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https://www.readbyqxmd.com/read/27913571/snord126-promotes-hcc-and-crc-cell-growth-by-activating-the-pi3k-akt-pathway-through-fgfr2
#1
Xianlong Fang, Dongmei Yang, Hongping Luo, Shuai Wu, Wenjie Dong, Jing Xiao, Sujing Yuan, Aimin Ni, Kang-Jian Zhang, Xin-Yuan Liu, Liang Chu
Small nucleolar RNA (snoRNA) dysfunctions have been associated with cancer development. SNORD126 is an orphan C/D box snoRNA that is encoded within introns 5-6 of its host gene, cyclin B1-interacting protein 1 (CCNB1IP1) The cancer-associated molecular mechanisms triggered by SNORD126 are not fully understood. Here, we demonstrate that SNORD126 is highly expressed in hepatocellular carcinoma (HCC) and colorectal cancer (CRC) patient samples. SNORD126 increased Huh-7 and SW480 cell growth and tumorigenicity in nude mice...
December 2, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27913459/children-with-rare-diseases-of-neutrophil-granulocytes-from-therapeutic-orphans-to-pioneers-of-individualized-medicine
#2
Christoph Klein
Neutrophil granulocytes are the most abundant immune cells in the blood yet the pathways orchestrating their differentiation and biological function remain incompletely understood. Studying (ultra-) rare patients with monogenetic defects of neutrophil granulocytes may open new horizons to understand basic principles of hematopoiesis and innate immunity. Here, recent insights into genetic factors controlling myelopoiesis and their more general role in biology will be presented in a clinical perspective. Advances in supportive care, first and foremost the use of recombinant human granulocyte-colony stimulating factor, has made a substantial difference for the quality of life and life expectancy of patients with congenital neutropenia (CN)...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913310/targeted-disruption-of-the-orphan-receptor-gpr151-does-not-alter-pain-related-behaviour-despite-a-strong-induction-in-dorsal-root-ganglion-expression-in-a-model-of-neuropathic-pain
#3
Fiona E Holmes, Niall Kerr, Ying-Ju Chen, Penny Vanderplank, Craig A McArdle, David Wynick
BACKGROUND: Gpr151 is an orphan GPCR whose function is unknown. The restricted pattern of neuronal expression in the habenula, dorsal horn of the spinal cord and dorsal root ganglion plus homology with the galanin family of receptors imply a role in nociception. RESULTS: Real-time quantitative RT-PCR demonstrated a 49.9±2.9 fold highly significant (P<0.001) increase in Gpr151 mRNA expression in the dorsal root ganglion 7days after the spared nerve injury model of neuropathic pain...
November 29, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27910955/pgc-1%C3%AE-dictates-endothelial-function-through-regulation-of-enos-expression
#4
Siobhan M Craige, Swenja Kröller-Schön, Chunying Li, Shashi Kant, Shenghe Cai, Kai Chen, Mayur M Contractor, Yongmei Pei, Eberhard Schulz, John F Keaney
Endothelial dysfunction is a characteristic of many vascular related diseases such as hypertension. Peroxisome proliferator activated receptor gamma, coactivator 1α (PGC-1α) is a unique stress sensor that largely acts to promote adaptive responses. Therefore, we sought to define the role of endothelial PGC-1α in vascular function using mice with endothelial specific loss of function (PGC-1α EC KO) and endothelial specific gain of function (PGC-1α EC TG). Here we report that endothelial PGC-1α is suppressed in angiotensin-II (ATII)-induced hypertension...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905482/pharmacologic-modulation-of-ror%C3%AE-t-translates-to-efficacy-in-preclinical-and-translational-models-of-psoriasis-and-inflammatory-arthritis
#5
Xiaohua Xue, Pejman Soroosh, Aimee De Leon-Tabaldo, Rosa Luna-Roman, Marciano Sablad, Natasha Rozenkrants, Jingxue Yu, Glenda Castro, Homayon Banie, Wai-Ping Fung-Leung, Luis Santamaria-Babi, Thomas Schlueter, Michael Albers, Kristi Leonard, Alison L Budelsky, Anne M Fourie
The IL-23/IL-17 pathway is implicated in autoimmune diseases, particularly psoriasis, where biologics targeting IL-23 and IL-17 have shown significant clinical efficacy. Retinoid-related orphan nuclear receptor gamma t (RORγt) is required for Th17 differentiation and IL-17 production in adaptive and innate immune cells. We identified JNJ-54271074, a potent and highly-selective RORγt inverse agonist, which dose-dependently inhibited RORγt-driven transcription, decreased co-activator binding and promoted interaction with co-repressor protein...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904831/orphan-drug-development-in-china-turning-challenges-into-opportunities
#6
Xiaowei Jin, Li Chen
Of over 7,000 known rare diseases, only 5% currently have an available treatment option worldwide. Moreover, the vast majority of rare disease patients in China have no access to treatment due to limited availability and the lack of appropriate infrastructure in China's healthcare system. Despite increased interest in orphan drug development, drug companies in China with active programs on drugs to treat rare diseases are still limited. Hence, there is a huge unmet need in China, with over 10 million patients suffering from rare diseases...
November 2016: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/27904685/phylogenetic-analysis-of-basic-helix-loop-helix-transcription-factors-in-the-genome-of-a-typical-human-disease-vector
#7
Meng-Yun Chen, Ying Dong, Rui-Xue Chang, Qian-Qian Ang, Ran Zhang, Yan-Yan Wu, Yi-Hui Xu, Wen-Sheng Lu, Xiao-Dong Zheng
Ixodes scapularis, the black-legged tick, is one of the most common human-disease vectors and transmits Borrelia species, such as B. burgdorferi, as well as Theileria microti, Anaplasma phagocytophilum, etc. As basic helix-loop-helix (bHLH) transcription factors have been recognized for many years as important regulators of various developmental processes, we performed phylogenetic analysis of the black-legged tick genome in order to identify the number and family of bHLH transcription factors. Because bHLH family members have been identified in many organisms, including silkworm and fruit fly, we were able to conduct this survey and identify 58 putative bHLH transcription factors...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904297/the-push-for-additional-orphan-drugs-can-the-fda-do-more-to-encourage-their-development
#8
Stephen Barlas
Can the FDA do more to encourage orphan drug development?
November 2016: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/27903760/interactions-between-intersubunit-transmembrane-domains-regulate-the-chaperone-dependent-degradation-of-an-oligomeric-membrane-protein
#9
Teresa M Buck, Alexa S Jordahl, Megan E Yates, Mike Preston, Emily Cook, Thomas R Kleyman, Jeffrey L Brodsky
The Epithelial Sodium Channel (ENaC) in kidney regulates blood pressure through control of sodium and volume homeostasis, and in lung ENaC regulates the volume of airway and alveolar fluids.  ENaC is a heterotrimer of homologous α-, β-, and γ-subunits, and assembles in the Endoplasmic Reticulum (ER) before it traffics and functions at the plasma membrane. Improperly folded or orphaned ENaC subunits are subject to ER quality control and targeted for ER associated degradation (ERAD). We previously established that a conserved, ER lumenal, molecular chaperone, Lhs1/GRP170, selects αENaC, but not β- or γENaC, for degradation when the ENaC subunits were individually expressed...
November 30, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27902884/synthesis-and-biological-evaluation-of-new-triazolo-and-imidazolopyridine-ror%C3%AE-t-inverse-agonists
#10
Samuel Hintermann, Christine Guntermann, Henri Mattes, David A Carcache, Juergen Wagner, Anna Vulpetti, Andreas Billich, Janet Dawson, Klemens Kaupmann, Joerg Kallen, Rowan Stringer, David Orain
Retinoic-acid-related orphan receptor γt (RORγt) is a key transcription factor implicated in the production of pro-inflammatory Th17 cytokines, which drive a number of autoimmune diseases. Despite diverse chemical series having been reported, combining high potency with a good physicochemical profile has been a very challenging task in the RORγt inhibitor field. Based on available chemical structures and incorporating in-house knowledge, a new series of triazolo- and imidazopyridine RORγt inverse agonists was designed...
November 30, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27901527/lysine-linkage-in-abasic-site-binding-ligand-thiazole-orange-conjugates-for-improved-binding-affinity-to-orphan-nucleobases-in-dna-rna-hybrids
#11
Yusuke Sato, Hiroki Saito, Daisuke Aoki, Norio Teramae, Seiichi Nishizawa
Introduction of lysine linkage in the conjugate between abasic site-binding ligands and thiazole orange significantly improved the binding affinity for target orphan adenine or uracil nucleobase in DNA/RNA hybrids.
November 30, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27901450/usefulness-of-serum-cardiac-troponin-i-concentration-as-a-marker-of-survival-of-harbor-seal-phoca-vitulina-pups-during-rehabilitation
#12
Sonja Fonfara, Janne Sundermeyer, Domingo Casamian Sorrosal, Corinna Weber, Tanja Rosenberger
OBJECTIVE To measure serum cardiac troponin I (cTnI) concentrations in orphaned harbor seal (Phoca vitulina) pups at various points during rehabilitation in a seal rescue center and determine whether cTnI concentration was associated with survival during rehabilitation and duration of rehabilitation. DESIGN Serial cross-sectional study. ANIMALS Fifty-five 2- to 9-day-old harbor seal pups. PROCEDURES Blood samples for serum cTnI concentration measurement, CBC, and serum biochemical analysis were obtained from seal pups at admission into a seal rescue center, after 2 weeks of rehabilitation at the center, and prior to release...
December 15, 2016: Journal of the American Veterinary Medical Association
https://www.readbyqxmd.com/read/27900053/receptor-tyrosine-kinases-in-carcinogenesis
#13
Xiao-Ying Zhang, Pei-Ying Zhang
Receptor tyrosine kinases (RTKs) are cell surface glycoproteins with enzymatic activity involved in the regulation of various important functions. In all-important physiological functions including differentiation, cell-cell interactions, survival, proliferation, metabolism, migration and signaling these receptors are the key players of regulation. Additionally, mutations of RTKs or their overexpression have been described in many human cancers and are being explored as a novel avenue for a new therapeutic approach...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899558/pathdip-an-annotated-resource-for-known-and-predicted-human-gene-pathway-associations-and-pathway-enrichment-analysis
#14
Sara Rahmati, Mark Abovsky, Chiara Pastrello, Igor Jurisica
Molecular pathway data are essential in current computational and systems biology research. While there are many primary and integrated pathway databases, several challenges remain, including low proteome coverage (57%), low overlap across different databases, unavailability of direct information about underlying physical connectivity of pathway members, and high fraction of protein-coding genes without any pathway annotations, i.e. 'pathway orphans'. In order to address all these challenges, we developed pathDIP, which integrates data from 20 source pathway databases, 'core pathways', with physical protein-protein interactions to predict biologically relevant protein-pathway associations, referred to as 'extended pathways'...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899502/bacillus-subtilis-early-colonization-of-arabidopsis-thaliana-roots-involves-multiple-chemotaxis-receptors
#15
Rosalie Allard-Massicotte, Laurence Tessier, Frédéric Lécuyer, Venkatachalam Lakshmanan, Jean-François Lucier, Daniel Garneau, Larissa Caudwell, Hera Vlamakis, Harsh P Bais, Pascale B Beauregard
: Colonization of plant roots by Bacillus subtilis is mutually beneficial to plants and bacteria. Plants can secrete up to 30% of their fixed carbon via root exudates, thereby feeding the bacteria, and in return the associated B. subtilis bacteria provide the plant with many growth-promoting traits. Formation of a biofilm on the root by matrix-producing B. subtilis is a well-established requirement for long-term colonization. However, we observed that cells start forming a biofilm only several hours after motile cells first settle on the plant...
November 29, 2016: MBio
https://www.readbyqxmd.com/read/27892826/assessing-factors-associated-with-hiv-testing-among-adolescents-in-malawi
#16
Paul Mkandawire
Despite being at high risk of HIV/AIDS, most young people do not know their HIV status. Using survey data (n = 2428) and applying multilevel models, this paper assesses factors associated with HIV testing among adolescents in Northern Malawi. The results show that among both boys (OR = 0.39) and girls (OR = 0.47), orphan status is associated with low likelihood of HIV testing. Correct knowledge about HIV/AIDS (OR = 2.55) and having secondary education (OR = 3.24) are associated with HIV testing among boys and girls, respectively...
November 28, 2016: Global Public Health
https://www.readbyqxmd.com/read/27889907/activation-of-nur77-in-microglia-attenuates-proinflammatory-mediators-production-and-protects-dopaminergic-neurons-from-inflammation-induced-cell-death
#17
Tian-Ya Liu, Xiao-Ying Yang, Long-Tai Zheng, Guang-Hui Wang, Xue-Chu Zhen
Microglia-mediated neuroinflammation plays a critical role in the pathological development of Parkinson's disease (PD). Orphan nuclear receptor Nur77 (Nur77) is abundant in neurons, while its role in microglia-mediated neuroinflammation remains unclear. The present data demonstrated that the expression of Nur77 in microglia was reduced accompanied with microglia activation in response to lipopolysaccharide (LPS) in vitro and in experimental MPTP-PD mouse model. Nur77 overexpression or application of Nur77 agonist CsnB suppressed the expression of proinflammatory genes, such as iNOS, COX-2, IL-1β, and TNF-α in the activated microglia, while silenced Nur77 exaggerated the inflammatory responses in microglia...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27889032/metastatic-anal-cancer-and-novel-agents
#18
REVIEW
Van Morris, Cathy Eng
Squamous cell carcinoma of the anal canal (SCCA) represents an orphan disease. Although prior infection with human papilloma virus is associated with the development of SCCA, knowledge of this relationship has proven ineffective in identifying therapeutic agents that have activity in the management of metastatic SCCA. Combination chemotherapy with traditional cytotoxic agents has demonstrated efficacy in multiple small series. However, immune checkpoint blockade agents have demonstrated efficacy for patients with refractory metastatic SCCA; these agents hold promise in the horizon for patients with metastatic SCCA...
January 2017: Surgical Oncology Clinics of North America
https://www.readbyqxmd.com/read/27888388/cardiac-bin1-cbin1-is-a-regulator-of-cardiac-contractile-function-and-an-emerging-biomarker-of-heart-muscle-health
#19
REVIEW
Kang Zhou, Tingting Hong
In recent decades, a cardiomyocyte membrane scaffolding protein bridging integrator 1 (BIN1) has emerged as a critical multifunctional regulator of transverse-tubule (t-tubule) function and calcium signaling in cardiomyocytes. Encoded by a single gene with 20 exons that are alternatively spliced, more than ten BIN1 protein isoforms are expressed with tissue and disease specificity. The recently discovered cardiac alternatively spliced isoform BIN1 (cBIN1 or BIN1+13+17) plays a crucial role in organizing membrane microfolds within cardiac t-tubules...
November 23, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27886141/comprehensive-transcriptome-analysis-provides-evidence-of-local-thermal-adaptation-in-three-loaches-genus-misgurnus
#20
Shaokui Yi, Sai Wang, Jia Zhong, Weimin Wang
The geographic distribution of three Misgurnus species, M. anguillicaudatus, M. bipartitus, and M. mohoity, displays a specific pattern in China, coincident with temperature zones. In this study, we sequenced the transcriptomes of these three species and used the sequences to investigate the lineage-specific adaptations within the genus Misgurnus. In total, 51 orphan genes (19 in M. anguillicaudatus, 18 in M. bipartitus, and 14 in M. mohoity) that may contribute to the species-specific adaptations were identified...
November 24, 2016: International Journal of Molecular Sciences
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