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Acid basic disorder

Farzaneh Ghafarian, Mehran Pashirzad, Majid Khazaei, Majid Rezayi, Seyed Mahdi Hassanian, Gordon A Ferns, Amir Avan
Cardiovascular disease (CVD) is the major cause of death globally; therefore, there is a need for the identification of a valid biomarker that accurately predicts the risk of developing CVD, and novel therapeutic approaches for its treatment. Exosomes are very small extracellular vesicles containing protein, lipid, transcription factors, messenger RNAs, noncoding RNA, and nucleic acid contents that are important players in intercellular communication, and that act via long-range signals or cell-to-cell contact...
December 10, 2018: Journal of Cellular Physiology
Sydney Zarriello, Julian Tuazon, Sydney Corey, Samantha Schimmel, Mira Rajani, Anna Gorsky, Diego Incontri, Bruce D Hammock, Cesar V Borlongan
Soluble epoxide hydrolase (sEH) degrades epoxides of fatty acids including epoxyeicosatrienoic acid isomers (EETs), which are produced as metabolites of the cytochrome P450 branch of the arachidonic acid pathway. EETs exert a variety of largely beneficial effects in the context of inflammation and vascular regulation. sEH inhibition is shown to be therapeutic in several cardiovascular and renal disorders, as well as in peripheral analgesia, via the increased availability of anti-inflammatory EETs. The success of sEH inhibitors in peripheral systems suggests their potential in targeting inflammation in the central nervous system (CNS) disorders...
November 14, 2018: Progress in Neurobiology
Maja Dembic, Henriette S Andersen, Jean Bastin, Thomas K Doktor, Thomas J Corydon, Jörn Oliver Sass, Alexandra Lopes Costa, Fatima Djouadi, Brage S Andresen
Resveratrol (RSV) is a small compound first identified as an activator of sirtuin 1 (SIRT1), a key factor in mediating the effects of caloric restriction. Since then, RSV received great attention for its widespread beneficial effects on health and in connection to many diseases. RSV improves the metabolism and the mitochondrial function, and more recently it was shown to restore fatty acid β-oxidation (FAO) capacities in patient fibroblasts harboring mutations with residual enzyme activity. Many of RSV's beneficial effects are mediated by the transcriptional coactivator PGC-1α, a direct target of SIRT1 and a master regulator of the mitochondrial fatty acid oxidation...
October 22, 2018: Molecular Genetics and Metabolism
Hans-Peter Landolt, Sebastian C Holst, Amandine Valomon
Sleep and wakefulness are highly complex processes that are elegantly orchestrated by fine-tuned neurochemical changes among neuronal and non-neuronal ensembles, nuclei, and networks of the brain. Important neurotransmitters and neuromodulators regulating the circadian and homeostatic facets of sleep-wake physiology include melatonin, γ-aminobutyric acid, hypocretin, histamine, norepinephrine, serotonin, dopamine, and adenosine. Dysregulation of these neurochemical systems may cause sleep-wake disorders, which are commonly classified into insomnia disorder, parasomnias, circadian rhythm sleep-wake disorders, central disorders of hypersomnolence, sleep-related movement disorders, and sleep-related breathing disorders...
November 16, 2018: Handbook of Experimental Pharmacology
Ethan B Russo
Neurological therapeutics have been hampered by its inability to advance beyond symptomatic treatment of neurodegenerative disorders into the realm of actual palliation, arrest or reversal of the attendant pathological processes. While cannabis-based medicines have demonstrated safety, efficacy and consistency sufficient for regulatory approval in spasticity in multiple sclerosis (MS), and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges remain. This review will examine the intriguing promise that recent discoveries regarding cannabis-based medicines offer to neurological therapeutics by incorporating the neutral phytocannabinoids tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), and cannabis terpenoids in the putative treatment of five syndromes, currently labeled recalcitrant to therapeutic success, and wherein improved pharmacological intervention is required: intractable epilepsy, brain tumors, Parkinson disease (PD), Alzheimer disease (AD) and traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE)...
2018: Frontiers in Integrative Neuroscience
Maximilian Weustenfeld, Reiner Eidelpes, Matthias Schmuth, William B Rizzo, Johannes Zschocke, Markus A Keller
The Sjögren-Larsson syndrome (SLS) is a rare autosomal recessive disorder caused by pathogenic variants in the ALDH3A2 gene, which codes for fatty aldehyde dehydrogenase (FALDH). FALDH prevents the accumulation of toxic fatty aldehydes by converting them into fatty acids. Pathogenic ALDH3A2 variants cause symptoms such as ichthyosis, spasticity, intellectual disability, and a wide range of less common clinical features. Interpreting patient-to-patient variability is often complicated by inconsistent reporting and negatively impacts on establishing robust criteria to measure the success of SLS treatments...
October 29, 2018: Human Mutation
S Paryzhak, T Dumych, I Mahorivska, M Boichuk, G Bila, S Peshkova, T Nehrych, R Bilyy
During NET formation, the content of neutrophils granules is released into the intercellular milieu. Consisting of many proteases and ROS species, formed NETs were shown to degrade cytokines (Schauer, Nat Med, 2014); while the content of neutrophil's azurophilic granules proved to contain glycosidases, secreted upon activation (Thaysen-Andersen, JBC, 2015), and formation of autoantibodies to neutrophil beta-glucoronidase was connected with the level of anti-MPO antibodies (Ab) (Martensson, Autoimmunity, 1992)...
October 28, 2018: Autoimmunity
Takahiro Ishimoto, Yusuke Masuo, Yukio Kato, Noritaka Nakamichi
The promotion of neurogenesis is considered to be an effective therapeutic strategy for neuropsychiatric disorders because impairment of neurogenesis is associated with the onset and progression of these disorders. We have previously demonstrated that orally ingested ergothioneine (ERGO), a naturally occurring antioxidant and hydrophilic amino acid, promotes neurogenesis in the hippocampal dentate gyrus (DG) with its abundant neural stem cells (NSCs) and exerts antidepressant-like effects in mice. Independent of its antioxidant activities, ERGO induces in cultured NSCs this differentiation through induction of the basic helix-loop-helix transcription factor Math1...
October 22, 2018: Cellular Signalling
Luisa A Ferreira, Alicyia Walczyk Mooradally, Boris Zaslavsky, Vladimir N Uversky, Steffen P Graether
Dehydrins are plant proteins that are able to protect plants from various forms of dehydrative stress such as drought, cold, and high salinity. Dehydrins can prevent enzymes from losing activity after freeze/thaw treatments. Previous studies had suggested that the dehydrins function by a molecular shield effect, essentially preventing a denatured enzyme from aggregating with another enzyme. Therefore, the larger the dehydrin, the larger the shield and theoretically the more effective the protection. Although this relationship holds for smaller dehydrins, it fails to explain why larger dehydrins are less efficient than would be predicted from their size...
November 6, 2018: Biophysical Journal
Tünde Juhász, Judith Mihály, Gergely Kohut, Csaba Németh, Károly Liliom, Tamás Beke-Somfai
Membrane-active, basic amphipathic peptides represent a class of biomolecules with diverse functions. Sequentially close protein segments also show similar behaviour in several ways. Here we investigated the effect of the lipid mediator lysophosphatidic acid (LPA) on the conformation of structurally disordered peptides including extracellular antimicrobial peptides (AMPs), and calmodulin-binding motifs derived from cytosolic and membrane target proteins. The interaction with associated LPA resulted in gain of ordered secondary structure elements, which for most cases were previously uncharacteristic of the particular peptide...
September 28, 2018: Scientific Reports
Myung Hee Park, Edith C Wolff
The natural amino acid hypusine [Ne-4-amino-2-hydroxybutyl(lysine)] is derived from the polyamine spermidine, and occurs only in a single family of cellular proteins, eukaryotic translation factor 5A (eIF5A) isoforms.  Hypusine is formed by conjugation of the aminobutyl moiety of spermidine to a specific lysine residue of this protein. The posttranslational synthesis of hypusine involves two enzymatic steps, catalyzed by deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). Hypusine is essential for eIF5A activity...
September 26, 2018: Journal of Biological Chemistry
Jan Fábry
A large number of structural determinations of compounds containing 2-hy-droxy-3,5-di-nitro-benzoic acid ( I ) and its various deprotonated forms, 2-hy-droxy-3,5-di-nitro-benzoate ( II ) or 2-carb-oxy-4,6-di-nitro-phenolate ( III ), are biased. The reason for the bias follows from incorrectly applied constraints or restraints on the bridging hydrogen , which is involved in the intra-molecular hydrogen bond between the neighbouring carb-oxy-lic/carboxyl-ate and oxo/hy-droxy groups. This hydrogen bond belongs to the category of resonance-assisted hydrogen bonds...
September 1, 2018: Acta Crystallographica. Section E, Crystallographic Communications
Fábio L S Costa, Maria Elena De Lima, Suely G Figueiredo, Rafaela S Ferreira, Núbia S Prates, Tetsu Sakamoto, Carlos E Salas
Background: Lethal factors are multifunctional oligomeric proteins found in the venomous apparatus of Scorpaeniformes fish. These toxins elicit not only an array of biological responses in vitro but also cardiovascular disorders and strong hemolytic, nociceptive and edematogenic activities in vivo. This work describes the cloning and molecular identification of two toxin subunits, denominated Sp-CTx-α and Sp-CTx-β, from scorpionfish venom ( Scorpaena plumieri ). Methods: The primary structures were deduced after cDNA amplification by PCR with primers from conserved sequences described in Scorpaeniformes toxins...
2018: Journal of Venomous Animals and Toxins Including Tropical Diseases
Omer Demir, Inci Sema Tas, Berrin Gunay, Funda Gungor Ugurlucan
BACKGROUND: Rosacea is a common, chronic disorder that can present with a variety of cutaneous or ocular manifestations. Skin involvement primarily affects the central face, with findings such as persistent centrofacial redness, papules, pustules, flushing, telangiectasia, and phymatous skin changes. The pathways that lead to the development of rosacea are not well understood. The relationship of pyoderma faciale (also known as rosacea fulminans) to rosacea also is uncertain. We aimed to write this article with the aim of showing how a pregnant patient who has been aggravated by the degree of lesions on the face during the first trimester of pregnancy is treated and to show what is in the literature in this issue...
August 20, 2018: Open Access Macedonian Journal of Medical Sciences
Emmanuel Somm, François R Jornayvaz
Discovered 20 years ago, fibroblast growth factor (FGF)19, and its mouse ortholog FGF15, were the first members of a new subfamily of FGFs able to act as hormones. During fetal life, FGF15/19 is involved in organogenesis, affecting the development of the ear, eye, heart, and brain. At adulthood, FGF15/19 is mainly produced by the ileum, acting on the liver to repress hepatic bile acid synthesis and promote postprandial nutrient partitioning. In rodents, pharmacologic doses of FGF19 induce the same antiobesity and antidiabetic actions as FGF21, with these metabolic effects being partly mediated by the brain...
December 1, 2018: Endocrine Reviews
Jan D Andersson, David Matuskey, Sjoerd J Finnema
In this review, we summarize the recent development of positron emission tomography (PET) radioligands for γ-aminobutyric acid A (GABAA ) receptors and their potential to measure changes in endogenous GABA levels and highlight the clinical and translational applications of GABA-sensitive PET radioligands. We review the basic physiology of the GABA system with a focus on the importance of GABAA receptors in the brain and specifically the benzodiazepine binding site. Challenges for the development of central nervous system radioligands and particularly for radioligands with increased GABA sensitivity are outlined, as well as the status of established benzodiazepine site PET radioligands and agonist GABAA radioligands...
August 10, 2018: Neuroscience Letters
Dmiry V Chistyakov, Alina A Astakhova, Marina G Sergeeva
Relationship between mood disorders and inflammation is now well-documented, although molecular mechanisms are not understood. Previously mostly pro-inflammatory cytokines of immune system (IL-6, TNF, etc.) were taken into account. However, recent understanding of resolution of inflammation as an active process drew attention to mediators of resolution, which include both proteins and ω-3 and ω-6 polyunsaturated fatty acids derivatives (resolvins, cyclopentenone prostaglandins, etc.). This review takes into account new data on resolution of inflammation and action of mediators of resolution in models of depression...
October 2018: Experimental and Molecular Pathology
Santu Bera, Sudipta Mondal, Sigal Rencus-Lazar, Ehud Gazit
The unique physiochemical properties and multiscale organization of layered materials draw the attention of researchers across a wide range of scientific disciplines. Layered structures are commonly found in diverse biological systems where they fulfill various functions. A prominent example of layered biological materials is the organization of proteins and polypeptides into the archetypal aggregated amyloidal structures. While the organization of proteins into amyloid structures was initially associated with various degenerative disorders, it was later revealed that proteins not related to any disease could also form identical layered assemblies...
September 18, 2018: Accounts of Chemical Research
Xu Wang, Fei Zhao, Xufeng Wang, Yabing Niu, Lijuan Niu, Chunling Wang
Depression is one of the leading causes of disability in the world. Current pharmaceutical treatment for depression remains unsatisfactory due to its limited therapeutic efficacy and undesirable side effects. There is increasing interest in looking for alternative strategies from diet for the treatment of depressive disorder. The nutrition factors have the potential to regulate several neurochemical pathways implicated in depression. This review gives an overview of the recent advances in depression treatment using nutrition factors including vitamins, polyunsaturated fatty acid, elements and natural products...
2018: Current Pharmaceutical Design
Francisco López-Muñoz, Winston W Shen, Pilar D'Ocon, Alejandro Romero, Cecilio Álamo
In this paper, the authors review the history of the pharmacological treatment of bipolar disorder, from the first nonspecific sedative agents introduced in the 19th and early 20th century, such as solanaceae alkaloids, bromides and barbiturates, to John Cade's experiments with lithium and the beginning of the so-called "Psychopharmacological Revolution" in the 1950s. We also describe the clinical studies and development processes, enabling the therapeutic introduction of pharmacological agents currently available for the treatment of bipolar disorder in its different phases and manifestations...
July 23, 2018: International Journal of Molecular Sciences
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