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https://www.readbyqxmd.com/read/28547659/quiescent-adult-stem-cells-in-murine-teeth-are-regulated-by-shh-signaling
#1
Yuko Ishikawa, Mitsushiro Nakatomi, Hiroko Ida-Yonemochi, Hayato Ohshima
The mechanisms regulating the maintenance of quiescent adult stem cells in teeth remain to be fully elucidated. Our aim is to clarify the relationship between BrdU label-retaining cells (LRCs) and sonic hedgehog (Shh) signaling in murine teeth. After prenatal BrdU labeling, mouse pups were analyzed during postnatal day 1 (P1) to week 5 (P5W). Paraffin sections were processed for immunohistochemistry for BrdU, Sox2, Gli1, Shh, Patched1 (Ptch1) and Ki67 and for in situ hybridization for Shh and Ptch1. Dense LRCs, Gli1-(+) cells and Ptch1-(+) cells were co-localized in the outer enamel epithelium of the apical bud and apical dental papilla of incisors...
May 26, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28547531/neonatal-hyperoxia-perturbs-neuronal-development-in-the-cerebellum
#2
Till Scheuer, Yuliya Sharkovska, Victor Tarabykin, Katharina Marggraf, Vivien Brockmöller, Christoph Bührer, Stefanie Endesfelder, Thomas Schmitz
Impaired postnatal brain development of preterm infants often results in neurological deficits. Besides pathologies of the forebrain, maldeveolopment of the cerebellum is increasingly recognized to contribute to psychomotor impairments of many former preterm infants. However, causes are poorly defined. We used a hyperoxia model to define neonatal damage in cerebellar granule cell precursors (GCPs) and in Purkinje cells (PCs) known to be essential for interaction with GCPs during development. We exposed newborn rats to 24 h 80% O2 from age P6 to P7 to identify postnatal and long-term damage in cerebellar GCPs at age P7 after hyperoxia and also after recovery in room air thereafter until P11 and P30...
May 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28539859/human-induced-pluripotent-stem-cells-generated-neural-cells-behaving-like-brain-and-spinal-cord-cells-an-insight-into-the-involvement-of-retinoic-acid-and-sonic-hedgehog-proteins
#3
Akinlolu Abdulazeez Adelaja
OBJECTIVES: The previous studies generated neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) using different protocols. However, the nature of the temporal or regional specificity of NPCs derived using these protocols is not well defined. Therefore, this study aimed to generate age- and region-specific NPCs from hiPSCs, which mimic in vivo fetal brain (FNPC-B) or spinal cord (FNPC-SC) tissues, in the absence or presence of retinoic acid (RA) and sonic hedgehog (SHH)...
April 2017: International Journal of Health Sciences
https://www.readbyqxmd.com/read/28537914/epigenomic-study-identifies-a-novel-mesenchyme-homeobox2-gli1-transcription-axis-involved-in-cancer-drug-resistance-overall-survival-and-therapy-prognosis-in-lung-cancer-patients
#4
Leonel Armas-López, Patricia Piña-Sánchez, Oscar Arrieta, Enrique Guzman de Alba, Blanca Ortiz-Quintero, Patricio Santillán-Doherty, David C Christiani, Joaquín Zúñiga, Federico Ávila-Moreno
Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536466/fipronil-induced-enantioselective-developmental-toxicity-to-zebrafish-embryo-larvae-involves-changes-in-dna-methylation
#5
Yi Qian, Cui Wang, Jinghua Wang, Xiaofeng Zhang, Zhiqiang Zhou, Meirong Zhao, Chensheng Lu
Enantioselectivity in the aquatic toxicity of chiral pesticides has been widely investigated, while the molecular mechanisms remain unclear. Thus far, few studies has focused on genomic expression related to selective toxicity in chiral pesticide, nor on epigenetic changes, such as DNA methylation. Here, we used fipronil, a broad-spectrum insecticide, as a model chemical to probe its enantioselective toxicity in embryo development. Our results showed that S-(+)-fipronil caused severer developmental toxicity in embryos...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536141/melk-and-ezh2-cooperate-to-regulate-medulloblastoma-cancer-stem-like-cell-proliferation-and-differentiation
#6
Hailong Liu, Qianwen Sun, Youliang Sun, Junping Zhang, Hongyu Yuan, Shuhuan Pang, Xueling Qi, Haoran Wang, Mingshan Zhang, Honwei Zhang, Chunjiang Yu, Chunyu Gu
Medulloblastoma is the most common malignant brain tumor in children. Although accumulated research has suggested that cancer stem-like cells play a key role in medulloblastoma tumorigenesis, the specific molecular mechanism regarding proliferation remains elusive. Here, we reported that more abundant expression of maternal embryonic leucine-zipper kinase (MELK) and enhancer of zeste homolog 2 (EZH2) in medulloblastoma stem-like cells than in neural stem cells and the interaction between the two proteins could mediate the self-renewal of sonic hedgehog (SHH)-subtype medulloblastoma...
May 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28535764/in-smokers-sonic-hedgehog-modulates-pulmonary-endothelial-function-through-vascular-endothelial-growth-factor
#7
Priscilla Henno, Stanislas Grassin-Delyle, Emeline Belle, Marion Brollo, Emmanuel Naline, Edouard Sage, Philippe Devillier, Dominique Israël-Biet
BACKGROUND: Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The Sonic hedgehog (SHH) pathway is involved in vascular physiology. We sought to establish whether the SHH pathway has a role in pulmonary endothelial dysfunction in smokers. METHODS: The ex vivo endothelium-dependent relaxation of pulmonary artery rings in response to acetylcholine (Ach) was compared in 34 current or ex-smokers and 8 never-smokers. The results were expressed as a percentage of the contraction with phenylephrine...
May 23, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28535369/packing-on-the-pounds-in-response-to-bacterial-growth-conditions
#8
Sabih Rashid, Lesley T MacNeil
Reporting in Nature Cell Biology, Lin and Wang (2017) show that bacterial methyl metabolism impacts host mitochondrial dynamics and lipid storage in C. elegans. The authors propose a model whereby bacterial metabolic products regulate a nuclear hormone receptor that promotes lipid accumulation through expression of a secreted Hedgehog-like protein.
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28533268/the-transcription-factor-gli3-promotes-b-cell-development-in-fetal-liver-through-repression-of-shh
#9
Anisha Solanki, Ching-In Lau, José Ignacio Saldaña, Susan Ross, Tessa Crompton
Before birth, B cells develop in the fetal liver (FL). In this study, we show that Gli3 activity in the FL stroma is required for B cell development. In the Gli3-deficient FL, B cell development was reduced at multiple stages, whereas the Sonic hedgehog (Hh [Shh])-deficient FL showed increased B cell development, and Gli3 functioned to repress Shh transcription. Use of a transgenic Hh-reporter mouse showed that Shh signals directly to developing B cells and that Hh pathway activation was increased in developing B cells from Gli3-deficient FLs...
May 22, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28525403/genetic-diseases-associated-with-an-increased-risk-of-skin-cancer-development-in-childhood
#10
Alexander L Fogel, Kavita Y Sarin, Joyce M C Teng
PURPOSE OF REVIEW: Childhood skin cancers are relatively rare and may indicate an underlying genetic disorder. The increasing elucidation of genetic pathways is changing the diagnosis and management of genetic skin cancer susceptibility syndromes. In this review, we provide an overview of genetic conditions that predispose to skin cancer development in childhood and signs that providers should assess when evaluating affected individuals. RECENT FINDINGS: In basal cell nevus syndrome (BCNS), the patched2 (PTCH2) and suppressor of fused (SUFU) genes have been implicated in disease pathogenesis...
May 18, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28525313/a-tunable-three-dimensional-in-vitro-culture-model-of-growth-plate-cartilage-using-alginate-hydrogel-scaffolds
#11
Alek G Erickson, Taylor D Laughlin, Sarah M Romereim, Catherine N Sargus-Patino, Angela K Pannier, Andrew T Dudley
Defining the final size and geometry of engineered tissues through precise control of the scalar and vector components of tissue growth is a necessary benchmark for regenerative medicine, but it has proved to be a significant challenge for tissue engineers. The growth plate cartilage that promotes elongation of the long bones is a good model system for studying morphogenetic mechanisms because cartilage is composed of a single cell type, the chondrocyte; chondrocytes are readily maintained in culture; and growth trajectory is predominately in a single vector...
May 18, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28523716/cd44-fibroblasts-increases-breast-cancer-cell-survival-and-drug-resistance-via-igf2bp3-cd44-igf2-signalling
#12
Yonglei Liu, Conghui Yu, Yonggang Wu, Xiangjun Sun, Quanping Su, Cuiping You, Hongwu Xin
CD44, a cell adhesion protein, involves in various process in cancer such as cell survival and metastasis. Most researches on CD44 in cancer focus on cancer cells. Recently, it is found that CD44 expression is high in fibroblasts of tumour microenvironment. However, its role in communication between fibroblasts and breast cancer cells is seldom known. In this study, CD44-positive (CD44(+) Fbs) and CD44-negative carcinoma-associated fibroblasts (CD44(-) Fbs) were isolated and cocultured with breast cancer cells for analysis of cell survival and drug resistance...
May 18, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28523596/pharmacokinetics-and-safety-of-vismodegib-in-patients-with-advanced-solid-malignancies-and-hepatic-impairment
#13
Ghassan K Abou-Alfa, Lionel D Lewis, Patricia LoRusso, Michael Maitland, Priya Chandra, Sravanthi Cheeti, Dawn Colburn, Sarah Williams, Brian Simmons, Richard A Graham
PURPOSE: Vismodegib is a Hedgehog pathway inhibitor approved for the treatment of advanced basal cell carcinoma. Currently, the pharmacokinetics (PK) and safety of vismodegib in patients with hepatic dysfunction are unknown and are the objective of this study. METHODS: Patients with advanced solid malignancies and hepatic impairment were enrolled into one of four cohorts: normal [bilirubin (bili) < upper limit of normal (ULN)], mild (ULN < bili ≤ 1...
May 18, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28523343/hh-signaling-in-regeneration-of-the-ischemic-heart
#14
REVIEW
Marina Dunaeva, Johannes Waltenberger
Myocardial infarction (MI) is caused by the occlusion of a coronary artery due to underlying atherosclerosis complicated by localized thrombosis. The blockage of blood flow leads to cardiomyocyte (CM) death in the infarcted area. Adult mammalian cardiomyocytes have little capacity to proliferate in response to injury; however, some pathways active during embryogenesis and silent during adult life are recruited in response to tissue injury. One such example is hedgehog (Hh) signaling. Hh is involved in the embryonic development of the heart and coronary vascular system...
May 18, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28522681/endothelial-nox1-oxidase-assembly-in-human-pulmonary-arterial-hypertension-driver-of-gremlin1-mediated-proliferation
#15
Imad Al Ghouleh, Sanghamitra Sahoo, Daniel N Meijles, Jefferson H Amaral, Daniel S de Jesus, John Sembrat, Mauricio Rojas, Dmitry A Goncharov, Elena A Goncharova, Patrick J Pagano
Background: Pulmonary arterial hypertension (PAH) is a rapidly degenerating and devastating disease of increased pulmonary vessel resistance leading to right heart failure. Palliative modalities remain limited despite recent endeavors to investigate the mechanisms underlying increased pulmonary vascular resistance, i.e. aberrant vascular remodeling and occlusion. However, little is known of the molecular mechanisms responsible for endothelial proliferation, a root cause of PAH-associated vascular remodeling...
May 18, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28521943/developmental-regulation-and-evolution-of-scaling-novel-insights-through-the-study-of-onthophagus-beetles
#16
REVIEW
Sofia Casasa, Daniel B Schwab, Armin P Moczek
Scaling relationships play critical roles in defining biological shape, trait functionality, and species characteristics, yet the developmental basis of scaling and its evolution remain poorly resolved in most taxa. In the horned beetle genus Onthophagus, scaling relationships of most traits are largely comparable across many species, however, the morphology and scaling of horns, a recent evolutionary invention, has diversified dramatically, ranging from modestly to highly positively linear to more complex sigmoidal allometries...
February 2017: Current Opinion in Insect Science
https://www.readbyqxmd.com/read/28521273/rapid-discovery-of-cyclopamine-analogs-from-fritillaria-and-veratrum-plants-using-lc-q-tof-ms-and-lc-qqq-ms
#17
Yuan Du, Zu-Guo Zheng, Yue Yu, Zi-Tian Wu, Dan Liang, Ping Li, Yan Jiang, Hui-Jun Li
Cyclopamine, an inhibitor of the Hedgehog (Hh) signaling pathway, has been paid much attention in treating a wide variety of tumors. However, isolation and purification of cyclopamine analogs from medicinal plants remain challengeable. We herein proposed an efficient strategy using liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS) and liquid chromatography triple-quadrupole mass spectrometry (LC-QqQ-MS) for rapid screening and targeted isolation of cyclopamine analogs in Fritillaria and Veratrum plants...
May 1, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28513578/crystal-structure-of-a-multi-domain-human-smoothened-receptor-in-complex-with-a-super-stabilizing-ligand
#18
Xianjun Zhang, Fei Zhao, Yiran Wu, Jun Yang, Gye Won Han, Suwen Zhao, Andrii Ishchenko, Lintao Ye, Xi Lin, Kang Ding, Venkatasubramanian Dharmarajan, Patrick R Griffin, Cornelius Gati, Garrett Nelson, Mark S Hunter, Michael A Hanson, Vadim Cherezov, Raymond C Stevens, Wenfu Tan, Houchao Tao, Fei Xu
The Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein-coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog signalling pathway. Here we report the crystal structure of the multi-domain human SMO, bound and stabilized by a designed tool ligand TC114, using an X-ray free-electron laser source at 2.9 Å. The structure reveals a precise arrangement of three distinct domains: a seven-transmembrane helices domain (TMD), a hinge domain (HD) and an intact extracellular cysteine-rich domain (CRD)...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28513431/dissection-of-zebrafish-shha-function-using-site-specific-targeting-with-a-cre-dependent-genetic-switch
#19
Kotaro Sugimoto, Subhra P Hui, Delicia Z Sheng, Kazu Kikuchi
Despite the extensive use of zebrafish as a model organism in developmental biology and regeneration research, genetic techniques enabling conditional analysis of gene function are limited. In this study, we generated Zwitch, a Cre-dependent invertible gene-trap cassette, enabling the establishment of conditional alleles in zebrafish by generating intronic insertions via in vivo homologous recombination. To demonstrate the utility of Zwitch, we generated a conditional sonic hedgehog a (shha) allele. Homozygous shha mutants developed normally; however, shha mutant embryos globally expressing Cre exhibited strong reductions in endogenous shha and shha target gene mRNA levels and developmental defects associated with null shha mutations...
May 17, 2017: ELife
https://www.readbyqxmd.com/read/28512846/melatonin-influences-the-sonic-hedgehog-signaling-pathway-in-porcine-cumulus-oocyte-complexes
#20
Sanghoon Lee, Jun-Xue Jin, Anukul Taweechaipaisankul, Geon A Kim, Curie Ahn, Byeong Chun Lee
Melatonin, which is synthesized in the pineal gland and peripheral reproductive organs, has antioxidant properties and regulates physiological processes. It is well known that melatonin affects in vitro maturation (IVM) of oocytes and embryonic development in many species. However, beneficial effects of melatonin on IVM have been explained mainly by indirect antioxidant effects and little information is available on the underlying mechanism by which melatonin directly acts on porcine cumulus oocyte complexes (COCs)...
May 17, 2017: Journal of Pineal Research
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