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https://www.readbyqxmd.com/read/28331370/can-the-hiv-1-splicing-machinery-be-targeted-for-drug-discovery
#1
REVIEW
Zodwa Dlamini, Rodney Hull
HIV-1 is able to express multiple protein types and isoforms from a single 9 kb mRNA transcript. These proteins are also expressed at particular stages of viral development, and this is achieved through the control of alternative splicing and the export of these transcripts from the nucleus. The nuclear export is controlled by the HIV protein Rev being required to transport incompletely spliced and partially spliced mRNA from the nucleus where they are normally retained. This implies a close relationship between the control of alternate splicing and the nuclear export of mRNA in the control of HIV-1 viral proliferation...
2017: HIV/AIDS: Research and Palliative Care
https://www.readbyqxmd.com/read/28329136/chronic-resveratrol-treatment-inhibits-mrc5-fibroblast-sasp-related-protumoral-effects-on-melanoma-cells
#2
Beatrice Menicacci, Anna Laurenzana, Anastasia Chillà, Francesca Margheri, Silvia Peppicelli, Elisabetta Tanganelli, Gabriella Fibbi, Lisa Giovannelli, Mario Del Rosso, Alessandra Mocali
Cellular senescence is related to organismal aging and is observed after DNA damaging cancer therapies, that induce tumor-suppressive modifications, but it is characterized by a strong increase in secreted factors, termed the "senescence-associated secretory phenotype" (SASP). Particularly, SASP from stroma senescent fibroblasts creates a cancer-favoring microenvironment, providing targets for anti-cancer interventions. In the present article, chronic treatment (5 weeks) with 5 µM resveratrol has been used to modulate senescence-related protumoral features of MRC5 fibroblasts, reducing SASP-related interleukins IL1α, IL1β, IL6, and IL8; transforming-growth-factor-β (TGFβ); matrix metallo-proteinases MMP3 and MMP2; urokinase plasminogen activator (uPA); receptor proteins uPAR, IL6R, insulin growth factor receptor-1 (IGF-1R), TGFβ-R2, and CXCR4...
January 20, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28317735/l-carnitine-ameliorates-the-oxidative-stress-response-to-angiotensin-ii-by-modulating-nadph-oxidase-through-a-reduction-in-protein-kinase-c-activity-and-nf-%C3%AE%C2%BAb-translocation-to-the-nucleus
#3
Antonio J Blanca, María V Ruiz-Armenta, Sonia Zambrano, José L Miguel-Carrasco, Francisco M González-Roncero, Ana Fortuño, Elisa Revilla, Alfonso Mate, Carmen M Vázquez
l-Carnitine (LC) exerts beneficial effects in arterial hypertension due, in part, to its antioxidant capacity. We investigated the signalling pathways involved in the effect of LC on angiotensin II (Ang II)-induced NADPH oxidase activation in NRK-52E cells. Ang II increased the generation of superoxide anion from NADPH oxidase, as well as the amount of hydrogen peroxide and nitrotyrosine. Co-incubation with LC managed to prevent these alterations and also reverted the changes in NADPH oxidase expression triggered by Ang II...
August 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28301045/beneficial-effect-of-ustekinumab-in-familial-pityriasis-rubra-pilaris-with-a-new-missense-mutation-in-card14
#4
S M Lwin, C-K Hsu, L Liu, H-Y Huang, N J Levell, J A McGrath
Pityriasis rubra pilaris (PRP) represents a group of rare chronic inflammatory skin disorders in which ~1 in 20 affected individuals show autosomal dominant inheritance. In such cases, there may be gain-of-function mutations in CARD14, encoding caspase recruitment domain-containing protein 14 (CARD14) that activates the non-canonical nuclear factor-kappa B (NF-κB) pathway, thereby promoting cutaneous inflammation. Here, we report a mother and son with PRP due to a new missense mutation in CARD14 and describe the beneficial clinical effects of ustekinumab, a monoclonal antibody against interleukins-12 and -23, in both subjects...
March 16, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28289288/3d-structures-of-individual-mammalian-genomes-studied-by-single-cell-hi-c
#5
Tim J Stevens, David Lando, Srinjan Basu, Liam P Atkinson, Yang Cao, Steven F Lee, Martin Leeb, Kai J Wohlfahrt, Wayne Boucher, Aoife O'Shaughnessy-Kirwan, Julie Cramard, Andre J Faure, Meryem Ralser, Enrique Blanco, Lluis Morey, Miriam Sansó, Matthieu G S Palayret, Ben Lehner, Luciano Di Croce, Anton Wutz, Brian Hendrich, Dave Klenerman, Ernest D Laue
The folding of genomic DNA from the beads-on-a-string-like structure of nucleosomes into higher-order assemblies is crucially linked to nuclear processes. Here we calculate 3D structures of entire mammalian genomes using data from a new chromosome conformation capture procedure that allows us to first image and then process single cells. The technique enables genome folding to be examined at a scale of less than 100 kb, and chromosome structures to be validated. The structures of individual topological-associated domains and loops vary substantially from cell to cell...
March 13, 2017: Nature
https://www.readbyqxmd.com/read/28288912/anti-inflammatory-and-hepatoprotective-effects-of-glycyrrhetinic-acid-on-ccl4-induced-damage-in-precision-cut-liver-slices-from-jian-carp-cyprinus-carpio-var-jian-through-inhibition-of-the-nf-k%C3%A6-pathway
#6
Liping Cao, Weidong Ding, Rui Jia, Jingliang Du, Tao Wang, Chunyun Zhang, Zhengyan Gu, Guojun Yin
In order to evaluate the antioxidant and anti-inflammatory effects of glycyrrhetinic acid (GA) on carbon tetrachloride (CCl4)-induced damage in precision-cut liver slices (PCLS) from Jian carp (Cyprinus carpio. Jian), an acute liver damage model was established in this study. The viability of PCLS, levels of anti-oxidases in liver homogenates, expression of inflammation-related genes including nuclear factor-κB (nf-κB)/c-rel, inducible nitric oxide synthase (inos), interleukin-1β (il-1β), interleukin-6 (il-6) and interleukin-8 (il-8), and protein levels of (nf-κB)/c-rel in liver tissues were measured...
March 10, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28263976/nlrp1-promotes-tumor-growth-by-enhancing-inflammasome-activation-and-suppressing-apoptosis-in-metastatic-melanoma
#7
Z Zhai, W Liu, M Kaur, Y Luo, J Domenico, J M Samson, Y G Shellman, D A Norris, C A Dinarello, R A Spritz, M Fujita
Inflammasomes are mediators of inflammation, and constitutively activated NLRP3 inflammasomes have been linked to interleukin-1β (IL-1β)-mediated tumorigenesis in human melanoma. Whereas NLRP3 regulation of caspase-1 activation requires the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain)), caspase-1 activation by another danger-signaling sensor NLRP1 does not require ASC because NLRP1 contains a C-terminal CARD domain that facilitates direct caspase-1 activation via CARD-CARD interaction...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28261375/parental-high-fat-diet-promotes-inflammatory-and-senescence-related-changes-in-prostate
#8
Kulbhushan Tikoo, Ajit Vikram, Shweta Shrivastava, Gopabandhu Jena, Heta Shah, Richa Chhabra
Background. Obesity and dietary habits are associated with increased incidences of aging-related prostatic diseases. The present study was aimed to investigate transgenerational effects of chronic high-fat diet (HFD) feeding on inflammation and senescence-related changes in prostate. Methods. Sprague-Dawley rats were kept on either normal or HFD one. Senescence-associated β-galactosidase (SA β-gal) activity, inflammation, and cellular proliferation were determined in the prostate. Results. Increased SA β-gal activity, expression of p53, and cell proliferation marker PCNA were observed in ventral prostate of HFD-fed rats...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28236616/nuclear-factor-kb-and-inhibitor-of-kb-acupuncture-protection-against-acute-focal-cerebral-ischemia-in-rodents
#9
Wei Huang, Zhongyu Zhou, Bijiang Wan, Guang Chen, Jia Li
Context • Acute, focal, cerebral ischemic stroke is a leading cause of morbidity and mortality worldwide. Acupuncture is an emerging alternative therapy for treatment of acute brain ischemia. Nevertheless, the precise mechanism underlying the neuroprotective effects of acupuncture has not been elucidated. Nuclear factor κB (NF-κB) and nuclear factor of κ light polypeptide gene enhancer in B cell inhibitor alpha (IκB-α) are involved in cerebral inflammation. However, the involvement of NF-κB and IκB-α in the protective effects of acupuncture on ischemic tolerance remains unknown...
February 27, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28236612/determining-the-effects-of-geraniol-on-liver-regeneration-via-the-nuclear-factor-kb-pathway-after-partial-hepatectomy
#10
Emre Ceyhan, Mediha Canbek
Context • Nuclear factor kB (NF-κB) is a dimeric transcription factor that is involved in the regulation of regenerative and apoptosic genes and plays a key role in liver regeneration after a partial hepatectomy (PH). Complementary medicine is used to treat various diseases and can be obtained from a large number of plants that are found in nature. One such plant is geraniol, and no studies have yet occurred assessing its in vivo effects on liver regeneration. Objective • The current study intended to assess the effects of geraniol on liver regeneration after a 70% PH in rats...
February 27, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28219599/aminophylline-effect-on-renal-ischemia-reperfusion-injury-in-mice
#11
K Seo, J W Choi, D-W Kim, D Han, S J Noh, H S Jung
BACKGROUND: Aminophylline increases the intracellular concentration of cAMP and exerts an anti-inflammatory effect. The aim of this study was to investigate the effect of aminophylline on renal ischemia-reperfusion (I/R) injury in mice. METHODS: Thirty C57BL/6 mice were divided into 3 groups. In the sham group (group S, n = 10), only right nephrectomy was performed. In the control group (group C, n = 10), after right nephrectomy, the mice were subjected to 30 minutes of left renal ischemia...
March 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28212354/the-effect-of-dexmedetomidine-on-oxidative-stress-response-following-cerebral-ischemia-reperfusion-in-rats-and-the-expression-of-intracellular-adhesion-molecule-1-icam-1-and-s100b
#12
Yanwen Li, Shikun Liu
BACKGROUND Ischemia-reperfusion injury of whole brain involves a complicated pathophysiology mechanism. Dexmedetomidine (Dex) has been shown to have neuro protective functions. This study observed the effect of Dex on serum S100B and cerebral intracellular adhesion molecule-1 (ICAM-1) in a rat model of cerebral ischemia-reperfusion. MATERIAL AND METHODS Healthy Sprague Dawley (SD) rats (males, 7 weeks old) were randomly divided into sham, model, and Dex groups (n=20 each). A cerebral ischemia-reperfusion model was prepared by clipping of the bilateral common carotid artery combined with hypotension...
February 17, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28193640/grk2-mediates-arginine-vasopressin-induced-il-6-production-via-nf-kb-signaling-in-neonatal-rat-cardiac-fibroblast
#13
Feifei Xu, Suzhen Sun, Xiaojun Wang, Eran Ni, Lingling Zhao, Weizhong Zhu
Elevated interleukin 6(IL-6) levels in congestive heart failure are associated with myocardial damage during acute exacerbation and with chronic inflammation. Arginine vasopressin (AVP), a hormone released in response to cardiac stress, could be a factor of inflammation and fibrosis in the pathogenesis of heart failure. Recently, we have shown that AVP promotes the proliferation of neonatal rat cardiac fibroblasts (NRCFs) through a V1Avasopressin receptor-mediated G protein-coupled receptor kinase2 (GRK2) signaling...
February 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28188410/simvastatin-inhibits-il-1%C3%AE-induced-apoptosis-and-extracellular-matrix-degradation-by-suppressing-the-nf-kb-and-mapk-pathways-in-nucleus-pulposus-cells
#14
Ji Tu, Wentian Li, Yukun Zhang, Xinghuo Wu, Yu Song, Liang Kang, Wei Liu, Kun Wang, Shuai Li, Wenbin Hua, Cao Yang
Statins are widely used hypocholesterolemic drugs that block the mevalonate pathway. Some studies have shown that statins may have the potential to inhibit intervertebral disk (IVD) degeneration (IDD). Interleukin (IL)-1β, a catabolic cytokine, is a key regulator of IDD. This study aimed to investigate the mechanism underlying the effect of simvastatin on IDD. The viability of nucleus pulposus (NP) cells was determined by the methyl-thiazolyl-tetrazolium (MTT) assay. The apoptosis of NP cells was measured by flow cytometric analysis, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and western blotting of relevant apoptotic proteins...
February 10, 2017: Inflammation
https://www.readbyqxmd.com/read/28186459/bioactivity-of-carotenoids-chasms-of-knowledge
#15
Torsten Bohn
Carotenoid dietary intake, especially within fruits/vegetables and their plasma levels have been associated in many epidemiological studies with a reduced risk of several chronic diseases, including type-2 diabetes, cardiovascular diseases, several types of cancer, and agerelated macular degeneration. However, intervention trials with isolated carotenoids (as supplements) have fallen short of fulfi lling the hopes that were placed in these lipophilic pigments, often producing no positive or even adverse effects, such as increased lung cancer rate or total mortality...
February 10, 2017: International Journal for Vitamin and Nutrition Research. Journal International de Vitaminologie et de Nutrition
https://www.readbyqxmd.com/read/28177524/in-vivo-expression-of-nurr1-nr4a2a-in-developing-retinal-amacrine-subtypes-in-zebrafish-tg-nr4a2a-egfp-transgenics
#16
Liana Goodings, Jie He, Alasdair Wood, William A Harris, Peter D Currie, Patricia R Jusuf
The Nuclear receptor subfamily 4 group A member 2 (Nr4a2) is crucial for the formation or maintenance of dopaminergic neurons in the central nervous system including the retina, where dopaminergic amacrine cells contribute to visual function. Little is known about which cells express Nr4a2 at which developmental stage. Furthermore, whether Nr4a2 functions in combination with other genes is poorly understood. Thus, we generated a novel transgenic to visualise Nr4a2 expression in vivo during zebrafish retinogenesis...
February 8, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28173812/anthocyanins-encapsulated-by-plga-peg-nanoparticles-potentially-improved-its-free-radical-scavenging-capabilities-via-p38-jnk-pathway-against-a%C3%AE-1-42-induced-oxidative-stress
#17
Faiz Ul Amin, Shahid Ali Shah, Haroon Badshah, Mehtab Khan, Myeong Ok Kim
BACKGROUND: In order to increase the bioavailability of hydrophilic unstable drugs like anthocyanins, we employed a polymer-based nanoparticles approach due to its unique properties such as high stability, improved bioavailability and high water-soluble drug loading efficiency. Anthocyanins constitute a subfamily of flavonoids that possess anti-oxidative, anti-inflammatory and neuroprotective properties. However, anthocyanins are unstable because their phenolic hydroxyl groups are easily oxidized into quinones, causing a reduced biological activity...
February 7, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28173800/oxidized-ldl-induced-jab1-influences-nf-%C3%AE%C2%BAb-independent-inflammatory-signaling-in-human-macrophages-during-foam-cell-formation
#18
Anja Schwarz, Gabriel A Bonaterra, Hans Schwarzbach, Ralf Kinscherf
BACKGROUND: Oxidized low-density lipoprotein (oxLDL) mediates the transformation of macrophages (MΦ) to cholesterol-rich foam cells and the release of pro-inflammatory cytokines during atherogenesis. JAB1 (Jun activation domain binding protein-1) is present in all stages of human plaques, involved in the Toll-like receptor-mediated activation of p38 mitogen-activated protein kinase (MAPK) and controls nuclear factor-kappa B (NF-κB) activation. Thus, we were interested in the role of JAB1 during foam cell formation of MΦ after oxLDL exposition...
February 7, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28160073/genistein-improves-schistosomiasis-liver-granuloma-and-fibrosis-via-dampening-nf-kb-signaling-in-mice
#19
Chunpeng Wan, Fen Jin, Youqin Du, Kang Yang, Liangliang Yao, Zhigang Mei, Weifeng Huang
In schistosomiasis, egg deposition in the liver contributes to the formation of hepatic granuloma and fibrosis, which are the most serious clinical pathological features. It has been proposed that activation of the nuclear factor kappa B (NF-κB) signaling pathways is closely associated with the development of hepatic granuloma and fibrosis. Genistein has been shown to inhibit the activity of NF-κB signaling pathways, which might be a potential agent to protect against Schistosoma japonicum egg-induced liver granuloma and fibrosis...
February 3, 2017: Parasitology Research
https://www.readbyqxmd.com/read/28152507/the-mutational-landscape-of-ocular-marginal-zone-lymphoma-identifies-frequent-alterations-in-tnfaip3-followed-by-mutations-in-tbl1xr1-and-crebbp
#20
Hyunchul Jung, Hae Yong Yoo, Seung Ho Lee, Sohyun Shin, Sang Cheol Kim, Sejoon Lee, Je-Gun Joung, Jae-Yong Nam, Daeun Ryu, Jae Won Yun, Jung Kyoon Choi, Ambarnil Ghosh, Kyeong Kyu Kim, Seok Jin Kim, Won Seog Kim, Woong-Yang Park, Young Hyeh Ko
Ocular marginal zone lymphoma is a common type of low-grade B-cell lymphoma. To investigate the genomic changes that occur in ocular marginal zone lymphoma, we analyzed 10 cases of ocular marginal zone lymphoma using whole-genome and RNA sequencing and an additional 38 cases using targeted sequencing. Major genetic alterations affecting genes involved in nuclear factor (NF)-κB pathway activation (60%), chromatin modification and transcriptional regulation (44%), and B-cell differentiation (23%) were identified...
January 31, 2017: Oncotarget
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