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https://www.readbyqxmd.com/read/29348675/stac2-negatively-regulates-osteoclast-formation-by-targeting-the-rank-signaling-complex
#1
Eutteum Jeong, Han Kyoung Choi, Jin Hee Park, Soo Young Lee
The receptor activator of nuclear factor-κB (RANK) protein activates various protein kinase signaling cascades, including those involving NF-κB, mitogen-activated protein kinase (MAPK), and Bruton tyrosine kinase (Btk)/tyrosine-protein kinase Tec. However, the mechanism underlying the negative regulation of RANK by downstream signaling molecules remains unclear. Here, we report that Src homology 3 domain and cysteine-rich domain-containing protein 2 (STAC2) is a novel RANK ligand-inducible protein that negatively regulates RANK-mediated osteoclast formation...
January 18, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29337184/when-drugs-plasticize-film-coatings-unusual-formulation-effects-observed-with-metoprolol-and-eudragit-rs
#2
Youness Karrout, Florence Siepmann, Youcef Benzine, Laurent Paccou, Yannick Guinet, Alain Hedoux, Juergen Siepmann
Metoprolol tartrate and metoprolol free base loaded pellet starter cores were coated with EudragitRS, plasticized with 25% triethyl citrate (TEC). The initial drug loading and coating level were varied from 10 to 40 and 0 to 20%, respectively. Drug release was measured in 0.1NHCl and phosphate buffer pH7.4. The water uptake and swelling kinetics, mechanical properties and TEC leaching of/from coated pellets and/or thin, free films of identical composition as the film coatings were monitored. The following unusual tendencies were observed: (i)the relative drug release rate from coated pellets increased with increasing initial drug content, and (ii)drug release from pellets was much faster for metoprolol free base compared to metoprolol tartrate, despite its much lower solubility (factor > 70)...
January 11, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29336881/influence-of-contracted-endodontic-access-on-root-canal-geometry-an-in%C3%A2-vitro-study
#3
Mario Alovisi, Damiano Pasqualini, Edoardo Musso, Elena Bobbio, Carlotta Giuliano, Davide Mancino, Nicola Scotti, Elio Berutti
INTRODUCTION: Contracted endodontic cavities (CECs) have developed from the concept of minimally invasive dentistry and provide an alternative to traditional endodontic cavities (TECs). They have been designed in an effort to preserve the mechanical stability of teeth. The contracted cavity design preserves more of the dentin but may influence the geometric shaping parameters. The aim of this micro-computed tomographic study was to evaluate the influence of contracted endodontic cavities on the preservation of the original root canal anatomy after shaping with nickel-titanium rotary instruments...
January 12, 2018: Journal of Endodontics
https://www.readbyqxmd.com/read/29330161/production-of-bmp4-by-endothelial-cells-is-crucial-for-endogenous-thymic-regeneration
#4
Tobias Wertheimer, Enrico Velardi, Jennifer Tsai, Kirsten Cooper, Shiyun Xiao, Christopher C Kloss, Katja J Ottmüller, Zeinab Mokhtari, Christian Brede, Paul deRoos, Sinéad Kinsella, Brisa Palikuqi, Michael Ginsberg, Lauren F Young, Fabiana Kreines, Sophia R Lieberman, Amina Lazrak, Peipei Guo, Florent Malard, Odette M Smith, Yusuke Shono, Robert R Jenq, Alan M Hanash, Daniel J Nolan, Jason M Butler, Andreas Beilhack, Nancy R Manley, Shahin Rafii, Jarrod A Dudakov, Marcel R M van den Brink
The thymus is not only extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood, and this capacity diminishes considerably with age. We show that thymic endothelial cells (ECs) comprise a critical pathway of regeneration via their production of bone morphogenetic protein 4 (BMP4) ECs increased their production of BMP4 after thymic damage, and abrogating BMP4 signaling or production by either pharmacologic or genetic inhibition impaired thymic repair...
January 12, 2018: Science Immunology
https://www.readbyqxmd.com/read/29324347/design-synthesis-and-biological-evaluation-of-7h-pyrrolo-2-3-d-pyrimidin-4-amine-derivatives-as-selective-btk-inhibitors-with-improved-pharmacokinetic-properties-for-the-treatment-of-rheumatoid-arthritis
#5
Linhong He, Heying Pei, Chufeng Zhang, Mingfeng Shao, Dan Li, Mingli Tang, Taijing Wang, Xiaoxin Chen, Mingli Xiang, Lijuan Chen
Bruton's tyrosine kinase (Btk) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) and Fcγ receptor (FcR) signaling pathways, which makes it a uniquely attractive target for the treatment of autoimmune diseases, such as rheumatoid arthritis (RA). We reported a series of compounds bearing 7H-pyrrolo [2,3-d]pyrimidin-4-amine scaffold that potently inhibited Btk in vitro. Analysis of the structure-activity relationships (SAR) and drug-like profiles led to the discovery of the optimal compound B16...
December 28, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29319845/il-37-inhibits-il-4-il-13-induced-ccl11-production-and-lung-eosinophilia-in-murine-allergic-asthma
#6
Jiaoyan Lv, Yingluo Xiong, Wenjing Li, Xinyi Cui, Xunjia Cheng, Qibin Leng, Rui He
BACKGROUND: IL-37 is emerging as an anti-inflammatory cytokine, particularly in innate inflammation. However, the role of IL-37 in Th2-mediated allergic lung inflammation remains uncertain. We sought to determine the role and the underlying mechanisms of IL-37 in the development of house dust mites (HDM)-induced murine asthma model. METHODS: We examined the effect of IL-37 administration during the sensitization or challenge phase on Th2-mediated allergic asthma induced by inhaled HDM...
January 10, 2018: Allergy
https://www.readbyqxmd.com/read/29306724/first-molecular-evidence-of-equine-granulocytic-anaplasmosis-in-pakistan
#7
Sehrish Saleem, Muhammad Ijaz, Shahid Hussain Farooqi, Muhammad Imran Rashid, Amjad Khan, Awais Masud, Amjad Islam Aqib, Kashif Hussain, Khalid Mehmood, Hui Zhang
Anaplasma phagocytophilum (A. phagocytophilum) is an obligate intracellular bacterium that causes equine granulocytic anaplasmosis (EGA) disease in equines. This pathogen has zoonotic potential, which makes it very important to be detected and controlled as early as possible. This study was aimed to assess the molecular prevalence, associated risk factors of EGA along with its effects on various hematological parameters. This study revealed an overall 10.67% prevalence in equine. Horses showed highest prevalence followed by mules and donkeys presenting 11...
January 4, 2018: Acta Tropica
https://www.readbyqxmd.com/read/29298829/cellularity-of-thymic-epithelial-cells-in-the-postnatal-mouse
#8
Mie Sakata, Izumi Ohigashi, Yousuke Takahama
The molecular and cellular biology of thymic epithelial cells (TECs) often relies on the analysis of TECs isolated in enzymatically digested single-cell suspensions derived from mouse thymus. Many independent studies have reported that the estimated cellularity of total TECs isolated from one adult mouse is on the order of up to 105 However, these numbers appear extremely small given that the cellularity of total thymocytes exceeds 108 and that TECs play multiple roles in thymocyte development and repertoire formation...
January 3, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29296914/severe-platelet-dysfunction-in-nhl-patients-receiving-ibrutinib-is-absent-in-patients-receiving-acalabrutinib
#9
Alexander P Bye, Amanda J Unsworth, Michael J Desborough, Catherine A T Hildyard, Niamh Appleby, David Bruce, Neline Kriek, Sophie H Nock, Tanya Sage, Craig E Hughes, Jonathan M Gibbins
The Bruton tyrosine kinase (Btk) inhibitor ibrutinib induces platelet dysfunction and causes increased risk of bleeding. Off-target inhibition of Tec is believed to contribute to platelet dysfunction and other side effects of ibrutinib. The second-generation Btk inhibitor acalabrutinib was developed with improved specificity for Btk over Tec. We investigated platelet function in patients with non-Hodgkin lymphoma (NHL) receiving ibrutinib or acalabrutinib by aggregometry and by measuring thrombus formation on collagen under arterial shear...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295871/exosomal-ccl2-from-tubular-epithelial-cells-is-critical-for-albumin-induced-tubulointerstitial-inflammation
#10
Lin-Li Lv, Ye Feng, Yi Wen, Wei-Jun Wu, Hai-Feng Ni, Zuo-Lin Li, Le-Ting Zhou, Bin Wang, Jian-Dong Zhang, Steven D Crowley, Bi-Cheng Liu
Albuminuria is a key instigator of tubulointerstitial inflammation associated with CKD, but the mechanism through which filtered albumin propagates renal injury remains unclear. In this study, we explored the role in this process of exosome mRNA released from tubular epithelial cells (TECs). Compared with control mice, acute and chronic kidney injury models had more exosomes containing inflammatory cytokine mRNA, particularly the chemokine CCL2, in kidneys and urine. In vitro stimulation of TECs with BSA recapitulated this finding...
January 2, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29283056/drug-coated-balloons-technologies-and-clinical-applications
#11
Huiying Ang, Jinjie Lin, Ying Ying Huang, Tze Tec Chong, Salvatore Cassese, Michael Joner, Nicolas Foin
The progress and development of drug-coated balloons (DCBs) represents an emerging alternative treatment in peripheral and coronary artery diseases, particularly when a non-stent approach is necessary. Several studies and meta-analyses have evaluated the clinical outcomes of DCBs in different lesions and this review aims to compile the progress and updated clinical data of DCB strategy in both peripheral artery diseases (PAD) and coronary artery diseases (CAD). The review highlights that clinical data encouraged the use of DCB for applications in PAD and in the treatment of coronary in-stent restenosis (ISR)...
December 27, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29277613/hypoxia-induced-activation-of-twist-mir-214-e-cadherin-axis-promotes-renal-tubular-epithelial-cell-mesenchymal-transition-and-renal-fibrosis
#12
Minna Liu, Limin Liu, Ming Bai, Lei Zhang, Feng Ma, Xiaoxia Yang, Shiren Sun
The epithelial-to-mesenchymal transition (EMT) induced by chronic hypoxia is one of the critical causes of renal fibrosis. Previous work reported that the transcription factors Twist plays an important role in hypoxia-induced EMT and renal fibrosis. Recent evidence indicates that miR-214 was regulated by Twist in many fibrotic diseases, but their role in hypoxia-induced EMT and renal fibrosis remains unknown. Here, we found that hypoxia significantly upregulated the expression of miR-214-3p in HK-2 cells, unilateral ureteral obstruction (UUO) nephropathy and patients with chronic kidney disease...
December 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29275580/-response-and-prognosis-of-neoadjuvant-dose-dense-or-standard-schedule-chemotherapy-with-anthracyclines-and-taxanes-for-luminal-b-breast-cancer
#13
A F Qiu, Z L Miao, G K Ge, C B Wang, J Bian, H Y Ma, Q Xu
Objective: To evaluate the efficacy and safety of neoadjuvant dose-dense or standard schedule chemotherapy with anthracyclines and taxanes for Luminal B (HER2-)Breast Cancer. Methods: From January 2010 to December 2014, 168 Luminal B (HER2-) breast cancer patients with stageⅡA-ⅢC confirmed by pathology were randomly assigned to receive one of the following regimens: (group A) concurrent TEC× 4 every 3 weeks, ( group B ) sequential EC× 4-T × 4 every 3 weeks, (group C ) dose-dense TEC× 4 every 2 weeks with G-CSF, (group D) sequential EC× 4(dose-dense)-T × 4 with dose-dense every 2 weeks ...
November 28, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29274114/the-y137h-mutation-in-the-fgcyp51b-protein-confers-reduced-sensitivity-to-tebuconazole-in-fusarium-graminearum
#14
Hengwei Qian, Juan Du, Mengyu Chi, Xiaomei Sun, Wenxing Liang, Jinguang Huang, Baodu Li
BACKGROUND: Fusarium graminearum is the main pathogen of Fusarium Head Blight (FHB), a worldwide plant disease and one of the most significant wheat diseases in China. Demethylation inhibitor (DMI) fungicides, such as tebuconazole (TEC), are widely used to control FHB, but long-term use leads to low efficacy against FHB. Earlier studies showed that DMI resistance is associated with the fungal sterol 14α-demethylase (CYP51) gene, and that point mutations in the CYP51 gene are the primary mechanism of resistance to DMI fungicides...
December 23, 2017: Pest Management Science
https://www.readbyqxmd.com/read/29273493/does-the-orifice-directed-dentin-conservation-access-design-debride-pulp-chamber-and-mesial-root-canal-systems-of-mandibular-molars-similar-to-a-traditional-access-design
#15
Prasanna Neelakantan, Khadija Khan, Geoffrey Pak Hei Ng, Chui Ying Yip, ChengFei Zhang, Gary Shun Pan Cheung
INTRODUCTION: Despite the increasing reports on mechanical aspects of contracted endodontic access cavities (CECs), we believe that the biological aspects (debridement) have not been adequately investigated. This study examined if 1 type of CEC (orifice-directed dentin conservation [DDC] access) was able to debride the pulp chamber, root canals, and isthmus of mesial roots of mandibular molars similar to a traditional endodontic access cavity (TEC). METHODS: Mandibular molars (N = 32) were selected and divided randomly into 2 experimental groups (n = 12) after micro-computed tomographic scanning (group 1: TEC and group 2: DDC) and histologic controls (n = 8)...
December 19, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/29259606/detection-of-quiescent-radioresistant-epithelial-progenitors-in-the-adult-thymus
#16
Maude Dumont-Lagacé, Hervé Gerbe, Tariq Daouda, Jean-Philippe Laverdure, Sylvie Brochu, Sébastien Lemieux, Étienne Gagnon, Claude Perreault
Thymic aging precedes that of other organs and is initiated by the gradual loss of thymic epithelial cells (TECs). Based on in vitro culture and transplantation assays, recent studies have reported on the presence of thymic epithelial progenitor cells (TEPCs) in young adult mice. However, the physiological role and properties of TEPC populations reported to date remain unclear. Using an in vivo label-retention assay, we previously identified a population of quiescent but non-senescent TECs. The goals of this study were therefore (i) to evaluate the contribution of these quiescent TECs to thymic regeneration following irradiation-induced acute thymic injury and (ii) to characterize their phenotypic and molecular profiles using flow cytometry, immunohistology, and transcriptome sequencing...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29259015/inactivation-of-cancer-associated-fibroblasts-caf-disrupts-oncogenic-signaling-in-pancreatic-cancer-cells-and-promotes-its-regression
#17
Patricia Dauer, Xianda Zhao, Vineet K Gupta, Nikita S Sharma, Kousik Kesh, Prisca Gnamlin, Vikas Dudeja, Selwyn M Vickers, Sulagna Banerjee, Ashok Saluja
Resident fibroblasts that contact tumor epithelial cells (TEC) can become irreversibly activated as cancer-associated-fibroblasts (CAF) which stimulate oncogenic signaling in TEC. In this study, we evaluated the crosstalk between CAF and TEC isolated from tumors generated in a mouse model of KRAS/mutp53-induced pancreatic cancer (KPC mice). Transcriptomic profiling conducted after treatment with the anticancer compound Minnelide revealed deregulation of the TGF-β signaling pathway in CAF, resulting in an apparent reversal of their activated state to a quiescent, non-proliferative state...
December 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/29238040/il-3r-alpha-blockade-inhibits-tumor-endothelial-cell-derived-extracellular-vesicle-ev-mediated-vessel-formation-by-targeting-the-%C3%AE-catenin-pathway
#18
Giusy Lombardo, Maddalena Gili, Cristina Grange, Claudia Cavallari, Patrizia Dentelli, Gabriele Togliatto, Daniela Taverna, Giovanni Camussi, Maria Felice Brizzi
The proangiogenic cytokine Interleukin-3 (IL-3) is released by inflammatory cells in breast and ovarian cancer tissue microenvironments and also acts as an autocrine factor for human breast and kidney tumor-derived endothelial cells (TECs). We have previously shown that IL-3-treated endothelial cells (ECs) release extracellular vesicles (EVs), which serve as a paracrine mechanism for neighboring ECs, by transferring active molecules. The impact of an anti-IL-3R-alpha blocking antibody on the proangiogenic effect of EVs released from TECs (anti-IL-3R-EVs) has therefore been investigated in this study...
December 14, 2017: Oncogene
https://www.readbyqxmd.com/read/29234732/endovascular-aneurysm-repair-evar-of-an-infrarenal-abdominal-aortic-aneurysm-aaa-in-a-young-patient-with-systemic-lupus-erythematosus-sle
#19
Nick Z P Ng, Tze Tec Chong
Introduction: While hypertension, pericardial, myocardial, and coronary artery disease are common cardiovascular manifestations of systemic lupus erythematosus (SLE), aortic aneurysms (AA) are rare but increasingly diagnosed, with the true incidence unknown. Case report: A 40 year old female suffering from SLE with a 5.3 cm saccular eccentric infrarenal abdominal aortic aneurysm (AAA) was treated successfully with endovascular aneurysm repair (EVAR) using the Medtronic Endurant II bifurcated stent graft and followed up 2 years post-operatively...
2017: EJVES Short Reports
https://www.readbyqxmd.com/read/29234112/a-switch-in-nucleotide-affinity-governs-activation-of-the-src-and-tec-family-kinases
#20
Freia von Raußendorf, Anita de Ruiter, Thomas A Leonard
The Tec kinases, closely related to Src family kinases, are essential for lymphocyte function in the adaptive immune system. Whilst the Src and Abl kinases are regulated by tail phosphorylation and N-terminal myristoylation respectively, the Tec kinases are notable for the absence of either regulatory element. We have found that the inactive conformations of the Tec kinase Itk and Src preferentially bind ADP over ATP, stabilising both proteins. We demonstrate that Itk adopts the same conformation as Src and that the autoinhibited conformation of Src is independent of its C-terminal tail...
December 12, 2017: Scientific Reports
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