Cynandione A mitigates ischemic injuries in rats with cerebral ischemia

Cynandione A, an acetophenone from the roots of Cynanchum auriculatum and other species in the genus attenuates neurotoxicity of a variety of neurotoxic agents such as l-glutamate in vitro. In this study, we sought to further characterize the neuroprotective effects of cynandione A and other acetophenones from the roots of C. auriculatum in pheochromocytoma tumor cell line PC12 and investigate whether cynandione A protected against ischemic injuries in rats with experimentally induced cerebral ischemia. Viability assays using the 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophen-yl)-2H-tetrazolium monosodium salt method and lactate dehydrogenase (LDH) release assays showed that cynandione A dose-dependently attenuated glutamate-induced cytotoxicity. Comparative proteomic analysis by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight MS/MS of PC12 cells treated with cynandione A showed 10 μM cynandione A caused broad changes in protein expression in PC12 cells including down-regulation of high mobility group box 1 (HMGB1) and dihydropyrimidinase-like 2 (DPYSL2). Immunoblotting studies showed that 10 μM cynandione A aborted glutamate-induced increase in DPYSL2 and HMGB1 levels in PC12 cells and 30 mg/kg cynandione A also attenuated the rise in HMGB1 levels and mitigated DPYSL2 cleavage in brain tissues of rats with cerebral ischemia. Furthermore, rats with cerebral ischemia treated with 30 mg/kg cynandione A exhibited markedly improved neurological deficit scores at 24 and 72 h compared with control and a 7.2% reduction in cerebral infarction size at 72 h (p < 0.05 vs. control). Our findings demonstrated that cynandione A mitigated ischemic injuries and should be further explored as a neuroprotective agent for ischemic stroke.     

Outcome of the first electron microscopy validation task force meeting

This Meeting Review describes the proceedings and conclusions from the inaugural meeting of the Electron Microscopy Validation Task Force organized by the Unified Data Resource for 3DEM (http://www.emdatabank.org) and held at Rutgers University in New Brunswick, NJ on September 28 and 29, 2010. At the workshop, a group of scientists involved in collecting electron microscopy data, using the data to determine three-dimensional electron microscopy (3DEM) density maps, and building molecular models into the maps explored how to assess maps, models, and other data that are deposited into the Electron Microscopy Data Bank and Protein Data Bank public data archives. The specific recommendations resulting from the workshop aim to increase the impact of 3DEM in biology and medicine.     

Reduced Expression of Uroplakin 1A Is Associated with the Poor Prognosis of Gastric Adenocarcinoma Patients

Background

The aim of this study was to investigate the expression and prognostic significance of Uroplakin1A (UPK1A) in gastric adenocarcinoma patients. Functional studies were also analyzed in vitro.

Methodology/Principal Findings

Real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical (IHC) staining methods were used to analyze the expression of UPK1A in primary gastric adenocarcinoma tissue samples. Compared with matched adjacent non-tumor, the expression of UPK1A in fresh surgical specimens was reduced, which was confirmed by RT-qPCR (P<0.01) and western blotting analysis (P<0.01). The paraffin specimens from a consecutive series of 445 gastric adenocarcinoma patients who underwent surgery between 2003 and 2006 were analyzed by IHC staining. The relationship between UPK1A expression, clinicopathological factors, and survival were evaluated. IHC staining analysis revealed that the reduced expression of UPK1A was observed in 224 cases (50.3%). Additionally, the correlation analysis of clinicopathological factors demonstrated that reduced expression of UPK1A was significantly associated with histological grade (P = 0.022), node metastasis (P<0.001) and tumor node metastasis (TNM) stage (P = 0.008) (7^th edition of the International Union Against Cancer (UICC)). Furthermore, Kaplan-Meier survival analysis revealed that the reduced expression of UPK1A was significantly associated with poor prognosis (P = 0.043). Cox hazards model analysis indicated that UPK1A expression was an independent risk factor at the 0.1 level (P = 0.094). The function of UPK1A in cell cycle, migration, and invasion was investigated by overexpressing UPK1A in the MKN45 gastric cancer cell line. The elevated expression of UPK1A cells induced G1 phase arrest and significantly inhibited migration and invasion.

Conclusions/Significance

The reduced expression of UPK1A might play a role in the progression of gastric cancer. Thus, UPK1A could be a potential favorable biomarker associated with gastric cancer prognosis.     

Comparative studies on the interactions of dihydroartemisinin and artemisinin with bovine serum albumin using spectroscopic methods

The interactions of dihydroartemisinin (DHA) and artemisinin (ART) with bovine serum albumin (BSA) have been investigated using fluorescence, UV/vis absorption and Fourier transform infrared (FTIR) spectra under simulated physiological conditions. The binding characteristics of DHA/ART and BSA were determined by fluorescence emission and resonance light scattering (RLS) spectra. The quenching mechanism between BSA and DHA/ART is static. The binding constants and binding sites of DHA/ART–BSA systems were calculated at different temperatures (293, 298, 304 and 310 K). According to Förster non‐radiative energy transfer theory, the binding distance of BSA to DHA/ART was calculated to be 1.54/1.65 nm. The effect of DHA/ART on the secondary structure of BSA was analyzed using UV/vis absorption, FTIR, synchronous fluorescence and 3D fluorescence spectra. In addition, the effects of common ions on the binding constants of BSA–DHA and BSA–ART systems were also discussed. Copyright © 2014 John Wiley & Sons, Ltd.     

参芎葡萄糖注射液联合脑蛋白水解物治疗急性脑梗塞的疗效及对神经功能缺损和血液流变学的影响

目的:探析参芎葡萄糖注射液与脑蛋白水解物联合治疗急性脑梗塞患者的临床疗效和对神经功能、血液流变学的影响。方法:入选急性脑梗患者130例,随机分为两组各65例。对照组在常规治疗基础上使用脑蛋白水解物治疗,治疗组在常规治疗基础上不仅使用脑蛋白水解物,还加用参芎葡萄糖注射液治疗,比较两组患者的临床效果、神经功能缺损评分改变和血液流变学情况。结果:治疗组有效率显著高于对照组(P0.05);神经功能缺损评分治疗后均有下降,但治疗组下降幅度更大(P0.05);治疗组红细胞压积、血小板聚集率和纤维蛋白原均显著下降(P0.05),且同期相比,治疗组纤维蛋白原和红细胞压积下降幅度显著优于对照组(P0.05)。结论:参芎葡萄糖注射液与脑蛋白水解物联合治疗急性脑梗塞患者疗效确切,安全可靠,值得临床推广。     

Aged-Related Changes in Body Composition and Association between Body Composition with Bone Mass Density by Body Mass Index in Chinese Han Men over 50-year-old

Objectives

Aging, body composition, and body mass index (BMI) are important factors in bone mineral density (BMD). Although several studies have investigated the various parameters and factors that differentially influence BMD, the results have been inconsistent. Thus, the primary goal of the present study was to further characterize the relationships of aging, body composition parameters, and BMI with BMD in Chinese Han males older than 50 years.

Methods

The present study was a retrospective analysis of the body composition, BMI, and BMD of 358 Chinese male outpatients between 50 and 89 years of age that were recruited from our hospital between 2009 and 2011. Qualified subjects were stratified according to age and BMI as follows: 50–59 (n = 35), 60–69 (n = 123), 70–79 (n = 93), and 80–89 (n = 107) years of age and low weight (BMI: < 20 kg/m²; n = 21), medium weight (20 ≤ BMI < 24 kg/m²; n = 118), overweight (24 ≤ BMI < 28 kg/m²; n = 178), and obese (BMI ≥ 28 kg/m²; n = 41). Dual-energy X-ray absorptiometry (DEXA) was used to assess bone mineral content (BMC), lean mass (LM), fat mass (FM), fat-free mass (FFM), lumbar spine (L1-L4) BMD, femoral neck BMD, and total hip BMD. Additionally, the FM index (FMI; FM/height²), LM index (LMI; LM/height²), FFM index (FFMI; [BMC+LM]/height²), percentage of BMC (%BMC; BMC/[BMC+FM+LM] × 100%), percentage of FM (%FM; FM/[BMC+FM+LM] × 100%), and percentage of LM (%LM; LM/(BMC+FM+LM) × 100%) were calculated. Osteopenia or osteoporosis was identified using the criteria and T-score of the World Health Organization.

Results

Although there were no significant differences in BMI among the age groups, there was a significant decline in height and weight according to age (p < 0.0001 and p = 0.0002, respectively). The LMI and FFMI also declined with age (both p < 0.0001) whereas the FMI exhibited a significant increase that peaked in the 80-89-years group (p = 0.0145). Although the absolute values of BMC and LM declined with age (p = 0.0031 and p < 0.0001, respectively), there was no significant difference in FM. In terms of body composition, there were no significant differences in %BMC but there was an increase in %FM (p < 0.0001) and a decrease in %LM (p < 0.0001) with age. The femoral neck and total hip BMD significantly declined with age (p < 0.0001 and p = 0.0027, respectively) but there were no differences in L1-L4. BMD increased at all sites (all p < 0.01) as BMI increased but there were declines in the detection rates of osteoporosis and osteopenia (both p < 0.001). A logistic regression revealed that when the medium weight group was given a BMI value of 1, a decline in BMI was an independent risk factor of osteoporosis or osteopenia, while an increase in BMI was a protective factor for BMD. At the same time, BMD in L1-L4 exhibited a significant positive association with FMI (p = 0.0003) and the femoral neck and total hip BMDs had significant positive associations with FFMI and LMI, respectively (both p < 0.0001).

Conclusions

These data indicate that LMI and FFMI exhibited significant negative associations with aging in Chinese Han males older than 50 years, whereas FMI had a positive association. BMD in the femoral neck and total hip declined with age but an increased BMI was protective for BMD. LMI and FFMI were protective for BMD in the femoral neck and total hip.