1.Immunity suppressive effect and possible mechanism of SEB as a superantigen
Xuran YANG ; Xu ZHANG ; Yuzhang WU
Journal of Third Military Medical University 2003;0(22):-
Objective To study the immunity suppressive effect of the staphylococcal enterotoxin as a super-antigen and investigate its mechanism.Methods BALB/c mice aged 8-12 weeks were randomly assigned to receive 0.2 ml injection of 50 ?g/ml staphylococcal enterotoxin B(SEB)(n=20) or 0.2 ml physiological saline(n=20).One day later,all mice were sacrifice to collect the splenocytes which were employed to detect the expression of TGF-?1 and to countthe cells expressing CD4 and CD25 by flow cytometry(FCM).Results FMC showed that a remarkable increase of cells that expressed CD4 and CD25 in the SEB-primed splenocytes as compared with the saline primed splenocytes.Conclusion SEB,which is used as a superantigen in vivo,can induce the regulatory cells bearing suppressive activity.This may be partial mechanism of SEB-induced hyporesponsiveness.
2.Recent progress of migraine and pregnancy
Liuqing WANG ; Xuran XU ; Shoucheng ZHANG ; Hong WANG ; Bei SHAO
Clinical Medicine of China 2017;33(6):551-554
As a kind of nervous system disease,migraine is more common in female,and has the clinical characteristics of repeated attacks,it is of great significance with standardized treatment in the control of the attacks.Yong female patients with migraine during pregnancy and lactation stage will face lots of special problems because they must first consider the impact of treatment on the mother and fetus.Generally,non-drug therapy is recommended as a first-line treatment,if it is not sufficiently effective,paracetamol is recommended during the pregnancy or sporadic use of sumatriptan,NSAIDs is not recommended during the first or third trimester of pregnancy.Preventive therapy should only be considered in the most severe cases.This review summarized recent documents of the safety of the most used antimigraine medications during pregnancy and breastfeeding,in order to provide treatment recommendations in clinical practice.
3.Chemical analysis of urinary calculi in pediatric patients exposed to infant formula milk powder contaminated with melamine
Li XU ; Xuran LI ; Xilai LI ; Lunjuan YANG ; Zhi CHEN ; Jun YIN ; Lijun TANG ; Xiaoyan LIN ; Lijuan WANG ; Yu SUN ; Hongzhan XIAO ; Ning SUN ; Weiping ZHANG ; Minglei LI ; Ying SHEN
Chinese Journal of Urology 2009;30(3):188-190
Objective To identify the main compositions of urinary calculi found in pediatric patients who had the history of exposing to infant formula milk powder contaminated with melamine and try to find out the urinary calculus formation mechanism in these patients.Methods Sixteen patients were studied.These infant patients with urinary calculi due to consumption of melamine tainted milk powder had been admitted to hospital from June,2008 to August,2008.The components of the urinary calculi were separated by liquid chromatograph,and identified by electrospray ionization mass spectrometry,electron bombard ionization mass spectrometry,Fourier transform infrared spectroscopy,and quantitatively determined by liquid chromatograph.Results The main chemical components of the urinary ealculi were melamine and uric acid.The molar ratio of uric acid tO melamine was 2:1.Conclusion The main urinary calculus formation mechanism in infant patients who exposed to the inrant formula milk powder contaminated with melamine is melamine and uric acid formed indissoluble complex.
4.Effect of Huangqintang on Intestinal Flora in Mice with Ulcerative Colitis and Its Protective Mechanism on Intestinal Mucosal Barrier
Yaqing LIU ; Hangyu XU ; Dunfang WANG ; Bin LIU ; Xuran MA ; Xue FENG ; Weipeng YANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(7):11-19
ObjectiveTo evaluate the pharmacodynamic effect of Huangqintang (HQT) on ulcerative colitis (UC) model mice and investigate its protective effect against UC by regulating intestinal flora. MethodMale Balb/c mice were randomly divided into control group,model group, high-, medium-, and low-dose HQT groups (20, 10, 5 g·kg-1), flora interference group, flora interference model group, and flora interference-drug treatment group (HQT, 20 g·kg-1). The flora interference model was constructed through intragastric administration of antibiotics (200 mg·kg-1 bacitracin and 200 mg·kg-1 vancomycin) for 8 d, and the UC model was constructed by allowing mice with free access to 3% dextran sulfate sodium (DSS) solution for 7 d. HQT was administered for 7 d. After the experiments, the mice were sacrificed, and blood, colon, and feces were collected. Hematoxylin-eosin (HE) staining was performed to observe the colonic lesions. The serum levels of interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression of Claudin1, MUC1, Occludin, and zonula occludens-1(ZO-1) in colon tissues was detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. The fecal DNA of mice was extracted and analyzed by high-throughput sequencing. ResultCompared with the normal group, the model group showed increased serum content of IL-4, IL-6, and TNF-α (P<0.05, P<0.01) and decreased IL-10 (P<0.05). Compared with the model group, the HQT groups displayed decreased serum levels of IL-4, IL-6, and TNF-α (P<0.05, P<0.01), increased IL-10 content (P<0.01), increased mRNA and protein expression levels of Claudin1, MUC1, Occludin, and ZO-1 (P<0.05, P<0.01). After flora interference, the diversity and abundance of intestinal bacteria decreased. To be specific, Proteobacteria increased (P<0.01), and Firmicutes and Bacteroidetes decreased (P<0.01). After UC induction by DSS, Bacteroidetes and Tenericutes decreased (P<0.05). The high-, medium-, and low-dose HQT groups showed increased Bacteroidetes and Tenericutes (P<0.05, P<0.01) and decreased Firmicutes (P<0.05). Additionally, the abundance of Lactobacillus, Lachnospiraceae NK4A136 group, Escherichia-Shigella, and Helicobacteris was positively proportional to the dose of HQT. ConclusionHQT can inhibit the inflammatory response of UC mice, restore the imbalance of intestinal flora, and repair the damaged intestinal mucosal barrier.
5.Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics.
Jian GAO ; Zhigui WU ; Mingxia ZHAO ; Rui ZHANG ; Manru LI ; Dongdong SUN ; Haibo CHENG ; Xianjia QI ; Yuxian SHEN ; Qiang XU ; Hongqi CHEN ; Dijun CHEN ; Yang SUN
Acta Pharmaceutica Sinica B 2022;12(1):149-166
Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.