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https://www.readbyqxmd.com/read/29348070/rational-approach-to-highly-potent-and-selective-apoptosis-signal-regulating-kinase-1-ask1-inhibitors
#1
Frank Lovering, Paul Morgan, Christophe Allais, Ann Aulabaugh, Joanne Brodfuehrer, Jeanne Chang, Jotham Coe, WeiDong Ding, Heather Dowty, Margaret Fleming, Richard Frisbie, Julia Guzova, David Hepworth, Jayasankar Jasti, Steve Kortum, Ravi Kurumbail, Shashi Mohan, Nikolaos Papaioannou, Joseph W Strohbach, Fabien Vincent, Katherine Lee, Christoph W Zapf
Many diseases are believed to be driven by pathological levels of reactive oxygen species (ROS) and oxidative stress has long been recognized as a driver for inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been reported to be activated by intracellular ROS and its inhibition leads to a down regulation of p38-and JNK-dependent signaling. Consequently, ASK1 inhibitors may have the potential to treat clinically important inflammatory pathologies including renal, pulmonary and liver diseases...
December 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29346770/integrative-analyses-of-de-novo-mutations-provide-deeper-biological-insights-into-autism-spectrum-disorder
#2
Atsushi Takata, Noriko Miyake, Yoshinori Tsurusaki, Ryoko Fukai, Satoko Miyatake, Eriko Koshimizu, Itaru Kushima, Takashi Okada, Mako Morikawa, Yota Uno, Kanako Ishizuka, Kazuhiko Nakamura, Masatsugu Tsujii, Takeo Yoshikawa, Tomoko Toyota, Nobuhiko Okamoto, Yoko Hiraki, Ryota Hashimoto, Yuka Yasuda, Shinji Saitoh, Kei Ohashi, Yasunari Sakai, Shouichi Ohga, Toshiro Hara, Mitsuhiro Kato, Kazuyuki Nakamura, Aiko Ito, Chizuru Seiwa, Emi Shirahata, Hitoshi Osaka, Ayumi Matsumoto, Saoko Takeshita, Jun Tohyama, Tomoko Saikusa, Toyojiro Matsuishi, Takumi Nakamura, Takashi Tsuboi, Tadafumi Kato, Toshifumi Suzuki, Hirotomo Saitsu, Mitsuko Nakashima, Takeshi Mizuguchi, Fumiaki Tanaka, Norio Mori, Norio Ozaki, Naomichi Matsumoto
Recent studies have established important roles of de novo mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the "de novo paradigm" of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244) and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29345141/creating-hierarchical-pores-by-controlled-linker-thermolysis-in-multivariate-metal-organic-frameworks
#3
Liang Feng, Shuai Yuan, Liang-Liang Zhang, Kui Tan, Jia-Luo Li, Angelo Kirchon, Ling-Mei Liu, Peng Zhang, Yu Han, Yves J Chabal, Hong-Cai Zhou
Sufficient pore size, appropriate stability and hierarchical porosity are three prerequisites for open frameworks designed for drug delivery, enzyme immobilization and catalysis involving large molecules. Herein, we report a powerful and general strate-gy, linker thermolysis, to construct ultra-stable hierarchically porous metal-organic frameworks (HP-MOFs) with tunable pore size distribution. Linker instability, usually an undesirable trait of MOFs, was exploited to create mesopores by generating crystal defects throughout a microporous MOF crystal via thermolysis...
January 18, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29344508/acid-base-and-electrolyte-disorders-in-patients-with-and-without-chronic-kidney-disease-an-update
#4
REVIEW
Tsering Dhondup, Qi Qian
Kidneys play a pivotal role in the maintenance and regulation of acid-base and electrolyte homeostasis, which is the prerequisite for numerous metabolic processes and organ functions in the human body. Chronic kidney diseases compromise the regulatory functions, resulting in alterations in electrolyte and acid-base balance that can be life-threatening. In this review, we discuss the renal regulations of electrolyte and acid-base balance and several common disorders including metabolic acidosis, alkalosis, dysnatremia, dyskalemia, and dysmagnesemia...
December 2017: Kidney Diseases
https://www.readbyqxmd.com/read/29343964/achalasia-following-reflux-disease-coincidence-consequence-or-accommodation-an-experience-based-literature-review
#5
András Vereczkei, Laura Bognár, András Papp, Örs Péter Horváth
Achalasia is a motility disorder of the esophagus characterized by the defective peristaltic activity of the esophageal body and impaired relaxation of the lower esophageal sphincter due to the degeneration of the inhibitory neurons in the myenteric plexus of the esophageal wall. The histopathological and pathophysiological changes in achalasia have been well described. However, the exact etiological factors leading to the disease still remain unclear. Currently, achalasia is believed to be a multifactorial disease, involving both extrinsic and intrinsic factors...
2018: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29343261/prenatal-exposure-to-perfluoroalkyl-and-polyfluoroalkyl-substances-and-childhood-atopic-dermatitis-a-prospective-birth-cohort-study
#6
Qian Chen, Rong Huang, Li Hua, Yifeng Guo, Lisu Huang, Yanjun Zhao, Xia Wang, Jun Zhang
BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been reported to suppress immune function. However, previous studies on prenatal exposure to PFASs and allergic disorders in offspring provided inconsistent results. We aimed to examine the association between prenatal exposure to PFASs and childhood atopic dermatitis (AD) in offspring up to 24 months of age. METHODS: A prospective birth cohort study involving 1056 pregnant women was conducted in two hospitals in Shanghai from 2012 to 2015...
January 17, 2018: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/29342113/mitochondria-oxidative-stress-and-the-kynurenine-system-with-a-focus-on-ageing-and-neuroprotection
#7
REVIEW
Katalin Sas, Elza Szabó, László Vécsei
In this review, the potential causes of ageing are discussed. We seek to gain insight into the main physiological functions of mitochondria and discuss alterations in their function and the genome, which are supposed to be the central mechanisms in senescence. We conclude by presenting the potential modulating role of the kynurenine pathway in the ageing processes. Mitochondrial dynamics are supposed to have important physiological roles in maintaining cell homeostasis. During ageing, a decrease in mitochondrial dynamics was reported, potentially compromising the function of mitochondria...
January 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29339355/re-evaluation-of-the-normal-range-of-serum-total-co2-concentration
#8
REVIEW
Jeffrey A Kraut, Nicolaos E Madias
A reliable determination of blood pH, PCO2, and [HCO3-] is necessary for assessing the acid-base status of a patient. However, most acid-base disorders are first recognized through abnormalities in serum total CO2 concentration ([TCO2]) in venous blood, a surrogate for [HCO3-]. In screening patients on the basis of serum [TCO2], we have been concerned about the wide limits of normal for serum [TCO2], 10-13 mEq/L, reported by many clinical laboratories. Indeed, we have encountered patients with serum [TCO2] values within the lower or upper end of the normal range of the reporting laboratory, who subsequently were shown to have a cardinal acid-base disorder...
January 16, 2018: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29338844/sfe-sfedp-adrenal-insufficiency-french-consensus-introduction-and-handbook
#9
Yves Reznik, Pascal Barat, Jérôme Bertherat, Claire Bouvattier, Frédéric Castinetti, Olivier Chabre, Philippe Chanson, Christine Cortet, Brigitte Delemer, Bernard Goichot, Damien Gruson, Laurence Guignat, Emmanuelle Proust-Lemoine, Marie-Laure Raffin Sanson, Rachel Reynaud, Dinane Samara Boustani, Dominique Simon, Antoine Tabarin, Delphine Zenaty
The French endocrinology society (SFE) and the French pediatric endocrinology society (DFSDP) have drawn up recommendations for the management of primary and secondary adrenal insufficiency in the adult and child, based on an analysis of the literature by 19 experts in 6 work-groups. A diagnosis of adrenal insufficiency should be suspected in the presence of a number of non-specific symptoms except hyperpigmentation which is observed in primary adrenal insufficiency. Diagnosis rely on plasma cortisol and ACTH measurement at 8am and/or the cortisol increase after synacthen administration...
January 12, 2018: Annales D'endocrinologie
https://www.readbyqxmd.com/read/29335845/carnosic-acid-as-a-promising-agent-in-protecting-mitochondria-of-brain-cells
#10
REVIEW
Marcos Roberto de Oliveira
Carnosic acid (CA; C20H28O4), a phenolic diterpene characterized as an ortho-dihydroquinone-type molecule, is a pro-electrophile agent that becomes an electrophile after reacting with free radicals. The electrophile generated from CA interacts with and activates the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, which is a major modulator of redox biology in mammalian cells. CA induces antioxidant and anti-inflammatory effects in several cell types, as observed in both in vitro and in vivo experimental models...
January 15, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29335813/organic-acidurias-in-adults-late-complications-and-management
#11
Ali Tunç Tuncel, Nikolas Boy, Marina A Morath, Friederike Hörster, Ulrike Mütze, Stefan Kölker
Organic acidurias (synonym, organic acid disorders, OADs) are a heterogenous group of inherited metabolic diseases delineated with the implementation of gas chromatography/mass spectrometry in metabolic laboratories starting in the 1960s and 1970s. Biochemically, OADs are characterized by accumulation of mono-, di- and/or tricarboxylic acids ("organic acids") and corresponding coenzyme A, carnitine and/or glycine esters, some of which are considered toxic at high concentrations. Clinically, disease onset is variable, however, affected individuals may already present during the newborn period with life-threatening acute metabolic crises and acute multi-organ failure...
January 15, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29333061/critical-appraisal-of-rome-iv-criteria-hypersensitive-esophagus-does-belong-to-gastroesophageal-reflux-disease-spectrum
#12
REVIEW
Leonardo Frazzoni, Marzio Frazzoni, Nicola de Bortoli, Salvatore Tolone, Irene Martinucci, Lorenzo Fuccio, Vincenzo Savarino, Edoardo Savarino
The Rome IV Committee introduced a major change in the classification of functional gastrointestinal disorders, proposing a more restrictive definition of gastroesophageal reflux disease (GERD). It was suggested that hypersensitive esophagus (HE) may sit more firmly within the functional realm. It was suggested that GERD diagnosis should be based upon abnormal acid exposure time (AET) only, implying no advantage of impedance-pH over pH monitoring. Symptom association probability (SAP), symptom index (SI) and heartburn relief with proton pump inhibitor (PPI) therapy were regarded as unreliable, whereas a lack of response to PPI was considered as evidence of functional heartburn...
January 2018: Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology
https://www.readbyqxmd.com/read/29333042/gas-chromatography-mass-spectrometry-profiling-in-methanolic-and-ethyl-acetate-root-and-stem-extract-of-corbichonia-decumbens-forssk-exell-from-thar-desert-of-rajasthan-india
#13
Sunita Arora, Manju Saini
Background: Corbichonia decumbens (Forssk.) Exell (Molluginaceae), recently has moved to Lophiocarpaceae as per angiospermic plant group (APG) III system, is an annual or short-lived, dwarf, glabrous subshrub, prefers to grow on rocky places and on sand-stones in dry, hot areas of Rajasthan. This is the potential plant with medicinal properties. Vegetative organs under study show antioxidant, anti-inflammatory, antiulcer, antimicrobial, and antinociception activity. Objective: This study was carried out to identify the phytoconstituents present in the methanolic and ethyl-acetate extract of root and stem of C...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29332257/kynurenic-acid-and-its-derivatives-are-able-to-modulate-the-adhesion-and-locomotion-of-brain-endothelial-cells
#14
Eszter Lajkó, Bernadett Tuka, Ferenc Fülöp, István Krizbai, József Toldi, Kálmán Magyar, László Vécsei, László Kőhidai
The neuroprotective actions of kynurenic acid (KYNA) and its derivatives in several neurodegenerative disorders [characterized by damage to the cerebral endothelium and to the blood-brain barrier (BBB)] are well established. Cell-extracellular matrix (ECM) adhesion is supposedly involved in recovery of impaired cerebral endothelium integrity (endothelial repair). The present work aimed to investigate the effects of KYNA and its synthetic derivatives on cellular behaviour (e.g. adhesion and locomotion) and on morphology of the GP8 rat brain endothelial cell line, modeling the BBB endothelium...
January 13, 2018: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29326171/abdominal-vagal-afferents-modulate-the-brain-transcriptome-and-behaviors-relevant-to-schizophrenia
#15
Melanie Klarer, Jean-Philippe Krieger, Juliet Richetto, Ulrike Weber-Stadlbauer, Lydia Günther, Christine Winter, Myrtha Arnold, Wolfgang Langhans, Urs Meyer
Reduced activity of vagal efferents has long been implicated in schizophrenia and appears to be responsible for diminished parasympathetic activity and associated peripheral symptoms such as low heart rate variability and cardiovascular complications in affected individuals. In contrast, only little attention has been paid to the possibility that impaired afferent vagal signaling may be relevant for the disorder's pathophysiology as well. The present study explored this hypothesis using a model of subdiaphragmatic vagal deafferentation (SDA) in male rats...
January 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29321515/nationwide-survey-on-cerebrotendinous-xanthomatosis-in-japan
#16
Yoshiki Sekijima, Shingo Koyama, Tsuneaki Yoshinaga, Masayoshi Koinuma, Yuji Inaba
Cerebrotendinous xanthomatosis (CTX) is likely to be underdiagnosed and precise epidemiological characteristics of CTX are largely unknown as knowledge on the disorder is based mainly on case reports. We conducted a nationwide survey on CTX to elucidate the frequency, clinical picture, and molecular biological background of Japanese CTX patients. In this first Japanese nationwide survey on CTX, 2541 questionnaires were sent to clinical departments across Japan. A total of 1032 (40.6%) responses were returned completed for further analysis...
January 10, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29320669/comorbidities-in-australian-women-with-hormone-dependent-breast-cancer-a-population-based-analysis
#17
Huah Shin Ng, Bogda Koczwara, David M Roder, Theo Niyonsenga, Agnes I Vitry
OBJECTIVE: To compare how frequently selected chronic diseases developed in women with breast cancer receiving endocrine therapy, and in women without cancer. DESIGN, SETTING AND PARTICIPANTS: Retrospective, rolling cohort study, analysing a random 10% sample of Pharmaceutical Benefits Scheme (PBS) data for the period 1 January 2003 - 31 December 2014. Women with breast cancer who first commenced endocrine therapy between January 2004 and December 2011 were identified, and age- and sex-matched (1:10) by comorbidity with control groups of women who did not have a dispensing record for antineoplastic agents during the study period or the comorbidity of interest at baseline...
January 15, 2018: Medical Journal of Australia
https://www.readbyqxmd.com/read/29316923/comparative-assessment-of-probiotics-and-monensin-in-the-prophylaxis-of-acute-ruminal-lactic-acidosis-in-sheep
#18
Leonardo Frasson Reis, Rejane Santos Sousa, Francisco Leonardo Costa Oliveira, Frederico Augusto Mazzocca Lopes Rodrigues, Carolina Akiko Sato Cabral Araújo, Enoch Brandão Souza Meira-Júnior, Raimundo Alves Barrêto-Júnior, Clara Satsuki Mori, Antonio Humberto Hamad Minervino, Enrico Lippi Ortolani
BACKGROUND: Acute ruminal lactic acidosis (ARLA) is a major nutritional and metabolic disorder usually characterized by excessive or non-adapted intake of diets rich in nonstructural carbohydrates. Feed additives that regulate the ruminal environment have been used to prevent ARLA, such as ionophores and, more recently, yeast culture. Thus, we aimed to compare the efficacy of a yeast-based culture (Saccharomyces cerevisiae) with that of monensin sodium in the prevention of ARLA in sheep...
January 9, 2018: BMC Veterinary Research
https://www.readbyqxmd.com/read/29312822/effect-of-dark-sweet-cherry-powder-consumption-on-the-gut-microbiota-short-chain-fatty-acids-and-biomarkers-of-gut-health-in-obese-db-db-mice
#19
Jose F Garcia-Mazcorro, Nara N Lage, Susanne Mertens-Talcott, Stephen Talcott, Boon Chew, Scot E Dowd, Jorge R Kawas, Giuliana D Noratto
Cherries are fruits containing fiber and bioactive compounds (e.g., polyphenolics) with the potential of helping patients with diabetes and weight disorders, a phenomenon likely related to changes in the complex host-microbiota milieu. The objective of this study was to investigate the effect of cherry supplementation on the gut bacterial composition, concentrations of caecal short-chain fatty acids (SCFAs) and biomarkers of gut health using an in vivo model of obesity. Obese diabetic (db/db) mice received a supplemented diet with 10% cherry powder (supplemented mice, n = 12) for 12 weeks; obese (n = 10) and lean (n = 10) mice served as controls and received a standard diet without cherry...
2018: PeerJ
https://www.readbyqxmd.com/read/29305858/identification-of-a-candidate-enhancer-for-dmrt3-involved-in-spastic-cerebral-palsy-pathogenesis
#20
Naoto Kubota, Toshifumi Yokoyama, Nobuhiko Hoshi, Mikita Suyama
Cerebral palsy (CP) is a major neuronal disease and the most common movement disorder in children. Although environmental factors leading to CP have been greatly investigated, the genetic mechanism underlying CP is not well understood. Here we focused on two clinical reports that characterized a deletion involving the KANK1 gene locus in the 9p24.3 region. One report shows spastic CP and the other shows no spastic CP phenotype. Based on the epigenetic status and evolutionary conservation, we first found a functional genomic element at the noncoding region that was deleted only in patients with spastic CP...
January 3, 2018: Biochemical and Biophysical Research Communications
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