1.Effects of emetine on insulin secretion in rat islets through GLP-1R
Huan XUE ; Zhi-Hong LU ; Bin WANG ; Si-Ting YU ; Xi ZHANG ; Bin HU ; Qing-Xuan ZENG ; Yi ZHANG
Chinese Pharmacological Bulletin 2024;40(7):1267-1272
Aim To study the effect of emetine on in-sulin secretion through glucagon-like peptide-1 receptor(GLP-1R).Methods Isolating rat islets were used to carry out insulin secretion experiment.Islets were incubated with different concentrations of emetine(2,10,50 μmol·L-1),different concentrations of glu-cose solution(2.8,11.1,16.7 mmol·L-1)or spe-cific GLP-1R antagonist Exendin(9-39).The amount of insulin secretion in the supernatant of each group was determined by an enzyme-linked radioimmunoas-say.Small molecule compounds were docked to GLP-1R(PDB code:5NX2)using SYBYL-X2.0 software.Results Emetine could promote insulin secretion in high glucose(11.1 mmol·L-1)in a dose-dependent manner.In low glucose(2.8 mmol·L-1),insulin secretion did not change after intervention of emetine.But in high glucose(11.1,16.7 mmol·L-1),insu-lin secretion significantly increased under the treatment of emetine in a glucose-dependent manner.The doc-king score of emetine and GLP-1R was Total Score=6.82,C Score=5,indicating that emetine had a good binding affinity with GLP-1R.Using Exendin(9-39)to block GLP-1R,the insulinotropic effect of emetine was reduced.Conclusion Emetine could promote in-sulin secretion,which is related to the activation of GLP-1R.
2.Research progress on the mechanism of CRMP2 phosphorylation in Alzheimer's disease
Xuan LIANG ; Jingran MU ; Yan LUO ; Tao XU ; Junwei ZENG
The Journal of Practical Medicine 2024;40(10):1467-1472
Alzheimer's disease(AD)is a common neurological degenerative disease.Collapsin response mediator protein2(CRMP2)plays an important role in the progression of AD.Hyperphosphorylation of CRMP2 results in decreased stability of axonal terminal microtubules and abnormal axoplasmic transport of neurons,which leads to abnormal mitochondrial dynamics of neurons,inhibits the ability of lysosomal autophagy,and leads to excessive activation of NMDA receptors.The phosphorylation of CRMP2 provides a new idea for AD drug develop-ment.In this review,the molecular mechanisms of CRMP2 involved in AD are reviewed,which can provide refer-ences for the development of targeted drugs.
3.Research progress on the activation of complement system is involved in the pathogenesis of Alzheimer′s disease
Jingran MU ; Yan LUO ; Xuan LIANG ; Tao XU ; Junwei ZENG ; Xiaohong LIU
Tianjin Medical Journal 2024;52(6):663-668
Alzheimer's disease(AD)is a common neurodegenerative disease,which is mainly caused by brain lesions.The activation of complement system plays an important role in the process of AD lesions.The activated complement can bind to cell membrane receptors and regulate downstream signals.Therefore,inhibiting complement activation provides a new idea for AD treatment.This article reviews the progress in the mechanism and drug development of complement activation in AD,which may provide a new perspective for the diagnosis,treatment and drug development of AD.
4.Combined Therapies of Traditional Chinese Medicine Treat Low-prognosis Patients Undergoing IVF-ET Again
Xuan ZHANG ; Wanting XIA ; Jinzhu HUANG ; Qianhong MA ; Yunji XU ; Qian ZENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):160-169
ObjectiveTo objectively evaluate the clinical efficacy of multiple therapies of traditional Chinese medicine (TCM) in low-prognosis patients who received antagonist protocol for in vitro fertilization and embryo transfer (IVF-ET) again. MethodA total of 128 patients with kidney Yin deficiency, liver depression, and blood stasis who planned to receive antagonist protocol for IVF-ET in the West China Second Hospital of Sichuan University were enrolled and assigned into two groups by random number table method. The observation group (64 casces) was treated by oral administration of Chinese medicine decoction + enema of kidney-tonifying and blood-activating method + auricular point sticking + oral administration of dehydroepiandrosterone (DHEA), while the control group (64 casces) was treated by only oral administration of DHEA. After treatment for three menstrual cycles, both groups received the antagonist protocol for IVF-ET. The TCM syndrome scores, basic sex hormone levels, antral follicle count (AFC), the usage of gonadotropin (Gn), endometrial receptivity indicators, embryo quality indicators, and pregnancy outcomes were compared between the two groups. ResultAfter treatment, the observation group showed decreased follicle-stimulating hormone (FSH)/luteinizing hormone (LH) ratio, lowered level of estradiol (E2), increased AFC, decreased amount and days of Gn usage, improved endometrial receptivity indicators (endometrial thickness on trigger and ET days, proportion of endometrial type A in endometrial types and the level of E2 on trigger day) and embryo quality indicators (the rates of mature follicles, fertilization, normal fertilization, and premium embryos), and decreased TCM syndrome scores (P<0.05, P<0.01). Moreover, the observation group had lower FSH/LH ratio, E2 level, and amount of Gn usage, higher AFC, poorer endometrial receptivity and embryo quality indicators, and lower TCM syndrome scores than the control group after treatment (P<0.05, P<0.01). In addition, except for 3 cases of natural pregnancy, the observation group outperformed the control group in terms of improving the clinical pregnancy rates during initiation cycle and transplantation cycle and clinical pregnancy rate and decreasing biochemical pregnancy rate and early abortion rate (P<0.05). ConclusionCombined therapies of TCM can alleviate the clinical symptoms, reduce TCM syndrome scores, reduce the Gn usage amount, improve the number and quality of embryos and endometrial receptivity, and coordinate the synchronous development of endometrium and embryo. In this way, they can increase the clinical pregnancy rate and reduce biochemical pregnancy rate and early abortion rate in the low prognosis patients with kidney yin deficiency, liver depression, and blood stasis who are undergoing IVF-ET again.
5.Clinical Efficacy of TCM Multi-channel Intervention Plus Antagonist Regimen on Ovarian Function,TCM Syndromes and Natural Conception in Poor Ovarian Responders Undergoing IVF-ET
Yunji XU ; Wanting XIA ; Xuan ZHANG ; Qianhong MA ; Jinzhu HUANG ; Qian ZENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):93-100
ObjectiveTo objectively analyze the effects of traditional Chinese Medicine (TCM) multi-channel intervention on the ovarian function,TCM syndromes and natural conception of poor ovarian responders(kidney-Yin deficiency,liver depression and blood stasis pattern) who planned to receive another in vitro fertilization embryo transfer(IVF-ET)antagonist regimen. MethodThe 128 low-prognosis patients (kidney Yin deficiency,liver depression and blood stasis pattern) who attended the West China Second University Hospital, Sichuan University and the Hospital of Chengdu University of Traditional Chinese Medicine from August 2020 to February 2023 and met the inclusion criteria were selected,and then divided into the treatment group and the control group according to the random number table,with 64 patients in each group. The control group was treated with oral dehydroepiandrosterone(DHEA),while the treatment group was treated with multi-channel TCM(oral TCM decoction + auricular point sticking + Bushen Huoxue prescription through retention enema). After 3 menstrual cycles,the relevant indicators for ovarian function evaluation,TCM syndrome scores and natural conception were collected from both groups. ResultCompared with the situation before treatment,the basal follicle stimulating hormone(bFSH),bFSH/basal luteinizing hormone(bLH),basal estradiol(bE2),antral follicle count(AFC),the number of oocytes obtained,the number of normal fertilization,the number of superior embryos and TCM syndrome scores in the treatment group were improved after treatment(P<0.05,P<0.01). For the control group, the bFSH/bLH and TCM syndrome scores were increased after treatment(P<0.05), while the bFSH,bFSH/bLH,bE2,AFC,the number of oocytes obtained,the number of normal fertilization,and the number of superior embryos showed no significant difference after treatment. Compared with the control group after treatment,bFSH,bFSH/bLH,bE2,AFC,the number of normal fertilization,the number of superior embryos and TCM syndrome scores in the treatment group were better (P<0.05,P<0.01),while there was no significant difference in the number of oocytes obtained. After treatment,there were 3 cases of natural conception in the treatment group,while there were no natural conception in the control group. ConclusionFor patients with poor ovarian response and kidney Yin deficiency,liver depression and blood stasis pattern,multi-channel intervention of TCM plus the antagonist regimen can reduce bFSH,bFSH/bLH values,improve the levels of bE2,increase AFC,the number of oocytes obtained,the number of normal fertilization and the number of superior embryos,improve ovarian function,menstruation and TCM syndromes,improve their quality of life,and even enable some patients to get pregnant naturally before re-progression and improve their pregnancy outcome.
6.Bibliometrics study on the pathogenesis of primary open angle glaucoma
Yan CHEN ; Hongmin ZHUO ; Fan ZHANG ; Xuan ZHOU ; Chengzhi YUAN ; Chang YU ; Qinghua PENG ; Meiyan ZENG ; Houpan SONG
International Eye Science 2024;24(5):704-711
AIM: To understand the publication status, research trends, and cutting-edge and hot topics in this field by conducting a bibliometrics analysis of relevant literatures on the pathogenesis of primary open angle glaucoma(POAG)in the past 30 a.METHODS:A total of 986 relevant literatures on the pathogenesis of POAG published on the core databases of China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)from 1 September 1993 to 1 September 2023 were retrieved. CiteSpace(6.2.R.4)and VOSviewer(1.6.18)software were used to conduct knowledge graph analysis on the retrieved literature, including publication volume, author, research institution, country/region, and keywords.RESULTS:The United States(243 articles)has the highest number of publications, followed by China(121 articles). The foreign institution with the highest number of publications is Harvard University(37 articles), while domestic institutions such as Zhongshan Ophthalmic Center, Sun Yat-sen University, ophthalmology department of Xuanwu Hospital of Capital Medical University, and Peking University First Hospital tied for the highest number of publications. Louis R. Pasquale(21 articles)is the most prolific English author. Wang Ningli is the most active Chinese researcher in this field. Keywords include trabecular meshwork, intraocular pressure, aqueous humor, glucocorticoid, hemorheology, etc.CONCLUSION: The research on the pathogenesis of POAG is in a period of vigorous development. The United States has the largest number of publications in this field, and Harvard University is a leading institution in this field. The research focus in the field of POAG has shifted from the structural aspect to the genetic level, and gene research and traditional Chinese medicine treatment have broad application prospects in this field.
7.Transcriptome Sequencing on Treatment of Kidney Deficiency and Blood Stasis-thin Endometrium in Rats with Bushen Huoxue Prescription Through Enema
Xuan ZHANG ; Wanting XIA ; Zhixing YIN ; Nana HAN ; Jinzhu HUANG ; Hang ZHOU ; Yi WANG ; Juan LI ; Qian ZENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):79-90
ObjectiveTo explore the mechanism of Bushen Huoxue enema in treating the rat model of kidney deficiency and blood stasis-thin endometrium (KDBS-TE) by transcriptome sequencing. MethodThe rat model of KDBS-TE was established by administration of tripterygium polyglycosides tablets combined with subcutaneous injection of adrenaline. The pathological changes of rat endometrium in each group were then observed. Three uterine tissue specimens from each of the blank group, model group, and Bushen Huoxue enema group were randomly selected for transcriptome sequencing. The differentially expressed circRNAs, lncRNAs, and miRNAs were screened, and the disease-related specific competitive endogenous RNA (ceRNA) regulatory network was constructed. Furthermore, the gene ontology (GO) functional annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed for the mRNAs in the network. ResultCompared with the blank group, the model group showed endometrial dysplasia, decreased endometrial thickness and endometrial/total uterine wall thickness ratio (P<0.01), and differential expression of 18 circRNAs, 410 lncRNAs, and 7 miRNAs. Compared with the model group, the enema and estradiol valerate groups showed improved endometrial morphology and increased endometrial thickness and ratio of endometrial to total uterine wall thickness (P<0.05). In addition, 21 circRNAs, 518 lncRNAs, and 17 miRNAs were differentially expressed in the enema group. The disease-related specific circRNA-miRNA-mRNA regulatory network composed of 629 nodes and 664 edges contained 2 circRNAs, 34 miRNAs, and 593 mRNAs. The lncRNA-miRNA-mRNA regulatory network composed of 180 nodes and 212 edges contained 5 lncRNAs, 10 miRNAs, and 164 mRNAs. The mNRAs were mainly enriched in Hippo signaling pathway, autophagy-animal, axon guidance, etc. ConclusionBushen Huoxue enema can treat KDBS-TE in rats by regulating specific circRNAs, lncRNAs, and miRNAs in the uterus and the ceRNA network.
8.Progress in mechanism of complement system involved in pathological pain
Yan LUO ; Xuan LIANG ; Jingran MU ; Tao XU ; Junwei ZENG
Chinese Journal of Pathophysiology 2024;40(2):343-350
The complement system comprises intrinsic complement components,complement regulatory pro-teins,and complement receptors.Complement activation plays a role in promoting the sensitization of peripheral pain re-ceptors,enhancing immune cell activity,and participating in the regulation of axon regeneration after nerve injury.The in-teraction of the complement system contributes to the development and maintenance of pathological pain,affecting the dor-sal root ganglion neurons,spinal dorsal horn,and brain.Consequently,targeting the complement system holds promise as a therapeutic approach for neuropathic pain treatment.This paper reviews the progress in understanding the functions of the complement system and its implications in pathological pain,offering valuable insights for the future development of targeted drug therapies.
9.Role of statins in chronic liver disease
Xikun YANG ; Hui LI ; Zijian ZENG ; Xuan WU ; Kaixin WANG
Journal of Clinical Hepatology 2024;40(10):2104-2108
Chronic liver disease is the"devil's trilogy"in which the liver progresses from inflammation and fibrosis to liver cirrhosis and hepatocellular carcinoma,which poses a great challenge for hepatologists worldwide.Statins have played a significant role in the treatment of cardiovascular diseases and hyperlipidemia since their introduction,and in recent years,they have also demonstrated the potential to improve hepatic steatosis,exert an anti-inflammatory effect,regulate the phenotype of hepatic stellate cells,reduce portal venous pressure,and improve hepatic microcirculation in chronic liver disease.This article reviews the latest advances in the basic and clinical studies of statins in chronic liver disease,in order to provide new insights into the research,prevention,and treatment of chronic liver disease.
10.Study on the mechanism of electroacupuncture stimulation to activate the acupoint effect and promote skeletal muscle repair
Yuting HUANG ; Jun LIAO ; Tianyu RAO ; Kezhi LIU ; Jia LIN ; Yuye LIN ; Chufan ZENG ; Guojun ZHANG ; Xia ZHANG ; Xiubing TONG ; Jingyu ZHANG ; Yu KAN ; Yanping FANG ; Xianghong JING ; Xuan WANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(8):1160-1170
Objective To investigate the mechanism of inducing macrophage polarization induced by acupoint effect of electroacupuncture to promote the repair of acute skeletal muscle injury.Methods 45 SD rats were randomly divided into blank group,model group,electroacupuncture group(EA group),sodium chrominate group (DSCG group) and electroacupuncture+sodium chrominate group (hereinafter referred to as EA+DSCG group),with 9 rats in each group. The rats in the EA group and the EA+DSCG group were subjected to EA intervention at the right "Chengshan" (BL57) and "Yanglingquan"(GB34),with a frequency of 2 Hz/100 Hz. The gait changes of rats were recorded by animal gait analyzer. The morphological changes of the right gastrocnemius were observed by HE staining. The changes of mast cell aggregation and degranulation in local skin muscles of "chengshan" point were observed by toluidine blue staining. The expressions of Pax7,MyoD and skin mast cells and 5-HT in the right gastrocnemius were detected by immunofluorescence method. The positive expressions of CD68 and CD206 in right gastrocnemius macrophage was observed by immunohistochemical staining.Results Compared with blank group,the wiggle time of the right hind leg in model group and DSCG group increased,stride length decreased,HE staining showed inflammatory cell infiltration,myocyte enlargement,degeneration and necrosis. The degranulation rate of local skin mast cells in "Chengshan" (BL57) area increased,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD,CD68 and CD206 increased (P<0.05). Compared with model group,the wiggle time of the right hind leg in EA group and EA+DSCG group decreased,stride length increased,HE staining showed that inflammatory cell infiltration was reduced,muscle cells were uniform in size and arranged neatly. Mast cell degranulation rate increased significantly in EA group,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased (P<0.05). Compared with EA+DSCG group,the degranulation rate of mast cells and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased in EA group (P<0.05). Conclusion EA "Chengshan" (BL57) and "Yanglingquan" (GB34) can stimulate acupuncture points to locally induce mast cell degranulation,promote the polarization of macrophages,and then activate muscle satellite cells to play the regulatory process of repairing skeletal muscle injury.

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