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https://www.readbyqxmd.com/read/29356144/beneficial-effects-of-oleuropein-on-glucose-uptake-and-on-parameters-relevant-to-the-normal-homeostatic-mechanisms-of-glucose-regulation-in-rat-skeletal-muscle
#1
Hakam Alkhateeb, Mohammed Al-Duais, Esam Qnais
Oleuropein, the main constituents of leaves and fruits of the olive tree, has been demonstrated to exert various therapeutic and pharmacological properties including antidiabetic effect. However, the effectiveness of oleuropein on glucose homeostasis in intact rat skeletal muscle ex vivo has never been explored. Therefore, our current study was carried out to investigate and confirm the beneficial effect of oleuropein (1.5 mM) on glucose uptake and on parameters relevant to the normal homeostatic mechanisms of glucose regulation in rat skeletal muscle...
January 22, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29355776/rhoa-inactivation-by-s-nitrosylation-regulates-vascular-smooth-muscle-contractive-signaling
#2
Li Lin, Chang Xu, Martha S Carraway, Claude A Piantadosi, A Richard Whorton, Sheng Li
S-nitrosothiols derived from nitric oxide are known to regulate cell signaling through thiol modification. Since small G protein RhoA contains cysteine residues in the GTP-binding domain which is critical for its function, modification these thiols may alter RhoA activity and lead to changes in the downstream signaling such as myosin light chain phosphorylation. However, it is still unclear that if RhoA activity and its downstream signals might be modulated by S-nitrosothiols and if the two cysteine residues located in the GTP-binding domain are critical for the regulation...
January 18, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29355736/a-role-for-hippo-yap-signaling-in-fgf-induced-lens-epithelial-cell-proliferation-and-fibre-differentiation
#3
L J Dawes, E J Shelley, J W McAvoy, F J Lovicu
Recent studies indicate an important role for the transcriptional co-activator Yes-associated protein (YAP), and its regulatory pathway Hippo, in controlling cell growth and fate during lens development; however, the exogenous factors that promote this pathway are yet to be identified. Given that fibroblast growth factor (FGF)-signaling is an established regulator of lens cell behavior, the current study investigates the relationship between this pathway and Hippo/YAP-signaling during lens cell proliferation and fibre differentiation...
January 17, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29355717/localization-and-promotion-of-recombinant-human-bone-morphogenetic-protein-2-bioactivity-on-extracellular-matrix-mimetic-chondroitin-sulfate-functionalized-calcium-phosphate-cement-scaffolds
#4
Baolin Huang, Zihan Wu, Sai Ding, Yuan Yuan, Changsheng Liu
Localization of recombinant human bone morphogenetic protein-2 (rhBMP-2) with continuous and effective osteogenic stimulation is still a great challenge in the field of bone regeneration. To achieve this aim, rhBMP-2 was tethered on chondroitin sulfate (CS)-functionalized calcium phosphate cement (CPC) scaffolds through specific noncovalent interactions. CS, one of the core glycosaminoglycans, was covalently conjugated onto CPC scaffolds with the assistance of polydopamine (PDA) and further immobilized rhBMP-2 in a biomimetic form...
January 17, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29355562/cilostazol-attenuates-indices-of-liver-damage-induced-by-thioacetamide-in-albino-rats-through-regulating-inflammatory-cytokines-and-apoptotic-biomarkers
#5
Sally A El Awdan, Mohamed M Amin, Azza Hassan
Even though cilostazol was assessed before in several models of atherosclerosis, so far its full systematic effect as a natural anti-inflammatory and anti-apoptotic mediator in the protection of liver damage and complication has not been fully clarified, which is the target of this study. For that purpose, we examined the protective effect of cilostazol (10 and 5mg/kg, p.o. b.wt.) in an acute hepatic injury model by orally injecting it for 3 weeks prior to a single dose of TAA (300mg/kg, i.p) injection. Ursodeoxycholic acid was used as a standard drug (50mg/kg, p...
January 17, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29353598/new-role-of-ltr-retrotransposons-for-emergence-and-expansion-of-disease-resistance-genes-and-high-copy-gene-families-in-plants
#6
Seungill Kim, Doil Choi
Long terminal repeat retrotransposons (LTR-Rs) are major elements creating new genome structure for expansion of plant genomes. However, in addition to the genome expansion, the role of LTR-Rs has been unexplored. In this study, we constructed new reference genome sequences of two pepper species (Capsicum baccatum and C. chinense), and updated the reference genome of C. annuum. We focused on the study for speciation of Capsicum spp. and its driving forces. We found that chromosomal translocation, unequal amplification of LTR-Rs, and recent gene duplications in the pepper genomes as major evolutionary forces for diversification of Capsicum spp...
January 22, 2018: BMB Reports
https://www.readbyqxmd.com/read/29353412/helicobacter-pylori-lps-induced-gastric-mucosal-spleen-tyrosine-kinase-syk-recruitment-to-tlr4-and-activation-occurs-with-the-involvement-of-protein-kinase-c%C3%AE
#7
B L Slomiany, A Slomiany
Spleen tyrosine kinase (Syk) has emerged recently as a major effector of proinflammatory genes expression induced by LPS-elicited TLR4 activation, and manifested by the up-amplification in the production of inflammatory mediators, including PGE2 and NO. Here, we investigated the nature of factors involved in the recruitment and interaction of Syk with TLR4 in gastric mucosa in response to H. pylori LPS. We show that stimulation of gastric mucosal cells with the LPS leads to localization of Syk with the membrane-associated TLR4 complex and its activation through phosphorylation on Tyr...
January 20, 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/29352975/pinocembrin-from-penthorum-chinense-pursh-suppresses-hepatic-stellate-cells-activation-through-a-unified-sirt3-tgf-%C3%AE-smad-signaling-pathway
#8
Fayang Zhou, Anqi Wang, Dan Li, Yitao Wang, Ligen Lin
The inactivation of hepatic stellate cells (HSCs) has been verified to be an effective therapeutic strategy for treatment of liver fibrosis. Penthorum chinense Pursh has been widely used to protect liver in China; while, the role of P. chinense Pursh in treatment of liver fibrosis is still unexplored. In the current study, the aqueous extract of P. chinense Pursh (PCE) was found to suppress the expressions of fibrotic markers, including collagen I and α-smooth muscle actin (α-SMA), in human HSCs (LX-2); and its major active constituent, pinocembrin (PIN), was discovered to inhibit the expressions of fibrotic markers in LX-2 cells and rat HSCs (HSC-T6)...
January 15, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29352876/structural-characterization-and-macrophage-activation-of-a-hetero-galactan-isolated-from-flammulina-velutipes
#9
Yue Meng, Jingmin Yan, Guang Yang, Zhen Han, Guihua Tai, Hairong Cheng, Yifa Zhou
We isolated and purified a new polysaccharide (WFVP-N-b1) with a molecular weight of 20 kDa from Flammulina velutipes. Results showed that WFVP-N-b1 is composed of an α (1 → 6)-linked D-galactan backbone and branched at the O-2 of its Galp residues by an α-D-(1 → 6)-linked Manp attached to t-β-D-Glcp or t-α-D-Fucp side chains. WFVP-N-b1 can significantly induce cytokines secretion and release of toxic molecules. On a cellular level, WFVP-N-b1 is recognized by Toll-like receptor 4 (TLR4). Thereby, the hetero-galactan increased the phosphorylation of mitogen-activated protein kinases (MAPKs) and Akt, promoted degradation of IκB-α and the nuclear translocation of the NF-κB p65 subunit...
March 1, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29352717/should-we-use-cell-of-origin-and-dual-protein-expression-in-treating-dlbcl
#10
REVIEW
Peter A Riedell, Sonali M Smith
Treatment outcomes in diffuse large B-cell lymphoma (DLBCL) following standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy is highly variable and dependent on a number of clinical, biologic, and genetic features. The identification of molecular heterogeneity via gene expression profiling dichotomizes patients based on the cell of origin (COO) model into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subsets, with ABC-DLBCL having a worse outcome...
December 24, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29352609/induction-of-mitophagy-in-the-hei-oc1-auditory-cell-line-and-activation-of-the-atg12-lc3-pathway-in-the-organ-of-corti
#11
Cristian Setz, Anne-Sophie Benischke, Anna Catharina Pinho Ferreira Bento, Yves Brand, Soledad Levano, Franziska Paech, Katharina Leitmeyer, Daniel Bodmer
Autophagy is a highly evolutionary conserved quality control defense mechanism within cells, which has also been implicated in cell death processes. In the mammalian inner ear, autophagy has been shown to play a role during early morphogenesis as well as in adult cochlear hair cells exposed to ototoxic insults. Mitophagy, a selective autophagic cell process targeting mitochondria, hasn't been studied in the inner ear so far. On this work, we searched for molecular indicators of mitophagy within House Ear Institute-Organ of Corti-1 (HEI-OC1) cells as well as in the organ of Corti (OC)...
January 11, 2018: Hearing Research
https://www.readbyqxmd.com/read/29352484/melatonin-ameliorates-a%C3%AE-42-induced-alteration-of-%C3%AE-app-processing-secretases-via-the-melatonin-receptor-through-the-pin1-gsk3%C3%AE-nf-%C3%AE%C2%BAb-pathway-in-sh-sy5y-cells
#12
Vorapin Chinchalongporn, Mayuri Shukla, Piyarat Govitrapong
Melatonin is involved in the physiological regulation of the β- amyloid precursor protein (βAPP) cleaving secretases which are responsible for generation of the neurotoxic amyloid beta (Aβ) peptide, one of the hallmarks of Alzheimer's disease (AD) pathology. In this study, we aimed to determine the underlying mechanisms of this regulation under pathological conditions. We establish that melatonin prevents Aβ42 -induced down-regulation of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) as well as up-regulation of β-site APP-cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) in SH-SY5Y cell cultures...
January 20, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29352300/5-aminosalicylic-acid-improves-lipid-profile-in-mice-fed-a-high-fat-cholesterol-diet-through-its-dual-effects-on-intestinal-ppar%C3%AE-and-ppar%C3%AE
#13
Zheng Wang, Debby Koonen, Marten Hofker, Zhijun Bao
Obesity is associated with a series of metabolic complications, including dyslipidemia and insulin resistance (IR) that lack effective therapies. In recent years, intestinal inflammation has been suggested to contribute to obesity related metabolic syndrome and targeting gut inflammation with 5-ASA improves diet induced IR, however, its role in dyslipidemia is unknown and has never been explored. In the present study, we reported for the first time that administration of 5-ASA for 12 weeks significantly improved lipid profile by repressing plasma triglycerides and free cholesterol levels in mice fed high-fat cholesterol diet (HFC)...
2018: PloS One
https://www.readbyqxmd.com/read/29352225/a-humanized-mouse-model-of-liver-fibrosis-following-expansion-of-transplanted-hepatic-stellate-cells
#14
Daniel Benten, Johannes Kluwe, Jan W Wirth, Nina D Thiele, Antonia Follenzi, Kuldeep K Bhargava, Christopher J Palestro, Michael Koepke, Reni Tjandra, Tassilo Volz, Marc Lutgehetmann, Sanjeev Gupta
Hepatic stellate cells (HSCs) are major contributors to liver fibrosis, as hepatic injuries may cause their transdifferentiation into myofibroblast-like cells capable of producing excessive extracellular matrix proteins. Also, HSCs can modulate engraftment of transplanted hepatocytes and contribute to liver regeneration. Therefore, understanding the biology of human HSCs (hHSCs) is important, but effective methods have not been available to address their fate in vivo. To investigate whether HSCs could engraft and repopulate the liver, we transplanted GFP-transduced immortalized hHSCs into immunodeficient NOD/SCID mice...
January 19, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29351737/identifying-genome-wide-immune-gene-variation-underlying-infectious-disease-in-wildlife-populations-a-next-generation-sequencing-approach-in-the-gopher-tortoise
#15
Jean P Elbers, Mary B Brown, Sabrina S Taylor
BACKGROUND: Infectious disease is the single greatest threat to taxa such as amphibians (chytrid fungus), bats (white nose syndrome), Tasmanian devils (devil facial tumor disease), and black-footed ferrets (canine distemper virus, plague). Although understanding the genetic basis to disease susceptibility is important for the long-term persistence of these groups, most research has been limited to major-histocompatibility and Toll-like receptor genes. To better understand the genetic basis of infectious disease susceptibility in a species of conservation concern, we sequenced all known/predicted immune response genes (i...
January 19, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29351342/a-homozygous-missense-variant-in-vwa2-encoding-an-interactor-of-the-fraser-complex-in-a-patient-with-vesicoureteral-reflux
#16
Amelie T van der Ven, Birgit Kobbe, Stefan Kohl, Shirlee Shril, Hans-Martin Pogoda, Thomas Imhof, Hadas Ityel, Asaf Vivante, Jing Chen, Daw-Yang Hwang, Dervla M Connaughton, Nina Mann, Eugen Widmeier, Mary Taglienti, Johanna Magdalena Schmidt, Makiko Nakayama, Prabha Senguttuvan, Selvin Kumar, Velibor Tasic, Elijah O Kehinde, Shrikant M Mane, Richard P Lifton, Neveen Soliman, Weining Lu, Stuart B Bauer, Matthias Hammerschmidt, Raimund Wagener, Friedhelm Hildebrandt
Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause (40-50%) of chronic kidney disease (CKD) in children. About 40 monogenic causes of CAKUT have so far been discovered. To date less than 20% of CAKUT cases can be explained by mutations in these 40 genes. To identify additional monogenic causes of CAKUT, we performed whole exome sequencing (WES) and homozygosity mapping (HM) in a patient with CAKUT from Indian origin and consanguineous descent. We identified a homozygous missense mutation (c...
2018: PloS One
https://www.readbyqxmd.com/read/29350405/reactive-oxygen-species-induced-parthanatos-of-immunocytes-by-human-cytomegalovirus-associated-substance
#17
Jung Heon Kim, Jiyeon Kim, Jin Roh, Chan-Sik Park, Ju-Young Seoh, Eung-Soo Hwang
Previous studies examined various immune evasion strategies of human cytomegalovirus (HCMV) to understand HCMV pathogenesis. Although the mechanism that underlies immunocyte destruction near HCMV-infected lesions has yet to be established, we show that substances produced by HCMV-infected cells induce death in several types of immunocytes, but not in fibroblasts or astrocytomas. These substances contain HCMV proteins and were termed HCMV-associated insoluble substance (HCMVAIS). We characterized this mechanism of cell death induced by HCMVAIS to understand the death of immunocytes near HCMV-infected lesions...
January 19, 2018: Microbiology and Immunology
https://www.readbyqxmd.com/read/29348827/molecular-genetic-profiling-and-high-throughput-in-vitro-drug-screening-in-nut-midline-carcinoma-an-aggressive-and-fatal-disease
#18
Anja Stirnweiss, Joyce Oommen, Rishi S Kotecha, Ursula R Kees, Alex H Beesley
NUT midline carcinoma (NMC) is a rare and aggressive cancer, with survival typically less than seven months, that can arise in people of any age. Genetically, NMC is defined by the chromosomal fusion of NUTM1 with a chromatin-binding partner, typically the bromodomain-containing protein BRD4. However, little is known about other genetic aberrations in this disease. In this study, we used a unique panel of cell lines to describe the molecular-genetic features of NMC. Next-generation sequencing identified a recurring high-impact mutation in the DNA-helicase gene RECQL5 in 75% of lines studied, and biological signals from mutation-signature and network analyses consistent with a general failure in DNA-repair...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348560/discovery-of-a-small-molecule-protein-kinase-c%C3%AE-selective-activator-with-promising-application-in-colon-cancer-therapy
#19
Cláudia Bessa, Joana Soares, Liliana Raimundo, Joana B Loureiro, Célia Gomes, Flávio Reis, Miguel L Soares, Daniel Santos, Chetna Dureja, Saumya R Chaudhuri, Cynthia Lopez-Haber, Marcelo G Kazanietz, Jorge Gonçalves, Maria F Simões, Patrícia Rijo, Lucília Saraiva
Protein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first small-molecule PKCδ-selective activator, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (Roy-Bz), which binds to the PKCδ-C1-domain. Roy-Bz potently inhibited the proliferation of colon cancer cells by inducing a PKCδ-dependent mitochondrial apoptotic pathway involving caspase-3 activation...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348472/viral-highway-to-nucleus-exposed-by-image-correlation-analyses
#20
Elina Mäntylä, Jenu V Chacko, Vesa Aho, Colin R Parrish, Victor Shahin, Michael Kann, Michelle A Digman, Enrico Gratton, Maija Vihinen-Ranta
Parvoviral genome translocation from the plasma membrane into the nucleus is a coordinated multistep process mediated by capsid proteins. We used fast confocal microscopy line scan imaging combined with image correlation methods including auto-, pair- and cross-correlation, and number and brightness analysis, to study the parvovirus entry pathway at the single-particle level in living cells. Our results show that the endosome-associated movement of virus particles fluctuates from fast to slow. Fast transit of single cytoplasmic capsids to the nuclear envelope is followed by slow movement of capsids and fast diffusion of capsid fragments in the nucleoplasm...
January 18, 2018: Scientific Reports
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