1.Visualization analysis of stem cell therapy for myocardial infarction based on Web of Science in recent ten years
Yukang SUN ; Lijuan SONG ; Chunli WEN ; Zhibin DING ; Hao TIAN ; Dong MA ; Cungen MA ; Xiaoyan ZHAI
Chinese Journal of Tissue Engineering Research 2024;28(7):1143-1148
BACKGROUND:Although traditional therapies,including drugs and surgery,cannot repair the damaged myocardial tissue,the mortality rate of myocardial infarction remains high.Stem cells provide the possibility to solve this problem due to their self-renewal and multi-directional differentiation potential. OBJECTIVE:To analyze the research progress of stem cell therapy for myocardial infarction in recent ten years by bibliometric analysis. METHODS:The related articles on stem cells and myocardial infarction published in SCI-E and SSCI from January 1,2012 to December 1,2022 in the Web of Science database were searched.EXCEL,CiteSpace and VOSviewer software were used to make statistical and visualization analyses of the data such as the number of publications,authors,institutions,journals,countries and keywords. RESULTS AND CONCLUSION:A total of 3 210 core articles were published,and the total number increased year by year.hausenloy,derek j.is the author with the largest number of publications,China is the country with the largest number of publications,and the Fourth Military Medical University is the institution with the largest number of publications.The research hotspots in this field are changing from cell experiments and animal experiments to clinical trials.In the past ten years,research in this field has been highly popular and still has great development prospects.It is necessary to promote international and inter-agency exchange and learning,and further explore the role of stem cells in the treatment of myocardial infarction.
2.Exploration of the Mechanism of Autophagy Induced by Morin in Non-small Cell Lung Cancer A549 Cells Based on mTOR/STAT3 Signaling Axis
Xinyue ZHAO ; Yingying TIAN ; Chuang LIU ; Yilin LI ; Yingnan LYU ; Shangyue YU ; Shiqiu TIAN ; Hailuan PEI ; Zeping ZUO ; Zhibin WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(3):317-324
Objective To investigate the mechanism of morin-induced autophagy in non-small cell lung cancer A549 cells based on mTOR/STAT3 signaling axis.Methods A549 cells were divided into blank group and 30,60,90,120 and 150 μg·mL-1 of morin groups.After 24,48 and 72 hours of culture,the cell proliferation activity was detected by CCK-8 method,and the cell inhibition rate was calculated.A549 cells were divided into blank group and 30,90,150 μg·mL-1 morin groups.After 14 days of culture,the cell proliferation was detected by colony formation assay.After 24 hours of culture,the cell proliferation ability was detected by BeyoClickTM EdU-488.Apoptosis was detected by flow cytometry;acridine orange staining was used to detect cell autophagy;the formation of autophagosomes was observed by transmission electron microscopy.Western Blot was used to detect the expression levels of apoptosis,autophagy and mTOR/STAT3 signaling axis-related proteins in cells.A549 cells were divided into blank group,blank group + chloroquine(10 μg·mL-1)group,morin(30,150 μg·mL-1)group,morin(30,150 μg·mL-1)+ chloroquine(10 μg·mL-1)group.After 48 hours of intervention,the cell activity was detected by CCK-8 method,and the cell survival rate was calculated.Results Compared with the blank group,the inhibition rate of A549 cells in 60,90,120,150 μ g·mL-1 of morin group was significantly increased after 24 hours of intervention(P<0.05,P<0.001).The inhibition rates of A549 cells in 30,60,90,120 and 150 μg·mL-1 of morin groups were significantly increased after 48 and 72 hours of intervention(P<0.001).The number of A549 cell colonies and the number of green fluorescent proliferation positive cells in the 30,90,150 μg·mL-1 of morin groups were significantly decreased(P<0.01,P<0.001),the apoptosis rate was significantly increased(P<0.01,P<0.001),and the protein expression level of cleaved-PARP was significantly increased(P<0.001).The protein expression levels of p-P38/P38 MAPK in A549 cells of 90 and 150 μg·mL-1 of morin groups were significantly increased(P<0.01,P<0.001).Different degrees of orange fluorescence appeared in A549 cells of 30,90 and 150 μg·mL-1 of morin groups,and the orange fluorescence of 90 and 150 μg·mL-1 of morin groups was significant.Autophagosomes and autolysosomes appeared in the cytoplasm of A549 cells in 150 μg·mL-1 of morin group,respectively.The protein expression of LC3-Ⅱ in A549 cells of 150 μg·mL-1 of morin group was significantly up-regulated(P<0.05).The protein expression of Atg16L1-Ⅱ in A549 cells of 90,150 μg·mL-1 of morin group was significantly up-regulated(P<0.001),and the protein expressions of p-mTOR/mTOR and p-STAT3/STAT3 were significantly down-regulated(P<0.001).Compared with the morin(150 μg·mL-1)group,the survival rate of A549 cells in the morin(150 μg·mL-1)+chloroquine(10 μg·mL-1)group was significantly increased(P<0.05).Conclusion Morin can promote the apoptosis of A549 cells and induce autophagy in A549 cells,and the mechanism may be related to mTOR/STAT3 axis.
3.Effect of Danhe Granules on Hypercholesterolemia Rats Based on Cholesterol Metabolism Pathway-related Proteins
Shiqiu TIAN ; Zeping ZUO ; Yingying TIAN ; Yilin LI ; Hailuan PEI ; Zhaozhou LIN ; Yingnan LYU ; Jianfang WANG ; Zhibin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):85-94
ObjectiveTo explore the therapeutic effect and mechanism of the Danhe granules on hypercholesterolemia rats by observing the changes in the efficacy indicators and the levels of proteins related to the cholesterol metabolism pathway in the rats under the intervention of Danhe granules. MethodSD rats were randomly assigned to either the blank group or the model group based on their body weight. The blank group had normal chow diets, while the model group was fed high-fat diets for seven weeks. One week after the establishment of the model, the content of the serum total cholesterol (TC) in the model rats was detected. According to the TC value, the model group was further randomly divided into a control group, pravastatin sodium tablet group(4.02 mg·kg-1), Xuezhikang capsule group(0.12 g·kg-1), high-dose, middle-dose, and low-dose groups of Danhe granules(4.536, 2.268, 1.134 g·kg-1). After grouping the model groups, each treatment group received continuous oral gavage for six weeks, with weekly measurements of body weight and food intake (the difference between feed intake and feed surplus). Six weeks later, the levels of serum TC, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured. The liver pathology and lipid droplet distribution were evaluated by hematoxylin-eosin (HE) staining and oil red O staining, with scoring and calculation conducted. Rat liver tissue was collected, and western blot and immunohistochemistry (IHC) were used to detect the expression levels of cholesterol metabolism-related proteins namely phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK), AMPK, 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR), low-density lipoprotein receptor (LDLR), cholesterol 7α-hydroxylase (CYP7A1), Acyl-coenzyme A: cholesterol acyltransferase 2 (ACAT2), and apolipoprotein B (ApoB) in hypercholesterolemia rats. ResultCompared with the blank group, the model group showed a significantly higher level of serum TC (P<0.01). The TG level had no significant change, and the HDL-C level was significantly decreased (P<0.05). The liver index, steatosis score, total score of pathological state, and the positive area ratio of oil red O staining were significantly increased (P<0.01), and the protein expression levels of p-AMPK, p-AMPK/AMPK, LDLR, and CYP7A1 were significantly decreased (P<0.05, P<0.01), while the protein expression levels of AMPK, HMGCR, and ACAT2 were significantly increased (P<0.05, P<0.01). Compared with the model group, the TC level in each dose group of Danhe granules was significantly decreased (P<0.05), and the positive area ratio of oil red O staining in the pravastatin sodium tablet group and medium-dose group of Danhe granules was significantly decreased (P<0.05). In each administration group, the protein expression levels of p-AMPK and p-AMPK/AMPK were significantly increased (P<0.05, P<0.01), and the levels of HMGCR and ACAT2 were significantly decreased (P<0.01). The ApoB level showed a downward trend. The CYP7A1 level in the pravastatin sodium tablet group and each dose group of Danhe granules was significantly increased (P<0.05, P<0.01), and the LDLR level in the pravastatin sodium tablet group, Xuezhikang capsule group, and high-dose and medium-dose groups of Danhe granules was significantly increased (P<0.05, P<0.01). ConclusionDanhe granules can reduce serum TC levels and improve hepatic steatosis. It may activate AMPK, down-regulate the expression of HMGCR, and inhibit cholesterol synthesis. It can also up-regulate the expression of LDLR and CYP7A1, promote cholesterol uptake and excretion, down-regulate the expression of ACAT2 and ApoB, reduce cholesterol absorption and assembly of LDL and other lipoproteins, and thus play a role in the treatment of hypercholesterolemia.
4.Optimization of Methods for Study of Antiallergic Activity in vitro and Screening of Chinese Medicine Anti-Allergic Activity
Yilin LI ; Zeping ZUO ; Yingying TIAN ; Chuang LIU ; Xinyue ZHAO ; Yingnan LYU ; Zhibin WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(5):1261-1268
Objective To optimize the screening methods for antiallergic activity of two Chinese medicines in vitro and compare the antiallergic activity of five medicine pairs in vitro.Methods The degranulation assay of RBL-2H3 cells was optimized,and the activity of the five drugs on inhibiting mast cell degranulation was compared by toluidine blue staining and the release of β-HEX and histamine(HIS).The hyaluronidase inhibition test was optimized to compare the hyaluronidase inhibition effect of five Chinese medicine pairs.Results In the experiment of degranulation of RBL-2H3 cells,5 medicine pairs could inhibit β-HEX release from model cells to different degrees(P<0.05),including Schizonepetae Herba-Saposhnicovia divaricata,Ephedrae Herba-Asarum,Saposhnicovia divaricata-Radix Angelicae dahuricae,Rhizoma Chuanxiong-Asarum.The β-HEX release rate in the supernatant of degranulated model cells was significantly increased(P<0.05)after coculture with Flos Magnoliae-Fructus Xanthii.All the five medicine pairs could reduce HIS release in the supernatant of degranulated model cells.In the hyaluronase inhibition rate test,the hyaluronase inhibition rate of each medicine pair was Rhizoma Chuanxion-Asarum>Saposhnicovia divaricate-Radix Angelicae dahuricae>Schizonepetae Herba-Saposhnicovia divaricate>Ephedrae Herba-Asarum,among which Rhizoma Chuanxiong-Asarum had the strongest anti-allergic activity.Conclusion The trend of antiallergic activity of different drugs obtained by the two methods is consistent in vitro,indicating that the two methods can be used for screening antiallergic activity in vitro.
5.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
6.HBV infection among blood donors from 18 domestic blood stations of prefecture-level cities
Dingding WANG ; Youhua SHEN ; Jianling ZHONG ; Hui ZHANG ; Zhibin TIAN ; Lin BAO ; Huixia ZHAO ; Jian ZHANG ; Peng WANG ; Yanqin HE ; Wei ZHANG ; Li LI ; Hao LI ; Dexu CHU ; Ying WANG ; Xin ZHANG ; Shouguang XU ; Min HUANG ; Yan QIU
Chinese Journal of Blood Transfusion 2023;36(2):172-176
【Objective】 To analyze the hepatitis B virus (HBV) infection data of blood donors from 18 domestic blood stations, so as to investigate the HBV infection situation of blood donors. 【Methods】 The positive rate of HBV and its distribution characteristics of regions, the percentage of HBsAg+ ELISA in first-time vs repeated blood donors, and the percentage of HBsAg-/HBV DNA+ blood donors of 18 domestic blood stations during 2017 to 2020 were collected from the Working Platform for Practice Comparison of Blood Centers, and the HBV infection among blood donors were statistically analyzed. 【Results】 From 2017 to 2020, the positive rate of HBV in blood donors among 18 domestic blood stations was 13.48/10 000-144.02/10 000, with the average HBV positive rate in eastern, central and western region at 26.14/10 000, 51.98/10 000 and 41.00/10 000, respectively. The HBsAg+ rate by ELISA among first-time and repeated blood donors was 14.55/10 000-305.39/10 000 vs 1.04/10 000-87.43/10 000 The HBsAg-/HBV DNA+ yield was 1.80/10 000-35.31/10 000. 【Conclusion】 The distribution of HBV infection in blood donors has regional characteristics, and HBV prevalence was low in repeated blood donors. HBsAg ELISA combined with HBV DNA detection can better ensure blood safety.
7.Effects of neuroendoscopic hematoma removal versus soft channel drainage in the treatment of chronic subdural hematoma
Jianbo SHEN ; Jie CUI ; Kaipeng QIAO ; Zhihua TIAN ; Zhibin DUAN ; Guiping CHEN ; Haifeng DUAN ; Min LI ; Kefeng HUANG ; Xiaohong RU
Chinese Journal of Primary Medicine and Pharmacy 2023;30(5):719-723
Objective:To investigate the clinical efficacy of neuroendoscopic hematoma removal versus soft channel drainage in the treatment of chronic subdural hematoma. Methods:The clinical data of 102 patients with chronic subdural hematoma who received treatment in Jincheng People's Hospital from May 2018 to May 2020 were retrospectively analyzed. They were divided into the neuroendoscopy group ( n = 50) and the soft channel group ( n = 52) according to different surgical methods. Perioperative indexes, hematoma clearance rate, China Stroke Scale score, the activity of daily living score, and oxidative stress indexes were compared between the two groups. All patients were followed up for 3 months. The incidence of complications during the follow-up period was calculated. Results:The retention time of the drainage tube in the neuroendoscopy group was shorter than that in the soft channel group [(2.45 ± 0.63) days vs. (3.30 ± 0.78) days, t = 6.06, P < 0.001]. The length of hospital stay in the neuroendoscopy group was shorter than that in the soft channel group [(7.14 ± 1.65) days vs. (9.07 ± 2.11) days, t = 5.15, P < 0.001]. The hematoma clearance rate at postoperative 7 days in the neuroendoscopy group was higher than that in the soft channel group [(93.45 ± 5.50)% vs. (81.86 ± 7.24)%, χ2 = 9.12, P < 0.001]. There were no significant differences in operation time and intraoperative blood loss between the two groups (both P > 0.05). At postoperative 30 days, the China Stroke Scale score in the neuroendoscopy group was lower than that in the soft channel group [(12.74 ± 2.23) points vs. (18.67 ± 2.45) points, t = 12.79, P < 0.001]. The activity of daily life score in the neuroendoscopy group was significantly higher than that in the soft channel group [(77.69 ± 7.11) points vs. (91.35 ± 7.25) points, t = 9.60, P < 0.001]. At postoperative 7 days, glutathione peroxidase level in the neuroendoscopy group was significantly lower than that in the soft channel group [(130.75 ± 13.66) U/L vs. (148.60 ± 14.64) U/L, t = 6.37, P < 0.001]. Malondialdehyde level in the neuroendoscopy group was significantly lower than that in the soft channel group [(5.11 ± 0.65) nmol/L vs. (6.19 ± 0.74) nmol/L, t = 7.83, P < 0.001]. Superoxide dismutase level in the neuroendoscopy group was significantly higher than that in the soft channel group [(275.60 ± 22.33) U/L vs. (254.60 ± 18.55) U/L, t = 5.15, P < 0.001]. There was no significant difference in the incidence of complications between the two groups ( P > 0.05). Conclusion:Compared with soft channel drainage, neuroendoscopic hematoma removal can obtain better short-term curative effects and less oxidative stress response in the treatment of chronic subdural hematoma. Neuroendoscopic hematoma removal does not increase the incidence of postoperative complications and is highly safe.
8.Dehydrocostus Lactone Inhibits Growth of Human Lung Cancer A549 Cells Through Activation of Apoptosis and Autophagy
Yingying TIAN ; Yilin LI ; Shiqiu TIAN ; Hailuan PEI ; Shangyue YU ; Zijian WANG ; Zeping ZUO ; Zhibin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(2):73-80
ObjectiveTo evaluate the effects of dehydrocostus lactone (DL) on the proliferation, apoptosis, and autophagy of human lung cancer cell A549 and to elucidate its related mechanism. MethodThe effect of DL with different concentrations (0, 5, 10, 15, 20, 25 μmol·L-1) on the proliferation of human lung cancer A549 cells was investigated by cell counting kit-8 (CCK-8), and its impact on the clonogenic ability of A549 cells was studied by cell clonogenic assay. The concentrations 10, 20 μmol·L-1 were selected as DL low-dose group and high-dose group. Hoechst 33258 staining and western blot were used to observe the effect of DL on apoptosis of A549 cells. Autolysosomes were detected by acridine orange staining, and the expression level of microtubule-associated protein 1 light chain 3 (LC3) was determined by immunofluorescence and western blot. In addition, the effects of DL in combination with autophagy inhibitors bafilomycin A1 (BAF-A1) or 3-methyladenine (3-MA) on the autophagy of A549 cells was checked by CCK-8 assay. Finally, the role of DL in the regulation of A549 cell signaling pathway was explored by Western blot. ResultCompared with the conditions in the control group, the survival rate of A549 cells in the DL groups (10, 15, 20, 25 μmol·L-1) was decreased (P<0.01), and 5 μmol·L-1 DL could inhibited the formation of A549 clone cells (P<0.01), indicating that DL could inhibit the proliferation of human lung cancer A549 cells. The number of apoptotic cells was higher in both DL low-dose and high-dose groups than that in the control group, and the expression of apoptosis-related proteins poly (ADP ribose) polymerase (PARP) and B lymphocytoma-2 (Bcl-2)-associated X protein (Bax) were up-regulated (P<0.05, P<0.01), while the expression of Bcl-2 was down-regulated (P<0.01) in DL high-dose group. The acridine orange staining showed that the orange fluorescence in the DL high-dose group was enhanced compared with that in the control group, indicating that DL could dramatically promote the formation of autolysosomes. Moreover, 20 μmol·L-1 DL could increase the orange fluorescent particles of LC3 and up-regulated the expression level of LC3 Ⅱ (P<0.01). After addition of autophagy inhibitors, the sensitivity of A549 cells to the effects of DL was attenuated (P<0.01), which suggested that autophagy was involved in DL-induced A549 cell death. Compared with the control group, DL high-dose group had increased expression of autophagy-related protein 3 (Atg3) and autophagy-related protein 5 (Atg5) while reduced phosphorylation levels of protein kinase B (Akt), mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3) (P<0.05, P<0.01). ConclusionDL could activate apoptosis and autophagy to inhibit the proliferation and clonogenic ability of A549 cells via suppressing Akt/mTOR/STAT3 signaling pathway.
9.Clinical antitumor application and pharmacological mechanisms of Dahuang Zhechong Pill.
Yingying TIAN ; Beibei MA ; Shangyue YU ; Yilin LI ; Hailuan PEI ; Shiqiu TIAN ; Xinyue ZHAO ; Chuang LIU ; Zeping ZUO ; Zhibin WANG
Chinese Herbal Medicines 2023;15(2):169-180
Cancer still has elevated morbidity and mortality, which undoubtedly impacts the life quality of affected individuals. Remarkable advances have been made in cancer therapy, although the toxicities of traditional therapies remain an obvious challenge. Dahuang Zhechong Pill (DHZCP), developed by Zhongjing Zhang in the Synopsis of the Golden Chamber, represents an effective anticancer traditional Chinese medicine (TCM). In this review, it was found that DHZCP is therapeutically utilized in liver, lung, gastric, pancreatic and other cancers in clinic. Pharmacological evidence showed that its anti-tumor mechanisms mainly involve induced cell cycle arrest, apoptosis and autophagy, as well as suppressed tumor cell proliferation, obstructed angiogenesis and metastasis, enhanced immunity, and reversal of multidrug resistance. The present review provides a solid basis for the clinical application of DHZCP and may promote the wide use of TCM in clinical antitumor application.
10.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.

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