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https://www.readbyqxmd.com/read/28651423/-advances-in-the-research-of-role-of-integrin-linked-kinase-in-angiogenesis
#1
W B Zhou, Y Y Li
Integrin-linked kinase (ILK) has been found for twenty years, and its biological characteristics have been extensively studied by multi-discipline. At present, studies of ILK are mainly focused on its roles in angiogenesis, tumor formation, and tissue fibrosis, etc. In recent years, the regulation effect of ILK in angiogenesis attracts attention of researchers. The studies showed that ILK can stimulate the secretion of angiogenic factor, promote the proliferation and migration of endothelial cells and inhibit their apoptosis, and therefore play an important role in the regulation of angiogenesis...
May 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28651362/possible-macrophage-activation-in-melanoma-patients-receiving-combined-kinase-inhibitor-therapy-following-anti-pd-1-therapy-a-cytokine-profiling-study-of-two-cases
#2
H Umemura, O Yamasaki, S Morizane, K Iwatsuki
No abstract text is available yet for this article.
June 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28651306/heme-oxygenase-1-induction-and-anti-inflammatory-actions-of-atractylodes-macrocephala-and-taraxacum-herba-extracts-prevented-colitis-and-was-more-effective-than-sulfasalazine-in-preventing-relapse
#3
Kyu-Hyun Han, Jong-Min Park, Migyeong Jeong, Young-Min Han, Eun-Jin Go, Juyeon Park, Hocheol Kim, Jae Gab Han, Oran Kwon, Ki Baik Hahm
Background/Aims: In inflammatory bowel disease (IBD), repeated bouts of remission and relapse occur in patients and can impose a risk of colitis-associated cancer. We hypothesized that plant extracts of Atractylodes macrocephala (AM) or Taraxacum herba (TH) may be better than sulfasalazine for treating this disease because these extracts can promote additional regeneration. Methods: Murine intestinal epithelial IEC-6 cells were pretreated with AM or TH before a lipopolysaccharide (LPS)-induced challenge...
June 27, 2017: Gut and Liver
https://www.readbyqxmd.com/read/28651290/anti-inflammatory-effects-of-boldine-and-reticuline-isolated-from-litsea-cubeba-through-jak2-stat3-and-nf-%C3%AE%C2%BAb-signaling-pathways
#4
Xinyao Yang, Xiaoli Gao, Yuan Cao, Qiang Guo, Shanshan Li, Zhixiang Zhu, Yunfang Zhao, Pengfei Tu, Xingyun Chai
The anti-inflammatory effects of boldine and reticuline isolated from Litsea cubeba were evaluated by using xylene-induced ear edema and carrageenan-induced paw edema in mice and rats. Our results demonstrated that intragastric administration with boldine and reticuline significantly mitigated ear weight in mice and decreased paw volume in rats. A combination administration of boldine (0.5 mg/kg) + reticuline (0.25 mg/kg) resulted in a potentiated inhibition in these two models. In parallel, boldine or reticuline reduce the infiltration of neutrophil leukocytes in rat paw tissue, respectively, and the combination of the two groups performed a better anti-inflammatory activity as shown in histopathologies...
June 26, 2017: Planta Medica
https://www.readbyqxmd.com/read/28651239/cardiaprotective-effect-of-crocetin-by-attenuating-apoptosis-in-isoproterenol-induced-myocardial-infarction-rat-model
#5
Weili Zhang, Yuhui Li, Zhiming Ge
Given study evaluates the cardioprotective effect of crocetin in myocardial infracted (MI) rats. MI was produced by administering isoproterenol (90mg/kg/day, i.p.) in rats for two consecutive days. all the animals were divided in to four groups such as control group receives only saline; MI group which receives only isoproterenol and crocetin treated group which receives crocetin (50, 100 and 200mg/kg/day, p.o.) for the duration of 15 days. At the end of dosing left ventricular functions was assessed to estimate its effect on cardiac functions...
June 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28651126/tnf-%C3%AE-exerts-cytotoxic-effects-on-multidrug-resistant-breast-cancer-mcf-7-mx-cells-via-a-non-apoptotic-death-pathway
#6
Morteza Ghandadi, Javad Behravan, Khalil Abnous, Melika Ehtesham Gharaee, Fatemeh Mosaffa
Tumor necrosis factor-α (TNF-α) is a cytokine involved in the various physiopathological processes such as autoimmune disorders and inflammation related diseases. Some multidrug resistant (MDR) cancer cell lines including MCF-7/MX are more vulnerable to cytotoxic effects of TNF-α than their parental lines. In this study, breast cancer cell line MCF-7 and its MDR derivative MCF-7/MX were exposed to TNF-α afterward various downstream signaling mediators of TNF-α were analyzed. Although, treatment of MCF-7 cells with TNF-α activated NF-kB and caused RIP1 ubiquitination, TNF-α exposure led to JNK and RIP1 phosphorylation in MCF-7/MX cells...
June 23, 2017: Cytokine
https://www.readbyqxmd.com/read/28651101/competitive-ligands-facilitate-dissociation-of-the-complex-of-bifunctional-inhibitor-and-protein-kinase
#7
Taavi Ivan, Erki Enkvist, Hedi Sinijarv, Asko Uri
Dissociation of the complex of a ligand and a protein usually follows the kinetic profile of the first order process and the rate of dissociation is not affected by the presence of competitive ligands. We discovered that dissociation of the complex between a bifunctional ligand and a protein kinase (the catalytic subunit of cAMP-dependent protein kinase), an enzyme possessing 2 different substrate binding sites, was accelerated (facilitated) over 50-fold in the presence of competitive ligands at higher concentrations...
June 20, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28650988/transcriptomic-analysis-to-uncover-genes-affecting-cold-resistance-in-the-chinese-honey-bee-apis-cerana-cerana
#8
Kai Xu, Qingsheng Niu, Huiting Zhao, Yali Du, Yusuo Jiang
The biological activity and geographical distribution of honey bees is strongly temperature-dependent, due to their ectothermic physiology. In China, the endemic Apis cerana cerana exhibits stronger cold hardiness than Western honey bees, making the former species important pollinators of winter-flowering plants. Although studies have examined behavioral and physiological mechanisms underlying cold resistance in bees, data are scarce regarding the exact molecular mechanisms. Here, we investigated gene expression in A...
2017: PloS One
https://www.readbyqxmd.com/read/28650961/mfpred-rapid-and-accurate-prediction-of-protein-peptide-recognition-multispecificity-using-self-consistent-mean-field-theory
#9
Aliza B Rubenstein, Manasi A Pethe, Sagar D Khare
Multispecificity-the ability of a single receptor protein molecule to interact with multiple substrates-is a hallmark of molecular recognition at protein-protein and protein-peptide interfaces, including enzyme-substrate complexes. The ability to perform structure-based prediction of multispecificity would aid in the identification of novel enzyme substrates, protein interaction partners, and enable design of novel enzymes targeted towards alternative substrates. The relatively slow speed of current biophysical, structure-based methods limits their use for prediction and, especially, design of multispecificity...
June 26, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28650960/phosphatidylserine-externalization-necroptotic-bodies-release-and-phagocytosis-during-necroptosis
#10
Sefi Zargarian, Inbar Shlomovitz, Ziv Erlich, Aria Hourizadeh, Yifat Ofir-Birin, Ben A Croker, Neta Regev-Rudzki, Liat Edry-Botzer, Motti Gerlic
Necroptosis is a regulated, nonapoptotic form of cell death initiated by receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL) proteins. It is considered to be a form of regulated necrosis, and, by lacking the "find me" and "eat me" signals that are a feature of apoptosis, necroptosis is considered to be inflammatory. One such "eat me" signal observed during apoptosis is the exposure of phosphatidylserine (PS) on the outer plasma membrane. Here, we demonstrate that necroptotic cells also expose PS after phosphorylated mixed lineage kinase-like (pMLKL) translocation to the membrane...
June 26, 2017: PLoS Biology
https://www.readbyqxmd.com/read/28650848/ser-thr-protein-kinase-b2-nadph-oxidase-2-signaling-in-thromboinflammation
#11
Jing Li, Jaehyung Cho
PURPOSE OF REVIEW: Interactions between neutrophils and platelets contribute to the progression of thromboinflammatory disease. However, the regulatory mechanism governing these interactions is poorly understood. The present review focuses on the crucial role of Ser/Thr protein kinase B (AKT)2-NADPH oxidase 2 (NOX2) signaling in regulating neutrophil and platelet activation and their heterotypic interactions under thromboinflammatory conditions. RECENT FINDINGS: Growing evidence has shown that platelets, leukocytes, and blood coagulation need to be considered to treat thromboinflammatory disease in which inflammation and thrombosis occur concurrently...
June 24, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28650718/subversion-of-rab5-regulated-autophagy-by-the-intracellular-pathogen-ehrlichia-chaffeensis
#12
Yasuko Rikihisa
Intracellular pathogens often exploit RAB functions to establish a safe haven in which to survive and proliferate. Ehrlichia chaffeensis, an obligatory intracellular bacterium, resides in specialized membrane-bound inclusions that have early endosome-like characteristics, e.g., resident RAB5 GTPase and RAB5 effectors, including VPS34 (the catalytic subunit of class III phosphatidylinositol 3-kinase), but the inclusions lack late endosomal or lysosomal markers. Within inclusions, Ehrlichia obtains host-derived nutrients by inducing RAB5-regulated autophagy using Ehrlichia translocated factor-1 deployed by its type IV secretion system...
June 26, 2017: Small GTPases
https://www.readbyqxmd.com/read/28650698/the-rock-isoforms-differentially-regulate-the-morphological-characteristics-of-carcinoma-cells
#13
Rachel J Jerrell, Mitchell J Leih, Aron Parekh
Rho-associated kinase (ROCK) activity drives cell migration via actomyosin contractility. During invasion, individual cancer cells can transition between two modes of migration, mesenchymal and amoeboid. Changes in ROCK activity can cause a switch between these migration phenotypes which are defined by distinct morphologies. However, recent studies have shown that the ROCK isoforms are not functionally redundant as previously thought. Therefore, it is unclear whether the ROCK isoforms play different roles in regulating migration phenotypes...
June 26, 2017: Small GTPases
https://www.readbyqxmd.com/read/28650650/prodrugs-of-pyrazolo-3-4-d-pyrimidines-from-library-synthesis-to-evaluation-as-potential-anticancer-agents-in-an-orthotopic-glioblastoma-model
#14
Giulia Vignaroli, Giulia Iovenitti, Claudio Zamperini, Federica Coniglio, Pierpaolo Calandro, Alessio Molinari, Anna Lucia Fallacara, Andrea Sartucci, Alessia Calgani, David Colecchia, Andrea Mancini, Claudio Festuccia, Elena Dreassi, Massimo Valoti, Francesca Musumeci, Mario Chiariello, Adriano Angelucci, Maurizio Botta, Silvia Schenone
Pyrazolo[3,4-d]pyrimidines are potent protein kinase inhibitors with promising antitumor activity but suboptimal aqueous solubility, consequently worth to be further optimized. Herein, we present the one-pot two-step procedure for the synthesis of a set of pyrazolo[3,4-d]pyrimidine prodrugs (1a-9a,e) with higher aqueous solubility and enhanced pharmacokinetic and therapeutic properties. ADME studies demonstrated for the most promising prodrugs a better aqueous solubility, a favorable hydrolysis in human and murine serum and an increased ability to cross cell membranes with respect to the parental drugs, explaining their better 24h in vitro cytotoxicity against human glioblastoma U87 cell line...
June 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28650561/craniosynostosis-in-patients-with-rasopathies-accumulating-clinical-evidence-for-expanding-the-phenotype
#15
Kimiko Ueda, Masako Yaoita, Tetsuya Niihori, Yoko Aoki, Nobuhiko Okamoto
RASopathies are phenotypically overlapping genetic disorders caused by dysregulation of the RAS/mitogen-activated protein kinase (MAPK) signaling pathway. RASopathies include Noonan syndrome, cardio-facio-cutaneous (CFC) syndrome, Costello syndrome, Neurofibromatosis type 1, Legius syndrome, Noonan syndrome with multiple lentigines, Noonan-like syndrome, hereditary gingival fibromatosis, and capillary malformation/arteriovenous malformation syndrome. Recently, six patients with craniosynostosis and Noonan syndrome involving KRAS mutations were described in a review, and a patient with craniosynostosis and Noonan syndrome involving a SHOC2 mutation has also been reported...
June 26, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28650560/uncovering-the-role-of-brain-derived-neurotrophic-factor-bdnf-trkb-signaling-in-head-and-neck-malignancies
#16
REVIEW
Juliana Kern de Moraes, Vivian Petersen Wagner, Felipe Paiva Fonseca, Pablo Agustin Vargas, Caroline Brunetto de Farias, Rafael Roesler, Manoela Domingues Martins
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that was first known as responsible for sustain the growth, function and plasticity of neural cells. BDNF exerts its effects by binding to the tyrosine kinase receptor B (TrkB). The BDNF/TrkB axis has been reported to be overexpressed in several neurogenic and non-neurogenic tumors. Its higher expression was associated with a poor prognosis to patients affected by different human malignancies, tumor growth, invasion and metastasis; epithelial-mesenchymal transition (EMT) and resistance to chemotherapy...
June 26, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28650526/a-dual-administration-microtracer-technique-to-characterize-the-absorption-distribution-metabolism-and-excretion-of-14-c-seletalisib-ucb5857-in-healthy-subjects
#17
Eric Helmer, Jean-Marie Nicolas, Jeff Long, Ad F Roffel, Emma Jones, Hugues Chanteux, Nieves Diaz, Holly Garratt, Tjerk Bosje
Phosphoinositide 3 kinases are targets for development of small-molecule inhibitors to disrupt progression of immune-inflammatory diseases. This phase 1 open-label study (Eudract 2014-005353-39) evaluated the safety and relative bioavailability of 2 new seletalisib (UCB5857) formulations (A and B) compared with a reference formulation. Absolute bioavailability (period 1a, n = 6) and disposition and metabolism (period 1b, n = 6) of the reference formulation were evaluated: healthy subjects received 30 mg orally plus ∼20 μg of a (14) C-labeled microtracer (intravenously in 1a, orally in 1b)...
June 26, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28650474/an-activating-mutation-of-gnb1-is-associated-with-resistance-to-tyrosine-kinase-inhibitors-in-etv6-abl1-positive-leukemia
#18
O Zimmermannova, E Doktorova, J Stuchly, V Kanderova, D Kuzilkova, H Strnad, J Starkova, M Alberich-Jorda, J H F Falkenburg, J Trka, J Petrak, J Zuna, M Zaliova
Leukemias harboring the ETV6-ABL1 fusion represent a rare subset of hematological malignancies with unfavorable outcomes. The constitutively active chimeric Etv6-Abl1 tyrosine kinase can be specifically inhibited by tyrosine kinase inhibitors (TKIs). Although TKIs represent an important therapeutic tool, so far, the mechanism underlying the potential TKI resistance in ETV6-ABL1-positive malignancies has not been studied in detail. To address this issue, we established a TKI-resistant ETV6-ABL1-positive leukemic cell line through long-term exposure to imatinib...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28650470/signaling-coupled-epigenomic-regulation-of-gene-expression
#19
REVIEW
R Kumar, S Deivendran, T R Santhoshkumar, M R Pillai
Inheritance of genomic information independent of the DNA sequence, the epigenetics, as well as gene transcription are profoundly shaped by serine/threonine and tyrosine signaling kinases and components of the chromatin remodeling complexes. To precisely respond to a changing external milieu, human cells efficiently translate upstream signals into post-translational modifications (PTMs) on histones and coregulators such as corepressors, coactivators, DNA-binding factors and PTM modifying enzymes. Because a protein with multiple residues for putative PTMs is expected to undergo more than one PTM in cells stimulated with growth factors, the outcome of combinational PTM codes on histones and coregulators is profoundly shaped by regulatory interplays between PTMs...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28650469/a-compartmentalized-phosphoinositide-signaling-axis-at-cilia-is-regulated-by-inpp5e-to-maintain-cilia-and-promote-sonic-hedgehog-medulloblastoma
#20
S E Conduit, V Ramaswamy, M Remke, D N Watkins, B J Wainwright, M D Taylor, C A Mitchell, J M Dyson
Sonic Hedgehog (SHH) signaling at primary cilia drives the proliferation and progression of a subset of medulloblastomas, the most common malignant paediatric brain tumor. Severe side effects associated with conventional treatments and resistance to targeted therapies has led to the need for new strategies. SHH signaling is dependent on primary cilia for signal transduction suggesting the potential for cilia destabilizing mechanisms as a therapeutic target. INPP5E is an inositol polyphosphate 5-phosphatase that hydrolyses PtdIns(4,5)P2 and more potently, the phosphoinositide (PI) 3-kinase product PtdIns(3,4,5)P3...
June 26, 2017: Oncogene
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