OBJECTIVETo study the effect of nadroparin in the migration of breast cancer cells MDA-MB-231 and its action mechanism.

METHODThe MTT test was adopted to observe the effect of different concentrations of naringenin on the growth capacity of breast cancer cells MDA-MB-231. Wound healing and transwell experiment analysis were conducted to detect the effect of naringenin on the migration of breast cancer cells MDA-MB-231. Western blotting was adopted to investigate the effect of naringenin on protein expressions of MDA-MB-231 cell Integrin β3, β1 and matrix metalloproteinase MMP-2 and MMP-9. The computer virtual docking technique was used to evaluate the combining capacity of naringenin and Integrin β3 in vitro.

RESULTNaringenin inhibited the migration of MDA-MB-231 cells in a dose-dependent manner. In wound healing and transwell experiments, with the increase in the concentration of naringenin, the number of migrant MDA-MB-231 cells and the invasion capacity of breast cancer cells decreased. Naringenin could inhibit the protein expression of Integrin β3 in a dose-dependent manner, but with unobvious effect on expression of Integrin β1. Besides, naringenin could significantly inhibit the protein expressions of MMP-2 and MMP-9. The results of the computer virtual docking showed a negative value in the combining capacity between naringenin and Integrin β3, indicating the high affinity between them.

CONCLUSIONNaringenin can inhibit the growth capacity of breast cancer cells MDA-MB-231 and block the migration and invasion of breast cancer cells MDA-MB-231. Its mechanism is to down-regulate MMP-2 and MMP-9 expressions after combining with Integrin β3.

Breast Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Flavanones ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Integrins ; genetics ; metabolism ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Neoplasm Invasiveness

A new phenolic glycoside was isolated from the spikes of Prunella vulgaris. Its structure was elucidated as gentisic acid 5-O-beta-D-(6'-salicylyl)-glucopyranoside by spectroscopic evidence and chemical analysis.

Apoptosis ; drug effects ; Asparaginase ; pharmacology ; HL-60 Cells ; Humans ; K562 Cells ; U937 Cells

Objective To analyze blood lipid components in simple obesity children and to explore the effects of obesity in the lipid metabolism and its clinical significance.Methods A total of 90 children,including 50 simple obesity children(obesity group)and 40 normal children(control group),were enrolled in this study.The age ranged from 2.5 to 16.0 years.Their blood lipid profiles of all the children were analyzed.The blood lipid profiles were examined by biochemical analysis,including triglyeride(TG),total cholesterol(TC),low density lipoprotein(LDL) and high density lipoprotein(HDL),and the livers of all the children were analyzed.The blood lipid profiles were examined by ultrasonograph.Results 1.There were no significant differences in age and height in obesity group and control group,but there were significant differences in body mass index(BMI) and blood pressure(P0.05),which had no statistical meaning.3.Liver ultra sonogram showed that 18 cases had fatty liver(36%) in simple obesity children.Conclusions Metabolic disorder of blood lipid is present in simple obesity children,who have a tendency to get fatty liver.LDL is markedly elevated in obesity group.Arteriosclerotic cardiovascular disease should be prevented at earlier period of childhood.

Objective To investigate the expression of Notch 1 receptor in renal tissues of patients with hepatitis B virus associated-glomerulonephritis (HBV-GN) and its role in the pathogenesis of HBV-GN.Methods A total of 48 patients with HBV-GN confirmed by renal biopsy during 2008-2010 were enrolled in the study.Distribution of Notch1 receptor in renal tissue of HBV-GN was detected by immunohistochemistry and the association between the distribution of Notch1 receptor and HBsAg was examined by double-label immunofluorescence assays.Correlations of Notch1 receptor expression with renal pathology and clinical parameters of HBV-GN were analyzed.Results Notch1 receptor distributed mainly in renal tubular epithelial cells and interstitial area as brownish red granules,and a few expression in glomerulus was also found.The positive score of Notch1 receptor expression in HBV-GN patients was significantly higher as compared to primary glomerulonephritis patients with serum HBsAg positive or negative and normal renal tissue controls.Notch1 receptor expression was more obvious in membrano-proliferative glomerulonephritis (MPGN) and mesangial proliferative nephritis (MsPGN) patients,but there was no significant difference among the different pathology groups.Distribution of Notch1 receptor was consistent with the distribution of HBsAg and its intensity was positively correlated with renal interstitial fibrosis (r=0.473,P=0.001),tubular atrophy (r=0.690,P=0.000),inflammatory cell infiltration (r=0.616,P=0.000).Negative correlation was found between renal function and the intensity of Notch1 receptor (r=-0.393,P=0.006).Conclusions Notch1 receptor expression increases in the renal tissues of HBV-GN patients and distributes mainly in renal tubular epithelial cells and interstitium,which is consistent with the distribution of HBsAg.Its intensity is closely correlated with renal interstitial lesions and renal function.Abnormal expression of Notchl receptor in renal tissue of HBV-GN may be involved in the progress of HBV-GN.

ObjectiveTo investigate the expression and distribution of Toll-like receptor 4 (TLR4) in renal tissue of HBV associated nephropathy (HBV-GN) and its role in the pathogenesis and clinical manifestations of HBV-GN.MethodsRenal tissues were sampled from 48 HBV-GN patients confirmed by renal biopsy and 154 non-HBV-GN patients.The distribution of TLR4 in renal tissue and the relationship between the distribution of TLR4 and HBsAg were detected by immunohistochemistry.Integrating case record,correlations between the expression of TLR4 with clinical parameters including pathology,glomeruli,kidney tubules lesions,renal interstitial inflammatory infiltration and blood serum HBV were analyzed.ResultsTLR4 mainly distributed in the renal tubular epithelial cells and interstitial areas as brownish red and granular,which was in consistent with HBsAg distribution.The TLR4 positive rate and score in HBV-GN group were higher than those in non-HBV-GN group (P ＜ 0.05 ).TLR4 positive score was slightly higher in mesangial proliferative glomerulonephritis group and focal segmental glomerulosclerosis group,which had no significant difference (P ＞ 0.05).Kidney tubules lesions were strongly associated with TLR4 expression (r =0.748,P ＜ 0.001 ) which increased with aggravation of renal interstitial fibrosis ( r =0.569,P ＜0.001 ),tubular atrophy ( r =0.577,P ＜ 0.001 ) and inflammatory cell infiltration ( r =0.684,P ＜0.001 ).No obvious correlation with glomeruli lesions was observed ( r =0.293,P =0.053 ).Negative correlation could be seen between TLR4 and the renal function ( R2 =0.784),systolic blood pressure ( R2 =0.869),high sensitivity C-reactive protein (R2 =0.979) and urinary protein (R2 =0.615 ) by regression analysis.Other clinical parameters had no statistical significances.ConclusionsThe expression of TLR4 is abnormal in the renal tissue of HBV-GN patients,mainly in renal tubular epithelial cells and interstitial,which is consistent with the distribution of HBsAg.Its intensity is closely related with renal interstitial lesions,renal function changes and inflammatory cell infiltration.A speculation,that HBV can promote abnormal expression of TLR4 in renal tissues of HBV-GN which may be involved in the lesion progress of HBV-GN,is made upon our study.

A study on the microbial transformation of glycyrrhetinic acid (GA) was conducted by a fungus, Cunninghamella blakesleeana CGMCC 3.970 systematically. After incubation with the cell cultures of C. blakesleeana CGMCC 3.970 at 25 degrees C for 7 days on a rotary shaker operating at 135 r x min(-1), GA was converted into one major product and five minor products. The products were extracted and purified by solvent extraction, macroporous adsorbent resin, silica gel column chromatography, and semi-preparative RP-HPLC chromatography. Their structures were identified as 3-oxo-15α-hydroxy-18β-glycyrrhetinic acid(1), 3-oxo-15β-hydroxy-18β-glycyrrhetinic acid (2), 7β,15α-dihydroxy-18β-glycyrrhetinic acid (3), 3-oxo-7β, 15α-dihydroxy-18β-glycyrrhetinic acid (4), 7β-hydroxy-18β-glycyrrhetinic acid(5) and 15α-hydroxy-18β-glycyrrhetinic acid(6) by the analyses of MS, 1H-NMR and 13C-NMR spectroscopic data respectively. Among them, 2 was a new compound. These results suggest that C. blakesleeana CGMCC 3.970 has the capability of selective ketonization and hydroxylation for GA. [Key words] glycyrrhetinic acid; Cunninghamella blakesleeana CGMCC 3. 970; microbial transformation
Biotransformation ; Cunninghamella ; metabolism ; Glycyrrhetinic Acid ; analogs & derivatives ; chemistry ; metabolism ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization

To study the pharmacokinetics of ~(131)I-Metuximab injection (Licartin) combined with transarterial chemoembolization (TACE) for treatment of hepatocellular carcinoma (HCC). MethodsLicartin (27.75 MBq/kg) and the mixture of anticancer drug and Lipiodol were sequentially administered with interval of 20 minutes to 15 patients with HCC via a transfemoral catheter.After the Licartin was administrated, the pharmacokinetic and biodistribution data were evaluated through venous blood samples,urine collections,and 4 γ-scintigraphies (SPECT) over 7 days. The pharmacokinetic parameters were determined from integration of the blood radioactivity-time curves using the SPSS 12.0 software. The tumor-no-tumor ratio (T/NT) was calculated by ROI. Absorbed doses in organ were estimated according to the medical internal radiation dose formalism. The biodistribution of licartin within patient's body at different time points was compared for various organs using analysis of variance for repeated measures, as well as the T/NT ratio. ResultsThe blood radioactivity-time curves followed the dynamics two-compartment model, with the major pharmacokinetic parameters including t_(1/2)α(1.96±1.65) h, and t_(1/2)α(19.07±5.91) h,and t_(1/2)β (57.09±10.92) h, and C_(max) 2.113×10~9min~(-1)·L~(-1), and AUC_(0-∞) 1.302×10~(11) h·min~(-1)·L~(-1), respectively. The accumulated urine radioactivity was 52.2% of administrated dosage during 144 h after administration. There were statistical significant difference of biodistribution of licartin and T/NT ratio between organs at different time points (F=6.583, P<0.01 and F=3.546, P<0.01). SPECT scans showed the significant accumulation of the radioconjugate in liver tumor and faint uptake in other organs for 14 days. Tumor-to-liver ratio decreased from 2.88±1.02 at 3 h to 1.64±0.40 at 168 h (n=7). Organ absorbed dose was (3.19±1.01) Gy in liver (n=12) and (0.55±0.09) Gy in red marrow (n=7). ConclusionLicartin combined with TACE for treatment of HCC is helpful to significantly accrete the radioconjugate in liver tumor, and protect normal organs from radiotoxictiy.

Objective To investigate the relationship of 24 h urinary potassium (K) measurement and the symptoms change in ketamine-associated cystitis.Methods Forty-three ketamine-associated cystitis patients (29 male cases,14 female cases) were analyzed.The average age was 22 (17-29) years.Thirty-two patients without indwelling urinary catheter were categorized as group A,while the other 11 patients with indwelling urinary catheter were in group B.The therapy regimes consisted of anti-inflammatory,antioxidant,relieving spasm and pain,improving the microcirculation and repairing the bladder epithelium barrier.Thirty healthy adults were selected as the controls.Urinary K,sodium (Na) and creatinine (Cr)were determined in 24 h urine samples from all patients and controls before and after treatments.24 h urinary Cr was used as the internal standard.24 h urinary K and Na concentrations of the patients were calculated as relative to the Cr concentrations.The pelvic pain and urgency/frequency symptom (PUF) was used for evaluation before and after the treatments.The differences of urinary K were compared within each group and between groups before and after treatments.In addition,relationship of urinary K and PUF were assessed.Results Urinary Cr concentrations in all groups were not significantly different (P ＞ 0.05).Patients in group A had lower average K-to-Cr ratios than those patients in group B and controls (A 1.80 ± 0.67 vs.B 6.22±0.92 mmolK/mmol Cr,P=0.0001; A 1.80±0.67 vs.controls 6.47 ±0.97 mmol K/mmol Cr,P =0.0001) before treatments.But the ratios of K-to-Cr in group A were not significantly different with group B and controls after treatments (A 6.23 ± 1.42 vs.B 6.02 ± 0.98 mmol K/mmol Cr,A 6.23 ± 1.42vs.controls 6.47 ±0.97 mmol K/mmol Cr,F =0.698,P =0.472).PUF in both groups was not significantly different before treatments.For group A,PUF was negatively correlated with urinary K before and after treatments (before: r=-0.637,P=0.0001; after: r=-0.427,P=0.015).For group B,PUF had no correlation with urinary K before treatment (r=0.581,P =0.188),while there was a negative correlation between them after treatments (r =-0.779,P =0.005).PUF scores in all patients (group A + B)were significantly decreased after treatments when compared to those before treatments (18.12 ± 2.83 vs.22.77 ± 3.63,P =0.0001).Conclusion Urinary potassium measurement may have a role in evaluating the disease status and efficacy of treatments of patients suffered from ketamine-associated cystitis.

Objective To explore the relationship between fluconazole resistance and expression of multidrug resistant protein genes,including CDR1,CDR2,MDRI.Methods The total RNA was extracted from fluconazole-resistant and -susceptible Candida albicans isolates,and cDNA was synthesized.The expression of CDR1,CDR2 and MDRl genes was then detected by quantitative real-time PCR.The?CT (threshold cycle) value was obtained by subtracting the CT value of 18S rRNA from that of the targeted gene.Results The?CT value of CDR2 was significantly lower in fluconazole-resistant isolates than in fluconazole- susceptible isolates (7.52?2.53 vs.9.28?3.15,t=2.367,P