Mitochondrial aldehyde dehydrogenase(ALDH2)rescues cardiac contractile dysfunction in an APP/PS1 murine model of Alzheimer's disease via inhibition of ACSL4-dependent ferroptosis

Alzheimer's disease(AD)is associated with high incidence of cardiovascular events but the mechanism remains elusive.Our previous study reveals a tight correlati...     

202例烧伤后瘢痕治疗的临床体会

目的探讨烧伤后瘢痕的治疗、术后恢复情况及烧伤后瘢痕的防治策略,为今后的瘢痕治疗提供更好的依据。 方法回顾性分析新疆维吾尔自治区人民医院烧伤、创面修复外科2007年1月至2017年2月间收治的202例烧伤后瘢痕手术患者的病例资料,根据患者瘢痕的不同部位、不同性质选择相应的手术方法。术后瘢痕组织送病理检查,统计上述患者住院时间、手术费用、术后病理结果、治疗效果及术后随访情况。 结果本组患者住院期间无死亡,无严重并发症出现,平均住院时间(14.50±6.04) d,平均手术费用(1.59±0.37)万元,术后瘢痕部位均得到适当松解,创面均愈合良好出院。术后病理提示发生恶变22例(10.89%),其中高分化鳞癌15例(7.43%),恶性黑色素瘤2例(0.99%),基底细胞癌1例(0.50%),梭形细胞癌1例(0.50%),低分化鳞癌1例(0.50%),局部恶变重度异性增生2例(0.99%)。术后随访时间中位数10个月,随访过程中复发3例。 结论目前手术仍是治疗烧伤后瘢痕挛缩的较为有效的方法之一,其防治较为复杂,建议严格把握手术时机及手术适应证,使用个体化治疗方案。     

融合脉诊信息的女性移动中医健康管理平台的研制

目的：构建融合脉诊信息的女性中医管理平台,方便女性对月经周期相关的健康问题进行中医健康状态辨识与调理。方法：采用云计算技术,以中医电子健康档案（EHR）和知识库为核心,根据女性月经周期相关健康问题的特点设计中医健康信息采集问卷,并融入中医脉诊手环采集的数据,知识库可辅助健康管理方案的制定,设计医生PC端与患者移动APP结合的平台框架。结果：平台有利于实现较客观的中医问诊和脉诊信息的采集与长期连续监测,并可辅助女性月经问题的健康状态辨识和健康调理计划的制定。结论：研究构建的平台对女性月经问题中医健康管理的实施具有较好的可操作性和实用性。     

An eight-lncRNA signature predicts survival of breast cancer patients: a comprehensive study based on weighted gene co-expression network analysis and competing endogenous RNA network

Breast Cancer Research and Treatment - To identify a lncRNA signature to predict survival of breast cancer (BRCA) patients. A total of 1222 BRCA case and control datasets were downloaded from the...     

Prevention of lipopolysaccharide-induced injury by 3,5-dicaffeoylquinic acid in endothelial cells

Aim： To investigate the effect of 3,5-dicaffeoylquinic acid （3,5-diCQA） on lipopolysaccharide （LPS）-induced injury in human dermal microvascular endothelial cells （HMEC-1）. Methods： The anti-oxidant effect was detected using the malondialdehyde （MDA） assay in a rat liver microsome model of lipid peroxidation. Cell viability was analyzed using the 3-（4,5-dimethylthiazol-2-yl）-2,5 diphenyltetrazolium bromide assay. Cell lipid peroxide injury was measured by lactate dehydrogenase （LDH） release. Apoptotic cells were detected by flow cytometry, and confirmed by DNA fragmentation analysis. Caspase-3 activity was measured using a specific assay kit. The level of intracellular reactive oxygen species （ROS） was determined by flow cytometry with a 2,7-dichlorodihydro-fluorescein diacetate fluorescence probe. Results： The exposure of microsomes to ascorbate-Fe^2＋ resulted in lipoperoxidation according to an increase in the level of MDA. MDA formation decreased in a dose-dependent manner on treatment with 5, 10, or 50 μmol/L 3,5-diCQA. Treatment with LPS for 16 h resulted in a 60% decrease in cell viability and an increase in LDH release from 47.6% to 61.5%. DNA laddering was observed by agarose gel electrophoresis. The level of apoptotic cells peaked at 27% after treatment with LPS for 12 h. Following treatment with LPS for 12 h, intracellular ROS and caspase-3 activity increased. Pretreatment with 3,5-diCQA at 5, 10, or 50 μmol/L for 1 h attenuated LPS-mediated endothelial cell injury. The anti-apoptotic action of 3,5-diCQA was partially dependent on its capacity for anti-oxidation and the suppression of caspase-3 activity. Conclusion： 3,5-diCQA displays anti-oxidative and anti-apoptotic activity in HMEC-1 due to scavenging of intracellular ROS induced by LPS, and the suppression of caspase-3 activity.     

Smooth-Muscle-Like Cells Derived from Human Embryonic Stem Cells Support and Augment Cord-Like Structures In Vitro

Engineering vascularized tissue is crucial for its successful implantation, survival, and integration with the host tissue. Vascular smooth muscle cells (v-SMCs) provide physical support to the vasculature and aid in maintaining endothelial viability. In this study, we show an efficient derivation of v-SMCs from human embryonic stem cells (hESCs), and demonstrate their functionality and ability to support the vasculature in vitro. Human ESCs were differentiated in monolayers and supplemented with platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta 1 (TGF-β1). Human ESC-derived smooth-muscle-like cells (SMLCs) were found to highly express specific smooth muscle cell (SMC) markers—including α-smooth muscle actin, calponin, SM22, and smooth muscle myosin heavy chain—to produce and secrete fibronectin and collagen, and to contract in response to carbachol. In vitro tubulogenesis assays revealed that these hESC-derived SMLCs interacted with human endothelial progenitor cell (EPCs) to form longer and thicker cord-like structures in vitro. We have demonstrated a simple protocol for the efficient derivation of highly purified SMLCs from hESCs. These in vitro functional SMLCs interacted with EPCs to support and augment capillary-like structures (CLSs), demonstrating the potential of hESCs as a cell source for therapeutic vascular tissue engineering.     

Cancer/testis antigen SSX2 enhances invasiveness in MCF-7 cells by repressing ERα signaling

Cancer/testis antigen (CTA) SSX2, which is silent in most normal adult tissues and expressed in various malignant tumors, has been identified for decades. Expression of SSX in tumors has been associated with advanced stages and worse patient prognosis. However, little is known about its role in breast cancer. The SSX2 expression plasmid constructed was stably transfected into the breast cancer cell line MCF-7. The influence of SSX2 on MCF-7 cells was assessed using MTT assay, flow cytometry, transwell invasion assay and in vivo tumorigenicity assay. A comparative proteomic approach was performed to identify and clarify the underlying molecular mechanisms. SSX2 expression was more pronounced in ERα-negative breast cancer cells compared with the positive ones. Overexpression of SSX2 induced cell growth and prompted cell invasion. Both ERα and E-cadherin expression were suppressed in the SSX2 overexpressing MCF-7 cells. Eleven known proteins were identified with significant differential expression. Among these, five were decreased, while other six were increased in the SSX2 overexpressing MCF-7 cells. These results suggested SSX2 may enhance invasiveness in MCF-7 cells both in vivo and in vitro. The regulation of ERα signaling by target proteins of SSX2 may explain the metastatic potential of breast cancer cells.     

Life-long suppression of growth hormone-insulin-like growth factor I activity in genetically altered rats could prevent age-related renal damage

To determine whether life-long reduction in the GH/IGF-I activity could be renoprotective and attenuate renal damage, we examined the kidneys of transgenic strain of rats whose GH gene was suppressed by an antisense GH transgene. Male rats homozygote for the transgene (tg/tg) had a reduced number of pituitary GH-secreting cells, and 53% less plasma concentration of IGF-I, compared with wild-type (wt/wt) rats at 6 months of age. We compared the kidneys obtained from male wild-type young (6 months) and old (24 months) rats with male homozygote transgenic young (6 months) and old (24 months) rats. The wild-type rats showed features of renal damage as they grew older, including glomerulosclerosis (higher sclerosis index at 24 months; P<0.0001), tubulointerstitial widening (increased interstitial volume at 24 months; P<0.0001), and presence of phenotypically altered myofibroblasts and increased accumulation of collagens. Life-long suppression of GH/IGF-I activity resulted in prevention of age-associated renal diseases in homozygote transgenic rats at 24 months (sclerosis index: 1.65+/-0.11 in wild-type vs. 0.463+/-0.061 in transgenic rats; interstitial volume: 34.2+/-0.82 in wild-type vs. 12.8+/-0.32 in homozygote transgenic rats at 24 months; P<0.0001). Such reno-protective effects in transgenic rats were associated with decreased renal accumulation of ED-1-positive macrophages, and less renal expression of pro-fibrogenic factors, including connective tissue growth factor and heat shock protein 47. Our in vivo genetic manipulation study provides direct evidence of reno-protective effects of life-long suppression of GH/IGF-I system, by reducing renal infiltration of inflammatory cells, and by suppressing the synthesis of profibrogenic factors and accumulation of extracellular matrix protein.     

Controlled release of PEI/DNA complexes from PLGA microspheres as a potent delivery system to enhance immune response to HIV vaccine DNA prime/MVA boost regime.

A novel approach involving the preparation of biodegradable PLGA microspheres containing entrapping complexes of DNA and polyethylenimine was developed to improve the delivery of DNA into antigen-presenting cells after intramuscular injection. Compared to the traditional biodegradable microspheres which release naked DNA, these microspheres released intact and penetrative PEI/DNA complexes over a period of 2 weeks in vitro. In addition, the DNA was not degraded during encapsulation in the PLGA microspheres, owing to the protection of polyethylenimine. After i.m. immunization, the microspheres induced significantly enhanced serum antibody responses 2-3 orders of magnitude greater than naked DNA. Additionally, in contrast to naked DNA, the microspheres induced potent CTL responses at a low dose.