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https://www.readbyqxmd.com/read/29132420/substance-p-and-patterned-silk-biomaterial-stimulate-periodontal-ligament-stem-cells-to-form-corneal-stroma-in-a-bioengineered-three-dimensional-model
#1
Jialin Chen, Wei Zhang, Peyman Kelk, Ludvig J Backman, Patrik Danielson
BACKGROUND: We aimed to generate a bioengineered multi-lamellar human corneal stroma tissue in vitro by differentiating periodontal ligament stem cells (PDLSCs) towards keratocytes on an aligned silk membrane. METHODS: Human PDLSCs were isolated and identified. The neuropeptide substance P (SP) was added in keratocyte differentiation medium (KDM) to evaluate its effect on keratocyte differentiation of PDLSCs. PDLSCs were then seeded on patterned silk membrane and cultured with KDM and SP...
November 13, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29076964/lysine-methylation-signaling-in-pancreatic-cancer
#2
Gaël S Roth, Alexandre G Casanova, Nathanaël Lemonnier, Nicolas Reynoird
PURPOSE OF REVIEW: Despite better knowledge of its genetic basis, pancreatic cancer is still highly lethal with very few therapeutic options. In this review, we discuss the potential impact of epigenetic therapies, focusing on lysine methylation signaling and its implication in pancreatic cancer. RECENT FINDINGS: Protein lysine methylation, a key mechanism of posttranslational modifications of histone proteins, has emerged as a major cell signaling mechanism regulating physiologic and pathologic processes including cancer...
October 25, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29029477/coexpression-analysis-identifies-nuclear-reprogramming-barriers-of-somatic-cell-nuclear-transfer-embryos
#3
Yongchun Zuo, Guanghua Su, Lei Cheng, Kun Liu, Yu Feng, Zhuying Wei, Chunling Bai, Guifang Cao, Guangpeng Li
The success of cloned animal "Dolly Sheep" demonstrated the somatic cell nuclear transfer (SCNT) technique holds huge potentials for mammalian asexual reproduction. However, the extremely poor development of SCNT embryos indicates their molecular mechanism remain largely unexplored. Deciphering the spatiotemporal patterns of gene expression in SCNT embryos is a crucial step toward understanding the mechanisms associated with nuclear reprogramming. In this study, a valuable transcriptome recourse of SCNT embryos was firstly established, which derived from different inter-/intra donor cells...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28985996/tlr-induced-secretion-of-novel-cytokine-il-27-is-defective-in-newly-diagnosed-type-2-diabetic-subjects
#4
Haridoss Madhumitha, Viswanathan Mohan, Subash Babu, Vivekanandhan Aravindhan
Toll-like receptors (TLRs), the innate immune receptors, act as sentinels bridging both innate and adaptive arms of immunity. In the present study, we estimated TLR-induced secretion of IL-27, IL-12, IL-23, IL-8, IP-10, IL-17, IL-6 and TNF-α (by ELISA) and expression of Human Leukocyte Antigen- (Human Leukocyte Antigen - antigen D Related (HLA-DR), CD69, CD80 (also known asB7-1) (by flowcytometry) and Activating Transcription Factor 3(ATF3) (by qRT-PCR) in whole blood cultures of control and type-2 diabetic (both newly diagnosed/NDD and known/KDM) subjects...
October 3, 2017: Cytokine
https://www.readbyqxmd.com/read/28630052/infection-exposure-promotes-etv6-runx1-precursor-b-cell-leukemia-via-impaired-h3k4-demethylases
#5
Guillermo Rodríguez-Hernández, Julia Hauer, Alberto Martín-Lorenzo, Daniel Schäfer, Christoph Bartenhagen, Idoia García-Ramírez, Franziska Auer, Inés González-Herrero, Lucia Ruiz-Roca, Michael Gombert, Vera Okpanyi, Ute Fischer, Cai Chen, Martin Dugas, Sanil Bhatia, René Martin Linka, Marta Garcia-Suquia, María Victoria Rascón-Trincado, Angel Garcia-Sanchez, Oscar Blanco, Maria Begoña García-Cenador, Francisco Javier García-Criado, César Cobaleda, Diego Alonso-López, Javier De Las Rivas, Markus Müschen, Carolina Vicente-Dueñas, Isidro Sánchez-García, Arndt Borkhardt
ETV6-RUNX1 is associated with the most common subtype of childhood leukemia. As few ETV6-RUNX1 carriers develop precursor B-cell acute lymphocytic leukemia (pB-ALL), the underlying genetic basis for development of full-blown leukemia remains to be identified, but the appearance of leukemia cases in time-space clusters keeps infection as a potential causal factor. Here, we present in vivo genetic evidence mechanistically connecting preleukemic ETV6-RUNX1 expression in hematopoetic stem cells/precursor cells (HSC/PC) and postnatal infections for human-like pB-ALL...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28548959/identification-of-the-histone-lysine-demethylase-kdm4a-jmjd2a-as-a-novel-epigenetic-target-in-m1-macrophage-polarization-induced-by-oxidized-ldl
#6
Xue Wang, Siqing Wang, Gang Yao, Dehai Yu, Kexin Chen, Qian Tong, Long Ye, Chuan Wu, Yue Sun, Haixia Li, Dirk M Hermann, Thorsten R Doeppner, Fengyan Jin, Yun Dai, Jiang Wu
Oxidized low density lipoprotein (oxLDL) induces macrophage activation, an event essential for atherosclerosis. Emerging evidence supports that epigenetic regulation plays important roles in macrophage activation and function. However, it remains unclear which epigenetic modulator is responsible for oxLDL-induced macrophage activation. Here, we identify for the first time KDM4A (JMJD2A) as an epigenetic modifying enzyme that controls oxLDL-induced pro-inflammatory M1 polarization of macrophages. OxLDL triggered M1 polarization of murine and human macrophages, characterized by expression of iNOS and robust production of inflammatory cytokines (e...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28546743/common-methods-of-biological-age-estimation
#7
REVIEW
Linpei Jia, Weiguang Zhang, Xiangmei Chen
At present, no single indicator could be used as a golden index to estimate aging process. The biological age (BA), which combines several important biomarkers with mathematical modeling, has been proposed for >50 years as an aging estimation method to replace chronological age (CA). The common methods used for BA estimation include the multiple linear regression (MLR), the principal component analysis (PCA), the Hochschild's method, and the Klemera and Doubal's method (KDM). The fundamental differences in these four methods are the roles of CA and the selection criteria of aging biomarkers...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28432280/small-molecules-targeting-histone-demethylase-genes-kdms-inhibit-growth-of-temozolomide-resistant-glioblastoma-cells
#8
Barbara Banelli, Antonio Daga, Alessandra Forlani, Giorgio Allemanni, Daniela Marubbi, Maria Pia Pistillo, Aldo Profumo, Massimo Romani
In glioblastoma several histone demethylase genes (KDM) are overexpressed compared to normal brain tissue and the development of Temozolomide (TMZ) resistance is accompanied by the transient further increased expression of KDM5A and other KDMs following a mechanism that we defined as "epigenetic resilience". We hypothesized that targeting KDMs may kill the cells that survive the cytotoxic therapy.We determined the effect of JIB 04 and CPI-455, two KDM inhibitors, on glioblastoma cells and found that both molecules are more effective against TMZ-resistant rather than native cells...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28346812/identification-of-a-novel-benzimidazole-pyrazolone-scaffold-that-inhibits-kdm4-lysine-demethylases-and-reduces-proliferation-of-prostate-cancer-cells
#9
David M Carter, Edgar Specker, Jessica Przygodda, Martin Neuenschwander, Jens Peter von Kries, Udo Heinemann, Marc Nazaré, Ulrich Gohlke
Human lysine demethylase (KDM) enzymes (KDM1-7) constitute an emerging class of therapeutic targets, with activities that support growth and development of metastatic disease. By interacting with and co-activating the androgen receptor, the KDM4 subfamily (KDM4A-E) promotes aggressive phenotypes of prostate cancer (PCa). Knockdown of KDM4 expression or inhibition of KDM4 enzyme activity reduces the proliferation of PCa cell lines and highlights inhibition of lysine demethylation as a possible therapeutic method for PCa treatment...
August 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28265301/assessing-histone-demethylase-inhibitors-in-cells-lessons-learned
#10
Stephanie B Hatch, Clarence Yapp, Raquel C Montenegro, Pavel Savitsky, Vicki Gamble, Anthony Tumber, Gian Filippo Ruda, Vassilios Bavetsias, Oleg Fedorov, Butrus Atrash, Florence Raynaud, Rachel Lanigan, LeAnne Carmichael, Kathy Tomlin, Rosemary Burke, Susan M Westaway, Jack A Brown, Rab K Prinjha, Elisabeth D Martinez, Udo Oppermann, Christopher J Schofield, Chas Bountra, Akane Kawamura, Julian Blagg, Paul E Brennan, Olivia Rossanese, Susanne Müller
BACKGROUND: Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The first KDM inhibitors for KDM1 have entered clinical trials, and efforts are ongoing to develop potent, selective and cell-active 'probe' molecules for this target class. Robust cellular assays to assess the specific engagement of KDM inhibitors in cells as well as their cellular selectivity are a prerequisite for the development of high-quality inhibitors...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28110151/selection-of-an-optimal-set-of-biomarkers-and-comparative-analyses-of-biological-age-estimation-models-in-korean-females
#11
COMPARATIVE STUDY
Haemi Jee, Jaehyun Park
To date, an optimal working model which predicts biological age (BA) with a set of working biomarkers has not been devised to represent the Korean female population. Accuracy of prediction and applicability are required of an optimal set of commonly assessed biomarkers to provide information on the health status. The goal of this study was to identify a set of biomarkers that represent the aging process and to develop and compare different BA prediction models to elucidate the most fitting and applicable model for providing information on health status in the Korean female population...
May 2017: Archives of Gerontology and Geriatrics
https://www.readbyqxmd.com/read/27819678/tet2-binds-the-androgen-receptor-and-loss-is-associated-with-prostate-cancer
#12
M L Nickerson, S Das, K M Im, S Turan, S I Berndt, H Li, H Lou, S A Brodie, J N Billaud, T Zhang, A J Bouk, D Butcher, Z Wang, L Sun, K Misner, W Tan, A Esnakula, D Esposito, W Y Huang, R N Hoover, M A Tucker, J R Keller, J Boland, K Brown, S K Anderson, L E Moore, W B Isaacs, S J Chanock, M Yeager, M Dean, T Andresson
Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumour genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumours in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2), which is altered in 5-15% of myeloid, kidney, colon and PCas. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma. We perform fine-mapping of PCa risk across TET2 using genotypes from the PEGASUS case-control cohort and identify six new risk variants in introns 1 and 2...
April 2017: Oncogene
https://www.readbyqxmd.com/read/27800026/hypoxia-increases-genome-wide-bivalent-epigenetic-marking-by-specific-gain-of-h3k27me3
#13
Peggy Prickaerts, Michiel E Adriaens, Twan van den Beucken, Elizabeth Koch, Ludwig Dubois, Vivian E H Dahlmans, Caroline Gits, Chris T A Evelo, Michelle Chan-Seng-Yue, Bradly G Wouters, Jan Willem Voncken
BACKGROUND: Trimethylation at histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) controls gene activity during development and differentiation. Whether H3K4me3 and H3K27me3 changes dynamically in response to altered microenvironmental conditions, including low-oxygen conditions commonly present in solid tumors, is relatively unknown. Demethylation of H3K4me3 and H3K27me3 is mediated by oxygen and 2-oxoglutarate dioxygenases enzymes, suggesting that oxygen deprivation (hypoxia) may influence histone trimethylation...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27739832/quantum-signature-of-chaos-and-thermalization-in-the-kicked-dicke-model
#14
S Ray, A Ghosh, S Sinha
We study the quantum dynamics of the kicked Dicke model (KDM) in terms of the Floquet operator, and we analyze the connection between chaos and thermalization in this context. The Hamiltonian map is constructed by suitably taking the classical limit of the Heisenberg equation of motion to study the corresponding phase-space dynamics, which shows a crossover from regular to chaotic motion by tuning the kicking strength. The fixed-point analysis and calculation of the Lyapunov exponent (LE) provide us with a complete picture of the onset of chaos in phase-space dynamics...
September 2016: Physical Review. E
https://www.readbyqxmd.com/read/27732873/systematic-analysis-of-known-and-candidate-lysine-demethylases-in-the-regulation-of-myoblast-differentiation
#15
Yoichi Munehira, Ze Yang, Or Gozani
Histone methylation dynamics plays a critical role in cellular programming during development. For example, specific lysine methyltransferases (KMTs) and lysine demethylases (KDMs) have been implicated in the differentiation of mesenchymal stem cells into various cell lineages. However, a systematic and functional analysis for an entire family of KMT or KDM enzymes has not been performed. Here, we test the function of all the known and candidate KDMs in myoblast and osteoblast differentiation using the C2C12 cell differentiation model system...
June 30, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27696458/iron-acquisition-and-siderophore-production-in-the-fish-pathogen-renibacterium-salmoninarum
#16
J Bethke, M Poblete-Morales, R Irgang, A Yáñez, R Avendaño-Herrera
Renibacterium salmoninarum is the causative agent of bacterial kidney disease, which significantly affects salmonid farming worldwide. Despite this impact, there is scarce data on its iron uptake ability, a factor of pathogenesis. This study investigated the iron acquisition mechanisms of R. salmoninarum and its capacity to uptake iron from different sources. Thirty-two Chilean isolates and the DSM20767(T) type strain grew in the presence of 2,2'-Dipyridyl at varying concentrations (250-330 μm), and all isolates positively reacted on chrome azurol S agar...
November 2016: Journal of Fish Diseases
https://www.readbyqxmd.com/read/27532610/low-physical-activity-and-its-association-with-diabetes-and-other-cardiovascular-risk-factors-a-nationwide-population-based-study
#17
Laura Brugnara, Serafín Murillo, Anna Novials, Gemma Rojo-Martínez, Federico Soriguer, Albert Goday, Alfonso Calle-Pascual, Luis Castaño, Sonia Gaztambide, Sergio Valdés, Josep Franch, Conxa Castell, Joan Vendrell, Roser Casamitjana, Anna Bosch-Comas, Elena Bordiú, Rafael Carmena, Miguel Catalá, Elias Delgado, Juan Girbés, Alfonso López-Alba, Maria Teresa Martínez-Larrad, Edelmiro Menéndez, Inmaculada Mora-Peces, Gemma Pascual-Manich, Manuel Serrano-Ríos, Ramon Gomis, Emilio Ortega
Low physical activity (PA), or sedentary lifestyle, is associated with the development of several chronic diseases. We aimed to investigate current prevalence of sedentariness and its association with diabetes and other cardiovascular risk factors. PA was evaluated in a population-based, cross-sectional, randomly sampled study conducted in 2009-2010 in Spain. International Physical Activity Questionnaire (SF-IPAQ) was used to assess PA. 4991 individuals (median age 50 years, 57% women) were studied. Prevalence of sedentariness was 32...
2016: PloS One
https://www.readbyqxmd.com/read/27514027/epigenetic-gene-regulation-by-histone-demethylases-emerging-role-in-oncogenesis-and-inflammation
#18
M K Kang, S Mehrazarin, N-H Park, C-Y Wang
Histone N-terminal tails of nucleosomes are the sites of complex regulation of gene expression through post-translational modifications. Among these modifications, histone methylation had long been associated with permanent gene inactivation until the discovery of Lys-specific demethylase (LSD1), which is responsible for dynamic gene regulation. There are more than 30 members of the Lys demethylase (KDM) family, and with exception of LSD1 and LSD2, all other KDMs possess the Jumonji C (JmjC) domain exhibiting demethylase activity and require unique cofactors, for example, Fe(II) and α-ketoglutarate...
September 2017: Oral Diseases
https://www.readbyqxmd.com/read/27458201/an-easy-and-efficient-inducible-crispr-cas9-platform-with-improved-specificity-for-multiple-gene-targeting
#19
Jian Cao, Lizhen Wu, Shang-Min Zhang, Min Lu, William K C Cheung, Wesley Cai, Molly Gale, Qi Xu, Qin Yan
The CRISPR/Cas9 system is a powerful genome editing tool and has been widely used for biomedical research. However, many challenges, such as off-target effects and lack of easy solutions for multiplex targeting, are still limiting its applications. To overcome these challenges, we first developed a highly efficient doxycycline-inducible Cas9-EGFP vector. This vector allowed us to track the cells for uniform temporal control and efficient gene disruption, even in a polyclonal setting. Furthermore, the inducible CRISPR/Cas9 system dramatically decreased off-target effects with a pulse exposure of the genome to the Cas9/sgRNA complex...
November 2, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27443988/suppressive-activity-of-a-viral-histone-h4-against-two-host-chromatin-remodelling-factors-lysine-demethylase-and-swi-snf
#20
Sunil Kumar, Prasad Venkata, Yonggyun Kim
Histone H4, a nucleosome subunit in eukaryotes, plays crucial roles in DNA package and regulation of gene expression through covalent modification. A viral histone H4 encoded in Cotesia plutellae bracovirus (CpBV), a polydnavirus, is called CpBV-H4. It is highly homologous to other histone H4 proteins excepting 38 extra amino acid residues in the N terminus. CpBV-H4 can form octamer with other histone subunits and alter host gene expression. In this study, CpBV-H4 was transiently expressed in a natural host (Plutella xylostella) and its suppressive activity on host gene expression was evaluated by the suppressive subtractive hybridization (SSH) technique...
October 2016: Journal of General Virology
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