1.Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52
Shengyou LI ; Xue GAO ; Yi ZHENG ; Yujie YANG ; Jianbo GAO ; Dan GENG ; Lingli GUO ; Teng MA ; Yiming HAO ; Bin WEI ; Liangliang HUANG ; Yitao WEI ; Bing XIA ; Zhuojing LUO ; Jinghui HUANG
Journal of Pharmaceutical Analysis 2024;14(1):86-99
A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.
2.Role of Abelson interactor 2 in progression and prognosis of gastric cancer and its regulatory mechanisms
Xiaohua CHEN ; Hui LU ; Ziliang WANG ; Lian WANG ; Yongsheng XIA ; Zhijun GENG ; Xiaofeng ZHANG ; Xue SONG ; Yueyue WANG ; Jing LI ; Jianguo HU ; Lugen ZUO
Journal of Southern Medical University 2024;44(9):1653-1661
Objective To explore the regulatory role of Abelson interactor 2(ABI2)in progression and prognosis of gastric cancer.Methods TIMER2.0,GEPIA,Kaplan-Meier Plotter and DAVID databases were used to analyze ABI2 expression in pan-cancer and its association with the prognosis of gastric cancer.Gastric cancer and adjacent tissues from 120 patients undergoing radical gastrectomy in our hospital between January,2016 and October,2018 were examined for ABI2 expression and its correlation with disease progression and prognosis.MGC-803 cell models of ABI2 knockdown and overexpression were established for observing the changes in cell proliferation,migration,and invasion,and the impact of ABI2 expression modulation on xenograft growth was evaluated in nude mice.Results Database analysis and examination of the clinical samples showed that ABI2 was highly expressed in gastric cancer tissues.Survival analysis suggested that gastric cancer patients with a high expression of ABI2 had a reduced postoperative 5-year survival rate(P<0.0001),and further Cox univariate and multivariate survival analyses indicated that a high ABI2 expression was an independent risk factor affecting the patients survival outcomes(P=0.022,HR=1.887,95%CI:1.096-3.249).Enrichment analysis suggested the involvement of ABI2 in Wnt signaling.In MGC-803 cells,ABI2 overexpression promoted cell proliferation and xenograft growth in nude mice,increased the expressions of vimentin and N-cadherin,and lowered E-cadherin expression,while ABI2 knockdown produced the opposite effects.Mechanistic analysis revealed that ABI2 overexpression promoted the expressions of Wnt2 and β-catenin in both MGC-803 cells and the xenografts,and their expressions were significantly lowered by ABI2 knockdown.Conclusion ABI2 is highly expressed in gastric cancer,which affects long-term prognosis of the patients,possible due to its regulatory effect on Wnt signaling to promote proliferation,migration and invasion of gastric cancer cells.
3.Role of Abelson interactor 2 in progression and prognosis of gastric cancer and its regulatory mechanisms
Xiaohua CHEN ; Hui LU ; Ziliang WANG ; Lian WANG ; Yongsheng XIA ; Zhijun GENG ; Xiaofeng ZHANG ; Xue SONG ; Yueyue WANG ; Jing LI ; Jianguo HU ; Lugen ZUO
Journal of Southern Medical University 2024;44(9):1653-1661
Objective To explore the regulatory role of Abelson interactor 2(ABI2)in progression and prognosis of gastric cancer.Methods TIMER2.0,GEPIA,Kaplan-Meier Plotter and DAVID databases were used to analyze ABI2 expression in pan-cancer and its association with the prognosis of gastric cancer.Gastric cancer and adjacent tissues from 120 patients undergoing radical gastrectomy in our hospital between January,2016 and October,2018 were examined for ABI2 expression and its correlation with disease progression and prognosis.MGC-803 cell models of ABI2 knockdown and overexpression were established for observing the changes in cell proliferation,migration,and invasion,and the impact of ABI2 expression modulation on xenograft growth was evaluated in nude mice.Results Database analysis and examination of the clinical samples showed that ABI2 was highly expressed in gastric cancer tissues.Survival analysis suggested that gastric cancer patients with a high expression of ABI2 had a reduced postoperative 5-year survival rate(P<0.0001),and further Cox univariate and multivariate survival analyses indicated that a high ABI2 expression was an independent risk factor affecting the patients survival outcomes(P=0.022,HR=1.887,95%CI:1.096-3.249).Enrichment analysis suggested the involvement of ABI2 in Wnt signaling.In MGC-803 cells,ABI2 overexpression promoted cell proliferation and xenograft growth in nude mice,increased the expressions of vimentin and N-cadherin,and lowered E-cadherin expression,while ABI2 knockdown produced the opposite effects.Mechanistic analysis revealed that ABI2 overexpression promoted the expressions of Wnt2 and β-catenin in both MGC-803 cells and the xenografts,and their expressions were significantly lowered by ABI2 knockdown.Conclusion ABI2 is highly expressed in gastric cancer,which affects long-term prognosis of the patients,possible due to its regulatory effect on Wnt signaling to promote proliferation,migration and invasion of gastric cancer cells.
4.Effect of Tongxie Yaofang with or Without Saposhnikoviae Radix on Water Metabolism and 5-HT Pathway in Irritable Bowel Syndrome Rats
Wei ZHANG ; Wen-jing GE ; Hui-sen WANG ; Xue-xia ZHANG ; Ming LIU ; Wei-feng CUI ; Jun WANG ; Geng-sheng LI ; Rui-feng LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(11):56-62
Objective:To investigate the effect of Saposhnikoviae Radix on Tongxie Yaofang in regulating water metabolism and 5-serotonin(5-HT) signal system in diarrhea type irritable bowel syndrome(IBS-D)rats. Method:The 40 IBS-D SD rats were randomly divided into model group, Tongxie Yaofang wituout Saposhnikoviae Radix group (26 g·kg-1), Tongxie Yaofang decoction group (30 g·kg-1), Tongxie Yaofang with double Saposhnikoviae Radix group (34 g·kg-1),another 10 normal SD rats were selected as the normal group.Except for normal group, the rats in other groups were separated from their mothers and induced by acetic acid to establish D-IBS model. These rats in the each group were administered with corresponding drugs for 14 days. The diarrhea indexs and the water contents of the feces were observed and calculated. The Na+-K+-ATPase activities in the intestinal mucosa were detected by micro method. The contents of 5-HT were detected by enzyme linked immunosorbent assay (ELISA). The activities of monoamine oxidase A (MAO-A) were detected by chemiluminescence method. The expressions of aquaporin 4 (AQP4) in colon were detected by immunohistochemistry. Protein expression levels of HT receptor 3 (5-HT3R), HT receptor 4 (5-HT4R) and serotonin transporter (SERT) in hypothalamus and colon were detected by Western blot. Result:Compared with normal group, the fecal water contents, contents of 5-HT in hypothalamus and colon, activities of MAO-A, expressions of 5-HT3R were significantly increased in model group (
5.Berberine prevents primary peritoneal adhesion and adhesion reformation by directly inhibiting TIMP-1.
Xin LIU ; Yunwei WEI ; Xue BAI ; Mingqi LI ; Huimin LI ; Lei WANG ; Shuqian ZHANG ; Xia LI ; Tong ZHAO ; Yang LIU ; Rui GENG ; Hao CUI ; Hui CHEN ; Ranchen XU ; Heng LIU ; Yong ZHANG ; Baofeng YANG
Acta Pharmaceutica Sinica B 2020;10(5):812-824
Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and represent the major cause of postsurgical morbidity. Enterolysis at repeat surgeries induces adhesion reformation that is more difficult to prevent than primary adhesion. Here we studied the preventive effects of different approaches of berberine treatment for primary adhesion, and its effects on adhesion reformation compared to Interceed. We found the primary adhesion was remarkably prevented by berberine through intraperitoneal injection 30 min before abrasive surgery (pre-berberine) or direct addition into injured cecum immediately after the surgery (inter-berberine). Rats with adhesion reformation had a more deteriorative collagen accumulation and tissue injury in abrasive sites than rats with primary adhesion. The dysregulated TIMP-1/MMP balance was observed in patients after surgery, as well as adhesion tissues from primary adhesion or adhesion reformation rats. Inter-berberine treatment had a better effect for adhesion reformation prevention than Interceed. Berberine promoted the activation of MMP-3 and MMP-8 by directly blocking TIMP-1 activation core, which was reversed by TIMP-1 overexpression in fibroblasts. In conclusion, this study suggests berberine as a reasonable approach for preventing primary adhesion formation and adhesion reformation.
6.Study on HPV infection types distribution in ASC-US ,LSIL and HSIL of uterine cervix
Yuelan LIANG ; Xue ZHAO ; Jianxiang GENG ; Jianyun LAN ; Zhaoxia YU ; Sijun XIA ; Jing MEI ; Honjing WANG ; Lin XIA
International Journal of Laboratory Medicine 2018;39(1):59-62
Objective To analyze the genotypes distribution and clinical significance of human papillomavir-us(HPV) infection in atypical squamous cells of undetermined significance (ASC-US) ,low squamous intraepi-thelial lesion (LSIL) and high squamous intraepithelial lesion (HSIL) of uterine cervix ,meanwhile to conduct the cervical histopathological diagnostic analysis in the patients with ASC-US、LSIL and HSIL .Methods The gene amplification technique (PCR) combined with gene-chips technology were adopted to conduct the 23 kinds of HPV genotype detection on 236 cases of cervical ASC-US ,36 cases of cervical LSIL and 61 cases of cervical HSIL specimens .All cases of ASC-US ,LSIL and HSIL were performed the cervical biopsy his-topathological diagnosis .And then the subjects related data were analyzed .Results Among 236 cases of cervi-cal ASC-US specimens ,139 cases of HPV infection were detected with the total HPV infection rate 58 .90%(139/236) ,in which the single genotypes infection rate was 38 .14% (90/236)and the multiple genotypes infec-tion rate was 20 .76% (49/236);26 cases of HPV infection were detected from 36 cases of cervical LSIL speci-mens with the total HPV infection rate of 72 .22% (26/36) ,in which the single genotypes infection rate was 52 .78% (19/36) and the multiple genotypes infection rate was 19 .44% (7/36);61 cases of HPV infection were detected from 58 cases of cervical HSIL specimens with the total HPV infection rate of 95 .08% (58/61) , in which the single genotypes infection rate was 68 .85% (42/61)and the multiple genotypes infection rate was 26 .23% (16/61) .The total infection rates had statistically significantly differences among the cervical ASC-US group ,LSIL group and HSIL group (P<0 .05) .Conclusion HPV16 ,52 ,58 are the main types in the patients with cervical ASC-US ,LSIL and HSIL .The gene-chip technology can be used in the HPV genotypes detection of cervical cells ,which has an important clinical significance for further distribution management on ASC-US patients and should draw great attention of gynecologist .
7.Research situation of pH low insertion peptides
Xue-li JIA ; Jia ZHANG ; Ting ZHAO ; Qing DU ; De-ying CAO ; Bai XIANG ; Ge-xia GENG ; Xian-rong QI
Acta Pharmaceutica Sinica 2018;53(3):375-382
Extracellular acidity has been associated with many pathological states, such as cancer, ischemic stroke, neurotrauma and infection, which makes it an effective target for therapy and diagnosis of such diseases. As a polypeptide vector, pH low insertion peptides (pHLIPs) are endowed with high sensitivity to extracellular acidic environment, which can insert the membrane and deliver payload to pathological cells in a pH dependent manner. Here, theranostic applications of pHLIP in disease, are reviewed in two aspects:pHLIP-mediated single-molecule transporter and nano-sized carrier.
8.Rapid identification of chemical components in Xingbei Zhike Keli by UPLC-Q-TOF-MS/MS.
Ning ZHANG ; Xia GAO ; Yu ZHOU ; Ting GENG ; Biao YANG ; Xue WANG ; Wen-Zhe HUANG ; Wei XIAO
China Journal of Chinese Materia Medica 2018;43(22):4439-4449
To analyze and identify the chemical components in Xingbei Zhike Keli by using ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS). The analysis was performed on Agilent Zorbax SB-C₁₈(4.6 mm×250 mm, 5 μm) column, with methanol-0.08% formic acid solution (including 0.1% ammonium formate) as the mobile phase for gradient elution. The flow rate was 1 mL·min⁻¹ and column temperature was 30 °C. The MS spectrum was acquired in both negative and positive ion modes by using electron spray ionization (ESI). These components were further analyzed based on accurate m/z, secondary fragmentation and other information combined with reference substance and literature data. As a result, 87 compounds were successfully identified and predicted, including alkaloids, flavonoids, coumarins and saponins, of which 23 compounds were verified by comparing with reference substances. These results provide reference for the quality control of Xingbei Zhike Keli, and lay the foundation for elucidating their effective components and mechanism of action.
Alkaloids
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Chromatography, High Pressure Liquid
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Drugs, Chinese Herbal
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Flavonoids
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Spectrometry, Mass, Electrospray Ionization
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Tandem Mass Spectrometry
9.Effect of Saposhnikoviae Radix on pharmacokinetics and tissue distributions of active components in Tongxie Yaofang in rats.
Rui-Feng LIANG ; Wen-Jing GE ; Zheng WEI ; Xue-Xia ZHANG ; Wei-Feng CUI ; Xue LIU ; Geng-Sheng LI
China Journal of Chinese Materia Medica 2017;42(19):3802-3808
Tongxie Yaofang (TXYF) is a famous formula that has been used for treating gastrointestinal diseases in traditional Chinese medicine(TCM). Saposhnikoviae Radix is considered as a meridian guiding drug in TXYF and could enhance the effectiveness of prescription. However, the scientific evidence for this effect is still not clear. To reveal the interactions of Saposhnikoviae Radix with other herbs, we conducted this study on the pharmacokinetic profile and tissue distribution of active ingredients of TXYF in rats. The concentrations of four components in blood and tissues were determined by UPLC-MS/MS after oral administration with TXYF. The detection was carried out by electrospray ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The positive and negative ion switching technique was performed in the same analysis. The results revealed that Saposhnikoviae Radix could enhance Cmax, AUC0-t, and AUC0-∞ of paeoniflorin and hesperidin, and increase the distribution of atractylenolide-I, paeoniflorin and hesperidin in liver, spleen, brain and small intestine. Saposhnikoviae Radix increased the ratio of brain to blood concentrations of atractylenolide-I, paeoniflorin and hesperidin. Meanwhile, it reduced the ratio of lung to blood concentrations of atractylenolide-I and paeoniflorin. Saposhnikoviae Radix, and may enhance the effectiveness of prescriptions by promoting distribution of other herbs in brain.
10.The study of HPV infection genotyping in vulva condyloma acuminate tissues of 691 women
Xiurong LONG ; Jingui JIANG ; Jianxiang GENG ; Zhaoxia YU ; Lin XIA ; Hongjing WANG ; Jing MEI ; Dongbin LI ; Xue ZHAO
International Journal of Laboratory Medicine 2017;38(17):2350-2352
Objective To explore the clinical distribution states of human papillomavirus genotypes in tissues of 691 women with vulva condyloma acuminates in Nanjing city and Zhenjiang city in Jiangsu Province and genotyping clinical significance.Methods Polymerase chain reaction(PCR)and gene-chips technology were utilized for the detection of 23 kinds of HPV genotypes in tissue specimens from 619 women of vulva condyloma acuminates in Nanjing city and Zhenjiang city in Jiangsu Province.And related materials of all subjects were analyzed.Results In 691 women of vulva condyloma acuminates,597 women of HPV infecton,total infection rate of HPV was 86.40%(597/691),including single genotype infection rate of HPV was 51.38%(355/691),11、6 and 16 genotypes are the most common in single genotypes,they are successively 51.55%(183/355)、41.97%(149/355)and 3.38%(12/355).multiple genotypes infection rate of HPV was 35.02%(242/691),6+11、11+18、6+16 and 11+16 genotypes are the most common in multiple genotypes,they are successively 9.92%(24/242)、9.09%(22/242)、4.96%(12/242)and 4.13%(10/242).Conclusion The low-risk HPV types are the main factors to cause the female vulva CA,a few high-risk HPV types may cause warts as well in tissues of women with vulva condyloma acuminates in Nanjing city and Zhenjiang city in Jiangsu Province.The vulva examine of HPV types should be held to the vulva CA patients.This precaution will has extremely important meaning to the prevention and treatment of the female vulva CA and cervical lesion in our nation.

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