血清胆红素、YKL-40、HMGB-1对糖尿病合并冠心病患者的临床意义

目的:探讨血清胆红素、人类软骨糖蛋白-39(YKL-40)、高迁移率族蛋白1(HMGB-1)对糖尿病合并冠心病患者的临床意义方法:选择2017年1月至2018年12月我院接诊的190例2型糖尿病患者,根据是否合并冠心病分为单纯糖尿病组121例和糖尿病合并冠心病组69例,并选择同期在我院接受体检的100例健康者作为对照组。比较三组临床生化指标、血清胆红素、YKL-40、HMGB-1及不同病变支数、不同病变程度糖尿病合并冠心病组血清胆红素、YKL-40、HMGB-1的表达。结果:三组空腹血糖(FBG)、糖化血红蛋白(HbA1c)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、血清胆红素、YKL-40、HMGB-1比较差异均有统计学意义(P0.05);不同病变支数、病变程度糖尿病合并冠心病患者血清胆红素、YKL-40、HMGB-1比较差异均有统计学意义(P0.05);经两两Pearson线性相关性分析结果显示,血清胆红素和Gensini评分呈负相关(r=-0.812,P0.01),YKL-40、HMGB-和Gensini评分正相关(r=0.873、0.801,P0.01)。结论:在糖尿病合并冠心病患者中,血清胆红素的表达明显降低,YKL-40、HMGB-1明显升高,且随着冠脉病变程度的加重变化更明显,本研究也为后期血清胆红素、YKL-40、HMGB-1在该病的早期诊断、预防、治疗效果评价等方面提供了依据     

肠道噬菌体组与人体健康

噬菌体作为肠道微生物群落的重要组成部分,自生命初期即定植于肠道,在不同生命时期均以较为稳定的状态存在于人体。目前已知的肠道噬菌体主要是DNA噬菌体,且大多以前噬菌体形式存在。肠道噬菌体可通过多种机制优化其宿主微生物群的结构和组成,并以多种方式直接或间接影响人体的生理状态,其结构变化与多种疾病相关。利用测序方法,能够直接获取噬菌体组信息。本文基于噬菌体组的相关研究,综述了肠道噬菌体组与人体健康相关的研究进展,并对该领域的研究方法和发展方向做出展望。     

Galactose-limited fed-batch cultivation of Escherichia coli for the production of lacto-N-tetraose

Lacto-N-tetraose (Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc) is one of the most abundant oligosaccharide structures in human milk. We recently described the synthesis of lacto-N-tetraose by a whole-cell biotransformation with recombinant Escherichia coli cells. However, only about 5% of the lactose was converted into lacto-N-tetraose by this approach. The major product obtained was the intermediate lacto-N-triose II (GlcNAc(β1-3)Gal(β1-4)Glc).In order to improve the bioconversion of lactose to lacto-N-tetraose, we have investigated the influence of the carbon source on the formation of lacto-N-tetraose and on the intracellular availability of the glycosyltransferase substrates, UDP-N-acetylglucosamine and UDP-galactose. By growth of the recombinant E. coli cells on D-galactose, the yield of lacto-N-tetraose (810.8 mg L⁻¹ culture) was 3.6-times higher compared to cultivation on D-glucose.Using fed-batch cultivation with galactose as sole energy and carbon source, a large-scale synthesis of lacto-N-tetraose was demonstrated. During the 26 h feeding phase the growth rate (μ = 0.05) was maintained by an exponential galactose feed. In total, 16 g L⁻¹ lactose were fed and resulted in final yields of 12.72 ± 0.21 g L⁻¹ lacto-N-tetraose and 13.70 ± 0.10 g L⁻¹ lacto-N-triose II. In total, 173 g of lacto-N-tetraose were produced with a space-time yield of 0.37 g L⁻¹ h⁻¹.     

Identification of Endothelin Receptor Subtype (ETB) in Human Cerebral Cortex Using Subtype-Selective Ligands

Abstract: Specific endothelin (ET) binding sites were characterized in membranes prepared from human cerebral cortices using binding assay and cross-linking analysis. The presence of immunoreactive (IR) ET-1 was studied by radioimmunoassay. Saturation binding experiments revealed that the K _D and B _max for ¹²⁵I-ET-1 and ¹²⁵l-ET-3 to membranes from gray matter were 25 ± 6 pM and 115 ± 15 fmol/mg of protein and 24 ± 5 p M and 108 ± 13 fmol/mg of protein, respectively. Similar results were obtained for white matter. In the presence of 10 n M sarafotoxin-6c, which is selective for ET_B receptors, ¹²⁵I-ET-1 and ¹²⁵l-ET-3 binding was totally abolished. However, in the presence of 1 μ M BQ123, which is selective for ET_Areceptors, both bindings were not affected. These results suggest that the human cerebral cortex contains only ET_Breceptors. Cross-linking of ¹²⁵I-ET-1 and ¹²⁵l-ET-3 to membranes with disuccinimidyl suberate resulted in the labeling of two bands of 48 and 31 kDa. Concentrations of IR-ET-1 in the gray and white matter were 7.0 ± 3.2 and 2.5 ± 1.7 fmol/g wet weight, respectively. The demonstration of high-affinity ET_B receptors and the presence of IRET-1 suggest that the peptide may act as a neurotransmitter or neuromodulator in the human cerebral cortex.     

人染色体脆性位点部位的显微光谱学研究 Study of Microspectroscopy for the Position of the Fragile Sites in Human Chromosome

采用显微分光光度法,对染色体脆性位点的部位进行了显微光谱学研究。实验证明,带有脆点的染色体其DNA含量大多数趋向减少,少数略有增加,推测染色体脆性部位的产生是由于染色质DNA在高度凝缩形成中期染色体过程中超旋结构改变的结果。 The position of fragile sites in human chromosome was studied by means of the microspectroscopy. The results show that the amount DNA in chromosome with fragile sites decreases in most condition. We can suppose that the fragile sites of chromosome is caused by the superhelix structure changes of chromosome DNA during the formation of metaphase chromosome which is formed in high condensation.     

Different susceptibility to polycyclic aromatic hydrocarbons (PAH)-induced DNA damage in lung tissue in male and female non-smokers

The levels of benzo(a)pyrene diol-epoxide (BPDE)-DNA adducts and polycyclic aromatic hydrocarbons (PAH) were analysed in a limited number of samples of autoptic lung tissue obtained from non-professionally exposed male (n= 13) and female (n= 12) non-smokers in an attempt to evaluate the relationship between gender, lung PAH levels (n= 25) and susceptibility to BPDE-DNA adduct formation (n= 18). Lung concentrations of chrysene, benzo(g,h,i)perylene and benzo(a)pyrene were significantly higher in males than in females (P     

The changing incidence of human papillomavirus-associated oropharyngeal cancer using multiple imputation from 2000 to 2010 at a Comprehensive Cancer Centre

Introduction Human papillomavirus (HPV) is a risk and prognostic factor for oropharyngeal cancer (OPC). Determining whether the incidence of HPV-associated OPC is rising informs health policy. Methods HPV status was ascribed using p16 immunohistochemistry in 683/1474 OPC patients identified from the Princess Margaret Hospital's Cancer Registry (from 2000 to 2010). Missing p16 data was estimated using multiple (n = 100) imputation (MI) and validated using an independent OPC cohort (n = 214). Non-OPC head and neck squamous cell carcinoma (HNSCC) (n = 3262) were also used for time-trend comparison. Regression was used to compare HNSCC subsets and time-trends. The c-index was used to measure the predictive ability of MI. Results The incidence of OPC rose from 23.3% of all HNSCC in 2000 to 31.2% in 2010 (p = 0.002). In the subset of OPC tested for p16, there was no change in p16 positivity over time (p = 0.9). However, p16 testing became more frequent over time (p < 0.0001), but was nonetheless biased, favouring never-smokers [OR 1.87 (95% CI 1.29–2.70)] and tumors of the tonsil [OR 2.30 (1.52–3.47)] or base-of-tongue [OR 1.72 (1.10–2.70)]. These same factors were also associated with p16-positivity [ORs 3.22 (1.27–8.16), 7.26 (3.50–15.1), 5.83 (2.70–12.7), respectively]. Following MI and normalization, the proportion of OPC that was p16-associated rose from 39.8% in 2000 to 65.0% in 2010, p = 0.002, fully explaining the rise in OPC in our patient population. Conclusion The rise in HNSCC referrals seen from 2000 to 2010 at our institution was driven primarily by p16-associated OPC. MI was necessary to derive reliable conclusions when cases with missing data are considerable.     

hZip1 (hSLC39A1) regulates zinc homoeostasis in gut epithelial cells

Zinc is an essential trace element required for enzyme catalysis, gene regulation and signal transduction. Zinc absorption takes place in the small intestine; however, the mechanisms by which cells accumulate zinc are not entirely clear. Zip1 (SLC39A1) is a predicted transmembrane protein that is postulated, but not conclusively proven to mediate zinc influx in gut cells. The aim of this study was to investigate a role for hZip1 in mediating zinc uptake in human enterocytes. Both hZip1 mRNA and protein were detected in human intestinal tissue. In non-differentiated Caco-2 human gut cells, hZip1 was partially localised to the endoplasmic reticulum. In contrast, in differentiated Caco-2 cells cultured in extracellular matrix, the hZip1 protein was located in proximity to the apical microvilli. Lack of surface antibody binding and internalisation indicated that hZip1 was not present on the plasma membrane. Functional studies to establish a role for hZip1 in cellular zinc accumulation were carried out using ⁶⁵Zn. In Caco-2 cells harbouring an hZip1 overexpression construct, cellular zinc accumulation was enhanced relative to the control. Conversely, Caco-2 cells with an hZip1 siRNA construct showed reduced zinc accumulation. In summary, we show that the Caco-2 cell differentiation endorses targeting of hZip1 to a region near the apical domain. Given the absence of hZip1 at the apical plasma membrane, we propose that hZip1 may act as an intracellular sensor to regulate zinc homoeostasis in human gut cells.