To explore novel coumarin derivatives with more potent anti-proliferative activity, a series of novel compounds were designed and synthesized by linking Schiff base and N, N-bis (2-chloroethyl) amine pharmacophore of nitrogen mustards to the coumarin's framework. Their structures were confirmed by 1H NMR, MS and element analysis techniques. In vitro anti-proliferative activities were evaluated against HepG2, DU145 and MCF7 cell lines by the standard MTT assay. The results showed that some of the target compounds exhibited strong anti-proliferative activities against selected tumor cells, and compounds 7c, 7f, 7g, 7h and 7q were better than or equal to the activities of positive control, they deserved further development.
Antineoplastic Agents ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Coumarins ; chemical synthesis ; pharmacology ; Drug Design ; Drug Screening Assays, Antitumor ; Humans ; Nitrogen Mustard Compounds ; chemical synthesis ; pharmacology ; Schiff Bases ; Structure-Activity Relationship

Humans ; Lung ; Lung Diseases ; rehabilitation ; Pneumoconiosis ; rehabilitation ; Respiratory Therapy

Objective Through the investigating the molecular expressions of integrin?_5?_1,Fn and CD_(44v6) in ovarian epithelial neoplasms,this study is trying to explore the relationship between the lymphatic spread of the tumor with these molecules.Methods The expression of 80 cases of integrin?_5?_1,Fn and CD_(44v6) was examined through ElivisionTM immunohistochemistry method in ovarian epithelial neoplasm.The system of image analysis was used to measure the expression of various molecules quantitatively.Results Qualitative and semi-quantitative results:The expression levels of integrin?_5?_1 and Fn in the ovarian epithe- lial neoplasms had downward tendency in the order of benign,boundary and malignant neoplasms and there was a significant difference in the expression levels of integrin?_5?_1 and Fn(P

Objective To observe effects and mechanisms of insulin on reperfusion injury after cerebral ischemia.Methods Sixty-six male Wistar rats were used in this study.All rats were divided into 3 groups as treated group(A),control group(B) and random sham-operated group(C).Four-vessel occlusion was used to establish global cerebral ischemia reperfusion model in study groups.The treated group were divided into 5 groups(A1-A5) and intraperineally injected with biosynthetic human insulin 2 IU/(kg?d) and 50%glucose 2 g/(kg?d) for 7 days,the blood glucose was monitored in preoperative and postoperative 3,6,12,24 h,and the blood glucose was maintained between 3.5-6.5 mmol/L.These animals of control group were given with saline 2 mL/(kg?d) for 7 days in abdominal cavity.All the rats were killed in the seventh day,brain homogenate was collected for detection of neuron specific enolase(NSE)and nitric oxide(NO).The hippocampus was separated for observation of electronic microscope.Results Concentration of NSE in brain tissue in group C was significantly higher than that of group A and group B,while the level in group A was higher than that of group B.Concentration of NO in group C was lower than that of group A and group B while the level of NO in group A was significantly lower than that of group B.Electron microscope showed that the ultrastructure of sham-operated group was nearly normal,damage degree of hippocampal neuron and gliacyte and capillary was gradually worse from group A1,A2 to A4,the damage degree of group B1,B2 and B4 was serious and there was no difference among them.Conclusion Insulin can really promote recovery of the cerebral injury after ischemia reperfusion.

Objective To investigate the antidiabetic effect of Acanthopanax senticosus extracts based on metabonomics by UPLC-MS/MS and to explore its mechanisms. Methods The type 2 diabetes mellitus(T2DM)mouse model was established by inject-ing streptozocin(streptozotocin,STZ)in combination with alloxan. The effect of A. senticosus extracts on the fasting blood glucose of mice was observed. Multivariate statistical analysis was employed to analyze serum metabolites. The differential metabolites were iden-tified by online and self-built databases. MetPA Was employed to analyze the corresponding metabolic pathways. Results The T2DM model was established successfully. Compared with the model group,the fasting blood glucose of mice in the A. senticosus extracts groups decreased significantly. Compared with the normal control group,the level of phenylalanine,LysoPC(16:0,18:0),tyrosine, serine,urea andβ-hydroxybutyric acid inecreased,while the level of alanine,glutamine,leucine,valine and lactic acid decreased significantly in the model group. Pathway enrichment displayed that these metabolites were mainly involved in five metabolic pathways. The above-mentioned metabolites reversed to the normal level in varying degrees after administration of A. senticosus glycosides or poly-saccharoses extracts. Conclusion The extracts of A. senticosus display a significant hypoglycemic effect which might be achieved by regulation of amino acid,energy and lipid metabolism.

OBJECTIVETo investigate results of total knee arthroplasty using the long-stem tibial component combined with metallic wedge of knee prosthesis for the treatment of proximal defects.

METHODSFrom January 2011 to May 2013, 10 patients (11 knees) were treated with total knee arthroplasties using the long-stem tibial component with metallic tibial wedge of knee prosthesis. All the patients were female and the average age was 67 years old (ranged, 60 to 77 years old). All the patients were osteoarthritis. All the patients were classified as T2A style. The patients were evaluated according to knee score system (KSS).

RESULTSAll the patients were followed up for 12 months on average (ranged 3 to 29 months). The clinical outcome was assessed using KSS score, including knee pain score, knee stability score, knee range of motion score and knee walking score, knee stairs score. There were significantly differences at 6 weeks, 3 months, 6 months and 12 months between pre-and postoperative KSS score.

CONCLUSIONThe mechanical stability of tibial fixation in primary TKA is significantly increased by using the long-stem tibial component with metallic wedge of knee prosthesis, even in the presence of poor proximal bone.

Aged ; Arthroplasty, Replacement, Knee ; Female ; Humans ; Knee Joint ; physiopathology ; surgery ; Knee Prosthesis ; Male ; Osteoarthritis, Knee ; physiopathology ; surgery ; Range of Motion, Articular ; Tibia ; abnormalities ; physiopathology ; surgery

OBJECTIVETo observe the dynamic expression of calcium-sensing receptor(CaSR) in myocardium of diabetic rats.

METHODSThirty male Wistar rats were randomly divided into 3 groups including control, diabetic-4 week and diabetic-8 week groups(n = 10). The type 2 diabetes mellitus models were established by intraperitoneal injection of streptozotocin (STZ, 30 mg/kg) after high-fat and high-sugar diet for one month. The cardiac morphology was observed by electron microscope. Western blot analyzed the expression of CaSR, phospholamban (PLN), a calcium handling regulator, and Ca+-ATPase(SERCA) in cardiac tissues.

RESULTSCompared with control group, the expressions of CaSR and SERCA were decreased, while the expression of PLN was significantly increased in a time-dependent manner in diabetic groups. Meanwhile diabetic rats displayed abnormal cardiac structure.

CONCLUSIONThese results indicate that the CaSR expression of myocardium is reduced in the progression of DCM, and its potential mechanism may be related to the imnaired intracellular calcium homeostasis.

Animals ; Calcium-Binding Proteins ; metabolism ; Diabetes Mellitus, Experimental ; complications ; Diabetes Mellitus, Type 2 ; Diabetic Cardiomyopathies ; metabolism ; physiopathology ; Disease Progression ; Heart ; physiopathology ; Male ; Myocardium ; metabolism ; pathology ; Rats ; Rats, Wistar ; Receptors, Calcium-Sensing ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism ; Streptozocin

OBJECTIVE Glioblastomas(GBM)are the most malignant brain tumors in humans and have a very poor prognosis. New therapeutics are urgently needed. Here, we reported 2-methoxy-6-acetyl-7-methyljuglone (MAM)-induced cell death in U87 and U251 glioma cancer cells. METHODS Cells were cultured and treated with MAM, the cell viability was determined by MTT assay and LDH assay. Intracellular reactive oxygen species (ROS) generation was observed by DCF fluorescence. The protein expression was determined by Western blotting. RESULTS MAM induced glioma cancer cell death without caspase activation. The cell death induced by MAM was attenuated by the pharmacological or genetic blockage of necroptosis signaling,including RIP1 inhibitor necrostatin-1s (Nec-1s)and siRNA-mediated gene silencing of RIP1 and RIP3,but was unaffected by caspase inhibitor z-vad-fmk or necrosis inhibitor 2-(1H-Indol-3-yl)-3-pentylamino-maleimide (IM54). MAM treated U87 and U251 glioma cancer cells induced RIP1/RIP3 complex formation, ROS level increased, ATP concentration decreased and loss of plasma membrane integrity, further confirmed this process was necroptosis.The essential role of ROS was confirmed by the protective effect of ROS scavenger NAC. Interestingly, MAM induced necroptosis both triggered by RIP1/RIP3 complex and ROS generation. Moreover, MAM induced necroptosis through cytosolic calcium (Ca2 +) accumulation and sustained c-Jun N-terminal kinase (JNK) activation. Both calcium chelator BAPTA-AM and JNK inhibitor SP600125 could attenuate cell death. Further, we found there exists a feedback loop between RIP1 and JNK activation.Finally,MAM induced necroptosis was inhibited by dicoumarol(a NQO1 inhibitor). Dicoumarol exposed glioma cancer cells were resistant to RIP1/RIP3 complex formation and ROS generation. MAM induced necroptosis was independent of MLKL. CONCLUSION MAM induced non-canonical necroptosis through the NQO1-dependent ROS and RIP1/RIP3 pathway.This study also provided new insights into the molecular regulation of necroptosis in human glioma cancer cells and a promising approach for GBM treatment.

Fifteen novel 5-substituted-2-(pyridyl)benzothiazole compounds were designed and synthesized by simple hydrolization and condensation reaction of the 2-amino-5-substituent benzothiazole. Activities of these synthesized compounds were evaluated on Bcap-37, HCT-15 and HepG2 tumor cells in vitro by standard MTT assay. 5-Fluorouracil (5-FU) was used as the positive control. The results revealed that most of the new compounds had potent effects on Bcap-37, HCT-15 and HepG2 tumor cells, and had no or less effect on 293T and L02 normal cells. Particularly, compounds 1c and 2e exhibited better activities on HCT-15 and HepG2 cells with IC50 values of 41.59 and 38.65 micromol x L(-1), and 1i showed excellent activities on Bcap-37 and HepG2 cells with IC50 values of 46.63 and 23.51 micromol x L(-1), respectively. The structure-activity relationship of 5-substituted-2-(pyridyl)benzothiazole compounds were also discussed preliminarily.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Benzothiazoles ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Screening Assays, Antitumor ; Humans ; Molecular Structure ; Structure-Activity Relationship

Bak Foong Pill has been used traditionally for treating gynecological disorders for several centuries but also with a newly modified formula for treating postmenopausal symptoms. Cumulating evidence indicates that Bak Foong Pill acts on multi-systems and affects various organ functions. The present review discusses the effects of Bak Foong Pill and its active components on overall body function, with particular focus on the gastrointestinal epithelial ion transport and the related underlying mechanisms.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Epithelial Cells ; metabolism ; Gastrointestinal Tract ; cytology ; Humans ; Ion Transport ; drug effects