A New Pathway for Senescence Regulation

<正>Research concerning senescence has become a hotspot since the conception of‘cellular senescence’was put forward by Drs.Hayflick and Moorhead over five decades ago[1].Recently,a paper published in Science by Kang and colleagues,which this article aims to comment on,provides evidence of a new pathway involved in senescence[2].Senescence is a physiological and pathological process induced by numerous factors,during which cell growth ceases     

Post-translational modifications of protein in response to ionizing radiation

Based on central dogma of genetics, protein is the embodiment and executor of genetic function, post-translational modifications (PTMs) of protein are particularly important and involved in almost all aspects of cell biology and pathogenesis. Studies have shown that ionizing radiation (IR) alters gene expression much more profoundly and a broad variety of cell-process pathways, lots of proteins are modified and activated. Our understanding of the protein in response to ionizing radiation is steadily increasing. Among the various biological processes known to induce radioresistance, PTMs have attracted marked attention in recent years. The present review summarizes the latest knowledge about how PTMs response to ionizing radiation and pathway analysis were conducted. The data provided insights into biological effects of IR and contributing to the development of novel IR-based strategies.     

Lack of an Efficient Endoplasmic Reticulum-localized Recycling System Protects Peroxiredoxin IV from Hyperoxidation

Typical 2-Cys peroxiredoxins are required to remove hydrogen peroxide from several different cellular compartments. Their activity can be regulated by hyperoxidation and consequent inactivation of the active-site peroxidatic cysteine. Here we developed a simple assay to quantify the hyperoxidation of peroxiredoxins. Hyperoxidation of peroxiredoxins can only occur efficiently in the presence of a recycling system, usually involving thioredoxin and thioredoxin reductase. We demonstrate that there is a marked difference in the sensitivity of the endoplasmic reticulum-localized peroxiredoxin to hyperoxidation compared with either the cytosolic or mitochondrial enzymes. Each enzyme is equally sensitive to hyperoxidation in the presence of a robust recycling system. Our results demonstrate that peroxiredoxin IV recycling in the endoplasmic reticulum is much less efficient than in the cytosol or mitochondria, leading to the protection of peroxiredoxin IV from hyperoxidation.     

Comparison of label-free and GFP multiphoton imaging of hair follicle-associated pluripotent (HAP) stem cells in mouse whiskers

Hair-follicle-associated pluripotent (HAP) stem cells can differentiate into many cell types, including neurons and heart muscle cells, and have been shown to repair peripheral nerves and the spinal cord in mice. HAP stem cells can be obtained from each individual patient for regenerative medicine which overcomes problems with immune rejection. Previously, we have demonstrated that genetically-encoded protein markers such as GFP in transgenic mice can be used to visualize HAP stem cells in vivo by multiphoton tomography. Detection and visualization of stem cells in vivo without exogenous labels such as GFP would be important for human application. In the present report, we demonstrate label-free visualization of hair follicle stem cells in mouse whiskers by multiphoton tomography due to the intrinsic fluorophores such as NAD(P)H/flavins. We compared multiphoton tomography of GFP-labeled HAP stem cells and unlabeled stem cells in isolated mouse whiskers. We show that observation of HAP stem cells by label-free multiphoton tomography is comparable to detection using GFP-labeled stem cells. The results described here have important implications for detection and isolation of human HAP stem cells for regenerative medicine.     

建立以TK基因为标记将外源基因导入臭曲霉（Asper—gillus...

A new system for selection of transformed Aspergillus foetidus was reported. In this system, TK- A. foetidus which were constructed by homologous recombination of mutated TK gene of vaccinia virus with TK gene of A. foetidus were screened by adding BUdR in agar plates. Conditions for screen of TK+ A. foetidus strain, transformation of A. foetidus and selection of transformed TK- A. foetidus have been studied. By using this system, several transformed A. foetidus which contained HBsAg gene derived bf a promoter H8 cloned from genomic DNA of A. foetidus were isolated. It was demonstrated that HBsAg gene was integrated into the chromosome DNA of A. foetidus by Southern blot after many passages of spores. ELISA showed that HBsAg was positive in the growth medium (p/n = 20). The 22 nm particles which were very similar to the HBsAg particles in human serum were found in the growth medium by immunoelectromicroscope. Western blot also gave the specific bands. All these data showed that HBsAg gene was expressed in A. foetidus and the products were secreted into the growth medium. The selection system using TK gene as marker could generally be used to study the expression of foreign gene in A. foetidus.     

Role of microRNA-26a in cartilage injury and chondrocyte proliferation and apoptosis in rheumatoid arthritis rats by regulating expression of CTGF

This study is carried out to investigate the role of microRNA-26a (miR-26a) in cartilage injury and chondrocyte proliferation and apoptosis in rats with rheumatoid arthritis (RA) by regulating expression of CTGF. A rat model of RA induced by type II collagen was established. The rats were assigned into normal, RA, RA + mimics negative control (NC), and RA + miR-26a mimics groups, and the cells were classified into blank, mimics NC, and miR-26a mimics groups. The degree of secondary joint swelling and arthritis index, expression of miR-26a, pathological changes, proliferation and apoptosis of chondrocytes, and expression of CTGF, interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α, Bax, and Bcl-2 were also determined through a series of experiments. The targeting relationship between miR-26a and CTGF was verified. Initially, downregulated miR-26a was found in cartilage tissues and inflammatory articular chondrocytes of RA rats. In addition, CTGF was determined as a direct target gene of miR-26a, and upregulation of miR-26a inhibited CTGF expression in cartilage tissues of RA rats. Furthermore, upregulation of miR-26a reduced swelling and inflammation of joints, inhibited cartilage damage, apoptosis of chondrocytes, inflammatory injury, promotes proliferation, and inhibited apoptosis of inflammatory articular chondrocytes, which may be correlated with the targeting inhibition of CTGF expression. Collectively, the results demonstrate that upregulating the expression of miR-26a could attenuate cartilage injury, stimulate the proliferation, and inhibit apoptosis of chondrocytes in RA rats.     

Epigenetic Regulation of Elf5 Is Associated with Epithelial-Mesenchymal Transition in Urothelial Cancer

E74-like factor 5 (Elf5) has been associated with tumor suppression in breast cancer. However, its role in urothelial cancer (UC) is completely unknown. Immunohistochemistry (IHC) and methylation specific PCR (MSP) were done to detect Elf5 expression level and its promoter methylation. Results revealed that low expression of Elf5 on protein and mRNA levels were associated with tumor progression, early relapse and poor survival. In vitro, down-regulation of Elf5 can increase epithelial-mesenchymal transition (EMT). Aberrant Elf5 methylation was identified as major mechanism for Elf5 gene silence. Accordingly, restoration of Elf5 by infection or demethylating treatment effectively reversed EMT processes. In conclusion, we identified Elf5 as a novel biomarker of UC on several biological levels and established a causative link between Elf5 and EMT in UC.