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https://www.readbyqxmd.com/read/28726775/oroxylin-a-activates-pkm1-hnf4-alpha-to-induce-hepatoma-differentiation-and-block-cancer-progression
#1
Libin Wei, Yuanyuan Dai, Yuxin Zhou, Zihao He, Jingyue Yao, Li Zhao, Qinglong Guo, Lin Yang
Liver cancer is the second cause of death from cancer worldwide, without effective treatment. Traditional chemotherapy for liver cancer has big side effects for patients, whereas targeted drugs, such as sorafenib, commonly have drug resistance. Oroxylin A (OA) is the main bioactive flavonoids of Scutellariae radix, which has strong anti-hepatoma effect but low toxicity to normal tissue. To date, no differentiation-inducing agents have been reported to exert a curative effect on solid tumors. Here our results demonstrated that OA restrained the proliferation and induced differentiation of hepatoma both in vitro and in vivo, via inducing a high PKM1 (pyruvate kinase M1)/PKM2 (pyruvate kinase M2) ratio...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28726396/the-potent-anti-inflammatory-and-anti-adipogenic-properties-of-bamboo-sasa-coreana-nakai-leaves-extract-and-its-major-constituent-flavonoids
#2
Ji Hye Yang, Moon-Hee Choi, Seung Hwa Yang, Sam Seok Cho, Su Jung Park, Hyun-Jae Shin, Sung Hwan Ki
The pro-inflammatory response and recruitment of macrophages into adipose tissue contribute to metabolic dysfunction. Here, we reported the anti-inflammatory and anti-adipogenic effects of the methanol (MeOH) extract and ethylacetate (EtOAc) fraction of bamboo leaf and its molecular mechanism in RAW264.7 cells and 3T3-L1 adipocytes, respectively. Functional macrophage migration assays also were performed. Surprisingly, EtOAc fraction of MeOH extracts from native Korean plant species Sasa coreana Nakai (SCN) has shown potent anti-inflammatory properties; SCN pretreatment inhibited nitric oxide (NO) production (p<0...
July 20, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28725984/cytokine-expression-and-barrier-disruption-in-human-corneal-epithelial-cells-induced-by-alarmin-released-from-necrotic-cells
#3
Ken Fukuda, Waka Ishida, Yusaku Miura, Tatsuma Kishimoto, Atsuki Fukushima
PURPOSE: Dying cells release endogenous molecules known as alarmins that signal danger to surrounding tissue. We investigated the effects of necrotic cell-derived alarmins on cytokine expression and barrier function in human corneal epithelial cells. METHODS: The release of interleukin (IL)-6 and IL-8 from immortalized human corneal epithelial (HCE) cells in culture was measured with enzyme-linked immunosorbent assays. The abundance of IL-6 and 8 mRNAs was quantitated by reverse transcription and real-time polymerase chain reaction analysis...
July 19, 2017: Japanese Journal of Ophthalmology
https://www.readbyqxmd.com/read/28725344/complete-response-of-mediastinal-clear-cell-sarcoma-to-pembrolizumab-with-radiotherapy
#4
Samuel Marcrom, Jennifer F De Los Santos, Robert M Conry
BACKGROUND: Clear cell sarcoma (CCS) is a rare, aggressive soft tissue sarcoma thought to derive from neural crest and characterized by a 12;22 translocation. The resulting fusion protein directly activates expression of the melanocyte master transcription factor and drives the same down-stream pathways in CCS and melanoma leading to significant clinical parallels between these malignancies. Striking success of immune checkpoint blockade in melanoma has promoted interest in immunotherapy of CCS...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28724916/involvement-of-the-p62-nrf2-signal-transduction-pathway-on-erythrophagocytosis
#5
Inês B Santarino, Michelle S Viegas, Neuza S Domingues, Ana M Ribeiro, Miguel P Soares, Otília V Vieira
Erythrophagocytosis, the phagocytic removal of damaged red blood cells (RBC), and subsequent phagolysosome biogenesis are important processes in iron/heme metabolism and homeostasis. Phagolysosome biogenesis implies the interaction of nascent phagosomes with endocytic compartments and also autophagy effectors. Here, we report that besides recruitment of microtubule-associated protein-1-light chain 3 (LC3), additional autophagy machinery such as sequestosome 1 (p62) is also acquired by single-membrane phagosomes at very early stages of the phagocytic process and that its acquisition is very important to the outcome of the process...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724756/lysosomal-targeting-of-sidt2-via-multiple-yxx%C3%AE-motifs-is-required-for-sidt2-function-in-the-process-of-rnautophagy
#6
Viorica Raluca Contu, Katsunori Hase, Hiroko Kozuka-Hata, Masaaki Oyama, Yuuki Fujiwara, Chihana Kabuta, Masayuki Takahashi, Fumihiko Hakuno, Shin-Ichiro Takahashi, Keiji Wada, Tomohiro Kabuta
RNA degradation is an essential process for maintaining cellular homeostasis. Previously, we have discovered a novel RNA degradation system, RNautophagy, during which direct import of RNA into lysosomes in an ATP-dependent manner followed by degradation takes place. The putative nucleic acids transporter, SID-1 transmembrane family member 2 (SIDT2), predominantly localizes to lysosomes and mediates the translocation of RNA into lysosomes during RNautophagy. However, little is known about the mechanisms of sorting SIDT2 to lysosomes...
July 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28724722/effect-of-directional-pulling-on-mechanical-protein-degradation-by-atp-dependent-proteolytic-machines
#7
Adrian O Olivares, Hema Chandra Kotamarthi, Benjamin J Stein, Robert T Sauer, Tania A Baker
AAA+ proteases and remodeling machines couple hydrolysis of ATP to mechanical unfolding and translocation of proteins following recognition of sequence tags called degrons. Here, we use single-molecule optical trapping to determine the mechanochemistry of two AAA+ proteases, Escherichia coli ClpXP and ClpAP, as they unfold and translocate substrates containing multiple copies of the titin(I27) domain during degradation initiated from the N terminus. Previous studies characterized degradation of related substrates with C-terminal degrons...
July 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28722750/protein-kinase-d-exerts-neuroprotective-functions-during-oxidative-stress-via-nuclear-factor-kappab-independent-signaling-pathways
#8
Hanna Liliom, Krisztián Tárnok, Zsófia Ábrahám, Bence Rácz, Angelika Hausser, Katalin Schlett
Members of the protein kinase D (PKD) family of serine/threonine kinases are known to exert diverse roles in neuronal stress responses. Here we show the transient activation and nuclear translocation of endogenous PKD upon oxidative stress induced by H2 O2 treatment in primary neuronal cultures. Using pharmacological inhibition we show that PKD activity protects neurons from oxidative stress induced cell death. Although members of the canonical NFκB pathway were phosphorylated upon H2 O2 treatment, it was found that the neuronal response to oxidative stress is not executed through the nuclear translocation and activity of RelA...
July 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28722655/key-steps-in-unconventional-secretion-of-fibroblast-growth-factor-2-reconstituted-with-purified-components
#9
Julia P Steringer, Sascha Lange, Sabína Čujová, Radek Šachl, Chetan Poojari, Fabio Lolicato, Oliver Beutel, Hans-Michael Müller, Sebastian Unger, Ünal Coskun, Alf Honigmann, Ilpo Vattulainen, Martin Hof, Christian Freund, Walter Nickel
FGF2 is secreted from cells by an unconventional secretory pathway. This process is mediated by direct translocation across the plasma membrane. Here, we define the minimal molecular machinery required for FGF2 membrane translocation in a fully reconstituted inside-out vesicle system. FGF2 membrane translocation is thermodynamically driven by PI(4,5)P2-induced membrane insertion of FGF2 oligomers. The latter serve as dynamic translocation intermediates of FGF2 with a subunit number in the range of 8-12 FGF2 molecules...
July 19, 2017: ELife
https://www.readbyqxmd.com/read/28722543/comparison-of-ovalbumin-and-ovalbumin-epitope-peptide-for-transdermal-delivery-and-vaccination-mediated-by-the-photothermal-effect-of-gold-nanorods
#10
Aung Thu Haine, Yuji Miyamoto, Taishi Higashi, Keiichi Motoyama, Hidetoshi Arima, Takuro Niidome
Transdermal protein delivery is a powerful and attractive method for protein therapy and dermal vaccination compared with other administrations. However, this delivery method is restricted by the low permeability of the stratum corneum, a hydrophobic barrier that restricts the entry of hydrophilic molecules such as proteins. In this study, we developed an improved gel patch system carrying ovalbumin and ovalbumin epitope peptide, and then compared their permeability into the skin. First, the gel patch was placed on mouse skin to allow contact with the polymer coated gold nanorods and then irradiated by a continuous-wave laser...
July 19, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28722226/biology-of-slac1-type-anion-channels-from-nutrient-uptake-to-stomatal-closure
#11
REVIEW
Rainer Hedrich, Dietmar Geiger
Contents 1 I. 1 II. 2 III. 5 IV. 8 V. 11 VI. 12 13 13 References 13 SUMMARY: Stomatal guard cells control leaf CO2 intake and concomitant water loss to the atmosphere. When photosynthetic CO2 assimilation is limited and the ratio of CO2 intake to transpiration becomes suboptimal, guard cells, sensing the rise in CO2 concentration in the substomatal cavity, deflate and the stomata close. Screens for mutants that do not close in response to experimentally imposed high CO2 atmospheres identified the guard cell-expressed Slowly activating anion channel, SLAC1, as the key player in the regulation of stomatal closure...
July 19, 2017: New Phytologist
https://www.readbyqxmd.com/read/28721437/erk1-is-dispensable-for-mouse-pancreatic-beta-cell-function-but-is-necessary-for-glucose-induced-full-activation-of-msk1-and-creb
#12
Michele Leduc, Joy Richard, Safia Costes, Dany Muller, Annie Varrault, Vincent Compan, Julia Mathieu, Jean-François Tanti, Gilles Pagès, Jacques Pouyssegur, Gyslaine Bertrand, Stéphane Dalle, Magalie A Ravier
AIMS/HYPOTHESIS: Insufficient insulin secretion from pancreatic beta cells, which is associated with a decrease in beta cell mass, is a characteristic of type 2 diabetes. Extracellular signal-related kinase 1 and 2 (ERK1/2) inhibition in beta cells has been reported to affect insulin secretion, gene transcription and survival, although whether ERK1 and ERK2 play distinct roles is unknown. The aim of this study was to assess the individual roles of ERK1 and ERK2 in beta cells using ERK1 (also known as Mapk3)-knockout mice (Erk1 (-/-) mice) and pharmacological approaches...
July 18, 2017: Diabetologia
https://www.readbyqxmd.com/read/28720835/exophagy-of-annexin-a2-via-rab11-rab8a-and-rab27a-in-ifn-%C3%AE-stimulated-lung-epithelial-cells
#13
Ying-Da Chen, Yi-Ting Fang, Yi-Lin Cheng, Chiou-Feng Lin, Li-Jin Hsu, Shu-Ying Wang, Robert Anderson, Chih-Peng Chang, Yee-Shin Lin
Annexin A2 (ANXA2), a phospholipid-binding protein, has multiple biological functions depending on its cellular localization. We previously demonstrated that IFN-γ-triggered ANXA2 secretion is associated with exosomal release. Here, we show that IFN-γ-induced autophagy is essential for the extracellular secretion of ANXA2 in lung epithelial cells. We observed colocalization of ANXA2-containing autophagosomes with multivesicular bodies (MVBs) after IFN-γ stimulation, followed by exosomal release. IFN-γ-induced exophagic release of ANXA2 could not be observed in ATG5-silenced or mutant RAB11-expressing cells...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720775/metformin-ameliorates-the-phenotype-transition-of-peritoneal-mesothelial-cells-and-peritoneal-fibrosis-via-a-modulation-of-oxidative-stress
#14
Hyun-Soo Shin, Jiyeon Ko, Dal-Ah Kim, Eun-Sun Ryu, Hye-Myung Ryu, Sun-Hee Park, Yong-Lim Kim, Eok-Soo Oh, Duk-Hee Kang
Phenotype transition of peritoneum is an early mechanism of peritoneal fibrosis. Metformin, 5'-adenosine monophosphate-activated protein kinase (AMPK) activator, has recently received a new attention due to its preventive effect on organ fibrosis and cancer metastasis by inhibiting epithelial-to-mesenchymal transition (EMT). We investigated the effect of metformin on EMT of human peritoneal mesothelial cells (HPMC) and animal model of peritoneal dialysis (PD). TGF-β1-induced EMT in HPMC was ameliorated by metformin...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720734/lack-of-acrb-efflux-function-confers-loss-of-virulence-on-salmonella-enterica-serovar-typhimurium
#15
Xuan Wang-Kan, Jessica M A Blair, Barbara Chirullo, Jonathan Betts, Roberto M La Ragione, Alasdair Ivens, Vito Ricci, Timothy J Opperman, Laura J V Piddock
AcrAB-TolC is the paradigm resistance-nodulation-division (RND) multidrug resistance efflux system in Gram-negative bacteria, with AcrB being the pump protein in this complex. We constructed a nonfunctional AcrB mutant by replacing D408, a highly conserved residue essential for proton translocation. Western blotting confirmed that the AcrB D408A mutant had the same native level of expression of AcrB as the parental strain. The mutant had no growth deficiencies in rich or minimal medium. However, compared with wild-type SL1344, the mutant had increased accumulation of Hoechst 33342 dye and decreased efflux of ethidium bromide and was multidrug hypersusceptible...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28720717/sting-is-an-essential-mediator-of-the-ku70-mediated-production-of-ifn-%C3%AE-1-in-response-to-exogenous-dna
#16
Hongyan Sui, Ming Zhou, Hiromi Imamichi, Xiaoli Jiao, Brad T Sherman, H Clifford Lane, Tomozumi Imamichi
We previously identified Ku70, a subunit of a DNA repair protein complex, as a cytosolic DNA sensor that induces the production of interferon-λ1 (IFN-λ1) by human primary cells and cell lines. IFN-λ1 is a type III IFN and has similar antiviral activity to that of the type I IFNs (IFN-α and IFN-β). We observed that human embryonic kidney (HEK) 293T cells, which are deficient in the innate immune adaptor protein STING (stimulator of IFN genes), did not produce IFN-λ1 in response to DNA unless they were reconstituted with STING...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28720588/ews-fli-is-a-master-regulator-of-metabolic-reprogramming-in-ewing-sarcoma
#17
Jason M Tanner, Claire Bensard, Peng Wei, Nathan M Krah, John C Schell, Jamie D Gardiner, Joshua D Schiffman, Stephen L Lessnick, Jared Rutter
Ewing sarcoma is a bone malignancy driven by a translocation event resulting in the fusion protein EWS/FLI1 (EF). EF functions as an aberrant and oncogenic transcription factor that misregulates the expression of thousands of genes. Previous work has focused principally on determining important transcriptional targets of EF, as well as characterizing important regulatory partnerships in EF-dependent transcriptional programs. Less is known, however, about EF-dependent metabolic changes or their role in Ewing sarcoma biology...
July 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28720576/deubiquitinating-enzyme-usp9x-suppresses-tumor-growth-via-lats-kinase-and-core-components-of-the-hippo-pathway
#18
Aleksandra Toloczko, Fusheng Guo, Hiu-Fung Yuen, Qing Wen, Stephen Andrew Wood, Yan Shan Ong, Pei Yi Chan, Asfa Alli Shaik, Jayantha Gunaratne, Mark John Dunne, Wanjin Hong, Siew Wee Chan
The core LATS kinases of the Hippo tumor suppressor pathway phosphorylate and inhibit the downstream transcriptional co-activators YAP and TAZ, which are implicated in various cancers. Recent studies have identified various E3 ubiquitin ligases that negatively regulate the Hippo pathway via ubiquitination, yet few deubiquitinating enzymes (DUB) have been implicated. In this study, we report the DUB USP9X is an important regulator of the core kinases of this pathway. USP9X interacted strongly with LATS kinase and to a lesser extent with WW45, KIBRA, and Angiomotin, and LATS co-migrated exclusively with USP9X during gel filtration chromatography analysis...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28719803/elevated-sterol-regulatory-elementary-binding-protein-1-and-glua2-levels-in-the-hippocampal-nuclear-fraction-of-genetic-absence-epilepsy-rats-from-strasbourg
#19
Sathiya Sekar, Entesar Omran, Venkat Gopalakrishnan, John G Howland, Terrance P Snutch, Changiz Taghibiglou
Studies in animal models and human tissues show that nuclear translocation of sterol regulatory element binding protein 1 (SREBP1) and glutamate A2 subunit (GluA2) of cell-surface AMPA receptor (AMPAR) trigger neuronal excitotoxicity-induced apoptosis in stroke. However, it is not known whether a similar type of underlying pathophysiology occurs in absence epilepsy. To explore this issue, we examined the levels of mature SREBP1, GluA2, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), p53, and activated to total caspase 3 ratio in nuclear fractions (NF) of hippocampal homogenate from 8 to 10 week old male Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and non-epileptic control (NEC) strains...
July 12, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28719465/predictors-of-outcome-in-adenoid-cystic-carcinoma-of-salivary-glands-a-clinicopathologic-study-with-correlation-between-myb-fusion-and-protein-expression
#20
Bin Xu, Esther Drill, Allen Ho, Alan Ho, Lara Dunn, Carlos Nicolas Prieto-Granada, Timothy Chan, Ian Ganly, Ronald Ghossein, Nora Katabi
Adenoid cystic carcinoma (ACC) is the second most common salivary gland malignancy and it has a high rate of recurrences and a poor long-term prognosis. Our aim was to assess the prognostic factors in ACC and study MYB-NFIB fusion and MYB protein expression in a large retrospective cohort of 135 patients with a median follow-up of 6.3 years. The 5- and 10-year local recurrence-free survival (RFS) rate of 94% and 78%, 5- and 10-year distant metastasis survival rate of 77% and 58%, and 5- and 10-year RFS of 66% and 44%...
July 17, 2017: American Journal of Surgical Pathology
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