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Total glucosides of paeony alleviates cGAS-STING-mediated diseases by blocking the STING-IRF3 interaction

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Chinese Journal of Natural Medicines 2024年第5期22卷 402-415页

作者： XIU Ye WANG Sihao ZHANG Ping LI Chengwei WU Zhixin WEN Jincai XU Yingjie LV Guiji ZHAO Xiaomei DONG Xu CHEN Yichong LI Junjie WANG Yan ZOU Liang XIAO Xiaohe BAI Zhaofang School of Pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350122China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijing 100039China China military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China Department of Pharmacy Medical Supplies Center of PLA General HospitalBeijing 100039China School of Food and Biological Engineering Chengdu UniversityChengdu 610106China National Key Laboratory of Kidney Diseases Chinese PLA General HospitalBeijing 100039China

In the realm of autoimmune and inflammatory diseases,the cyclic GMP-AMP synthase(cGAS)stimulator of interferon genes(STING)signaling pathway has been thoroughly investigated and *** this,the clinical approval of drugs targeting the cGAS-STING pathway has been *** Total glucosides of paeony(TGP)is highly anti-inflammatory and is commonly used in the treatment of rheumatoid arthritis(RA),emerged as a subject of our *** found that the TGP markedly reduced the activation of the cGAS-STING signaling pathway,triggered by various cGAS-STING agonists,in mouse bone marrow-derived macrophages(BMDMs)and Tohoku hospital Pediatrics-1(THP-1)*** inhibition was noted alongside the suppression of interferon regulatory factor 3(IRF3)phosphorylation and the expression of interferon-beta(IFN-β),C-X-C motif chemokine ligand 10(CXCL10),and inflammatory mediators such as tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6).The mechanism of action appeared to involve the TGP’s attenuation of the STING-IRF3 interaction,without affecting STING oligomerization,thereby inhibiting the activation of downstream signaling *** vivo,the TGP hindered the initiation of the cGAS-STING pathway by the STING agonist dimethylxanthenone-4-acetic acid(DMXAA)and exhibited promising therapeutic effects in a model of acute liver injury induced by lipopolysaccharide(LPS)and D-galactosamine(D-GalN).Our findings underscore the potential of the TGP as an effective inhibitor of the cGAS-STING pathway,offering a new treatment avenue for inflammatory and autoimmune diseases mediated by this pathway.

关键词： Total glucosides of gaeony cGAS-STING pathway Inflammation LPS/D-GalN STING inhibitor

Construction of sperm-specific lactate dehydrogenase DNA vaccine and experimental study of its immuno-contraceptive effect on mice

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Science China(Life Sciences) 2008年第4期51卷 308-316页

作者： CHEN Yong ZHANG Duo XIN Na XIONG YongZhong CHEN Ping LI Bo TU XiangDong LAN FengHua Research Laboratory of Medical Genetics PLA Institute of Technology for Birth ControlFetal Health and Child GrowthFuzhou General Hospital of Nanjing Military RegionFuzhou 350025China

Lactate dehydrogenase C4 (LDHC4) is a key enzyme for sperm metabolism. It is distributed specifically in testis and is highly immunogenic. In this study, two DNA vaccines pVAX1-hLDHC and pVAX1-mLDHC were constructed by inserting coding sequences of human and mice LDHC4 into the eukaryotic ex-pression vector pVAX1. The production of LDHC4 specific antibodies was induced in the sera of vac-cinated mice and the reproductive tract secretions of vaccinated female mice through immunization by mucosal surface instillation. Furthermore, the antibody titer increased with the times of immunization. In the mating experiment, the number of newborns of the vaccinated mice reduced significantly and some immunized female mice even lost the ability to bear any offsprings, suggesting that the difference between the immunized and control mice was statistically significant. Sperm agglutination analysis indicated that both the antisera from immunized mice and the reproductive tract secretions of vacci-nated female mice could agglutinate normal sperms. Results of immunohistochemistry showed that the antibodies present in the sera of immunized mice and the reproductive tract secretions of vaccinated female mice could specifically react with LDHC4 antigen, which mainly locates in the cytoplasm, acrosome membrane externa and acrosome capsule of the sperm. Taken together, our results indicated that the constructed contraceptive DNA vaccines did yield immunocontraceptive effects on mice and this would enable clinical trials in near future.

关键词： sperm-specific lactate dehydrogenase DNA vaccine contraceptive vaccine mucosal immunization

Mesenchymal stem cells alleviate TNBS-induced colitis by modulating inflammatory and autoimmune responses

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World Journal of Gastroenterology 2013年第29期19卷 4702-4717页

作者： Qian-Qian Chen Li Yan Chang-Zheng Wang Wei-Hua Wang Hui Shi Bin-Bin Su Qing-Huan Zeng Hai-Tao Du Jun Wan Department of Gastroenterology Chinese PLA General Hospital Medical College of PLA Department of Gastroenterology Chinese PLA General Hospital

AIM: To investigate the potential therapeutic effects of mesenchymal stem cells (MSCs) in inflammatory bowel disease (IBD), we transplanted MSCs into an experimental model of IBD. METHODS: A rectal enema of trinitrobenzene sulfonic acid (TNBS) (100 mg/kg body weight) was administered to female BALB/c mice. Bone marrow mesenchymal stem cells (BMSCs) were derived from male green fluorescent protein (GFP) transgenic mice and were transplanted intravenously into the experimental animals after disease onset. Clinical activity scores and histological changes were evaluated. GFP and Sex determining region Y gene (SRY ) expression were used for cell tracking. Ki67 positive cells and Lgr5-expressing cells were determined to measure proliferative activity. Inflammatory response was determined by mea-suring the levels of different inflammatory mediators in the colon and serum. The inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-6, IL-17, IL-4, IL-10, and transforming growth factor (TGF-β). Master regulators of Th1 cells (T-box expressed in T cells, T-bet), Th17 cells (retinoid related orphan receptor gamma(t), RORγt), Th2 cells (GATA family of transcription factors 3, GATA3) and regulatory T cells (forkhead box P3, Foxp3) were also determined. RESULTS: Systemic infusion of GFP-BMSCs ameliorated the clinical and histopathologic severity of colitis, including body weight loss, diarrhea and inflammation, and increased survival (P < 0.05). The cell tracking study showed that MSCs homed to the injured colon. MSCs promoted proliferation of intestinal epithelial cells and differentiation of intestinal stem cells (P < 0.01). This therapeutic effect was mainly mediated by downregulation of both Th1-Th17-driven autoimmune and inflammatory responses (IL-2, TNF-α, IFN-γ, T-bet; IL-6, IL-17, RORγt), and by up-regulation of Th2 activities (IL-4, IL-10, GATA-3) (P < 0.05). MSCs also induced activated CD4 + CD25 + Foxp3 + regulat

关键词： Mesenchymal stem cells Transplantation Inflammatory bowel disease Inflammatory response Immunomodulation Trinitrobenzene sulfonic acid colitis Therapy

Liposomes for systematic delivery of vancomycin hydrochloride to decrease nephrotoxicity:Characterization and evaluation

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Asian Journal of Pharmaceutical Sciences 2015年第3期10卷 212-222页

作者： Junli Liu Zhonglan Wang Fubing Li Jinhua Gao Longmei Wang Guihua Huang The School of Pharmaceutical Science Shandong UniversityJi'nanChina Research Institue of Orthopaedic Trauma of pla Kunming General Hospital of Chengdu Military CommandKunmingChina

Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute *** formulations of VANH have already been manipulated and characterized,which was a mean of increasing their therapeutic index,reducing their toxicity and altering drug *** of the challenges for preparing VANH-Lips is their low encapsulation efficiency(EE).In the present study,we aim to improve the liposomal formulation of VANH for higher EE,longer systemic circulation,reduced nephrotoxicity and enhanced antimicrobial *** hydrochloride-loaded liposomes(VANH-Lips)were formulated by the method of modified reverse phase *** on the optimization of formulation with orthogonal experimental design,the average drug encapsulation efficiency and the mean particle size of VANH-Lips were found to be 40.78±2.56%and 188.4±2.77 *** vitro drug release of VANH-Lips possessed a sustained release characteristic and their release behavior was in accordance with the Weibull *** intravenous injection to mice,the mean residence time(MRT)of VANH-Lips group was significantly prolonged in vivo and the AUC value was improved as well compared with the vancomycin hydrochloride solution(VANH-Sol)***,the biodistribution results in mice showed that VANH-Lips decreased the accumulation of VANH in kidney after intravenous *** conclusion,VANH-Lips may be a potential delivery system for VANH to decrease nephrotoxicity in the treatment of osteomyelitis.

关键词： Biodistribution Nephrotoxicity Pharmacokinetic Systematic delivery Vancomycin hydrochloride liposome

Transcriptome Sequencing Reveals Astrocytes as a Therapeutic Target in Heat-Stroke

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Neuroscience Bulletin 2017年第6期33卷 627-640页

作者： Bing Niu Tao Zhang Huaiqiang Hu Bingzhen Cao Department of Neurology General Hospital of Jinan Military Region Department of Neurology The 303rd Hospital of the People's Liberation Army

Heat-stroke is a serious form of hyperthermia with high mortality, and can induce severe central nervous system disorders. The neurovascular unit（NVU）, which consists of vascular cells, glial cells, and neurons, controls blood-brain barrier（BBB） permeability and cerebral blood flow, and maintains the proper functioning of neuronal circuits. However, the detailed function of each BBB component in heat-stroke remains unknown. In order to interpret alterations caused by heat stress, we performed transcriptome comparison of neuron and astrocyte primary cultures after heat treatment. Differentially-expressed genes were then selected and underwent Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Gene-act networks were also constructed, and the expression of pivotal genes was validated by quantitative PCR, as well as single-cell q PCR in heatstroke rats. Our work provides valuable information on the transcriptional changes in NVU cells after heat stress,reveals the diverse regulatory mechanisms of two of these cellular components, and shows that a cell-type-specificapproach may be a promising therapeutic strategy for heatstroke treatments.

关键词： Heat stroke RNA-seq Neuron Astrocyte Primary culture Single-cell qPCR

Endoscopic sphincterotomy with needleshaped knife: report of 476 cases

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Hepatobiliary & Pancreatic Diseases International 2002年第3期1卷 434-437页

作者： Bing-Yin Zhang Fu-Zhou Tian Yu Wang Da-Rong Huang Li Gong the Department of general Surgery, pla chengdu general hospital, chengdu 610083, China Department of general Surgery PLA Chengdu General Hospital Chengdu 610083 China.

Objectives: To evaluate endoscopic duodenal sphinc- terotomy and improve its success rate. Methods: Needle-shaped knife was used for endoscop- ic sphincterotomy (EST) in 476 patients with biliary or pancreatic diseases from March 1995 to October 2000. Results: Direct incision was made in 243 patients, papillary fenestration in 89, and opposite incision in 144. The papilla located beside and in the diverticu- lum in 56 and 12 patients, respectively. EST emer- gency was made in 147 patients. ERCP after EST be- cause of the difficulty in intubation was made suc- cessfully in 62 patients. Mild complications occurred in 14 patients (2.94%), all of whom were cured af- ter symptomatic treatment. Conclusions: EST with needle-shaped knife has such advantages as safety in operation and convenience in incision. It is suitable for the papilla with different shape, with a higher success rate.

关键词： endoscope endoscopic sphincterotomy needle-shaped knife

plasma metabolites and risk of myocardial infarction:a bidirectional Mendelian randomization study

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Journal of Geriatric Cardiology 2024年第2期21卷 219-231页

作者： Dong-Hua LI Qiang WU Jing-Sheng LAN Shuo CHEN You-Yi HUANG Lan-Jin WU Zhi-Qing QIN Ying HUANG Wan-Zhong HUANG Ting ZENG Xin HAO Hua-Bin SU Qiang SU Department of Cardiovascular Medicine Minzu Hospital of Guangxi Zhuang Autonomous RegionGuangxiChina Senior Department of Cardiology the Sixth Medical CenterChinese PLA General HospitalBeijingChina Library of Graduate School Chinese PLA General HospitalBeijingChina Department of Cardiology Jiangbin Hospital of Guangxi Zhuang Autonomous RegionGuangxiChina Health Management Institute the Second Medical CenterChinese PLA General HospitalBeijingChina

BACKGROUND Myocardial infarction(MI)is a critical cardiovascular event with multifaceted etiology,involving several genetic and environmental *** is essential to understand the function of plasma metabolites in the development of MI and unravel its complex *** This study employed a bidirectional Mendelian randomization(MR)approach to investigate the causal relationships between plasma metabolites and MI *** used genetic instruments as proxies for plasma metabolites and MI and conducted MR analyses in both directions to assess the impact of metabolites on MI risk and vice *** addition,the large-scale genome-wide association studies datasets was used to identify genetic variants associated with plasma metabolite(1400 metabolites)and MI(20,917 individuals with MI and 440,906 individuals without MI)*** variance weighted was the primary method for estimating causal *** estimates are expressed as beta coefficients or odds ratio(OR)with 95%*** We identified 14 plasma metabolites associated with the occurrence of MI(Pplasma metabolites[propionylglycine levels(OR=0.922,95%CI:0.881–0.965,Pplasma metabolites[1-palmitoyl-2-arachidonoyl-GPE(16:0/20:4)levels(OR=1.051,95%CI:1.018–1.084,P=0.002),behenoyl dihydrosphingomyelin(d18:0/22:0)levels(OR=1.076,95%CI:1.027–1.128,P=0.002),1-stearoyl-2-docosahexaenoyl-GPE(18:0/22:6)levels(OR=1.067,95%CI:1.027–1.109,P=0.001),alpha-ketobutyrate levels(OR=1.108,95%

关键词： infarction alterations diagnosis

Compatibility with Fructus Ligustri Lucidi Effectively Mitigates Idiosyncratic Liver Injury of Epimedii Folium by Modulating NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 159-170页

作者： Xiao-Mei Zhao Zhi-Xin Wu Yan Wang Ying-Jie Xu Ye Xiu Xu Dong Jun-Jie Li Gui-Ji Lv Si-Hao Wang Yu-Rong Li Zhao-Fang Bai Xiao-He Xiao Department of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijingChina Department of military Patient Management The Fifth Medical Center of PLA General HospitalBeijingChina Department of Hepatology China military Institute of Chinese Materia The Fifth Medical Center of PLA General HospitalBeijingChina Departmentof Hepatology National Key Laboratory of Kidney DiseasesBeijingChina

Background: Idiosyncratic drug-induced liver injury(IDILI) is a serious side effect of drugs, Epimedii Folium(EF) is unequivocally implicated in idiosyncratic liver injury onset, potentially due to its ability to perturb the NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome. Fructus Ligustri Lucidi(FLL), a frequently used medicinal combination with EF, has not yet been investigated for its ability to ameliorate EF-associated hepatotoxicity. Aims and Objectives: Study on the mechanism of compatibility of FLL to alleviate liver injury caused by EF. Materials and Methods: Western blot was used to determine the expression of related proteins, ELISA was used to detect the secretion of related inflammatory factors IL-1β, IL-18, IL-6 and TNF-α, liver injury indexes were detected and liver pathological tissue staining was used to evaluate the liver injury. Results: Our results demonstrated that EF exerted a particular augmenting effect on the stimulation of the NLRP3 inflammasome mediated by nigericin or ATP, whereas FLL suppressed the NLRP3 inflammasome stimulation. Furthermore, an equal EF to FLL ratio significantly reduced the stimulatory effects of EF. Moreover, EF has the potential to induce hepatic injury and augment pro-inflammatory cytokine synthesis in rats subjected to LPS. However, when combined with FLL, the detrimental effects of EF were mitigated. Conclusions: FLL possesses the capacity to attenuate EF-associated hepatotoxicity by suppressing EF-triggered NLRP3 inflammasome activation. Thus, FLL holds promise for improving the clinical safety profile of EF, shedding light on the potential of compatibility and detoxification theories in traditional Chinese medicine.

关键词： Epimedii Folium Fructus Ligustri Lucidi idiosyncratic drug-induced liver injury NOD-like receptor family pyrin domain containing 3 inflammasome traditional Chinese medicine

T2 relaxation time measurements in the brains of scalded rats

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Science China(Life Sciences) 2017年第1期60卷 5-10页

作者： Tao Jiang Liqi Xie Xin Lou Dawei Li Zhiye Chen Huafeng Xiao Lin Ma Department of Radiology PLA General Hospital Department of Radiology PLA 401 Hospital Department of Burn and plastic Surgery PLA 304 Hospital Department of Radiology PLA 302 Hospital

This study aimed to evaluate the T2 relaxation time of the brain in severely scalded rats using a magnetic resonance （MR） T2 mapping sequence, and to investigate the correlation between T2 relaxation time and plasma glucose level. Twenty-eight Wistar rats were randomly divided into the scalded group （n = 21）and control group （n = 7）. Magnetic resonance scans were performed with T1WI, T2WI, and T2-mapping sequences in the scalded group; the scans were performed 1 day prior to scalding and 1, 3, 5, and 7 days post-scalding; in addition, identical MR scans were performed in the control group at the same time points. T2-maps were generated and T2 relaxation times were acquired from the following brain regions： the hippocampus, thalamus, caudate-putamen, and cerebrum. Pathological changes of the hippocampus were observed. The plasma glucose level of each rat was measured before each MR scan, and a correlation analysis was performed between T2 relaxation time and plasma glucose level. We found that conventional T 1WI and T2WI did not reveal any abnormal signals or morphological changes in the hippocampus, thalamus, caudate-putamen,： or cerebrum post-scalding. Both the T2 relaxation times of the selected brain regions and plasma glucose levels increased 1, 3, and 5 days post-scalding, and returned to normal levels 7 days post-scalding. The most marked increase of T2 relaxation time was found in the hippocampus; similar changes were also revealed in the thalamus, caudate-putamen, and cerebrum. No correlation was found between T2 relaxation time and plasma glucose level in scalded rats. Pathological observation of the hippocampus showed edema 1, 3, and 5 days post-scalding, with recovery to normal findings at 7 days post-scalding. Thus, we concluded that T2 mapping is a sensitive method for detecting and monitoring scald injury in the rat brain. As the hippocampus is the main region for modulating a stress reaction, it showed significantly increased water content along with

关键词： burns magnetic resonance imaging T2 relaxation time hippocampus