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101.
An Yun Guo Kwok Sui Leung Parco Ming Fai Siu Jiang Hui Qin Simon Kwoon Ho Chow Ling Qin Chi Yu Li Wing Hoi Cheung 《Experimental Animals》2015,64(4):425-433
Sarcopenia is an age-related systemic syndrome with progressive deterioration in skeletal
muscle functions and loss in mass. Although the senescence-accelerated mouse P8 (SAMP8)
was reported valid for muscular ageing research, there was no report on the details such
as sarcopenia onset time. Therefore, this study was to investigate the change of muscle
mass, structure and functions during the development of sarcopenia. Besides the average
life span, muscle mass, structural and functional measurements were also studied. Male
SAMP8 animals were examined at month 6, 7, 8, 9, and 10, in which the right gastrocnemius
was isolated and tested for ex vivo contractile properties and fatigability while the
contralateral one was harvested for muscle fiber cross-sectional area (FCSA) and typing
assessments. Results showed that the peak of muscle mass appeared at month 7 and the onset
of contractility decline was observed from month 8. Compared with month 8, most of the
functional parameters at month 10 decreased significantly. Structurally, muscle fiber type
IIA made up the largest proportion of the gastrocnemius, and the fiber size was found to
peak at month 8. Based on the altered muscle mass, structural and functional outcomes, it
was concluded that the onset of sarcopenia in SAMP8 animals was at month 8. SAMP8 animals
at month 8 should be at pre-sarcopenia stage while month 10 at sarcopenia stage. It is
confirmed that SAMP8 mouse can be used in sarcopenia research with established time line
in this study. 相似文献
102.
103.
In eukaryotic cells, repair of DNA double-strand breaks (DSBs) by the nonhomologous end-joining (NHEJ) pathway is critical for genome stability. In contrast to the complex eukaryotic repair system, bacterial NHEJ apparatus consists of only two proteins, Ku and a multifunctional DNA ligase (LigD), whose functional mechanism has not been fully clarified. We show here for the first time that Sir2 is involved in the mycobacterial NHEJ repair pathway. Here, using tandem affinity purification (TAP) screening, we have identified an NAD-dependent deacetylase in mycobacteria which is a homologue of the eukaryotic Sir2 protein and interacts directly with Ku. Results from an in vitro glutathione S-transferase (GST) pull-down assay suggest that Sir2 interacts directly with LigD. Plasmid-based end-joining assays revealed that the efficiency of DSB repair in a sir2 deletion mutant was reduced 2-fold. Moreover, the Δsir2 strain was about 10-fold more sensitive to ionizing radiation (IR) in the stationary phase than the wild-type. Our results suggest that Sir2 may function closely together with Ku and LigD in the nonhomologous end-joining pathway in mycobacteria. 相似文献
104.
Zhang J Lian Q Zhu G Zhou F Sui L Tan C Mutalif RA Navasankari R Zhang Y Tse HF Stewart CL Colman A 《Cell Stem Cell》2011,8(1):31-45
The segmental premature aging disease Hutchinson-Gilford Progeria syndrome (HGPS) is caused by a truncated and farnesylated form of Lamin A called progerin. HGPS affects mesenchymal lineages, including the skeletal system, dermis, and vascular smooth muscle (VSMC). To understand the underlying molecular pathology of HGPS, we derived induced pluripotent stem cells (iPSCs) from HGPS dermal fibroblasts. The iPSCs were differentiated into neural progenitors, endothelial cells, fibroblasts, VSMCs, and mesenchymal stem cells (MSCs). Progerin levels were highest in MSCs, VSMCs, and fibroblasts, in that order, with these lineages displaying increased DNA damage, nuclear abnormalities, and HGPS-VSMC accumulating numerous calponin-staining inclusion bodies. Both HGPS-MSC and -VSMC viability was compromised by stress and hypoxia in vitro and in vivo (MSC). Because MSCs reside in low oxygen niches in vivo, we propose that, in HGPS, this causes additional depletion of the MSC pool responsible for replacing differentiated cells lost to progerin toxicity. 相似文献
105.
Advances in stem cell research and recent work on clinical trials employing stem cells have heightened the prospect of stem cell applications in regenerative medicine. The eventual clinical application of stem cells will require transforming cell production from laboratory practices to robust processes. Most stem cell applications will require extensive ex vivo handling of cells, from isolation, cultivation, and directed differentiation to product cell separation, cell derivation, and final formulation. Some applications require large quantities of cells in each defined batch for clinical use in multiple patients; others may be for autologous use and require only small-scale operations. All share a common requirement: the production must be robust and generate cell products of consistent quality. Unlike the established manufacturing process of recombinant protein biologics, stem cell applications will likely see greater variability in their cell source and more fluctuations in product quality. Nevertheless, in devising stem cell-based bioprocesses, much insight could be gained from the manufacturing of biological materials, including recombinant proteins and anti-viral vaccines. The key to process robustness is thus not only the control of traditional process chemical and physical variables, but also the sustenance of cells in the desired potency or differentiation state through controlling non-traditional variables, such as signaling pathway modulators. 相似文献
106.
Micro- and nanoparticulate drug-delivery systems (DDSs) play a significant role in formulation sciences. Most particulate DDSs are scaffold-free, although some particles are encapsulated inside other biomaterials for controlled release. Despite rapid progress in recent years, challenges still remain in controlling the homogenicity of micro-/nanoparticles, especially for two crucial factors in particulate DDSs: the size and shape of the particles. Recent approaches make use of microfabrication techniques to generate micro-/nanoparticles with highly controllable architectures free of scaffolds. This review presents an overview of a burgeoning field of DDSs, which can potentially overcome some drawbacks of conventional techniques for particle fabrication and offer better control of particulate DDSs. 相似文献
107.
Timmers L Lim SK Hoefer IE Arslan F Lai RC van Oorschot AA Goumans MJ Strijder C Sze SK Choo A Piek JJ Doevendans PA Pasterkamp G de Kleijn DP 《Stem cell research》2011,6(3):206-214
Recent studies suggest that the therapeutic effects of stem cell transplantation following myocardial infarction (MI) are mediated by paracrine factors. One of the main goals in the treatment of ischemic heart disease is to stimulate vascular repair mechanisms. Here, we sought to explore the therapeutic angiogenic potential of mesenchymal stem cell (MSC) secretions. Human MSC secretions were collected as conditioned medium (MSC-CM) using a clinically compliant protocol. Based on proteomic and pathway analysis of MSC-CM, an in vitro assay of HUVEC spheroids was performed identifying the angiogenic properties of MSC-CM. Subsequently, pigs were subjected to surgical left circumflex coronary artery ligation and randomized to intravenous MSC-CM treatment or non-CM (NCM) treatment for 7 days. Three weeks after MI, myocardial capillary density was higher in pigs treated with MSC-CM (645 ± 114 vs 981 ± 55 capillaries/mm(2); P = 0.021), which was accompanied by reduced myocardial infarct size and preserved systolic and diastolic performance. Intravenous MSC-CM treatment after myocardial infarction increases capillary density and preserves cardiac function, probably by increasing myocardial perfusion. 相似文献
108.
Long noncoding RNAs(IncRNAs)act as essential regulators of various diseases.However,the func-tions of IncRNAs in sepsis-induced acute lung injury(SALI)remain un... 相似文献
109.
Qianying Hu Na Zhang Tingting Sui Guanlin Li Zhiyao Wang Mingyue Liu Xiaojuan Zhu Baiqu Huang Jun Lu Zhanjun Li Yu Zhang 《The EMBO journal》2023,42(1)
Hutchinson‐Gilford progeria syndrome (HGPS) is a lethal premature aging disorder without an effective therapeutic regimen. Because of their targetability and influence on gene expression, microRNAs (miRNAs) are attractive therapeutic tools to treat diseases. Here we identified that hsa‐miR‐59 (miR‐59) was markedly upregulated in HGPS patient cells and in multiple tissues of an HGPS mouse model (Lmna G609G/G609G ), which disturbed the interaction between RNAPII and TFIIH, resulting in abnormal expression of cell cycle genes by targeting high‐mobility group A family HMGA1 and HMGA2. Functional inhibition of miR‐59 alleviated the cellular senescence phenotype of HGPS cells. Treatment with AAV9‐mediated anti‐miR‐59 reduced fibrosis in the quadriceps muscle, heart, and aorta, suppressed epidermal thinning and dermal fat loss, and yielded a 25.5% increase in longevity of Lmna G609G/G609G mice. These results identify a new strategy for the treatment of HGPS and provide insight into the etiology of HGPS disease. 相似文献
110.
原位椭圆偏振术研究牛血清清蛋白在固/液界面的吸附 总被引:1,自引:0,他引:1
用原位椭圆偏振术系统研究了硅片表面因素及缓冲液环境因素对牛血清清蛋白在固/液界面吸附的影响。在生理条件下,疏水表面与亲水表面相比BSA吸附量较大。随着硅片表面电荷密度增加,BSA吸附量增加。BSA吸附量当体溶液pH值等于BSA等电点时达到最大。而随着体溶液离子强度增加,BSA吸附量亦上升。实验结果提示:除了熵驱动作用之外,硅片表面与BSA分子及BSA分子之间的静电作用在BSA吸附中起着十分重要的作用。 相似文献