OBJECTIVETo investigate the effects of 4OH-Tamoxifen (OHT) on proliferation and apoptosis of primary cultured prostate stromal cells.

METHODSPrimarily cultured prostate stromal cells in vitro were treated with various concentrations (10(-8) mol/L - 10(-5) mol/L) of estradiol (E2), diethylstilbestrol (DES), OHT and the mixture of E2 (10(-8) mol/L - 10(-6) mol/L) with OHT (10(-7) mol/L) and then MTT and TUNEL were used to detect their proliferation and apoptosis respectively.

RESULTSThere was a significant difference (P < 0.05) between OHT and estrogens in the effects on the apoptosis and proliferation of the primarily cultured prostate stromal cells. OHT suppressed proliferation of the prostate stromal cells at the concentrations from 10(-7) mol/L to 10(-5) mol/L (P < 0.05), and this effect was concentration related (r = -0.383, P = 0.005); OHT (10(-7) mol/L) suppressed the proliferation stimulation effect of E2 at the concentrations from 10(-8) mol/L to 10(-6) mol/L (P < 0.05). OHT induced apoptosis at the concentrations from 10(-8) mol/L to 10(-5) mol/L (P < 0.05), and this effect was concentration related (r = 0.349, P = 0.012). The apoptosis induced by OHT could not be reversed by E2 at the concentrations from 10(-8) mol/L to 10(-5) mol/L (P > 0.05).

CONCLUSIONOHT can obviously suppressed the proliferation and promote the apoptosis of primarily cultured prostate stromal cells, which might not be totally attributed to the competitive inhibition of the estrogen receptor.

Antineoplastic Agents, Hormonal ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Humans ; Male ; Prostate ; cytology ; Stromal Cells ; cytology ; drug effects ; Tamoxifen ; pharmacology

Background: Insulin-treated patients with long duration of type 2 diabetes mellitus (T2DM) are at increased risk of ketoacidosis related to sodium-glucose co-transporter 2 inhibitor (SGLT2i). The extent of circulating ketone elevation in these patients remains unknown. We conducted this study to compare the serum ketone response between dapagliflozin, an SGLT2i, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, among insulin-treated T2DM patients. Methods: This was a randomized, open-label, active comparator-controlled study involving 60 insulin-treated T2DM patients. Participants were randomized 1:1 for 24-week of dapagliflozin 10 mg daily or sitagliptin 100 mg daily. Serum β-hydroxybutyrate (BHB) levels were measured at baseline, 12 and 24 weeks after intervention. Comprehensive cardiometabolic assessments were performed with measurements of high-density lipoprotein cholesterol (HDL-C) cholesterol efflux capacity (CEC), vibration-controlled transient elastography and echocardiography. Results: Among these 60 insulin-treated participants (mean age 58.8 years, diabetes duration 18.2 years, glycosylated hemoglobin 8.87%), as compared with sitagliptin, serum BHB levels increased significantly after 24 weeks of dapagliflozin (P=0.045), with a median of 27% increase from baseline. Change in serum BHB levels correlated significantly with change in free fatty acid levels. Despite similar glucose lowering, dapagliflozin led to significant improvements in body weight (P=0.006), waist circumference (P=0.028), HDL-C (P=0.041), CEC (P=0.045), controlled attenuation parameter (P=0.007), and liver stiffness (P=0.022). Average E/e’, an echocardiographic index of left ventricular diastolic dysfunction, was also significantly lower at 24 weeks in participants treated with dapagliflozin (P=0.037). Conclusion Among insulin-treated T2DM patients with long diabetes duration, compared to sitagliptin, dapagliflozin modestly increased ketone levels and was associated with cardiometabolic benefits.

INTRODUCTION: An echocardiographic calcium score (ECS) predicts cardiovascular disease (CVD) in the general population. Its utility in peritoneal dialysis (PD) patients is unknown. METHODS: This cross-sectional study assessed 125 patients on PD. The ECS (range 0-8) was compared between subjects with CVD and those without. RESULTS: Among the subjects, 54 had CVD and 71 did not. Subjects with CVD were older (69 years vs. 56 years, P < 0.001) and had a higher prevalence of diabetes mellitus (DM) (81.5% vs. 45.1%, P < 0.001). They had lower diastolic blood pressure (72 mmHg vs. 81 mmHg, P < 0.001), lower phosphate (1.6 mmol/L vs. 1.9 mmol/L, P = 0.002), albumin (30 g/L vs. 32 g/L, P = 0.001), parathyroid hormone (34.4 pmol/L vs. 55.8 pmol/L, P = 0.002), total cholesterol (4.5 vs. 4.9, P = 0.047), LDL cholesterol (2.4 mmol/L vs. 2.8 mmol/L, P = 0.019) and HDL cholesterol (0.8 mmol/L vs. 1.1 mmol/L, P = 0.002). The ECS was found to be higher in subjects with CVD than in those without (2 vs. 1, P = 0.001). On multivariate analysis, only DM and age were independently associated with CVD. CONCLUSION The ECS was significantly higher in PD patients with CVD than in those without, reflecting a higher vascular calcification burden in the former. It is a potentially useful tool to quantify vascular calcification in PD patients.
Humans ; Cardiovascular Diseases/diagnostic imaging* ; Cross-Sectional Studies ; Calcium ; Peritoneal Dialysis/adverse effects* ; Vascular Calcification/epidemiology* ; Echocardiography

OBJECTIVE: To compare the differences and indications of three evaluation methods for fitness evaluation of removable partial denture (RPD). METHODS: A RPD was fabricated and seated on the stone cast of a partially edentulous mandible, and the spaces between RPD and stone cast were recorded with polyvinyl siloxane (PVS) impression material forming PVS replicas. Using cross sectional measurement, the average thicknesses of PVS replicas were measured under stereomicroscope with different numbers of selected measuring points in the denture base, major connector, occlusal rest of the RPD, and the average thicknesses of the PVS replicas measured with different numbers of measuring points were compared using one-way analysis of variance (ANOVA) and independent sample t test. Three kinds of method, including cross sectional measurement, three-dimensional analysis on the stone cast, and three-dimensional analysis on the polyether cast, were applied to measure the average thicknesses of the PVS replicas, and the average thicknesses of the PVS replicas measured by these three evaluation methods were compared with ANOVA. RESULTS: For cross sectional measurement, statistically significant differences were found in the average thicknesses of the PVS replicas in the denture base and the major connector among the different numbers of measuring points (P < 0.05), but no differences were found in the average thicknesses of the PVS replicas in the occlusal rest (P>0.05). There were significant differences among the average thicknesses of the PVS replicas measured by these three evaluation methods in each component of the RPD (P < 0.01). The average thickness measured by three-dimensional analysis on the stone cast and three-dimensional analysis on polyether cast were smaller than that measured by cross sectional measurement (P < 0.05). And there were no differences between the average thicknesses of PVS replicas measured by three-dimensional analysis on stone cast and three-dimensional analysis on polyether cast (P>0.05). CONCLUSION For cross sectional measurement, the average thickness of the PVS replicas was influenced by the number of measuring points, and the measurement accuracy of cross sectional measurement was not reliable enough. Three-dimensional analysis on stone cast which is suitable for evaluation in vitro and three-dimensional analysis on polyether cast which is suitable for evaluation in vivo can evaluate the fitness of RPD more comprehensively and effectively than that of cross sectional measurement.
Computer-Aided Design ; Cross-Sectional Studies ; Denture, Partial, Removable ; Exercise ; Research Design

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.