Notch配体Delta-like-1和Jagged-1 mRNA在骨髓增生异常综合征患者骨髓间充质干细胞中表达研究

本研究检测骨髓增生异常综合征（MDS）患者骨髓间充质干细胞Notch信号通路配体Delta-like-1和Jagged-1 mRNA表达水平,探讨其与MDS发病的关系。采用实时荧光定量聚合酶链反应检测38例M DS患者和16例正常对照者骨髓间充质干细胞中Delta-like-1和Jagged-1的基因表达水平。结果表明,MDS患者的Delta-like-1和Jagged-1 mRNA表达水平较正常对照组均明显升高（P〈0.05）。在WHO分组中,RA/RARS、RCMD及RAEB组Delta-like-1的表达量均高于正常对照组（P〈0.05）,RARB组Jagged-1与正常对照组差异有显著性（P〈0.05）。Delta-like-1表达与骨髓原始细胞比例有显著相关性（r=0.502,P〈0.05）。伴染色体异常MDS组Deltalike-1和Jagged-1 mRNA表达水平较无染色体异常MDS组明显升高（P〈0.05）。在IPSS分组中,较高危组Deltalike-1表达显著高于较低危组（P〈0.01）,而Jagged-1表达在两组间无统计学差异（P〉0.05）。结论：MSC中Delta-like-1和Jagged-1高表达可能参与了M DS的发病过程。     

自体骨髓单个核细胞移植联合益气活血中药治疗下肢动脉缺血性疾病23例

目的:探讨自体骨髓单个核细胞移植与中药合用对下肢缺血的治疗作用.方法:治疗对象为23例严重下肢缺血患者.术前用集落细胞刺激因子使患者骨髓处于增生活跃状态,抽取骨髓液后分离单个核细胞,细胞总量达到1×109以上.移植采用缺血肢体多点注射.移植后1 d起服益气活血中药.观察患者手术前后肢体疼痛、冷感评分、踝/肱指数(ankle/brachial index,ABI)以及溃疡创面情况.结果:治疗后患肢疼痛及冷感评分逐渐降低,治疗1个月后与治疗前比较有显著性差异(P＜0.05);ABI在治疗后逐渐升高,治疗后1个月平均升高了0.15.而足部溃疡面积改善不明显.结论:自体骨髓单个核细胞移植结合中药治疗可以迅速改善下肢缺血患者的疼痛及冷感,能有效改善局部的血液循环.     

Lactobacillus plantarum GKM3 Promotes Longevity,Memory Retention,and Reduces Brain Oxidation Stress in SAMP8 Mice

(1) Background: An age-related cognitive decline is commonly affecting the life of elderly with symptoms involved in progressive impairments to memory and learning. It has been proposed that probiotics could modulate age-related neurological disorders via the gut–brain axis. (2) Methods: To investigate the anti-aging effect of probiotic Lactobacillus plantarum GKM3, both survival tests and cognitive experiments were conducted in the SAMP8 mice model. The six-month-old SAMP8 (n = 20 in each gender) were fed with probiotic GKM3 at a dosage of 5.1 × 10⁹ and 1.0 × 10⁹ cfu/ kg B.W./day until their natural death. Then, the life span was investigated. Three-month-old SAMP8 (n = 10 in each gender) were administered GKM3 for 14 weeks. Then, the behavior tests and oxidation parameters were recorded. (3) Results: GKM3 groups showed significantly increased latency in the passive avoidance test and time of successful avoidance in the active avoidance test. The TBARS and 8-OHdG from mice brains also showed a significant reduction in the groups treated with GKM3. In addition, lower accumulation of the amyloid-β protein was found in SAMP8 mice brains with the supplement of GKM3. (4) Conclusions: These results indicated that L. plantarum GKM3 delayed the process of aging, alleviated age-related cognitive impairment, and reduced oxidative stress.     

Renoprotective Effect of Pediococcus acidilactici GKA4 on Cisplatin-Induced Acute Kidney Injury by Mitigating Inflammation and Oxidative Stress and Regulating the MAPK,AMPK/SIRT1/NF-κB,and PI3K/AKT Pathways

Acute kidney injury (AKI) describes a sudden loss of kidney function and is associated with a high mortality. Pediococcus acidilactici is a potent producer of bacteriocin and inhibits the growth of pathogens during fermentation and food storage; it has been used in the food industry for many years. In this study, the potential of P. acidilactici GKA4 (GKA4) to ameliorate AKI was investigated using a cisplatin-induced animal model. First, mice were given oral GKA4 for ten days and intraperitoneally injected with cisplatin on the seventh day to create an AKI mode. GKA4 attenuated renal histopathological alterations, serum biomarkers, the levels of inflammatory mediators, and lipid oxidation in cisplatin-induced nephrotoxicity. Moreover, GKA4 significantly decreased the expression of inflammation-related proteins and mitogen-activated protein kinase (MAPK) in kidney tissues. Eventually, GKA4 also increased the levels of related antioxidant enzymes and pathways. Consistently, sirtuin 1 (SIRT1) upregulated the level of autophagy-related proteins (LC3B, p62, and Beclin1). Further studies are needed to check our results and advance our knowledge of the mechanism whereby PI3K inhibition (wortmannin) reverses the effect of GKA4 on cisplatin-treated AKI. Taken together, GKA4 provides a therapeutic target with promising clinical potential after cisplatin treatment by reducing oxidative stress and inflammation via the MAPK, AMP-activated protein kinase (AMPK)/SIRT1/nuclear factor kappa B (NF-κB), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) axes.     

Oral anticoagulation use by patients with atrial fibrillation in Germany. Adherence to guidelines, causes of anticoagulation under-use and its clinical outcomes, based on claims-data of 183,448 patients

Atrial fibrillation (AF) is the most common significant cardiac rhythm disorder. Oral anticoagulation (OAC) is recommended by guidelines in the presence of a moderate to high risk of stroke. Based on an analysis of claims-based data, the aim of this contribution is to quantify the stroke-risk dependent OAC utilisation profile of German AF patients as well as the possible causes and the associated clinical outcomes of OAC under-use. Our data set was derived from two large mandatory German medical insurance funds. Risk stratification of patients was based on the CHADS2-score and the CHA2DS2-VASc-score. Two different scenarios were constructed to deal with factors potentially disfavouring OAC use. Causes of OAC under-use and its clinical consequences were analysed using multivariate analysis. Observation year was 2008. A total of 183,448 AF patients met the inclusion criteria. This represents an AF prevalence of 2.21%. The average CHADS2-score was 2.8 (CHA2DS2-VASc-score: 4.3). On between 40.5 and 48.7% of the observed patient-days, there was no antithrombotic protection by OAC, other anticoagulants or aspirin. Older female patients with a high number of comorbidities had a higher risk of OAC under-use. Patients who had already experienced a thromboembolic event had a lower risk of OAC under-use. In the observation year, 3,367 patients experienced a stroke (incidence rate 1.8%). In our multi-level Poisson random effects estimate, OAC use decreases the stroke rate by almost 80% (IRR 0.236). In conclusion, OAC under-use is widespread in the German market. It is associated with severe clinical consequences.     

骨髓增生异常综合征患者骨髓间充质干细胞成骨分化功能的研究

目的:研究骨髓增生异常综合征(myelodysplastic syndromes,MDS)患者骨髓间充质干细胞(bone marrow mesenchymal stem cells,BM M SC)成骨分化功能及其在M DS发病机制中的作用。方法:分离培养M DS患者及正常人的BMMSC,并在体外诱导其向成骨细胞分化;荧光定量PCR法检测BMMSC成骨分化转录因子Runt相关转录因子2(RUNX2)和Osterix的mRNA表达水平,以及成骨诱导分化第7、14、21天成骨相关基因碱性磷酸酶(alkaline phosphatase,ALP)、骨涎蛋白(Bone sialoprotein,BSP)、骨桥素(Osteopontin,OPN)和骨钙素(osteocalcin,OCN)的mRNA表达情况;碱性磷酸酶活性检测试剂盒检测成骨诱导第3、7、10天ALP活性;茜素红染色观察诱导分化第21天钙结节形成情况。结果:低危MDS组BMMSC成骨分化转录因子RUNX2和Osterix mRNA表达水平较正常对照组均明显降低(P0.05),成骨诱导分化第3天低危MDS组ALP活性水平明显低于正常对照组(P0.05),成骨诱导分化第21天茜素红染色显示,低危MDS组钙结节含量也明显少于正常对照组(P0.05)。在成骨诱导分化不同时间点成骨早期标志ALP、BSP和后期标志OPN、OCN在低危MDS组中的mRNA表达水平也显著降低(P0.05),而高危MDS组在一系列成骨分化检测指标上与正常对照组之间没有统计学差异。结论:低危MDS组BM MSC成骨分化能力明显减弱,而高危M DS组相对正常。异常的成骨分化功能可能是造成低危组M DS骨髓支持造血能力减弱的重要原因。