AIM:To investigate the apoptotic pathway of MCF-7 breast cancer induced by the grub extract in vitro.METHODS:MTT assay was used to determine the effect of the grub extract on proliferation of MCF-7 human breast cancer cell line and cell toxicity.Morphological changes of the apoptosis in cancer cells were observed by HE staining through invert microscope,light microscope,AO/EB double fluorescent staining under fluorescent microscope.FCM was used to assay the change of apoptotic rate.The expression of Bcl-2,Fas,caspase-9,caspase-3 in apoptotic pathway was detected with immunocytochemical method before and after exposure to the grub extract,and the effect of that on apoptotic pathway was explored.RESULTS:(1)The MTT test showed that the growth of MCF-7 human breast cancer cell line was significantly inhibited by the grub extract in dose and time dependent manners.The inhibitory rate in exposure group was significantly different from that in control group(P

0.05).There was a significant difference in the percentage of malignant calcified nodules between the patients of 45 years and older with those younger than 45 years(39.2% and 69.3%,respectively;P

Objective:To determine effects of BEZ235,an inhibitor of phosphoionsitol-3-kinase (PI3K)/ mTOR,on the cell proliferation and migration in human prostate carcinoma lines including RWPE-1,PC3,and DU 145 cells.Methods:Viability of RWPE-1,PC3,and DU145 cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay,while cell migration was analyzed by wound healing assay.Western blot and immunofluorescence were used to examine the changes of relevant protein expression.Results:The proliferation of PC3 and DU145 cells was effectively inhibited by BEZ235 (P<0.01),whereas RWPE-1 was not obviously inhibited.Invasion and migration of PC3 and DU145 cells were attenuated by BEZ235 via EMT pathway.Conclusion:The PI3K/mTOR dual inhibitor BEZ235 shows substantial anti-tumor activity in human prostate carcinoma lines of PC3 and DU145 cells,which may be involved in the EMT pathway.

BACKGROUND:Bone morphogenetic protein-7 can promote proliferation of bone marrow mesenchymal stem cels and has important significance in terms of inducing new bone formation. OBJECTIVE:To observe the protein and mRNA expression of bone morphogenetic protein-7 in bone marrow mesenchymal stem cels transfected with bone morphogenetic protein-7. METHODS:Rat bone marrow mesenchymal stem cels were isolated and cultured, and then identified by the morphology and cel surface markers. Lentiviral vectors carrying bone morphogenetic protein-7 were constructed to transfect bone marrow mesenchymal stem cels. After total RNA extraction, the protein and mRNA expression of bone morphogenetic protein-7 was detected by RT-PCR and western blot methods. RESULTS AND CONCLUSION:PLV-sfGFP(2A)-BMP7 recombinant plasmids were successfuly constructed and transferred into rat bone marrow mesenchymal stem cels. The mRNA and protein expression of bone morphogenetic protein-7 in the transfection group was significantly higher than that in the blank vector and blank groups (P < 0.05), indicating exogenous bone morphogenetic protein-7 gene is effectively integrated into the bone marrow mesenchymal stem cels.

Objective To discuss the relationship between TCM constitutional types and the levels of transforming growth factor beta 1 (TGF-β1) of patients with knee osteoarthritis (KOA). Methods A total of 161 patients with KOA as a case group filled out questionnaires about 9 TCM constitution types, and 50 cases of unrelated healthy volunteers were selected randomly as control group. The serum samples of two groups were collected. The levels of TGF-β1 were detected and compared by double antibody sandwich ELISA. Results Compared with the control group, the level of TGF-β1 in the case group decreased, with statistical significance (P<0.05). Compared with the control group, the levels of TGF-β1 significantly decreased in the case group of qi deficiency type, with statistical significance (P<0.05). There were no types of special intrinsic and blood stasis. Compared with the control group, the levels of TGF-β1 in the other six types of patients with KOA had no statistical significance (P>0.05). Conclusion The incidence of KOA with qi deficiency type may be related to the decrease of TGF-β1 level. The decreasing level of TGF-β1 may be one of the mechanisms of molecular biology that qi deficiency was linked to KOA.

OBJECTIVE: CDKN2B-AS1 polymorphisms were shown to associate with the risk of stroke in European. The goal of this study was to evaluate the contribution of CDKN2B-AS1 rs1333049 to the risk of hemorrhagic stroke (HS) and brain tumor (BT) in Han Chinese. METHODS: A total of 142 HSs, 115 BTs, and 494 controls were included in the current association study. The genotyping test was performed using the melting temperature shift method. RESULTS: We failed to validate the association of CDKN2B-AS1 rs1333049 with the risk of brain disease. Significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p=0.027), high-density lipoprotein cholesterol (HDL-C) (p<0.001) and total cholesterol (TC) (p<0.001) were found in HSs in the genotype GG/GC carriers, but not the genotype CC carriers (p>0.05). The meta-analysis of 10 studies among 133,993 individuals concluded that rs1333049 of CDKN2B-AS1 gene was likely to increase a 16% incidence rate of cerebrovascular disease (CD) among various populations (odds ratio 1.16, 95% confidence interval 1.08–1.25; p<0.0001, random-effect method). CONCLUSION: Our case-control study identified rs1333049 genotypes showed different association with the concentration of the LDL-C, HDL-C and TC in the HS patients. Meta-analysis supported the association between rs1333049 and CD risk in various populations, although we were unable to observe association between rs1333049 and the risk of HSs in Han Chinese.
Asian Continental Ancestry Group ; Brain Diseases* ; Brain Neoplasms ; Brain* ; Case-Control Studies* ; Cerebrovascular Disorders ; Cholesterol ; Freezing ; Genotype ; Humans ; Incidence ; Lipoproteins ; Methods ; Stroke

OBJECTIVETo assess the association of BDNF gene Val66Met polymorphism with efficacy of antidepressant treatment and plasma BDNF level.

METHODSTwo hundred and forty-nine ethnic Han Chinese patients with depression(study group), who have met the diagnostic criteria of DSM-IV, were prescribed with venlafaxine or paroxetine. Two hundred and two healthy individuals were recruited as the control group. General demographic information such as gender, age, educational status, occupation, and marriage status were collected. HAMD-17 was adopted as the primary rating tool to evaluate the severity of depression on the baseline and at the end of 1st, 2nd, 4th, 6th week of treatment. PCR-restriction fragment length polymorphism was applied to determine the Val66Met polymorphism of the BDNF gene in the two groups. Plasma BDNF concentration was measured with ELISA before and after 6 weeks of treatment.

RESULTSNo significant differences have been found in HAMD scores and reduction of HAMD scores on the baseline and at the end of 1 st, 2nd, 4th, 6th weeks of treatment for each genotype. Nor were significant differences found in the Val66Met genotypes and allelic frequency between patients who achieved remission or not after 6 weeks' treatment as well as the healthy volunteers. The plasma BDNF level in depression patients was lower than that in healthy controls. The BDNF level has increased significantly after 6 weeks' treatment with both venlafaxine and paroxetine, but was still lower than the healthy controls. The BDNF level in the patients achieved remission who were treated with venlafaxine was similar to the normal controls, while those treated with paroxetine was still lower than normal controls. The BDNF level in patients who have not achieved remission was lower than normal controls. The BDNF level was not associated with the Val66Met polymorphism on the baseline and the end of 6th week.

CONCLUSIONNo association has been found between the efficacy of venlafaxine or paroxetine and the BDNF Val66Met polymorphism. The BDNF level of patients with depression is significantly lower than healthy controls on the baseline, and can be enhanced with the treatment. Particularly, the BDNF level in patients who achieved remission after the treatment of venlafaxine can rise to normal. The level of BDNF has certain value in the forecasting of efficacy in the anti-depression therapy. BDNF level is not associated with the Val66Met polymorphism of the BDNF gene.

Adolescent ; Adult ; Aged ; Antidepressive Agents ; therapeutic use ; Brain-Derived Neurotrophic Factor ; blood ; genetics ; Depression ; blood ; drug therapy ; genetics ; Female ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic

Type 2 Diabetes Mellitus(T2DM)is a chronic metabolic disease characterized by disorders of insulin and glucose.As a disease closely related to our daily diet,the molecular mechanism of its pathogenesis is still unclear.Sweet taste receptors are a kind of G protein-coupled receptors with 7 times transmembrane.Although the research on the pathogenesis of T2DM has been gradually deepened,there are few studies on the mechanism of sweet taste damage in the state of disease.Therefore,in-depth study of the pathological mechanism of T2DM sweet taste receptor damage is of great significance to further understand the molecular characteristics of sweet taste receptors and explore new targets of traditional Chinese medicine in the treatment of T2DM.In this paper,the biological characteristics of sweet taste receptors,signal transduction mechanism of sweet taste receptors,sweet taste receptors and T2DM,sweet taste receptors and"spleen is sweet"are reviewed in order to provide the latest opinions for the targeted prevention and treatment of this kind of diseases by traditional Chinese medicine and the elucidation of related pathological mechanism.

BACKGROUND:Osteonecrosis is a common refractory disease in clinical practice,and observational studies have suggested that micronutrients may have a prognostic role in osteonecrosis.However,the specific causal association between micronutrients and osteonecrosis is not known. OBJECTIVE:To explore the causal association between micronutrients and osteonecrosis by Mendelian randomization using summary data from a large population-based genome-wide association study(GWAS)for clinical diagnosis and treatment. METHODS:The required exposure and outcome data(calcium,magnesium,iron,vitamin E,carotenoids,retinol&osteonecrosis)were extracted from the IEU OpenGWAS database,GWAS catalog database,and FinnGen database.Data were analyzed by bidirectional Mendelian randomization with inverse-variance weighted as the primary study method,and weighted median method,simple mode method,weighted mode method,and MR-Egger regression to complement the results.The reliability of the data was then verified through sensitivity analyses. RESULTS AND CONCLUSION:(1)The results found a positive correlation between serum iron concentration and osteonecrosis,while no correlation was found for other micronutrients.There was no reverse causality in all the data.(2)The results of sensitivity analysis showed a robust causality.(3)By Mendelian randomization method,this study provided evidence of causality between serum iron concentration and osteonecrosis,and understanding the causality of micronutrient elements on osteonecrosis can help in the clinical diagnosis and treatment of osteonecrosis,which is of great clinical significance.

OBJECTIVETo investigate the association of concomitant BRAFV600E mutation with central lymph node metastases in papillary thyroid carcinoma (PTC).

METHODSThe clinicopathological data of 126 PTC patients who underwent surgical treatment within a period of 2 years were retrospectively analyzed. The BRAF V600E gene mutation was detected by quantitative fluorescence PCR.

RESULTSThe BRAF mutation rate was 69.0% (87/126). The univariate analysis showed that BRAF mutation status was significantly associated with central lymph node metastasis (P<0.05), while the gender, multiple lesions, tumor size, extra-thyroidal invasion, Hashimoto's thyroiditis and tumor stage were not significantly associated with the BRAF mutation (P>0.05 for all). The multivariate analysis showed that only central lymph node metastasis was significantly correlated with BRAF mutation (P<0.05). When the diameter of tumor was ≤10 mm, BRAF mutation was statistically not significantly correlated to central lymph node metastasis (P>0.05). When the diameter of tumor was >10 mm, the central lymph node metastasis rate was significantly higher in patients with positive BRAF mutation than that in patients with a negative BRAF mutation (P<0.05).

CONCLUSIONSThe presence of BRAF mutation is an independent predictive factor for central lymph node metastasis. When PTC is with preoperative positive BRAF mutation, the cervical dissection should be routinely performed. The larger the tumor diameter is, the more important is the central lymph node dissection. There should be re-evaluated the necessity of preventative central lymph node dissection when the tumor diameter was ≤5 mm in patients with negative BRAF mutation.

Carcinoma ; epidemiology ; genetics ; metabolism ; Carcinoma, Papillary ; Hashimoto Disease ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; diagnosis ; genetics ; Mutation ; Polymerase Chain Reaction ; Proto-Oncogene Proteins B-raf ; genetics ; Retrospective Studies ; Thyroid Neoplasms ; epidemiology ; genetics ; metabolism