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.

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

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

Background Trans-arachidonic acids (TAAs) are specific lipid markers of nitrative stress and the major products of NO2·-mediated ismoerization of aracchidonic acid(AA),and they represent a possible new mechanism of NO2·-induced toxicity in ischemic retinopathy.Our previous study demonstrated that high glucose induce nitrative stress response. Objective This study aimed to evaluate the effect of nitrative stress on retinal capillary in diabetic rats by detecting the TAAs with gas chromatography and mass spectrometry(GC/MS).Methods One hundred 2-week-old clean male SD rats were randomly divided into control group and diabetic group.Diabetic rat models were induced by intraperitoneal injection of streptozoticin of 60 mg/kg,and the successful models were identified as the blood glucose level>16.7 mmol/L.The synthesis method was modified in this study andaraehidonic acid w8$utilized as starting material.14E-AA was obtained as a standard sample via expoxidation and deoxidation in a safe and practical pattern.Serum TAAs and AA in diabetic rats were detected by GC/MS in 2,4,8,12 and 16 weeks after injection of streptozoticin.The ratio of peak area of TAAs to AA with selected ion of 79 was estimated and compared with normal rats. Results Fifty rats had been in Diabetic models were established in 50 rats with the successful rate 100%,and the high blood glucose level in model rats retained throughout the experimental duration.GC/MS results showed that the 14E-AA was obtained with the purity of 97.3%,which provided a standard sample to nitrative stress-related research as a premise. No significant differences were found in serum TAAs/AA values at 2 weeks and 4 weeks between model group and control group (t =-0. 376, t =-0. 642,P>0. 05). However,serum TAAs/AA values in at 8,12 and 16 weeks after streptozoticin injection were considerably elevated in comparison with those of control group (0. 0832 vs 0. 1042,0. 0910 vs 0. 1568, 0. 1100 vs 0. 1895;t=-36.409,t=-166.714,t=-148.212,P<0. 05). Conclusion Elevation of serum TAAs/AA is associated with diabetic duration,implying that damage of nitrative stress to retinal capillary is a parallel procedure to diabetic course.Establishment of GC/MS detection system offers a new evaluating indicator in the research on microvascular ischemic disease and could be implemented in clinical testing.

Background Dry eye syndrome is a frequent postoperative complication of laser in situ keratomileusis (LASIK).Some studies reported that the hinge location of corneal flap has influence on dry eye syndrome following LASIK,but others showed inverse views.Objective This systematic review was to evaluate and compare the effects of a superior-and nasal/temporal-hinge location on dry eye syndrome after LASIK.Methods A systematic literature retrieval was conducted in the Medline,Embase,Cochrane Library and CNKI from 1990 to 2011 according to designed searching strategy and relevant words.Published randomized-controlled clinical trial (RCT) data of the effect of superior-and nasal/temporal-hinge location on dry eye syndrome were extracted by two researchers separately.The outcome parameters,such as tear film breakup time (BUT),Schirmer Ⅰ test and corneal sensation were analyzed 1 week,3 months and 6-12 months postoperatively.The statistical analysis was performed using a RevMan 5.0 software and the quality of included literatures were graded according to the Jadad scale.Fixedeffect model was used for the inhomogeneity multiple studies (P≥0.1,homogeneity test I2 ＜50％),and random-effect model was used for the homogeneity studies.Results Ten pieces RCT papers were searched and 3 of them were rejected because of the lack of outcome data.In 7 included studies,652 eyes of 331 patients were involved in the Meta analysis,with the Jadad scores ≥ 3.BUT assessment was performed in 5 trials (530 eyes),Schirmer Ⅰ test evaluation was in 7 trials (652 eyes) and corneal sensation observation was in 4 trials (320 eyes),without significant homogeneity among the relevant literature(I2＜50％).Meta analysis revealed that BUT in the eyes with superior-hinge group was obvious shorter than that in the eyes nasal/temporal-hinge group at 1 week (WMD =-0.42,95％ CI:-0.79 to-0.06,P=0.020),but there was no signifieant difference in 3 months and 6-12 months duration postoperatively.Better corneal sensation was found at postoperative 3 months (WMD=-0.62,95％CI:-l.09 to-0.19,P=0.005) in the nasal/temporal-hinge group,but there was no difference in 1 week and 6-12 months duration postoperatively.No significant difference was seen between the two groups in Schirmer Ⅰ test during the follow-up period (P＞0.05).Conclusions LASIK with nasal/temporal-hinge corneal flap can improve the corneal sensation and relief the dry eye syndrome after LASIK to some extent.More high-quality evidence-based studies are still needed for the further clinical evaluation.