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https://www.readbyqxmd.com/read/28724384/deficiency-of-pi3-kinase-catalytic-isoforms-p110%C3%AE-and-p110%C3%AE-in-mice-enhances-the-il-17-g-csf-axis-and-induces-neutrophilia
#1
Kirsten Bucher, Fee Schmitt, Benedikt Mothes, Carolin Blumendeller, Daniel Schäll, Roland Piekorz, Emilio Hirsch, Bernd Nürnberg, Sandra Beer-Hammer
BACKGROUND: Phosphoinositide 3-kinase γ (PI3Kγ) and PI3Kδ are second messenger-generating enzymes with key roles in proliferation, differentiation, survival, and function of leukocytes. Deficiency of the catalytic subunits p110γ and p110δ of PI3Kγ and PI3Kδ in p110γ/δ(-/-) mice leads to defective B- and T-cell homeostasis. Here we examined the role of p110γ and p110δ in the homeostasis of neutrophils by analyzing p110γ(-/-), p110δ(-/-) and p110γ/δ(-/-) mice. METHODS: Neutrophils and T cells in leukocyte suspensions from the bone marrow (BM), blood, spleen and lung were analyzed by flow cytometry...
July 19, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28718684/role-of-gsk-3%C3%AE-in-regulation-of-canonical-wnt-%C3%AE-catenin-signaling-and-pi3-k-akt-oncogenic-pathway-in-colon-cancer
#2
Shelly Jain, Preety Ghanghas, Chandan Rana, S N Sanyal
Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents because of their ability in blocking cellular proliferation, and thereby tumor development, and also by promoting apoptosis. GSK-3β, a serine threonine kinase and a negative regulator of the oncogenic Wnt/β-catenin signaling pathway, plays a critical role in the regulation of oncogenesis. Celecoxib and etoricoxib, the two cyclooxygenase-2 (COX-2) selective NSAIDs, and Diclofenac, a preferential COX-2 inhibitory NSAID, had shown uniformly the chemopreventive and anti-neoplastic effects in the early stage of colon cancer by promoting apoptosis as well as an over-expression of GSK-3β while down-regulating the PI3-K/Akt oncogenic pathway...
July 18, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28716954/synaptically-driven-phosphorylation-of-ribosomal-protein-s6-is-differentially-regulated-at-active-synapses-versus-dendrites-and-cell-bodies-by-mapk-and-pi3k-mtor-signaling-pathways
#3
Patricia Salgado Pirbhoy, Shannon Farris, Oswald Steward
High-frequency stimulation of the medial perforant path triggers robust phosphorylation of ribosomal protein S6 (rpS6) in activated dendritic domains and granule cell bodies. Here we dissect the signaling pathways responsible for synaptically driven rpS6 phosphorylation in the dentate gyrus using pharmacological agents to inhibit PI3-kinase/mTOR and MAPK/ERK-dependent kinases. Using phospho-specific antibodies for rpS6 at different sites (ser235/236 versus ser240/244), we show that delivery of the PI3-kinase inhibitor, wortmannin, decreased rpS6 phosphorylation throughout the somatodendritic compartment (granule cell layer, inner molecular layer, outer molecular layer), especially in granule cell bodies while sparing phosphorylation at activated synapses (middle molecular layer)...
August 2017: Learning & Memory
https://www.readbyqxmd.com/read/28714320/anticancer-effect-of-polyphyllin-%C3%AE-in-colorectal-cancer-cells-through-ros-dependent-autophagy-and-g2-m-arrest-mechanisms
#4
Si Yu, Lijiao Wang, Zhixing Cao, Daoyin Gong, Qianyi Liang, Hanting Chen, Huizhu Fu, Wenwen Wang, Xue Tang, Zihao Xie, Yang He, Cheng Peng, Yuzhi Li
Polyphyllin Ι is a steroidal saponin isolated from the rhizoma of Paris polyphylla. In the present study, we aimed to investigate the anticancer effects of polyphyllin Ι in colorectal cancer and to elucidate the potential underlying molecular mechanisms. Using, CCK8 assay, flow cytometry, laser confocal microscope analysis and western blot, the anticancer effects of the polyphyllin Ι were analysed in colorectal cells. Our results indicate that polyphyllin Ι significantly decreased cell viability of HCT 116 cells and induced autophagy...
July 16, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28711932/the-pan-bcl-2-blocker-obatoclax-gx15-070-and-the-pi3-kinase-mtor-inhibitor-bez235-produce-cooperative-growth-inhibitory-effects-in-all-cells
#5
Gabriele Stefanzl, Daniela Berger, Sabine Cerny-Reiterer, Katharina Blatt, Gregor Eisenwort, Wolfgang R Sperr, Gregor Hoermann, Karin Lind, Alexander W Hauswirth, Peter Bettelheim, Heinz Sill, Junia V Melo, Ulrich Jäger, Peter Valent
Acute lymphoblastic leukemia (ALL) is characterized by leukemic expansion of lymphoid blasts in hematopoietic tissues. Despite improved therapy only a subset of patients can be cured. Therefore, current research is focusing on new drug-targets. Members of the BCL-2 family and components of the PI3-kinase/mTOR pathway are critically involved in the regulation of growth and survival of ALL cells. We examined the effects of the pan-BCL-2 blocker obatoclax and the PI3-kinase/mTOR-inhibitor BEZ235 on growth and survival of ALL cells...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28708672/artemisinin-disrupts-androgen-responsiveness-of-human-prostate-cancer-cells-by-stimulating-the-26s-proteasome-mediated-degradation-of-the-androgen-receptor-protein
#6
Andrea M Steely, Jamin A Willoughby, Shyam N Sundar, Vasiliki I Aivaliotis, Gary L Firestone
Androgen receptor (AR) expression and activity is highly linked to the development and progression of prostate cancer and is a target of therapeutic strategies for this disease. We investigated whether the antimalarial drug artemisinin, which is a sesquiterpene lactone isolated from the sweet wormwood plant Artemisia annua, could alter AR expression and responsiveness in cultured human prostate cancer cell lines. Artemisinin treatment induced the 26S proteasome-mediated degradation of the receptor protein, without altering AR transcript levels, in androgen-responsive LNCaP prostate cancer cells or PC-3 prostate cancer cells expressing exogenous wild-type AR...
July 13, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28708578/hyperglycemia-and-advanced-glycation-end-products-ages-suppress-the-differentiation-of-3t3-l1-preadipocytes
#7
Chia-Chu Chang, Chen-Yu Chen, Geen-Dong Chang, Ting-Huan Chen, Woan-Ling Chen, Hui-Chin Wen, Chih-Yang Huang, Chung-Ho Chang
Aging is characterized by mild hyperglycemia and accumulation of advanced glycation end products (AGEs). Effects of chronic exposure to hyperglycemia or AGEs on the adipogenic differentiation of 3T3-L1 preadipocytes remain unclear. We examined the chronic effect of AGEs and high glucose on the differentiation of 3T3-L1 cells by culturing 3T3-L1 cells in the presence of AGEs or 25 mM glucose for 1 month. Chronic incubation of 3T3-L1 cells with AGEs or high glucose blocked their differentiation into mature adipocytes as evidenced by reduced levels of adipocyte markers such as accumulated oil droplets, GPDH, aP2, adiponectin and of adipogenesis regulators PPARγ and C/EBPα...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28704451/targeting-of-x-linked-inhibitor-of-apoptosis-protein-and-pi3-kinase-akt-signaling-by-embelin-suppresses-growth-of-leukemic-cells
#8
Kirti S Prabhu, Kodappully S Siveen, Shilpa Kuttikrishnan, Ahmad Iskandarani, Magdalini Tsakou, Iman W Achkar, Lubna Therachiyil, Roopesh Krishnankutty, Aijaz Parray, Michal Kulinski, Maysaloun Merhi, Said Dermime, Ramzi M Mohammad, Shahab Uddin
The X-linked inhibitor of apoptosis (XIAP) is a viable molecular target for anticancer drugs that overcome apoptosis-resistance of malignant cells. XIAP is an inhibitor of apoptosis, mediating through its association with BIR3 domain of caspase 9. Embelin, a quinone derivative isolated from the Embelia ribes plant, has been shown to exhibit chemopreventive, anti-inflammatory, and apoptotic activities via inhibiting XIAP activity. In this study, we found that embelin causes a dose-dependent suppression of proliferation in leukemic cell lines K562 and U937...
2017: PloS One
https://www.readbyqxmd.com/read/28704388/the-mir-23a-27a-24-2-microrna-cluster-buffers-transcription-and-signaling-pathways-during-hematopoiesis
#9
Jeffrey L Kurkewich, Justin Hansen, Nathan Klopfenstein, Helen Zhang, Christian Wood, Austin Boucher, Joseph Hickman, David E Muench, H Leighton Grimes, Richard Dahl
MicroRNA cluster mirn23a has previously been shown to promote myeloid development at the expense of lymphoid development in overexpression and knockout mouse models. This polarization is observed early in hematopoietic development, with an increase in common lymphoid progenitors (CLPs) and a decrease in all myeloid progenitor subsets in adult bone marrow. The pool size of multipotential progenitors (MPPs) is unchanged; however, in this report we observe by flow cytometry that polarized subsets of MPPs are changed in the absence of mirn23a...
July 13, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28698124/the-role-of-phosphatidylinositol-3-oh-kinase-pi3-kinase-and-respiratory-burst-enzymes-in-the-omim-bf4-mediated-toxic-mode-of-action-in-mussel-hemocytes
#10
Alexia Belavgeni, Stefanos Dailianis
The present study investigates the role of phosphatidylinositol-3-OH-kinase (PI3-kinase) and respiratory burst enzymes, NADPH oxidase and NO synthase, in the 1-methyl-3-octylimidazolium tetrafluoroborate ([omim][BF4])-mediated toxic mode of action in mussel hemocytes. Specifically, cell viability (using the neutral red uptake assay) was primarily tested in hemocytes treated with different concentrations of [omim][BF4] (0.1-10 mg L(-1)) and thereafter [omim][BF4]-mediated oxidative (in terms of superoxide anions/O2(-) and nitric oxide/NO generation, as well as the enhancement of lipid peroxidation by-products, in terms of malondialdehyde/MDA) and genotoxic (in terms of DNA damage) effects were determined in hemocytes treated with 1 mg L(-1) [omim][BF4]...
July 8, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28688216/molecular-aspects-of-diabetes-mellitus-resistin-microrna-and-exosome
#11
Mohammad Javad Saeedi Borujeni, Ebrahim Esfandiary, Gholamreza Taheripak, Pilar Codoñer-Franch, Eulalia Alonso-Iglesias, Hamed Mirzaei
Diabetes mellitus (DM) is known as one of important common endocrine disorders which could due to deregulation of a variety of cellular and molecular pathways. A large numbers studies indicated that various pathogenesis events including mutation, serin phosphorylation and increasing/decreasing expression of many genes could contribute to initiation and progression of DM. Insulin resistance is one of important factors which could play critical roles in DM pathogenesis. It has been showed that insulin resistance via targeting a sequence of cellular and molecular pathways (e...
July 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28684064/protective-role-of-vitamin-e-preconditioning-of-human-dermal-fibroblasts-against-thermal-stress-in-vitro
#12
Hira Butt, Azra Mehmood, Muhammad Ali, Saba Tasneem, Muhammad Sohail Anjum, Moazzam N Tarar, Shaheen N Khan, Sheikh Riazuddin
AIMS: Oxidative microenvironment of burnt skin restricts the outcome of cell based therapies of thermal skin injuries. The aim of this study was to precondition human dermal fibroblasts with an antioxidant such as vitamin E to improve their survival and therapeutic abilities in heat induced oxidative in vitro environment. MAIN METHODS: Fibroblasts were treated with 100μM vitamin E for 24h at 37°C followed by heat shock for 10min at 51°C in fresh serum free medium...
July 3, 2017: Life Sciences
https://www.readbyqxmd.com/read/28682056/a-dry-transition-state-more-compact-than-the-native-state-is-stabilized-by-non-native-interactions-during-the-unfolding-of-a-small-protein
#13
Sreemantee Sen, Rama Reddy Goluguri, Jayant B Udgaonkar
To define the role of non-native interactions in directing the course of protein folding or unfolding reactions, has been a difficult challenge. In particular, it is not known to what extent such interactions play a productive role by stabilizing the structures of transition states (TSs) found on the folding and unfolding pathways of proteins. On the contrary, it is thought that the TSs are expanded forms of the native (N) state stabilized by native interactions, and it is not known whether non-native interactions can modulate TS structure...
July 6, 2017: Biochemistry
https://www.readbyqxmd.com/read/28679075/first-report-of-immunohistochemical-detection-of-peste-des-petit-ruminants-parainfluenza-3-and-respiratory-syncytial-viral-antigens-in-lungs-of-nigerian-goats
#14
Theophilus A Jarikre Aghogho, Benjamin Obukowho Emikpe
This study determined the of involvement of PPR, PI3 and RS viruses in the pathology of caprine pneumonia across Nigeria. 150 goats were selected randomly. PI3 and RSV monoclonal antibodies and PPR polyclonal antibody were used for the immunolocalisation of the antigens. Histologically, 61 of the goats had broncho-interstitial pneumonia, 25 had interstitial pneumonia, 42 had bronchopneumonia, 12 had bronchiolitis and 10 were normal. PPR, PI3 and RS viral antigens were demonstrated in: intact and desquamated bronchial, bronchiolar epithelial cells, macrophages, leukocytes, pneumocytes and giant cells...
July 5, 2017: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/28676089/effects-of-silica-nanoparticle-exposure-on-mitochondrial-function-during-neuronal-differentiation
#15
Angélique D Ducray, Andrea Felser, Jana Zielinski, Aniela Bittner, Julia V Bürgi, Jean-Marc Nuoffer, Martin Frenz, Meike Mevissen
BACKGROUND: Nanomedicine offers a promising tool for therapies of brain diseases, but potential effects on neuronal health and neuronal differentiation need to be investigated to assess potential risks. The aim of this study was to investigate effects of silica-indocyanine green/poly (ε-caprolactone) nanoparticles (PCL-NPs) engineered for laser tissue soldering in the brain before and during differentiation of SH-SY5Y cells. Considering adaptations in mitochondrial homeostasis during neuronal differentiation, metabolic effects of PCL-NP exposure before and during neuronal differentiation were studied...
July 4, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28671992/signaling-pathways-induced-by-serine-proteases-to-increase-intestinal-epithelial-barrier-function
#16
Kelcie A Lahey, Natalie J Ronaghan, Judie Shang, Sébastien P Dion, Antoine Désilets, Richard Leduc, Wallace K MacNaughton
Changes in barrier function of the gastrointestinal tract are thought to contribute to the inflammatory bowel diseases Crohn's disease and ulcerative colitis. Previous work in our lab demonstrated that apical exposure of intestinal epithelial cell lines to serine proteases results in an increase in transepithelial electrical resistance (TER). However, the underlying mechanisms governing this response are unclear. We aimed to determine the requirement for proteolytic activity, epidermal growth factor receptor (EGFR) activation, and downstream intracellular signaling in initiating and maintaining enhanced barrier function following protease treatment using a canine intestinal epithelial cell line (SCBN)...
2017: PloS One
https://www.readbyqxmd.com/read/28665107/stepwise-assembly-of-%C3%AE-sheet-structure-during-the-folding-of-an-sh3-domain-revealed-by-a-pulsed-hydrogen-exchange-mass-spectrometry-study
#17
Nilesh Aghera, Jayant B Udgaonkar
Dissecting temporally the sequence of secondary structural changes, and determining how these specific changes modulate conformational heterogeneity, remain major goals of protein folding studies. In this study, the folding of the SH3 domain of PI3 kinase has been characterized using pulsed hydrogen exchange mass spectrometry (HX-MS). The folding could be described as a four-state process, U ↔ IVE ↔ IE ↔ N, where IVE and IE are structurally heterogeneous intermediate ensembles. Compared to U, early intermediate IVE has a marginally increased level of protection against HX of amides along the entire length of the polypeptide...
July 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28663750/anaphylatoxins-activate-ca-2-akt-pi3-kinase-and-foxo1-foxp3-in-the-retinal-pigment-epithelium
#18
Catharina Busch, Balasubramaniam Annamalai, Khava Abdusalamova, Nadine Reichhart, Christian Huber, Yuchen Lin, Emeraldo A H Jo, Peter F Zipfel, Christine Skerka, Gerhild Wildner, Maria Diedrichs-Möhring, Bärbel Rohrer, Olaf Strauß
PURPOSE: The retinal pigment epithelium (RPE) is a main target for complement activation in age-related macular degeneration (AMD). The anaphylatoxins C3a and C5a have been thought to mostly play a role as chemoattractants for macrophages and immune cells; here, we explore whether they trigger RPE alterations. Specifically, we investigated the RPE as a potential immunoregulatory gate, allowing for active changes in the RPE microenvironment in response to complement. DESIGN: In vitro and in vivo analysis of signaling pathways...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28656644/activation-of-gsk-3-disrupts-cholinergic-homoeostasis-in-nucleus-basalis-of-meynert-and-frontal-cortex-of-rats
#19
Yue Wang, Qing Tian, En-Jie Liu, Li Zhao, Jie Song, Xin-An Liu, Qing-Guo Ren, Xia Jiang, Juan Zeng, Yu-Tao Yang, Jian-Zhi Wang
The cholinergic impairment is an early marker in Alzheimer's disease (AD), while the mechanisms are not fully understood. We investigated here the effects of glycogen synthase kinse-3 (GSK-3) activation on the cholinergic homoeostasis in nucleus basalis of Meynert (NBM) and frontal cortex, the cholinergic enriched regions. We activated GSK-3 by lateral ventricular infusion of wortmannin (WT) and GF-109203X (GFX), the inhibitors of phosphoinositol-3 kinase (PI3-K) and protein kinase C (PKC), respectively, and significantly decreased the acetylcholine (ACh) level via inhibiting choline acetyl transferase (ChAT) rather than regulating acetylcholinesterase (AChE)...
June 28, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28656507/the-stem-cell-factor-scf-c-kit-signalling-in-testis-and-prostate-cancer
#20
Henrique J Cardoso, Marília I Figueira, Sílvia Socorro
The stem cell factor (SCF) is a cytokine that specifically binds the tyrosine kinase receptor c-KIT. The SCF/c-KIT interaction leads to receptor dimerization, activation of kinase activity and initiation of several signal transduction pathways that control cell proliferation, apoptosis, differentiation and migration in several tissues. The activity of SCF/c-KIT system is linked with the phosphatidylinositol 3-kinase (PI3-K), the Src, the Janus kinase/signal transducers and activators of transcription (JAK/STAT), the phospholipase-C (PLC-γ) and the mitogen-activated protein kinase (MAPK) pathways...
June 27, 2017: Journal of Cell Communication and Signaling
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