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https://www.readbyqxmd.com/read/29458203/precision-pharmacology-for-alzheimer-s-disease
#1
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/29458176/grp78-promotes-hepatocellular-carcinoma-proliferation-by-increasing-fat10-expression-through-the-nf-%C3%AE%C2%BAb-pathway
#2
Chenglin Luo, Haixia Xiong, Leifeng Chen, Xiuxia Liu, Shubing Zou, Jiafu Guan, Kai Wang
Glucose-regulated protein 78(GRP78) and the ubiquitin-like protein FAT10 each promote proliferation in hepatocellular carcinoma(HCC). However, the relationship of GRP78 and FAT10 in HCC proliferation are still not known. In this study, we found that GRP78 and FAT10 were significantly overexpressed in HCC tissues compare with adjacent non-cancerous tissues, and a positive correlation was found between their expression and associated proliferation characteristics. High expression of GRP78 and FAT10 were positively correlated with tumor proliferation and poor prognosis in HCC...
February 16, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29458175/maintenance-of-hematopoietic-stem-and-progenitor-cells-in-fetal-intra-aortic-hematopoietic-clusters-by-the-sox17-notch1-hes1-axis
#3
Kiyoka Saito, Ikuo Nobuhisa, Kaho Harada, Satomi Takahashi, Maha Anani, Heiko Lickert, Masami Kanai-Azuma, Yoshiakira Kanai, Tetsuya Taga
The aorta-gonad-mesonephros region, from which definitive hematopoiesis first arises in midgestation mouse embryos, has intra-aortic hematopoietic clusters (IAHCs) containing hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). We previously reported expression of the transcription factor Sox17 in IAHCs, and overexpression of Sox17 in CD45low c-KIThigh cells comprising IAHCs maintains the formation of cell clusters and their multipotency in vitro over multiple passages. Here, we demonstrate the importance of NOTCH1 in IAHC formation and maintenance of the HSC/HPC phenotype...
February 16, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29458173/deregulation-of-nrf2-are-signaling-pathway-causes-susceptibility-of-dystrophin-deficient-myotubes-to-menadione-induced-oxidative-stress
#4
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/29458169/inhibition-of-microsomal-prostaglandin-e-synthase-1-facilitates-liver-repair-after-hepatic-injury-in-mice
#5
Nobuyuki Nishizawa, Yoshiya Ito, Koji Eshima, Hirotoki Ohkubo, Ken Kojo, Tomoyoshi Inoue, Joan Raouf, Per-Johan Jakobsson, Satoshi Uematsu, Shizuo Akira, Shuh Narumiya, Masahiko Watanabe, Masataka Majima
BACKGROUND & AIMS: Liver repair following hepatic ischemia/reperfusion (I/R) injury is crucial to survival. This study aims to examine the role of endogenous prostaglandin E2 (PGE2 ) produced by inducible microsomal PGE synthase-1 (mPGES-1), a terminal enzyme of PGE2 generation, in liver injury and repair following hepatic I/R. METHODS: mPGES-1 deficient (mPGES-1-/- ) mice or their wild counterparts (WT) were subjected to partial hepatic ischemia followed by reperfusion...
February 16, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29458166/statistical-approach-for-selection-of-biologically-informative-genes
#6
Samarendra Das, Anil Rai, D C Mishra, S N Rai
Selection of informative genes from high dimensional gene expression data has emerged as an important research area in genomics. Many gene selection techniques have been proposed so far are either based on relevancy or redundancy measure. Further, the performance of these techniques has been adjudged through post selection classification accuracy computed through a classifier using the selected genes. This performance metric may be statistically sound but may not be biologically relevant. A statistical approach, i...
February 16, 2018: Gene
https://www.readbyqxmd.com/read/29458158/toll-like-receptor-tlr-9-promotor-polymorphisms-and-gene-expression-are-associated-with-persistent-staphylococcus-aureus-nasal-carriage
#7
Dennis Nurjadi, Klaus Heeg, Alexander N R Weber, Philipp Zanger
OBJECTIVES: Toll-like receptor (TLR) -9 could have importance in human S. aureus immunity, but population level evidence for this hypothesis is missing. METHODS: We phenotyped 603 volunteers for S. aureus nasal carriage using four consecutive swabs, genotyped TLR9 promotor variants in 106 persistent carriers and 219 non-carriers, measured TLR9-mRNA expression in whole blood after stimulation with viable S. aureus, and studied mutual associations of carriage, transcriptional activity, and single nucleotide polymorphisms while accounting for sex and hormonal contraceptive use (HCU+/- )...
February 16, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29458156/how-to-isolate-identify-and-determine-antimicrobial-susceptibility-of-anaerobic-bacteria-in-routine-laboratories
#8
REVIEW
Elisabeth Nagy, Lyudmila Boyanova, Ulrik S Justesen
BACKGROUND: There has been an increased interest in the study of anaerobic bacteria, which cause human infection during the past decade. Many new genera and species have been described by to use 16S rRNA gene sequencing of clinical isolates obtained from different infection sites with commercially available special culture media to support the growth of anaerobes. Several systems, such as anaerobic pouches, boxes, jars and chambers provide suitable anaerobic culture conditions to isolate even strict anaerobic bacteria successfully from clinical specimens...
February 16, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29458150/pink1-protects-auditory-hair-cells-and-spiral-ganglion-neurons-from-cisplatin-induced-ototoxicity-via-inducing-autophagy-and-inhibiting-jnk-signaling-pathway
#9
Qianqian Yang, Gaoying Sun, Haiyan Yin, Hongrui Li, Zhixin Cao, Jinghan Wang, Meijuan Zhou, Haibo Wang, Jianfeng Li
Phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1) gene encodes a serine/threonine kinase, which acts as a molecular sensor of mitochondrial health necessary for mitochondrial quality control. The present study was designed to examine whether PINK1 expressed in C57BL/6 murine cochlea and HEI-OC1 cells and, if so, to investigate the possible mechanisms underlying the action of PINK1 in cisplatin-induced death of sensory hair cells (HCs) and spiral ganglion neurons (SGNs) in vitro. The expression pattern of PINK1, formation of parkin particles, and autophagy were determined by immunofluorescent staining...
February 16, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29458148/untimely-oxidative-stress-in-%C3%AE-cells-leads-to-diabetes-role-of-circadian-clock-in-%C3%AE-cell-function
#10
REVIEW
J Lee, K Ma, M Moulik, V Yechoor
Diabetes results from a loss of β-cell function. With the number of people with diabetes reaching epidemic proportions globally, understanding mechanisms that are contributing to this increasing prevalence is critical. One such factor has been circadian disruption, with shift-work, light pollution, jet-lag, increased screen time, all acting as potential contributory factors. Though circadian disruption has been epidemiologically associated with diabetes and other metabolic disorders for many decades, it is only recently that there has been a better understanding of the underlying molecular mechanisms...
February 16, 2018: Free Radical Biology & Medicine
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
#11
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/29458137/bisphenol-a-alters-oocyte-maturation-by-prematurely-closing-gap-junctions-in-the-cumulus-cell-oocyte-complex
#12
Deyanira Guadalupe Acuña-Hernández, Laura Arreola-Mendoza, Ramsés Santacruz-Márquez, Sihomara Patricia García-Zepeda, Lyda Yuliana Parra-Forero, Jesús Alberto Olivares-Reyes, Isabel Hernández-Ochoa
In ovarian follicles, cumulus cells communicate with the oocyte through gap junction intercellular communication (GJIC), to nurture the oocyte and control its meiosis arrest and division. Bisphenol A (BPA) is a monomer found in polycarbonate-made containers that can induce functional alterations, including impaired oocyte meiotic division and reduced molecule transfer in GJIC. However, how BPA alters oocyte meiotic division is unclear. We investigated whether BPA effects on oocyte meiotic division were correlated with reduced transfer in GJIC...
February 16, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29458129/honeysuckle-encoded-microrna2911-inhibits-enterovirus-71-replication-via-targeting-vp1-gene
#13
Xihan Li, Ying Huang, Menghuai Sun, Hong Ji, Hui Dou, Jia Hu, Yanfeng Yan, Xu Wang, Leiyao Chen
Enterovirus 71 (EV71) is the primary pathogen of hand-foot-and-mouth disease (HFMD) in children and virus infections are associated with severe neurological dysfunctions and even death. MIR2911 is a honeysuckle-encoded atypical microRNA with extremely stability. Here, we report that MIR2911 directly inhibits EV71 replication by targeting the VP1 gene. Bioinformatics prediction and luciferase reporter assay showed that MIR2911 could target the VP1 gene of EV71. Transfection experiments using synthetic MIR2911 and extracted RNA from HS decoction shown that each of these preparations was capable of inhibiting EV71 VP1 protein expression; however, these preparations did not impact EV71 mutants in which the MIR2911-binding sites were mutated...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29458125/pluripotent-stem-cells-for-uncovering-the-role-of-mitochondria-in-human-brain-function-and-dysfunction
#14
REVIEW
Annika Zink, Josef Priller, Alessandro Prigione
Mitochondrial dysfunctions are a known pathogenetic mechanism of a number of neurological and psychiatric disorders. At the same time, mutations in genes encoding for components of the mitochondrial respiratory chain cause mitochondrial diseases, which commonly exhibit neurological symptoms. Mitochondria are therefore critical for the functionality of the human nervous system. The importance of mitochondria stems from their key roles in cellular metabolism, calcium handling, redox and protein homeostasis, and overall cellular homeostasis through their dynamic network...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29458109/modulation-of-cyp1a1-metabolism-from-adverse-health-effects-to-chemoprevention-and-therapeutic-options
#15
Melina Mescher, Thomas Haarmann-Stemmann
The human cytochrome P450 (CYP) 1A1 gene encodes a monooxygenase that metabolizes multiple exogenous and endogenous substrates. CYP1A1 has become infamous for its oxidative metabolism of benzo[a]pyrene and related polycyclic aromatic hydrocarbons, converting these chemicals into very potent human carcinogens. CYP1A1 expression is mainly controlled by the aryl hydrocarbon receptor (AHR), a transcription factor whose activation is induced by binding of persistent organic pollutants, including polycyclic aromatic hydrocarbons and dioxins...
February 16, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29458104/a-new-l-glutaminase-from-streptomyces-pratensis-nrc-10-gene-identification-enzyme-purification-and-characterization
#16
Sanaa E Tork, Magda M Aly, Omar Elsemin
In the current study, the purified l-glutaminase from Streptomyces pratensis NRC10 (GenBank number KC857622) was characterized. Its molecular weight was estimated to be 46 kDa and isoelectric point 7.4. Its Vmax was calculated to be 2.19 U/mg/min, while Km was 0.175 mM. The optimum pH and temperature were 9 and 45 °C, respectively. It was thermostable at 45 °C but thermally inactivated at 60 °C after 50 min. Moreover, its enzymatic activity was enhanced by K+ ions and inhibited by Mg2+ , Cu2+ , Ag+ , Hg2+ , Ni2+ , Fe2+ , Cr2 , Na+ , Ca2+ , and EDTA...
February 16, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29458096/identification-of-macrophage-related-candidate-genes-in-lupus-nephritis-using-bioinformatics-analysis
#17
Bingyan Shu, Yi Fang, Weichun He, Junwei Yang, Chunsun Dai
Lupus nephritis (LN) is a chronic autoimmune disorder. Here we try to identify the candidate genes in macrophages related to LN. We performed a systematic search in the Gene Expression Omnibus (GEO) database for microarray in human mononuclear cells and mouse macrophages of LN. The results of clustering and venn analysis of different GEO datasets showed that 8 genes were up-regulated and 2 genes down-regulated in samples from both human and mouse LN. The data from gene network and GO analysis revealed that CD38 and CCL2 were localized in the core of the network...
February 16, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29458094/a-conserved-interferon-regulation-factor-1-irf-1-from-pacific-oyster-crassostrea-gigas-functioned-as-an-activator-of-ifn-pathway
#18
Mengmeng Lu, Chuanyan Yang, Meijia Li, Qilin Yi, Guangxia Lu, Yichen Wu, Chen Qu, Lingling Wang, Linsheng Song
Interferon regulatory factors (IRFs), a family of transcription factors with a novel helix-turn-helix DNA-binding motif, play important roles in regulating the expression of interferons (IFNs) and IFN-stimulated genes. In the present study, an interferon regulation factor 1 was identified from oyster Crassostrea gigas (designated CgIRF-1), and its immune function was characterized to understand the regulatory mechanism of interferon system against viral infection in invertebrates. The open reading frame (ORF) of CgIRF-1 was 993 bp, encoding a polypeptide of 330 amino acids with a typical IRF domain (also known as DNA-binding domain)...
February 16, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29458091/role-of-the-ssek1-gene-in-the-pathogenicity-of-salmonella-enterica-serovar-enteritidis-in-vitro-and-in-vivo
#19
Yadong Yang, Chuan Yu, Ke Ding, Chunjie Zhang, Chengshui Liao, Yanyan Jia, Jing Li, Xiangchao Cheng
Salmonella enteritidis is a common food-borne pathogen associated with consumption of contaminated poultry meat and eggs, which frequently causes gastroenteritis in humans. Salmonella secreted effector K1 (SseK1), as a translocated and secreted protein has been identified to be essential for the virulence of Salmonella typhimurium in host cells. However, the role of the sseK1 gene in the pathogenicity of S. enteritidis remain unclear. In this study, a sseK1 deletion mutant of S. enteritidis was constructed and its biological characteristics were examined...
February 16, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29458069/high-expression-of-nprl2-is-linked-to-poor-prognosis-in-patients-with-prostate-cancer
#20
Zhixiong Chen, Shengjun Luo, Yanlin Chen, Xuemei Xie, Zhongbo Du, Li Jiang
As a tumor suppressor candidate gene, NPRL2 has anti-cancer effects against several cancers, but its potential role in prostate cancer (PCa) has not been reported. The present study aimed to explore the expression of NPRL2 in PCa and its potential clinical significance. Our results showed that expression of NPRL2 in PCa tissues was significantly higher than in non-PCa tissues (P<.001). High NPRL2 expression in PCa tissue was significantly correlated with a high Gleason grade group (P<.001), high pT stage (P<...
February 16, 2018: Human Pathology
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