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https://www.readbyqxmd.com/read/29245051/magnesium-phosphate-ceramics-incorporating-a-novel-indene-compound-promote-osteoblast-differentiation-in%C3%A2-vitro-and-bone-regeneration-in%C3%A2-vivo
#1
Ju Ang Kim, Hui-Suk Yun, Young-Ae Choi, Jung-Eun Kim, So-Young Choi, Tae-Geon Kwon, Young Kyung Kim, Tae-Yub Kwon, Myung Ae Bae, Nak Jeong Kim, Yong Chul Bae, Hong-In Shin, Eui Kyun Park
Incorporating bioactive molecules into synthetic ceramic scaffolds is challenging. In this study, to enhance bone regeneration, a magnesium phosphate (MgP) ceramic scaffold was incorporated with a novel indene compound, KR-34893. KR-34893 induced the deposition of minerals and expression of osteoblast marker genes in primary human bone marrow mesenchymal stem cells (BMSCs) and a mouse osteoblastic MC3T3-E1 cell line. Analysis of the mode of action showed that KR-34893 induced the phosphorylation of MAPK/extracellular signal-regulated kinase and extracellular signal-regulated kinase, and subsequently the expression of bone morphogenetic protein 7, accompanied by SMAD1/5/8 phosphorylation...
December 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/29245047/polyriboinosinic-polyribocytidylic-acid-facilitates-interleukin-6-and-interleukin-8-secretion-in-human-dermal-fibroblasts-via-the-jak-stat3-and-p38-mapk-signal-transduction-pathways
#2
Zhang Ying Zhu, Cong Zhuo Jia, Jian Min Luo, Li Wang
Polyriboinosinic-polyribocytidylic acid (polyI:C) is a viral dsRNA analoguethat promotes wounds healing, accelerates re-epithelialization, granulation and neovascularization, and induces pro-inflammatory cytokine release. Little is known about polyI:C mediated induction of inflammatory mediators in human dermal fibroblast (HDFs), which form the primary scaffold for epithelial cells covering the wound. Here, we found that polyI:C enhances IL-6 and IL-8 mRNA expression and induces of IL-6 and IL-8 production in a concentration-dependent and time-dependent manner in HDFs...
December 12, 2017: Cytokine
https://www.readbyqxmd.com/read/29245030/osmotin-a-plant-defense-tool-against-biotic-and-abiotic-stresses
#3
REVIEW
Hakim, Abid Ullah, Amjad Hussain, Muhammad Shaban, Aamir Hamid Khan, Muna Alariqi, Summia Gul, Zhang Jun, Sun Lin, Jianying Li, Shuangxia Jin, Muhammad Farooq Hussain Munis
Plants are prone to a number of pathogens and abiotic stresses that cause various disorders. However, plants possess a defense mechanism to cope with these stresses. The osmotin protein belongs to the PR-5 family of Pathogenesis-related (PR) proteins, which are produced in response to diseases caused by various biotic and abiotic stresses. Osmotin uses a signal transduction pathway to inhibit the activity of defensive cell wall barriers and increases its own cytotoxic efficiency. However, in response to cytotoxic effects, this pathway stimulates a mitogen-activated protein kinase (MAPK) cascade that triggers changes in the cell wall and enables osmotin's entrance into the plasma membrane...
December 7, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29244751/spirulina-extract-enhanced-a-protective-effect-in-type-1-diabetes-by-anti-apoptosis-and-anti-ros-production
#4
Jiyeong Lee, Arum Park, Mi Jeong Kim, Hee-Joung Lim, Young-Ah Rha, Hee-Gyoo Kang
Interest in the nutritional value and pharmacological activities of blue-green algae has gradually increased. Spirulina extracts show protective effects against apoptosis and inflammatory damage in various cell types. Here, we investigated the protective effects of extracts from Spirulina maxima in a cytokine-mediated type 1 diabetes model in vitro and in streptozotocin-induced diabetic Wistar rats in vivo. Interleukin-1β and interferon-gamma induced substantial cytotoxicity to RINm5F rat insulinoma cells, increasing nitric oxide (NO) production, nuclear factor-kappa B (NF-κB) activity, the expression of endoplasmic reticulum (ER) stress genes, and activation of mitogen-activated protein kinases and key genes related apoptosis...
December 15, 2017: Nutrients
https://www.readbyqxmd.com/read/29244485/critical-role-of-trp-588-of-presynaptic-munc13-1-for-ligand-binding-and-membrane-translocation
#5
Joydip Das, Noemi Kedei, Jessica S Kelsey, Youngki You, Satyabrata Pany, Gary A Mitchell, Nancy E Lewin, Peter M Blumberg
Munc13-1 is a presynaptic active-zone protein essential for neurotransmitter release and presynaptic plasticity in the brain. This multi-domain scaffold protein contains a C1 domain that binds to the activator diacylglycerol/phorbol ester. Although the C1 domain bears close structural homology with the C1 domains of protein kinase C (PKC), the tryptophan residue at position 22 (588 in the full-length Munc13-1) occludes the activator binding pocket, which is not the case for PKC. To elucidate the role of this tryptophan, we generated W22A, W22K, W22D, W22Y and W22F substitutions in the full-length Munc13-1, expressed the GFP- tagged constructs in Neuro-2a cells, and measured their membrane translocation in response to phorbol ester treatment by imaging of the live cells using confocal microscopy...
December 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/29243930/structure-based-kinase-profiling-to-understand-the-polypharmacological-behavior-of-therapeutic-molecules
#6
Devawati Dutta, Ranjita Das, Chhabinath Mandal, Chitra Mandal
Several drugs elicit their therapeutic efficacy by modulating multiple cellular targets and possess varied polypharmacological actions. The identification of the molecular targets of a potent bioactive molecule is essential in determining its overall polypharmacological profile. Experimental procedures are expensive and time-consuming. Therefore, computational approaches are actively implemented in rational drug discovery. Here, we demonstrate a computational pipeline, based on reverse virtual screening technique using several consensus scoring strategies, and perform structure-based kinase profiling of 12 FDA-approved drugs...
December 15, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29243851/alterations-in-gene-expression-in-vitamin-d-deficiency-down-regulation-of-liver-cyp7a1-and-renal-oat3-in-mice
#7
Holly P Quach, Keumhan Noh, Stacie Y Hoi, Adrie Bruinsma, Geny M M Groothuis, Albert P Li, Edwin C Y Chow, K Sandy Pang
The vitamin D-deficient model, established in C57BL/6 mouse after 8-week feeding of vitamin D-deficient diets in absence or presence of added calcium, was found associated with elevated levels of plasma parathyroid hormone (PTH) and plasma and liver cholesterol, and reduction in cholesterol 7α-hydroxylase (Cyp7a1, rate-limiting enzyme for cholesterol metabolism) and renal Oat3 mRNA/protein expression levels. There was, however, no change in plasma calcium and phosphate levels. Appraisal of the liver revealed up-regulation of mRNA expressions of the small heterodimer partner (Shp) and attenuation of Cyp7a1, which contributed to hypercholesterolemia in vitamin D-deficiency...
December 15, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29243822/nrf2-promotes-oesophageal-cancer-cell-proliferation-via-metabolic-reprogramming-and-detoxification-of-reactive-oxygen-species
#8
Yuki Kitano, Yoshifumi Baba, Shigeki Nakagawa, Keisuke Miyake, Masaaki Iwatsuki, Takatsugu Ishimoto, Yo-Ichi Yamashita, Naoya Yoshida, Masayuki Watanabe, Mitsuyoshi Nakao, Hideo Baba
Cancer cells consume a large amount of energy and maintain high levels of anabolism to promote cell proliferation via metabolic reprogramming. Nuclear factor erythroid 2-related factor 2 (Nrf2; NFE2L2) is a master transcription regulator of stress responses and promotes metabolic reprogramming to support cell proliferation in various types of cancer. As oesophageal cancer is one of the most aggressive gastrointestinal cancers, we aimed to clarify the effect of Nrf2 on metabolic reprogramming in oesophageal cancer...
December 15, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29243812/dysregulated-mitogen-activated-protein-kinase-signalling-as-an-oncogenic-basis-for-clear-cell-sarcoma-of-the-kidney
#9
Colin Kenny, Naomi McDonagh, Antonio Lazaro, Elaine O'Meara, Rut Klinger, Darran O'Connor, Fiona Roche, Karsten Hokamp, Maureen J O'Sullivan
The oncogenic mechanisms and tumour biology underpinning Clear Cell Sarcoma of Kidney (CCSK), the second commonest paediatric renal malignancy, are poorly understood and currently therapy depends heavily on doxorubicin with cardiotoxic side-effects. Previously, we characterised the balanced t(10;17)(q22;p13) chromosomal translocation, identified at that time as the only recurrent genetic aberration in CCSK. This translocation results in an in-frame fusion of the genes YWHAE (encoding 14-3-3ε)and NUTM2, with a somatic incidence of 12%...
December 15, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29243778/apatinib-resensitizes-cisplatin-resistant-non-small-cell-lung-carcinoma-a549-cell-through-reversing-multidrug-resistance-and-suppressing-erk-signaling-pathway
#10
Z-L Liu, B-J Jin, C-G Cheng, F-X Zhang, S-W Wang, Y Wang, B Wu
OBJECTIVE: To observe the reversal effect of apatinib on the resistance to cisplatin (DDP) of A549/cisplatin (A549/DDP) cells and its relevant mechanism. MATERIALS AND METHODS: A549/DDP cells were treated with the control method, apatinib alone, DDP alone and DDP combined with apatinib. The cell proliferation was detected by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the cell clone formation assay. The cell apoptosis was detected by Hoechst 33258 staining and annexin V and propidium iodide (PI) double labeling...
December 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29243777/mirna-338-3p-regulates-cervical-cancer-cells-proliferation-by-targeting-macc1-through-mapk-signaling-pathway
#11
F-F Hua, S-S Liu, L-H Zhu, Y-H Wang, X Liang, N Ma, H-R Shi
OBJECTIVE: Aberrant expression of miR-338-3p has recently involved in the progression and development of various types of malignant tumors, but its role in the progression of cervical cancer remains unknown. This study aims to investigate the role of miR-338-3p/MACC1 axis in the progression of cervical cancer. PATIENTS AND METHODS: MiR-338-3p and metastasis-associated in colon cancer 1 (MACC1) expression was determined in cervical cancer by quantitative real-time PCR (qRT-PCR)...
December 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29243286/conformational-dynamics-of-human-protein-kinase-ck2%C3%AE-and-its-effect-on-function-and-inhibition
#12
Ashutosh Srivastava, Tsuyoshi Hirota, Stephan Irle, Florence Tama
Protein Kinase CK2 is ubiquitously expressed and highly conserved protein kinase that shows constitutive activity. It phosphorylates a diverse set of proteins and plays crucial role in several cellular processes. The catalytic subunit of this enzyme (CK2α) shows remarkable flexibility as evidenced in numerous crystal structures determined till now. Here, using analysis of multiple crystal structures and long timescale molecular dynamics simulations, we explore the conformational flexibility of CK2α. The enzyme shows considerably higher flexibility in the solution as compared to that observed in crystal structure ensemble...
December 15, 2017: Proteins
https://www.readbyqxmd.com/read/29243243/shikonin-inhibits-myeloid-differentiation-protein-2-to-prevent-lipopolysaccharide-induced-acute-lung-injury
#13
Yali Zhang, Tingting Xu, Zheer Pan, Xiangting Ge, Chuchu Sun, Chun Lu, Hongjin Chen, Zhongxiang Xiao, Bing Zhang, Yuanrong Dai, Guang Liang
BACKGROUND AND PURPOSE: Acute lung injury (ALI) is a challenging clinical syndrome which manifests as an acute inflammatory response. Myeloid differentiation protein 2 (MD2) has an important role in mediating lipopolysaccharide (LPS)-induced inflammation. Currently, there are no effective molecular-based therapies for ALI or viable biomarkers for predicting the severity of disease. Recent preclinical studies have shown that shikonin (SHI), a natural naphthoquinone, prevents LPS-inflammation...
December 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29243095/ca2-camkk%C3%AE-pathway-is-required-for-adiponectin-induced-secretion-in-rat-submandibular-gland
#14
Chong Ding, Zhi-Hao Du, Sheng-Lin Li, Li-Ling Wu, Guang-Yan Yu
Adiponectin functions as a promoter of saliva secretion in rat submandibular gland via activation of adenosine monophosphate-activated protein kinase (AMPK) and increased paracellular permeability. Ca2+ mobilization is the primary signal for fluid secretion in salivary acinar cells. However, whether intracellular Ca2+ mobilization is involved in adiponectin-induced salivary secretion is unknown. Here, we found that full-length adiponectin (fAd) increased intracellular Ca2+ and saliva secretion in submandibular glands...
December 14, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29243084/quantification-of-breast-cancer-protein-biomarkers-at-different-expression-levels-in-human-tumors
#15
Yi Chen, David Britton, Elizabeth R Wood, Stephen Brantley, Michelle Fournier, Marek Wloch, Vonetta L Williams, Joseph Johnson, Anthony Magliocco, Ian Pike, John M Koomen
Liquid chromatography-selected reaction monitoring (LC-SRM) mass spectrometry has developed into a versatile tool for quantification of proteins with a wide range of applications in basic science, translational research, and clinical patient assessment. This strategy uniquely complements traditional pathology approaches, like hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC). The multiplexing capabilities offered by mass spectrometry are currently unmatched by other techniques. However, quantification of biomarkers in tissue specimens without the other data obtained from H&E-stained slides or IHC, including tumor cellularity or percentage of positively stained cells inter alia, may not provide as much information that is needed to fully understand tumor biology or properly assess the patient...
December 15, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29243082/dihydroquercetin-ameliorated-acetaminophen-induced-hepatic-cytotoxicity-via-activating-jak2-stat3-pathway-and-autophagy
#16
Wenjing Zai, Wei Chen, Jingyun Luan, Jiajun Fan, Xuyao Zhang, Zimei Wu, Tao Ding, Dianwen Ju, Hongrui Liu
Acetaminophen (APAP) overdose is currently the leading cause of acute liver disease, but therapeutic treatment strategies are commonly limited. Although dihydroquercetin (DHQ) is an attractive botanical antioxidant, its protective potential for liver disease remains elusive. The present study investigated the protective effects of DHQ against APAP-induced hepatic cytotoxicity. Primary mouse hepatocytes were treated with different concentrations of DHQ followed by APAP administration. Our data showed that DHQ relieved APAP-induced growth inhibition and lactate dehydrogenase (LDH) release in a dose-dependent manner, as well as inhibited APAP-induced necrosis and extracellular signal regulated kinase-c-Jun-N-terminal kinase (ERK-JNK) stress...
December 14, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29243030/sinapic-acid-inhibits-the-il-1%C3%AE-induced-inflammation-via-mapk-downregulation-in-rat-chondrocytes
#17
Xiaojian Huang, Qiyong Pan, Zekai Mao, Rui Zhang, Xiaohu Ma, Yang Xi, Hongbo You
Osteoarthritis (OA) is a degenerative joint disease frequently seen in the elderly population. Sinapic acid (SA), a commonly found phenolic acid, has been pharmacologically evaluated for its anti-inflammation effects in various studies. To explore its potential therapeutic role for OA, rat chondrocytes were treated with IL-1β (10 ng/ml) with different concentrations of SA in vitro. Our study revealed that SA could inhibit the IL-1β-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2). Consistent with these findings, the increased protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (Cox)-2 could also be downregulated by SA...
December 14, 2017: Inflammation
https://www.readbyqxmd.com/read/29242851/in-depth-ptdins-3-4-5-p3-signalosome-analysis-identifies-dapp1-as-a-negative-regulator-of-gpvi-driven-platelet-function
#18
Tom N Durrant, James L Hutchinson, Kate J Heesom, Karen E Anderson, Len R Stephens, Phillip T Hawkins, Aaron J Marshall, Samantha F Moore, Ingeborg Hers
The class I phosphoinositide 3-kinase (PI3K) isoforms play important roles in platelet priming, activation, and stable thrombus formation. Class I PI3Ks predominantly regulate cell function through their catalytic product, the signaling phospholipid phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3], which coordinates the localization and/or activity of a diverse range of binding proteins. Notably, the complete repertoire of these class I PI3K effectors in platelets remains unknown, limiting mechanistic understanding of class I PI3K-mediated control of platelet function...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29242808/small-peptide-substrates-and-high-resolution-peptide-gels-for-the-analysis-of-site-specific-protein-phosphorylation-and-dephosphorylation
#19
Laura Johnson Battle, Timothy C Chambers
Protein phosphorylation and dephosphorylation reactions play key regulatory roles in many fundamental cellular processes. Due to the large number of kinases and phosphatases in the genome, the identification of the specific enzymes responsible for a given site in a given protein is immensely challenging. However, because protein kinases and phosphatases recognize local specificity determinants within proteins, it is possible to use small peptides to study the characteristics of site-specific phosphorylation...
2017: Journal of Biological Methods
https://www.readbyqxmd.com/read/29242632/quantitative-assessment-of-cell-fate-decision-between-autophagy-and-apoptosis
#20
Bing Liu, Zoltán N Oltvai, Hülya Bayır, Gary A Silverman, Stephen C Pak, David H Perlmutter, Ivet Bahar
Autophagy and apoptosis are cellular processes that regulate cell survival and death, the former by eliminating dysfunctional components in the cell, the latter by programmed cell death. Stress signals can induce either process, and it is unclear how cells 'assess' cellular damage and make a 'life' or 'death' decision upon activating autophagy or apoptosis. A computational model of coupled apoptosis and autophagy is built here to analyze the underlying signaling and regulatory network dynamics. The model explains the experimentally observed differential deployment of autophagy and apoptosis in response to various stress signals...
December 14, 2017: Scientific Reports
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