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https://www.readbyqxmd.com/read/29245156/selection-and-targeting-of-epcam-protein-by-ssdna-aptamer
#1
Walhan Alshaer, Nida Ababneh, Mamon Hatmal, Heba Izmirli, Moujab Choukeife, Alaa Shraim, Nour Sharar, Aya Abu-Shiekah, Fadwa Odeh, Abeer Al Bawab, Abdalla Awidi, Said Ismail
Aptamers are molecules that reveal highly complex and refined molecular recognition properties. These molecules are capable of binding with high affinity and selectivity to targets, ranging from small molecules to whole living cells. Several aptamers have been selected for targeting cellular proteins and they have also used in developing therapeutics and diagnostic strategies. Epithelial cell adhesion molecule (EpCAM) is considered as a cancer stem cell (CSC) biomarker and one of the most promising targets for aptamer selection against CSCs...
2017: PloS One
https://www.readbyqxmd.com/read/29245072/phloretin-attenuates-mucus-hypersecretion-and-airway-inflammation-induced-by-cigarette-smoke
#2
Hao Wang, Ting Yang, Tao Wang, Nanya Hao, Yongchun Shen, Yanqiu Wu, Zhicheng Yuan, Lei Chen, Fuqiang Wen
BACKGROUNDS: Cigarette smoke (CS)-induced airway mucus hypersecretion and inflammation are the prominent features of chronic obstructive pulmonary disease (COPD). As an anti-inflammatory flavonoid, phloretin was found to be involved in various inflammatory disorders such as sepsis. In this study, the effects of phloretin on CS-induced airway mucin secretion and inflammation were investigated in vivo and in vitro. METHODS: Phloretin dissolved in 1% DMSO was daily injected intraperitoneally to mice, which were then exposed to CS for four weeks...
December 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29245067/lin28a-functionally-modulates-bupivacaine-induced-dorsal-root-ganglion-neuron-apoptosis-through-trka-activation
#3
Liangsheng Yu, Yuanxu Jiang, Bin Tang
PURPOSE: Lin-28 Homolog A gene (Lin28a) is an important regulator in nerve system. In this study, we investigated the functional mechanism of Lin28a during the process of bupivacaine (BUP)-induced neuronal apoptosis of spinal cord dorsal root ganglion neurons (DRGNs). METHODS: Young mouse DRGNs were cultured in vitro and treated with series concentrations of BUP. Apoptosis was evaluated by TUNEL assay. Corresponding Lin28a mRNA and protein expressions were evaluated by qRT-PCR and western blot (WB) assays...
December 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29245059/proteomic-analysis-of-six-and-twelve-month-hippocampus-and-cerebellum-in-a-murine-down-syndrome-model
#4
Guido N Vacano, David S Gibson, Abdullah Arif Turjoman, Jeremy W Gawryluk, Jonathan D Geiger, Mark Duncan, David Patterson
This study was designed to investigate the brain proteome of the Ts65Dn mouse model of Down syndrome. We profiled the cerebellum and hippocampus proteomes of 6- and 12-month-old trisomic and disomic mice by difference gel electrophoresis. We quantified levels of 2082 protein spots and identified 272 (170 unique UniProt accessions) by mass spectrometry. Four identified proteins are encoded by genes trisomic in the Ts65Dn mouse. Three of these (CRYZL11, EZR, and SOD1) were elevated with p-value <0.05, and 2 proteins encoded by disomic genes (MAPRE3 and PHB) were reduced...
November 26, 2017: Neurobiology of Aging
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
#5
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/29245026/ketogenic-diet-induced-extension-of-longevity-in-epileptic-kcna1-null-mice-is-influenced-by-gender-and-age-at-treatment-onset
#6
Kyoung-Chul Chun, Shun-Chieh Ma, Hyoungil Oh, Jong M Rho, Do Young Kim
Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature mortality in patients with epilepsy, and has been linked to multiple risk factors, including gender and early age at seizure onset. Despite the lack of a targeted therapy for SUDEP, it has recently been shown that a high-fat, low carbohydrate ketogenic diet (KD) enhances longevity in the epileptic Kcna1-null (KO) mouse, a validated model of SUDEP. Here, we asked whether the KD-driven prolongation of lifespan in KO mice is dependent on sex and/or age at treatment onset...
November 21, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/29245008/on-the-design-of-combination-cancer-therapy
#7
James H Doroshow, Richard M Simon
Combination therapy programs are the hallmark of the successful treatment of all forms of human malignancies. In this issue of Cell, Palmer and Sorger present data suggesting that cell culture results indicative of synergistic anticancer drug interactions rarely translate clinically and that the results of combination therapies in mouse models or human clinical trials, even if successful, are best explained by the independent activities of the individually administered drugs.
December 14, 2017: Cell
https://www.readbyqxmd.com/read/29245000/does-traumatic-brain-injury-hold-the-key-to-the-alzheimer-s-puzzle
#8
Robert E Becker, Dimitrios Kapogiannis, Nigel H Greig
INTRODUCTION: Neurodegenerative disorders have been a graveyard for hundreds of well-intentioned efforts at drug discovery and development. Concussion and other traumatic brain injuries (TBIs) and Alzheimer's disease (AD) share many overlapping pathologies and possible clinical links. METHODS: We searched the literature since 1995 using MEDLINE and Google Scholar for the terms concussion, AD, and shared neuropathologies. We also studied a TBI animal model as a supplement to transgenic (Tg) mouse AD models for evaluating AD drug efficacy by preventing neuronal losses...
December 12, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29244957/hypercementosis-associated-with-enpp1-mutations-and-gaci
#9
V Thumbigere-Math, A Alqadi, N I Chalmers, M B Chavez, E Y Chu, M T Collins, C R Ferreira, K FitzGerald, R I Gafni, W A Gahl, K S Hsu, M S Ramnitz, M J Somerman, S G Ziegler, B L Foster
Mineralization of bones and teeth is tightly regulated by levels of extracellular inorganic phosphate (Pi) and pyrophosphate (PPi). Three regulators that control pericellular concentrations of Pi and PPi include tissue-nonspecific alkaline phosphatase (TNAP), progressive ankylosis protein (ANK), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). Inactivation of these factors results in mineralization disorders affecting teeth and their supporting structures. This study for the first time analyzed the effect of decreased PPi on dental development in individuals with generalized arterial calcification of infancy (GACI) due to loss-of-function mutations in the ENPP1 gene...
December 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/29244955/dose-and-diet-sources-of-arsenic-intake-in-mouse-in-utero-exposure-scenarios
#10
Manuela Murko, Brittany Elek, Miroslav Styblo, David James Thomas, Kevin A Francesconi
In humans, early life exposure to inorganic arsenic is associated with adverse health effects. Inorganic arsenic in utero or in early postnatal life also produces adverse health effects in offspring of pregnant mice that consumed drinking water containing low part per billion levels of inorganic arsenic. Because aggregate exposure of pregnant mice to inorganic arsenic from both drinking water and food has not been fully evaluated in experimental studies, quantifying arsenic exposure of the developing mouse is problematic...
December 15, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29244873/fatty-acids-in-non-alcoholic-steatohepatitis-focus-on-pentadecanoic-acid
#11
Wonbeak Yoo, Donjeta Gjuka, Heather L Stevenson, Xiaoling Song, Hong Shen, Suk Young Yoo, Jing Wang, Michael Fallon, George N Ioannou, Stephen A Harrison, Laura Beretta
Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and ranges from isolated steatosis to NASH. To determine whether circulating fatty acids could serve as diagnostic markers of NAFLD severity and whether specific fatty acids could contribute to the pathogenesis of NASH, we analyzed two independent NAFLD patient cohorts and used the methionine- and choline-deficient diet (MCD) NASH mouse model. We identified six fatty acids that could serve as non-invasive markers of NASH in patients with NAFLD...
2017: PloS One
https://www.readbyqxmd.com/read/29244868/cyclodextrin-containing-hydrogels-as-an-intraocular-lens-for-sustained-drug-release
#12
Xiao Li, Yang Zhao, Kaijie Wang, Lei Wang, Xiaohui Yang, Siquan Zhu
To improve the efficacy of anti-inflammatory factors in patients who undergo cataract surgery, poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (p(HEMA-co-MMA)) hydrogels containing β-cyclodextrin (β-CD) (pHEMA/MMA/β-CD) were designed and prepared as intraocular lens (IOLs) biomaterials that could be loaded with and achieve the sustained release of dexamethasone. A series of pHEMA/MMA/β-CD copolymers containing different ratios of β-CD (range, 2.77 to 10.24 wt.%) were obtained using thermal polymerization...
2017: PloS One
https://www.readbyqxmd.com/read/29244860/lithium-reduces-blood-glucose-levels-but-aggravates-albuminuria-in-btbr-ob-ob-mice
#13
Theun de Groot, Lars Damen, Leanne Kosse, Mohammad Alsady, Rosalinda Doty, Ruben Baumgarten, Susan Sheehan, Johan van der Vlag, Ron Korstanje, Peter M T Deen
Glycogen synthase kinase 3 (GSK3) plays an important role in the development of diabetes mellitus and renal injury. GSK3 inhibition increases glucose uptake in insulin-insensitive muscle and adipose tissue, while it reduces albuminuria and glomerulosclerosis in acute kidney injury. The effect of chronic GSK3 inhibition in diabetic nephropathy is not known. We tested the effect of lithium, the only clinical GSK3 inhibitor, on the development of diabetes mellitus and kidney injury in a mouse model of diabetic nephropathy...
2017: PloS One
https://www.readbyqxmd.com/read/29244815/analysis-of-the-efficacy-of-taiwanese-freeze-dried-neurotoxic-antivenom-against-naja-kaouthia-naja-siamensis-and-ophiophagus-hannah-through-proteomics-and-animal-model-approaches
#14
Chien-Chun Liu, Chen-Hsien You, Po-Jung Wang, Jau-Song Yu, Guo-Jen Huang, Chien-Hsin Liu, Wen-Chin Hsieh, Chih-Chuan Lin
In Southeast Asia, envenoming resulting from cobra snakebites is an important public health issue in many regions, and antivenom therapy is the standard treatment for the snakebite. Because these cobras share a close evolutionary history, the amino acid sequences of major venom components in different snakes are very similar. Therefore, either monovalent or polyvalent antivenoms may offer paraspecific protection against envenomation of humans by several different snakes. In Taiwan, a bivalent antivenom-freeze-dried neurotoxic antivenom (FNAV)-against Bungarus multicinctus and Naja atra is available...
December 15, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29244804/conditional-knockout-mice-for-the-distal-appendage-protein-cep164-reveal-its-essential-roles-in-airway-multiciliated-cell-differentiation
#15
Saul S Siller, Himanshu Sharma, Shuai Li, June Yang, Yong Zhang, Michael J Holtzman, Wipawee Winuthayanon, Holly Colognato, Bernadette C Holdener, Feng-Qian Li, Ken-Ichi Takemaru
Multiciliated cells of the airways, brain ventricles, and female reproductive tract provide the motive force for mucociliary clearance, cerebrospinal fluid circulation, and ovum transport. Despite their clear importance to human biology and health, the molecular mechanisms underlying multiciliated cell differentiation are poorly understood. Prior studies implicate the distal appendage/transition fiber protein CEP164 as a central regulator of primary ciliogenesis; however, its role in multiciliogenesis remains unknown...
December 15, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29244787/loss-of-podocalyxin-causes-a-novel-syndromic-type-of-congenital-nephrotic-syndrome
#16
Hee Gyung Kang, Moses Lee, Kyoung Boon Lee, Michael Hughes, Bo Sang Kwon, Sangmoon Lee, Kelly M McNagny, Yo Han Ahn, Jung Min Ko, Il-Soo Ha, Murim Choi, Hae Il Cheong
Many cellular structures directly imply specific biological functions. For example, normal slit diaphragm structures that extend from podocyte foot processes ensure the filtering function of renal glomeruli. These slits are covered by a number of surface proteins, such as nephrin, podocin, podocalyxin and CD2AP. Here we report a human patient presenting with congenital nephrotic syndrome, omphalocele and microcoria due to two loss-of-function mutations in PODXL, which encodes podocalyxin, inherited from each parent...
December 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29244217/the-follow-up-of-progressive-hypertrophic-cardiomyopathy-using-magnetic-resonance-rotating-frame-relaxation-times
#17
Muhammad Arsalan Khan, Hanne Laakso, Svetlana Laidinen, Sanna Kettunen, Tommi Heikura, Seppo Ylä-Herttuala, Timo Liimatainen
Magnetic resonance rotating frame relaxation times are an alternative non-contrast agent choice for the diagnosis of chronic myocardial infarct. Fibrosis typically occurs in progressive hypertrophic cardiomyopathy. Fibrosis has been imaged in myocardial infarcted tissue using rotating frame relaxation times, which provides the possibility to follow up progressive cardiomyopathy without contrast agents. Mild and severe left ventricular hypertrophy were induced in mice by transverse aortic constriction, and the longitudinal rotating frame relaxation times (T1ρ ) and relaxation along the fictitious field (TRAFF2 , TRAFF3 ) were measured at 5, 10, 24, 62 and 89 days after transverse aortic constriction in vivo...
December 15, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/29244204/respiratory-viral-infections-and-atopic-development-from-possible-mechanisms-to-advances-in-treatment
#18
REVIEW
Lisa M Martorano, Mitchell H Grayson
Atopic sensitization and allergic diseases are increasing in modernized countries. These diseases affect millions of individuals, but the mechanisms behind their development are not fully understood. One hypothesis relates to early life respiratory viral infections driving the development of atopic disease including asthma. This review presents the current state of the field, focusing on epidemiologic data supporting a role for early life respiratory viruses in the development of specific IgE, both against aeroallergens and the respiratory virus...
December 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29244185/loss-of-imprinting-mutations-define-both-distinct-and-overlapping-roles-for-misexpression-of-igf2-and-of-h19-lncrna
#19
Ki-Sun Park, Apratim Mitra, Beenish Rahat, Keekwang Kim, Karl Pfeifer
Imprinted genes occur in discrete clusters that are coordinately regulated by shared DNA elements called Imprinting Control Regions. H19 and Igf2 are linked imprinted genes that play critical roles in development. Loss of imprinting (LOI) at the IGF2/H19 locus on the maternal chromosome is associated with the developmental disorder Beckwith Wiedemann Syndrome (BWS) and with several cancers. Here we use comprehensive genetic and genomic analyses to follow muscle development in a mouse model of BWS to dissect the separate and shared roles for misexpression of Igf2 and H19 in the disease phenotype...
December 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29244179/sedaxane-use-of-nuclear-receptor-transactivation-assays-toxicogenomics-and-toxicokinetics-as-part-of-a-mode-of-action-framework-for-rodent-liver-tumors
#20
Richard C Peffer, David E Cowie, Richard A Currie, Daniel J Minnema
Experimental data demonstrate a mode of action (MOA) for liver tumors in male rats and mice treated with sedaxane that starts with activation of CAR, followed by altered expression of CAR-responsive genes, increased cell proliferation, and eventually clonal expansion of preneoplastic cells, leading to the development of altered foci and tumors. This MOA is non-relevant to human risk assessments. Methods and results in the MOA work for sedaxane illustrate promising directions that future MOA studies may be able to employ, in the spirit of "Tox21" and reduction of in vivo animal use: 1) currently available in vitro CAR and PXR reporter assays demonstrated that sedaxane is a direct CAR activator in mice and rats, and a weak PXR activator in rats; 2) mouse liver microarray results compared to a published CAR biomarker signature (based on 83 genes) showed a clear, statistical match, and a lack of correlation to similar biomarker signatures for AhR, PPARα, and STAT5B; 3) Ki67 immunohistochemistry and zonal image analysis showed significant increases in this marker of cell proliferation in mouse liver, without the need to dose a DNA labelling agent; and 4) toxicokinetic analysis of Cmax levels of sedaxane in blood showed a marked species difference between mice and rats that helps to explain differences in sensitivity to sedaxane...
December 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
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