Acceleration ; Acyl-CoA Dehydrogenase, Long-Chain ; genetics ; Animals ; Aorta ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; Gene Expression ; Heart ; Heme Oxygenase (Decyclizing) ; genetics ; Male ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley

Objective To explore the effects of extract of Gingko biloba leaves (EGb) on learning, memory and hippoeampal heine oxygenase-1 (HO-1) expression in diabetic rats.Methods The behaviors of streptozotoein-induced diabetic rats were observed by Morris water maze for learning and memory after 6 months of diabetes.The HO-1 mRNA expression and protein expression in hippocampus of diabetic rats were detected by RT- PCR and immunohistochemistry respectively.Results The escape latency time in Morris water maze of diabetic rats was prolonged markedly.HO-1 mRNA and HO-1 protein expressions in hippocampus of diabetic rats were increased (1.635?0.326 vs 0.978?0.214,7.2?1.7 vs 1.9?0.5,respectively,both P＜0.01).The escape latency times in EGb (100,50 mg/kg) treated groups were shortened.HO-1 mRNA and HO-1 protein expressions in hippocampus were decreased at the same time as compared with diabetic group (100 mg/kg:0.954?0.144,2.0?0.8;50 mg/kg:0.988?0.154,2.5?0.6,all P＜0.01).Conclusion EGb can significantly inhibit HO-1 expression in hippocampus and improve learning and memory dysfunction in diabetic rats.

Zebrafish (Danio rerio) is a simple biological labora-tory animal, with similar biological structure and physiological functions to mammals. Almost transparent embryos, in vitro de-velopment of embryos and up to 87% of human genetic similari- ties enable a wide application of zebrafish in the field of pharma-ceutical research. In this paper, we have studied the application of zebrafish in drug metabolism, the research of Chinese medi-cine, the evaluation of drug toxicology and safety, the screening of drugs and the discovery of new drugs, the research of regener- ative drugs, so as to provide new ideas of zebrafish in the field of pharmacy.

Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.
Animals ; Biological Products ; CHO Cells ; Cricetulus ; Drug Interactions ; Fatty Acids, Monounsaturated ; pharmacology ; Flavonoids ; pharmacology ; Indoles ; pharmacology ; Inhibitory Concentration 50 ; Organic Anion Transporters ; genetics ; metabolism ; Rosuvastatin Calcium ; pharmacology ; Structure-Activity Relationship

To study the effect of sodium aescinate in inducing human breast cancer MCF-7 cells apoptosis and its possible mechanism. MTT assay was used to detect the inhibitory effect of sodium aescinate on the proliferation of MCF-7 cells. The morphological changes were observed under inverted microscope. DAPI nuclear staining was used to detect the changes in cell nucleus. Annexin V-FITC/PI flow cytometry was adopted to test the apoptosis rate. Changes in apoptosis-related proteins (PARP, cleaved caspase-8 and pro-caspase-3), cell survival-associated signal molecules (AKT and ERK) and their common upstream kinase SRC was detected by Western blotting. The result showed that after different concentrations of sodium aescinate were used to treat breast cancer MCF-7 cells, they inhibited the proliferation of MCF-7 cells in a dose-dependent manner, induced cell apoptosis (typical morphological changes in nucleus, significant increase in cell apoptosis rate). The expressions of cleaved PARP and caspase-8 increased, while the expression of pro-caspase-3 decreased, which further verified sodium aescinate's effect in inducing cell apoptosis. Sodium aescinate significantly inhibited the phosphorylation of cell survival-related signal molecules (AKT, ERK) and down-regulate the activation of their common up-stream kinase SRC. The findings indicated that sodium aescinate can block signals transiting to downstream molecules AKT, ERK, inhibit the proliferation of breast cancer cell MCF-7 cell apoptosis and induced cell apoptosis by suppressing the activation of SRC.
Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Breast Neoplasms ; drug therapy ; enzymology ; genetics ; physiopathology ; Down-Regulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; genetics ; metabolism ; Female ; Humans ; MCF-7 Cells ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Saponins ; pharmacology ; Signal Transduction ; drug effects ; Triterpenes ; pharmacology ; src-Family Kinases ; genetics ; metabolism

In the basis of a large amount of literatures, this article sumed up the characteristics and application of eggshell membrane.

Objective To investigate clinical characteristics of relapsing polychondritis(RP)and to improve early recognition for it.Methods Clinical and laboratory data of 56 patients with RP were analyzed retrospectively.Results Ratio of number of male patients to female ones was 1.2.Age at onset was(46?11)years(ranging from 27 to 71)and average interval between onset and diagnosis was(21? 35)months,(8?6),(16?31)and(29?37)months for patients initial onset with auricle,respiratory tract and joints involved,respectively.Site involved included airway in 40 patients(71.4%),auricle in 32 (57.1%),joints in 32(57.1%),eyes in 27(48.2%),nasal chondritis in 25(44.6%)and inner ear in 13(23.2%).At initial stage of the course,17 patients were misdiagnosed as respiratory infection (30.4%),nine as perichondritis(16.1%),six as pulmonary tuberculosis(10.7%),five as rheumatoid arthritis(8.9%).Seven of 40 patients with airway involvement received metallic stents for their tracheobronchial stenosis.Four patients whose condition never improved after regular therapy all had respiratory involvement.Conclusions Patients of RP with initial onset at non-auricle,non-nasal sites tended to be misdiagnosed.Prevalence of airway involvement was not so low with a poor prognosis in patients of RP.

OBJECTIVETo compare the therapeutic effects of acupuncture and Motilium on diabetic gastroparesis (DGP).

METHODSSeventy-two cases of DGP were randomly divided into a treatment group and a control group. The treatment group were treated with needling method for harmonizing spleen-stomach as main, with Quchi (LI 11), Hegu (LI 4), Zhongwan (CV 12), Zusanli (ST 36), Fenglong (ST 40), Yinlingquan (SP 9), Sanyinjiao (SP 6), Xuehai (SP 10), Diji (SP 8), and others selected, twice each day, 10 days constituting one course, with an in terval of 2 days; the control group were treated with oral administration of Motilium 10 mg, 3 times each day, 30 min before meals.

RESULTSThe total effective rate of 91.7% in the treatment group was better than 77.8% in the control group (P < 0.05).

CONCLUSIONThe therapeutic effect of the needling method for harmonizing spleen-stomach on diabetic gastroparesis is better than that of Motilium.

Acupuncture Therapy ; methods ; Adult ; Diabetes Complications ; therapy ; Female ; Gastroparesis ; therapy ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Spleen ; physiopathology ; Stomach ; physiopathology

Psychrotrophs were isolated by using four media from low-temperature sewage of sewage treatment plant in Urumqi, Xinjiang. Totally, 154 strains were obtained including 12 filamentous fungi, 46 yeasts, 6 actinomycetes and 90 bacteria. The results of tolerance tests of the isolates to salt, phenol and SDS, and enzyme producing characters of amylase, proteinase and esterase were shown. Then 60 bacterial strains were chosen for 16S rRNA gene sequencing and analysis. The blasting results showed that the strains were assigned to 13 recognized genera , and the Strain 39 exhibited 96.6% similarity to Acinetobacter lwoffii(DSM2403), indicating that it might be a novel species. These results suggested that there were a lot of psychrotrophs and rich bacterial diversity in low-temperature sewage. In addition, which maybe an important and potential library of microbial resources.

The vitamin K epoxide reductase complex subunit 1 (VKORC1), the rate-limiting enzyme for vitamin K recycling, is significantly down-regulated in the kidneys of urolithiasis patients. This study searched for direct evidence to define the inhibitory activity of VKORC1 against calcium oxalate (CaOx) crystal formation. In the experiment of VKORC1 overexpression, HK-2 cells were transfected with the pFLAG-CMV-7.1-VKORC1 plasmid as a pFLAG-CMV-7.1-VKORC1 transfection group or the pFLAG-CMV-7.1 plasmid as a pFLAG-CMV-7.1 control group. In the experiment of VKORC1 knockdown, HK-2 cells were transfected with the PGPU6/GFP/Neo-VKORC1shRNA-2 as a PGPU6/GFP/Neo-VKORC1shRNA-2 transfection group or the PGPU6/GFP/Neo-shRNA-NC plasmid as a PGPU6/GFP/Neo-shRNA-NC control group. The expression of VKORC1 in HK-2 cells was detected by real-time quantitative PCR and Western blotting. The CaOx crystal formation was observed under the laser-scanning confocal microscope. It was found that the expression levels of VKORC1 mRNA and protein were significantly higher in the pFLAG-CMV-7.1-VKORC1 transfection group than in the pFLAG-CMV-7.1 control group (P<0.01). The number of CaOx crystals in HK-2 cells incubated in fluorescently labeled CaOx monohydrate (COM) crystal medium for 48 h was 14±4 per field (100×) in the pFLAG-CMV-7.1-VKORC1 transfection group and 26±5 per field (100×) in the pFLAG-CMV-7.1 control group respectively under the laser-scanning confocal microscope. The amount of CaOx crystal aggregation and formation in the pFLAG-CMV-7.1-VKORC1 transfection group was significantly reduced as compared with the pFLAG-CMV-7.1 control group (P<0.05). The expression levels of VKORC1 mRNA and protein were significantly lower in the PGPU6/GFP/Neo-VKORC1shRNA-2 transfection group than in the PGPU6/GFP/Neo-shRNA-NC control group (P<0.05). The number of CaOx crystals in HK-2 cells incubated in fluorescently labeled COM crystal medium was 65±11 per field (100×) in the PGPU6/GFP/Neo-VKORC1shRNA-2 transfection group and 24±6 per field (100×) in the PGPU6/GFP/Neo-shRNA-NC control group respectively under the laser-scanning confocal microscope. The amount of CaOx crystal aggregation and formation in the PGPU6/GFP/Neo-VKORC1shRNA-2 transfection group was significantly increased as compared with the PGPU6/GFP/Neo-shRNA-NC control group (P<0.05). These findings suggested that the VKORC1 protein could inhibit CaOx salt crystallization, adhesion and aggregation. This research would help us to understand the mechanisms involving the interaction between crystallization and epithelial cells and the formation of CaOx.