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https://www.readbyqxmd.com/read/28107776/activity-based-probes-for-the-multicatalytic-proteasome
#1
REVIEW
David S Hewings, John A Flygare, Ingrid E Wertz, Matthew Bogyo
Proteasomes are multisubunit protease complexes responsible for degrading most intracellular proteins. In addition to removing damaged proteins, they regulate many important cellular processes through the controlled degradation of transcription factors, cell cycle regulators and enzymes. Eukaryotic proteasomes have three catalytic subunits, β1, β2 and β5, that each have different substrate specificities. Additionally, although we know that diverse cell types express proteasome variants with distinct activity and specificity profiles, the functions of these different pools of proteasomes are not fully understood...
January 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28107775/beta-caryophyllene-protects-against-alcoholic-steatohepatitis-by-attenuating-inflammation-and-metabolic-dysregulation-in-mice
#2
Zoltan V Varga, Csaba Matyas, Katalin Erdelyi, Resat Cinar, Daniela Nieri, Andrea Chicca, Balazs Tamas Nemeth, Janos Paloczi, Tamas Lajtos, Lukas Corey, Gyorgy Hasko, Bin Gao, George Kunos, Jürg Gertsch, Pal Pacher
BACKGROUND AND AIMS: Beta-caryophyllene (BCP) is a plant-derived FDA approved food additive with anti-inflammatory properties. Some of its beneficial effects in vivo reported to involve activation of cannabinoid 2 receptors (CB2) that are predominantly expressed in immune cells. Herein, we evaluated the translational potential of BCP using a well-established model of chronic and binge alcohol-induced liver injury. METHODS: In this study we investigated the effects of BCP on liver injury induced by chronic plus binge alcohol feeding in mice in vivo by using biochemical assays, real-time PCR and histology analyses...
January 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28107769/the-transcriptional-modulator-ifrd1-controls-pgc-1%C3%AE-expression-under-short-term-adrenergic-stimulation-in-brown-adipocytes
#3
Gyujin Park, Tetsuhiro Horie, Takashi Kanayama, Kazuya Fukasawa, Takashi Iezaki, Yuki Onishi, Kakeru Ozaki, Yukari Nakamura, Yukio Yoneda, Takeshi Takarada, Eiichi Hinoi
Sympathetic tone activates the function of classical brown adipocytes, which constitutively exist in the brown adipose tissue, and inducible brown adipocytes (so-called beige adipocytes), which sporadically reside within the white adipose tissue. Here we identified the transcriptional modulator interferon-related developmental regulator 1 (Ifrd1) as a negative regulator of thermogenic and mitochondrial gene expression in brown adipocytes. Ifrd1 expression was markedly induced by cold exposure and administration of CL-316243 (a β3 adrenergic agonist) in interscapular brown adipose and inguinal subcutaneous white adipose tissues, but not in epididymal visceral white adipose tissue, in vivo...
January 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28107746/induced-differentiation-of-human-gingival-fibroblasts-into-vsmc-like-cells
#4
Xuqian Liu, Jie Wang, Fusheng Dong, Hexiang Li, Yali Hou
Vascular smooth muscle cells (VSMCs) are major component of the vascular wall, and they play an essential role in maintaining the basic physiological function and stable structure of the vascular wall. In the present study, human gingival fibroblasts (HGFs) were cultured and induced into VSMC-like cells in vitro to confirm that HGFs with properties of stem cells have the potential for differentiation. The epithelium isolated from patients was extracted from normal human gingiva consisting of epithelium and connective tissue...
January 17, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/28107698/the-natural-flavonoid-apigenin-sensitizes-human-cd44-prostate-cancer-stem-cells-to-cisplatin-therapy
#5
Suat Erdogan, Kader Turkekul, Rıza Serttas, Zeynep Erdogan
Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death among men. Development of chemoresistance, tumor relapse and metastasis remain major barriers to effective treatment and all been identified to be associated with cancer stem cells (CSCs). Natural flavonoids such as apigenin have been shown to have the ability to improve the therapeutic efficacy of common chemotherapy agents through CSCs sensitization. Thus, the aim of this study was to evaluate the combination of apigenin with cisplatin on CD44(+) PCa stem cell growth and migration...
January 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28107692/rna-binding-protein-msi2-positively-regulates-flt3-expression-in-myeloid-leukemia
#6
Ayuna Hattori, Daniel McSkimming, Natarajan Kannan, Takahiro Ito
FLT3 is frequently mutated and overexpressed in acute myelogenous leukemia (AML) and other hematologic malignancies. Although signaling events downstream of FLT3 receptor tyrosine kinase has been studied in depth, molecular mechanisms of how FLT3 expression is regulated at the post-transcriptional level in particular remain elusive. In this study, we investigated the roles of an RNA binding protein MSI2 as a regulator of FLT3 expression. MSI2 and FLT3 are significantly co-regulated in human AML and chronic myelogenous leukemia in blast crisis (BC-CML)...
January 11, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28107688/sequencing-and-de-novo-assembly-of-visceral-mass-transcriptome-of-the-critically-endangered-land-snail-satsuma-myomphala-annotation-and-ssr-discovery
#7
Se Won Kang, Bharat Bhusan Patnaik, Hee-Ju Hwang, So Young Park, Jong Min Chung, Dae Kwon Song, Hongray Howrelia Patnaik, Jae Bong Lee, Changmu Kim, Soonok Kim, Young-Su Park, Hong Seog Park, Seung-Hwan Park, Yeon Soo Han, Jun Sang Lee, Yong Seok Lee
Satsuma myomphala is critically endangered through loss of natural habitats, predation by natural enemies, and indiscriminate collection. It is a protected species in Korea but lacks genomic resources for an understanding of varied functional processes attributable to evolutionary success under natural habitats. For assessing the genetic information of S. myomphala, we performed for the first time, de novo transcriptome sequencing and functional annotation of expressed sequences using Illumina Next-Generation Sequencing (NGS) platform and bioinformatics analysis...
October 29, 2016: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/28107678/nobiletin-and-its-colonic-metabolites-suppress-colitis-associated-colon-carcinogenesis-by-down-regulating-inos-inducing-antioxidative-enzymes-and-arresting-cell-cycle-progression
#8
Xian Wu, Mingyue Song, Zili Gao, Yue Sun, Minqi Wang, Fang Li, Jinkai Zheng, Hang Xiao
Nobiletin (NOB) is a major citrus polymethoxyflavone (PMF) with various beneficial biological activities. We reported previously that dietary NOB significantly inhibited colitis-associated colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice, and the chemopreventive effects were associated with NOB metabolites found in the mouse colonic tissues. In this study, to better understand the role of colonic metabolites of NOB, we determined the anti-inflammation and anticancer effects of a mixture of NOB and its major metabolites (NOB-Met) at the concentrations equivalent to those found in colonic tissues of NOB-fed mice...
January 11, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28107648/parp-1-controls-the-adipogenic-transcriptional-program-by-parylating-c-ebp%C3%AE-and-modulating-its-transcriptional-activity
#9
Xin Luo, Keun Woo Ryu, Dae-Seok Kim, Tulip Nandu, Carlos J Medina, Rebecca Gupte, Bryan A Gibson, Raymond E Soccio, Yonghao Yu, Rana K Gupta, W Lee Kraus
Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification of proteins mediated by PARP family members, such as PARP-1. Although PARylation has been studied extensively, few examples of definitive biological roles for site-specific PARylation have been reported. Here we show that C/EBPβ, a key pro-adipogenic transcription factor, is PARylated by PARP-1 on three amino acids in a conserved regulatory domain. PARylation at these sites inhibits C/EBPβ's DNA binding and transcriptional activities and attenuates adipogenesis in various genetic and cell-based models...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28107647/programmed-ribosomal-frameshifting-generates-a-copper-transporter-and-a-copper-chaperone-from-the-same-gene
#10
Sezen Meydan, Dorota Klepacki, Subbulakshmi Karthikeyan, Tõnu Margus, Paul Thomas, John E Jones, Yousuf Khan, Joseph Briggs, Jonathan D Dinman, Nora Vázquez-Laslop, Alexander S Mankin
Metal efflux pumps maintain ion homeostasis in the cell. The functions of the transporters are often supported by chaperone proteins, which scavenge the metal ions from the cytoplasm. Although the copper ion transporter CopA has been known in Escherichia coli, no gene for its chaperone had been identified. We show that the CopA chaperone is expressed in E. coli from the same gene that encodes the transporter. Some ribosomes translating copA undergo programmed frameshifting, terminate translation in the -1 frame, and generate the 70 aa-long polypeptide CopA(Z), which helps cells survive toxic copper concentrations...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28107631/overcoming-the-heat-endurance-of-tumor-cells-by-interfering-the-anaerobic-glycolysis-metabolism-for-improved-photothermal-therapy
#11
Wei-Hai Chen, Guo-Feng Luo, Qi Lei, Sheng Hong, Wen-Xiu Qiu, Li-Han Liu, Si-Xue Cheng, Xian-Zheng Zhang
In this study, we developed a general method to decorate plasmonic gold nanorods (GNRs) with a CD44-targeting functional polymer, containing hyaluronic acid (HA) targeting moiety and a small molecule Glut1 inhibitor of diclofenac (DC), to obtain GNR/HA-DC. This nanosystem exhibited the superiority of selectively sensitizing tumor cells for photothermal therapy (PTT) by inhibiting the unique anaerobic glycolysis. Upon specifically targeting CD44, sequentially time-dependent DC release could be achieved by the trigger of hyaluronidase (HAase), which abundantly existed in tumor tissue...
January 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28107608/the-increased-expression-of-tcf3-is-correlated-with-poor-prognosis-in-chinese-patients-with-nasopharyngeal-carcinoma
#12
Xiaohe Shen, Jizhao Yuan, Mengjie Zhang, Wenhua Li, Bing Ni, Yuzhang Wu, Li Jiang, Weiping Fan, Zhiqiang Tian
OBJECTIVES: Regulatory factors controlling stem cell identity and self-renewal are often active in aggressive cancers and are thought to promote cancer growth and progression. B-cell-specific transcription factor 3 (TCF3/E2A) is a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family that is central to regulating epidermal and embryonic stem cell identity. It has been reported that TCF3 was connected with the development and progression of a number of human cancers...
January 20, 2017: Clinical Otolaryngology
https://www.readbyqxmd.com/read/28107606/dishevelled-segment-polarity-protein-3-dvl3-a-novel-and-easily-applicable-recurrence-predictor-in-localized-prostate-adenocarcinoma
#13
Pil-Jong Kim, Ji Y Park, Hong-Gee Kim, Yong Mee Cho, Heounjeong Go
OBJECTIVE: To identify new biomarkers for the biochemical recurrence (BCR) of prostate adenocarcinoma. PATIENTS AND METHODS: Clinical information of 500 prostate adenocarcinoma patients and their 152 RNA-sequencing and protein-array data from The Cancer Genome Atlas (TCGA) were separated into a discovery-set and a validation-set. Each dataset was analyzed according to the Gleason grade groups reflecting BCR. The results obtained from the analysis using TCGA dataset were confirmed by immunohistochemistry analyses of the confirmation cohort composed of 395 localized prostate adenocarcinoma patients...
January 20, 2017: BJU International
https://www.readbyqxmd.com/read/28107571/increased-pd-l1-expression-in-breast-and-colon-cancer-stem-cells
#14
Yanheng Wu, Mingshui Chen, Peihong Wu, Chen Chen, Zhi Ping Xu, Wenyi Gu
Here we report the expression of programmed cell death ligand 1/2 (PD-L1/L2) in breast and colon cancer stem cells (CSCs). The stemness of these cells was confirmed by their surface markers. Using flow cytometry analysis we demonstrated that PD-L1 expression was higher in CSCs of both cancers compared to non-stem like cancer cells. Consistent with this, detection of cellular PD-L1 proteins by Western blot assay also showed increased PD-L1 protein in CSCs. In contrast, only trance amounts of PD-L2 were detected in CSCs of both cancers...
January 20, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28107519/cudraflavone-c-induces-tumor-specific-apoptosis-in-colorectal-cancer-cells-through-inhibition-of-the-phosphoinositide-3-kinase-pi3k-akt-pathway
#15
Hsien-Chuen Soo, Felicia Fei-Lei Chung, Kuan-Hon Lim, Veronica Alicia Yap, Tracey D Bradshaw, Ling-Wei Hii, Si-Hoey Tan, Sze-Jia See, Yuen-Fen Tan, Chee-Onn Leong, Chun-Wai Mai
Cudraflavone C (Cud C) is a naturally-occurring flavonol with reported anti-proliferative activities. However, the mechanisms by which Cud C induced cytotoxicity have yet to be fully elucidated. Here, we investigated the effects of Cud C on cell proliferation, caspase activation andapoptosis induction in colorectal cancer cells (CRC). We show that Cud C inhibits cell proliferation in KM12, Caco-2, HT29, HCC2998, HCT116 and SW48 CRC but not in the non-transformed colorectal epithelial cells, CCD CoN 841. Cud C induces tumor-selective apoptosis via mitochondrial depolarization and activation of the intrinsic caspase pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28107514/karyopherin-alpha-proteins-regulate-oligodendrocyte-differentiation
#16
Benjamin M Laitman, John N Mariani, Chi Zhang, Setsu Sawai, Gareth R John
Proper regulation of the coordinated transcriptional program that drives oligodendrocyte (OL) differentiation is essential for central nervous system myelin formation and repair. Nuclear import, mediated in part by a group of karyopherin alpha (Kpna) proteins, regulates transcription factor access to the genome. Understanding how canonical nuclear import functions to control genomic access in OL differentiation may aid in the creation of novel therapeutics to stimulate myelination and remyelination. Here, we show that members of the Kpna family regulate OL differentiation, and may play distinct roles downstream of different pro-myelinating stimuli...
2017: PloS One
https://www.readbyqxmd.com/read/28107512/nonstructural-5a-protein-of-hepatitis-c-virus-interferes-with-toll-like-receptor-signaling-and-suppresses-the-interferon-response-in-mouse-liver
#17
Takeya Tsutsumi, Kazuya Okushin, Kenichiro Enooku, Hidetaka Fujinaga, Kyoji Moriya, Hiroshi Yotsuyanagi, Hideki Aizaki, Tetsuro Suzuki, Yoshiharu Matsuura, Kazuhiko Koike
The hepatitis C virus nonstructural protein NS5A is involved in resistance to the host immune response, as well as the viral lifecycle such as replication and maturation. Here, we established transgenic mice expressing NS5A protein in the liver and examined innate immune responses against lipopolysaccharide (LPS) in vivo. Intrahepatic gene expression levels of cytokines such as interleukin-6, tumor necrosis factor-α, and interferon-γ were significantly suppressed after LPS injection in the transgenic mouse liver...
2017: PloS One
https://www.readbyqxmd.com/read/28107503/osteopontin-affects-insulin-vesicle-localization-and-ca2-homeostasis-in-pancreatic-beta-cells-from-female-mice
#18
Anna Wendt, Inês G Mollet, Anki Knutsson, Victor S Bolmgren, Anna Hultgårdh-Nilsson, Maria F Gomez, Lena Eliasson
Type 2 diabetic patients suffer from insulin resistance and reduced insulin secretion. Osteopontin (OPN), a versatile protein expressed in several tissues throughout the body including the islets of Langerhans, has previously been implicated in the development of insulin resistance. Here we have investigated the role of OPN in insulin secretion using an OPN knock out mouse model (OPN-/-). Ultra-structural analyzes of islets from OPN-/- and WT mice indicated weaker cell-cell connections between the islet cells in the OPN-/- mouse compared to WT...
2017: PloS One
https://www.readbyqxmd.com/read/28107494/protective-roles-for-rgs2-in-a-mouse-model-of-house-dust-mite-induced-airway-inflammation
#19
Tresa George, Matthew Bell, Mainak Chakraborty, David P Siderovski, Mark A Giembycz, Robert Newton
The GTPase-accelerating protein, regulator of G-protein signalling 2 (RGS2) reduces signalling from G-protein-coupled receptors (GPCRs) that signal via Gαq. In humans, RGS2 expression is up-regulated by inhaled corticosteroids (ICSs) and long-acting β2-adrenoceptor agonists (LABAs) such that synergy is produced in combination. This may contribute to the superior clinical efficacy of ICS/LABA therapy in asthma relative to ICS alone. In a murine model of house dust mite (HDM)-induced airways inflammation, three weeks of intranasal HDM (25 μg, 3×/week) reduced lung function and induced granulocytic airways inflammation...
2017: PloS One
https://www.readbyqxmd.com/read/28107481/bet-inhibitors-disrupt-rad21-dependent-conformational-control-of-kshv-latency
#20
Horng-Shen Chen, Alessandra De Leo, Zhuo Wang, Andrew Kerekovic, Robert Hills, Paul M Lieberman
Kaposi's Sarcoma-associated Herpesvirus (KSHV) establishes stable latent infection in B-lymphocytes and pleural effusion lymphomas (PELs). During latency, the viral genome persists as an epigenetically constrained episome with restricted gene expression programs. To identify epigenetic regulators of KSHV latency, we screened a focused small molecule library containing known inhibitors of epigenetic factors. We identified JQ1, a Bromodomain and Extended Terminal (BET) protein inhibitor, as a potent activator of KSHV lytic reactivation from B-cells carrying episomal KSHV...
January 20, 2017: PLoS Pathogens
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