1.Influence of anti- angiogenesis therapy on proliferation and apoptosis of fibroblasts derived from keloid
Yunchun MAO ; Xuemei MA ; Shufang SHI ; Yinguang GAO ; Hongjiao QI ; Shuyuan CHEN
International Journal of Surgery 2011;38(7):461-465,506
Objective To investigate the influence of anti-angiogenesis therapy on proliferation and apoptosis of fibroblasts derived from keloids. Methods Thirty pieces of keloids from a patient were implanted into subcutaneous tissue of the nude mice, 24 pieces of which survived were divided into three groups which were treated with perilesional injection of vascular endothelial growth factor( VEGF) (0.4 mg/0.2 mL) , Endostar(0.125 g/0.2 mL) and physiological saline (0.2 mL)on the 21 d, 23 d, 25 d, 27 d after implantation. Sample were collected on the 10th day after perilesional injection, the proliferating fibroblasts in keloid tissue were immunohistochemically detected by proliferating cell nuclear antigen (PCNA) expression. The apoptotic cell was detected by terminal deoxynucleotidyl transferase dUTP-nick end labeling (TUNEL) staining. Results IHC staining indicated that PCNA expression of fibroblasts was significantly increased in keloid tissue after VEGF injection, PCNA expression of fibroblasts was significantly reduced in keloid tissue after Endostar injection,TUNEL assay revealed lower apoptotic cells expression in the keloid tissue after VEGF injection and higher in the Endostar group than control group. The rate of proliferative index (PI) , apoptotic index(AI) and AI/PI of fibroblasts in keloid after VEGF (PI:41.13 ±2.29,AI:5.75 ±1.28,AI/PI: 0.14 ± 0.04)or Endostar injection (PI:27.25 ±2.61,AI:11.00±1.31,AI/PI:0.41 ±0.09)and control group (PI: 34.75 ±3.62,AI:7. 88 ± 1.64,AI/PI:0. 23 ±0.07) showed statistical differences. Conclusion Anti-angiogenesis therapy is shown to induce keloid regression through suppression of keloid fibroblast proliferation,induction of apoptosis, which may be a new approach for the treatment of keloids.
2.Clinical Observation on Angong Niuhuang Wan Including In-Vitro Cultured Calcul us Bovis in Treating Epi-demic Encephalitis B
Hongjiao CAI ; Xiaoqin ZHANG ; Genrong MAI ; Jinyu XIA ; Wei XIN ; Hong XIE ; Qi WANG ; Shilon LAI
Traditional Chinese Drug Research & Clinical Pharmacology 1993;0(03):-
0.05).The results of electrocardiography and the laboratory ex-amination showed that neither ANWin cluding natural Calculus Bovis nor A NWincluding in -vitro cultured Calc ulus Bo-vis had obviously toxic and side effe cts in treating epidemic encephalitis B.Conclusion ANW including in -vitro cul-tured Calculus Bovis has an markedly effect in the treatment of epidemic e ncephalitis B.
3.Clinical Studies on In-vitro-cultured Calculus Bovis in the Treatment of Apoplexy
Hongjiao CAI ; Xiaoqin ZHANG ; Chengyan LI ; Chaoyun HAUNG ; Qi WANG ; Shilong LAI
Traditional Chinese Drug Research & Clinical Pharmacology 1993;0(04):-
0.05).Conclusion In-vitro-cultured CB has good effects in the treatment of apoplexy.Neither in-vitro-cultrued CB nor natural CB for apoplexy has obvious adverse reaction.
4.Fungistasis of nanometer silvers synthesized by different methods on Candida al-bicans
Lulu ZHANG ; Qi MIAO ; Zhaojiao YE ; Hongjiao LI ; Yuanying JIANG ; Yongbing CAO
Journal of Pharmaceutical Practice 2015;(4):328-330,358
Objective To explore the in vitro fungistasis of nanometer silvers made by different methods on Candida al-bicans .Methods The minimal inhibitory concentrations (MICs) of Candida albicans strains stimulated to silver nanoparticles were determined by microdilution method .The combination effects of silver nanoparticles with fluconazole were determined by chess board check assay .Results The inhabitation effect of two kinds of silver nanoparticles were different on the growth of Candida albicans .Silver nanoparticles had a synergistic effect with fluconazole on Candida albicans .Conclusion The two kinds of silver nanoparticles had various antifungal activities in vitro and had a synergistic effect with fluconazole on Candida albicans .
6.Analysis on Components Absorbed into Blood of Citri Reticulatae Pericarpium in Rats Based on Sequential Metabolism and UPLC-HRMS
Hongjiao CHEN ; Wei LIU ; Xueyan LI ; Dongying QI ; Shuang YU ; Huining LIU ; Haibo LIU ; Yang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(9):179-187
ObjectiveTo study the metabolism of chemical components from Citri Reticulatae Pericarpium(CRP)in different parts of rats by sequential metabolism and ultra performance liquid chromatography-high resolution mass spectrometry(UPLC-HRMS). MethodSD male rats were employed as experimental subjects, and blood samples of intestinal metabolism and hepatic metabolism were prepared after administration of CRP ethanol extract by in situ intestinal perfusion, and comprehensive metabolic samples were collected after intragastric administration. UPLC-HRMS was used to analyze the samples with acetonitrile(A)-0.1% formic acid aqueous solution(B)as the mobile phase for gradient elution(0-10 min, 10%-30%A; 10-30 min, 30%-95%A; 30-31 min, 95%-10%A; 31-35 min, 10%A)at a flow rate of 0.35 mL·min-1, using a heated electrospray ionization with positive and negative ion mode scanning in the range of m/z 100-1 500. Under these conditions, the differences in the profiles of CRP ethanol extract, blank plasma and drug-containing plasma under different treatment groups were compared, and the chemical components of each sample were analyzed and identified based on the retention time, accurate relative molecular mass, primary and secondary ion fragments, and the information of reference substances. ResultA total of 44 chemical components were identified in the CRP ethanol extract, including flavone-O-glycosides, flavone-C-glycosides and polymethoxyflavonoids, etc. The results of sequential metabolism showed that 22 chemical components in CRP were detected in the intestinal metabolic sample, 18 chemical components were detected in the hepatic metabolic sample, and 9 identical chemical components(narirutin, hesperidin, meranzin, 5,7,8,3ʹ,4ʹ,5ʹ-hexamethoxy-flavone, isosinensetin, sinensetin, 3,5,6,7,8,3ʹ,4ʹ-heptamethoxyflavone, nobiletin and tangeretin)could be detected in all three metabolic samples, with a total of 22 compounds entering the blood in prototype form. ConclusionThe identified 21 components with well-defined structures entering the blood as prototypes may be potential active components of CRP, and differences in the components at different metabolic parts can provide an experimental basis for elucidating the in vivo biotransformation process of the metabolic components of CRP.
7.Metabolic Analysis of Tongfengding Capsules in vivo Based on Sequential Metabolism
Hongjiao CHEN ; Wenning YANG ; Renfang YIN ; Yan ZHU ; Dongying QI ; Xueyan LI ; Huining LIU ; Shuang YU ; Yanli PAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(24):160-170
ObjectiveBased on sequential metabolism and ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS), to identify the prototype components and metabolites of Tongfengding capsules in rat plasma. MethodAn ACQUITY UPLC BEH Shield RP18 column (2.1 mm×100 mm, 1.7 µm) was used for gradient elution with 0.1% formic acid aqueous solution (A)-acetonitrile (B) as the mobile phase (0-1 min, 5%B; 1-2.4 min, 5%-10%B; 2.4-13.5 min, 10%-32%B; 13.5-18.5 min, 32%-90%B; 18.5-19 min, 90%-5%B; 19-21 min, 5%B) at a flow rate of 0.3 mL·min-1, injection volume of 2 μL and column temperature at 35 ℃. The heated electrospray ionization (HESI) was applied under positive and negative ion modes, and the scanning range was m/z 100-1 500. By comparing the differences between the administered plasma and the blank plasma, the prototype components and metabolites in intestinal metabolism sample and liver metabolism sample prepared by intestinal perfusion with parallel blood collection, and comprehensive metabolism sample prepared by intragastric administration method were identified. ResultA total of 76, 53, 74 chemical components were detected in the intestinal metabolism sample, the liver metabolism sample and the comprehensive metabolism sample. A total of 100 components were identified from these different plasma samples, including 64 prototype components (34 alkaloids, 12 terpenoids, 9 organic acids, 6 flavonoids and 3 other components) and 36 metabolites. The main metabolic reactions involved in the formation of metabolites were glucuronidation, deglucosylation, dehydrogenation and hydroxylation. ConclusionThe chemical components of Tongfengding capsules can undergo a series of metabolic reactions in the intestine and liver, and a large number of metabolites are generated, among which alkaloids may be the leading component group for efficacy, which can lay the foundation for systematic elucidating the material basis of Tongfengding capsules in vivo.
8.Design of a highly potent GLP-1R and GCGR dual-agonist for recovering hepatic fibrosis.
Nazi SONG ; Hongjiao XU ; Jiahua LIU ; Qian ZHAO ; Hui CHEN ; Zhibin YAN ; Runling YANG ; Zhiteng LUO ; Qi LIU ; Jianmei OUYANG ; Shuohan WU ; Suijia LUO ; Shuyin YE ; Runfeng LIN ; Xi SUN ; Junqiu XIE ; Tian LAN ; Zhongdao WU ; Rui WANG ; Xianxing JIANG
Acta Pharmaceutica Sinica B 2022;12(5):2443-2461
Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl4, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl4-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl4-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.