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https://www.readbyqxmd.com/read/28454429/polyphenolic-compounds-from-korean-lonicera-japonica-thunb-induces-apoptosis-via-akt-and-caspase-cascade-activation-in-a549-cells
#1
Kwang Il Park, Hyeonsoo Park, Arulkumar Nagappan, Gyeong Eun Hong, Silvia Yumnam, Ho Jeong Lee, Eun Hee Kim, Won Sup Lee, Sung Chul Shin, Jin A Kim, Sang Joon Lee, Jin Yeul Ma, Taesun Min, Jeong Doo Heo, Gon Sup Kim
Lonicera japonica Thunb. (L. japonica T.) has historically been used in Korean herbal medicine due to its anticancer and protective effects on the respiratory system. In the present study, the polyphenolic compounds in L. japonica T. were investigated using high-performance liquid chromatography coupled with tandem mass spectrometry, and its anticancer effects on A549 non-small-cell lung cancer cells were studied. Polyphenolic compounds potentially inhibit A549 cells in a dose-dependent manner. Flow cytometry and western blot analysis demonstrated that polyphenolic compounds induce apoptosis by regulating the protein expression levels of caspases, poly-(ADP-ribose) polymerase and the B-cell lymphoma-2-associated X-protein/B-cell lymphoma-extra large ratio...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454271/intracellular-and-extracellular-factors-influencing-the-genotoxicity-of-nitric-oxide-and-reactive-oxygen-species
#2
Min Young Kim
A number of factors affect cellular responses to nitric oxide (NO(•)) and reactive oxygen species (ROS), including their source, concentration, cumulative dose, target gene and biological milieu. This limits the extrapolation of data to in vivo pathological states in which NO(•) and ROS may be important. The present study investigated lethality and mutagenesis in the HPRT and TK1 genes of human lymphoblastoid TK6 cells exposed to NO(•) and ROS derived from two delivery methods: A reactor system and a Transwell™ co-culture...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453984/functional-and-genetic-evidence-that-nucleoside-transport-is-highly-conserved-in-leishmania-species-implications-for-pyrimidine-based-chemotherapy
#3
Khalid J H Alzahrani, Juma A M Ali, Anthonius A Eze, Wan Limm Looi, Daniel N A Tagoe, Darren J Creek, Michael P Barrett, Harry P de Koning
Leishmania pyrimidine salvage is replete with opportunities for therapeutic intervention with enzyme inhibitors or antimetabolites. Their uptake into cells depends upon specific transporters; therefore it is essential to establish whether various Leishmania species possess similar pyrimidine transporters capable of drug uptake. Here, we report a comprehensive characterization of pyrimidine transport in L. major and L. mexicana. In both species, two transporters for uridine/adenosine were detected, one of which also transported uracil and the antimetabolites 5-fluoruracil (5-FU) and 5F,2'deoxyuridine (5F,2'dUrd), and was designated uridine-uracil transporter 1 (UUT1); the other transporter mediated uptake of adenosine, uridine, 5F,2'dUrd and thymidine and was designated Nucleoside Transporter 1 (NT1)...
April 20, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28453865/saliva-and-plasma-levels-of-cardiac-related-biomarkers-in-post-myocardial-infarction-patients
#4
N Rathnayake, K Buhlin, B Kjellström, B Klinge, C Löwbeer, A Norhammar, L Rydén, T Sorsa, T Tervahartiala, A Gustafsson
AIM: To relate cardiac biomarkers, such as Cystatin C and Growth differentiation factor-15 (GDF-15) in saliva to myocardial infarction (MI) and to periodontal status, and to investigate the relation between salivary and plasma cardiac biomarkers. MATERIALS AND METHODS: 200 patients with MI admitted to coronary care units and 200 matched controls without MI were included. Dental examination and collection of blood and saliva samples was performed 6-10 weeks after the MI for patients and in close proximity thereafter for controls...
April 28, 2017: Journal of Clinical Periodontology
https://www.readbyqxmd.com/read/28453847/human-immunodeficiency-virus-persistence-and-t-cell-activation-in-blood-rectal-and-lymph-node-tissue-in-human-immunodeficiency-virus-infected-individuals-receiving-suppressive-antiretroviral-therapy
#5
Gabriela Khoury, Rémi Fromentin, Ajantha Solomon, Wendy Hartogensis, Marisela Killian, Rebecca Hoh, Ma Somsouk, Peter W Hunt, Valerie Girling, Elizabeth Sinclair, Peter Bacchetti, Jenny L Anderson, Frederick M Hecht, Steven G Deeks, Paul U Cameron, Nicolas Chomont, Sharon R Lewin
Background.: Immune activation and inflammation remain elevated in human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART) and may contribute to HIV persistence. Methods.: Using flow cytometry expression of CD38, HLA-DR and PD-1 were measured in blood (n = 48), lymph node (LN; n = 9), and rectal tissue (n = 17) from virally suppressed individuals. Total and integrated HIV DNA, 2-LTR circles, and cell-associated unspliced HIV RNA were quantified...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28453702/a-phase-2-randomized-double-blind-placebo-%C3%A2-controlled-study-of-chemo-immunotherapy-combination-using-motolimod-with-pegylated-liposomal-doxorubicin-in-recurrent-or-persistent-ovarian-cancer-a-gynecologic-oncology-group-partners-study
#6
B J Monk, M F Brady, C Aghajanian, H A Lankes, T Rizack, J Leach, J M Fowler, R Higgins, P Hanjani, M Morgan, R Edwards, W Bradley, T Kolevska, P Foukas, E M Swisher, K S Anderson, R Gottardo, J K Bryan, M Newkirk, K L Manjarrez, R S Mannel, R M Hershberg, G Coukos
Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28449351/long-term-plasticity-of-corticostriatal-synapses-is-modulated-by-pathway-specific-co-release-of-opioids-through-kappa-opioid-receptors
#7
Sarah L Hawes, Armando G Salinas, David M Lovinger, Kim T Blackwell
Synaptic plasticity in striatum adjusts behaviour adaptively during skill learning, or maladaptively in the case of addiction. Just as dopamine plays a critical role in synaptic plasticity underlying normal skill learning and addiction, endogenous and exogenous opiates also modulate learning and addiction-related striatal plasticity. Though the role of opioid receptors in long-term depression in striatum has been characterized, their effect on long-term potentiation (LTP) remains unknown. In particular, direct pathway (Dopamine D1 Receptor containing; D1R) - spiny projection neurons (SPNs) co-release the opioid neuropeptide dynorphin, which acts at presynaptic kappa opioid receptors (KORs) on dopaminergic afferents and can negatively regulate dopamine release...
April 27, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28448610/characterization-and-expression-analysis-of-galnts-in-developing-strongylocentrotus-purpuratus-embryos
#8
Amber L Famiglietti, Zheng Wei, Thomas M Beres, Adina L Milac, Duy T Tran, Divya Patel, Robert C Angerer, Lynne M Angerer, Lawrence A Tabak
Mucin-type O-glycosylation is a ubiquitous posttranslational modification in which N-Acetylgalactosamine (GalNAc) is added to the hydroxyl group of select serine or threonine residues of a protein by the family of UDP-GalNAc:Polypeptide N-Acetylgalactosaminyltransferases (GalNAc-Ts; EC 2.4.1.41). Previous studies demonstrate that O-glycosylation plays essential roles in protein function, cell-cell interactions, cell polarity and differentiation in developing mouse and Drosophila embryos. Although this type of protein modification is highly conserved among higher eukaryotes, little is known about this family of enzymes in echinoderms, basal deuterostome relatives of the chordates...
2017: PloS One
https://www.readbyqxmd.com/read/28448568/inhibitory-effects-of-fenretinide-metabolites-n-4-methoxyphenyl-retinamide-mpr-and-4-oxo-n-4-hydroxyphenyl-retinamide-3-keto-hpr-on-fenretinide-molecular-targets-%C3%AE-carotene-oxygenase-1-stearoyl-coa-desaturase-1-and-dihydroceramide-%C3%AE-4-desaturase-1
#9
Eugenia Poliakov, William Samuel, Todd Duncan, Danielle B Gutierrez, Nathan L Mata, T Michael Redmond
The therapeutic capacity of fenretinide (N-[4-hydroxyphenyl] retinamide; 4-HPR) has been demonstrated for several conditions, including cancer, obesity, diabetes, and ocular disease. Yet, the mechanisms of action for its pleiotropic effects are still undefined. We hypothesized that investigation of two of the major physiological metabolites of fenretinide, N-[4-methoxyphenyl]retinamide (MPR) and 4-oxo-N-(4-hydroxyphenyl)retinamide (3-keto-HPR), might begin to resolve the multifaceted effects of this synthetic retinoid...
2017: PloS One
https://www.readbyqxmd.com/read/28448566/il-33-st2-pathway-drives-regulatory-t-cell-dependent-suppression-of-liver-damage-upon-cytomegalovirus-infection
#10
Branka Popovic, Mijo Golemac, Jürgen Podlech, Jelena Zeleznjak, Lidija Bilic-Zulle, Miodrag L Lukic, Luka Cicin-Sain, Matthias J Reddehase, Tim Sparwasser, Astrid Krmpotic, Stipan Jonjic
Regulatory T (Treg) cells dampen an exaggerated immune response to viral infections in order to avoid immunopathology. Cytomegaloviruses (CMVs) are herpesviruses usually causing asymptomatic infection in immunocompetent hosts and induce strong cellular immunity which provides protection against CMV disease. It remains unclear how these persistent viruses manage to avoid induction of immunopathology not only during the acute infection but also during life-long persistence and virus reactivation. This may be due to numerous viral immunoevasion strategies used to specifically modulate immune responses but also induction of Treg cells by CMV infection...
April 27, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28448252/hypothyroidism-in-carcinoma-of-the-tongue-with-adjuvant-treatment
#11
Sabita Kumari, Jonathan Gondi, Hemantkumar Nemade, L M Chandra Sekhara Rao, Deleep Gudipudi, T Subramanyeshwar Rao
OBJECTIVE: The objective of this study was to evaluate the incidence of hypothyroidism with adjuvant treatment in oral tongue carcinoma patients treated primarily with surgery. MATERIALS AND METHODS: A retrospective review was carried out to analyze hypothyroidism incidence and its relation to adjuvant treatment (radiation/radio-chemotherapy) in oral tongue carcinoma after the primary surgical ablation and neck dissection. Hypothyroidism was analyzed in relation with dose of radiation, gender, and adjuvant treatment modality...
March 29, 2017: Rambam Maimonides Medical Journal
https://www.readbyqxmd.com/read/28448128/total-chemical-synthesis-and-folding-of-all-l-and-all-d-variants-of-oncogenic-kras-g12v
#12
Adam Marc Levinson, John H McGee, Andrew G Roberts, Gardner Creech, Ting Wang, Michael T Peterson, Ronald C Hendrickson, Gregory L Verdine, Samuel J Danishefsky
The Ras proteins are essential GTPases involved in the regulation of cell proliferation and survival. Mutated oncogenic forms of Ras alter effector binding and innate GTPase activity, leading to deregulation of downstream signal transduction. Mutated forms of Ras are involved in approximately 30% of human cancers. Despite decades of effort to develop direct Ras inhibitors, Ras has long been considered 'undruggable' due to its high affinity for GTP and its lack of hydrophobic binding pockets. Herein, we report a total chemical synthesis of all-L- and all-D-amino acid biotinylated variants of oncogenic mutant KRas(G12V)...
April 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28448082/effects-of-gender-and-age-on-immune-responses-of-human-peripheral-blood-mononuclear-cells-to-probiotics-a-large-scale-pilot-study
#13
Y-H Ho, Y-T Huang, Y-C Lu, S-Y Lee, M-F Tsai, S-P Hung, T-Y Hsu
BACKGROUND: Despite the widely accepted concept that probiotics confer miscellaneous benefits to hosts, the controversies surrounding these health-promoting claims cannot be ignored. These controversies hinder development and innovation in this field. RESULTS: To clarify the effects of age and gender on probiotic-induced immune responses, we recruited 1613 Taiwanese individuals and calculated the ratio of IFN-γ to IL-10 production after each individual's PBMCs were stimulated by six probiotic strains (L...
2017: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/28447602/spatial-computation-of-intratumoral-t-cells-correlates-with-survival-of-patients-with-pancreatic-cancer
#14
Julienne L Carstens, Pedro Correa de Sampaio, Dalu Yang, Souptik Barua, Huamin Wang, Arvind Rao, James P Allison, Valerie S LeBleu, Raghu Kalluri
The exact nature and dynamics of pancreatic ductal adenocarcinoma (PDAC) immune composition remains largely unknown. Desmoplasia is suggested to polarize PDAC immunity. Therefore, a comprehensive evaluation of the composition and distribution of desmoplastic elements and T-cell infiltration is necessary to delineate their roles. Here we develop a novel computational imaging technology for the simultaneous evaluation of eight distinct markers, allowing for spatial analysis of distinct populations within the same section...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28447399/genome-wide-association-study-of-hiv-associated-neurocognitive-disorder-hand-a-charter-group-study
#15
Peilin Jia, Zhongming Zhao, Todd Hulgan, William S Bush, David C Samuels, Cinnamon S Bloss, Robert K Heaton, Ronald J Ellis, Nicholas Schork, Christina M Marra, Ann C Collier, David B Clifford, Benjamin B Gelman, Ned Sacktor, Susan Morgello, David M Simpson, J Allen McCutchan, Jill S Barnholtz-Sloan, Donald R Franklin, Debralee Rosario, Scott L Letendre, Igor Grant, Asha R Kallianpur
HIV-associated neurocognitive disorder (HAND) often complicates HIV infection despite combination antiretroviral therapy (ART) and may be influenced by host genomics. We performed a genome-wide association study (GWAS) of HAND in 1,050 CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) Study participants. All participants underwent standardized, comprehensive neurocognitive, and neuromedical assessments to determine if they had cognitive impairment as assessed by the Global Deficit Score (GDS), and individuals with comorbidities that could confound diagnosis of HAND were excluded...
April 26, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28447072/a-randomized-trial-of-the-effects-of-the-no-carrageenan-diet-on-ulcerative-colitis-disease-activity
#16
Sumit Bhattacharyya, Theresa Shumard, Hui Xie, Amar Dodda, Krista A Varady, Leo Feferman, Allan G Halline, Jay L Goldstein, Stephen B Hanauer, Joanne K Tobacman
BACKGROUND: Carrageenan is a very common food additive in Western diets, but predictably causes inflammation in thousands of cell-based and animal experiments. OBJECTIVE: To assess the impact of carrageenan exposure on the interval to relapse in patients with ulcerative colitis in remission. METHODS: A randomized, double-blind, placebo-controlled, multicenter, clinical trial was conducted to assess if patients with ulcerative colitis in remission would have a longer interval to relapse if they followed a diet with no carrageenan...
March 31, 2017: Nutrition and Healthy Aging
https://www.readbyqxmd.com/read/28446880/shifts-in-the-gut-microbiota-composition-due-to-depleted-bone-marrow-beta-adrenergic-signaling-are-associated-with-suppressed-inflammatory-transcriptional-networks-in-the-mouse-colon
#17
Tao Yang, Niousha Ahmari, Jordan T Schmidt, Ty Redler, Rebeca Arocha, Kevin Pacholec, Kacy L Magee, Wendi Malphurs, Jennifer L Owen, Gregory A Krane, Eric Li, Gary P Wang, Thomas W Vickroy, Mohan K Raizada, Christopher J Martyniuk, Jasenka Zubcevic
The brain-gut axis plays a critical role in the regulation of different diseases, many of which are characterized by sympathetic dysregulation. However, a direct link between sympathetic dysregulation and gut dysbiosis remains to be illustrated. Bone marrow (BM)-derived immune cells continuously interact with the gut microbiota to maintain homeostasis in the host. Their function is largely dependent upon the sympathetic nervous system acting via adrenergic receptors present on the BM immune cells. In this study, we utilized a novel chimera mouse that lacks the expression of BM beta1/2 adrenergic receptors (b1/2-ARs) to investigate the role of the sympathetic drive to the BM in gut and microbiota homeostasis...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28446731/the-antigenic-identity-of-human-class-i-mhc-phosphopeptides-is-critically-dependent-upon-phosphorylation-status
#18
Fiyaz Mohammed, Daniel H Stones, Angela L Zarling, Carrie R Willcox, Jeffrey Shabanowitz, Kara L Cummings, Donald F Hunt, Mark Cobbold, Victor H Engelhard, Benjamin E Willcox
Dysregulated post-translational modification provides a source of altered self-antigens that can stimulate immune responses in autoimmunity, inflammation, and cancer. In recent years, phosphorylated peptides have emerged as a group of tumour-associated antigens presented by MHC molecules and recognised by T cells, and represent promising candidates for cancer immunotherapy. However, the impact of phosphorylation on the antigenic identity of phosphopeptide epitopes is unclear. Here we examined this by determining structures of MHC-bound phosphopeptides bearing canonical position 4-phosphorylations in the presence and absence of their phosphate moiety, and examining phosphopeptide recognition by the T cell receptor (TCR)...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28446667/disparate-contributions-of-human-retrovirus-capsid-subdomains-to-gag-gag-oligomerization-virus-morphology-and-particle-biogenesis
#19
Jessica L Martin, Luiza Mendonça, Isaac Angert, Joachim D Mueller, Wei Zhang, Louis M Mansky
The capsid domain (CA) of the retroviral Gag protein is a primary determinant of Gag oligomerization, which is a critical step for immature Gag lattice formation and virus particle budding. Although the human immunodeficiency virus type 1 (HIV-1) CA carboxy-terminal domain (CTD) is essential for CA-CA interactions, the CA CTD has been suggested to be largely dispensable for human T-cell leukemia virus type 1 (HTLV-1) particle biogenesis. To more clearly define the roles of the HTLV-1 CA amino-terminal domain (NTD) and CA CTD in particle biogenesis, we generated and analyzed a panel of Gag proteins with chimeric HIV-1/HTLV-1 CA domains...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446640/ref-1-ape1-as-transcriptional-regulator-and-novel-therapeutic-target-in-pediatric-t-cell-leukemia
#20
Jixin Ding, Melissa L Fishel, April M Reed, Erin McAdams, Magdalena Czader, Angelo A Cardoso, Mark R Kelley
The increasing characterization of childhood acute lymphoblastic leukemia (ALL) has led to the identification of multiple molecular targets, but have yet to translate into more effective targeted therapies, particularly for high-risk, relapsed T-cell ALL. Searching for master regulators controlling multiple signaling pathways in T-ALL, we investigated the multi-functional protein redox factor-1 (Ref-1/APE1), which acts as a signaling "node" by exerting redox regulatory control of transcription factors important in leukemia...
April 26, 2017: Molecular Cancer Therapeutics
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