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https://www.readbyqxmd.com/read/28714416/application-of-kinase-inhibitors-for-anti-aging-intervention
#1
Mercedes Cano, Antonio Ayala, Francesco Marotta, Sandro Argüelles
Protein phosphorylation, mediated by protein kinases, has important physiological and pathological implications in our lives . Targeting kinase is one of the most interesting of the emerging topics in the pharmaceutical industry, especially since there is a focus on cancer therapy. Given that kinases may be involved in the aging process the focus will be on using the kinase inhibitor for anti-aging intervention to enhance healthspan and increase longevity. In this review , we will summarize: (i) the impact of the phosphoproteomic approach to elucidate molecular mechanisms of diseases; (ii) importance of the drug discovery approach for targeting kinases; (iii) the dysregulation of Janus kinase (JAK) / signal-transducing adapter molecules (STAT) and p70 ribosomal protein S6 kinase (S6Ks) pathway in aging and the age-related process; (iv) the epidemiological studies available in order to see whether a correlation between JAK/STAT and S6Ks mRNA expression levels exist in cancer and in patient outcome; (v) finally, we will show selected inhibitors of these kinases approved by the US Food and Drug Administration (FDA)...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28698127/dietary-protein-levels-regulated-antibacterial-activity-inflammatory-response-and-structural-integrity-in-the-head-kidney-spleen-and-skin-of-grass-carp-ctenopharyngodon-idella-after-challenged-with-aeromonas-hydrophila
#2
Wei-Dan Jiang, Jing Xu, Xiao-Qiu Zhou, Pei Wu, Yang Liu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Lin Feng
This study investigated the effects of dietary protein levels on disease resistance, immune function and structural integrity in the head kidney, spleen and skin of grass carp (Ctenopharyngodon idella). A total of 540 grass carp (264.11 ± 0.76 g) were fed six diets containing graded levels of protein (143.1, 176.7, 217.2, 257.5, 292.2 and 322.8 g digestible protein kg(-1) diet) for 8 weeks. After the growth trial, fish were challenged with Aeromonas hydrophila for 14 days. The results indicated that optimal levels of dietary protein: (1) (1) increased the lysozyme (LA) and acid phosphatase (ACP) activities and the complement 3 (C3) and C4 contents, up-regulated antimicrobial peptides, anti-inflammatory cytokines, inhibitor of κBα, target of rapamycin and ribosomal protein S6 kinases 1 mRNA levels, whereas down-regulated pro-inflammatory cytokines, nuclear factor kappa B (NF-κB) P65, IKKβ, IKKγ, eIF4E-binding proteins (4E-BP) 1 and 4E-BP2 mRNA levels in the head kidney, spleen and skin of grass carp (P < 0...
July 8, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28696944/mitoriboscins-mitochondrial-based-therapeutics-targeting-cancer-stem-cells-cscs-bacteria-and-pathogenic-yeast
#3
Bela Ozsvari, Marco Fiorillo, Gloria Bonuccelli, Anna Rita Cappello, Luca Frattaruolo, Federica Sotgia, Rachel Trowbridge, Richard Foster, Michael P Lisanti
The "endo-symbiotic theory of mitochondrial evolution" states that mitochondrial organelles evolved from engulfed aerobic bacteria, after millions of years of symbiosis and adaptation. Here, we have exploited this premise to design new antibiotics and novel anti-cancer therapies, using a convergent approach. First, virtual high-throughput screening (vHTS) and computational chemistry were used to identify novel compounds binding to the 3D structure of the mammalian mitochondrial ribosome. The resulting library of ~880 compounds was then subjected to phenotypic drug screening on human cancer cells, to identify which compounds functionally induce ATP-depletion, which is characteristic of mitochondrial inhibition...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28693280/improved-antitumor-effect-of-ionizing-radiation-in-combination-with-rapamycin-for-treating-nasopharyngeal-carcinoma
#4
Di Wang, Lichen Gao, Xueting Liu, Chuang Yuan, Guihua Wang
The aim of the present study is to investigate if rapamycin is a radiosensitizer of nasopharyngeal carcinoma (NPC), and to identify which pathways are involved in radiation sensitization. In vitro, using untreated cells as the control, NPC cells were treated with rapamycin, ionizing radiation (IR) or both. Differences in the phosphorylation of ribosomal protein S6 and glycogen synthase kinase (GSK) 3β, expression of cyclin D1, clonogenic survival, number of phosphorylated histone subunit 2AX (γH2AX) foci, and cell cycle status between the study groups were compared...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28693237/inhibitory-effects-of-delphinidin-on-the-proliferation-of-ovarian-cancer-cells-via-pi3k-akt-and-erk-1-2-mapk-signal-transduction
#5
Whasun Lim, Gwonhwa Song
Delphinidin is a member of the anthocyanidin family and is a natural pigment in red cabbage, berries, sweet potatoes and grapes. It possesses nutraceutical properties against various chronic diseases and types of cancer. However, little is known about its preventative effects on epithelial ovarian cancer, a disease that is associated with a low survival rate, a poor prognosis and a high rate of recurrence. The results of the present study demonstrated that the proliferation of SKOV3 cells decreased in a dose-dependent manner in response to treatment with delphinidin, and the phosphorylation of carcinogenic protein kinases associated with the progression of epithelial ovarian cancer was affected by delphinidin treatment...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28690185/selection-of-similar-single-domain-antibodies-from-two-immune-vhh-libraries-obtained-from-two-alpacas-by-using-different-selection-methods
#6
Tengfei Li, Matthias Vandesquille, Sylvie Bay, Marc Dhenain, Benoît Delatour, Pierre Lafaye
The two most used methods to select camelid single-domain antibody-fragments (VHHs) are: displaying their repertoires on the surface of filamentous bacteriophages (phage display) or linking them to ribosomes (ribosome display). In this study, we compared specific VHHs isolated from two different immune libraries coming from two different alpacas by using these two selection methods. Three anti-GFAP (glial fibrillary acidic protein) VHHs were derived from an immune library obtained by ribosome display after immunization of one alpaca with purified GFAP, a protein expressed by astroglial cells...
July 6, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28683309/the-complete-structure-of-the-mycobacterium-smegmatis-70s-ribosome
#7
Jendrik Hentschel, Chloe Burnside, Ingrid Mignot, Marc Leibundgut, Daniel Boehringer, Nenad Ban
The ribosome carries out the synthesis of proteins in every living cell. It consequently represents a frontline target in anti-microbial therapy. Tuberculosis ranks among the leading causes of death worldwide, due in large part to the combination of difficult-to-treat latency and antibiotic resistance. Here, we present the 3.3-Å cryo-EM structure of the 70S ribosome of Mycobacterium smegmatis, a close relative to the human pathogen Mycobacterium tuberculosis. The structure reveals two additional ribosomal proteins and localizes them to the vicinity of drug-target sites in both the catalytic center and the decoding site of the ribosome...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28669564/eriocalyxin-b-a-novel-autophagy-inducer-exerts-anti-tumor-activity-through-the-suppression-of-akt-mtor-p70s6k-signaling-pathway-in-breast-cancer
#8
Xunian Zhou, Grace Gar-Lee Yue, Andrew Man-Lok Chan, Stephen Kwok-Wing Tsui, Kwok-Pui Fung, Handong Sun, Jianxin Pu, Clara Bik-San Lau
Eriocalyxin B (EriB), a natural ent-kaurane diterpenoid presented in the plant Isodon eriocalyx var. laxiflora, has been reported to diminish angiogenesis-dependent breast tumor growth. In the present study, the effects of EriBon human breast cancer and its underlying mechanisms were further investigated. The in vitro anti-breast cancer activity of EriB was determined using MCF-7 and MDA-MB-231 cell lines. MDA-MB-231 xenograft model of human breast cancer was also established to explore the anti-tumor effect in vivo...
June 29, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28664270/curcin-c-a-novel-type-i-ribosome-inactivating-protein-from-the-post-germinating-cotyledons-of-jatropha-curcas
#9
Yangxue Zhang, Qian Yang, Chenyang Li, Mengmeng Ding, Xueyan Lv, Chengqiu Tao, Hongwu Yu, Fang Chen, Ying Xu
A novel type I ribosome-inactivating protein (RIP), designated as curcin C, was purified from Jatropha curcas, an important feedback source of bio-fuel. Molecular mass and isoelectric point of curcin C were 31.398 kDa and 7.12 as detected by MALTI-TOF assay and capillary electrophoresis assay, respectively. N-terminal sequence and LC-MS/MS analyses confirmed that curcin C is a type I RIP having high homology, but not the exactly the same with curcin, another type 1 RIP isolated from the endosperm of J. curcas...
June 29, 2017: Amino Acids
https://www.readbyqxmd.com/read/28660501/the-anti-m%C3%A3-llerian-hormone-amh-induces-forkhead-box-l2-foxl2-expression-in-primary-culture-of-human-granulosa-cells-in-vitro
#10
Sandro Sacchi, Federica Marinaro, Susanna Xella, Tiziana Marsella, Daniela Tagliasacchi, Antonio La Marca
PURPOSE: Anti-Müllerian hormone (AMH) and forkhead box L2 (FOXL2) are two pivotal genes expressed in human granulosa cells (hGCs) where both genes share similar inhibitory functions on activation and follicular growth in order to preserve the ovarian follicle reserve. Furthermore, AMH and FOXL2 contribute to inhibit steroidogenesis, decreasing or preventing the activation of gonadotrophin-dependent aromatase CYP19A1 cytochrome P450 family 19 subfamily A member 1 (CYP19A1). The purpose of this study is to evaluate the role of AMH in regulating the expression of FOXL2...
June 29, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28659908/pterostilbene-a-methoxylated-resveratrol-derivative-efficiently-eradicates-planktonic-biofilm-and-intracellular-mrsa-by-topical-application
#11
Shih-Chun Yang, Chih-Hua Tseng, Pei-Wen Wang, Po-Liang Lu, Yi-Han Weng, Feng-Lin Yen, Jia-You Fang
Pterostilbene is a methoxylated derivative of resveratrol originated from natural sources. We investigated the antibacterial activity of pterostilbene against drug-resistant Staphylococcus aureus and the feasibility of using it to treat cutaneous bacteria. The antimicrobial effect was evaluated using an in vitro culture model and an in vivo mouse model of cutaneous infection. The minimum inhibitory concentration (MIC) assay demonstrated a superior biocidal activity of pterostilbene compared to resveratrol (8~16-fold) against methicillin-resistant S...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28654654/identification-and-characterization-of-acka-dependent-protein-acetylation-in-neisseria-gonorrhoeae
#12
Deborah M B Post, Birgit Schilling, Lorri M Reinders, Alexandria K D'Souza, Margaret R Ketterer, Steven J Kiel, Aroon T Chande, Michael A Apicella, Bradford W Gibson
Neisseria gonorrhoeae, the causative agent of gonorrhea, has a number of factors known to contribute to pathogenesis; however, a full understanding of these processes and their regulation has proven to be elusive. Post-translational modifications (PTMs) of bacterial proteins are now recognized as one mechanism of protein regulation. In the present study, Western blot analyses, with an anti-acetyl-lysine antibody, indicated that a large number of gonococcal proteins are post-translationally modified. Previous work has shown that Nε-lysine acetylation can occur non-enzymatically with acetyl-phosphate (AcP) as the acetyl donor...
2017: PloS One
https://www.readbyqxmd.com/read/28652238/characterization-of-the-activities-of-dinuclear-thiolato-bridged-arene-ruthenium-complexes-against-toxoplasma-gondii
#13
Afonso P Basto, Joachim Müller, Riccardo Rubbiani, David Stibal, Federico Giannini, Georg Süss-Fink, Vreni Balmer, Andrew Hemphill, Gilles Gasser, Julien Furrer
The in vitro effects of 18 dinuclear-thiolato bridged arene ruthenium complexes, (1 mono-, 4 di- and 13-tri-thiolato compounds), originally designed as anti-cancer agents, were studied in the apicomplexan parasite Toxoplasma gondii grown in human foreskin fibroblast host cells (HFF). Some tri-thiolato compounds exhibited anti-parasitic efficacy at 250 nM and below. Among those, complex 1 and complex 2 inhibited T. gondii proliferation with IC50 values of 34 and 62 nM, respectively, and they did not affect HFF at dosages of 200 μM or above, resulting in selectivity indices of > 23' 000...
June 26, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28650175/bioactive-peptide-natural-products-as-lead-structures-for-medicinal-use
#14
Tam Dang, Roderich D Süssmuth
The need for new drugs for the treatment of various diseases is enormous. From the previous century until the present, numerous peptide and peptide-derived natural products have been isolated from bacteria and fungi. Hence, microorganisms play a pivotal role as sources for novel drugs with an emphasis on anti-infective agents. Various disciplines from biology, chemistry, and medicine are involved in early stages of the search for peptide natural products including taxonomy, microbiology, bioanalytics, bioinformatics, and medicinal chemistry...
June 26, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28640897/impact-of-selected-non-steroidal-anti-inflammatory-pharmaceuticals-on-microbial-community-assembly-and-activity-in-sequencing-batch-reactors
#15
Cong Jiang, Jinju Geng, Haidong Hu, Haijun Ma, Xingsheng Gao, Hongqiang Ren
This study covers three widely detected non-steroidal anti-inflammatory pharmaceuticals (NSAIDs), diclofenac (DCF), ibuprofen (IBP) and naproxen (NPX), as NSAIDs pollutants. The objective is to evaluate the impact of NSAIDs at their environmental concentrations on microbial community assembly and activity. The exposure experiments were conducted under three conditions (5 μg L-1 DCF, 5 μg L-1 DCF+5 μg L-1 IBP and 5 μg L-1 DCF+5 μg L-1 IBP+ 5 μg L-1 NPX) in sequencing batch reactors (SBRs) for 130 days...
2017: PloS One
https://www.readbyqxmd.com/read/28622108/fluctuations-of-pol-i-and-fibrillarin-contents-of-the-nucleoli
#16
M Hornáček, L Kováčik, T Mazel, D Cmarko, E Bártová, I Raška, E Smirnov
Nucleoli are formed on the basis of ribosomal DNA (rDNA) clusters called Nucleolus Organizer Regions (NORs). Each NOR contains multiple genes coding for RNAs of the ribosomal particles. The prominent components of the nucleolar ultrastructure, fibrillar centers (FC) and dense fibrillar components (DFC), together compose FC/DFC units. These units are centers of rDNA transcription by RNA polymerase I (pol I), as well as the early processing events, in which an essential role belongs to fibrillarin. Each FC/DFC unit probably corresponds to a single transcriptionally active gene...
June 16, 2017: Nucleus
https://www.readbyqxmd.com/read/28587595/proteomic-analysis-by-itraq-mrm-of-soybean-resistance-to-lamprosema-indicate
#17
Weiying Zeng, Zudong Sun, Zhaoyan Cai, Huaizhu Chen, Zhenguang Lai, Shouzhen Yang, Xiangmin Tang
BACKGROUND: Lamprosema indicate is a major leaf feeding insect pest to soybean, which has caused serious yield losses in central and southern China. To explore the defense mechanisms of soybean resistance to Lamprosema indicate, a highly resistant line (Gantai-2-2) and a highly susceptible line (Wan 82-178) were exposed to Lamprosema indicate larval feedings for 0 h and 48 h, and the differential proteomic analyses of these two lines were carried out. RESULTS: The results showed that 31 differentially expressed proteins (DEPs) were identified in the Gantai-2-2 when comparing 48 h feeding with 0 h feeding, and 53 DEPs were identified in the Wan 82-178...
June 6, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28585192/rsk2-knockout-affects-emotional-behavior-in-the-intellicage
#18
Matthias Fischer, Victoria Cabello, Sandy Popp, Sven Krackow, Leif Hommers, Jürgen Deckert, Klaus-Peter Lesch, Angelika G Schmitt-Böhrer
Ribosomal s6 kinase 2 is a growth factor activated serine/threonine kinase and member of the ERK signaling pathway. Mutations in the Rsk2 gene cause Coffin-Lowry syndrome, a rare syndromic form of intellectual disability. The Rsk2 KO mouse model was shown to have learning and memory defects. We focused on the investigation of the emotional behavioral phenotype of Rsk2 KO mice mainly in the IntelliCage. They exhibited an anti-depressive, sucrose reward seeking phenotype and showed reduced anxiety. Spontaneous activity was increased in some conventional tests...
June 6, 2017: Behavior Genetics
https://www.readbyqxmd.com/read/28573746/rifaximin-exerts-beneficial-effects-in-pi-ibs-mouse-model-beyond-gut-microbiota
#19
Yu Jin, Xiaoyang Ren, Gangping Li, Ying Li, Lei Zhang, Huan Wang, Wei Qian, Xiaohua Hou
BACKGROUND AND AIMS: Rifaximin is a minimally absorbed antibiotic which has shown efficacy in irritable bowel syndrome (IBS) patients. However, the mechanism how it effects in IBS is still incompletely defined. In this study, we used Trichinella spiralis infected PI-IBS mouse model, to assess the action of rifaximin on visceral hypersensitivity, barrier function, gut inflammation and microbiota. METHODS: PI-IBS model was established by Trichinella spiralis infection in mice...
June 1, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28556833/blockade-of-interleukin-6-receptor-in-the-periphery-promotes-rapid-and-sustained-antidepressant-actions-a-possible-role-of-gut-microbiota-brain-axis
#20
J-C Zhang, W Yao, C Dong, C Yang, Q Ren, M Ma, K Hashimoto
Depression is a common, severe and chronic psychiatric disease. Although the currently available antidepressants have been used in the treatment of depression, their beneficial effects are limited. Accumulating evidence suggests that pro-inflammatory cytokines such as interleukin-6 (IL-6) have an important role in the pathogenesis of depression. This study was undertaken to examine whether anti-mouse IL-6 receptor antibody (MR16-1) induces antidepressant effects in a social defeat stress model. Intravenous injection of MR16-1 induced rapid-onset and long-lasting antidepressant effects in susceptible mice after social defeat stress through its anti-inflammatory actions...
May 30, 2017: Translational Psychiatry
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