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Amino Acid Therapy

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https://www.readbyqxmd.com/read/28819028/padi2-mediated-citrullination-promotes-prostate-cancer-progression
#1
Lin Wang, Guanhua Song, Xiang Zhang, Tingting Feng, Jihong Pan, Weiwen Chen, Muyi Yang, Xinnuo Bai, Yu Pang, Jindan Yu, Jinxiang Han, Bo Han
Onset of castration-resistance prostate cancer (CRPC) after long-term androgen-deprivation therapy remains a major obstacle in the treatment of prostate cancer (PCa). The peptidylarginine deiminase PADI2 has been implicated in chronic inflammatory diseases and cancer. Here we show that PADI2 is an androgen-repressed gene and is upregulated in CRPC. PADI2 expression was required for survival and cell cycle progression of PCa cells, and PADI2 promoted proliferation of PCa cells under androgen-deprived or castration conditions in vitro and in vivo...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28814513/escape-of-tick-borne-flavivirus-from-2-c-methylated-nucleoside-antivirals-is-mediated-by-a-single-conservative-mutation-in-ns5-that-has-a-dramatic-effect-on-viral-fitness
#2
Ludek Eyer, Hirofumi Kondo, Darina Zouharova, Minato Hirano, James J Valdés, Memi Muto, Tomas Kastl, Shintaro Kobayashi, Jan Haviernik, Manabu Igarashi, Hiroaki Kariwa, Marketa Vaculovicova, Jiri Cerny, Rene Kizek, Andrea Kröger, Stefan Lienenklaus, Milan Dejmek, Radim Nencka, Martin Palus, Jiri Salat, Erik De Clercq, Kentaro Yoshii, Daniel Ruzek
Tick-borne encephalitis virus (TBEV) causes a severe and potentially fatal neuroinfection in humans. Despite its high medical relevance, no specific antiviral therapy is currently available. Here we demonstrate that treatment with a nucleoside analog, 7-deaza-2' -C-methyladenosine (7-deaza-2' -CMA), substantially improved disease outcome, increased survival, and reduced signs of neuroinfection and viral titers in the brains of mice infected with a lethal dose of TBEV. To investigate the mechanism of action of 7-deaza-2' -CMA, two drug-resistant TBEV clones were generated and characterized...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28813452/plasma-metabolomics-reveals-membrane-lipids-aspartate-asparagine-and-nucleotide-metabolism-pathway-differences-associated-with-chloroquine-resistance-in-plasmodium-vivax-malaria
#3
Karan Uppal, Jorge L Salinas, Wuelton M Monteiro, Fernando Val, Regina J Cordy, Ken Liu, Gisely C Melo, Andre M Siqueira, Belisa Magalhaes, Mary R Galinski, Marcus V G Lacerda, Dean P Jones
BACKGROUND: Chloroquine (CQ) is the main anti-schizontocidal drug used in the treatment of uncomplicated malaria caused by Plasmodium vivax. Chloroquine resistant P. vivax (PvCR) malaria in the Western Pacific region, Asia and in the Americas indicates a need for biomarkers of resistance to improve therapy and enhance understanding of the mechanisms associated with PvCR. In this study, we compared plasma metabolic profiles of P. vivax malaria patients with PvCR and chloroquine sensitive parasites before treatment to identify potential molecular markers of chloroquine resistance...
2017: PloS One
https://www.readbyqxmd.com/read/28811315/quantitative-whole-genome-sequencing-of-circulating-tumor-cells-enables-personalized-combination-therapy-of-metastatic-cancer
#4
Natali Gulbahce, Mark Jesus M Magbanua, Robert Chin, Misha R Agarwal, Xuhao Luo, Jia Liu, Daniel M Hayden, Qing Mao, Serban Ciotlos, Zhenyu Li, Yanxiang Chen, Xingpeng Chen, Yuxiang Li, Rebecca Yu Zhang, Katharine Lee, Rick Tearle, Emily Park, Snezana Drmanac, Hope S Rugo, John W Park, Radoje Drmanac, Brock A Peters
Much effort has been dedicated to developing circulating tumor cells (CTC) as a noninvasive cancer biopsy, but with limited success as yet. In this study, we combine a method for isolation of highly pure CTCs using immunomagnetic enrichment/fluorescence-activated cell sorting with advanced whole genome sequencing (WGS), based on long fragment read technology, to illustrate the utility of an accurate, comprehensive, phased, and quantitative genomic analysis platform for CTCs. Whole genomes of 34 CTCs from a patient with metastatic breast cancer were analyzed as 3,072 barcoded subgenomic compartments of long DNA...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28810879/quantification-of-mutant-spop-proteins-in-prostate-cancer-using-mass-spectrometry-based-targeted-proteomics
#5
Hui Wang, Christopher E Barbieri, Jintang He, Yuqian Gao, Tujin Shi, Chaochao Wu, Athena A Schepmoes, Thomas L Fillmore, Sung-Suk Chae, Dennis Huang, Juan Miguel Mosquera, Wei-Jun Qian, Richard D Smith, Sudhir Srivastava, Jacob Kagan, David G Camp, Karin D Rodland, Mark A Rubin, Tao Liu
BACKGROUND: Speckle-type POZ protein (SPOP) is an E3 ubiquitin ligase adaptor protein that functions as a potential tumor suppressor, and SPOP mutations have been identified in ~10% of human prostate cancers. However, it remains unclear if mutant SPOP proteins can be utilized as biomarkers for early detection, diagnosis, prognosis or targeted therapy of prostate cancer. Moreover, the SPOP mutation sites are distributed in a relatively short region with multiple lysine residues, posing significant challenges for bottom-up proteomics analysis of the SPOP mutations...
August 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28807514/highly-selective-activation-of-heat-shock-protein-70-by-allosteric-regulation-provides-an-insight-into-efficient-neuroinflammation-inhibition
#6
Li-Chao Wang, Li-Xi Liao, Hai-Ning Lv, Dan Liu, Wei Dong, Jian Zhu, Jin-Feng Chen, Meng-Ling Shi, Ge Fu, Xiao-Min Song, Yong Jiang, Ke-Wu Zeng, Peng-Fei Tu
Heat shock protein 70 (Hsp70) is widely involved in immune disorders, making it as an attractive drug target for inflammation diseases. Nonselective induction of Hsp70 upregulation for inflammation therapy could cause extensive interference in inflammation-unrelated protein functions, potentially resulting in side effects. Nevertheless, direct pharmacological activation of Hsp70 via targeting specific functional amino acid residue may provide an insight into precise Hsp70 function regulation and a more satisfactory treatment effect for inflammation, which has not been extensively focused...
August 9, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28803916/mitigating-ischemic-injury-of-stem-cell-derived-insulin-producing-cells-after-transplant
#7
Gaetano Faleo, Holger A Russ, Steven Wisel, Audrey V Parent, Vinh Nguyen, Gopika G Nair, Jonathan E Freise, Karina E Villanueva, Gregory L Szot, Matthias Hebrok, Qizhi Tang
The advent of large-scale in vitro differentiation of human stem cell-derived insulin-producing cells (SCIPC) has brought us closer to treating diabetes using stem cell technology. However, decades of experiences from islet transplantation show that ischemia-induced islet cell death after transplant severely limits the efficacy of the therapy. It is unclear to what extent human SCIPC are susceptible to ischemia. In this study, we show that more than half of SCIPC die shortly after transplantation. Nutrient deprivation and hypoxia acted synergistically to kill SCIPC in vitro...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28796151/potential-development-of-tumor-targeted-oral-anti-cancer-prodrugs-amino-acid-and-dipeptide-monoester-prodrugs-of-gemcitabine
#8
Yasuhiro Tsume, Adam J Drelich, David E Smith, Gordon L Amidon
One of the main obstacles for cancer therapies is to deliver medicines effectively to target sites. Since stroma cells are developed around tumors, chemotherapeutic agents have to go through stroma cells in order to reach tumors. As a method to improve drug delivery to the tumor site, a prodrug approach for gemcitabine was adopted. Amino acid and dipeptide monoester prodrugs of gemcitabine were synthesized and their chemical stability in buffers, resistance to thymidine phosphorylase and cytidine deaminase, antiproliferative activity, and uptake/permeability in HFF cells as a surrogate to stroma cells were determined and compared to their parent drug, gemcitabine...
August 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28792540/antibiotics-resistance-in-el-tor-vibrio-cholerae-01-isolated-during-cholera-outbreaks-in-mozambique-from-2012-to-2015
#9
Liliana Candida Dengo-Baloi, Cynthia Amino Semá-Baltazar, Lena Vania Manhique, Jucunu Elias Chitio, Dorteia Luísa Inguane, José Paulo Langa
RATIONALE: Mozambique has recorded cyclically epidemic outbreaks of cholera. Antibiotic therapy is recommended in specific situations for management and control of cholera outbreaks. However, an increase in resistance rates to antibiotics by Vibrio cholerae has been reported in several epidemic outbreaks worldwide. On the other hand, there are few recent records of continuous surveillance of antibiotics susceptibility pattern of V. cholerae in Mozambique. GOALS: The purpose of this study was to evaluate antibiotics resistance pattern of Vibrio cholerae O1 Ogawa isolated during Cholera outbreaks in Mozambique to commonly used antibiotics...
2017: PloS One
https://www.readbyqxmd.com/read/28782844/long-term-management-with-adipose-tissue-derived-mesenchymal-stem-cells-and-conventional-treatment-in-a-dog-with-hepatocutaneous-syndrome
#10
A Nam, S-M Han, D-M Go, D-Y Kim, K-W Seo, H-Y Youn
Hepatocutaneous syndrome (HS) is an uncommon skin disorder that occurs in conjunction with liver disease and is diagnosed based on decreased plasma concentrations of amino acids and the histopathology of skin lesions. The survival period generally is <6 months. A 10-year-old castrated male Maltese dog was presented for evaluation of lethargy, polyuria, polydipsia, and skin lesions including alopecia, erythema, and crusts. Based on increased liver enzyme activity, low plasma amino acid concentrations, and findings from liver cytology and skin biopsy, the dog was diagnosed with HS...
August 7, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28780668/new-anabolic-therapies-for-osteoporosis
#11
REVIEW
Salvatore Minisola, Cristiana Cipriani, Marco Occhiuto, Jessica Pepe
Osteoporosis is characterized by low bone mass and qualitative structural abnormalities of bone tissue, leading to increased bone fragility that results in fractures. Pharmacological therapy is aimed at decreasing the risk of fracture, mainly correcting the imbalance between bone resorption and formation at the level of bone remodeling units. Anabolic therapy has the capability to increase bone mass to a greater extent than traditional antiresorptive agents. The only currently available drug licensed is parathyroid hormone 1-34 (teriparatide); new drugs are on the horizon, targeting the stimulation of bone formation, and therefore improving bone mass, structure and ultimately skeletal strength...
August 5, 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/28779878/adult-classical-homocystinuria-requiring-parenteral-nutrition-pitfalls-and-management
#12
REVIEW
Christel Tran, Luisa Bonafé, Jean-Marc Nuoffer, Julie Rieger, Mette M Berger
BACKGROUND: Homocystinuria due to cystathionine beta synthase (CBS) deficiency presents with a wide clinical spectrum. Treatment by the enteral route aims at reducing homocysteine levels by using vitamin B6, possibly methionine-restricted diet, betaine and/or folate and vitamin B12 supplementation. Currently no nutritional guidelines exist regarding parenteral nutrition (PN) under acute conditions. METHODS: Exhaustive literature search was performed, in order to identify the relevant studies describing the pathogenesis and nutritional intervention of adult classical homocystinuria requiring PN...
July 25, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28774709/treatment-with-antioxidants-ameliorates-oxidative-damage-in-a-mouse-model-of-propionic-acidemia
#13
Ana Rivera-Barahona, Esmeralda Alonso-Barroso, Belén Pérez, Michael P Murphy, Eva Richard, Lourdes R Desviat
Oxidative stress contributes to the pathogenesis of propionic acidemia (PA), a life threatening disease caused by the deficiency of propionyl CoA-carboxylase, in the catabolic pathway of branched-chain amino acids, odd-number chain fatty acids and cholesterol. Patients develop multisystemic complications including seizures, extrapyramidal symptoms, basal ganglia deterioration, pancreatitis and cardiomyopathy. The accumulation of toxic metabolites results in mitochondrial dysfunction, increased reactive oxygen species and oxidative damage, all of which have been documented in patients' samples and in a hypomorphic mouse model...
July 25, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28769581/clinical-utility-of-nitisinone-for-the-treatment-of-hereditary-tyrosinemia-type-1-ht-1
#14
REVIEW
Anibh Martin Das
Medical therapy for hereditary hepatorenal tyrosinemia (hereditary tyrosinemia type 1, HT-1) with nitisinone was discovered incidentally, and is a by-product of agrochemistry. It blocks the catabolic pathway of tyrosine, thereby leading to a reduction in the accumulation of toxic metabolites in HT-1. It has to be combined with a low-protein diet supplemented with amino acid mixtures devoid of tyrosine and phenylalanine. This treatment option has completely changed the clinical course of patients suffering from HT-1 who used to die in the first few months to years of life from liver failure, renal dysfunction, and/or hepatocellular carcinoma (HCC)...
2017: Application of Clinical Genetics
https://www.readbyqxmd.com/read/28769554/the-modulation-of-enzyme-indoleamine-2-3-dioxygenase-from-dendritic-cells-for-the-treatment-of-type-1-diabetes-mellitus
#15
REVIEW
Débora Moitinho Abram, Luis Gustavo Romani Fernandes, Antônio Celso Saragossa Ramos Filho, Patrícia Ucelli Simioni
Diabetes mellitus type 1 (DM1) is an autoimmune disease in which β-cells of the pancreas islet are destroyed by T lymphocytes. Specific T cells are activated by antigen-presenting cells, mainly dendritic cells (DCs). It is already known that the regulation of tryptophan pathway in DC can be a mechanism of immunomodulation. The enzyme indoleamine 2,3-dioxygenase (IDO) is present in many cells, including DC, and participates in the metabolism of the amino acid tryptophan. Recent studies suggest the involvement of IDO in the modulation of immune response, which became more evident after the in vitro demonstration of IDO production by DC and of the ability of these cells to inhibit lymphocyte function through the control of tryptophan metabolism...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28767081/new-insights-in-the-design-of-bioactive-peptides-and-chelating-agents-for-imaging-and-therapy-in-oncology
#16
REVIEW
Anna Lucia Tornesello, Luigi Buonaguro, Maria Lina Tornesello, Franco Maria Buonaguro
Many synthetic peptides have been developed for diagnosis and therapy of human cancers based on their ability to target specific receptors on cancer cell surface or to penetrate the cell membrane. Chemical modifications of amino acid chains have significantly improved the biological activity, the stability and efficacy of peptide analogues currently employed as anticancer drugs or as molecular imaging tracers. The stability of somatostatin, integrins and bombesin analogues in the human body have been significantly increased by cyclization and/or insertion of non-natural amino acids in the peptide sequences...
August 2, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28760902/mycobacterium-abscessus-l-d-transpeptidases-are-susceptible-to-inactivation-by-carbapenems-and-cephalosporins-but-not-penicillins
#17
Pankaj Kumar, Varsha Chauhan, José Rogério A Silva, Jerônimo Lameira, Felipe d'Andrea, Shaogang Li, Stephan L Ginell, Joel S Freundlich, Cláudio Nahum Alves, Scott Bailey, Keira A Cohen, Gyanu Lamichhane
As a growing number of clinical isolates of Mycobacterium abscessus are resistant to most antibiotics, new treatment options that are effective against these drug-resistant strains are desperately needed. The majority of the linkages in the cell wall peptidoglycan of M. abscessus are synthesized by non-classical transpeptidases, namely the L,D-transpeptidases. Emerging evidence suggests that these enzymes represent a new molecular vulnerability in this pathogen. Recent studies have demonstrated that inhibition of these enzymes by the carbapenem class of β-lactams determines their activity against M...
July 31, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28759215/discovery-of-a-para-acetoxy-benzyl-ester-prodrug-of-a-hydroxamate-based-glutamate-carboxypeptidase-ii-inhibitor-as-oral-therapy-for-neuropathic-pain
#18
Rana Rais, Jan Vávra, Tomáš Tichý, Ranjeet P Dash, Alexandra J Gadiano, Lukas Tenora, Lenka Monincova, Cyril Barinka, Jesse Alt, Sarah C Zimmermann, C Ethan Slusher, Ying Wu, Krystyna Wozniak, Pavel Majer, Takashi Tsukamoto, Barbara S Slusher
4-Carboxy-α-[3-(hydroxyamino)-3-oxopropyl]-benzenepropanoic acid 1 is a potent hydroxamate-based inhibitor of glutamate carboxypeptidase II. In attempt to improve its poor oral pharmacokinetics, we synthesized a series of prodrugs by masking its hydrophilic hydroxamate group. Prodrugs were evaluated for oral availability in mice and showed varying degree of plasma exposure to 1. Of these, para-acetoxybenzyl-based, 4-(5-(((4-acetoxybenzyl)oxy)amino)-2-carboxy-5-oxopentyl)benzoic acid, 12, provided 5-fold higher plasma levels of 1 compared to oral administration of 1 itself...
July 31, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28756217/maternal-insulin-therapy-does-not-restore-foetoplacental-endothelial-dysfunction-in-gestational-diabetes-mellitus
#19
Mario Subiabre, Luis Silva, Roberto Villalobos-Labra, Fernando Toledo, Mario Paublo, Marcia A López, Rocío Salsoso, Fabián Pardo, Andrea Leiva, Luis Sobrevia
Pregnant women diagnosed with gestational diabetes mellitus subjected to diet (GDMd) that do not reach normal glycaemia are passed to insulin therapy (GDMi). GDMd associates with increased human cationic amino acid transporter 1 (hCAT-1)-mediated transport of L-arginine and nitric oxide synthase (NOS) activity in foetoplacental vasculature, a phenomenon reversed by exogenous insulin. Whether insulin therapy results in reversal of the GDMd effect on the foetoplacental vasculature is unknown. We assayed whether insulin therapy normalizes GDMd-associated foetoplacental endothelial dysfunction...
July 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28755525/a-distinct-serum-metabolic-signature-of-distant-metastatic-papillary-thyroid-carcinoma
#20
Chen-Tian Shen, Yinan Zhang, Yu-Min Liu, Shan Yin, Xin-Yun Zhang, Wei-Jun Wei, Zhen-Kui Sun, Hong-Jun Song, Zhong-Ling Qiu, Cong-Rong Wang, Quan-Yong Luo
BACKGROUND: Although the incidence rate for thyroid cancer seems to have begun stabilizing in recent years, an increased rate of advanced stage of this disease has been reported. Additionally, distant metastasis is one of the most important prognostic factors of patients with papillary thyroid carcinoma (PTC). Unfortunately, the underlying mechanisms of distant metastasis as well as cell status like metabolism changes in distant metastatic tumors have not been clearly elucidated. OBJECTIVE: To identify serum metabolic signature of distant metastatic PTC...
July 29, 2017: Clinical Endocrinology
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