1.Chinese Materia Medica by Regulating Nrf2 Signaling Pathway in Prevention and Treatment of Ulcerative Colitis: A Review
Yasheng DENG ; Lanhua XI ; Yanping FAN ; Wenyue LI ; Tianwei LIANG ; Hui HUANG ; Shan LI ; Xian HUANG ; Chun YAO ; Guochu HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):321-330
Ulcerative colitis(UC) is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulceration of the colonic mucosa and submucosa, and its complex pathogenesis involves immune abnormality, oxidative stress and other factors. The nuclear transcription factor E2-related factor 2(Nrf2), encoded by the Nfe212 gene, plays a central role in antioxidant responses. It not only activates various antioxidant response elements such as heme oxygenase-1(HO-1) and quinone oxidoreductase 1(NQO1), but also enhances the activity of glutathione-S-transferase(GST) and superoxide dismutase 1(SOD1), effectively eliminating reactive oxygen species(ROS) accumulated in the body, and mitigating oxidative stress-induced damage to intestinal mucosa. In addition, Nrf2 can reduce the release of inflammatory factors and infiltration of immune cells by regulating immune response, cell apoptosis and autophagy pathways, thereby alleviating intestinal inflammation and promoting the repair and regeneration of damaged mucosa. Based on this, this paper reviews the research progress of Chinese materia medica in the prevention and treatment of UC by modulating the Nrf2 signaling pathway. It deeply explores the physiological role of Nrf2, the molecular mechanism of activation, the protective effect in the pathological process of UC, and how active ingredients in Chinese materia medica regulate the Nrf2 signaling pathway through multiple pathways to exert their potential mechanisms. These studies have revealed in depth that Chinese materia medica can effectively combat oxidative stress by regulating the Nrf2 signaling pathway. It can also play a role in anti-inflammatory, promoting autophagy, inhibiting apoptosis, protecting the intestinal mucosal barrier, and promoting intestinal mucosal repair, providing new ideas and methods for the multi-faceted treatment of UC.
2.Estimation model for exposure of intravenous busulfan in patients receiving autologous hematopoietic stem cell transplantation
Jin-Wen LI ; Yan XU ; Xiao-Dan WANG ; Ying-Xi LIAO ; Shuai HE ; Shan XU ; Ping ZHANG ; Wen-Juan MIAO
Chinese Pharmacological Bulletin 2024;40(6):1193-1198
Aim To establish limited sampling strategy to esti-mate area under the drug concentration versus time curve(AUC0-t)of lymphoma patients treated with autologous stem cell transplantation(ASCT)who had busulfan intravenous infu-sion.Methods Twelve lymphoma patients treated with ASCT received a conditioning regimen containing busulfan 105 mg·m-2,Ⅳ infusion for 3 h.Blood samples were obtained 1 h after the start of the first dose of the busulfan infusion,at 5 min,1 h,2 h,4 h,6 h and 18 h after the end of the drug administration.LC-MS/MS was used to determine the busulfan serum concentra-tion.After obtaining the clinical pharmacokinetic parameters of busulfan by traditional pharmacokinetic method,multiple linear stepwise regression analysis was used to establish the AUC0-t es-timation model of busulfan based on limited sampling method.The model was further verified by Jackknife and Bootstrap meth-od.Bland-Altman plots were used to evaluate the consistency between the limited sampling method and the classical pharma-cokinetic method.Results The multiple linear regression equa-tion analysis of C60min,C180min and C300min was obtained by the limited sampling method.The regression equation was AUC0-t=295.003C60min+233.050C180min+273.163C300min-1202.713,r2=0.995,MPE=-0.87%,RMSE=2.40%.Conclusion The limited sampling model with three-point estimation can be used to estimate the AUC0-t of busulfan exposure in lymphoma patients with ASCT to provide reference for clinical application of busulfan.
3.Role of TGR5 in proliferation and migration of vascular smooth muscle cells
Xi YANG ; Li ZHANG ; Yao YANG ; Jia WANG ; Xiong-Shan SUN ; Qiang WANG
Chinese Pharmacological Bulletin 2024;40(8):1447-1454
Aim To explore the role of Takeda G pro-tein-coupled receptor 5(TGR5)in the proliferation and migration of vascular smooth muscle cells(VSMCs)within the intimal layer of mice.Methods Mouse VSMCs were stimulated for proliferation and migration with PDGF-BB,followed by administration of INT-777 for activation of TGR5.CCK-8 assay and Ki-67 immunofluorescence staining were employed to eval-uate cell proliferation.The scratch assay was utilized to assess migration.Western blot analysis was conducted to monitor TGR5 protein expression.To further investi-gate the role of TGR5 in intimal hyperplasia in vivo,20 male wild-type C57BL/6J mice were randomly divided into four groups:sham group,carotid artery endothelial injury group,sham+UDCA(ursodeoxy-cholic acid,a TGR5 agonist)group,and carotid artery endothelial injury+UDCA group(n=5 in each group).After the establishment of endothelial injury model,mice were orally fed with regular maintenance feed containing 0.5%UDCA for 21 days.Subsequent-ly,samples were collected for Hematoxylin and Eosin(HE)staining to assess the neointimal hyperplasia.Immunofluorescence(IF)staining was used to exam-ine the proliferation of VSMCs within the carotid inti-ma.Results The specific activation of TGR5 marked-ly diminished cell viability,the proportion of Ki-67-positive cells,and slowed down the rate of wound-heal-ing.Notably,the specific activation of TGR5 increases the expression of UCP2 in cells and reduces the levels of reactive oxygen species(ROS).The inhibitory effect of TGR5 on VSMC proliferation and migration was neutralized upon the restoration of intracellular ROS level with H2O2.Activation of TGR5 was found to mitigate intimal thickening following carotid artery inju-ry.Conclusion TGR5 may inhibit the proliferation and migration of mouse VSMCs by attenuating intracel-lular oxidative stress.
4.Porcine SIRT5 promotes replication of foot and mouth disease virus type O in PK-15 cells
Guo-Hui CHEN ; Xi-Juan SHI ; Xin-Tian BIE ; Xing YANG ; Si-Yue ZHAO ; Da-Jun ZHANG ; Deng-Shuai ZHAO ; Wen-Qian YAN ; Ling-Ling CHEN ; Mei-Yu ZHAO ; Lu HE ; Hai-Xue ZHENG ; Xia LIU ; Ke-Shan ZHANG
Chinese Journal of Zoonoses 2024;40(5):421-429
The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.
5.Expression of UBE2C in liver cancer tissues and its effect on proliferation and invasion of hepatocellular carcinoma cells HepG2
Ping ZHAO ; Dan PANG ; Xi-Zeng ZHU ; Hai-Xia SHAN ; Hui-Wen JIA
Chinese Journal of Current Advances in General Surgery 2024;27(7):511-516
Objective:To investigate the expression level of UBE2C in liver cancer tissues and its effect on the proliferation and invasion of hepatocellular carcinoma cells HepG2 after UBE2C silencing.Methods:The data set of liver cancer was downloaded from the TCGA database.Ac-cording to the median expression level of UBE2C mRNA in liver cancer tissues,all liver cancer pa-tients were divided into UBE2C higher(n=169)and lower expression group(n=205),respectively.The expression level of UBE2C mRNA in liver cancer tissues and its relationship with the patients prognosis was analyzed.COX regression was used to analyze the influencing factors of the liver cancer patients prognosis.The human hepatocellular carcinoma cell lines(HepG2,Huh7 and SMMC-7721)and human nromal hepatic epithelial cell line(THLE-3)were selected,and the ex-pression level of UBE2C in the four cell lines were detected by Western blot and real-time fluores-cence quantitative PCR,respectively.The HepG2 cell line was protein and mRNA expression leves divided into control group,NC group and si-UBE2C group according to UBE2C silencing.The ef-fects of UBE2C silencing on proliferation and invasion of HepG2 cell line were analyzed.Results:The expression level of UBE2C mRNA in liver cancer tissues and adjacent normal liver tissues were 4.342(3.239,5.635)and 0.905(0.587,1.230),respectively.Compared with adjacent normal liver tissues,UBE2C mRNA levels in liver cancer tissues were significantly higher(P<0.001).The UBE2C mRNA expression levels in liver cancer tissues and paired adjacent normal liver tissues were 4.266(3.342,5.054)and 0905(0.587,1.230),respectively.Compared with paired adjacent normal liver tissues,UBE2C mRNA expression levels in liver cancer tissues were significantly higher(P<0.001).The median survival time of UBE2C mRNA higher and lower expression groups was 48.85 months and 69.38 months.Compared with the lower expression group,the median survival time of UBE2C mRNA higher expression group was significantly shortened(P=0.045).T staging(T3/T4)and UBE2C expression(higher expression)were independent risk factors for poor prognosis in patients with liver cancer(P<0.05).Compared with human liver epithelial cell line THLE-3,UBE2C protein and mRNA were significantly higher expressed in human hepatocellular carcinoma cell line HepG2,Huh7 and SMMC-7721(P<0.05).The expression level of UBE2C protein and mRNA expression was the most significant in human hepatocellular carcinoma cell line HepG2 relative to cell line Huh7 and SMMC-7721.The CCK-8 results show that the cell proliferation rate in si-UBE2C group were significantly decreased protein and mRNA expression levels compared to control group and NC group at 72 h and 96 h,and the differences were significant(P<0.05).The number of invasive cells in control group,NC group and si-UBE2C group were(23.12±3.45),(24.33±2.83)and(10.21±1.14),respectively.Compared with control group and NC group,the number of invasive cells in si-UBE2C group was significantly decreased(P<0.05).Conclusion:UBE2C was higher expressed in liver cancer,and can be used as a biomarker for poor prognosis of patients with liver cancer.After silencing of UBE2C gene can significantly inhibit proliferation and invasion of HepG2.
6.Protective effect of Naru-3 on collagen-induced arthritis in rats
Hai-Yue ZHAO ; Xiao-Shan ZHANG ; Sha-Sha DUAN ; Yi-Lu SHI ; Min-Jie ZHANG ; Shu-Rong YUN ; Ya-Xi WANG
Chinese Traditional Patent Medicine 2024;46(6):1842-1849
AIM To investigate the protective effect of Mongolian medicine Naru-3 on rat rheumatoid arthritis(RA)using imaging method.METHODS With the rats divided into the normal group,the model group,the positive medicine group,and the low,medium and high dose Naru-3 groups(0.1,0.2 and 0.4 g/kg),the rat model of collagen-induced arthritis(CIA)was established by immune induction method.After 4 weeks of corresponding drug administration,the rats had their changes of arthritis index(AI)level and body weight observed;their serum levels of VEGF,TNF-α and IL-1 detected by ELISA;their synovial hyperplasia and neovascularization evaluated by high-frequency ultrasound and contrast-enhanced ultrasound(CEUS);their bone destruction of ankle joint evaluated by X-ray and high-resolution micro-CT;and their synovial membrane and expressions of CD31,VEGF,TNF-α and IL-1 β observed by HE and immunohistochemistry.RESULTS Compared with the model group,the Naru-3 groups displayed increased rat weight(P<0.05);no significantly changed AI score(P>0.05);and overally decreased levels of serum VEGF,TNF-α,synovial membrane thickness,blood flow signal by power Doppler imaging(PDI)and contrast intensity revealed,X-ray score,and CD31 expression(P<0.05),in addition to the decreased level of IL-1 and HE score in high-dose group(P<0.05).CONCLUSION Naru-3 is protective to the joint tissue in rat model of RA through alleviating synovitis,bone erosion and delaying the progress of the disease by inhibiting synovial neovascularization and inflammatory cytokines.
7.Chemical constituents from the large polar fraction of the roots of Lindera reflexa and their antitumor activities
Zhi-Hao TIAN ; Xiao-Ya SUN ; Shan-Shan ZHANG ; Zhi-Ning GAO ; Yan LI ; Ruo-Xi CHEN ; Sui-Qing CHEN
Chinese Traditional Patent Medicine 2024;46(8):2617-2623
AIM To study the chemical constituents from the large polar fraction of the roots of Lindera reflexa Hemsl.and their antitumor activities.METHODS The large polar fraction from the roots of L.reflexa was isolated and purified by silica gel column,Sephadex LH-20 gel column,semi-preparative HPLC and ODS medium pressure column,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT method.RESULTS Thirteen compounds were isolated and identified as 2,6-dimethoxy-4-hydroxyphenyl-1-O-β-D-glucopyranoside(1),3-hydroxy-4,5-dimethoxyphenol-β-D-glucopyranoside(2),syringin(3),1-O-3,4-dimethoxy-5-hydroxyphenyl-(6-O-3,5-dimethoxygalloyl)-β-D-glucopyranoside(4),p-cymen-7-yl β-D-glucopyranoside(5),pisumionoside(6),staphylionoside D(7),dendranthemoside B(8),lynoiside(9),nudiposide(10),icariside B1(11),(2S)-pinocembrin-7-O-(6-O-α-L-rhamnopyranosyl-β-D-glucopyranoside)(12),(+)-N-(methoxycarbonyl)-N-norboldine(13).Compounds 3 and 13 showed obvious cytotoxicity against human lung cancer cells(A549)and human gastric cancer cells(MGC80-3).CONCLUSION Compounds 1-13 are isolated from the roots of L.reflexa for the first time.Compounds 3 and 13 have good anti-tumor activities.
8.Evaluation of prophylactic use of metal clips after cold resection of 6-10 mm intestinal polyps
Zhongxin SUN ; Can WU ; Mei YANG ; Li LIU ; Liu LIU ; Zhengkui ZHOU ; Weidong XI ; Jing SHAN ; Lin JIANG ; Yu LEI ; Xiaobin SUN
Chinese Journal of Digestive Endoscopy 2024;41(7):550-554
Objective:To investigate whether prophylactic use of metal clips is necessary after cold snare polypectomy (CSP) of colorectal polyps of 6-10 mm.Methods:A total of 200 patients with 6-10 mm polyps that met the criteria of cold snare resection in Chengdu Third People's Hospital from 15 February 2022 to 30 May 2022 were randomly divided into two groups: a group that received preventive metal clip treatment and an observation group. Age, gender, body mass index (BMI), Boston score, endoscopy entry time, wound size, operation time, intraoperative bleeding time, postoperative delayed bleeding rate and cost between the two groups were compared and analyzed.Results:Ninety-eight patients in the metal clip group had 122 polyps removed, and 97 patients in the observation group had 119 polyps removed. There was no significant difference in the age, gender, BMI, Boston score, endoscopy entry time or wound size between the two groups. There were significant differences in the operation time (171.03±90.78 s VS 69.81±43.26 s, t=2.266, P=0.010), intraoperative bleeding time (19.98±17.37 s VS 29.16±17.56 s, t=-2.875, P=0.006) and surgery cost (571.63±110.92 yuan VS 366.32±13.2 yuan, t=18.102, P<0.001) between the metal clip group and the observation group. There was no significant difference in the delayed bleeding incidence[0.0%(0/98)VS 1.0%(1/97), P=0.497]between the two groups. Conclusion:For patients with continuous bleeding time <60 seconds after CSP of 6-10 mm colonic polyps, the prophylactic use of metal clips may reduce the bleeding time, but may increase the operation time and cost. Metal clips have little effect on preventing postoperative complications.
9.Blocking performance test method of disposable check valves for infusion equipment
Xi-Yun DANG ; Su-Hua XU ; Xue BAI ; Jun KE ; Zhi TANG ; Shan FENG ; Shuo-Han LIN
Chinese Medical Equipment Journal 2024;45(9):78-83
YY 0585.4-2009 and ISO 8536-12:2021 standards were compared in terms of the blocking performance test method of disposable check valves for infusion equipment.The affecting factors and possible errors were analyzed when the blocking performance test was carried out according to YY 0585.4-2009,and it's pointed out ISO 8536-12:2021 gained advantages over YY 0585.4-2009 in the blocking performance test method of check valves.References and guidance were provided for standard revision and actual operation.[Chinese Medical Equipment Journal,2024,45(9):78-83]
10.Design of portable intramedullary injection device
Li-Hong LIU ; Yao WANG ; Shan LU ; Chen-Xi LU ; Ming-Hui XIE
Chinese Medical Equipment Journal 2024;45(11):109-112
Objective To design a portable intramedullary injection device to facilitate visualized precision puncture.Methods The portable intramedullary injection device was mainly composed of a holding shell,a display,a puncture needle,a controller and a power supply.The holding shell had a L-shaped structure,which was made of new high-performance thermoplastic resin and was provided with a polyethylene-vinyl acetate copolymer non-slip adhesive tape at its handle;the display was made of transparent nano-microcrystalline glass;the puncture needle consisted of an inner needle and an outer needle,which was made of austenitic stainless steel;a lithium iron phosphate battery was used for power supply.Results The portable intramedullary injection device facilitated safe and rapid puncture,and had the function of real-time monitoring of puncture pressure and depth.Conclusion The portable intramedullary injection device realizes visualized precision puncture with high convenience,portability,safety and durability,and contributes to enhancing the success rate for casualty treatment.[Chinese Medical Equipment Journal,2024,45(11):109-112]

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