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Ayyaraju Middepogu, Jie Hou, Xuan Gao, Daohui Lin
Titanium dioxide nanoparticles (n-TiO2 ) have been used in numerous applications, which results in their release into aquatic ecosystems and impact algal populations. A possible toxic mechanism of n-TiO2 on algae is via the disruption of the photosynthetic biochemical pathways, which yet remains to be demonstrated. In this study, Chlorella pyrenoidosa was exposed to different concentrations (0, 0.1, 1, 5, 10, and 20 mg/L) of a type of anatase n-TiO2 , and the physiological, biochemical, and molecular responses involved in photosynthesis were investigated...
June 14, 2018: Ecotoxicology and Environmental Safety
Andrew J Fisher, Peter A Beal
All messenger RNAs in eukaryotes are modified co-transcriptionally and post-transcriptionally. They are all capped at the 5'-end and polyadenylated at the 3'-end. However, many mRNAs are also found to be chemically modified internally for regulation of mRNA processing, translation, stability, and to recode the message. This review will briefly summarize the structural basis for formation of the two most common modifications found at internal sites in mRNAs; methylation and deamination. The structures of the enzymes that catalyze these modifications show structural similarity to other family members within each modifying enzyme class...
June 15, 2018: Current Opinion in Structural Biology
Elif Bulut, Abdulsamet Erden, Omer Karadag, Kader Karli Oguz, Seza Ozen
PURPOSE: To increase the knowledge of central nervous system (CNS) imaging features in deficiency of adenosine deaminase 2 (DADA2) by examining magnetic resonance imaging (MRI) studies of a relatively large number of patients. METHODS: We retrospectively examined neuroimages of 12 patients (7 male, 5 female) diagnosed with DADA2. The mean age of the patients at the time of initial brain MRI was 16.7±10.2 years. Seven patients (58.3%) fulfilled the classification criteria of polyarteritis nodosa...
June 15, 2018: Journal of Neuroradiology. Journal de Neuroradiologie
Christopher D Lopez, Jonathan M Bekisz, Carmen Corciulo, Aranzazu Mediero, Paulo G Coelho, Lukasz Witek, Roberto L Flores, Bruce N Cronstein
Adenosine receptor activation has been investigated as a potential therapeutic approach to heal bone. Bone has enhanced regenerative potential when influenced by either direct or indirect adenosine receptor agonism. As investigators continue to elucidate how adenosine influences bone cell homeostasis at the cellular and molecular levels, a small but growing body of literature has reported successful in vivo applications of adenosine delivery. This review summarizes the role adenosine receptor ligation plays in osteoblast and osteoclast biology and remodeling/regeneration...
June 15, 2018: Advanced Drug Delivery Reviews
Manuel Soliño, Ester María López, Manuel Rey-Funes, César Fabián Loidl, Ignacio M Larrayoz, Alfredo Martínez, Elena Girardi, Juan José López-Costa
Light induced retinal degeneration (LIRD) is a useful model that resembles human retinal degenerative diseases. The modulation of adenosine A1 receptor is neuroprotective in different models of retinal injury. The aim of this work was to evaluate the potential neuroprotective effect of the modulation of A1 receptor in LIRD. The eyes of rats intravitreally injected with N6-cyclopentyladenosine (CPA), an A1 agonist, which were later subjected to continuous illumination (CI) for 24 h, showed retinas with a lower number of apoptotic nuclei and a decrease of Glial Fibrillary Acidic Protein (GFAP) immunoreactive area than controls...
2018: PloS One
Yu-On Jeong, Soo Jung Shin, Jun Yong Park, Bo Kyeong Ku, Ji Soo Song, Jwa-Jin Kim, Seong Gak Jeon, Sang Min Lee, Minho Moon
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits, neuroinflammation, and neuronal death. The primary pathogenic cause is believed to be the accumulation of pathogenic amyloid beta (Aβ) assemblies in the brain. Ghrelin, which is a peptide hormone predominantly secreted from the stomach, is an endogenous ligand for the growth hormone secretagogue-receptor type 1a (GHS-R1a). MK-0677 is a ghrelin agonist that potently stimulates the GHS-R1a ghrelin receptor...
June 18, 2018: International Journal of Molecular Sciences
Kathleen G Essel, Kathleen N Moore
Niraparib, an orally available selective inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP) is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germline or somatic mutation in the breast cancer gene (BRCA). Overall niraparib is well tolerated and its toxicities, primarily hematologic, are manageable especially with recently released initial dose modification guidelines based on weight and baseline platelet count. The role of niraparib as maintenance following front-line platinum-based chemotherapy as well as in the treatment of recurrent high grade serous ovarian cancer (HGSOC) is an active area of investigation...
June 17, 2018: Expert Review of Anticancer Therapy
Tinne C J Mertens, Ankit Hanmandlu, Ly Tu, Carole Phan, Scott D Collum, Ning-Yuan Chen, Tingting Weng, Jonathan Davies, Chen Liu, Holger K Eltzschig, Soma S K Jyothula, Keshava Rajagopal, Yang Xia, Ashrith Guha, Brian A Bruckner, Michael R Blackburn, Christophe Guignabert, Harry Karmouty-Quintana
Background: Pulmonary hypertension (PH) is a devastating and progressive disease characterized by excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) and remodeling of the lung vasculature. Adenosine signaling through the ADORA2B receptor has previously been implicated in disease progression and tissue remodeling in chronic lung disease. In experimental models of PH associated with chronic lung injury, pharmacological or genetic inhibition of ADORA2B improved markers of chronic lung injury and hallmarks of PH...
2018: Frontiers in Physiology
Laura López-Cruz, John D Salamone, Mercè Correa
Major depressive disorder is one of the most common and debilitating psychiatric disorders. Some of the motivational symptoms of depression, such anergia (lack of self-reported energy) and fatigue are relatively resistant to traditional treatments such as serotonin uptake inhibitors. Thus, new pharmacological targets are being investigated. Epidemiological data suggest that caffeine consumption can have an impact on aspects of depressive symptomatology. Caffeine is a non-selective adenosine antagonist for A1 /A2A receptors, and has been demonstrated to modulate behavior in classical animal models of depression...
2018: Frontiers in Pharmacology
Chang Zhang, Yue Jiang, Jia Liu, Meina Jin, Nan Qin, Ying Chen, Wenyan Niu, Hongquan Duan
Introduction: The Chinese herb Potentilla chinensis can reduce blood glucose level of diabetic mice. Tiliroside is the main effective component, but the detailed mechanism is not clear. Skeletal muscles play an important role in whole body glucose homeostasis. Insulin and exercise/contraction stimulate glucose uptake by muscle cells via redistribution of glucose transporter GLUT4 to the cell surface. Materials and methods: We explored the effects of tiliroside derivatives on cell surface GLUT4 level (GLUT4 translocation) and the underlying mechanism in L6-GLUT4 myc muscle cells...
2018: Drug Design, Development and Therapy
Satyendra Kumar Sonkar, Satish Kumar, Neeraj Kumar Singh
Hypokalemia is a serious and life-threatening clinical condition. We present a case of a 45-year-old male, with known hyperthyroidism presenting with profound tremor, irritability, quadriparesis, and labored breathing since morning, on the day of admission. Arterial blood gas analysis showed severe hypokalemia. Patient's vital was stabilized and patient's oxygen saturation was maintained on oxygen inhalation. Intravenous potassium chloride infusion was administered with regular monitoring of vitals and electrolytes...
May 2018: Indian Journal of Critical Care Medicine
Martin Tresguerres, Cristina Salmerón
The enzyme soluble adenylyl cyclase (sAC) is the most recently identified source of the messenger molecule cyclic adenosine monophosphate. sAC is evolutionarily conserved from cyanobacteria to human, is directly stimulated by [Formula: see text] ions, and can act as a sensor of environmental and metabolic CO2 , pH, and [Formula: see text] levels. sAC genes tend to have multiple alternative promoters, undergo extensive alternative splicing, be translated into low mRNA levels, and the numerous sAC protein isoforms may be present in various subcellular localizations...
2018: Methods in Enzymology
Wadih Ghattas, Virginie Dubosclard, Arne Wick, Audrey Bendelac, Régis Guillot, Rémy Ricoux, Jean-Pierre Mahy
Artificial metalloenzymes are known to be promising tools for biocatalysis, but their recent compartmentalization has led to compatibly with cell components thus shedding light on possible therapeutic applications. We prepared and characterized artificial metalloenzymes based on the A2A adenosine receptor embedded in the cytoplasmic membranes of living human cells. The wild type receptor was chemically engineered into metalloenzymes by its association with strong antagonists that were covalently bound to copper(II) catalysts...
June 18, 2018: Journal of the American Chemical Society
Flavia Varano, Daniela Catarzi, Fabrizio Vincenzi, Matteo Falsini, Silvia Pasquini, Pier Andrea Borea, Vittoria Colotta, Katia Varani
This paper describes the synthesis and characterization of N5 -(hetero)arylalkyl-substituted-thiazolo [5,4-d]pyrimidine-5,7-diamine derivatives (4-19) as novel human (h) A2A adenosine receptor (AR) inverse agonists. Competition binding and cyclic AMP assays indicate that the examined compounds behave as hA2A AR inverse agonists showing binding affinity values in the nanomolar or subnanomolar range. Notably, compounds 4, 5, 6 and 11 showed two affinity values for the hA2A ARs with the highest (KH) falling in the femtomolar range and the lowest (KL) of the nanomolar order...
June 9, 2018: European Journal of Medicinal Chemistry
Amira M Soliman, Ahmed M Fathalla, Ahmed A Moustafa
Although adenosine plays a key role in multiple motor, affective, and cognitive processes, it has received less attention in the neuroscience field compared to other neurotransmitters (e.g., dopamine). In this review, we highlight the role of adenosine in behavior as well as its interaction with other neurotransmitters, such as dopamine. We also discuss brain disorders impacted by alterations to adenosine, and how targeting adenosine can ameliorate Parkinson's disease motor symptoms. We also discuss the role of caffeine (as an adenosine antagonist) on cognition as well as a neuroprotective agent against Parkinson's disease (PD)...
February 3, 2018: Pharmacological Reports: PR
Tian-Sin Fan, Ruey-Meei Wu, Han-I Lin, Chieh Cheng, Chin-Hsien Lin
Mutations in the phosphodiesterase 8B gene (PDE8B) were recently linked to autosomal-dominant striatal degeneration clinically presenting as slowly progressive parkinsonism. PDE8B degrades cyclic adenosine monophosphate (cAMP), a second messenger involved in dopamine signaling. Dopamine deficiency is the pathognomonic feature of Parkinson's disease (PD). Few studies have explored the role of PDE8B in PD. We aim to address the genetic contribution of PDE8B in early-onset and familial PD in a Taiwanese population...
May 26, 2018: Neurobiology of Aging
Paul DiSilvestro, Angeles Alvarez Secord
Approximately 1% of women in the United States will be diagnosed with epithelial ovarian cancer (EOC) during their lifetime. It is most likely to present at a more advanced stage, requiring aggressive therapeutic measures, and most women will succumb to this illness. Due to advancements in therapy, the oncology community has begun to shift its focus to molecular targeted agents, alternative dosing schedules, and maintenance therapy. Women who achieve a response to initial adjuvant chemotherapy may be candidates for maintenance therapy, with the goal of inducing a lasting remission or prolonging the disease-free interval before recurrence...
June 5, 2018: Cancer Treatment Reviews
Anemari Horvat, Nina Vardjan
To maintain a high level of specificity and normal cell function, the cyclic adenosine monophosphate (cAMP) pathway is tightly regulated in space and time. Recent advances in cAMP reporter technology have provided insights into spatial-temporal characteristics of cAMP signalling in individual living cells, including astrocytes. Astrocytes are glial cells in the central nervous system with many homeostatic functions. In contrast to neurons, astrocytes are electrically silent, but, in response to extracellular stimuli through activation of surface receptors, they can increase intracellular levels of secondary messengers, e...
June 13, 2018: Neuroscience Letters
Leifang Zhang, Chenming Xu, Xiaoming Chen, Qiwen Shi, Weike Su, Hang Zhao
Smoke inhalation leads to acute lung injury (ALI), a devastating clinical problem associated with high mortality rates. Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of proinflammatory cytokine signaling. We have found that adenoviral gene transfer of SOCS-1 ameliorates smoke inhalation-induced lung injury in C57BL/6 mice. We also found that the release of adenosine triphosphate (ATP) was increased post smoke exposure, while oxidized ATP, an inhibitor of purinergic P2X7 receptor, suppressed smoke-induced NALP3 inflammasome assembly, caspase-1 activation, and K+ efflux...
June 16, 2018: Inflammation
Hao Wang, Zhixin Tian
Analysis of phosphoproteins always faces the challenge of low stoichiometry, which demands highly selective and efficient enrichment in the initial sample preparation. Here we report our synthesis of the novel titanium (IV) ion immobilized adenosine triphosphate functionalized silica nanoparticles (Ti4+ -ATP-NPs) for efficient enrichment of intact phosphoproteins. The average diameter of Ti4+ -ATP-NPs was about 128 nm with good dispersibility and the saturated adsorption capacity for β-casein was 1046.5 mg/g...
June 6, 2018: Journal of Chromatography. A
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