1.Suppression of nicotinic ACh receptors-mediated currents by activation of Eph/Ephrin-B1 signaling involves Src tyrosine kinase and mitogen-activated protein kinase in ciliary ganglion neurons.
Yuan-Peng XIA ; Bo HU ; Yu-Nan ZHOU ; Ling MAO ; Ruo-Lian DAI ; Li-Ping DONG
Acta Physiologica Sinica 2008;60(4):462-468
Recent studies showed that Eph/Ephrin tyrosine kinase family plays an important role in the development and functional maintenance of the nervous system, but its function in the sympathetic nervous system is still obscure. In the present study, we examined the effect of Eph/Ephrin-B1 signaling on the whole-cell currents mediated by either alpha7 or alpha3-nicotinic acetylcholine receptors (nAChRs) in acutly dissociated ciliary ganglion (CG) neurons. Firstly, we detected the effect of Ephrin-B1 on nAChRs currents. The neurons were randomly divided into control group, Ephrin-B1Fc-treated group that was stimulated by recombinant Ephrin-B1Fc, IgG-treated group, and Ephrin-B1-treated group. Secondly, we studied the regulatory mechanism of Ephrin-B1Fc on nAChRs currents. The neurons were randomly divided into control group, Ephrin-B1Fc-treated group, PP2 (inhibitor of Src tyrosine kinase) or PD98095 (antagonist of mitogen-activated protein kinase)-treated group, Ephrin-B1Fc + PP2 or PD98095-treated group. The results showed that there was no significant difference between the currents in control group, IgG-treated group and Ephrin-B1-treated group, but Ephrin-B1Fc significantly suppressed both alpha3-nAChRs and alpha7-nAChRs-mediated currents (P=0.002, P=0.003). Pretreatment with PP2 or PD98095 could partially rescue the Ephrin-B1Fc-induced suppression of currents mediated by alpha3-nAChRs or alpha7-nAChRs respectively. These results suggest that the Eph/Ephrin-B1 signaling may inhibit alpha3-nAChRs and alpha7-nAChRs-mediated currents on CG neurons, involving Src tyrosine kinase and mitogen-activated protein kinase signaling in the regulation of sympathetic nervous system.
Ephrin-B1
;
metabolism
;
Ganglia, Parasympathetic
;
enzymology
;
Mitogen-Activated Protein Kinases
;
metabolism
;
Neurons
;
enzymology
;
Receptors, Nicotinic
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metabolism
;
Signal Transduction
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alpha7 Nicotinic Acetylcholine Receptor
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metabolism
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src-Family Kinases
;
metabolism
2.Research Progress on Animal Models of Menopausal Syndrome: A Review
Dan-ni ZHOU ; Ruo-nan WEI ; Meng-jiao KANG ; Jia CHEN ; Lin-hua ZHAO ; Wei ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2021;27(18):243-250
In order to explore the pathological mechanism of perimenopausal syndrome and seek prevention and treatment measures, it is necessary to establish animal models that similar to human perimenopausal syndrome, so as to provide reference for drug research, new drug development and clinical application. In this paper, the keywords of "perimenopausal period" "perimenopausal syndrome" "menopause" "menopausal syndrome""menopausal period" "menopausal syndrome" and "animal" were searched in China National Knowledge Infrastructure (CNKI), Chongqing Weipu, China Biomedical Literature Database (CBM) and Pubmed. In addition, the selection of domestic peripheral menopausal syndrome model animals in recent years and the advantages and disadvantages of corresponding models were summarized. A total of 673 studies were identified, of which 61 were included in the analysis. The most common animal model of perimenopausal syndrome is castration model, while the immunodeficiency model is less used. With the aging of the population and the rapid increase of psychosocial stress, the incidence of perimenopausal syndrome is high. Therefore, it is particularly important to explore the mechanism of perimenopausal syndrome. According to the experimental purpose, experimental period, experimental technology and other factors, the selection of appropriate model animals and modeling methods is the key of the success of the experiment of perimenopausal syndrome.
3.Research progress in epigenetic pharmacological effects of rhein.
Zi-Wei ZHU ; Ruo-Nan ZHOU ; Wen-Bin SHANG
China Journal of Chinese Materia Medica 2023;48(24):6545-6550
Rhein, which is one of the main active components of Rheum palmatum, has a range of pharmacological activities such as the regulation of the metabolism of glucose and lipids, anti-inflammatory, anti-tumor, anti-fibrosis, etc. Epigenetics refers to the heritable variation of gene expression without altering the DNA sequence. It is involved in the emergence and development of inflammation, renal fibrosis, diabetes, cancer, atherosclerosis, and other diseases, thus becoming a new strategy for the treatment of many di-seases. A series of studies have shown that epigenetic modification may be a common molecular mechanism of various pharmacological effects of rhein. This paper summarized the effects of rhein on the regulation of epigenetic modification and its underlying mechanisms, which involve the regulation of DNA methylation, protein acetylation, and RNA methylation, so as to provide a basis for the development and application of rhein.
Humans
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Anthraquinones/pharmacology*
;
DNA Methylation
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Epigenesis, Genetic
;
Neoplasms/drug therapy*
;
Fibrosis
4.Dosimetric effect of calculation grid size on stereotactic body radiation therapy of lung cancer in helical tomotherapy planning system
Xia-Yu HANG ; Wan-Rong JIANG ; Yi-Kun LI ; Jun HU ; Yan ZHANG ; Ruo-Qi CAO ; Nan XU ; Lei WANG ; Jin-Da ZHOU ; Xiang-Dong SUN
Chinese Medical Equipment Journal 2024;45(2):52-57
Objective To investigate the dosimetric effects of different calculation grid size(CGS)in helical tomotherapy(HT)planning system on stereotactic body radiation therapy(SBRT)for non-small cell lung cancer(NSCLC).Methods Nine NSCLC patients receiving radiation therapy for the first time at some hospital from March 2019 to December 2022 were selected as the subjects.SBRT planning was carried out through the HT system with three different CGS plans(Fine,Normal,and Coarse)and the same pitch,modulation factor(MF)and optimization conditions,and the target area indexes of the three CGS plans were compared including conformity index(CI),homogeneity index(HI),dosimetric parameters of the organ at risk(OAR),point dose verification pass rate,treatment time,number of monitor units and Sinograms.SPSS 22.0 was used for statistical analysis.Results For target area HI,there weres significant differences between CGS Fine plan and Coarse plan and between CGS Normal plan and Coarse plan(P<0.05),while no statistical differences were found between CGS Fine plan and Normal plan(P>0.05).For target area CI,there were significant differences between CGS Fine plan and Coarse plan(P<0.05),while no statistical differences were found between CGS Fine plan and Normal plan and between CGS Normal plan and Coarse plan(P>0.05).For OAR dosimetric parameters,CGS Fine plan and Coarse plan had significant differences in heart Dmax and Dmean,esophageal Dmax and Dmean,V5,V20,V30 and Dmean of the whole lung and affected lung,V5 and Dmax of the affected lung and heart V10 and V30(P<0.05),CGS Normal plan and Coarse plan had obvious differences in esophageal Dmax(P<0.05),and the remained dosimetric parameters were not statistically significant(P>0.05).Fine,Normal and Coarse plans had the point dose verifica-tion pass rates being 0.96%,1.50%and 1.77%,respectively.In terms of treatment time and number of monitor units,there were significant differences between Fine plan and Coarse plan(P<0.05)while no statistical differences were found between Fine and Normal plans and between Normal and Coarse plans(P>0.05).Sinograms analyses showed Fine plan had evenly distributed segment color gradient,Coarse plan had areas of very dark and very light color gradients and Normal plan was somewhere in between.Conclusion Low CGS has to be used as much as possible to obtain accurate dose distribution during SBRT planning for NSCLC patients,which contributes to the execution of the radiation therapy plan and the prevention of ad-verse effects.[Chinese Medical Equipment Journal,2024,45(2):52-57]
5.Research progress on the effect of diacerein in the regulation of glucose and lipid metabolism
Ying-Ying XIANG ; Ruo-Nan ZHOU ; Wen-Bin SHANG
Chinese Pharmacological Bulletin 2024;40(5):811-816
Diacerein(DCN),an interleukin-1β(IL-1β)inhib-itor,has been clinically used for osteoarthritis.Chronic inflam-mation is considered as a causal factor of metabolic disorders,such as obesity and type 2 diabetes.Anti-inflammation therapy has emerged as an important strategy for improving the dysregu-lation of glucose and lipid metabolism.A series of domestic and international studies have shown that DCN regulates the disorders of glucose and lipid,which implies its potential application for the treatment of metabolic diseases.This paper summarized the effects and mechanisms of DCN on regulating glucose homeosta-sis and lipid metabolism.The mechanisms might involve the im-munomodulatory and anti-inflammatory action,the effect of anti-oxidative stress,the modulation of adipokine secretion,the regu-lation of programmed cell death,and the enhancement of insulin signaling transduction.These findings provide perspective for further development and application of DCN.
6.Effect of Xiongcan Yishen Formula on ferroptosis in mouse TM3 Leydig cells after oxidative stress injury
A-Jian PENG ; Gang NING ; Hui WU ; Bo-Nan LI ; Ruo-Bing SHI ; Hao-Yu WANG ; Wei LIU ; Xue TANG ; Xing ZHOU
National Journal of Andrology 2024;30(7):640-647
Objective:To investigate the effects of Xiongcan Yishen Formula(XYF)on ferroptosis in mouse TM3 Leydig cells after oxidative stress injury(OSI)induced by H2O2.Methods:An oxidative stress injury model was established in mouse TM3 Leydig cells using H2O2 induction.The modeled TM3 cells were randomly divided into OSI group,XYF group,the ferroptosis inhibitor Ferrostatin-1(F-1)group,and F-1+XYF group,which were respectively intervened with blank serum,20%drug-containing serum,2μmol/L F-1,and2μmol/L F-1+20%drug-containing serum.A control group(normal TM3 cells+blank serum)was also set up.The morphology of cells in each group was observed,and the levels of testosterone,superoxide dismutase(SOD),reactive oxygen spe-cies(ROS),malondialdehyde(MDA),ferritin heavy chain 1(FTH1),solute carrier family 7 member 11(SLC7A11),glutathione(GSH),glutathione peroxidase 4(GPX4),fatty acid CoA ligase 4(FACL4),total iron ions,and ferrous ions were detected.Re-sults:Compared with the model group,the control group showed significantly decreased expression of ROS,MDA,FACL4,total iron,and ferrous ions(P<0.05),and significantly increased levels of testosterone,SOD,GSH,FTH1,SLC7A11,and GPX4(P<0.05).The male silkworm kidney-tonifying formula group significantly promoted testosterone secretion by TM3 cells and upregulated the expression of FTH1,SLC7A11,GPX4,GSH,and SOD in TM3 cells(P<0.05),while significantly downregulating ROS,MDA,FACL4,total iron ions,and ferrous ions(P<0.05).Conclusion:Following H2O2 exposure,oxidative stress can induce ferroptosis in mouse TM3 Leydig cells.XYF can antagonize OSI and ferroptosis in TM3 cells by activating the SLC7A11/GSH/GPX4 axis,which may underlie the mechanism of XYF in the treatment of male late-onset hypogonadism.
7. Effect of Huangqi Guizhi Wuwu Tang on Angiogenesis in Osteoarthritis
Le ZHAO ; Yan-yan LI ; Yong-hui WANG ; Xiao-jun DONG ; Ran ZHOU ; Ruo-nan ZHANG ; Li-wei SUN
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(3):87-93
Objective: To study the effect of Huangqi Guizhi Wuwu Tang on angiogenesis of osteoarthritis with Yang deficiency and cold coagulation.Method: Totally 60 female SD rats were randomly divided into control group, model group, celecoxib group (20.82 mg·kg-1) and low, medium, high-dose Huangqi Guizhi Wuwu Tang groups (3.24, 6.48, 12.96 g·kg-1). All groups, except for control group, were involved in duplicating the osteoarthritis(OA) model through frozen and knee fixation, as well as 42-day cold environmental stimulation. After modeling, all drug-group rats were respectively administrated with corresponding drugs for 28 days, once a day. Meanwhile, control group and model group were given equivalent distilled water by gavage. 24 hours after the last gavage, vascular endothelial growth factor (VEGF),prostaglandin E2(PGE2) and transforming growth factor-β1(TGF-β1) in serum were detected with enzyme linked immunosorbent assay(ELISA) method, VEGF expressions in cartilage and synovial with immunohistochemical method, and interleukin-17(IL-17) and VEGF levels in synovial with Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).Result: Compared with normal group, the expression of VEGF in serum, cartilage and synovial were significantly increased (P<0.01), and PGE2 and TGF-β1 expressions, IL-17 level were increased significantly (P<0.01) as well. Compared with model group, VEGF in serum, cartilage and synovial were significantly decreased in the 4 drug groups. Meanwhile, PGE2, TGF-β1 and IL-17 level were decreased significantly (P<0.05). Among drug groups, IL-17 of high-dose group in synovial was higher than that of celecoxib group (P<0.05), and VEGF of medium and high-dose Huangqi Guizhi Wuwu Tang groups in synovial was higher than that of celecoxib group (P<0.05). There was no significant difference among other drug groups.Conclusion: Huangqi Guizhi Wuwu Tang has an effect in suppressing angiogenesis of knee and alleviate cartilage lesion by regulating VEGF and its upstream cytokines PGE2 and TGF-β1.
8.Clinical effects of pulsed dye laser dynamically combined with triamcinolone acetonide in the treatment of keloids.
Zhen Nan LIU ; Yue Min ZHOU ; Ruo Xuan LIU ; Ya Ling LI ; Qing LI ; Ting ZHANG ; Shu Man ZHANG
Chinese Journal of Burns 2022;38(9):822-829
Objective: To explore the clinical effects of pulsed dye laser (PDL) dynamically combined with triamcinolone acetonide (TAC) in the treatment of keloids. Methods: A retrospectively observational study was conducted. From April 2015 to October 2020, 34 keloid patients (46 keloids) who met the inclusion criteria were admitted to Huaihe Hospital of Henan University. The patients were divided into TAC group and dynamic treatment group according to their treatment methods. There were 18 patients (26 keloids) in TAC group, including 8 males and 10 females, aged (30±12) years, who were treated with TAC injection alone. There were 16 patients (20 keloids) in dynamic treatment group, including 6 males and 10 females, aged (26±11) years, who were treated with TAC injection, PDL, or PDL combined with TAC injection according to the Vancouver scar scale (VSS) score before each treatment. Before the first treatment (hereinafter referred to as before treatment) and 12 months after the first treatment (hereinafter referred to as after treatment), the keloids were assessed by VSS, patient and observer scar assessment scale (POSAS), and the effect of keloids on the quality of life of patients was evaluated with dermatology life quality index (DLQI) scale. Twelve months after treatment, the curative effect of keloid was evaluated according to the VSS score and the effective rate was calculated. The first effective time and the cumulative times of TAC injection at the first effective time, the number of follow-up and the occurrence of adverse reactions of keloids within 12 months after treatment were recorded, and the incidence of adverse reactions was calculated. Data were statistically analyzed with paired sample t test, independent sample t test, Wilcoxon rank-sum test, Mann-Whitney U test, chi-square test, and Fisher's exact probability test. Results: The total VSS scores of patients' keloids in TAC group and dynamic treatment group 12 months after treatment were significantly lower than those before treatment (with t values of 7.53 and 8.09, respectively, P<0.01), and the total scores of pigmentation and vascularity in VSS and POSAS, the total POSAS score, and the DLQI scale score were significantly lower than those before treatment (with Z values of -3.71, -4.04, -4.21, -4.11, -3.76, -3.73, -3.92, and -3.93, respectively, P<0.01). The total scores of pigmentation and vascularity in VSS and POSAS of patients' keloids in dynamic treatment group 12 months after treatment were significantly lower than those in TAC group (with Z values of -2.03 and -2.12, respectively, P<0.05). Twelve months after treatment, the effective rate of patients' keloids in dynamic treatment group was significantly higher than that in TAC group (χ2=3.88, P<0.05). The first effective time of patients' keloids in dynamic treatment group was 5.5 (2.0, 6.0) months, which was significantly shorter than 6.0 (2.3, 10.3) months in TAC group (χ2=4.02, P<0.05). The cumulative times of TAC injection at the first effective time of patients' keloids in dynamic treatment group was 3.2±1.7, which was significantly less than 4.2±1.8 in TAC group (t=2.09, P<0.05). The number of follow-up of patients' keloids within 12 months after treatment in dynamic treatment group was significantly more than that in TAC group (t=-2.94, P<0.01), and the total incidence of adverse reactions was lower than that in TAC group but without statistically significant difference (P>0.05). Conclusions: Compared with TAC injection alone, PDL dynamically combined with TAC in the treatment of keloid can shorten the effective time, reduce the number of TAC injection, and improve the patient's compliance and clinical efficacy.
Female
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Humans
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Keloid/pathology*
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Lasers, Dye/therapeutic use*
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Male
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Quality of Life
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Retrospective Studies
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Treatment Outcome
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Triamcinolone Acetonide/therapeutic use*
9. Effects of NF-κB/NOX1 signaling pathway in TNF-α-induced apoptosis of A549 cells
Fang ZHOU ; Feng-xian SHI ; Shu NIU ; Ruo-nan ZHAI ; Ming-ze MA ; Ke LI ; Hang WANG ; Chun-yan XU ; Rong ZHOU ; Wu YAO
China Occupational Medicine 2021;48(03):241-246
OBJECTIVE: To investigate the effects of nuclear transcription factor-κB(NF-κB)/amide adenine dinucleotide phosphate oxidase 1(NOX1) signaling pathway in tumor necrosis factor-α(TNF-α) induced apoptosis of A549 cells. METHODS: i) A549 cells were stimulated with TNF-α at the concentrations of 0.00, 0.25, 0.50, and 1.00 nmol/L. CCK-8 assay was used to detect the cell viability to screen the optimal stimulating concentration of TNF-α. ii) A549 cells at logarithmic growth stage were randomly divided into four groups, the control group, the TNF-α group, the BAY11-7082(NF-κB inhibitor) group and the TNF-α+BAY11-7082 group. The cells in the control group were not treated. The TNF-α and BAY11-7082 groups were stimulated with 0.50 nmol/L TNF-α and 5 μmol/L BAY11-7082, respectively. The TNF-α+BAY11-7082 group was stimulated by both TNF-α and BAY11-7082. After 24 hours of culture, the cell survival rate was detected by CCK-8 assay. Flow cytometry was used to detect cell apoptotic rate, and Western blotting was used to detect the relative expression of NF-κB(p65) and NOX1 proteins. RESULTS: i) When A549 cells were stimulated with TNF-α at the concentration of 0.50 nmol/L, the cell proliferative activity was reduced and the cell apoptosis was promoted. This concentration was selected as the stimulation dose of TNF-α in subsequent experiments. ii) The survival rate of A549 cells in the TNF-α group decreased(P<0.05), the apoptotic rate and the protein expressions of NF-κB(p65) and NOX1 increased in TNF-α group(all P<0.05) compared with the control group. In BAY11-7082 group, the survival rate and the relative expression of NF-κB(p65) and NOX1 of A549 cells were decreased(all P<0.05), and the apoptotic rate of A549 cells was increased(P<0.05) compared with the control group. A549 cells in TNF-α+BAY11-7082 group changed from a long spindle shape to an irregular one. The cell survival rate increased(P<0.05), the apoptotic rate and the relative expression of NF-κB(p65) and NOX1 decreased(all P<0.05) compared with the TNF-α group. CONCLUSION: NF-κB/NOX1 signaling pathway is involved in A549 cells apoptosis induced by TNF-α.
10.Analysis on quality value transmitting of substance benchmark of Houpo Wenzhong Decoction.
Qing ZHANG ; Ju-Yuan LUO ; Wen-Jun HU ; Ruo-Nan SHEN ; Xue-Chun LIU ; Yue-Ying ZHAO ; Xing-Yue HUANG ; Chang-Hai WANG ; Ze-Kang ZHANG ; Yang LU ; Ning HAN ; Wen-Yan ZHOU
China Journal of Chinese Materia Medica 2021;46(4):810-819
By preparing 15 batches of lyophilized powder samples of substance benchmark in Houpo Wenzhong Decoction,the fingerprint,index component content and extract rate were determined,and the characteristic peaks,the range of similarity with the reference map,the content range and transfer rate range of magnolol,hesperidin,glycyrrhizic acid and pinocembrin,the extract rate range and the change range were clarified. The results showed that the similarity between the fingerprint of substance benchmark and the reference map R generated from the 15 batches of substance benchmark samples was higher than 0. 90. The assignment of the characteristic peaks in the full prescription's fingerprint of the herbs except Poria cocos was clarified. Nineteen characteristic peaks were assigned,and 12 characteristic peaks were assigned by the reference substance,of which 4 were from Magnolia ocinalis Cortex,5 from Exocarpium Citri Rubrum,2 from Radix aucklandiae,3 from Glycyrrhiza Radix et Rhizoma,4 from Semen Alpiniae Katsumadai,and one from Rhizoma Zingiberis and Zingiber officinale Roscoe. The index component content range and transfer rate range were 0. 80%-1. 14% and 20. 25%-39. 61% for hesperidin,0. 49%-0. 79% and 23. 09%-33. 87%for glycyrrhizic acid,0. 03%-0. 07% and 3. 55%-10. 09% for pinocembrin,0. 15%-0. 38% and 8. 08%-24. 35% for magnolol. The extract rate range and the change range were22. 60%-25. 57% and 12. 67%-23. 68% respectively. In this study,we introduced the concepts of index component content,fingerprint,extract rate,explored the transfer relation of quality value transmitting of substance benchmark in Houpo Wenzhong Decoction,and initially established the quality standard of Houpo Wenzhong Decoction,all of which would provide ideas for the development and research of similar prescriptions.
Benchmarking
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Chromatography, High Pressure Liquid
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Drugs, Chinese Herbal
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Glycyrrhiza
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Quality Control