1.Epigallocatechin gallate suppresses 1-methy1-4-phenyl-pyridinium-induced the damage of oxidative stress in PC12 cells by activating nuclear factor-related factor 2
Qinyong YE ; Xianjie XU ; Linfeng YE ; Xiaodong ZHANG ; Bixia HUANG ; Yuangui ZHU ; Xiaochun CHEN
Chinese Journal of Neurology 2012;45(6):387-391
Objective To investigate the relationship between the neuroprotective effect of epigallocatechin gallate ( EGCG ) for PC12 cells induced by 1-methyl-4-phenyl-pyridinium ( MPP+ ) and activating nuclear factor-related factor 2 ( NRF2 ).Methods Well differentiated PC12 cells treated with MPP+ were used as the in vitro cell models,and PC12 cells were pretreated with different concentrations of EGCG.MTT assay was used to investigate the cell viability.Western blot was used to observe the expression of NRF2 in cells and distribution in the nucleus and the cytoplasm.Real-time PCR was used to observe the antioxidant enzymes,HO-1 and NQO1 mRNA expression.Results Pretreatment of PC12 cells with different concentrations of EG CG for an hour could restore cell viability.Western blot showed that expression of NRF2 in cells treated with MPP+ for 24 hours was increased 148% +5% compared with the control group (t =6.102,P <0.01 ).The level of NRF2 in EGCG pretreated group was 188% + 6% compared with the control group(t =11.172,P <0.01 ).Moreover the NRF2 protein level in the nuclear was also increased.Western blot showed that the NRF2 protein level in the nuclear was 258% +2% compared with the control group (t =21.995,P < 0.01 ).Further research found U 120,an inhibitor of ERK,could inhibit the effect of EGCG.The levels of NRF2 in both samples were 148% ± 15% and 158% ± 1% compared with their respective control groups(t =6.118,8.058,both P <0.01 ).In accordance with the NRF2 data,real-time PCR indicated that the levels of HO-1 and NQO1 mRNA expression increased obviously in the group pretreated with EGCG.Likewise,U120 could also inhibit HO-1 and NQO1 mRNA expression induced by EGCG.Conclusions EGCG can repair oxidative damage to PC12 cells induced by MPP+.The protective effect may be related through the ways to activate ERK-NRF2 and induce downstream of antioxidant enzyme expression,such as HO-1 and NQO1.
2.Study on Application Law of Stimulation Parameters of Transcutaneous and Transcranial Electrical Stimulation for Post-Stroke Movement Disorders Based on Data Mining
Jingyun XIU ; Liangxiao MA ; Linghui MA ; Tianyi SUN ; Xu QIAN ; Qinyong ZHANG ; Xiuyan WANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(3):42-47
Objective To explore the application low of stimulation parameters of transcutaneous electrical acupoint stimulation(TEAS)and transcranial direct current stimulation(tDCS)for post-stroke movement disorders based on data mining.Methods The relevant clinical research literature was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed and Web of Science from January 2000 to May 2023.A database was set up after quality assessment.Frequency analysis,association rules and complex network analysis were used to explore the application law of core acupoints and electrical stimulation parameters.Results A total of 79 articles were included and 128 groups of data were contained.For TEAS,the core acupoints included Waiguan(TE5),Shousanli(LI10),Zusanli(ST36),Hegu(LI4),Neiguan(PC6),Yanglingquan(GB34),etc.,while the most commonly used acupoint combinations of upper limb and lower limb were Shousanli(LI10)-Waiguan(TE5)and Yanglingquan(GB34)-Zusanli(ST36).Among the electrical stimulation parameters of TEAS,the frequencies used vary widely,and 100 Hz was most commonly used,while 2 Hz TEAS was also mainly used for stimulating acupoints located on upper limbs in the treatment of flaccid paralysis.The application of other electrical stimulation parameters was relatively consistent.The bidirectional symmetrical square-wave with 200-250 μs pulse-width was used in majority of studies.The stimulus intensity was mostly determined by patient tolerance.For tDCS,stimulation electrodes were often positioned on the projection of the primary M1,and the safe stimulus intensity was mostly set as 1 to 2 mA.Conclusion In the treatment of post-stroke movement disorders,appropriate acupoints and electrical stimulation parameters of TEAS should be determined on the muscle strength and muscle tension of stroke patients at different stages after stroke,particularly the selection of electric stimulating frequency.
3.Taking "Seven Emotions Scale" as an Example to Explore the Suitability of Four Qualitative Methods in the Development of TCM Scale
Simeng YAO ; Xiaoying NING ; Qinyong XU ; Yuanfang CHEN ; Wei ZHENG ; Jihong LIU ; Fengbin LIU ; Zhengkun HOU
Journal of Traditional Chinese Medicine 2024;65(20):2102-2108
ObjectiveTo explore the suitability of four qualitative research methods in the development of TCM scale. MethodsTaking the development of "Seven Emotions Scale" as an example, we conducted semi-structured interviews with 31 patients of emotional disorders and 10 healthy people by objective sampling, and collected psychological feelings and emotional cognition data related to seven emotions according to the interview outline. Two qualitative methods, descriptive qualitative research and descriptive phenomenology, were used to analyze the data and construct the item library of the scale. The conceptual framework of the scale was constructed by using commonly used grounded theory and frame analysis. ResultsDuring data analysis, it is found that the themes extracted from descriptive phenomenology were not easily understood by the interviewees, and it is difficult for the researchers to truly achieve the "suspension" required by phenomenology. Considering the feasibility and convenience of the researchers' actual operation, as well as whether the initial purpose of the scale research can be intuitively included in the interviewees' views and feelings, descriptive phenomenology is not suitable for the formation of scale items. Using descriptive qualitative research method to analyze the interview data of healthy people and patients with emotional disorders, 306 and 476 scale items were obtained respectively. Through grounded theory, five selective codes were obtained: physical symptoms, external manifestations, psychological feelings, behaviors and emotional control. Using frame analysis, four themes including physical symptoms, psychological feelings, behavior and emotional cognition were constructed. Both methods can be used to construct the conceptual frame of scale, but the framework analysis is more convenient and can better ensure the transparency of the research. ConclusionDescriptive qualitative research methods can be used to form the item library of TCM scales. Framework analysis is more suitable for the construction of the conceptual framework of the scale than grounded theory, while descriptive phenomenology is not suitable for the development of TCM scales.
4.Targeting macrophagic 17β-HSD7 by fenretinide for the treatment of nonalcoholic fatty liver disease.
Xiaoyu DONG ; Yiting FENG ; Dongqin XU ; Mengya ZHANG ; Xiao WEN ; Wenhao ZHAO ; Qintong HU ; Qinyong ZHANG ; Hui FU ; Jie PING
Acta Pharmaceutica Sinica B 2023;13(1):142-156
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and macrophage polarization plays an important role in its pathogenesis. However, which molecule regulates macrophage polarization in NAFLD remains unclear. Herein, we showed NAFLD mice exhibited increased 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7) expression in hepatic macrophages concomitantly with elevated M1 polarization. Single-cell RNA sequencing on hepatic non-parenchymal cells isolated from wild-type littermates and macrophage-17β-HSD7 knockout mice fed with high fat diet (HFD) for 6 weeks revealed that lipid metabolism pathways were notably changed. Furthermore, 17β-HSD7 deficiency in macrophages attenuated HFD-induced hepatic steatosis, insulin resistance and liver injury. Mechanistically, 17β-HSD7 triggered NLRP3 inflammasome activation by increasing free cholesterol content, thereby promoting M1 polarization of macrophages and the secretion of pro-inflammatory cytokines. In addition, to help demonstrate that 17β-HSD7 is a potential drug target for NAFLD, fenretinide was screened out from an FDA-approved drug library based on its 17β-HSD7 dehydrogenase inhibitory activity. Fenretinide dose-dependently abrogated macrophage polarization and pro-inflammatory cytokines production, and subsequently inhibited fat deposition in hepatocytes co-cultured with macrophages. In conclusion, our findings suggest that blockade of 17β-HSD7 signaling by fenretinide would be a drug repurposing strategy for NAFLD treatment.