1.Effect of neuregulin 1 on pyroptosis of retinal ganglion cells in early-stage di-abetic rats by regulating NOD-like receptor family pyrin domain containing protein 3/Caspase-1/Gasdermin D pathway
Yuteng ZHU ; Miao CUI ; Changjing SONG ; Haibo YAN ; Baojun WANG
Recent Advances in Ophthalmology 2024;44(12):950-954
Objective To observe the effect of neuregulin-1(NRG-1)on retinal ganglion cells(RGCs)in Zucker Di-abetic Fatty(ZDF)rats and explore the mechanism of NRG-1 in exerting neuroprotective effects on the retina.Methods Twenty-four 8-week-old male ZDF rats(24 eyes)were selected.Diabetic obese rat models were established by feeding a high-fat and high-sugar diet(Purina 5008).After 16 weeks,they were randomly divided into the ZDF group and the NRG-1 group(12 rats in each group).Rats in the NRG-1 group received intravitreal injection of human recombinant NRG-1(once a week for a total of two times),rats in the ZDF group were used as negative controls,and Zucker lean control(ZLC)rats were selected as blank controls(ZCL group).The changes in the number of RGCs in rats of each group were observed by immunofluorescence staining.The protein expressions of NOD-like receptor family pyrin domain containing protein 3(NLRP3),Caspase-1,and Gasdermin D(GSDMD)in the retina of rats in each group were observed by immuno-histochemistry and Western blot.Results After 16 weeks of eating a high-fat diet,compared with the ZLC group,the fasting blood glucose of rats in the ZDF group significantly increased(P<0.001).The results of immunofluorescence stai-ning showed that the RGCs of rats in the ZLC group were continuously and neatly arranged;compared with the ZLC group,the number of RGCs of rats in the ZDF group significantly decreased(P<0.001);compared with the ZDF group,the num-ber of RGCs of rats in the NRG-1 group significantly increased(P<0.01).The immunohistochemical results showed that there were statistically significant differences in the average optical density values of NLRP3,Caspase-1 and GSDMD in the retina of rats in each group(all P<0.01);compared with the ZLC group,the average optical density values of NLRP3,Caspase-1 and GSDMD in the retina of rats in the ZDF group were higher(all P<0.01);compared with the ZDF group,the average optical density values of NLRP3,Caspase-1 and GSDMD in the retina of rats in the NRG-1 group significantly de-creased(all P<0.05).Western blot results showed that there were statistically significant differences in the protein ex-pression levels of Brn3a,NLRP3,Caspase-1 and GSDMD in the retina of rats among all groups(all P<0.01);compared with the ZLC group,the protein expression of Brn3a significantly decreased,while the protein expressions of NLRP3,Caspase-1 and GSDMD significantly increased in the ZDF group(all P<0.01);compared with the ZDF group,the protein expression of Brn3a significantly increased,while the protein expressions of NLRP3,Caspase-1 and GSDMD significantly decreased in the NRG-1 group(all P<0.01).Conclusion After retinal lesions occur in diabetic rats,NLRP3,Caspase-1 and GSDMD are all significantly activated.NRG-1 can reduce the expressions of NLRP3,Caspase-1 and GSDMD,reducing damage to RGCs.
3.Shenlian extract attenuates TNF-α-induced ECV304 injury by regulating Nrf2/Keap1 signaling pathway.
Chun-Miao WANG ; Yu-Jie LI ; Jing-Jing LI ; Yuan-Long ZANG ; Xi-He CUI ; Min SONG ; Qing YANG ; Ying CHEN ; Qi LI ; Wei-Yan CAI ; Xiao-Gang WENG ; Ya-Jie WANG ; Xiao-Xin ZHU
China Journal of Chinese Materia Medica 2021;46(13):3402-3409
This study aimed to investigate the effect and the possible mechanism of Shenlian( SL) extract on tumor necrosis factor-α( TNF-α)-induced ECV304 injury. After the establishment of TNF-α-induced ECV304 cells injure model,MTT assay was used to detect cell viability and the level of reactive oxygen species( ROS) was measured by flow cytometry. The contents of superoxide dismutase( SOD),malondialdehyde( MDA),nitric oxide( NO),endothelin-1( ET-1) and interleukin-1β( IL-1β) in the supernatant were detected by biochemical method and enzyme linked immunosorbent assay( ELISA). The expression levels of apoptosis-related proteins B-lymphoma-2 gene( Bcl-2),Bcl-2 associated X protein( Bax),caspase-3,caspase-9 and nuclear factor E2 associated factor2( Nrf2)/Kelch like epichlorohydrin associated protein-1( Keap1) signaling pathway related proteins Nrf2,Keap1,quinone oxidoreductase( NQO1) and heme oxygenase 1( HO-1) were detected by Western blot. The results showed that 50 μg·L-1 TNF-α significantly damaged ECV304 cells,induced the impairment of cell viability( P<0. 01),the increase of ROS production,the decrease of SOD activity,and the increase of MDA,NO,ET-1 and IL-1β( P<0. 01),meanwhile,it caused the up-regulation of Keap1,caspase-9 and Bax protein expression,and down-regulation of NQO1 and Bcl-2 protein expression( P<0. 05) compared with the control group.Compared with the model group,SL extract reduced the damage of ECV304 cells induced by TNF-α,improved cell viability,reduced ROS production,increased SOD activity and decreased MDA,NO,ET-1,IL-1β content( P<0. 01 or P<0. 05). In addition,SL extract also down-regulated the protein expression levels of Keap1,caspase-3,caspase-9 and Bax,and increased the protein expressions of Nrf2,NQO1,HO-1 and Bcl-2( P<0. 01 or P<0. 05). The above results indicate that SL extract can provide protective effect on ECV304 cells injury induced by TNF-α,alleviate oxidative stress injury,inflammation and apoptosis,and its mechanism may be related to regulating Nrf2/Keap1 signaling pathway.
Apoptosis
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Kelch-Like ECH-Associated Protein 1/metabolism*
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NF-E2-Related Factor 2/metabolism*
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Oxidative Stress
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Plant Extracts
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Signal Transduction
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Tumor Necrosis Factor-alpha/genetics*
4.Current situation and influence factors of suicidal self-injurious behavior in teenagers in Guangdong
Yan XU ; Sui-yun WENG ; Song-kang LIU ; Miao-ling JIANG ; Min YU ; Cui-wei CHEN
Shanghai Journal of Preventive Medicine 2021;33(7):566-569
Objective:To investigate the current situation of suicidal self-injurious behavior in teenagers and analyze its influencing factors. Methods:From January to November 2020, a stratified sampling method was used to investigate 707 teenagers in Guangdong. The “questionnaire of health-related behaviors of Chinese teenagers” compiled by the Chinese Center for Disease Control and Prevention was used anonymously to investigate the current situation of suicidal self-injurious behavior of the teenagers. The chi-square test was used for univariate analysis, and logistic regression was used for multivariate analysis. Results:The incidence rate of suicidal self-injurious behavior was 14.57% (103/707). It was 13.31% (45/338) in males, 15.72% (58/369) in females, 13.83% (48/347) in junior high school students and 15.28% (55/360) in senior high school students. There was no statistical significance in the incidence of suicidal self-injurious behavior of teenagers between different genders, different learning stages, smoking or not, asexual behavior or not, gambling or not, and fighting or not (all
5.Data Mining-Based Macroscopic Exploration of Clinical Medication of Chinese Medicine for Liver Cancer
Ya-gang SONG ; Ming BAI ; Lin-lin CUI ; Yan LI ; Li-ling XIANG ; Le KANG ; Ming-san MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2021;27(13):146-152
Objective:To explore the macroscopic medication rule of Chinese medicine for the treatment of primary liver cancer and provide references for clinical medication. Method:The databases of CNKI,VIP, and Wanfang Data were searched for research articles published from September 1959 to June 2019 with the terms of "Chinese medicine" and "liver cancer". A database was established based on the collected Chinese medicinal prescriptions for the treatment of primary liver cancer. The frequency,clustering, and association rules were analyzed by Excel, etc. Result:In this study,106 effective articles were included,and after the modified prescriptions were removed, 92 effective prescriptions were screened out,involving 281 Chinese herbal medicines used for 1 181 times in total. The top 5 high-frequency drugs were Poria (deficiency-tonifying),Astragali Radix (heat-clearing),Bupleuri Radix (blood-activating and stasis-resolving),Paeoniae Radix Alba (urination-promoting and dampness-draining), and Codonopsis Radix (Qi-regulating). The analysis of drug flavor with a frequency higher than 10 showed that most of the drugs were sweet,bitter, and pungent in flavor,cold,warm, and plain in nature,and acted on spleen and liver meridians. Four combinations and 10 herbal pairs were obtained by the cluster analysis of high-frequency drugs and association analysis, respectively. The high-frequency drugs and potential herbal pairs were classified targeting the specific clinical syndromes in different stages of liver cancer. Conclusion:Replenishing Qi, invigorating spleen,clearing heat, removing toxin,activating blood, and resolving stasis were the basic principles for the treatment of primary liver cancer. The combination of those drugs was the main therapeutic strategy. In addition,the resulting 10 potential herbal pairs from high-frequency drugs and cluster analysis could inspire the clinical treatment of primary liver cancer in different clinical stages with various clinical syndromes, which was of reference value for the clinical medication.
6.Dose selection of chloroquine phosphate for treatment of COVID-19 based on a physiologically based pharmacokinetic model.
Cheng CUI ; Miao ZHANG ; Xueting YAO ; Siqi TU ; Zhe HOU ; Valerie Sia JIE EN ; Xiaoqiang XIANG ; Jing LIN ; Ting CAI ; Ning SHEN ; Chunli SONG ; Jie QIAO ; Shun ZHANG ; Haiyan LI ; Dongyang LIU
Acta Pharmaceutica Sinica B 2020;10(7):1216-1227
Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships. The model was also validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID, Days 2-5: 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1: 750 mg and 500 mg, Days 2-3: 500 mg BID, Days 4-5: 250 mg BID, CQ phosphate), and other vulnerable populations (.., renal and hepatic impairment and elderly patients, Days 1-5: 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.
7. Analysis and Significance of Autophagy in Liver Cancer Cells Induced by Traditional Chinese Medicine
Ya-gang SONG ; Lin-lin CUI ; Yan LI ; Ming-san MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(24):179-187
Traditional Chinese medicine(TCM) and its components play a role in the field of anti-hepatocarcinoma. The definition of its mechanism of action in autophagy contributes to the development of TCM in the field of anti-hepatocarcinoma. In this paper, we summarized reports on the autophagy of liver cancer cells induced by TCM and its active ingredients, including those on promoting apoptosis and cycle inhibition induced by autophagy and inhibiting autophagy to block tumor cell cycle, but with a lack of systematic summarization. In this paper, according to different effect of TCM on autophagy induced by hepatocarcinoma, the TCM and its components were inductively analyzed in four aspects:inducing killing autophagy, inhibiting protective autophagy, inducing protective autophagy in liver cancer, and inducing unclear autophagy. According to the findings, TCMs and components that cause killing autophagy can inhibit the occurrence of autophagy, arrest cell cycle, induce cell senescence or promote apoptosis. TCMs and components that inhibit protective autophagy can inhibit protective autophagy and hepatoma cell proliferation. TCMs and components that induce protective autophagy have a significant anti-hepatocarcinoma effect, shall be considered to be combined with autophagy inhibitors to enhance the lethality of drugs on liver cancer cells, and become a new way for such drugs to treat liver cancer. TCMs and components with an unclear inductive effect shall be first identified for their type of autophagy, then combined with autophagy agonists or blockers according to the type of autophagy to enhance their anti-liver cancer effect, and provide a new clinical therapeutic approach for liver cancer. In the aspect of autophagy, this study not only reveals the molecular mechanism of anti-hepatocarcinoma of TCM, but also makes it a new way to study anti-hepatocarcinoma by TCM.
8.Spontaneous Regional Brain Activity in Healthy Individuals is Nonlinearly Modulated by the Interaction of ZNF804A rs1344706 and COMT rs4680 Polymorphisms.
Lingling CUI ; Fei WANG ; Miao CHANG ; Zhiyang YIN ; Guoguang FAN ; Yanzhuo SONG ; Yange WEI ; Yixiao XU ; Yifan ZHANG ; Yanqing TANG ; Xiaohong GONG ; Ke XU
Neuroscience Bulletin 2019;35(4):735-742
ZNF804A rs1344706 has been identified as one of the risk genes for schizophrenia. However, the neural mechanisms underlying this association are unknown. Given that ZNF804A upregulates the expression of COMT, we hypothesized that ZNF804A may influence brain activity by interacting with COMT. Here, we genotyped ZNF804A rs1344706 and COMT rs4680 in 218 healthy Chinese participants. Amplitudes of low-frequency fluctuations (ALFFs) were applied to analyze the main and interaction effects of ZNF804A rs1344706 and COMT rs4680. The ALFFs of the bilateral dorsolateral prefrontal cortex showed a significant ZNF804A rs1344706 × COMT rs4680 interaction, manifesting as a U-shaped modulation, presumably by dopamine signaling. Significant main effects were also found. These findings suggest that ZNF804A affects the resting-state functional activation by interacting with COMT, and may improve our understanding of the neurobiological effects of ZNF804A and its association with schizophrenia.
9.Expert consensus statement on Pudilan Xiaoyan Oral Liquid in clinical practice.
Lian-Xin WANG ; Qing MIAO ; Yan-Ming XIE ; Da-Can CHEN ; Su-Lun SUN ; Hong-Chun ZHANG ; Zhong-Wu JIA ; Tie-Nan LI ; Jia ZHU ; Li-Qing SHI ; Ping SONG ; Feng GAO ; Bao-Lin WEI ; Cui-Ling FENG ; Yi-Qing QU ; Ni-Ni QU ; Xue-Feng YU ; Nian-Zhi ZHANG ; Xue-Qing YU
China Journal of Chinese Materia Medica 2019;44(24):5277-5281
Pudilan Xiaoyan Oral Liquid has effects in clearing away heat and detoxifying,and is used to treat pharynx and throat swelling caused by the syndrome of excessive heat and toxin accumulation. Its efficacy is to relieve swelling and pain( redness,swelling and hot pain). It is included in the Chinese Pharmacopoeia of 2015 Edition,and has been listed in provincial health insurance directories of Shaanxi,Jiangsu,Liaoning,Hunan,Tianjin,Xinjiang and Hebei. It has been recommended by health departments of Beijing,Chongqing and other provinces as a preferred drug for the prevention and treatment of H1 N1 and HFMD,and listed in the diagnosis and Treatment Guide of HFMD by the Ministry of Health,the Clinical Application Guide of Chinese Patent Medicine edited by the Lung Department Disease Branch of China Association of Chinese Medicine,and the Clinical Practice Guide of Single Administration/Combined Administration of Antibiotics in Treatment of Common Infectious Diseases by China Association of Chinese Medicine. To further improve the clinician's understanding of drugs and better guide the rational clinical application,we invited front-line clinical experts from respiratory department,infectious department and dermatology of traditional Chinese and Western medicine to develop and compile the expert consensus. The consensus fully considered the clinical evidence and the expert clinical experience to give recommendations for clinical problems with evidence support and consensus suggestions for clinical problems without evidence support by the nominal group method.This consensus is based on clinical research evidence and expert experience in a simple and clear format,which provides a preliminary reference for the clinical use of the drug.
China
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Consensus
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Drugs, Chinese Herbal/therapeutic use*
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Humans
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Medicine, Chinese Traditional
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Nonprescription Drugs
10.Effect of GnRHa controlled ovarian hyperstimulation on mouse embryo implantation and its mechanism.
Qiong WU ; Hua-Zhou XU ; Jiang-Xia YANG ; Zhi-Li LI ; Tian FU ; Hui-Lan DU ; Cui-Miao SONG
Acta Physiologica Sinica 2018;70(5):489-496
The purpose of the present study was to investigate the effects and underlying mechanism of gonadotropin-releasing hormone agonist (GnRHa) controlled ovarian hyperstimulation (COH) on embryo implantation in mice. Forty female Kunming mice aged 9 weeks were randomly divided into two groups (control and COH groups). The COH group received intraperitoneal (i.p.) injections of aminocyclin acetate (GnRHa), human menopausal gonadotropin (HMG) and human chorionic gonadotropin (hCG), while the control group was given equal amount of physiological saline by i.p. injection. One male mouse and two female mice were put into the same cage at 16:00 on the hCG injection day, and on the fourth day of pregnancy, 10 mice from each group were killed. The levels of serum estradiol (E) and progesterone (P) were measured by radioimmunoassay; HE staining was used to observe the morphology of ovarian and endometrial tissues. The protein expression levels of endometrial leukemia inhibitory factor (LIF), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), heparin-binding epidermal growth factor-like growth factor (HB-EGF) and glycodelin A were detected by Western blot and immunohistochemistry. Ten mice from each group were sacrificed on the eighth day of pregnancy, and the status of the uterus and the average number of blastocysts were observed. The results showed that, compared with control group, the serum E level in COH group was significantly decreased (P < 0.05), while the P level was increased significantly (P < 0.05); the ovarian follicles at different developmental stages were rare, corpus lutea (CL) were visible and multiple, the endometrium was thinned, and the number of endometrial glands was reduced (P < 0.05); the contents of LIF, p-STAT3, HB-EGF and glycodelin A in the endometrium were decreased significantly (P < 0.05) on the fourth day of pregnancy; mouse blastocysts developed slowly and were decreased in number on the eighth day of pregnancy (P < 0.05). The above results suggest that GnRHa COH can affect embryo implantation in mice. The mechanism may be related to the imbalance of gonadal hormone, the changes in the structure of the endometrium and the expressions of LIF, p-STAT3, HB-EGF and glycodelin A in the implantation stage, which may lead to the decrease of endometrial receptivity and the abnormal dialogue between the embryo and the uterus.

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