人胃癌MG7抗原在胃癌早期诊断中的研究进展

人胃癌MG7抗原(MG7-Ag)是一种中性糖脂类肿瘤相关抗原,其在正常胃黏膜中不表达或低表达,而在早期胃癌中的特异性高表达让其有可能成为早期胃癌诊断的预警分子。从普通胃炎到胃癌,MG7-Ag参与了胃癌的发展过程,故针对MG7-Ag过表达肿瘤的靶向治疗在临床上成为可能。该文现对MG7-Ag在胃癌早期诊断进行综述,为临床诊疗提供参考。     

Thrombomodulin Functional Domains Support Osteoblast Differentiation and Bone Healing in Diabetes in Mice

Thrombomodulin (TM) is a transmembrane glycoprotein that contains five functional domains. Soluble TM (sTM), comprising extracellular domains TMD1 (lectin-like), TMD2 (epidermal growth factor [EGF]-like repeat containing), and TMD3 (serine-threonine rich), can be shed from cells by the intramembrane protease rhomboid-like-2 (RHBDL2). TM is expressed by osteoblasts, yet its role there has not been determined. Herein we aimed to investigate the properties of TM and its domains in osteoblast function and bone repair following injury in diabetes. In response to a scratch injury of cultured osteoblast-like MG63 cells, expression of TM and RHBDL2 was enhanced, with increased release of sTM. Conditioned media from the injured cells promoted osteoblast migration, an effect that was lacking with conditioned media from MG63 cells in which TM was silenced by shRNA. Exogenous recombinant TMD1 had no effect on osteoblast activities or on bone repair in vivo. However, TM domains 2 and 3 (TMD2/3), induced MG63 cell migration, proliferation and mineralization in vitro, and when locally administered in mice, improved in vivo healing of injured calvarium. This beneficial effect of TMD2/3, mediated via fibroblast growth factor receptor (FGFR)/ERK signaling pathways, was also observed in vitro under high glucose conditions where endogenous TM expression was reduced, and in vivo in diabetic mice following tibia fracture or calvarium injury, where the osteoblastic response and healing were otherwise dampened. Taken together, osteoblast TM participates in bone healing, and recombinant TMD2/3 holds promise as a novel therapy for diabetic bone defect healing. © 2020 American Society for Bone and Mineral Research.     

Protective effect of dry olive leaf extract in adrenaline induced DNA damage evaluated using in vitro comet assay with human peripheral leukocytes

Excessive release of stress hormone adrenaline is accompanied by generation of reactive oxygen species which may cause disruption of DNA integrity leading to cancer and age-related disorders. Phenolic-rich plant product dry olive leaf extract (DOLE) is known to modulate effects of various oxidants in human cells. The aim was to evaluate the effect of commercial DOLE against adrenaline induced DNA damage in human leukocytes by using comet assay. Peripheral blood leukocytes from 6 healthy subjects were treated in vitro with three final concentrations of DOLE (0.125, 0.5, and 1 mg/mL) for 30 min at 37 °C under two different protocols, pretreatment and post-treatment. Protective effect of DOLE was assessed from its ability to attenuate formation of DNA lesions induced by adrenaline. Compared to cells exposed only to adrenaline, DOLE displayed significant reduction (P < 0.001) of DNA damage at all three concentrations and under both experimental protocols. Pearson correlation analysis revealed a significant positive association between DOLE concentration and leukocytes DNA damage (P < 0.05). Antigenotoxic effect of the extract was more pronounced at smaller concentrations. Post-treatment with 0.125 mg/mL DOLE was the most effective against adrenaline genotoxicity. Results indicate genoprotective and antioxidant properties in dry olive leaf extract, strongly supporting further explorations of its underlying mechanisms of action.     

A Czechoslovakian teenager with Hb E-β∘-thalassemia [IVS-I-1 (G → A)] complicated by the presence of an α-globin gene triplication

Summary We have examined the molecular basis of three inherited hemoglobin (Hb) disorders present in a Czechoslovakian girl with a severe, transfusion-dependent, hemolytic anemia. She is heterozygous for Hb E (on a genetic background specific for Czechoslovakian families), heterozygous for the -thalassemia (thal) allele IVS-I-1 (G A), and heterozygous for an -globin gene triplication. The combination of these three undesirable traits results in a severe chain imbalance that is the basis of the serious hemolytic disorder observed in this teenager.This study was supported in part by USPHS Research Grant HLB-41544. This is contribution 1282 from the Department of Cell and Molecular Biology at the Medical College of Georgia in Augusta     

Effect of alcohol administration on plasma growth hormone response to insulin-induced hypoglycemia.

Plasma growth hormone (HGH) response to insulin-induced hypoglycemia was assessed in a group of normal adult volunteers, with and without prior consumption of ethanol. A significant difference was found in peak HGH concentrations on the two occasions, indicating that prior consumption of ethanol attenuates the normal HGH response to insulin-induced hypoglycemia. It is suggested that ethanol may deplete catecholamine stores in the neurons of the ventromedial nucleus of the hypothalamus and may thereby impair secretion of growth hormone releasing factor. Under certain circumstances this could be of importance in the pathogenesis of alcohol-induced hypoglycemia.     

Spread of Streptococcus pneumoniae Serotype 8-ST63 Multidrug-Resistant Recombinant Clone,Spain

Since 2004, a total of 131 isolates of Streptococcus pneumoniae multidrug-resistant invasive serotype 8 have been detected in Spain. These isolates showed resistance to erythromycin, clindamycin, tetracycline, and ciprofloxacin. All isolates were obtained from adult patients and shared a common genotype (sequence type [ST]63; penicillin-binding protein 1a [pbp1a], pbp2b, and pbp2x gene profiles; ermB and tetM genes; and a ParC-S79F change). Sixty-eight isolates that required a ciprofloxacin MIC ≥16 μg/mL had additional gyrA gene changes. Serotype 8-ST63 pbp2x sequences were identical with those of antimicrobial drug–susceptible serotype 8-ST53 isolates. Serotype 8-ST63 pbp2b sequences were identical with those of the multidrug-resistant Sweden 15A-ST63 clone. Recombination between the capsular locus and flanking regions of an ST53 isolate (donor) and an ST63 pneumococcus (recipient) generated the novel 15A-ST63 clone. One recombination point was upstream of pbp2x and another was within pbp1a. A serotype 8-ST63 clone was identified as a cause of invasive disease in Spain.     

人冠状病毒HCoV-HKU1和HCoV-NL63双重实时荧光RT-PCR检测方法的研究

目的建立一种快速、灵敏、高效的人冠状病毒HKU1(HCoV-HKU1)和NL63(HCoV-NL63)双重实时荧光RTPCR检测方法。方法根据GENBANK数据库中HCoV-HKU1和HCoV-NL63的基因序列,利用BIOEDIT5.0软件进行序列比对分析,选择基因组的保守序列,并借助引物设计生物信息学软件,设计筛选出一套针对HCoV-HKU1和HCoV-NL63双重实时荧光PCR扩增的引物。从特异性、最低检测限、重复性等方面进行评估,建立了HCoV-HKU1和HCoV-NL63双重实时荧光PCR检测方法。结果分别以HCoV-HKU1和HCoV-NL63质粒为模板,HCoV-HKU1和HCoV-NL63双重实时荧光PCR方法的最低检测量分别为4.96×102 copies/ml和4.96×102 copies/ml。该方法针对其他病原微生物及人类基因组无反应信号,特异性好。4个梯度稀释质粒样本的4次重复检测Ct值变异系数均5%,重复性好。结论 HCoV-HKU1和HCoV-NL63双重实时荧光RT-PCR方法准确性好、灵敏度高、稳定性好,在临床鉴别诊断和口岸冠状病毒的监测中具有很好的应用前景。     

Glycation of human high density lipoprotein by methylglyoxal: Effect on HDL-paraoxonase activity

Objective

Methylglyoxal (MG), a reactive carbonyl compound formed primarily from triose phosphates, appears to be involved in the molecular mechanisms of diabetes, end-stage renal disease and neurodegenerative diseases. Methylglyoxal exerts several biological activities. Among these it promotes advanced glycation end products (AGEs), which are crucial in pathogenesis of human disease. Previous studies have demonstrated that MG reacts with proteins and compositional modifications reflect loss of biological activity. The aim of the study was to investigate the effect of in vitro MG-induced glycation on human high density lipoprotein (HDL) and on the activity of the enzyme paraoxonase-1 (PON1).

Methods

HDL was incubated in the absence or in the presence of MG (0.2 mmol/L and 1.0 mmol/L) (MG-HDL) for different times (3, 6, 24 h) at 37 ° C. We evaluated apoprotein compositional changes, in both control and MG treated HDL, using intrinsic fluorescence of tryptophan and monitoring the decrease of free amino groups. Furthermore we evaluated fluorescent advanced glycation end products (Ex = 370 nm, Em = 440 nm) and the activity of HDL-paraoxonase.

Results

We demonstrated that human HDL is susceptible to glycation by MG (0.2 mmol/L and 1 mmol/L). The decrease of free amino groups and of intrinsic fluorescence of tryptophan demonstrates HDL apoprotein modifications in HDL incubated with MG. The compositional changes are associated with a significant increase in fluorescent advanced glycation end products and with a significant decrease of paraoxonase-1 enzyme activity associated with the HDL surface.

Conclusions

HDL-associated paraoxonase is responsible for the anti-inflammatory and anti-oxidative properties of HDL and detoxification against homocysteine-thiolactone. Therefore, modifications of apoprotein composition and the decrease of paraoxonase-1 activity in MG-treated HDL could affect the protective effect exerted by HDL against oxidative damage and could contribute to complications in patients affected by diseases associated with aging and oxidative stress.