1.Microbial metabolite 3-indolepropionic acid alleviated PD pathologies by decreasing enteric glia cell gliosis via suppressing IL-13Rα1 related signaling pathways.
Meiyu SHANG ; Jingwen NING ; Caixia ZANG ; Jingwei MA ; Yang YANG ; Zhirong WAN ; Jing ZHAO ; Yueqi JIANG ; Qiuzhu CHEN ; Yirong DONG ; Jinrong WANG ; Fangfang LI ; Xiuqi BAO ; Dan ZHANG
Acta Pharmaceutica Sinica B 2025;15(4):2024-2038
Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.
2.Erratum: Author correction to "Microbial metabolite 3-indolepropionic acid alleviated PD pathologies by decreasing enteric glia cell gliosis via suppressing IL-13Rα1 related signaling pathways" Acta Pharm Sin B 15 (2025) 2024-2038.
Meiyu SHANG ; Jingwen NING ; Caixia ZANG ; Jingwei MA ; Yang YANG ; Zhirong WAN ; Jing ZHAO ; Yueqi JIANG ; Qiuzhu CHEN ; Yirong DONG ; Jinrong WANG ; Fangfang LI ; Xiuqi BAO ; Dan ZHANG
Acta Pharmaceutica Sinica B 2025;15(9):4972-4972
[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].
3.Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases
Chunli CHEN ; Siyu YAN ; Bangbei WAN ; Yangyiyi YU ; Jinrong ZENG ; Lina TAN ; Jianyun LU
Journal of Central South University(Medical Sciences) 2024;49(6):932-942
Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases. Methods:The two-sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10-8).Causal effect estimates were generated using the inverse-variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed. Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn's disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema. Conclusion:Eczema is associated with an increased risk of Crohn's disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.
4.Effect of tetrahydropalmatine on expression of Cav1. 2 in dorsal root ganglion neurons in mice with sciatic nerve chronic constriction injury
Haibo JIANG ; Jun WANG ; Jianhua SU ; Mingming FANG ; Nan YANG ; Jiawei YANG ; Fen WAN ; Hang XIAO ; Jinrong TANG
Chinese Pharmacological Bulletin 2015;(11):1598-1602,1603
Aim To investigate the analgesic effect of tetrahydropalmatine on Cav1 . 2 expression in the dorsal root ganglion ( DRG) of mice with sciatic nerve chronic constriction injury ( CCI ) -induced neuropathic pain. Methods Forty male C57 BL/6 mice were randomly divided into 5 groups ( n =5 ): sham group ( group S) , CCI group ( group C ) and L-THP group ( group L) . Steady mice models of neuropathic pain were es-tablished by inducing CCI of sciatic nerve. According to development of neuropathic pain in mice, L group was divided into induction period, induction with ma-intenance period and long-term low-dose group. The mice were intraperitoneally administered with 45 mg · kg-1 tetrahydropalmatine in induction ( day 0~5 ) , in-duction with maintenance ( day 0~5 , 14~19 ) period of neuropathic pain state. From the instant after opera-tion, 15 mg · kg-1 tetrahydropalmatine was injected into the long-term low-dose group once per day for 19 days. Then, the behavior changes of mice were moni-tored. Moreover, the threshold of mechanical and ther-mal stimuli was tested. In addition, the expression of Cav1 . 2 protein was detected by Western blot and im-munohistochemical staining. Results The lowest ex-pression of Cav1 . 2 was observed in group C and the highest expression level of Cav1 . 2 was found in group S. Cav1. 2 expression was significantly up-regulated in induction period group, induction with maintenance period group and long-term low-dose group ( P<0. 05 , P<0. 01). Compared with group C, high dose of tet-rahydropalmatine in induction period group, induction with maintenance period group and long-term low-dose group showed reduced mechanical allodynia and ther-mal hyperalgesia induced by nerve injury ( P <0. 05 , P<0. 01). Meanwhile, high dose of tetrahydropalma-tine significantly relieved the mechanical allodynia in induction period group, induction with maintenance period group and thermal hyperalgesia in maintenance period group (P<0. 05). However, there was no ob-vious effect on mechanical allodynia and thermal hyper-algesia induced by nerve injury ( P >0. 05 ) in long-term low-dose group. Conclusions High dose of tet-rahydropalmatine in induction period group, induction with maintenance period group and low-dose among the whole experiment process obviously relieves the neuro-pathic pain induced by nerve injury. The analgesic effect of tetrahydropalmatine on neuropathic pain may be due to the increased expression of Cav1 . 2 protein in DRG neurons.
5.Imaging Dynamic Follow-up of SARS:A Report of 15 Cases
Yong FAN ; Ping LI ; Gang LIU ; Xiang CHENG ; Jigang WANG ; Huisheng JIANG ; Jinrong WAN ; Jun CUI ; Long LI ; Zunyi MA
Journal of Practical Radiology 2001;0(05):-
Objective To follow-up the imaging findings in the SARS.Methods The serial thoracic images in 15 cases of SARS were taken in 7 months from the onset of this disease,and the imaging findings were analysed.Results The detecting rate of the pathological changes in lung by spiral CT was higher than that of X-ray film(t = 5.5228,P

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