cytokines such as interleukin(IL)-6,IL-8,and IL-22 were determined using enzyme-linked immunosorbent assay at baseline and 2 weeks after each treatment.Improvement was determined by a blinded assessment of photographs taken before and after the final evaluation.Results:Inflammation was significantly reduced on both the treated and untreated sides,and symptoms of AV lesions were alleviated.All patients showed a significant increase in serum IL-22 levels after the first laser therapy,with no significant difference in serum IL-6 and IL-8 levels.After the second laser therapy,serum IL-6,IL-8,and IL-22 levels were significantly decreased.No significant side effects such as bruising,edema,hyperpigmentation,hypopigmentation,or scarring were reported.Conclusion:Half-face treatment with 595-and 1064-nm dual-wavelength laser for moderate and severe AV showed a significant effect of full-face remission,which was associated with a gradual decrease in IL-6,IL-8,and IL-22 levels after half-face topical treatment.This suggests that reducing

关键词： Acne vulgaris Dual-wavelength laser inflammatory cytokines Serum