1.Discovery of natural BH3 mimetics and research on related mechanism
Si-Meng GU ; Shuai-Shuai LIU ; Yue ZHANG ; Xue-Jun LI
Chinese Journal of Pharmacology and Toxicology 2018;32(4):281-282
In the past two decades,with the increase of smoking population,more and more people are suffering from small cell lung cancer(SCLC).Besides,it is difficult to find an effective way to cure SCLC,since patience can easily develop drug resistance.On the other hand,with the development of science and technology,people began to study the anti-cancer strategy to increase apoptosis,such as inhibiting the overexpression of survival factors.In these survival factors,BCL-2 family has attracted a lot of attention.BH3-only protein is a member of BCL-2 family and it can directly inhibit the expression of BCL-2 protein,thereby prompting apoptosis.Since the BH3-only protein itself is difficult to become a clinical drug, to find alternatives BH3-only protein-BH3 mimetics is particularly important. Plus, more and more researchers have paid attention on the natural BH3 mimetic since it has less side-effect than artificial BH3 mimetics.To find possible BH3 mimetics,we made a primary screening with this pharma-cophore on a small molecular compounds library via Discovery Studio software. And then MTS assay were introduced to verify the activity of compounds. After that, we use Western Blot and Co-IP meth-ods to test the effect of BH3 mimetics.And finally use CDOCKER to predict the further mechanism on autophagy and apoptosis.In our studies, we found 3 possible BH3 mimetics compounds from 170,000 natural small molecular compounds via pharmacophore-based virtual screening.Furthermore,we dem-onstrated AD23,one of the 3 possible natural BH3 mimetics,induced autophagy and apoptosis simulta-neously in dose-time dependence in SCLC cell line. Finally, we use Molecular Docking to predict the further mechanism on autophagy and apoptosis. We believe our works would provide evidences and clues for the structural optimizing and further study of new drugs in the future.
2.Inhibitory effect of ZX-1201 on pancreatic cancer and the relevant molecular mechanism
Shuai-Shuai LIU ; Si-Meng GU ; Jian-Hui DUAN ; Xue-Jun LI
Chinese Journal of Pharmacology and Toxicology 2018;32(4):295-296
Pancreatic ductal adenocarcinoma (PDAC) is one of the five most malignant cancer. ZX-1201 is one of the active constituents in Alismatis Rhizoma,a well-known traditional Chinese medi-cine with a wide variety of pharmacological properties including diuretic,anti-hyperlipidemic,anti-atheroscle-rotic,anti-cancer,anti-inflammatory and anti-oxidative activities.We investigated the inhibitory effect of ZX-1201 on pancreatic cancer and the relevant molecular mechanism in vitro and in vivo. ZX-1201 inhibited the growth and metastasis of PANC-1 cells in BALB/c nude mice significantly.ZX-1201 inhibited the function of AQP1 via directly interaction and involved in the reversion process of ZX-1201 on TGF-β1. CTGF was an important protein in the reversion process of ZX-1201 on TGF-β1.ZX-1201 inhibited the migration of PANC-1 and CPFAC-1 cells induced by TGF-β1in vitro.ZX-1201 reversed the down-regu-lated of epithelial markers and up-regulated of mesenchymal markers, as well as the up-regulated of Snail and p-Smad2/3 induced by TGF-β1.And ZX-1201 reversed Epithelial-Mesenchymal Transition by down-regulating AQP1 and inhibiting translocation of β-catenin, the promotor of CTGF. According to these,ZX-1201 inhibited the migration of pancreatic cancer cells.We concluded that ZX-1201 inhibited the growth and metastasis of PANC-1 cells in vivo significantly.And AQP1,β-catenin and CTGF were the pivotal proteins in the process of ZX-1201 inhibiting PANC-1 cells migration induced by TGF-β1.
3.Clinical analysis of effect of Dexmedetomidine on postoperative cognitive function and preoperative inflammation in the elderly patients undergoing general anesthesia
Haibing MENG ; Wei LAI ; Jun SHUAI ; Guoyou DING
The Journal of Practical Medicine 2014;(14):2300-2301
Objective To study the effect of dexmedetomidine (DEX) on postoperative cognitive function and preoperative inflammation in the elderly patients undergoing general anesthesia. Methods 70 elderly patients undergoing general anesthesia operation were chosen and divided into observation group and control group randomly. DEX and physiological saline were applied in observation group on the basis of routine general anesthesia. The cognitive function of patients in both groups were tested by mini-mental state examination (MMSE) and the incidence rate of cognitive dysfunction (POCD) were measured at 1 day before surgery, 1 day, 3 days, 5 days, and 7 days after surgery. The level of interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) were tested before anesthesia, during skin incision, rightly after operation and 1h after operation. Results MMSE scores were significantly higher and the incident rates of POCD were lower in observation group than those in control group at 1 day and 3 days after surgery (P<0.05). The levels of IL-6 and TNF-αincreased obviously during skin incision and postoperative period, and they were significantly lower in observation group (P<0.05). The levels of IL-6 and TNF-αdecreased to the levels before anesthesia in observation group, and were still much higher in control group than that of preanesthesia (P < 0.05). Conclusions DEX infusion intraoperatively may effectively decrease the incidence of early POCD, whose mechanism could be reducing inflammation response.
4.Farnesoid X receptor regulates glucose and lipid metabolisms.
Qian JIANG ; Jun PENG ; Shuai-nan LIU ; Zhu-fang SHEN
Acta Pharmaceutica Sinica 2015;50(3):245-251
As a member of nuclear receptor superfamily, farnesoid X receptor (FXR) has been shown to regulate numerous metabolic pathways, which include playing an important role in bile acid metabolism, maintaining lipid and glucose homeostasis when FXR is activated. With the prevalence of the glucose and lipids disorder, FXR attracts increasing attention. It may be a potential target for the treatment of type 2 diabetes mellitus and lipid disorders.
Bile Acids and Salts
;
Diabetes Mellitus, Type 2
;
Glucose
;
metabolism
;
Homeostasis
;
Humans
;
Lipid Metabolism
;
Receptors, Cytoplasmic and Nuclear
;
metabolism
5.The application of a new type of laparoscopic training method in the standardized training for res-idents
Fangyu ZHU ; Hang ZHOU ; Shuai LIU ; Jun GONG ; Fang LUO
Chinese Journal of Medical Education Research 2016;15(1):103-106
For a long time, limited by the factors such as laparoscopic technology, and limited medical resources , the residents accepting standardized training are lack of mastery of the technology . Meanwhile, it is the key to the training of personnel training and reserve in the field for residents to contact the laparoscope as soon as possible and carry out scientific and effective training. Therefore, based on the traditional method, we have developed a new type of laparoscopic teaching system for the standardized training residents and increased and integrated the LAP GAME R operations training system and the real-time multimedia teaching platform. The preliminary practice effect is good.
6.Enhance Training About the Doctor-patient Communication Ability of Stomatology Medical Graduates During Clinical Practice Stage
Yong WU ; Shuai FU ; Ming LI ; Jun LI ; Baofan LI
Chinese Medical Ethics 2017;30(3):339-342
It is significant to enhance the doctor-patient communication ability for medical graduates during clinical practice stage and establish appropriate doctor-patient communication sense,which is also important to promote medical education quality and cultivate qualified medical talents.This paper analyzed the common problems in doctor-patient communication for medical graduates.For example,patients did not trust the intern students;the students were nervous when faced with patients;some did not pay attention to their images;some called patients improperly.Then,it put forward some measures:to set up the communication and training courses,to carry out the communication skill training in clinical practice,and to attach importance to the doctor-patient communication skill practice.
7.Professor LIU Yi-min's Treatment for Infantile Anorexia and Commonly Used TCM Pairs
Jianping XU ; Ruojun YANG ; Jun XU ; Shuai CHEN
Chinese Journal of Information on Traditional Chinese Medicine 2017;24(9):108-110
Anorexia is a common pediatric and multiple chronic appetite disorder disease. Long-term anorexia can easily lead to adverse effects on nutritional status, growth, intellectual development and physical and mental health of children. Professor LIU Yi-min, the national famous TCM doctor in Yunnan University of Traditional Chinese Medicine, has much experience in treating this disease, believing that the pathogenesis key is spleen and stomach disharmony and inability to transport. According to clinical experience, it should be treated from indigestion of stomach, spleen dampness, spleen qi deficiency, and spleen weakenness and liver excess. The treatment is to eliminate indigestion, tonify spleen and expel humidity, tonify spleen and nourish qi, and tonify spleen and harmonize liver. The commonly used TCM pairs were Charred Triplet and Galli Gigerii Endothelium Corneum, Plantaginis Herba and Dioscoreae Rhizoma, Hungaian Morningglory Root and Marginate Rockbell Herb and Capsella bursa-pastoris and Chrysanthemi Flos.
8.Expression of STIM1 gene in human hypopharyngeal carcinoma cell line FaDu and its effect on FaDu cell apoptosis
Shuai WU ; Xiaobo CUI ; Yuanhao SUN ; Jun WANG ; Boqian WANG
Journal of Regional Anatomy and Operative Surgery 2016;25(3):167-170
Objective To study the expression of STIM 1 gene in human hypopharyngeal carcinoma cell line FaDu and its effect on FaDu cell apoptosis .Methods Lentivirus infection was used to knock STIM 1 down in FaDu cells .Group STIM1-siRNA: the expression of STIM1 in FaDu cell was inhibited by STIM 1-siRNA lentivirus .Group control:FaDu cells were infected by negative control siRNA lentivirus . Real-Time PCR was applied to identify the efficacy of lenticirus infection and the expression of STIM 1 in FaDu cells.Western blot was used to identify the expression of STIM 1 protein after lenticirus infection .Flow cytometry assay was performed to detect the apoptosis of FaDu cells in the two groups.The data were statistically analyzed with SPSS 17.0 software.Results Compared with GAPDH (Ct=12.08 ±0.05),the expression of STIM1 in FaDu cells was significant expressed (Ct=22.21 ±0.05,P<0.001).Real-Time PCR analysis the relative mRNA expression of STIM1 in FaDu cells of control group and STIM 1-siRNA group were (1.00 ±0.08) and (0.12 ±0.01) respectively (P<0.001). Western blot showed that the expression of STIM 1 gene and protein in FaDu cells were inhibited significantly after STIM 1-siRNA lentiviral in-fection,which was in accordance with the results of Real-Time PCR analysis.Flow cytometry assay showed that the siRNA-mRNA group had a higher apoptosis percentage (9.81 ±0.56)% compared to the control group (4.36 ±1.32)%,with statistically significant difference (P<0.05).Conclusion STIM1 gene correlated significantly with FaDu cell apoptosis .It inhibits apoptosis of FaDu cells ,and it may be a potential diagnostic and therapeutic target for the hypopharyngeal carcinoma .
9.Three-dimensional Speckle Tracking Echocardiography for Evaluating Cardiac Function in Breast Cancer Patients Treated with Anthracycline
Shuai ZHANG ; Xiaohong XU ; Kang ZHANG ; Lijuan LIU ; Jun XIE
Chinese Journal of Medical Imaging 2014;(10):745-748,753
Purpose To investigate the value of three-dimensional speckle tracking echocardiography in evaluating the cardiac function in breast cancer patients treated with Anthracycline. Materials and Methods Thirty-two breast cancer patients were followed with three-dimensional echocardiography prechemotherapy (group A), 2 cycles (group B) and 4 cycles (group B) postchemotherapy to compare left ventricle global longitudinal strain (GLS), global radial strain (GRS), global circular strain (GCS), global area strain (GAS), early diastolic global area strain rate (EASR), and early diastolic 3D velocity (3DVe). Results GCS, GAS and EASR were signiifcantly lower in group C than group A (t=3.555, 3.692 and 3.590, P<0.01);EASR was lower in group B than group A with statistical significance (t=2.190, P<0.05). GLS, GRS and 3DVe were not significantly different among three groups (F=2.305, 1.957 and 1.205, P>0.05). EASR was negatively correlated with IVRT (r=-0.44, P<0.01); EASR was positively correlated with Em (r=0.49, P<0.01) and Em/Am (r=0.32, P<0.01). GSR was positively correlated with Sm (r=0.21, P<0.05). Conclusion Three-dimensional echocardiography sensitively detects the early changes in diastole function in breast cancer patients treated with Anthracycline.
10.Clinical analysis of 16 cases of childhood necrotizing pneumonia.
Chinese Journal of Contemporary Pediatrics 2014;16(10):993-996
Child
;
Child, Preschool
;
Female
;
Humans
;
Infant
;
Male
;
Necrosis
;
Pneumonia
;
microbiology
;
therapy
;
Retrospective Studies