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https://www.readbyqxmd.com/read/28732358/lenalidomide-restores-the-osteogenic-differentiation-of-bone-marrow-mesenchymal-stem-cells-from-multiple-myeloma-patients-via-deactivating-notch-signaling-pathway
#1
Juan Guo, Chengming Fei, Youshan Zhao, Sida Zhao, Qingqing Zheng, Jiying Su, Dong Wu, Xiao Li, Chunkang Chang
Multiple myeloma (MM) always presents osteolytic bone lesions, resulting from the abnormal osteoblastic and osteoclastic function in patients. MM patients exhibit the impairment of osteogenic differentiation of BMMSCs (bone marrow mesenchymal stem cells) and osteoblast deficiency. Effects of the drug, lenalidomide on the osteoblastic functions and the involved mechanisms remain unexplored. In the present study, it is observed that the osteogenic differentiation of BMMSCs from MM patients (MM-MSCs) is impaired and activation of Notch signaling pathway in MM-MSCs is abnormal...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28729529/a-novel-matrix-protein-pfy2-functions-as-a-crucial-macromolecule-during-shell-formation
#2
Yi Yan, Dong Yang, Xue Yang, Chuang Liu, Jun Xie, Guilan Zheng, Liping Xie, Rongqing Zhang
Biomineralization, including shell formation, is dedicatedly regulated by matrix proteins. PfY2, a matrix protein detected in the ethylene diamine tetraacetic acid (EDTA)-soluble fraction from both prismatic layer and nacreous layer, was discovered by our group using microarray. It may play dual roles during biomineralization. However, the molecular mechanism is still unclear. In this research, we studied the function of PfY2 on crystallization in vivo and in vitro, revealing that it might be a negative regulator during shell formation...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729032/a-novel-model-of-autosomal-recessive-polycystic-kidney-questions-the-role-of-the-fibrocystin-c-terminus-in-disease-mechanism
#3
Patricia Outeda, Luis Menezes, Erum A Hartung, Stacey Bridges, Fang Zhou, Xianjun Zhu, Hangxue Xu, Qiong Huang, Qin Yao, Feng Qian, Gregory G Germino, Terry Watnick
Autosomal recessive polycystic kidney disease (OMIM 263200) is a serious condition of the kidney and liver caused by mutations in a single gene, PKHD1. This gene encodes fibrocystin/polyductin (FPC, PD1), a large protein shown by in vitro studies to undergo Notch-like processing. Its cytoplasmic tail, reported to include a ciliary targeting sequence, a nuclear localization signal, and a polycystin-2 binding domain, is thought to traffic to the nucleus after cleavage. We now report a novel mouse line with a triple HA-epitope "knocked-in" to the C-terminus along with lox P sites flanking exon 67, which encodes most of the C-terminus (Pkhd1(Flox67HA))...
July 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28720126/a-small-molecule-cytokine-combination-enhances-hematopoietic-stem-cell-proliferation-via-inhibition-of-cell-differentiation
#4
Lan Wang, Xin Guan, Huihui Wang, Bin Shen, Yu Zhang, Zhihua Ren, Yupo Ma, Xinxin Ding, Yongping Jiang
BACKGROUND: Accumulated evidence supports the potent stimulating effects of multiple small molecules on the expansion of hematopoietic stem cells (HSCs) which are important for the therapy of various hematological disorders. Here, we report a novel, optimized formula, named the SC cocktail, which contains a combination of three such small molecules and four cytokines. METHODS: Small-molecule candidates were individually screened and then combined at their optimal concentration with the presence of cytokines to achieve maximum capacity for stimulating the human CD34(+) cell expansion ex vivo...
July 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28718798/co-expression-network-and-pathway-analyses-reveal-important-modules-of-mirnas-regulating-milk-yield-and-component-traits
#5
Duy N Do, Pier-Luc Dudemaine, Ran Li, Eveline M Ibeagha-Awemu
Co-expression network analyses provide insights into the molecular interactions underlying complex traits and diseases. In this study, co-expression network analysis was performed to detect expression patterns (modules or clusters) of microRNAs (miRNAs) during lactation, and to identify miRNA regulatory mechanisms for milk yield and component traits (fat, protein, somatic cell count (SCC), lactose, and milk urea nitrogen (MUN)) via miRNA target gene enrichment analysis. miRNA expression (713 miRNAs), and milk yield and components (Fat%, Protein%, lactose, SCC, MUN) data of nine cows at each of six different time points (day 30 (D30), D70, D130, D170, D230 and D290) of an entire lactation curve were used...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28716889/cytokines-transcription-factors-and-the-initiation-of-t-cell-development
#6
Hiroyuki Hosokawa, Ellen V Rothenberg
Multipotent blood progenitor cells migrate into the thymus and initiate the T-cell differentiation program. T-cell progenitor cells gradually acquire T-cell characteristics while shedding their multipotentiality for alternative fates. This process is supported by extracellular signaling molecules, including Notch ligands and cytokines, provided by the thymic microenvironment. T-cell development is associated with dynamic change of gene regulatory networks of transcription factors, which interact with these environmental signals...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28714363/portulaca-oleracea-extract-can-inhibit-nodule-formation-of-colon-cancer-stem-cells-by-regulating-gene-expression-of-the-notch-signal-transduction-pathway
#7
Heiying Jin, Li Chen, Shuiming Wang, Deng Chao
To investigate whether Portulaca oleracea extract affects tumor formation in colon cancer stem cells and its chemotherapy sensitivity. In addition, to analyze associated genetic changes within the Notch signal transduction pathway. Serum-free cultures of colon cancer cells (HT-29) and HT-29 cancer stem cells were treated with the chemotherapeutic drug 5-fluorouracil to assess sensitivity. Injections of the stem cells were also given to BALB/c mice to confirm tumor growth and note its characteristics. In addition, the effect of different concentrations of P...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28712938/ascl1-reorganizes-chromatin-to-direct-neuronal-fate-and-suppress-tumorigenicity-of-glioblastoma-stem-cells
#8
Nicole I Park, Paul Guilhamon, Kinjal Desai, Rochelle F McAdam, Ellen Langille, Madlen O'Connor, Xiaoyang Lan, Heather Whetstone, Fiona J Coutinho, Robert J Vanner, Erick Ling, Panagiotis Prinos, Lilian Lee, Hayden Selvadurai, Gurnit Atwal, Michelle Kushida, Ian D Clarke, Veronique Voisin, Michael D Cusimano, Mark Bernstein, Sunit Das, Gary Bader, Cheryl H Arrowsmith, Stephane Angers, Xi Huang, Mathieu Lupien, Peter B Dirks
Glioblastomas exhibit a hierarchical cellular organization, suggesting that they are driven by neoplastic stem cells that retain partial yet abnormal differentiation potential. Here, we show that a large subset of patient-derived glioblastoma stem cells (GSCs) express high levels of Achaete-scute homolog 1 (ASCL1), a proneural transcription factor involved in normal neurogenesis. ASCL1(hi) GSCs exhibit a latent capacity for terminal neuronal differentiation in response to inhibition of Notch signaling, whereas ASCL1(lo) GSCs do not...
July 11, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28711903/notch-system-is-differentially-expressed-and-activated-in-pituitary-adenomas-of-distinct-histotype-tumor-cell-lines-and-normal-pituitaries
#9
Sofia Perrone, Lautaro Zubeldia-Brenner, Elias Gazza, Gianina Demarchi, Leticia Baccarini, Agustin Baricalla, Freya Mertens, Guillermina Luque, Hugo Vankelecom, Silvia Berner, Damasia Becu-Villalobos, Carolina Cristina
Pituitary adenomas are among the most frequent intracranial neoplasms and treatment depends on tumor subtype and clinical features. Unfortunately, non responder cases occur, then new molecular targets are needed.Notch system component expression and activation data are scarce in pituitary tumorigenesis, we therefore aimed to characterize Notch system in pituitary tumors of different histotype. In human pituitary adenomas we showed NOTCH1-4 receptors, JAGGED1 ligand and HES1 target gene expression with positive correlations between NOTCH1,2,4 and HES1, and NOTCH3 and JAGGED1 denoting Notch system activation in a subset of tumors...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28711779/hyperactive-foxo1-results-in-lack-of-tip-stalk-identity-and-deficient-microvascular-regeneration-during-kidney-injury
#10
Lan T H Dang, Takahide Aburatani, Graham A Marsh, Bryce G Johnson, Stella Alimperti, Christine J Yoon, Angela Huang, Suzanne Szak, Naoki Nakagawa, Ivan Gomez, Shuyu Ren, Sarah K Read, Chris Sparages, Alfred C Aplin, Roberto F Nicosia, Chris Chen, Giovanni Ligresti, Jeremy S Duffield
Loss of the microvascular (MV) network results in tissue ischemia, loss of tissue function, and is a hallmark of chronic diseases. The incorporation of a functional vascular network with that of the host remains a challenge to utilizing engineered tissues in clinically relevant therapies. We showed that vascular-bed-specific endothelial cells (ECs) exhibit differing angiogenic capacities, with kidney microvascular endothelial cells (MVECs) being the most deficient, and sought to explore the underlying mechanism...
July 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28711012/osteopontin-in-hepatocellular-carcinoma-a-possible-biomarker-for-diagnosis-and-follow-up
#11
Manuela Cabiati, Melania Gaggini, Maria Michela Cesare, Chiara Caselli, Paolo De Simone, Franco Filipponi, Giuseppina Basta, Amalia Gastaldelli, Silvia Del Ry
Recently osteopontin (OPN), a protein of the extracellular matrix, has generated in hepatocellular carcinoma (HCC) a significant interest as a prognostic factor. Aim of this study was to confirm, in liver tissues of subjects with HCV-positive HCC undergoing liver transplantation (RL, n=10) and of donors (DL, n=14), the increase of OPN plasma and tissue concentration, the OPN splicing isoforms expression profiling together with those of thrombin, and to evaluate a possible association between OPN measurements...
July 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28708309/bone-healing-in-an-aged-murine-fracture-model-is-characterized-by-sustained-callus-inflammation-and-decreased-cell-proliferation
#12
John H Hebb, Jason W Ashley, Lee McDaniel, Luke A Lopas, John Tobias, Kurt D Hankenson, Jaimo Ahn
Geriatric fractures take longer to heal and heal with more complications than those of younger patients; however, the mechanistic basis for this difference in healing is not well understood. To improve this understanding, we investigated cell and molecular differences in fracture healing between 5 month-old (young adult) and 25 month-old (geriatric) mice healing utilizing high-throughput analysis of gene expression. Mice underwent bilateral tibial fractures and fracture calluses were harvested at 5, 10, and 20 days post fracture (DPF) for analysis...
July 14, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28707430/multi-genic-pattern-found-in-rare-type-of-hypopituitarism-a-whole-exome-sequencing-study-of-han-chinese-with-pituitary-stalk-interruption-syndrome
#13
Qing-Hua Guo, Cheng-Zhi Wang, Zhi-Qiang Wu, Yan Qin, Bai-Yu Han, An-Ping Wang, Bao-An Wang, Jing-Tao Dou, Xiao-Sheng Wu, Yi-Ming Mu
Pituitary stalk interruption syndrome (PSIS) is a rare type of hypopituitarism manifesting various degrees of pituitary hormone deficiency. Although mutations have been identified in some familial cases, the underpinning mechanisms of sporadic patients with PSIS who are in a vast majority remain elusive, necessitating a comprehensive study using systemic approaches. We postulate that other genetic mechanisms may be responsible for the sporadic PSIS. To test this hypothesis, we conducted a study in 24 patients with PSIS of Han Chinese with no family history using whole-exome sequencing (WES) and bioinformatic analysis...
July 14, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28705915/microarray-analysis-of-bone-marrow-lesions-in-osteoarthritis-demonstrates-upregulation-of-genes-implicated-in-osteochondral-turnover-neurogenesis-and-inflammation
#14
Anasuya Kuttapitiya, Lena Assi, Ken Laing, Caroline Hing, Philip Mitchell, Guy Whitley, Abiola Harrison, Franklyn A Howe, Vivian Ejindu, Christine Heron, Nidhi Sofat
OBJECTIVE: Bone marrow lesions (BMLs) are well described in osteoarthritis (OA) using MRI and are associated with pain, but little is known about their pathological characteristics and gene expression. We evaluated BMLs using novel tissue analysis tools to gain a deeper understanding of their cellular and molecular expression. METHODS: We recruited 98 participants, 72 with advanced OA requiring total knee replacement (TKR), 12 with mild OA and 14 non-OA controls...
July 13, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28698260/phospholipase-c%C3%AE-1-mediates-intima-formation-through-akt-notch1-signaling-independent-of-the-phospholipase-activity
#15
Dongyang Jiang, Jianhui Zhuang, Wenhui Peng, Yuyan Lu, Hao Liu, Qian Zhao, Chen Chi, Xiankai Li, Guofu Zhu, Xiangbin Xu, Chen Yan, Yawei Xu, Junbo Ge, Jinjiang Pang
BACKGROUND: Vascular smooth muscle cell proliferation, migration, and dedifferentiation are critical for vascular diseases. Recently, it was demonstrated that Notch receptors have opposing effects on intima formation after vessel injury. Therefore, it is important to investigate the specific regulatory pathways that activate the different Notch receptors. METHODS AND RESULTS: There was a time- and dose-dependent activation of Notch1 by angiotensin II and platelet-derived growth factor in vascular smooth muscle cells...
July 11, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28695677/combined-genetic-analyses-can-achieve-efficient-diagnostic-yields-for-subjects-with-alagille-syndrome-and-incomplete-alagille-syndrome
#16
Kei Ohashi, Takao Togawa, Tokio Sugiura, Koichi Ito, Takeshi Endo, Kohei Aoyama, Yutaka Negishi, Toyoichiro Kudo, Reiko Ito, Shinji Saitoh
AIM: We evaluated combined genetic analyses with targeted next-generation sequencing (NGS), multiplex ligation probe amplification (MLPA) of Jagged1 (JAG1) genes and microarray comparative genomic hybridisation (CGH) in subjects with Alagille syndrome, incomplete clinical features of Alagille syndrome and biliary atresia. METHODS: Subjects recruited from April 2013 to December 2015 underwent a targeted NGS analysis, including JAG1 and Notch homolog 2 (NOTCH2). If no mutations were detected in JAG1 or NOTCH2, or if copy number variations were suggested by the NGS analysis, we performed an MLPA analysis of JAG1...
July 11, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/28694468/interactome-and-reciprocal-activation-of-pathways-in-topical-mesenchymal-stem-cells-and-the-recipient-cerebral-cortex-following-traumatic-brain-injury
#17
Ping K Lam, Kevin K W Wang, Anthony W I Lo, Cindy S W Tong, Don W C Ching, Kenneth Wong, Zhihui Yang, Themis Kong, Kin K Y Lo, Richard K W Choy, Paul B S Lai, George K C Wong, Wai S Poon
In this study, GFP-MSCs were topically applied to the surface of cerebral cortex within 1 hour of experimental TBI. No treatment was given to the control group. Three days after topical application, the MSCs homed to the injured parenchyma and improved the neurological function. Topical MSCs triggered earlier astrocytosis and reactive microglia. TBI penumbra and hippocampus had higher cellular proliferation. Apoptosis was suppressed at hippocampus at 1 week and reduced neuronal damaged was found in the penumbral at day 14 apoptosis...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28692652/developmental-transcriptomic-analyses-for-mechanistic-insights-into-critical-pathways-involved-in-embryogenesis-of-pelagic-mahi-mahi-coryphaena-hippurus
#18
Elvis Genbo Xu, Edward M Mager, Martin Grosell, John D Stieglitz, E Starr Hazard, Gary Hardiman, Daniel Schlenk
Mahi-mahi (Coryphaena hippurus) is a commercially and ecologically important species of fish occurring in tropical and temperate waters worldwide. Understanding early life events is crucial for predicting effects of environmental stress, which is largely restricted by a lack of genetic resources regarding expression of early developmental genes and regulation of pathways. The need for anchoring developmental stages to transcriptional activities is highlighted by increasing evidence on the impacts of recurrent worldwide oil spills in this sensitive species during early development...
2017: PloS One
https://www.readbyqxmd.com/read/28688656/notch-signaling-promotes-ductular-reactions-in-biliary-atresia
#19
Jessica A Zagory, William Dietz, Alex Park, Michael Fenlon, Jiabo Xu, Sarah Utley, Nirmala Mavila, Kasper S Wang
BACKGROUND: Biliary atresia (BA) is a congenital, progressive, fibro-obliterative disease of the extrahepatic biliary tree and the most common cause of end-stage liver disease in children. BA is characterized by extensive intrahepatic proliferating ductular reactions that may contribute to biliary fibrosis. Lineage tracing during experimental cholestasis indicates that cells within ductular reactions derive from PROM1-expressing hepatic progenitor cells. Given the role of Notch signaling in normal biliary development, we hypothesize that activated Notch signaling promotes the formation of ductular reactions in BA...
July 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28684878/hepatocyte-nuclear-factor-1beta-enhances-the-stemness-of-hepatocellular-carcinoma-cells-through-activation-of-the-notch-pathway
#20
Jing-Ni Zhu, Lu Jiang, Jing-Hua Jiang, Xue Yang, Xiao-Yong Li, Jian-Xin Zeng, Rong-Yu Shi, Yang Shi, Xiao-Rong Pan, Zhi-Peng Han, Li-Xin Wei
Hepatocyte nuclear factor-1beta plays an important role in the development and progression of liver cancer. In recent years, the expression of HNF-1β has been reported to be associated with risk for a variety of cancers. The purpose of this study is to investigate whether the expression of HNF-1β promotes the malignancy of HCC and its mechanism. We retrospectively investigated the expression of HNF-1β in 90 patients with hepatocellular carcinoma and found that the high expression of HNF-1β indicated poor prognosis...
July 6, 2017: Scientific Reports
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