Transforming growth factor-β is an important cytokine with various bioactivities, including embryonic development, wound healing, chemotaxis and cell cycle regulation. Epithelial-mesenchymal transition (EMT) is the main pathway of tumor cell to obtain the ability of invasion and metastasis. The TGF-β is the key factor known to induce EMT in cancer cells and plays an important role in the process. In recent years, some progress has been obtained. Some TGF-β inhibitors have approved in the market or in clinical trials. TGF-β inhibitors can play an important role on the treatment of tumors, glaucoma, liver and kidney fibrosis disease and scar repair. Novel TGF-β inhibitors reported in recent years were reviewed in this article.
Epithelial-Mesenchymal Transition ; Humans ; Neoplasms ; Transforming Growth Factor beta ; antagonists & inhibitors ; Wound Healing

The starting material L-tryptophan reacted with 4-chlorobenzaldehyde via Pictet-Spengler condensation and followed by oxidation and decarboxylation to afford the 1-(4-chlorophenyl)-beta-carboline. The intermediate was further reacted with alkyl halogenide by N(9)-alkylation and N2-quaternarization to obtain 12 novel 1-(4-chlorophenyl)-beta-carboline derivatives. The chemical structures of all target compounds were characterized by elemental analyses, MS and 1H NMR spectra. The antitumor activities of the target compounds were evaluated by MTT method. The results demonstrated that N2-quaternarized compounds enhanced the antitumor activity significantly. In particular, compound 15 was found to be the most potent compound with IC50 values lower than 5 micromol x L(-1) against 6 human tumor cells. These results confirmed that the N2-alkyl or aralkyl substituent on the beta-carboline ring played an important role in the modulation of the antitumor activities.

Objective:To compare the clinical effects of restrictive blood transfusion combined with hyperbaric oxygen preconditioning (HBOPC) and restrictive blood transfusion in the treatment of hip,knee arthroplasty (THA,THA).Methods:40 patients in the period of epidural anesthesia,femoral nerve hysteresis hip and knee arthroplasty were selected and randomly divided into two groups:restrictive transfusion group (maintain 80 g/L≤ Hb ＜100 g/L,n=20) and restrictive blood transfusion combined with HBOPC (HBOPC+maintain 80 g/L =Hb ＜100 g/L,n=20).The red blood cell transfusion,red blood cell transfusion rate,perioperative Hb,blood oxygen saturation (SO2),the incidence of hypotension during operation,hospitalization time and postoperative cerebral infarction,acute pulmonary embolism,pneumonia,myocardial infarction,wound infection rate and 90 days mortality rate were compared between two groups.Results:Compared with the restrictive transfusion group,the postoperative Hb,blood oxygen saturation (SO2) of restrictive blood transfusion combined with HBOPC group were significantly increased(P ＜ 0.05);the red blood cell transfusion,red blood cell transfusion rate,incidence of pneumonia,wound infection rate were significantly decreased (P＜0.05).Conclusion:Restrictive blood transfusion combined with hyperbaric oxygen preconditioning could improve the anoxic state of the hip,knee arthroplasty patients,which could effectively reduce red blood cell transfusion,reduce postoperative complications,has good clinical curative effect.

With more and more attention and investment on acupuncture scientific researches, considerable outcomes and achievements has been acquired, but the shortcoming of low transformation rate of acupuncture research achievements is gradually exposed. Nowadays there is no related report on this problem, so based on achievement translational research in other areas and practical situation of acupuncture, the existing problems and solutions are analyzed. As a result, the existing problems include (1) the research content is mainly basic research and clinical research but less acupuncture device research, leading to limited transformation efficiency; (2) the evaluation system and transformation pattern are still needed to be perfect. The solutions are (1) to properly evaluate the research achievements of acupuncture, (2) to advocate the concept and method of translational medicine, (3) to reform the policy and system, and (4) to establish valid platforms covering research, outcomes and transformation.
Acupuncture ; economics ; legislation & jurisprudence ; manpower ; Biomedical Research ; Biotechnology ; economics ; legislation & jurisprudence ; manpower ; China ; Humans ; Technology Transfer

Objective To investigate the effect of histone deacetylase inhibitor trichostatin A (TSA) on the chemotherapy sensibility of 5-fluorouracil (5-Fu) in colorectal cancer cell line Lovo, and to explore the possible mechanisms.Methods According to the treatment methods, the cells were divided into control group, 5-Fu group, TSA group, TSA preconditioning group and combination group (TSA+5-Fu).MTT assay was used to detect cell proliferation at 24 h, 48 h and 72 h after drugs treatment.Transwell assay was used to test cell invasion after 24 h drugs treatment.Flow cytometer was applied to observe the apoptosis after 24 h drugs treatment.The expressions of thymidylate synthase (TS) were detected by Western blot after 24 h drugs treatment.Results Compared with control group, the 5-Fu group, TSA preconditioning group and combination group had a growth inhibition to Lovo cell at 24 h, 48 h and 72 h (P ＜ 0.05), and compared with 5-Fu group, the growth inhibition of TSA preconditioning group and combination group were distinctive at 48 h and 72 h (P ＜ 0.05).However, the inhibition between TSA preconditioning group and combination group were no significant (P ＞ 0.05).Interfered after 24 h, the number of cells penetrating the matrigel in control group, 5-Fu group, TSA group,TSA preconditioning group and combination group were (25.0±4.2), (16.8±2.8), (19.6± 2.5), (8.2±3.2) and (6.5±2.6), respectively (P ＜ 0.05), and the apoptosis rates were (4.26±1.36) ％, (11.66± 3.18) ％, (8.57±2.69) ％, (39.79±8.53) ％ and (45.18±10.07) ％, respectively (P ＜ 0.05).Compared with control group, the number of cells penetrating the matrigel in the experimental groups was significantly decreased, and the apoptosis rate was significantly increased (P ＜ 0.05).Compared with 5-Fu group, the numbers of cells penetrating the matrigel in TSA preconditioning group and combination group were markedly decreased, and the apoptosis rates were markedly increased (P ＜ 0.05), but the number of cells penetrating the matrigel and the apoptosis rate between TSA preconditioning group and combination group were not different (P ＞ 0.05).The difference of TS expression between control group and 5-Fu group was not significant (P ＞ 0.05).Compared with that in control group and 5-Fu group, TS expressions in TSA group, TSA preconditioning group and combination group were markedly decreased (P ＜ 0.05), but TS expressions among the last three groups were not different (P ＞ 0.05).Conclusion TSA can increase the chemotherapy sensibility of 5-Fu in Lovo cells, which may be dependent on reducing the TS expression.

OBJECTIVETo find out an effective therapy for obesity induced by antipsychotic agents.

METHODSOne hundred and one cases of obesity who were being treated with antipsychotic agents were randomly divided into an observation group and a control group. The observation group were treated with electroacupuncture at Quchi (LI 11), Zusanli (ST 36), Fenglong (ST 40), Shangjuxu (ST 37) and Xiajuxu (ST 39), once a day for 8 weeks; and no treatment was given to the control group. The Brief Psychiatric Rating Scale (BPRS) was used for assessment of therapeutic effect and the Treatment Emergent Symptom Scale (TESS) for adverse effects.

RESULTSThe clinically effective rate of the observation group (54.9%) was superior to the control group (10.0%) with a significant difference between the two groups (P<0.05). The BPRS score-reducing rate was 24.92% and 28.62% in the both groups respectively, and with no adverse effects.

CONCLUSIONElectroacupuncture has a good therapeutic effect on obesity induced by antipsychotic agents, and it improves the patient's compliance with no adverse effect.

In this study, the human umbilical vein endothelial cell model was used to study the regulating effect of lipophilic components in Salvia miltiorrhiza on angiogenesis, and explore its possible mechanism. The cell model was established to determine the effect of lipophilic components in S. miltiorrhiza on the proliferative activity and migration capacity of endothelial cells. Then the realtime fluorescence quantification PCR technology was applied to detect the changes in the gene expressions of angiogenesis-related cytokines VEGF-A, VEGF-C and MMP-9. The results showed that 5 mg x L(-1) lipophilic components in S. miltiorrhiza could inhibit the proliferation and migration of endothelial cells, and reduce the expression of VEGF-A and MMP-9 genes. It indicated that lipophilic components in S. miltiorrhiza may inhibit the proliferation and migration of endothelial cells by inhibiting the expression of VEGF-A and MMP-9 genes, so as to show the inhibitory effect on angiogenesis.
Angiogenesis Inhibitors ; chemistry ; pharmacology ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Salvia miltiorrhiza ; chemistry ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

This study aimed to investigate the effects of Shiquan Dabu Tang (SDT) on growth and angiogenesis of subcutaneously implanted tumors, hepatic metastases, and incision-implanted tumors after surgical removal of primary colon tumor in mice.

Applications of network pharmacology are increasingly widespread and methods abound in the field of drug development and pharmacological research. In this study, we choose rosiglitazone compound as the object to predict the targets and to discuss the mechanism based on three kinds of prediction methods of network pharmacology. Comparison of the prediction result has identified that the three kinds of prediction methods had their own characteristics: targets and pathways predicted were not in accordance with each other. However, the calcium signaling pathway could be predicted in the three kinds of methods, which associated with diabetes and cognitive impairment caused by diabetes by bioinformatics analysis. The above conclusion indicates that the calcium signaling pathway is important in signal pathway regulation of rosiglitazone compound, which provides a clue to further explain the mechanism of the compound and also provides a reference for the selection and application of methods of network pharmacology in the actual research.
Calcium Signaling ; Cognitive Dysfunction ; Computational Biology ; Diabetes Mellitus ; Humans ; Pharmacology ; methods ; Thiazolidinediones ; pharmacology

Objective To study the protective effect of sodium pyruvate solution to intestinal barrier in Hemorrhagic shock rats by intraperitoneal resuscitation.Methods A total of 40 Male SD ratswere healthy and clean,were randomly (random number) divided into four groups:sham operation group (group Ⅰ),hemorrhagic shock model group (group Ⅱ),the recovery of the compound sodium chloride intravenous + intraperitoneal recovery of the PD-2 liquid group (group iiⅢ),the recovery of the compound sodium chloride intravenous + sodium pyruvate abdominal recovery group (group Ⅳ) (n =10).In addition to the group Ⅰ,the other three groups are used the HS model by The Wiggers improvement prepared,group Ⅲ,Ⅳ were used the same amount of intravenous recovery,At the same time to the abdominal cavity were respectively injected 20 mL 2.5％ PD-2 liquid and 20 m 2.5％ sodium pymvate solution.After 2 h,each group were taken arterial blood measured arterial blood gases (pH,PaCO2,PaO2) and D-lactic acid,small intestine specimens under the light microscope to observe the morphological changes of the rat small intestinal mucosa.Results Blood gas analysis:group Ⅲ and Ⅳ was significantly increased compared with group Ⅱ in pH levels and PaO2 content (P ＜ 0.01),and comoared to group Ⅲ,pH levels and PO2 levels of group Ⅳ increased more significantly (P ＜ 0.05) ; D-LA content:Group Ⅲ,Ⅳgroup is significantly lower than group Ⅱ (P ＜ 0.01) ; compared with group Ⅲ and group Ⅳ,D-LA significantly decreased (P ＜ 0.05).Light microscope,the group Ⅱ,the rat small intestine layer of a high degree of villous edema,submucosal vascular collapse within the lamina propria glands focal area of necrosis,and large areas of mucosal villi necrosis,defects; group Ⅲ and group Ⅳof small intestinal damage compared to group Ⅱ significantly reduced; Ⅳgroup of the rat small intestine villi edema,lodging and the degree of necrosis in group Ⅲ.Intestinal epithelial damage index score:the Ⅳ group than in group Ⅱ and Ⅲ group (P ＜ 0.01 or P ＜ 0.05).Conclusions The venous recovery and intraperitoneal resuscitation can significantly reduce the plasma D-LA content of hemorrhagic shock in rats,correct acidosis,increase the oxygen partial pressure ; and intestinal mucosal barrier function,the protective of sodium pyruvate solution is better than the PD-2 liquid.