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Protein kinase C

Y Jiang, H Y Chao, X W Zhang, M Zhou, X Z Lu, R Zhang, C He, Q Wang
Objective: To explore the effects and possible mechanisms of the novel pan-FGFR inhibitor BGJ398 on KG-1 cells in vitro. Methods: Effects of BGJ398 on cells proliferation were detected by CCK-8, the apoptosis was assessed by Annexin V-FITC. Reverse transcriptionquantitative polymerase chain reaction (q-PCR) analysis was used to detect the expression of apoptosis-related genes B cell lymphoma-2 (Bcl-2) and caspase-3. Western blotting analysis was performed to explore the proteins expression levels of Bcl-2, caspase-3 and the expression of p-AKT, p-S6K, p-ERK and FGFR1...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Y Jiang, D Cao, C G Xu
Objective: To investigate the expressions of growth arrest-specific protein (GAS1), IL-1 receptor accessory protein (IL-1RAP) and perforin (PRF1) in patients with anaplastic lymphoma kinase positive, anaplastic large cell lymphoma (ALK+ ALCL) and their relationships with clinical significances and the prognoses of ALK+ ALCL. Methods: Twenty-six formalin-fixed paraffin-embedded (FFPE) samples of ALK+ ALCL patients who were diagnosed from January 2011 to September 2016 were collected. Twelve FFPE samples of patients with ALK+ ALCL, 13 FFPE samples of patients with peripheral T cell lymphoma (not otherwise specified) (PTCL-NOS) and 8 FFPE samples of patients with angioimmunoblastic T-cell lymphoma (AITL) were used as control groups...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Leonardo C de Oliveira, Bruno S A F Brasil, Bethany Unger, Giliane S Trindade, Jonatas S Abrahão, Erna G Kroon, Paula Traktman, Cláudio A Bonjardim
Evolution has equipped poxvirus genomes with the coding capacity for several virus-host interaction products which interfere with host cell gene expression and protein function, creating an adequate intracellular environment for a productive infection. We show here that Vaccinia virus (VACV) induces the expression of the cellular transcription factor EGR-1 (early growth response-1) in Mouse Embryonic Fibroblasts (MEFs) through the MEK (mitogen-activated protein kinase (MAPK)/ERK)/ERK (extracellular signal-regulated kinases) pathway, from 3 to 12 h post infection (h...
March 21, 2018: Viruses
Wuxing Dong, Alison C Todd, Angelika Bröer, Sarah R Hulme, Stefan Bröer, Brian Billups
Astrocytes are glial cells that have an intimate physical and functional association with synapses in the brain. One of their main roles is to recycle the neurotransmitters glutamate and gamma-aminobutyric acid (GABA), as a component of the glutamate/GABA-glutamine cycle. They perform this function by sequestering neurotransmitters and releasing glutamine via the neutral amino acid transporter SNAT3. In this way, astrocytes regulate the availability of neurotransmitters and subsequently influence synaptic function...
March 21, 2018: International Journal of Molecular Sciences
Liaoyuan Wang, Qing Wang, Yue Zhou, Qian Xue, Xiao Sun, Zhinong Wang, Guangyu Ji
RATIONALE: Carney complex (CNC) accounts for up to two-thirds of familial cardiac myxoma, which is a rare autosomal dominant syndrome characterized by multiple mucocutaneous lesions and endocrine tumors. Mutation in the cAMP-dependent protein kinase A (PKA) regulatory (R) subunit 1 (PRKAR1A) gene has been identified as a cause of CNC. In this article, we report 3 first-degree relatives with cardiac myxoma who were diagnosed with CNC and underwent surgical resection. PRESENTING CONCERNS: The recurrence of cardiac myxoma was detected in a 45-year-old male by echocardiography 5 years after the resection was carried out, without any additional symptoms...
March 2018: Medicine (Baltimore)
Rajiv Gandhi Govindaraj, Misagh Naderi, Manali Singha, Jeffrey Lemoine, Michal Brylinski
Rare, or orphan, diseases are conditions afflicting a small subset of people in a population. Although these disorders collectively pose significant health care problems, drug companies require government incentives to develop drugs for rare diseases due to extremely limited individual markets. Computer-aided drug repositioning, i.e., finding new indications for existing drugs, is a cheaper and faster alternative to traditional drug discovery offering a promising venue for orphan drug research. Structure-based matching of drug-binding pockets is among the most promising computational techniques to inform drug repositioning...
2018: NPJ Systems Biology and Applications
Ya-Li Ma, Fang Chen, Jun Shi
Background: Rhein, an anthraquinone derivative of rhubarb, is traditionally used in Chinese herbal medicine. Now emerging studies suggest its antitumor properties in many human cancers. The present study aims to investigate the antitumor role of Rhein and its possible mechanism in human renal cell carcinoma (RCC). Materials and methods: Three RCC cell lines (A489, 786-O and ACHN) were used as the cell models. We applied CCK-8, cell counting, colony formation, wound healing and Transwell assays to assess the antitumor roles of Rhein in RCC cells in vitro...
2018: OncoTargets and Therapy
Laura C O'Brien, Zachary A Graham, Qun Chen, Edward J Lesnefsky, Christopher Cardozo, Ashraf S Gorgey
STUDY DESIGN: Cross-sectional design. OBJECTIVES: This study examined the relationships between circulating adiponectin levels, body composition, metabolic profile, and measures of skeletal muscle mitochondrial enzyme activity and biogenesis. SETTINGS: Clinical Research in a Medical Center. METHODS: Plasma adiponectin was quantified in 19 individuals with chronic spinal cord injury (SCI). Body composition was evaluated by dual x-ray absorptiometry and magnetic resonance imaging...
March 20, 2018: Spinal Cord
Ummi Ammarah, Amit Kumar, Rajesh Pal, Naresh C Bal, Gauri Misra
Microtubule associated serine/threonine kinase (MASTL) is an important Ser/Thr kinase belonging to the family of AGC kinases. It is the human orthologue of Greatwall kinase (Gwl) that plays a significant role in mitotic progression and cell cycle regulation. Upregulation of MASTL in various cancers and its association with poor patient survival establishes it as an important drug target in cancer therapy. Nevertheless, the target remains unexplored with the paucity of studies focused on identification of inhibitors against MASTL, which emphasizes the relevance of our present study...
March 20, 2018: Scientific Reports
Marta Markiewicz-Potoczny, Michael Lisby, David Lydall
Dna2 is a nuclease and helicase that functions redundantly with other proteins in Okazaki fragment processing, double strand break (DSB) resection and checkpoint kinase activation. Dna2 is an essential enzyme, required for yeast and mammalian cell viability. Here we report that numerous mutations affecting the DNA damage checkpoint suppress dna2Δ lethality in Saccharomyces cerevisiae dna2Δ cells are also suppressed by deletion of helicases, PIF1 and MPH1 , and by deletion of POL32 , a subunit of DNA polymerase δ...
March 20, 2018: Genetics
Manoj P Dandekar, Tao Peng, David D McPherson, Joao Quevedo, Jair C Soares, Shaoling Huang
AIM: Similar to ketamine, xenon gas acts as a glutamatergic N-methyl-d -aspartate receptor antagonist, but devoid of propensity to cause untoward effects. Herein, we loaded xenon gas into a liposomal carrier called xenon-containing liposomes (Xe-liposome) for systemic delivery, and investigated its effect as an antidepressant and also analyzed synaptic biomarkers including brain-derived neurotrophic factor (BDNF), protein kinase B (AKT), mammalian target of rapamycin (mTOR), protein kinase C (PKC) and extracellular signal-regulated kinase-1/2 (ERK1/2) in blood and brain...
March 17, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Shi-Yun Jin, Jun Huang, Hai-Juan Zhu, Hao Wu, Shi-Jin Xu, Michael G Irwin, Shu-Fang He, Ye Zhang
Remifentanil preconditioning (RPC) exerts protection in normal hearts, but has not been investigated in heart failure. The aim of the present study was to evaluate the effect of RPC in a chronic failing rat heart model and the mechanisms involving mitogen-activated protein kinases (MAPK) and Bcl-2 protein family. The doxorubicin induced failing rat hearts were subjected to 30min ischemia / 120min reperfusion (IR) with or without RPC by using Langendorff apparatus. RPC was induced by three cycles of 5min remifentanil / 5min drug-free perfusion before IR, with three different concentrations: 25, 50 and 100μg/l...
March 17, 2018: European Journal of Pharmacology
Yuri Ishiuchi, Hitoshi Sato, Narumi Komatsu, Hideo Kawaguchi, Takashi Matsuwaki, Keitaro Yamanouchi, Masugi Nishihara, Taku Nedachi
Skeletal muscle is an endocrine organ that secretes several proteins, which are collectively termed myokines. Although many studies suggest that exercise regulates myokine secretion, the underlying mechanisms remain unclear and all the exercise-dependent myokines have not yet been identified. Therefore, in this study, we attempted to identify novel exercise-dependent myokines by using our recently developed in vitro contractile model. Differentiated C2C12 myotubes were cultured with or without electrical pulse stimulation (EPS) for 24 h to induce cell contraction, and the myokines secreted in conditioned medium were analyzed using a cytokine array...
March 17, 2018: Cytokine
Jia-Nan Wang, Hao-Jian Zhang, Jia-Qi Li, Wan-Jing Ding, Zhong-Jun Ma
Nine new indolocarbazoles (1-9) were isolated from the marine-derived Streptomyces sp. DT-A61. Among them compounds 1-8 featured a hydroxy group at the C-3 or C-9 position. All purified compounds were identified by 1D and 2D NMR and HRESIMS data. The absolute configurations of 4-6, 8, and 9 were determined by electronic circular dichroism spectroscopic data. Compound 7 exhibited significant activity against human prostate PC-3 cancer cells with an IC50 value of 0.16 μM. Compounds 1, 5, 6, and 9 showed moderate inhibition against the same cell line with IC50 values of 8...
March 20, 2018: Journal of Natural Products
Ruoxing Lei, Jessica P Lee, Matthew B Francis, Sanjay Kumar
Intrinsically disordered proteins (IDPs) play central roles in numerous cellular processes. While IDP structure and function are often regulated by multisite phosphorylation, the biophysical mechanisms linking these post-translational modifications to IDP structure remain elusive. For example, the intrinsically disordered C-terminal sidearm domain of the neurofilament heavy subunit (NFH-SA) forms a dense brush along axonal NF backbones and is subject to extensive serine phosphorylation. Yet, biophysical insight into the relationship between phosphorylation and structure has been limited by the lack of paradigms in which NF brush conformational responses can be measured in the setting of controlled phosphorylation...
March 20, 2018: Biochemistry
Xiaohui Zhang, Miao Zhang, Yanan Su, Zhe Wang, Qiling Zhao, Huaisen Zhu, Zhuang Qian, Jiao Xu, Shu Tang, Di Wu, Ye Lin, Nicole Kemper, Joerg Hartung, Endong Bao
1. This experiment investigated the anti-apoptosis effects and the mechanism of aspirin action in the heat shock response of chicken myocardial cells in vivo, via changes in the heat stress protein Hsp90 and the rate of apoptosis. Broiler chickens were administered aspirin (1 mg/kg body weight) 2 h before exposure to heat stress, and then exposed to 40±1°C for 0, 1, 2, 3, 5, 7, 10, 15 and 24 h. 2. The induction and consumption of the heat stress factor HSF-1, and reductions of HSF-2 and HSF-3 induced by heat stress led to a delay in Hsp90 expression...
March 20, 2018: British Poultry Science
Cheong-Yong Yun, Seon Mi Ko, Yong Pyo Choi, Beom Joon Kim, Jungno Lee, Jae Mun Kim, Ju Yeon Kim, Jin Yong Song, Song-Hee Kim, Bang Yeon Hwang, Jin Tae Hong, Sang-Bae Han, Youngsoo Kim
Rationale: cAMP up-regulates microphthalmia-associated transcription factor subtype M (MITF-M) and tyrosinase (Tyro) in the generation of heavily pigmented melanosomes. Here, we communicate a therapeutic mechanism of hyperpigmented disorder by α-viniferin, an active constituent of Caragana sinica . Methods: We used cAMP-elevated melanocyte cultures or facial hyperpigmented patches for pigmentation assays, and applied immunoprecipitation, immunobloting, RT-PCR or reporter gene for elucidation of the antimelanogenic mechanism...
2018: Theranostics
Dong-Gyu Leem, Ji-Sun Shin, Kyung-Tack Kim, Sang Yoon Choi, Myung-Hee Lee, Kyung-Tae Lee
A previous study reported that a novel dammarane-type triterpene saponin, ginsenoside-Rg18, derived from the root of Panax ginseng , displayed hydroxyl radical scavenging, anti-bacterial and cytotoxic activities. However, the underlying molecular mechanisms of its anti-proliferative effect on non-small cell lung cancer (NSCLC) A549 cells remains unclear. In the present study, it was determined that Rg18 inhibited the proliferation of A549 cells with a half-maximal inhibitory concentration of 150 µM. Flow cytometry analysis indicated that cell cycle progression was blocked by Rg18 at G1 phase in A549 cells, which was accompanied by downregulation of cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclin D1, cyclin D2, cyclin E and phosphorylated retinoblastoma protein expression at the protein level...
April 2018: Oncology Letters
Ilaria J Chicca, Michael R Milward, Iain Leslie C Chapple, Gareth Griffiths, Rod Benson, Thomas Dietrich, Paul R Cooper
Neutrophil extracellular traps (NETs) are DNA-based antimicrobial web-like structures whose release is predominantly mediated by reactive oxygen species (ROS); their purpose is to combat infections. However, unbalanced NET production and clearance is involved in tissue injury, circulation of auto-antibodies and development of several chronic diseases. Currently, there is lack of agreement regarding the high-throughput methods available for NET investigation. This study, therefore, aimed to develop and optimize a high-content analysis (HCA) approach, which can be applied for the assay of NET production and for the screening of compounds involved in the modulation of NET release...
2018: Frontiers in Immunology
Suzanne Scheele, Jennifer A Geiger, Amy E DeRocher, Ryan Choi, Tess R Smith, Matthew A Hulverson, Rama Subba Rao Vidadala, Lynn K Barrett, Dustin J Maly, Ethan A Merritt, Kayode K Ojo, Wesley C Van Voorhis, Marilyn Parsons
In Toxoplasma gondii , calcium-dependent protein kinase 1 (CDPK1) is an essential protein kinase required for invasion of host cells. We have developed several hundred CDPK1 inhibitors, many of which block invasion. Inhibitors with similar IC50 s were tested in thermal shift assays for their ability to stabilize CDPK1 in cell lysates, in intact cells, or in purified form. Compounds that inhibited parasite growth stabilized CDPK1 in all assays. In contrast, two compounds that showed poor growth inhibition stabilized CDPK1 in lysates but not in cells...
March 19, 2018: Antimicrobial Agents and Chemotherapy
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