Aim ToinvestigatetheeffectsofmiRNA-181 a on breast cancer resistance protein ( BCRP ) . Methods Bioinformaticspredictedbindingsitesof BCRP mRNA-3ˊUTR region and miR-181 a;further lu-ciferase reporter gene analysis confirmed that miR-181 a could combine with BCRP mRNA-3ˊUTR; qRT-PCR and Western blot detected related mRNA and protein expressionlevels.Results Comparedwithnegative transfection group, after the miR-181a mimic and PGL3-BCRP 3ˊUTR were co-transfected, luciferase ac-tivity was significantly decreased ( P <0 . 05 ) . After miR-181a mimic transfected MCF7/MX cells for 48h, compared to the negative group, the expression of miR-181 a in MCF-7/MX cells was increased ( P<0. 05 ) , BCRP mRNA, BCRP protein expression were signifi-cantly decreased ( P<0 . 05 ) , while mRNA expression and protein levels of MRP, P-gp, LRP did not change significantly ( P >0. 05 ); after transfecting miR-181 a inhibitor for 48h, compared to the negative group, the expression of miR-181 a in MCF-7 cells was reduced (P<0. 05). Meanwhile,BCRP mRNA expression and BCRP protein expression were also significantly in-creased ( P<0. 05 ) . The mRNA expression and pro-tein levels of MRP, P-gp, LRP did not change signifi-cantly(P>0.05).Conclusion miR-181acanregu-late BCRP expression by targeting the BCRP mRNA-3ˊUTR region.

To study the protective effect and the mechanism of asiatic acid (AA) from Potentilla chinensis on alcohol hepatic injury in rats. Male Wistar rats were randomly divided into six groups: the normal control group, the AA control group (8 mg · kg(-1) AA), the model group (5.0-9.0 g · kg(-1) alcohol) and high, medium and low-dose AA-treated groups (alcohol + 8, 4, 2 mg · kg(-1) AA). Each group was orally administered with the corresponding drugs once a day for 24 weeks. Approximately 1. 5 hours after the final administration, all rats were killed, and their blood samples and hepatic tissues were collected. The AST and ALT in rat serum and the contents of MPO, TNF-α, IL-1β, SOD, GSH-Px, GSH-Rd and MDA in hepatic tissues were detected. The expressions of NF-κB, TLR4, CD14, MyD88, TRIF and protein expression in hepatic tissues were measured by western blot. The pathological changes in liver tissues were observed by histological examination. The results showed that compared with the model group, the AA-treated groups showed significant decreases in serum ALT, AST and MDA and increases in the activities of SOD, GSH-Px, GSH-Rd and MPO. Moreover, AA markedly inhibited the expressions of TNF-α, IL-1β, TLR4, CD14, MyD88 and NF-κB. The histological examination showed alleviated hepatic issue ijury to varying degrees. In short, asiatic acid (AA) from P. chinensis could protect alcohol-induced hepatic injury in rats. Its mechanism may be related to the inhibition of NF-κB inactivation and the reduction of inflammatory response.
Animals ; Liver ; drug effects ; pathology ; Liver Diseases, Alcoholic ; prevention & control ; Male ; NF-kappa B ; physiology ; Pentacyclic Triterpenes ; pharmacology ; Potentilla ; chemistry ; Protective Agents ; pharmacology ; Rats ; Rats, Wistar ; Toll-Like Receptor 4 ; antagonists & inhibitors

To investigate the anticancer effects of ring C in 18β-glycyrrhetinic acid (GA), a series of GA derivatives featured with 9(11)-ene moiety in ring C were designed and synthesized. The structures were confirmed by IR, LC-MS and 1H NMR. Their inhibitory effects towards human prostate cancer PC-3 and leukemia HL-60 cell lines were determined. Most of the derivatives displayed stronger antiproliferative activities than GA. Particularly, compound 14 showed promising anticancer activity with the GI50 values of 4.48 µmol · L(-1) and 1.2 µmol · L(-1) against PC-3 and HL-60 cells respectively, which is worth further study.
Antineoplastic Agents ; chemistry ; pharmacology ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; drug effects ; Drug Design ; Glycyrrhetinic Acid ; analogs & derivatives ; chemistry ; HL-60 Cells ; drug effects ; Humans ; Male ; Prostatic Neoplasms ; pathology

Rutaecarpine (Rut) is a type of indole quinazoline alkaloid exracted from Ruticarpum. Studies showed that Rut has a wide range of pharmacological effects, such as anti-hypertension, anticancer, anti-inflammation, anti-thrombus formation. Currently, many scholars are committed to developing it into a new antihypertensive and anti-inflammatory drug with all new mechanisms. But studies found that Rut is a highly fat-soluble drug with low water and oil solubility. Its high insolubility is the main obstacle in its oral absorption and application, which greatly reduced its bioavailability. Therefore, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was used as the inclusion material to prepare Rut-HP-beta-CD inclusion complex in this experiment, in order to increase its water solubility and bioavailability. In this experiment, the inclusion complex was prepared by the stirring-freeze-dry method. The preparation process was optimized by the orthogonal test, with the inclusion rate as the index, and molar ratio between host and guest molecules, inclusion temperature, time and stirring speed as the impacting factors. Moreover, the inclusion complex was verified by detecting the apparent solubility, thin layer chromatography, microscopic identification, melting point detection and dissolution study. The results showed that under the conditions of the molar ratio between Rut and HP-beta-CD of 1: 1, temperature at 60 degrees C, inclusion time of 4h and stirring speed at 600 r x min(-1), the inclusion rate of Rut-HP-beta-CD reached 91.04%. Therefore, the preparation process of Rut-HP-beta-CD inclusion under the optimum conditions is simple and feasible, with a highest inclusion rate and reproducibility, and could significantly improve Rut's solubility and bioavailability, and provide a reliable experimental basis for its clinical application.
2-Hydroxypropyl-beta-cyclodextrin ; Alkaloids ; chemistry ; Chemistry, Pharmaceutical ; methods ; Drug Carriers ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Rutaceae ; chemistry ; Solubility ; beta-Cyclodextrins ; chemistry

Adolescent ; Bile Reflux ; etiology ; Child ; Child, Preschool ; Female ; Gastritis ; etiology ; Gastroscopy ; Helicobacter Infections ; complications ; diagnosis ; Helicobacter pylori ; Humans ; Male

OBJECTIVETo investigate the precise locations of the blood vessels and nerves surrounding the seminal vesicles (SV) in men and provide some anatomical evidence for SV-related minimally invasive surgery.

METHODSWe observed the courses and distribution of the blood vessels and nerves surrounding SVs and obtained the data for positioning the SV neuroplexes in 20 male pelvises.

RESULTSOne branch of the neuroplexes was distributed to the SVs bilaterally with the neurovascular bundles, (2.85 ± 0.18) cm from the median sulcus of the prostate (MSP), while another branch ran through the Denonvillier fascia behind the SV, (0.81 ± 0.06) cm from the MSP. The arterial SVs (ASV) originated from the inferior vesical artery and fell into 4 types, 55% going directly to the SVs as one branch, 15% running between the SV and the ampulla of the deferent duct as another branch, 25% downward as 2 branches to the SV and between the SV and the ampulla of the deferent duct respectively, and 5% as the other ASVs. The shortest distance from the ASV through the prostatic neuroplexus to the posterior SV was (1.08 ± 0.09) cm.

CONCLUSIONIn SV resection, neuroplexus injury can be reduced with a bilateral distance of < 2.85 cm and a posterior distance of < 0.81 cm from the MSP, and so can bleeding by vascular ligation between the SV and the ampulla of the deferent duct.

Biopsy ; Humans ; Male ; Prostate ; blood supply ; innervation ; Seminal Vesicles ; blood supply ; innervation ; Vas Deferens ; blood supply ; innervation

Objective To establish an simple and convenient animal model of cardiac arrest for studying cerebral resuscitation.Method Clean male Sprague Dawley rats were randomly divided into sham group and experimental group.Cardiac arrest was induced by asphyxiation and ice-cold 0.5 mol KCl with blood flow cut off for 5 minutes.Animals were resuscitated with external cardiopulmonary resuscitation (CPR),mechanical ventilation,and epinephrine injection.Blood pressure,heart rate,successful ratio of resuscitation after 72 hours, time of cardiac arrest (T_(CA)) and return of spontaneous circulation (T_(ROSC)) were recorded.Neural deficit scores (NDS) and levels of maleic dialdehyde (MDA) in plasma were evaluated at 3,6,12,24,48,72 hours after ROSC.The damage score of cortex was measured by transmission electron microscope examination at 3 hours and 72 hours after ROSC.Results All the rats in experimental group had cardiac arrest rapidly.T_(CA) and T_(ROSC) were (137.3?10.2) seconds and (64.4?9.3) seconds,respectively,while the successful rate of resuscitation was 82.5%.The lowest NDS was at 3 hours after ROSC,while the NDS increased gradually.After CPR,the level of MDA in plasma increased significantly,slightly declined at 72 hours after ROSC,but still significantly higher than before the model.Electron microscope examination of cortex showed neuron slightly,organelle and astrocyte,but became better after 72 hours post ROSC.Conclusions The model of cardiac arrest was easy to establish,and the data provided was accurate,which is useful to study the mechanism of cerebral resuscitation.

Objective To investigate the iodine nutrition level of the vulnerable population in the high risk region of iodine deficiency disorders for providing a scientific basis for the development of effective preventive measures in Qinghai province. Methods The non-iodized salt coverage rate ＞ 5％ of Delingha city, the coverage rate of iodized salt and the rate of qualified iodized salt ≤80％ of Jiuzhi, Wulan, Nangqian, Zaduo, Geermu,Yushu, Gande, Chengduo, and Dulan counties(cities), the median of urinary iodine ＜ 100 μg/L of Huangyuan county of 11 areas were chosen as monitoring area in 2009. Five townships(towns) were selected by their location of east, west, south, north and center in each county (city), and one school was selected in each township (town),and 60 household salt samples were collected in each school, and quantitatively determined by direct titration of iodine(GB/T 13025.7-1999). Three townships(towns) were selected in each county(city), and two schools were selected in each township(town). The content of urinary iodine of 40 children aged 8 - 10 and 20 women of childbearing age aged 18 - 40 was analyzed by As3+-Ce4+ catalytic spectrophotometry (WS/T 107-2006). ResultsThree thousand two hundred and sixty-one edible salt samples were tested. The coverage rate of iodized salt was 79.88％.The iodized salt qualification rate was 95.16％. The qualified iodized salt consumption rate was 76.02％. The noniodized salt coverage rate was 20.12％. In Nangqian, Zaduo, Yushu and Geermu counties(cities), the non-iodized salt coverage rate was 88.89％, 45.05％, 43.00％ and 12.67％, respectively. The median of urine iodine of 2536 children aged 8 - 10 was 155.8 μg/L, with ≤50 μg/L about 13.6％ (346/2536), ＞ 100 μg/L about 67.5％(1711/2536), and it was 75.1, 94.6 μg/L in Nangqian and Zaduo counties, respectively. The median of urine iodine of 665 women of childbearing age was 129.7 μg/L, with ≤50 μg/L about 22.7％(151/665), ＞ 100 μg/L about 59.2％(394/665), and it was 21.0, 54.7, 72.7 μg/L in Zaduo, Nangqian and Chengduo counties, respectively.Conclusions Insufficient intake of iodine exits in children and women of childbearing age in high risk region of iodine deficiency disorders in Qinghai province, which should be corrected as soon as possible.

Objective To study the lysozyme activity in Oncomelania hupensis and observe its inhibitory effect on bacterial growth.Methods Soft tissues of Oncomelania hupensis were initially homogenized and immersed in Tris-HCl-TritonX-114 buffer solution for 24 hours then the supernatant was collected after centrifugation at 10 000 × g for 10 minutes.The supernatant was incubated in a 37 ℃ water bath for 15 minutes and centrifuged again at 2000 × g for 10 minutes.The precipitate was put into ultrafiltration tube (relative retention molecular mass =3000) and centrifuged at 4 ℃,5 000 × g for 30 minute to obtain concentrated enzyme.The protein content,lysozyme activity and the antibacterial effect on Micrococcus lysodeikticus,Shigella dysenteriae,Staphylococcus aureus,Escherichia coli and Candida albicans were measured with bicinchonininc acid(BCA) method,turbidimetric method and agar diffusion (K-B) method,respectively.Results The antibacterial protein lysozyme was identified in gastropod protein concentration of the concentrated enzyme was 3.428 g/L.Average activity,total activity,and specific activity were (760 ± 120) × 103 U/L,(1520 ± 240) × 103 U/L and (221.70 ± 35.00)U/mg,respectively.The enzyme had produced exclusive inhibitory effects on growth of Micrococcus lysodeikticus and Shigella dysenteriae.Average inhibitory diameters were 10-12 and 12-15 mm,respectively.No inhibition zone was observed in saline control,Staphylococcus aureus,Escherichia coli and Candida albicans.Conclusions Lysozyme can be extracted from soft tissues of Oncomelania hupensis with Tris-HCl-TritonX-114 buffer solution,and the enzyme has inhibitory effect on growth of Micrococcus lysodeikticus and Shigella dysenteriae but has no antibacterial effect on Staphylococcus aureus,Escherichia coli and Candida albicans.

ABSTRACT:Objective To observe the effects of late Na current (INa‐L ) and rapidly activating delayed rectifier K current (IKr ) on ventricular heterogeneity and frequency dependency by using high resolution voltage sensitive optical mapping technology .Methods The model of 12 isolated hearts was constructed in rabbits . Voltage sensitive dye Di‐4‐ANEPPS were perfused into the isolated hearts by Langendorff method .LED source with the wave length of 532 nm was used to record APD80 and APD50 of the left and right ventricles .Experimental groups were divided into 3 groups by perfusion drugs dofetillide (30 nmol/L) ,dofetillide+ATX‐Ⅱ(1 nmol/L) ,and dofetillide +ATX‐Ⅱ +mexiletine (10μmol/L) .The subjects were intervened by the above drugs in order ,and they were self‐compared before dosing .After each drug administration ,the hearts were stimulated respectively with the BCL of 2 000 ms ,1 000 ms ,500 ms ,and 300 ms .Then we observed the changes of APD80 and APD50 in the left and right ventricles before and after the interventions .Results ① In the control group ,APD80 and APD50 of the right ventricle were longer than those of the left ventricle in response to different stimulation , and the differences increased with the decrease of stimulating frequency .② When BCL was 1000 ms ,APD80 and APD50 of the left and right ventricles were prolonged respectively after administration of dofetillide , but the differences in APD80 and APD50 were insignificant between the left and right ventricles (P>0 .05) .ΔAPD80 of the two ventricles increased significantly with the decrease of stimulating frequency . ③ After administration of ATX‐Ⅱ , when BCL was 1000 ms ,APD80 and APD50 of the left and right ventricles increased significantly compared with those in the control group and dofetillide intervention group (P<0 .05) .And the increase of APD in the left ventricle was greater than that of the right ventricle .ΔAPD80 of the two ventricles increased significantly with the decrease of stimulating frequency .④ After administration of mexiletine ,when BCL was 1000 ms ,APD80 and APD50 of the left and right ventricles reduced significantly compared with those of the primary state (P<0 .05) .APD80 and APD50 of the left and right ventricles reduced significantly compared with those of the control group (P< 0 .05) and ATX‐Ⅱ group (P>0 .05) .The increase of ΔAPD80 of the two ventricles became milder when the stimulating frequency decreased . Conclusion ① IKr blocked by dofetillide did not affect the heterogeneity between the two ventricles , which showed reverse‐frequency dependence . ② In the context of blocking IKr , ATX‐Ⅱ increased the heterogeneity between the left and right ventricles and enhanced the reverse‐frequency dependence .In contrast ,mexiletine ,the blocker of INa‐L ,decreased the heterogeneity between the two ventricles and reverse‐frequency dependence .