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Abbi R Hernandez, Caesar M Hernandez, Keila T Campos, Leah M Truckenbrod, Yasemin Sakarya, Joseph A McQuail Ph D, Christy S Carter, Jennifer L Bizon, Andrew P Maurer, Sara N Burke
Nutritional ketosis is induced by high fat/low carbohydrate dietary regimens, which produce high levels of circulating ketone bodies, shifting metabolism away from glucose utilization. While ketogenic diets (KD) were initially introduced to suppress seizures, they are garnering attention for their potential to treat a myriad of neurodegenerative and metabolic disorders that are associated with advanced age. The feasibility and physiological impact of implementing a long-term KD in old animals, however, has not been systematically examined...
October 12, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Xiaolu Wang, Mengjia Liu, Yuqing Wang, Hongyan Fan, Jie Wu, Chao Huang, Hongwei Hou
To develop coordination polymers (CPs) as catalysts to selectively catalyze the reaction of C-H bond activation of arylalkanes to their homologous ketones, three new Cu(I)-based coordination polymers (Cu(I)-CPs) [CuI(aas-TPB)]n (1), [CuBr(ass-TPB)CH3CN]n (2), and {[Cu(ass-TPB)]Cl}n (3) (TPB = N,N,N-tris(3-pyridinyl)-1,3,5-benzenetricarboxamide) were synthesized. Structural variations from a herringbone fashion one-dimensional framework of 1 to a two-dimensional framework of 2 containing a 48-membered macrocycle and a cationic three-dimensional framework of 3 filled with Cl(-) anions were observed arising from the different halogen ions (I(-), Br(-), and Cl(-))...
October 16, 2017: Inorganic Chemistry
Ehsan Zahedi, Samaneh Shaabani, Abolfazl Shiroudi
The synergetic use of bonding evolution theory (BET) and non-covalent interaction (NCI) analysis allows to obtain new insight into the bond breaking/forming processes and electron redistribution along the reaction path to understand the molecular mechanism of a reaction and recognize regions of strong and weak electron pairing. This viewpoint has been considered for cheletropic extrusion of CO from unsaturated cyclic ketones cyclohepta-3,5-dien-1-one CHD, cyclopent-3-en-1-one CPE and bicyclo[2.2.1]hept-2-en-7-one BCH by using hybrid functional MPWB1K in conjugation with aug-cc-pVTZ basis set...
October 15, 2017: Journal of Physical Chemistry. A
Ursula H Neumann, Jessica S S Ho, Sam Chen, Yuen Yi C Tam, Pieter R Cullis, Timothy J Kieffer
OBJECTIVE: Hyperglucagonemia is present in many forms of diabetes and contributes to hyperglycemia, and glucagon suppression can ameliorate diabetes in mice. Leptin, a glucagon suppressor, can also reverse diabetes in rodents. Lipid nanoparticle (LNP) delivery of small interfering RNA (siRNA) effectively targets the liver and is in clinical trials for the treatment of various diseases. We compared the effectiveness of glucagon receptor (Gcgr)-siRNA delivered via LNPs to leptin in two mouse models of diabetes...
October 2017: Molecular Metabolism
Ke Chen, Shuai Liu, Dan Wang, Wen-Juan Hao, Peng Zhou, Shu-Jiang Tu, Bo Jiang
The combination of AgTFA and Sc(OTf)3 enables the bimetallic synergistic catalysis of β-alkynyl ketones and para-quinone methides (p-QMs), allowing direct synthesis of 17 examples of benzo[c]xanthenes with generally good yields through a benzannulation/1,6-addition/cyclization sequence. Exchanging p-QMs for quinone imine ketal resulted in 10 examples of tetracyclic naphtho[1,2-b]benzofurans via a similar benzannulation/1,4-addition/cyclization cascade. During these reaction processes, AgTFA and Sc(OTf)3 could be perfectly compatible, together with the realization of C(sp(3))-H functionalization adjacent to carbonyl group on the β-alkynyl ketone unit...
October 18, 2017: Journal of Organic Chemistry
Jimmy Hu, Phillip Cantrell, Aklesh Nand
Urethane products that contain isocyanates are extensively used in the motor vehicle repair (MVR) industry and other industries such as furniture and cabinet-making as two-pack spray paints, clears, and adhesives. Attention has recently been refocussed on isocyanate-containing chemicals, particularly in paints. The spray painters in the MVR industry had a propensity to develop industrial asthma at a rate 80 times higher than the general public, which was previously reported in the UK. To track workers exposure to isocyanates, urine samples were collected from 196 spray painters who worked mainly in 78 MVR shops across 54 New South Wales (NSW) towns and suburbs...
October 1, 2017: Annals of Work Exposures and Health
Maki Goda, Tomoko Yamakura, Kazuyo Sasaki, Takumi Tajima, Makoto Ueno
Objective To evaluate the safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus (T2DM) in clinical settings. Methods We conducted a 1-year post-marketing surveillance (PMS) of canagliflozin in almost all the elderly patients (≥65 years old) with T2DM who began taking canagliflozin during the first 3 months after its launch in Japan. The main outcomes included the incidences of adverse drug reactions (ADRs), serious ADRs and the changes of laboratory tests as well as efficacy variables...
October 13, 2017: Current Medical Research and Opinion
Heeoon Han, Amos B Smith
An effective [3+2] annulation tactic for the construction of diverse bicyclic compounds possessing highly functionalized cyclopentane rings has been developed employing soft ketone enolates as the initial nucleophile for anion relay chemistry (ARC). The protocol entails a highly diastereoselective aldol/Brook rearrangement/cyclization cascade.
October 10, 2017: Angewandte Chemie
Sandra Del Pozo, Silvia Vera, Mikel Oiarbide, Claudio Palomo
The catalytic asymmetric α-functionalization of prochiral barbituric acids, a subtype of pseudosymmetric 1,3-diamides, to yield the corresponding 5,5-disubstituted (quaternary) derivatives remains essentially unsolved. In this study 2-alkylthio-4,6-dioxopirimidines are designed as key 1,3-diamide surrogates that perform exceedingly in amine-squaramide catalyzed C-C bond forming reactions with vinyl ketones or Morita-Baylis-Hillmann-type allyl bromides as electrophiles. Mild acid hydrolysis of adducts affords barbituric acid derivatives with an in-ring quaternary carbon in unprecedented enantioselectivity, offering valuable materials for biological evaluations...
October 17, 2017: Journal of the American Chemical Society
Xiquan Cheng, Xu Jiang, Yanqiu Zhang, Cher Hon Lau, Zongli Xie, Derrick Ng, Stefan J D Smith, Matthew R Hill, Lu Shao
Membrane separation is a promising technology that can be used to purify temperature-sensitive organic molecules from solvents. However, a lack of membrane materials that are permeable towards organic solvents yet highly selective curtails large-scale membrane applications. To overcome these limitations, additional molecular transportation pathways are constructed in ultrathin polyamide membranes using high hydrostable metal organic frameworks with diverse functional surface architecture. Additional passageways enhance water permeance by 84 % (15...
October 12, 2017: ACS Applied Materials & Interfaces
L Gupta, D Khandelwal, S Kalra, P Gupta, D Dutta, S Aggarwal
Ketogenic diet (KD) is a high-fat, adequate-protein, and low-carbohydrate diet that leads to nutritional ketosis, long known for antiepileptic effects and has been used therapeutically to treat refractory epilepsy. This review attempts to summarize the evidence and clinical application of KD in diabetes, obesity, and other endocrine disorders. KD is usually animal protein based. An empiric vegetarian Indian variant of KD has been provided keeping in mind the Indian food habits. KD has beneficial effects on cardiac ischemic preconditioning, improves oxygenation in patients with respiratory failure, improves glycemic control in diabetics, is associated with significant weight loss, and has a beneficial impact on polycystic ovarian syndrome...
October 2017: Journal of Postgraduate Medicine
Maike Lenz, Niels Borlinghaus, Leonie Weinmann, Bettina M Nestl
Imine reductases are nicotinamide-dependent enzymes that catalyze the asymmetric reduction of various imines to the corresponding amine products. Owing to the increasing roles of chiral amines and heterocyclic compounds as intermediates for pharmaceuticals, the demand for novel selective synthesis strategies is vitally important. Recent studies have demonstrated the discovery and structural characterization of a number of stereoselective imine reductase enzymes. Here, we highlight recent progress in applying imine reductases for the formation of chiral amines and heterocycles...
October 11, 2017: World Journal of Microbiology & Biotechnology
Pei Wang, Ronghui Wang, Yingdong Zhu, Shengmin Sang
[6]-Shogaol (6S), one of the major bioactive components in dry ginger, is attracting considerable attention because of its wide spectrum of biological activities, but its metabolic fate is still not fully understood. In the present study, the microbial metabolism of 6S was examined for the first time in in vitro batch fecal fermentation system and in mice. Two major microbial metabolites were detected and identified as 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol (M9) and 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M11)...
October 11, 2017: Journal of Agricultural and Food Chemistry
Yongguk Oh, Yeon Jeong Jang, Mijin Jeon, Hyung Sik Kim, Jong Hwan Kwak, Kyu Hyuck Chung, Suhkneung Pyo, Young Hoon Jung, In Su Kim
The first total synthesis and biological evaluation of penchinone A and its structural analogs are described. The key steps for the preparation of penchinone A derivatives involve the oxime-directed palladium(II)-catalyzed oxidative acylation, Claisen rearrangement and base-mediated olefin migration. This transformation efficiently provides a range of allyl-substituted biaryl ketones with site-selectivity and functional group compatibility. In addition, all synthetic compounds were screened for anti-inflammatory activity against nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) with lipopolysaccharide (LPS)-induced RAW264...
October 11, 2017: Journal of Organic Chemistry
Hae-Yun Chung, Yoo Kyoung Park
Ketogenic diet has been used for more than 80 years as a successful dietary regimen for epilepsy. Recently, dietary modulation by carbohydrate depletion via ketogenic diet has been suggested as an important therapeutic strategy to selectively kill cancer cells and as adjuvant therapy for cancer treatment. However, some researchers insist ketogenic diet to be highly undesirable as ketogenic diet may trigger and/or exacerbate cachexia development and usually result in significant weight loss. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possibility of the use of ketogenic diet for oncology patients...
September 2017: Journal of Cancer Prevention
Chong-Lei Ji, Xin Hong
N-glutarimide amides have recently emerged as an exceptional group of compounds with unusually high reactivity in amide C-N bond activation. To understand the key factors that control the remarkable reactivity of these resonance destabilized amides, we explored the Ni-catalyzed decarbonylative and non-decarbonylative Suzuki-Miyaura coupling with N-glutarimide amides through density functional theory (DFT) calculations. Two leading effects are responsible for the C-N cleavage activity of N-glutarimide amides, the coordinating N-substituents and the geometric twisting...
October 10, 2017: Journal of the American Chemical Society
Edoardo Bertero, Leticia Prates Roma, Pietro Ameri, Christoph Maack
The effects of intense glycaemic control on macrovascular complications in patients with type 2 diabetes are incompletely resolved, and many glucose-lowering medications negatively affect cardiovascular outcomes. Recently, the EMPA-REG OUTCOME trial revealed that empagliflozin, an inhibitor of the sodium-glucose cotransporter 2 (SGLT2), substantially reduced the risk of hospitalization for heart failure, death from cardiovascular causes, and all-cause mortality in patients with type 2 diabetes mellitus at high cardiovascular risk...
August 4, 2017: Cardiovascular Research
Jonas Höjer
Alcoholic ketoacidosis - a review A chronic alcoholic with severe metabolic acidosis presents a difficult diagnostic problem in the emergency room. Over and above methanol- and ethylene glycol intoxication, alcoholic ketoacidosis is a common but less recognized etiology. The disorder occurs in alcoholics who have had a recent binge drinking followed by the abrupt cessation of alcohol consumption because of abdominal pain and vomiting, with resulting dehydration, starvation, and then a β-hydroxybutyrate dominated ketoacidosis...
October 3, 2017: Läkartidningen
Zhangjian Huang, Yi Mou, Xiaojun Xu, Di Zhao, Yisheng Lai, Yuwen Xu, Cen Chen, Ping Li, Sixun Peng, Jide Tian, Yihua Zhang
Currently, no effective and safe medicines are available to treat diabetic nephropathy (DN). Bardoxolone methyl (CDDO-Me) has displayed promising anti-DN activity but serious side-effects in the clinical trial, probably because the highly reactive α-cyano-α,β-unsaturated ketone (CUK) in ring A of CDDO-Me can covalently bind to thiol functionalities in many biomacromolecules. In this study, we designed and synthesized a γ-glutamyl transpeptidase (GGT)-based and CUK-modified derivative 2 of CDDO-Me to address this issue...
October 10, 2017: Journal of Medicinal Chemistry
Frank Weinhold
We employ ab initio and density functional methods to investigate the equilibrium structure and vibrational frequencies of extended cumulene monoketones [CH2=(C=)mO] and diketones [O=(C=)mO], in order to elucidate the electronic origin of the curious "kinked'" spine geometries that are common in such species. The dominant role of symmetry-breaking nO(π)-σ*CC interactions between the p-type lone pair of the terminal oxygen and adjacent unfilled CC antibonding orbital is demonstrated by NBO 2nd-order delocalization energies, Fock matrix deletions, and natural resonance theory (NRT) descriptors, showing the general connection between cumulene kinking and CC bond-breaking reactions that split off CO...
October 9, 2017: Journal of Organic Chemistry
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