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Amino Acid Therapy

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https://www.readbyqxmd.com/read/28924147/tumor-suppression-via-inhibition-of-swi-snf-complex-dependent-nf-%C3%AE%C2%BAb-activation
#1
Kazuyoshi Kobayashi, Hiroaki Hiramatsu, Shinya Nakamura, Kyousuke Kobayashi, Takeshi Haraguchi, Hideo Iba
The transcription factor NF-κB is constitutively activated in many epithelial tumors but few NF-κB inhibitors are suitable for cancer therapy because of its broad biological effects. We previously reported that the d4-family proteins (DPF1, DPF2, DPF3a/b) function as adaptor proteins linking NF-κB with the SWI/SNF complex. Here, using epithelial tumor cell lines, A549 and HeLaS3, we demonstrate that exogenous expression of the highly-conserved N-terminal 84-amino acid region (designated "CT1") of either DPF2 or DPF3a/b has stronger inhibitory effects on anchorage-independent growth than the single knockdown of any d4-family protein...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28919713/layer-by-layer-nanoparticles-co-loading-gemcitabine-and-platinum-iv-prodrugs-for-synergistic-combination-therapy-of-lung-cancer
#2
Rongrong Zhang, Yun Ru, Yiping Gao, Jinyin Li, Shilong Mao
PURPOSE: Cisplatin plus gemcitabine (GEM) is a standard regimen for the first-line treatment of advanced non-small cell lung cancer. The aim of this study was to prepare biocompatible and biodegradable polymeric prodrugs and construct nanoparticles (NPs) with layer-by-layer (LbL) technique. METHODS: Platinum (Pt) (IV) complex with a carboxyl group was conjugated to the amino group of chitosan (CH), resulting in a CH-Pt conjugation with positive charge. GEM with amino group was conjugated to the carboxyl group of hyaluronic acid (HA), resulting in a HA-GEM conjugation with negative charge...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28919256/metabolic-links-between-plasma-cell-survival-secretion-and-stress
#3
REVIEW
Wing Y Lam, Deepta Bhattacharya
Humoral immunity is generated and maintained by antigen-specific antibodies that counter infectious pathogens. Plasma cells are the major producers of antibodies during and after infections, and each plasma cell produces some thousands of antibody molecules per second. This magnitude of secretion requires enormous quantities of amino acids and glycosylation sugars to properly build and fold antibodies, biosynthetic substrates to fuel endoplasmic reticulum (ER) biogenesis, and additional carbon sources to generate energy...
September 11, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28916119/safety-and-efficacy-of-glycerol-phenylbutyrate-for-management-of-urea-cycle-disorders-in-patients-aged-2months-to-2years
#4
Susan A Berry, Nicola Longo, George A Diaz, Shawn E McCandless, Wendy E Smith, Cary O Harding, Roberto Zori, Can Ficicioglu, Uta Lichter-Konecki, Beth Robinson, Jerry Vockley
INTRODUCTION: Glycerol phenylbutyrate (GPB) is approved in the US for the management of patients 2months of age and older with urea cycle disorders (UCDs) that cannot be managed with protein restriction and/or amino acid supplementation alone. Limited data exist on the use of nitrogen conjugation agents in very young patients. METHODS: Seventeen patients (15 previously on other nitrogen scavengers) with all types of UCDs aged 2months to 2years were switched to, or started, GPB...
September 8, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28912687/alterations-in-properties-of-glutamatergic-transmission-in-the-temporal-cortex-and-hippocampus-following-pilocarpine-induced-acute-seizures-in-wistar-rats
#5
Dmitry V Amakhin, Sergey L Malkin, Julia L Ergina, Kirill A Kryukov, Ekaterina A Veniaminova, Olga E Zubareva, Aleksey V Zaitsev
Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy in humans, and is often developed after an initial precipitating brain injury. This form of epilepsy is frequently resistant to pharmacological treatment; therefore, the prevention of TLE is the prospective approach to TLE therapy. The lithium-pilocarpine model in rats replicates some of the main features of TLE in human, including the pathogenic mechanisms of cell damage and epileptogenesis after a primary brain injury. In the present study, we investigated changes in the properties of glutamatergic transmission during the first 3 days after pilocarpine-induced acute seizures in Wistar rats (PILO-rats)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28905885/long-term-correction-of-hemophilia-a-mice-following-lentiviral-mediated-delivery-of-an-optimized-canine-factor-viii-gene
#6
J M Staber, M J Pollpeter, C-G Anderson, M Burrascano, A L Cooney, P L Sinn, D T Rutkowski, W C Raschke, P B McCray
Current therapies for hemophilia A include frequent prophylactic or on-demand intravenous factor treatments which are costly, inconvenient and may lead to inhibitor formation. Viral vector delivery of factor VIII (FVIII) cDNA has the potential to alleviate the debilitating clotting defects. Lentiviral-based vectors delivered to murine models of hemophilia A mediate phenotypic correction. However, a limitation of lentiviral-mediated FVIII delivery is inefficient transduction of target cells. Here, we engineer a feline immunodeficiency virus (FIV) -based lentiviral vector pseudotyped with the baculovirus GP64 envelope glycoprotein to mediate efficient gene transfer to mouse hepatocytes...
September 14, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28904834/methionine-mediated-synthesis-of-magnetic-nanoparticles-and-functionalization-with-gold-quantum-dots-for-theranostic-applications
#7
Arūnas Jagminas, Agnė Mikalauskaitė, Vitalijus Karabanovas, Jūrate Vaičiūnienė
Biocompatible superparamagnetic iron oxide nanoparticles (NPs) through smart chemical functionalization of their surface with fluorescent species, therapeutic proteins, antibiotics, and aptamers offer remarkable potential for diagnosis and therapy of disease sites at their initial stage of growth. Such NPs can be obtained by the creation of proper linkers between magnetic NP and fluorescent or drug probes. One of these linkers is gold, because it is chemically stable, nontoxic and capable to link various biomolecules...
2017: Beilstein Journal of Nanotechnology
https://www.readbyqxmd.com/read/28904446/levodopa-history-and-therapeutic-applications
#8
Sujith Ovallath, Bahiya Sulthana
Levodopa - the aromatic amino acid L-3,4-dihydroxy phenylalanine has held the attention of neurologists and pharmacologists alike for more than half a century. Even though extensive research has been done across the globe in treatment of Parkinson's disease, with different molecules, none could replace the gold standard treatment or provide complete relief for the debilitated. Although research brought us better tips and tricks to modulate the dopamine blood levels to balance between the desired and deleterious effects, it could never replace the basic substrate...
July 2017: Annals of Indian Academy of Neurology
https://www.readbyqxmd.com/read/28904440/primary-hyperoxaluria-type-1-with-homozygosity-for-a-double-mutated-agxt-allele-in-a-2-year-old-child
#9
S Krishnamurthy, G B Kartha, V S Venkateswaran, M Prasannakumar, S Mahadevan, M Gowda, A Pelle, D Giachino
Primary hyperoxaluria (PH) Type 1 is a rare, genetic disorder caused by deficiency of the liver enzyme alanine-glyoxylate aminotransferase, which is encoded by AGXT gene. We report a 2-year-old South Indian Tamil child with nephrocalcinosis due to PH Type 1, in whom a homozygous genotype for two missense mutations in the AGXT gene was found: first, a C to G transversion (c. 32C>G) in exon 1 resulting in the amino acid substitution p.Pro11Arg; second, a T to A transversion (c. 167T>A) in exon 2 resulting in p...
September 2017: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/28903985/molecular-tools-for-the-detection-and-deduction-of-azole-antifungal-drug-resistance-phenotypes-in-aspergillus-species
#10
REVIEW
Anna Dudakova, Birgit Spiess, Marut Tangwattanachuleeporn, Christoph Sasse, Dieter Buchheidt, Michael Weig, Uwe Groß, Oliver Bader
The incidence of azole resistance in Aspergillus species has increased over the past years, most importantly for Aspergillus fumigatus. This is partially attributable to the global spread of only a few resistance alleles through the environment. Secondary resistance is a significant clinical concern, as invasive aspergillosis with drug-susceptible strains is already difficult to treat, and exclusion of azole-based antifungals from prophylaxis or first-line treatment of invasive aspergillosis in high-risk patients would dramatically limit drug choices, thus increasing mortality rates for immunocompromised patients...
October 2017: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/28900492/identification-of-novel-epitopes-with-agonistic-activity-for-the-development-of-tumor-immunotherapy-targeting-trail-r1
#11
Lu Guo, Xin Sun, Zhichao Hao, Jingjing Huang, Xiaojian Han, Yajie You, Yaying Li, Meiying Shen, Tatsuhiko Ozawa, Hiroyuki Kishi, Atsushi Muraguchi, Aishun Jin
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-1/2 (TRAIL-R1/R2), also known as death receptors, are expressed in a wide variety of tumor cells. Although TRAIL can induce cell apoptosis by engaging its cognate TRAIL-R1/R2, some tumor cells are or become resistant to TRAIL treatment. Monoclonal antibodies (mAbs) against TRAIL-R1/R2 have been developed to use as potential antitumor therapeutic agents instead of TRAIL. However, TRAIL-R1/R2-based tumor therapy has not yet been realized...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28899403/effects-of-hla-drb1-alleles-on-susceptibility-and-clinical-manifestations-in-japanese-patients-with-adult-onset-still-s-disease
#12
Tomoyuki Asano, Hiroshi Furukawa, Shuzo Sato, Makiko Yashiro, Hiroko Kobayashi, Hiroshi Watanabe, Eiji Suzuki, Tomoyuki Ito, Yoshifumi Ubara, Daisuke Kobayashi, Nozomi Iwanaga, Yasumori Izumi, Keita Fujikawa, Satoshi Yamasaki, Tadashi Nakamura, Tomohiro Koga, Toshimasa Shimizu, Masataka Umeda, Fumiaki Nonaka, Michio Yasunami, Yukitaka Ueki, Katsumi Eguchi, Naoyuki Tsuchiya, Shigeto Tohma, Koh-Ichiro Yoshiura, Hiromasa Ohira, Atsushi Kawakami, Kiyoshi Migita
BACKGROUND: HLA-DRB1 alleles are major determinants of genetic predisposition to rheumatic diseases. We assessed whether DRB1 alleles are associated with susceptibility to particular clinical features of adult onset Still's disease (AOSD) in a Japanese population by determining the DRB1 allele distributions. METHODS: DRB1 genotyping of 96 patients with AOSD and 1,026 healthy controls was performed. Genomic DNA samples from the AOSD patients were also genotyped for MEFV exons 1, 2, 3, and 10 by direct sequencing...
September 12, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28891933/tyrosine-kinase-inhibitors-therapies-with-mainly-anti-angiogenic-activity-in-advanced-renal-cell-carcinoma-value-of-pet-ct-in-response-evaluation
#13
REVIEW
Girolamo Ranieri, Ilaria Marech, Artor Niccoli Asabella, Alessandra Di Palo, Mariangela Porcelli, Valentina Lavelli, Giuseppe Rubini, Cristina Ferrari, Cosmo Damiano Gadaleta
Renal cell carcinoma (RCC) is the most frequent renal tumor and the majority of patients are diagnosed with advanced disease. Tumor angiogenesis plays a crucial role in the development and progression of RCC together with hypoxia and glucose metabolism. These three pathways are strictly connected to the cell growth and proliferation, like a loop that is self-feeding. Over the last few years, the ever-deeper knowledge of its contribution in metastatic RCC led to the discovery of numerous tyrosine kinase inhibitors (TKIs) targeting pro-angiogenic receptors at different levels such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib...
September 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28888999/role-of-cellular-metabolism-in-regulating-type-i-interferon-responses-implications-for-tumour-immunology-and-treatment
#14
Duale Ahmed, Edana Cassol
Type I interferons (IFN) are increasingly recognized for their role in regulating anti-tumour immune responses. However, chronic activation of these pathways can result in immunosuppression and has been linked to poor responses to genotoxic and radiotoxic therapies. Emerging evidence suggests energy, lipid and amino acid metabolism play an important role in regulating and fine tuning type I IFN responses. Further, dysregulation of these processes has been implicated in the pathogenesis of chronic viral infections and autoimmune disorders...
September 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28887792/liver-failure-as-the-presentation-of-ornithine-transcarbamylase-deficiency-in-a-13-month-old-female
#15
Farrah Rajabi, Lance H Rodan, Maureen M Jonas, Janet S Soul, Nicole J Ullrich, Ann Wessel, Susan E Waisbren, Wen-Hann Tan, Gerard T Berry
Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder with variable expressivity in heterozygous females. While liver function testing is often abnormal in patients with OTCD, liver failure is uncommon on presentation. A 13-month-old female with no significant past medical history presented with irritability, right arm weakness, and decreased appetite. Initial workup revealed hepatic dysfunction with an INR of 3.4, ammonia level of 75 μmol/L, and abnormal brain MRI with gyral edema with restricted diffusion, and patchy signal abnormality in basal ganglia...
September 9, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28886462/genetic-polymorphism-of-thymidine-kinase-tk-and-dna-polymerase-pol-of-clinical-varicella-zoster-virus-vzv-isolates-collected-over-three-decades
#16
Anja Hoffmann, Kristin Döring, Natalja Tatjana Seeger, Martina Bühler, Michael Schacke, Andi Krumbholz, Andreas Sauerbrei
BACKGROUND: Genotypic resistance testing of varicella-zoster virus (VZV) strains to antivirals is of high relevance in immunocompromised patients with VZV reactivations unresponsive to therapy. However, the knowledge on mutations associated with natural gene polymorphism or resistance is limited. OBJECTIVES: To examine the genotype of the thymidine kinase (TK) and DNA polymerase (pol) of unselected clinical VZV isolates collected between 1984 and 2014 and to verify the phenotype related to novel amino acid (aa) substitutions...
September 1, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28879639/nitisinone-induced-keratopathy-in-alkaptonuria-a-challenging-diagnosis-despite-clinical-suspicion
#17
Andrew White, Michel C Tchan
Alkaptonuria is a rare disorder of amino acid metabolism that causes premature large joint and spine arthropathy and cardiac valvular disease. It is characterised by elevated levels of homogentisic acid. Nitisinone (NTBC) is a benzoylcyclohexane-1,3-dione that reversibly inhibits the activity of the enzymatic step immediately prior to homogentisate dioxygenase, hence reducing the production of homogentisic acid. Thus it is thought that nitisinone might be a treatment for alkaptonuria. A side effect of NTBC therapy is elevation of plasma tyrosine levels in a manner analogous to tyrosinemia type 2, another related condition which causes a painful palmoplantar hyperkeratosis and eye pathology described as conjunctivitis and herpetic-like corneal ulceration...
September 7, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28875501/the-protein-kinase-c-super-family-member-pkn-is-regulated-by-mtor-and-influences-differentiation-during-prostate-cancer-progression
#18
Chun-Song Yang, Tiffany A Melhuish, Adam Spencer, Li Ni, Yi Hao, Kasey Jividen, Thurl E Harris, Chelsi Snow, Henry F Frierson, David Wotton, Bryce M Paschal
BACKGROUND: Phosphoinositide-3 (PI-3) kinase signaling has a pervasive role in cancer. One of the key effectors of PI-3 kinase signaling is AKT, a kinase that promotes growth and survival in a variety of cancers. Genetically engineered mouse models of prostate cancer have shown that AKT signaling is sufficient to induce prostatic epithelial neoplasia (PIN), but insufficient for progression to adenocarcinoma. This contrasts with the phenotype of mice with prostate-specific deletion of Pten, where excessive PI-3 kinase signaling induces both PIN and locally invasive carcinoma...
September 6, 2017: Prostate
https://www.readbyqxmd.com/read/28875490/immune-cell-metabolism-in-tumor-microenvironment
#19
Yongsheng Li, Yisong Y Wan, Bo Zhu
Tumor microenvironment (TME) is composed of tumor cells, immune cells, cytokines, extracellular matrix, etc. The immune system and the metabolisms of glucose, lipids, amino acids, and nucleotides are integrated in the tumorigenesis and development. Cancer cells and immune cells show metabolic reprogramming in the TME, which intimately links immune cell functions and edits tumor immunology. Recent findings in immune cell metabolism hold the promising possibilities toward clinical therapeutics for treating cancer...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28873470/comparative-genomics-and-phylogenomic-analyses-of-lysine-riboswitch-distributions-in-bacteria
#20
Sumit Mukherjee, Danny Barash, Supratim Sengupta
Riboswitches are cis-regulatory elements that regulate the expression of genes involved in biosynthesis or transport of a ligand that binds to them. Among the nearly 40 classes of riboswitches discovered so far, three are known to regulate the concentration of biologically encoded amino acids glycine, lysine, and glutamine. While some comparative genomics studies of riboswitches focusing on their gross distribution across different bacterial taxa have been carried out recently, systematic functional annotation and analysis of lysine riboswitches and the genes they regulate are still lacking...
2017: PloS One
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