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https://www.readbyqxmd.com/read/29458214/effect-of-tetrahedral-dna-nanostructures-on-proliferation-and-osteo-odontogenic-differentiation-of-dental-pulp-stem-cells-via-activation-of-the-notch-signaling-pathway
#1
Mi Zhou, Nan-Xin Liu, Si-Rong Shi, Yong Li, Qi Zhang, Quan-Quan Ma, Tao-Ran Tian, Wen-Juan Ma, Xiao-Xiao Cai, Yun-Feng Lin
Dental pulp stem cells (DPSCs) derived from the human dental pulp tissue have multiple differentiation capabilities, such as osteo/odontogenic differentiation. Therefore, DPSCs are deemed as ideal stem cell sources for tissue regeneration. As new nanomaterials based on DNA, tetrahedral DNA nanostructures (TDNs) have tremendous potential for biomedical applications. Here, the authors aimed to explore the part played by TDNs in proliferation and osteo/odontogenic differentiation of DPSCs, and attempted to investigate if these cellular responses could be driven by activating the canonical Notch signaling pathway...
February 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29458203/precision-pharmacology-for-alzheimer-s-disease
#2
REVIEW
Harald Hampel, Andrea Vergallo, Lisi Flores Aguilar, Norbert Benda, Karl Broich, A Claudio Cuello, Jeffrey Cummings, Bruno Dubois, Howard J Federoff, Massimo Fiandaca, Remy Genthon, Marion Haberkamp, Eric Karran, Mark Mapstone, George Perry, Lon S Schneider, Lindsay A Welikovitch, Janet Woodcock, Filippo Baldacci, Simone Lista
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses...
February 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29458193/attenuation-of-neuro-inflammation-improves-survival-and-neurodegeneration-in-a-mouse-model-of-severe-neonatal-hyperbilirubinemia
#3
Simone Vodret, Giulia Bortolussi, Alessandra Iaconcig, Elena Martinelli, Claudio Tiribelli, Andrés F Muro
All pre-term newborns and a high proportion of term newborns develop neonatal jaundice. Neonatal jaundice is usually a benign condition and self-resolves within few days after birth. However, a combination of unfavorable complications may lead to acute hyperbilirubinemia. Excessive hyperbilirubinemia may be toxic for the developing nervous system leading to severe neurological damage and death by kernicterus. Survivors show irreversible neurological deficits such as motor, sensitive and cognitive abnormalities...
February 16, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29458182/a-direct-gateway-into-the-extracellular-space-unconventional-secretion-of-fgf2-through-self-sustained-plasma-membrane-pores
#4
REVIEW
Julia P Steringer, Walter Nickel
As illustrated by a diverse set of examples in this special issue, multiple mechanisms of protein secretion have been identified in eukaryotes that do not involve the endoplasmic reticulum (ER) and the Golgi apparatus. Here we focus on the type I pathway with Fibroblast Growth Factor 2 (FGF2) being the most prominent example. Unconventional secretion of FGF2 from cells is mediated by direct protein translocation across the plasma membrane. A unique feature of this process is the ability of FGF2 to form its own membrane translocation intermediate through oligomerization and membrane insertion...
February 16, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29458173/deregulation-of-nrf2-are-signaling-pathway-causes-susceptibility-of-dystrophin-deficient-myotubes-to-menadione-induced-oxidative-stress
#5
Su Jin Choi, Hye Sun Kim
Duchenne muscular dystrophy (DMD) is an X chromosome-linked disorder caused by a mutation in the dystrophin gene. Many previous studies reported that the skeletal muscles of DMD patients were more susceptible to oxidative stress than those of healthy people. However, not much has been known about the responsible mechanism of the differential susceptibility. In this study, we established dystrophin knock-down (DysKD) cell lines by transfection of dystrophin shRNA lentiviral particles into C2 cells and found that DysKD myotubes are more vulnerable to menadione-induced oxidative stress than control myotubes...
February 16, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29458170/downregulation-of-metabotropic-glutamate-receptor-5-inhibits-hepatoma-development-in-a-neurotoxin-rotenone-induced-parkinson-s-disease-model
#6
Xiao Xu Bai, Li Gu, Hui Min Yang, Shao Song Xi, Ning Xia, Song Zhang, Hong Zhang
Clinical epidemiological studies have shown that there is a link between Parkinson's disease (PD) and cancer, but how PD regulates cancer development remains unknown. In our study, the effect of metabotropic glutamate receptor 5 (mGlu5 ) on hepatoma was explored in a rotenone-induced PD model both in vitro and in vivo. We found that conditioned media derived from MN9D dopaminergic neuronal cells by rotenone-induced toxicity inhibited the growth, migration, invasion and promoted apoptosis of Hepa1-6 cells, which corresponded with decreased expression of mGlu5 ...
February 16, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29458159/strawberry-extracts-efficiently-counteract-inflammatory-stress-induced-by-the-endotoxin-lipopolysaccharide-in-human-dermal-fibroblast
#7
Massimiliano Gasparrini, Francesca Giampieri, Tamara Y Forbes-Hernandez, Sadia Afrin, Danila Cianciosi, Patricia Reboredo-Rodriguez, Alfonso Varela-Lopez, JiaoJiao Zhang, Josè L Quiles, Bruno Mezzetti, Stefano Bompadre, Maurizio Battino
A protracted pro-inflammatory state is the common denominator in the development, progression and complication of the common chronic diseases. Dietary antioxidants represent an efficient tool to counteract this inflammatory state. The aim of the present work was to evaluate the effects of strawberry extracts on inflammation evoked by E. Coli lipopolysaccharide in Human Dermal Fibroblast, by measuring reactive oxygen species production, apoptosis rate, antioxidant enzymes activity, mitochondria functionality and also investigating the molecular pathway involved in inflammatory and antioxidant response...
February 16, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29458146/enhanced-anticancer-effects-of-scutellaria-barbata-d-don-in-combination-with-traditional-chinese-medicine-components-on-non-small-cell-lung-cancer-cells
#8
Qian Wang, Narayan Acharya, Zhongwei Liu, Xianmei Zhou, Meghan Cromie, Jia Zhu, Weimin Gao
ETHNOPHARMACOLOGICAL RELEVANCE: Experience-based herbal medicine as a complementary to modern western medicine has triggered an array of studies in quest of novel anticancer drugs. Scutellaria barbata D. Don (SB) is commonly used to treat different types of cancers, but its molecular mechanism of action is not clearly understood. In this study, we attempted to elucidate the mode of action of a traditional Chinese medicine prescription with a total of 14 components, named Lian-Jia-San-Jie-Fang (LJSJF, in Chinese), where SB works as the "principle" against non-small cell lung cancer (NSCLC) cells...
February 16, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29458130/impact-of-rna-polymerase-i-inhibitor-cx-5461-on-viral-kinase-dependent-and-independent-cytomegalovirus-replication
#9
Kristen N Westdorp, Scott S Terhune
Human cytomegalovirus (HCMV) infections cause congenital birth defects and disease in immunosuppressed individuals. Antiviral compounds can control infection yet their use is restricted due to concerns of toxicity and the emergence of drug resistant strains. We have evaluated the impact of an RNA Polymerase I (Pol I) inhibitor, CX-5461 on HCMV replication. CX-5461 inhibits Pol I-mediated ribosomal DNA transcription by binding G-quadruplex DNA structures and also activates cellular stress response pathways. The addition of CX-5461 at both early and late stages of the HCMV infection inhibited viral DNA synthesis and virus production...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29458087/ngf-fak-signal-pathway-is-implicated-in-angiogenesis-after-acute-cerebral-ischemia-in-rats
#10
Hai-Ting Zhao, Yu-Hu Zhang, Ying-Hui Zhang, Yue Shen, Yi-Dan Zhang, Fang-Fang Bi, Bo Xiao, Hao Zhang, Wen Ye, Hong-Hai Zhang, Yi-Wei Liao
Neurogenesis in the cerebral infarction after an ischemic event is important to the rehabilitation of patients. However, the mechanism of angiogenesis around cerebral ischemia is not clear. Our study designed to test whether the nerve growth factor (NGF)-P-focal adhesion kinase (FAK) signaling pathway for associations with angiogenesis plays a key role in post-acute cerebral ischemia of rats. Firstly, we implanted the Matrigel, a carrier of basement membrane matrix, into the abdominal skin of rats to identify the relevant components of the NGF-P-FAK signaling pathway related to angiogenesis...
February 16, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29458080/transcriptomic-and-phenotypic-profiling-in-developing-zebrafish-exposed-to-thyroid-hormone-receptor-agonists
#11
Derik E Haggard, Pamela D Noyes, Katrina M Waters, Robert L Tanguay
There continues to be a need to develop in vivo high-throughput screening (HTS) and computational methods to screen chemicals for interaction with the estrogen, androgen, and thyroid pathways and as complements to in vitro HTS assays. This study explored the utility of an embryonic zebrafish HTS approach to identify and classify endocrine bioactivity using phenotypically-anchored transcriptome profiling. Transcriptome analysis was conducted on zebrafish embryos exposed to 25 estrogen-, androgen-, or thyroid-active chemicals at concentrations that elicited adverse malformations or mortality at 120 hours post-fertilization in 80% of animals exposed...
February 16, 2018: Reproductive Toxicology
https://www.readbyqxmd.com/read/29458060/crim1-is-required-for-maintenance-of-the-ocular-lens-epithelium
#12
Oliver H Tam, David Pennisi, Lorine Wilkinson, Melissa H Little, Fatima Wazin, Victor L Wan, Frank J Lovicu
The development and growth of the vertebrate ocular lens is dependent on the regulated proliferation of an anterior monolayer of epithelial cells, and their subsequent differentiation into elongate fiber cells. The growth factor rich ocular media that bathes the lens mediates these cellular processes, and their respective intracellular signaling pathways are in turn regulated to ensure that the proper lens architecture is maintained. Recent studies have proposed that Cysteine Rich Motor Neuron 1 (Crim1), a transmembrane protein involved in organogenesis of many tissues, might influence cell adhesion, polarity and proliferation in the lens by regulating integrin-signaling...
February 16, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29458058/lithium-modulates-the-muscarinic-facilitation-of-synaptic-plasticity-and-theta-gamma-coupling-in-the-hippocampal-prefrontal-pathway
#13
Rafael N Ruggiero, Matheus T Rossignoli, Cleiton Lopes-Aguiar, João P Leite, Lezio S Bueno-Junior, Rodrigo N Romcy-Pereira
Mood disorders are associated to functional unbalance in mesolimbic and frontal cortical circuits. As a commonly used mood stabilizer, lithium acts through multiple biochemical pathways, including those activated by muscarinic cholinergic receptors crucial for hippocampal-prefrontal communication. Therefore, here we investigated the effects of lithium on prefrontal cortex responses under cholinergic drive. Lithium-treated rats were anesthetized with urethane and implanted with a ventricular cannula for muscarinic activation, a recording electrode in the medial prefrontal cortex (mPFC), and a stimulating electrode in the intermediate hippocampal CA1...
February 16, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29458057/roles-of-the-insulin-signaling-pathway-in-insect-development-and-organ-growth
#14
Xianyu Lin, Guy Smagghe
Organismal development is a complex process as it requires coordination of many aspects to grow into fit individuals, such as the control of body size and organ growth. Therefore, the mechanisms of precise control of growth are essential for ensuring the growth of organisms at a correct body size and proper organ proportions during development. The control of the growth rate and the duration of growth (or the cessation of growth) are required in size control. The insulin signaling pathway and the elements involved are essential in the control of growth...
February 16, 2018: Peptides
https://www.readbyqxmd.com/read/29458046/bmp-2-induces-angiogenesis-by-provoking-integrin-%C3%AE-6-expression-in-human-endothelial-progenitor-cells
#15
Wei-Cheng Chen, Ching-Hu Chung, Yung-Chang Lu, Min-Huan Wu, Po-Hsun Chou, Juei-Yu Yen, Yu-Wei Lai, Guo-Shou Wang, Shih-Chia Liu, Jen-Kun Cheng, Yih-Jer Wu, Hung-I Yeh, Li-Yu Wang, Shih-Wei Wang
Bone morphogenetic proteins-2 (BMP-2) is a multifunctional cytokine, capable of governing several cellular functions, including proliferation, motility, differentiation, and angiogenesis. Circulating endothelial progenitor cells (EPCs) have been shown to facilitate tissue repair, postnatal neovascularization, and tumor associated angiogenesis. Nevertheless, the impact of BMP-2 on angiogenesis of human EPCs has largely remained a mystery. In this study, we found that BMP-2 promoted cell migration and tube formation of EPCs in a concentration-dependent manner, indicating BMP-2 induced in vitro angiogenesis in human EPCs...
February 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29458018/5-chloro-n4-2-isopropylsulfonyl-phenyl-n2-2-methoxy-4-4-4-methylpiperazin-1-yl-methyl-1h-1-2-3-triazol-1-yl-phenyl-pyrimidine-2-4-diamine-wy-135-a-novel-alk-inhibitor-induces-cell-cycle-arrest-and-apoptosis-through-inhibiting-alk-and-its-downstream-pathways
#16
Mengting Han, Jiwei Shen, Lijing Wang, Yu Wang, Xin Zhai, Yao Li, Meiqiao Liu, Zengqiang Li, Daiying Zuo, Yingliang Wu
Anaplastic lymphoma kinase (ALK)-positive cancers have rising morbidity and mortality in recent years, and novel chemotherapeutic drugs with no drug resistance and high activity for treating ALK-positive cancers are needed urgently. In this study, we investigated the anti-cancer effect of 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-((4-methylpiperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)phenyl)pyrimidine-2,4-diamine (WY-135), a novel ALK inhibitor, on nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) positive cancer cell line Karpas299 and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) positive cancer cell line H2228...
February 16, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29457969/an-evaluation-of-the-operational-model-when-applied-to-quantify-functional-selectivity
#17
Xiao Zhu, David B Finlay, Michelle Glass, Stephen B Duffull
BACKGROUND AND PURPOSE: Functional selectivity describes the ability of ligands to differentially regulate multiple signalling pathways when coupled to a single receptor and the operational model is commonly used to analyse these data. Here, we assess the mathematical properties of the operational model and evaluate the impact of fixing parameters on model performance. EXPERIMENTAL APPROACH: The operational model was evaluated using both a mathematical identifiability analysis and simulation...
February 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29457946/the-provision-of-ambulatory-systemic-anti-cancer-therapy
#18
Susan Cooper, Kate de Lord
This article reflects on the changing nature of the provision of care and delivery of ambulatory systemic anti-cancer therapy (SACT) services. It reviews the national guidance and looks at ambulatory SACT in terms of patients being treated closer to home, i.e. ambulatory care in its truest sense. It considers the impact on quality of life for patients receiving treatments at a place of their choice. It explores the role of the nurse as an advanced practitioner while also examining the safety and delivery of complex regimens ensuring robust pathways are in place to deliver care in a safe and standardised way...
February 22, 2018: British Journal of Nursing: BJN
https://www.readbyqxmd.com/read/29457929/growth-of-the-james-cook-university-medical-program-maintaining-quality-continuing-the-vision-developing-postgraduate-pathways
#19
Tarun Sen Gupta, Peter Johnson, Roy Rasalam, Richard Hays
BACKGROUND: James Cook University (JCU) enrolled its first cohort of 64 in 2000 into a 6-year undergraduate medical program aimed at producing graduates capable of meeting the needs of North Queensland, Australia, with a focus on rural, remote, Indigenous and tropical health. The school's 1465 graduates over 13 cohorts who have a pattern of practice likely to meet the region's health needs. The JCU course was the first new Australian medical program for 25 years. The number of Australian medical schools has since doubled, while enrollments have almost tripled...
February 19, 2018: Medical Teacher
https://www.readbyqxmd.com/read/29457904/conflict-in-the-mechanism-and-kinetics-of-the-barrierless-reaction-between-sh-and-no-2-radicals
#20
Ramanpreet Kaur, Vikas
There are some unsettled issues regarding the mechanism and kinetics of an important atmospheric reaction of NO2 radical with the SH radical. The existing mechanism is based on the formation of HSO and NO radicals, both of which can result only along one barrierless channel. However, the detection of NO radical has never been reported though the formation of HSO radical has been followed in some studies to determine the rate constants. The latter are mainly obtained by monitoring the SH decay, but rate constants are reported to be highly conflicting among the existing studies reporting its value ranging from 10-10 to 10-12 cm3 molecule-1 sec-1 ...
February 19, 2018: Journal of Physical Chemistry. A
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