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https://www.readbyqxmd.com/read/28550735/clarithromycin-inhibits-tnf-%C3%AE-induced-muc5ac-mucin-gene-expression-via-the-mkp-1-p38mapk-dependent-pathway
#1
Said Ahmad Shah, Hajime Ishinaga, Kazuhiko Takeuchi
Clarithromycin is a 14-membered macrolide antibiotic. Low-dose, long-term macrolide therapy is effective in patients with chronic airway diseases, such as diffuse panbronchitis, chronic bronchitis, and chronic sinusitis. However, the mechanism underlying this clinical efficacy remains unclear. The dual specificity phosphatase MKP-1 (MAPK phosphatase-1), also called DUSP (dual specificity phosphatase-1), was initially identified as an in vitro ERK-specific phosphatase, but depending on the cell type, it can also dephosphorylate other members of the MAPK family, such as p38 and JNK, and thus suppress downstream signaling of these kinases...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28550639/philadelphia-chromosome-positive-acute-myeloid-leukemia-with-masses-and-osteolytic-lesions-finding-of-18f-fdg-pet-ct
#2
Zhan Su, Fengyu Wu, Weiyu Hu, Xiaodan Liu, Shaoling Wu, Xianqi Feng, Zhongguang Cui, Jie Yang, Zhenguang Wang, Hongzai Guan, Hongguo Zhao, Wei Wang, Chunting Zhao, Jun Peng
Philadelphia chromosome-positive acute myeloid leukemia is controversial and difficult to distinguish from the blast phase of chronic myeloid leukemia. As a myeloid neoplasm, rare cases of this leukemia manifest multiple soft-tissue tumors or bone lytic lesions. In this paper, we describe a 49-year-old male patient who had an abrupt onset with sharp chest pain, fever, fatigue, emaciation, and splenomegaly. 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) result showed diffuse and uneven hypermetabolic lesions in the bone marrow with peripheral bone marrow expansion, multiple soft tissue neoplasms with high 18F-FDG uptake, and lytic bone lesions...
May 27, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28550180/a-novel-de-novo-mutation-in-prkag2-gene-infantile-onset-phenotype-and-signaling-pathway-involved
#3
Yanchun Xu, Alex Gray, David Grahame Hardie, Alper Uzun, Sunil Shaw, James F Padbury, Chanika Phornphutkul, Yi-Tang Tseng
PRKAG2 encodes the γ2-subunit isoform of the 5' AMP-activated protein kinase (AMPK), a heterotrimeric enzyme with major roles in regulation of energy metabolism in response to cellular stress. Mutations in PRKAG2 have been implicated in a unique hypertrophic cardiomyopathy (HCM) characterized by cardiac glycogen overload, ventricular preexcitation and hypertrophy. We identified a novel, de novo PRKAG2 mutation (K475E) in a neonate with prenatal onset of HCM. We aimed to investigate the cellular impact, signaling pathways involved and therapeutic options for K475E mutation using cells stably expressing human wild type (WT) or the K475E mutant...
May 26, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28550120/hiv-1-decreases-nrf2-are-activity-and-phagocytic-function-in-alveolar-macrophages
#4
Bashar S Staitieh, Lingmei Ding, Wendy A Neveu, Paul Spearman, David M Guidot, Xian Fan
Respiratory complications occur frequently in individuals living with human immunodeficiency-1 virus (HIV) infection, and there is evidence that HIV-related oxidative stress impairs alveolar macrophage immune function. We hypothesized that nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a master transcription factor that activates the antioxidant response element (ARE) and regulates antioxidant defenses, has an important role in alveolar macrophage (AMs) immune dysfunction in individuals with HIV infections...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550040/kras-g12d-expression-in-lung-resident-myeloid-cells-promotes-pulmonary-lch-like-neoplasm-sensitive-to-statin-treatment
#5
Tamihiro Kamata, Susan Giblett, Catrin Pritchard
Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm associated with somatic mutations in the genes involved in the RAF/MEK/ERK signaling pathway. Recently, oncogenic mutations in NRAS/KRAS, upstream regulators of the RAF/MEK/ERK pathway, have been reported in pulmonary, but not in non-pulmonary, LCH cases, suggesting organ-specific contribution of oncogenic RAS to LCH pathogenesis. Using a mouse model expressing KRAS(G12D) in the lung by nasal delivery of adenoviral Cre, here we show that KRAS(G12D) expression in lung-resident myeloid cells induces pulmonary LCH-like neoplasms comprised of pathogenic CD11c(high)F4/80+CD207+ cells...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28549992/thyroid-hormone-treatment-activates-protective-pathways-in-both-in-vivo-and-in-vitro-models-of-neuronal-injury
#6
Jianrong Li, Ines Donangelo, Kiyomi Abe, Oscar Scremin, Sujie Ke, Feng Li, Anna Milanesi, Yan-Yun Liu, Gregory A Brent
Thyroid hormone plays an important role in brain development and adult brain function, and may influence neuronal recovery after Traumatic Brain Injury (TBI). We utilized both animal and cell culture models to determine the effects of thyroid hormone treatment, post TBI or during hypoxia, on genes important for neuronal survival and neurogenesis. We show that TBI in rats is associated with a reduction in serum thyroxine (T4) and triiodothyronine (T3). A single dose of levothyroxine (T4), one hour after injury, increased serum T4 and normalized serum T3 levels...
May 23, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28549853/molecular-fingerprinting-of-principal-neurons-in-the-rodent-hippocampus-a-neuroinformatics-approach
#7
D J Hamilton, C M White, C L Rees, D W Wheeler, G A Ascoli
Neurons are often classified by their morphological and molecular properties. The online knowledge base Hippocampome.org primarily defines neuron types from the rodent hippocampal formation based on their main neurotransmitter (glutamate or GABA) and the spatial distributions of their axons and dendrites. For each neuron type, this open-access resource reports any and all published information regarding the presence or absence of known molecular markers, including calcium-binding proteins, neuropeptides, receptors, channels, transcription factors, and other molecules of biomedical relevance...
April 29, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28549828/deficiency-of-long-isoforms-of-nfe2l1-sensitizes-min6-pancreatic-%C3%AE-cells-to-arsenite-induced-cytotoxicity
#8
Qi Cui, Jingqi Fu, Yuxin Hu, Yongfang Li, Bei Yang, Lu Li, Jing Sun, Chengjie Chen, Guifan Sun, Yuanyuan Xu, Qiang Zhang, Jingbo Pi
Increasing evidence indicates that chronic inorganic arsenic exposure is associated with type 2 diabetes (T2D), a disease of growing prevalence. Pancreatic β-cells were targeted and damaged by oxidative stress induced by arsenite. We previously showed that nuclear factor erythroid 2 like 2 (Nfe2l2)-deficient pancreatic β-cells were vulnerable to cell damage induced by oxidative stressors including arsenite, due to a muted antioxidant response. Like nuclear factor erythroid 2 like 2 (NFE2L2), NFE2L1 also belongs to the cap 'n' collar (CNC) basic-region leucine zipper (bZIP) transcription factor family, and regulates antioxidant response element (ARE) related genes...
May 23, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28549739/characterization-of-a-major-facilitator-superfamily-transporter-in-shiraia-bambusicola
#9
Huaxiang Deng, Ruijie Gao, Xiangru Liao, Yujie Cai
Reactive oxygen species (ROS) generated by photo-activated hypocrellin from Shiraia bambusicola are detrimental to cellular macromolecules. However, S. bambusicola can still maintain excellent morphology during continuous hypocrellin production, indicating an extraordinary autoresistance system that protects against the harmful ROS. In this study, a major facilitator superfamily transporter (MFS) was isolated from S. bambusicola and deleted using the clustered regularly interspaced short palindromic repeat sequences (CRISPR)/Cas9 system...
May 23, 2017: Research in Microbiology
https://www.readbyqxmd.com/read/28549153/chippi-a-novel-method-for-mapping-chimeric-protein-protein-interactions-uncovers-selection-principles-of-protein-fusion-events-in-cancer
#10
Milana Frenkel-Morgenstern, Alessandro Gorohovski, Somnath Tagore, Vaishnovi Sekar, Miguel Vazquez, Alfonso Valencia
Fusion proteins, comprising peptides deriving from the translation of two parental genes, are produced in cancer by chromosomal aberrations. The expressed fusion protein incorporates domains of both parental proteins. Using a methodology that treats discrete protein domains as binding sites for specific domains of interacting proteins, we have cataloged the protein interaction networks for 11 528 cancer fusions (ChiTaRS-3.1). Here, we present our novel method, chimeric protein-protein interactions (ChiPPI) that uses the domain-domain co-occurrence scores in order to identify preserved interactors of chimeric proteins...
May 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28549065/c-elegans-daf-16-foxo-interacts-with-tgf-%C3%A3-bmp-signaling-to-induce-germline-tumor-formation-via-mtorc1-activation
#11
Wenjing Qi, Yijian Yan, Dietmar Pfeifer, Erika Donner V Gromoff, Yimin Wang, Wolfgang Maier, Ralf Baumeister
Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS) is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß)/bone morphogenic protein (BMP) signaling pathway causes germline hyperplasia and results in disruption of the basement membrane...
May 26, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28548960/severe-hypertriglyceridemia-due-to-two-novel-loss-of-function-lipoprotein-lipase-gene-mutations-c310r-e396v-in-a-chinese-family-associated-with-recurrent-acute-pancreatitis
#12
Yu Lun, Xiaofang Sun, Ping Wang, Jingwei Chi, Xu Hou, Yangang Wang
Lipoprotein lipase (LPL) is widely expressed in skeletal muscles, cardiac muscles as well as adipose tissue and involved in the catabolism of triglyceride. Herein we have systematically characterized two novel loss-of-function mutations in LPL from a Chinese family in which afflicted members were manifested by severe hypertriglyceridemia and recurrent pancreatitis. DNA sequencing revealed that the proband was a heterozygote carrying a novel c.T928C (p.C310R) mutation in exon 6 of the LPL gene. Another member of the family was detected to be a compound heterozygote who along with the c...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548933/kir2dl5-mutation-and-loss-underlies-sporadic-dermal-neurofibroma-pathogenesis-and-growth
#13
Corina Anastasaki, Sonika Dahiya, David H Gutmann
Dermal neurofibromas (DNFs) are benign peripheral nerve sheath tumors thought to originate from Schwann cell progenitors. These tumors represent one of the hallmarks of the neurofibromatosis type 1 (NF1) tumor predisposition syndrome, where they can number in the thousands. While NF1-DNFs arise due to mutations in the NF1 gene, the vast majority of DNFs occur sporadically (sp-DNFs), where the genetic etiology is currently unknown. Herein, we employed whole-exome sequencing of sp-DNFs to identify a recurrent mutation in the KIR2DL5 gene, which codes for a protein suppressor of natural killer (NK) cell activity...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548246/comparison-of-three-different-types-of-scaffolds-preseeded-with-human-bone-marrow-mononuclear-cells-on-the-bone-healing-in-a-femoral-critical-size-defect-model-of-the-athymic-rat
#14
Maren Janko, Julian Sahm, Alexander Schaible, Jan C Brune, Marlene Bellen, Katrin Schröder, Caroline Seebach, Ingo Marzi, Dirk Henrich
Large bone defects often pose major difficulties in orthopedic surgery. The application of long term cultured stem cells combined with a scaffold lead to a significant improvement of bone healing in recent experiments but is strongly restricted by EU-law. Bone marrow mononuclear cells (BMC), however, can be isolated and transplanted within few hours and have been proven effective in experimental models of bone healing. The effectivity of the BMC supported therapy might be influenced by the type of scaffold...
May 26, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28548108/drugging-the-pain-epigenome
#15
REVIEW
Ellen Niederberger, Eduard Resch, Michael J Parnham, Gerd Geisslinger
More than 20% of adults worldwide experience different types of chronic pain, which are frequently associated with several comorbidities and a decrease in quality of life. Several approved painkillers are available, but current analgesics are often hampered by insufficient efficacy and/or severe adverse effects. Consequently, novel strategies for safe, highly efficacious treatments are highly desirable, particularly for chronic pain. Epigenetic mechanisms such as DNA methylation, histone modifications and microRNAs (miRNAs) strongly affect the regulation of gene expression, potentially for long periods over years or even generations, and have been associated with pathophysiological pain...
May 26, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28548091/cellular-interplay-via-cytokine-hierarchy-causes-pathological-cardiac-hypertrophy-in-raf1-mutant-noonan-syndrome
#16
Jiani C Yin, Mathew J Platt, Xixi Tian, Xue Wu, Peter H Backx, Jeremy A Simpson, Toshiyuki Araki, Benjamin G Neel
Noonan syndrome (NS) is caused by mutations in RAS/ERK pathway genes, and is characterized by craniofacial, growth, cognitive and cardiac defects. NS patients with kinase-activating RAF1 alleles typically develop pathological left ventricular hypertrophy (LVH), which is reproduced in Raf1(L613V/+) knock-in mice. Here, using inducible Raf1(L613V) expression, we show that LVH results from the interplay of cardiac cell types. Cardiomyocyte Raf1(L613V) enhances Ca(2+) sensitivity and cardiac contractility without causing hypertrophy...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28547570/the-effect-of-iloprost-on-cell-proliferation-and-angiogenesis-related-gene-expression-in-human-periodontal-ligament-cells
#17
Thanomsuk Jearanaiphaisarn, Teeranuch Sanharati, Prasit Pavasant, Chalida Nakalekha Limjeerajarus
Periodontal ligament is considered a rich source of mesenchymal stem cells for pulp regeneration. This study investigated the effect of iloprost, a prostacyclin analog, on cell proliferation and the expression of angiogenesis-related genes in human periodontal ligament cells (hPDLs) in vitro. The hPDLs were treated with 10(-9)-10(-6) M iloprost for 1, 6 and 24 h. Cell proliferation was determined by an MTT assay. Vascular endothelial growth factor (VEGF), alpha-1 type I collagen (COL1), and basic fibroblast growth factor (bFGF) mRNA expression were determined by semi-quantitative and qPCR...
May 25, 2017: Odontology
https://www.readbyqxmd.com/read/28547344/alteration-of-a-recombinant-protein-n-glycan-structure-in-silkworms-by-partial-suppression-of-n-acetylglucosaminidase-gene-expression
#18
Tatsuya Kato, Kotaro Kikuta, Ayumi Kanematsu, Sachiko Kondo, Hirokazu Yagi, Koichi Kato, Enoch Y Park
OBJECTIVE: To synthesize complex type N-glycans in silkworms, shRNAs against the fused lobe from Bombyx mori (BmFDL), which codes N-acetylglucosaminidase (GlcNAcase) in the Golgi, was expressed by recombinant B. mori nucleopolyhedrovirus (BmNPV) in silkworm larvae. RESULTS: Expression was under the control of the actin promoter of B. mori or the U6-2 and i.e.-2 promoters from Orgyia pseudotsugata multiple nucleopolyhedrovirus (OpMNPV). The reduction of specific GlcNAcase activity was observed in Bm5 cells and silkworm larvae using the U6-2 promoter...
May 25, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28547212/the-kinetics-in-mathematical-models-on-segmentation-clock-genes-in-zebrafish
#19
Kuan-Wei Chen, Kang-Ling Liao, Chih-Wen Shih
Somitogenesis is the process for the development of somites in vertebrate embryos. This process is timely regulated by synchronous oscillatory expression of the segmentation clock genes. Mathematical models expressed by delay equations or ODEs have been proposed to depict the kinetics of these genes in interacting cells. Through mathematical analysis, we investigate the parameter regimes for synchronous oscillations and oscillation-arrested in an ODE model and a model with transcriptional and translational delays, both with Michaelis-Menten type degradations...
May 25, 2017: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/28547133/hsf1-acetylation-decreases-its-transcriptional-activity-and-enhances-glucolipotoxicity-induced-apoptosis-in-rat-and-human-beta-cells
#20
Indri Purwana, Jun J Liu, Bernard Portha, Jean Buteau
AIMS/HYPOTHESIS: Heat shock factor protein 1 (HSF1) is a transcription factor that regulates the expression of key molecular chaperones, thereby orchestrating the cellular response to stress. This system was recently implicated in the control of insulin sensitivity and is therefore being scrutinised as a novel therapeutic avenue for type 2 diabetes. However, the regulation and biological actions of HSF1 in beta cells remain elusive. Herein, we sought to investigate the regulation of HSF1 in pancreatic beta cells and to study its potential role in cell survival...
May 25, 2017: Diabetologia
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