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https://www.readbyqxmd.com/read/29342010/the-ever-expanding-saga-of-the-proprotein-convertases-and-their-roles-in-body-homeostasis-emphasis-on-novel-proprotein-convertase-subtilisin-kexin-number-9-functions-and-regulation
#1
Nabil G Seidah, Michel Chrétien, Majambu Mbikay
PURPOSE OF REVIEW: The nine members of the proprotein convertase family play major physiological roles during development and in the adult, and their dysregulation leads to various diseases. The primary objective of this article is to review recent findings on the clinical importance of some of these convertases concentrating mostly on PCSK9, the ninth member of the convertase family. This includes the transcriptional and translational regulation of PCSK9, its ability to enhance the degradation of LDL receptor (LDLR), and the implication of PCSK9 in inflammation and sepsis...
January 15, 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29339380/negative-regulation-of-the-keap1-nrf2-pathway-by-a-p62-sqstm1-splicing-variant
#2
Shun Kageyama, Tetsuya Saito, Miki Obata, Ryo-Hei Koide, Yoshinobu Ichimura, Masaaki Komatsu
A key anti-oxidant pathway, the Keap1-Nrf2 system, is regulated by p62/Sqstm1 via multiple mechanisms, including gene expression, post-translational modifications such as ubiquitination and phosphorylation, and autophagic degradation of p62/Sqstm1 and Keap1. Herein, we demonstrate a novel mode of regulation of the Keap1-Nrf2 system, mediated by a splicing variant of p62/Sqstm1 pre-mRNA. Ensembl database search and subsequent biochemical analyses in mice revealed the presence of an mRNA that encodes p62/Sqstm1 protein lacking the Keap1-interacting region (KIR), which is essential for the interaction with Keap1...
January 16, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29339093/the-proteoglycan-biglycan-mediates-inflammatory-response-by-activating-tlr-4-in-human-chondrocytes-inhibition-by-specific-sirna-and-high-polymerized-hyaluronan
#3
Angela Avenoso, Angela D'Ascola, Michele Scuruchi, Giuseppe Mandraffino, Alberto Calatroni, Antonino Saitta, Salvatore Campo, Giuseppe M Campo
Cartilage degeneration are hallmarks of wear, tear, mechanical and inflammatory damage of the joint cartilage. Tissue degradation as well as compromising the integrity and function of the organ, produces different intermediates, directly able to stimulate further inflammatory effect, therefore, amplifying the inflammation response. Biglycan is a soluble component of the extracellular matrix that is released during tissue injury. It has been reported that released biglycan is an endogenous ligand for TLR-2/4 in some cell type...
January 12, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29339067/molecular-characterization-and-function-of-%C3%AE-n-acetylglucosaminidase-from-ridgetail-white-prawn-exopalaemon-carinicauda
#4
Yuying Sun, Jiquan Zhang, Jianhai Xiang
Chitin degradation is catalyzed by a two-component chitinolytic enzyme system, chitinase and β-N-acetylglucosaminidase (NAGase). In this paper, the full-length cDNA sequence encoding NAGase (EcNAG) was obtained from Exopalaemon carinicauda. The deduced amino acid sequence of EcNAG open reading frame (ORF) contained one Glycohydro_20b2 domain and one Glyco_hydro_20 domain. Based on the cDNA sequence, the genomic structure of EcNAG was characterized and it was composed of six exons and five introns. EcNAG mRNA majorly expressed in the hepatopancreas and epidermis...
January 12, 2018: Gene
https://www.readbyqxmd.com/read/29338692/emerging-roles-for-microrna-in-the-regulation-of-drosophila-circadian-clock
#5
REVIEW
Yongbo Xue, Yong Zhang
BACKGROUND: The circadian clock, which operates within an approximately 24-h period, is closely linked to the survival and fitness of almost all living organisms. The circadian clock is generated through a negative transcription-translation feedback loop. microRNAs (miRNAs) are small non-coding RNAs comprised of approximately 22 nucleotides that post-transcriptionally regulate target mRNA by either inducing mRNA degradation or inhibiting translation. RESULTS: In recent years, miRNAs have been found to play important roles in the regulation of the circadian clock, especially in Drosophila...
January 16, 2018: BMC Neuroscience
https://www.readbyqxmd.com/read/29337437/canonical-signaling-and-nuclear-activity-of-mtor-a-teamwork-effort-to-regulate-metabolism-and-cell-growth
#6
REVIEW
Vincent Giguère
Mechanistic (or mammalian) target of rapamycin (mTOR) is a kinase that regulates almost all functions related to cell growth and metabolism in response to extra- and intracellular stimuli such as availability of nutrients, presence of growth factors or the energy status of the cell. As part of two distinct protein complexes, mTORC1 and mTORC2, the kinase has been shown to influence cell growth and proliferation by controlling ribosome biogenesis, mRNA translation, carbohydrate and lipid metabolism, protein degradation, autophagy as well as microtubule and actin dynamics...
January 16, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29336147/urolithins-attenuate-lps-induced-neuroinflammation-in-bv2microglia-via-mapk-akt-and-nf-%C3%AE%C2%BAb-signaling-pathways
#7
Jialin Xu, Chunhui Yuan, Guihua Wang, Jiaming Luo, Hang Ma, Li Xu, Yu Mu, Yuanyuan Li, Navindra P Seeram, Xueshi Huang, Liya Li
Emerging data suggest that urolithins, gut microbiota metabolites of ellagitannins, contribute toward multiple health benefits attributed to ellagitannin-rich foods, including walnuts, red raspberry, strawberry, and pomegranate. However, there is limited data on whether the potential neuroprotective effects of these ellagitannin-rich foods are mediated by urolithins. Herein, we evaluated the potential mechanisms of antineuroinflammatory effects of urolithins (urolithins A, B, and C; 8-methyl-O-urolithin A; and 8,9-dimethyl-O-urolithin C) in BV2 murine microglia in vitro...
January 16, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29333604/adiponectin-inhibits-inflammatory-cytokines-production-by-beclin-1-phosphorylation-and-bcl-2-mrna-destabilization-role-for-autophagy-induction
#8
Nirmala Tilija Pun, Pil-Hoon Park
BACKGROUND AND PURPOSE: Adiponectin potently suppresses inflammatory mediator production. Autophagy is known to play a critical role in modulating inflammatory responses by adiponectin. However, the underlying mechanisms are not clearly understood. Interaction between Beclin-1 and Bcl-2 is a critical event in autophagy induction. We examined the effects of globular adiponectin (gAcrp) on the Beclin-1/Bcl-2 association and its underlying mechanisms. EXPERIMENTAL APPROACH: The effect of gAcrp on the interaction between Beclin-1 and Bcl-2 was examined by immunoprecipitation followed by Western blotting...
January 14, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29329594/modelling-the-structure-of-a-cerna-theoretical-bipartite-microrna-mrna-interaction-network-regulating-intestinal-epithelial-cellular-pathways-using-r-programming
#9
J M Robinson, W A Henderson
OBJECTIVE: We report a method using functional-molecular databases and network modelling to identify hypothetical mRNA-miRNA interaction networks regulating intestinal epithelial barrier function. The model forms a data-analysis component of our cell culture experiments, which produce RNA expression data from Nanostring Technologies nCounter® system. The epithelial tight-junction (TJ) and actin cytoskeleton interact as molecular components of the intestinal epithelial barrier. Upstream regulation of TJ-cytoskeleton interaction is effected by the Rac/Rock/Rho signaling pathway and other associated pathways which may be activated or suppressed by extracellular signaling from growth factors, hormones, and immune receptors...
January 12, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29327347/unique-anti-myeloma-activity-by-thiazolidine-2-4-dione-compounds-with-pim-inhibiting-activity
#10
Shiro Fujii, Shingen Nakamura, Asuka Oda, Hirokazu Miki, Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Ariunzaya Bat-Erdene, Yusaku Maeda, Masahiro Oura, Mamiko Takahashi, Masami Iwasa, Itsuro Endo, Sumiko Yoshida, Ken-Ichi Aihara, Kiyoe Kurahashi, Takeshi Harada, Kumiko Kagawa, Michiyasu Nakao, Shigeki Sano, Masahiro Abe
Proviral Integrations of Moloney virus 2 (PIM2) is overexpressed in multiple myeloma (MM) cells, and regarded as an important therapeutic target. Here, we aimed to validate the therapeutic efficacy of different types of PIM inhibitors against MM cells for their possible clinical application. Intriguingly, the thiazolidine-2,4-dione-family compounds SMI-16a and SMI-4a reduced PIM2 protein levels and impaired MM cell survival preferentially in acidic conditions, in contrast to other types of PIM inhibitors, including AZD1208, CX-6258 and PIM447...
January 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29325918/bioactive-fraction-of-rhodiola-algida-against-chronic-hypoxia-induced-pulmonary-arterial-hypertension-and-its-anti-proliferation-mechanism-in-rats
#11
Xingmei Nan, Shanshan Su, Ke Ma, Xiaodong Ma, Ximeng Wang, Dongzhu Zhaxi, Rili Ge, Zhanqiang Li, Dianxiang Lu
BACKGROUND: Rhodiola algida has long been used to prevent acute and chronic altitude sickness. In our previous study, we screened for a bioactive fraction from R. algida. However, the effects and mechanisms of this bioactive fraction on chronic hypoxia-induced pulmonary arterial hypertension remain to be elucidated. OBJECTIVE: The aim of this study was to determine the effect of bioactive fraction from R. algida (ACRT) on chronic hypoxia-induced pulmonary arterial hypertension (HPAH) and to understand the possible mechanism of its pharmacodynamic actions...
January 8, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29325553/sitagliptin-improved-glucose-assimilation-in-detriment-of-fatty-acid-utilization-in-experimental-type-ii-diabetes-role-of-glp-1-isoforms-in-glut4-receptor-trafficking
#12
E Ramírez, B Picatoste, A González-Bris, M Oteo, F Cruz, A Caro-Vadillo, J Egido, J Tuñón, M A Morcillo, Ó Lorenzo
BACKGROUND: The distribution of glucose and fatty-acid transporters in the heart is crucial for energy consecution and myocardial function. In this sense, the glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, improves glucose homeostasis but it could also trigger direct cardioprotective actions, including regulation of energy substrate utilization. METHODS: Type-II diabetic GK (Goto-Kakizaki), sitagliptin-treated GK (10 mg/kg/day) and wistar rats (n = 10, each) underwent echocardiographic evaluation, and positron emission tomography scanning for [18F]-2-fluoro-2-deoxy-D-glucose (18FDG)...
January 11, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29323465/multiplexed-digital-mrna-expression-analysis-profiles-system-wide-changes-in-mrna-abundance-and-responsiveness-of-upr-specific-gene-expression-changes-during-batch-culture-of-recombinant-chinese-hamster-ovary-cells
#13
Rodrigo Maldonado-Agurto, Alan J Dickson
The unfolded protein response (UPR) signalling pathway is viewed as critical for setting the effectiveness of recombinant protein expression in CHO cells. In this study, we used Nanostring nCounter technology to study expression of a group of genes associated with cellular processes linked to UPR activation under ER stress and the changing environment of a batch culture. Time course induction of ER stress, using tunicamycin (TM), showed a group of genes such as Chop, Trb3, Sqstm1, Grp78 and Herpud1 responded rapidly to TM inhibition of N-glycosylation, whilst others such as Atf5, Odz4 and Birc5 exhibited a delayed response...
January 11, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29323338/ulinastatin-attenuates-lps-induced-inflammation-in-mouse-macrophage-raw264-7-cells-by-inhibiting-the-jnk-nf-%C3%AE%C2%BAb-signaling-pathway-and-activating-the-pi3k-akt-nrf2-pathway
#14
Si-Tong Li, Qi Dai, Shu-Xian Zhang, Ya-Jun Liu, Qiu-Qiong Yu, Fei Tan, Shu-Hong Lu, Quan Wang, Jian-Wen Chen, He-Qing Huang, Pei-Qing Liu, Min Li
Ulinastatin (UTI) is a broad-spectrum serine protease inhibitor isolated and purified from human urine with strong anti-inflammatory and cytoprotective actions, which is widely used for the treatment of various diseases, such as pancreatitis and sepsis. Although the therapeutic effects of UTI are reported to be associated with a variety of mechanisms, the signaling pathways mediating the anti-inflammatory action of UTI remain to be elucidated. In the present study we carried out a systematic study on the anti-inflammatory and anti-oxidative mechanisms of UTI and their relationships in LPS-treated RAW264...
January 11, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29321388/suppression-of-abdominal-aortic-aneurysm-formation-in-mice-by-teneligliptin-a-dipeptidyl-peptidase-4-inhibitor
#15
Yusuke Takahara, Tomotake Tokunou, Toshihiro Ichiki
AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors lower blood glucose levels through inhibition of incretin degradation, which stimulates insulin secretion. Recent studies reported that DPP-4 inhibitors suppressed atherogenesis in apolipoprotein E-knockout (ApoEKO) mice. In this study, we investigated whether teneligliptin, a DPP-4 inhibitor, affects the development of abdominal aortic aneurysms (AAA) in ApoEKO mice. METHODS: ApoEKO mice were fed a high-fat diet (HFD) and infused with angiotensin (Ang) II by osmotic mini pumps for 4 weeks to induce AAA with (DPP-4i group) or without (control group) teneligliptin administered orally from 1 week before HFD and Ang II infusion to the end of the experiment...
January 10, 2018: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/29321085/microrna-519d-3p-inhibits-proliferation-and-promotes-apoptosis-by-targeting-hif-2%C3%AE-in-cervical-cancer-under-hypoxic-conditions
#16
Lixia Jiang, Shaohua Shi, Qiaofa Shi, Huijuan Zhang, Yu Xia, Tianyu Zhong
HIF-2α knockdown inhibits proliferation, arrests the cell cycle, and promotes apoptosis and autophagy under hypoxic conditions in cervical cancer. However, the upstream regulatory mechanism of HIF-2α expression is unclear. MicroRNAs (miRNAs) degrade target mRNA by binding to the 3' untranslated region of mRNA. In this study, we investigated the role of miRNA in the regulation of HIF-2α expression in cervical cancer under hypoxic conditions. miRNAs regulating HIF-2α expression were predicted using TargetScan and miRanda, and were determined in cervical cancer under hypoxic conditions by qRT-PCR...
January 10, 2018: Oncology Research
https://www.readbyqxmd.com/read/29320940/methylation-mediated-loss-of-sfrp2-enhances-invasiveness-of-non-small-cell-lung-cancer-cells
#17
X Zhang, X Rong, Y Chen, L Su
The malignancy of non-small cell lung cancer (NSCLC) largely results from its invasive manner. Secreted frizzled-related proteins (SFRPs) have been recently found to suppress the invasiveness of some cancers. On the other hand, the methylation of SFRPs increases protein degradation to reduce the activity of SFRPs, resulting in increased tumor cell invasion and cancer metastasis. However, the role of SFRPs in the invasion of NSCLC has not been reported. Here we analyzed the regulation of SFRPs in NSCLC cells and its effects on cell invasion...
February 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29319934/identification-and-functional-characterization-of-type-ii-toxin-antitoxin-systems-in-aggregatibacter-actinomycetemcomitans
#18
Blair Schneider, Whitney Weigel, Maryta Sztukowska, Donald R Demuth
Type II toxin/antitoxin (TA) systems contribute to the formation of persister cells and biofilm formation for many organisms. A. actinomycetemcomitans thrives in the complex oral microbial community subjected to continual environmental flux. Little is known regarding the presence and function of type II TA systems in this organism or their contribution to adaptation and persistence in the biofilm. We identified 11 TA systems that are conserved across all seven serotypes of A. actinomycetemcomitans and represent the RelBE, MazEF and HipAB families of type II TA systems...
January 10, 2018: Molecular Oral Microbiology
https://www.readbyqxmd.com/read/29317217/crucial-role-of-ho-1-irf4-dependent-apoptosis-induced-by-panobinostat-and-lenalidomide-in-multiple-myeloma
#19
Sishi Tang, Dan Ma, Bingqing Cheng, Qing Fang, Xinyi Kuang, Kunling Yu, Weili Wang, Bo Hu, Jishi Wang
Inhibition of histone deacetylase (HDAC) is a promising therapeutic strategy for various hematologic cancers. Panobinostat has been approved for treating patients with multiple myeloma (MM) by the FDA. Since the mechanism for the resistance of panobinostat to MM remains elusive, we aimed to clarify this mechanism and the synergism of panobinostat with lenalidomide. The mRNA and protein of transcription factor IRF4 were overexpressed in CD138+ mononuclear cells from MM patients compared with in those from healthy donors...
January 6, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29315381/chchd10-mutations-p-r15l-and-p-g66v-cause-motoneuron-disease-by-haploinsufficiency
#20
Sarah J Brockmann, Axel Freischmidt, Patrick Oeckl, Kathrin Müller, Srinivas K Ponna, Anika M Helferich, Christoph Paone, Jörg Reinders, Kerstin Kojer, Michael Orth, Manu Jokela, Mari Auranen, Bjarne Udd, Andreas Hermann, Karin M Danzer, Peter Lichtner, Paul Walther, Albert C Ludolph, Peter M Andersen, Markus Otto, Petri Kursula, Steffen Just, Jochen H Weishaupt
Mutations in the mitochondrially located protein CHCHD10 cause motoneuron disease by an unknown mechanism. In this study, we investigate the mutations p.R15L and p.G66V in comparison to wild-type CHCHD10 and the non-pathogenic variant p.P34S in vitro, in patient cells as well as in the vertebrate in vivo model zebrafish. We demonstrate a reduction of CHCHD10 protein levels in p.R15L and p.G66V mutant patient cells to approximately 50%. Quantitative real-time PCR revealed that expression of CHCHD10 p.R15L, but not of CHCHD10 p...
January 5, 2018: Human Molecular Genetics
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