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Cao Y.,Beijing Institute of Radiation Medicine | Zhang L.,Beijing Institute of Radiation Medicine | Zhang L.,Dalian Medical University
Cellular and Molecular Life Sciences | Year: 2013

Since being discovered and intensively studied for over a decade, Smad ubiquitylation regulatory factor-1 (Smurf1) has been linked with several important biological pathways, including the bone morphogenetic protein pathway, the non-canonical Wnt pathway, and the mitogen-activated protein kinase pathway. Multiple functions of this ubiquitin ligase have been discovered in cell growth and morphogenesis, cell migration, cell polarity, and autophagy. Smurf1 is related to physiological manifestations in terms of age-dependent deficiency in bone formation and invasion of tumor cells. Smurf1-knockout mice have a significant phenotype in the skeletal system and considerable manifestations during embryonic development and neural outgrowth. In depth studying of Smurf1 will help us to understand the etiopathological mechanisms of related disorders. Here, we will summarize historical and recent studies on Smurf1, and discuss the E3 ligase-dependent and -independent functions of Smurf1. Moreover, intracellular regulations of Smurf1 and related physiological phenotypes will be described in this review. © 2012 Springer Basel.

To identify susceptibility variants for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we conducted a genome-wide association study by genotyping 440,794 SNPs in 355 chronic HBV carriers with HCC and 360 chronic HBV carriers without HCC, all of Chinese ancestry. We identified one intronic SNP (rs17401966) in KIF1B on chromosome 1p36.22 that was highly associated with HBV-related HCC and confirmed this association in five additional independent samples, consisting of 1,962 individuals with HCC, 1,430 control subjects and 159 family trios. Across the six studies, the association with rs17401966 was highly statistically significant (joint odds ratio = 0.61, P = 1.7 x 10(-18)). In addition to KIF1B, the association region tagged two other plausible causative genes, UBE4B and PGD. Our findings provide evidence that the 1p36.22 locus confers susceptibility to HBV-related HCC, and suggest that KIF1B-, UBE4B- or PGD-related pathways might be involved in the pathogenesis of this malignancy.

Li L.,Beijing Institute of Radiation Medicine | Li W.,The Texas Institute | Li W.,University of Texas Health Science Center at Houston
Pharmacology and Therapeutics | Year: 2015

The epithelial-mesenchymal transition (EMT) is a developmental process that is important for embryogenesis, wound healing, organ fibrosis, and cancer metastasis. Cancer-associated EMT is not a simple process to acquire migration and invasion ability, but a complicated and comprehensive reprogramming, involved in metabolism, epigenetics and differentiation, through which differentiated epithelial cancer cells reverse to an undifferentiated state, not only expressing stem cell markers, but also acquiring stem cell-like functions. Here we review recent ideas and discoveries that illustrate the links among metabolism, epigenetics, and dedifferentiation during EMT, with special emphasis on the primary driving force and ultimate goal of cancer-associated EMT - of the energy and for the energy. Furthermore, we highlight on the specificity of epigenetic modification during EMT, with an aim to explain how the repression of epithelial genes and activation of mesenchymal genes are coordinated simultaneously through EMT. Finally, we provide an outlook on anti-EMT therapeutic approach on epigenetic and metabolic levels, and discuss its potential for clinical application. © 2015 Elsevier Inc. All rights reserved.

Ding L.,Beijing Institute of Radiation Medicine
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2013

This study was purposed to investigate the immune reconstitution of T-cells in patients who received haploidentical hematopoietic stem cell transplantation (hiHSCT). The peripheral blood was harvested from 22 patients before transplantation and at month 1, 3, 6 after hiHSCT. The proportions of T lymphocyte subtypes including CD3(+), CD4(+), CD8(+), CD45RO(+), and CD45RA(+)CD62L(+) were analyzed by flow cytometry, followed by the calculation of T cell numbers according to the amounts of peripheral blood leukocytes. Adenosine triphosphate (ATP) value in CD4(+) T cells was measured by ImmuKnow method to evaluate the function of lymphocytes. The results showed that the CD3(+) cell absolute value before transplantation was 833.75 ± 359.84/μl, but those values at month 1, 3, 6 after transplantation were 318.87 ± 266.71/μl, 1006.76 ± 512.32/μl and 1296.38 ± 958.77/μl respectively. The CD4(+) cell absolute value before transplantation was 336.99 ± 211.11/μl, but such values at month 1, 3, 6 after transplantation were 45.89 ± 44.21/μl, 142.97 ± 114.85/μl, and 181.78 ± 120.61/μl respectively. The CD8(+) cell absolute value before transplantation was 430.21 ± 159.48/μl, but those values at month 1, 3, 6 after transplantation were 230.44 ± 195.89/μl, 621.64 ± 318.83/μl, and 823.07 ± 633.55/μl respectively. The CD4(+)CD45RO(+) memory T cell absolute value before transplantation was 227.44 ± 73.34/μl, but such values at month 1, 3, 6 after transplantation were 43.47 ± 43.40/μl, 138.69 ± 110.17/μl, 147.73 ± 82.94/μl respectively. The CD8(+)CD45RO(+) memory T cell absolute value before transplantation was 212.70 ± 98.48/μl, but such values at month 1, 3, 6 after transplantation were 184.76 ± 168.65/μl, 445.90 ± 252.50/μl, 519.80 ± 475.53/μl respectively. CD4(+)CD45RA(+)CD62L(+) naive T cell number before transplantation was 68.94 ± 59.74/μl, but such cell numbers at month 1, 3, 6 after transplantation decreased to 2.44 ± 2.93/μl, 3.14 ± 3.48/μl, 23.22 ± 38.38/μl respectively. The CD8(+)CD45RA(+)CD62L(+) naive T cell absolute value before transplantation was 124.82 ± 60.95/μl, but those values at month 1, 3, 6 decreased to 19.37 ± 17.71/μl, 76.63 ± 50.85/μl, and 114.49 ± 174.29/μl respectively. The ATP value in CD4(+) T cells decreased to 210.19 ± 119.37 ng/ml at month 1 after transplantation and increased to 280.62 ± 110.03 ng/ml at month 3, and 357.28 ± 76.18 ng/ml at month 6 after transplantation. It is concluded that CD8(+) memory T cell reconstruction contributes critically to T cell recovery early after hiHSCT, while the thymic output function remains low. However, T cell function recovers to normal range at month 3 after transplantation.

Shi Y.,Baylor College of Medicine | Xu P.,Beijing Institute of Radiation Medicine | Qin J.,Baylor College of Medicine
Molecular and Cellular Proteomics | Year: 2011

Ubiquitin (Ub) is a small and highly conserved protein that can covalently modify protein substrates. Ubiquitination is one of the major post-translational modifications that regulate a broad spectrum of cellular functions. The advancement of mass spectrometers as well as the development of new affinity purification tools has greatly expedited proteome-wide analysis of several post-translational modifications (e.g. phosphorylation, glycosylation, and acetylation). In contrast, large-scale profiling of lysine ubiquitination remains a challenge. Most recently, new Ub affinity reagents such as Ub remnant antibody and tandem Ub binding domains have been developed, allowing for relatively large-scale detection of several hundreds of lysine ubiquitination events in human cells. Here we review different strategies for the identification of ubiquitination site and discuss several issues associated with data analysis. We suggest that careful interpretation and orthogonal confirmation of MS spectra is necessary to minimize false positive assignments by automatic searching algorithms. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

Xiao Y.,Beijing Institute of Radiation Medicine
Journal of integrative medicine | Year: 2013

To evaluate whether Shenfu injection (SFI) protects against cardiac myocyte injury induced by Fupian injection (FPI) in vitro. H9c2 cells were separately treated with FPI, Renshen injection (RSI) and SFI. Cell viability, lactate dehydrogenase (LDH) release, spontaneous beating rate of primative cardical cells, caspase-3/7 activity, cell apoptosis, and cytochrome P450 2J3 (CYP2J3) mRNA expression were analyzed. The viability of H9c2 cells treated with SFI (37 and 75 mg/mL) was significantly higher than that of H9c2 cells treated with FPI (25 and 50 mg/mL) (P<0.05, P<0.01, respectively). LDH activity of H9c2 cells treated with SFI (75 mg/mL) was significantly decreased (P<0.01) compared with that of H9c2 cells treated with FPI (50 mg/mL). SFI (150 mg/mL) significantly attenuated FPI (100 mg/mL)-induced spontaneous beating rate decrease in primary myocardial cells after 4-hour treatment. Compared with FPI (12 and 25 mg/mL), SFI (18 and 37 mg/mL) treatment could effectively reverse the change of caspase-3/7 activity (P<0.01 and P<0.01, respectively). Compared with FPI (6 and 25 mg/mL), apoptotic cells decreased significantly (P<0.05, P<0.01, respectively) when H9c2 cells were incubated with SFI (9 and 37 mg/mL). The expression of CYP2J3 mRNA was down-regulated by FPI, while RSI and SFI could up-regulate the expression of CYP2J3 (P<0.01), which suggested the potential mechanism of protection of RSI against cardiac myocyte damage induced by FPI treatment. These observations indicate that SFI has the potential to exert cardioprotective effects against FPI toxicity. The effect was possibly correlated with the activation of CYP2J3.

Yang L.,Beijing Institute of Radiation Medicine | Peng R.,Beijing Institute of Radiation Medicine
Stem Cell Reviews and Reports | Year: 2010

Adult mammalian skin consists of the epidermis, hair follicles (HFs), and sebaceous glands (SGs). Each of these three epithelial lineages contains its own stem cell (SC) population for normal tissue homeostasis, HF cycling, and repair of the epidermis following injury. Here, we provide an overview of the current knowledge on follicle SCs of the adult skin, including their essential features and, most importantly, the control of follicle SC fate. Wnt/β-catenin is required for follicle SC maintenance and niche biology, and β-catenin activation is essential for promoting quiescent follicle SCs to proliferate and terminally differentiate along the hair cell lineage. Further, β-catenin stabilization promotes de novo HF morphogenesis, and constitutively active β-catenin expression results in pilomatricoma. Both bone morphogenetic protein (BMP) and transforming growth factor-β (TGF-β) signals are required for quiescent niche maintenance: BMP deletion results in SC activation, whereas TGF-β may play a role in SC identity maintenance. © 2010 Springer Science+Business Media, LLC.

Shu W.,Beijing Institute of Radiation Medicine | Chen H.,Beijing Institute of Radiation Medicine | Bo X.,Beijing Institute of Radiation Medicine | Wang S.,Beijing Institute of Radiation Medicine
Nucleic Acids Research | Year: 2011

To understand the molecular mechanisms that underlie global transcriptional regulation, it is essential to first identify all the transcriptional regulatory elements in the human genome. The advent of next-generation sequencing has provided a powerful platform for genome-wide analysis of different species and specific cell types; when combined with traditional techniques to identify regions of open chromatin [DNaseI hypersensitivity (DHS)] or specific binding locations of transcription factors [chromatin immunoprecipitation (ChIP)], and expression data from microarrays, we become uniquely poised to uncover the mysteries of the genome and its regulation. To this end, we have performed global meta-analysis of the relationship among data from DNaseI-seq, ChIP-seq and expression arrays, and found that specific correlations exist among regulatory elements and gene expression across different cell types. These correlations revealed four distinct modes of chromatin domain structure reflecting different functions: repressive, active, primed and bivalent. Furthermore, CCCTC-binding factor (CTCF) binding sites were identified based on these integrative data. Our findings uncovered a complex regulatory process involving by DNaseI HS sites and histone modifications, and suggest that these dynamic elements may be responsible for maintaining chromatin structure and integrity of the human genome. Our integrative approach provides an example by which data from diverse technology platforms may be integrated to provide more meaningful insights into global transcriptional regulation. © 2011 The Author(s).

Wang C.,Beijing Institute of Radiation Medicine
Free radical research | Year: 2013

Non-ionizing radiation electromagnetic pulse (EMP) is generally recorded to induce the generation of free radicals in vivo. Though mitochondria are the primary site to produce free radicals, a rare report is designed to directly investigate the EMP effects on free radical generation at mitochondrial level. Thus the present work was designed to study how EMP induces free radical generation in rat liver mitochondria in vitro using electron paramagnetic resonance technique. Surprisingly, our data suggest that EMP prevents free radical generation by activating antioxidant enzyme activity and reducing oxygen consumption and therefore free radical generation. Electron spin resonance measurements clearly demonstrate that disordering of mitochondrial lipid fluidity and membrane proteins mobility are the underlying contributors to this decreased oxygen consumption. Therefore, our results suggest that EMP might hold the potentiality to be developed as a non-invasive means to benefit certain diseases.

Li P.Y.,Beijing Institute of Radiation Medicine
Yi chuan = Hereditas / Zhongguo yi chuan xue hui bian ji | Year: 2011

microRNAs (miRNAs) are a highly conserved class of small noncoding RNAs that regulate gene expression by post-transcriptional degradation or translational repression. miRNAs are involved in the regulation of cell apoptosis, proliferation, differentiation and other physiological processes, and are closely related with the development of cancer. More recently, it has been proposed that the presence of genetic variations (e.g., single nucleotide polymorphism and copy number variation) in microRNA genes, their biogenesis pathway and target binding sites affect the miRNA processing machinery and targeting, and have a significant genetic effect. In this review, we focus on the miRNA-related genetic variations and cancer susceptibility and progression.

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