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Metabolic modulation

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https://www.readbyqxmd.com/read/29684858/a-novel-triazine-ring-compound-md568-exerts-in-vivo-and-in-vitro-effects-on-lipid-metabolism
#1
Dan Jia, Ziwen Li, Ying Gao, Yifan Feng, Weimin Li
In this study, we investigated the toxicity and biological activity of a novel triazine ring compound named magnolol derivative 568 (MD568). The LD50 of MD568 was determined in Sprague-Dawley (SD) rats by intraperitoneal injection. Treatment of high fat diet-induced obese rats with MD568 demonstrated that MD568 displayed significant anti-obesity effects. MD568 markedly reduced body weight, blood lipid contents, white adipose tissue (WAT) and liver mass in obese rats. In addition, MD568 modulated lesions in WAT through regulating PPAR-Ɣ, C/EBP-a, SREBP-1c and FABP-4 proteins in the liver through regulating PPAR-α, SREBP-1c and FABP-4...
April 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29684583/a-novel-rpe65-inhibitor-cu239-suppresses-visual-cycle-and-prevents-retinal-degeneration
#2
Younghwa Shin, Gennadiy Moiseyev, Konstantin Petrukhin, Christopher L Cioffi, Parthasarathy Muthuraman, Yusuke Takahashi, Jian-Xing Ma
The retinoid visual cycle is an ocular retinoid metabolism specifically dedicated to support vertebrate vision. The visual cycle serves not only to generate light-sensitive visual chromophore 11-cis-retinal, but also to clear toxic byproducts of normal visual cycle (i.e. all-trans-retinal and its condensation products) from the retina, ensuring both the visual function and the retinal health. Unfortunately, various conditions including genetic predisposition, environment and aging may attribute to a functional decline of the all-trans-retinal clearance...
April 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29684520/phosphate-toxicity-and-tumorigenesis
#3
REVIEW
Ronald B Brown, Mohammed S Razzaque
In this brief opinion article, we briefly summarized evidence that cellular phosphate burden from phosphate toxicity is a pathophysiological determinant of cancer cell growth. Tumor cells express more phosphate cotransporters and store more inorganic phosphate than normal cells, and dysregulated phosphate homeostasis is associated with the genesis of various human tumors. High dietary phosphate consumption causes the growth of lung and skin tumors in experimental animal models. Experimental studies show that excessive phosphate burden induces growth-promoting cell signaling, stimulates neovascularization, and is associated with chromosome instability and metastasis...
April 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29684378/identification-of-a-pyrrogallol-derivative-as-a-potent-and-selective-human-tlr2-antagonist-by-structure-based-virtual-screening
#4
Maria Grabowski, Manuela S Murgueitio, Marcel Bermudez, Jörg Rademann, Gerhard Wolber, Günther Weindl
Toll-like receptor 2 (TLR2) induces early inflammatory responses to pathogen and damage-associated molecular patterns trough heterodimerization with either TLR1 or TLR6. Since overstimulation of TLR2 signaling is linked to several inflammatory and metabolic diseases, TLR2 antagonists may provide therapeutic benefits for the control of inflammatory conditions. We present virtual screening for the identification of novel TLR2 modulators, which combines analyses of known ligand sets with structure-based approaches...
April 20, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29684108/pituitary-diseases-and-bone
#5
Gherardo Mazziotti, Stefano Frara, Andrea Giustina
Neuroendocrinology of bone is a new area of research based on the evidence that pituitary hormones may directly modulate bone remodeling and metabolism. Skeletal fragility associated with high risk of fractures is a common complication of several pituitary diseases such as hypopituitarism, Cushing disease, acromegaly and hyperprolactinemia. As in other forms of secondary osteoporosis, pituitary diseases generally affect bone quality more than bone quantity and fractures may occur even in the presence of normal or low-normal bone mineral density as measured by dual-energy X-ray absorptiometry, making difficult the prediction of fractures in these clinical settings...
April 19, 2018: Endocrine Reviews
https://www.readbyqxmd.com/read/29684084/local-and-systemic-inflammatory-lipid-profiling-in-a-rat-model-of-osteoarthritis-with-metabolic-dysregulation
#6
H M de Visser, S C Mastbergen, S Ravipati, P M J Welsing, F C Pinto, F P J G Lafeber, V Chapman, D A Barrett, H Weinans
OBJECTIVE: Bioactive oxidised lipids (oxylipins) are important signalling mediators, capable of modulating the inflammatory state of the joint and anticipated to be of importance in joint homeostasis and status of osteoarthritis. The aim of this study was to quantify oxylipin levels in plasma and synovial fluid from rats with experimentally induced osteoarthritis to investigate the potential role of oxylipins as a marker in the disease process of early osteoarthritis. DESIGN: Forty rats were randomly allocated to a standard or high-fat diet group...
2018: PloS One
https://www.readbyqxmd.com/read/29683489/regulation-of-cellular-senescence-via-the-foxo4-p53-axis
#7
REVIEW
Benjamin Bourgeois, Tobias Madl
Forkhead box O (FOXO) and p53 proteins are transcription factors that regulate diverse signalling pathways to control cell cycle, apoptosis and metabolism. In the last decade both FOXO and p53 have been identified as key players in aging, and their misregulation is linked to numerous diseases including cancers. However, many of the underlying molecular mechanisms remain mysterious, including regulation of ageing by FOXOs and p53. Several activities appear to be shared between FOXOs and p53, including their central role in the regulation of cellular senescence...
April 23, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29683457/measurement-of-mitochondrial-oxygen-consumption-in-permeabilized-fibers-of-drosophila-using-minimal-amounts-of-tissue
#8
Chloé J Simard, Guillaume Pelletier, Luc H Boudreau, Etienne Hebert-Chatelain, Nicolas Pichaud
The fruit fly, Drosophila melanogaster, represents an emerging model for the study of metabolism. Indeed, drosophila have structures homologous to human organs, possess highly conserved metabolic pathways and have a relatively short lifespan that allows the study of different fundamental mechanisms in a short period of time. It is, however, surprising that one of the mechanisms essential for cellular metabolism, the mitochondrial respiration, has not been thoroughly investigated in this model. It is likely because the measure of the mitochondrial respiration in Drosophila usually requires a very large number of individuals and the results obtained are not highly reproducible...
April 7, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29683328/dietary-clostridium-butyricum-induces-a-phased-shift-in-fecal-microbiota-structure-and-increases-the-acetic-acid-producing-bacteria-in-a-weaned-piglet-model
#9
Jie Zhang, Xiyue Chen, Ping Liu, Jinbiao Zhao, Jian Sun, Wenyi Guan, Lee J Johnston, Crystal L Levesque, Peixin Fan, Ting He, Guolong Zhang, Xi Ma
Clostridium butyricum (C. butyricum) is known as a butyrate producer and a regulator of gut health,but whether it exerts beneficial effect as a dietary supplement via modulating the intestinal microbiota remains elusive. This study investigated the impact of C. butyricum on the fecal microbiota composition and their metabolites on d 14 and d 28 after weaned with 10 g/kg dietary supplementation of C. butyricum. Dynamic changes of microbial compositions showed dramatically increasing Selenomonadales and decreasing Clostridiales on d 14 and d 28...
April 23, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29683320/proteomic-analysis-reveals-inflammation-modulation-of-%C3%AE%C2%BA-%C3%AE-carrageenan-hexaoses-in-lps-induced-raw264-7-macrophages
#10
Juanjuan Guo, Jinghao Chen, Xu Lu, Zebin Guo, Zhiwei Huang, Shaoxiao Zeng, Yi Zhang, Baodong Zheng
κ/ι-Carrageenan hexaoses (κ/ι-neocarrahexaoses, KCO-4) are a type of carrageenan oligosaccharide that have a broad spectrum of bioactivities due to the presence of sulfate groups. However, the anti-inflammatory capacity of purified carrageenan oligosaccharides and the underlying mechanism has not been completely elucidated. The present study aimed to investigate inflammatory signaling modulation of KCO-4 in LPS-induced macrophages using a quantitative proteomic strategy. KCO-4 inhibited the over-secretion of inflammatory mediators (i...
April 23, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29682219/cardiovascular-disease-related-mirnas-expression-potential-role-as-biomarkers-and-effects-of-training-exercise
#11
REVIEW
Simona Ultimo, Giorgio Zauli, Alberto M Martelli, Marco Vitale, James A McCubrey, Silvano Capitani, Luca M Neri
Cardiovascular diseases (CVDs) are one of the most important causes of mortality worldwide, therefore the need of effective preventive strategies is imperative. Aging is associated with significant changes in both cardiovascular structure and function that lower the threshold for clinical signs and symptoms, making older people more susceptible to CVDs morbidity and mortality. microRNAs (miRNAs) modulate gene expression at post-transcriptional level and increasing evidence has shown that miRNAs are involved in cardiovascular physiology and in the pathogenesis of CVDs...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29681862/increased-o-glcnacylation-of-endothelial-nitric-oxide-synthase-compromises-the-anti-contractile-properties-of-perivascular-adipose-tissue-in-metabolic-syndrome
#12
Rafael M da Costa, Josiane F da Silva, Juliano V Alves, Thiago B Dias, Diane M Rassi, Luis V Garcia, Núbia de Souza Lobato, Rita C Tostes
Under physiological conditions, the perivascular adipose tissue (PVAT) negatively modulates vascular contractility. This property is lost in experimental and human obesity and in the metabolic syndrome, indicating that changes in PVAT function may contribute to vascular dysfunction associated with increased body weight and hyperglycemia. The O -linked β-N-acetylglucosamine ( O -GlcNAc) modification of proteins ( O -GlcNAcylation) is a unique posttranslational process that integrates glucose metabolism with intracellular protein activity...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29681858/aqueous-extract-of-black-maca-prevents-metabolism-disorder-via-regulating-the-glycolysis-gluconeogenesis-tca-cycle-and-ppar%C3%AE-signaling-activation-in-golden-hamsters-fed-a-high-fat-high-fructose-diet
#13
Wenting Wan, Hongxiang Li, Jiamei Xiang, Fan Yi, Lijia Xu, Baoping Jiang, Peigen Xiao
Maca ( Lepidium meyenii Walpers) has been used as a dietary supplement and ethnomedicine for centuries. Recently, maca has become a high profile functional food worldwide because of its multiple biological activities. This study is the first explorative research to investigate the prevention and amelioration capacity of the aqueous extract of black maca (AEM) on high-fat, high-fructose diet (HFD)-induced metabolism disorder in golden hamsters and to identify the potential mechanisms involved in these effects...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29681853/caffeine-promotes-conversion-of-palmitic-acid-to-palmitoleic-acid-by-inducing-expression-of-fat-5-in-caenorhabditis-elegans-and-scd1-in-mice
#14
Xiaocui Du, Qin Huang, Yun Guan, Ming Lv, Xiaofang He, Chongye Fang, Xuanjun Wang, Jun Sheng
The synthesis and metabolism of fatty acids in an organism is related to many biological processes and is involved in several diseases. The effects of caffeine on fatty acid synthesis and fat storage in Caenorhabditis elegans and mice were studied. After 6 h of food deprivation, adult C. elegans were treated with 0.1 mg/mL caffeine for 24 h. Quantitative reverse-transcription polymerase chain reaction showed that, among all the genes involved in fat accumulation, the mRNA expression of fat-5 in caffeine-treated C...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29680823/prodomain-of-furin-promotes-phospholipid-transfer-protein-proteasomal-degradation-in-hepatocytes
#15
Yang Yu, Xia Lei, Hui Jiang, Zhiqiang Li, John W M Creemers, Ming Zhang, Shucun Qin, Weijun Jin, Xian-Cheng Jiang
BACKGROUND: Phospholipid transfer protein (PLTP) is one of the major modulators of lipoprotein metabolism and atherosclerosis development; however, little is known about the regulation of PLTP. The effect of hepatic prodomain of furin (profurin) expression on PLTP processing and function is investigated. METHODS AND RESULTS: We used adenovirus expressing profurin in mouse liver to evaluate PLTP activity, mass, and plasma lipid levels. We coexpressed PLTP and profurin in human hepatoma cell line cells and studied their interaction...
April 21, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29680477/yap1-tead1-signaling-controls-angiogenesis-and-mitochondrial-biogenesis-through-pgc1%C3%AE
#16
Akiko Mammoto, Megan Muyleart, Andrew Kadlec, David Gutterman, Tadanori Mammoto
Mitochondria contribute to key processes of cellular function, while mitochondrial dysfunction is implicated in metabolic disorders, neurodegenerative diseases, and cardiovascular diseases, in which angiogenesis - the formation of new blood capillaries - is dysregulated. The Hippo signaling transducer, Yes-associated protein (YAP1) binds to the TEA domain (TEAD1) transcription factor and controls angiogenesis. YAP1 also regulates glucose metabolism through peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC1α), a major player controlling mitochondrial biogenesis...
April 19, 2018: Microvascular Research
https://www.readbyqxmd.com/read/29680326/a-hybrid-mathematical-modeling-approach-of-the-metabolic-fate-of-a-fluorescent-sphingolipid-analogue-to-predict-cancer-chemosensitivity
#17
J A Molina-Mora, M Kop-Montero, I Quirós-Fernández, S Quiros, J L Crespo-Mariño, R A Mora-Rodríguez
Sphingolipid (SL) metabolism is a complex biological system that produces and transforms ceramides and other molecules able to modulate other cellular processes, including survival or death pathways key to cell fate decisions. This signaling pathway integrates several types of stress signals, including chemotherapy, into changes in the activity of its metabolic enzymes, altering thereby the cellular composition of bioactive SLs. Therefore, the SL pathway is a promising sensor of chemosensitivity in cancer and a target hub to overcome resistance...
April 13, 2018: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/29679645/sequencing-of-pt5282-ctxm-p13190-kpc-and-p30860-nr-and-comparative-genomics-analysis-of-incx8-plasmids
#18
Haihong Fang, Jiao Feng, Yuanhong Xu, Ying Zhang, Zhe Zhan, Zhe Yin, Xiongbo Duan, Bo Gao, Yigang Tong, Jinglin Wang, Yanping Luo, Erhei Dai, Dongsheng Zhou
This study proposed a replicon-based scheme for typing IncX into nine separately clustering subgroups, including IncX1α, IncX1β and IncX2-8. The complete nucleotide sequences of three IncX8 plasmids, namely pT5282-CTXM and p30860-NR from Enterobacter cloacae and p13190-KPC from Klebsiella pneumoniae, were determined and compared with all the other two previously sequenced IncX8 plasmids pCAV1043-58 and pCAV1741-16. These five plasmids possessed conserved IncX8 backbones with limited genetic variations with respect to gene content and organization, and each of them carried one or three accessory modules that harbored resistance markers and metabolic gene clusters as well as transposons, insertion sequence (IS)-based transposition units and miniature inverted repeat transposable elements, indicating that the relatively small IncX8 backbones were able to integrate various foreign genetic contents...
April 18, 2018: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29679509/pharmacokinetic-properties-of-wogonin-and-its-herb-drug-interactions-with-docetaxel-in-rats-with-mammary-tumors
#19
Ting Wang, Fangyi Long, Gang Jiang, Hong Cai, Qian Jiang, Kai Cheng, Zhiqiang Hu, Yuxi Wang
Docetaxel, frequently used for the treatment of breast cancer, is mainly metabolized via hepatic cytochrome P450 (CYP) 3A in humans and is also a substrate of P-glycoprotein (P-gp). Wogonin has been shown to be able to modulate the activities of CYPs and P-gp, and it could be served as an adjuvant chemotherapeutic agent. However, the impacts of co-administration of wogonin and docetaxel on their pharmacokinetics have not been studied for lacking analytical method of their simultaneous measurement. In the present study, we established an HPLC-MS/MS method for simultaneous measurement of wogonin and docetaxel in rat plasma, and it was then utilized to explore the pharmacokinetics of wogonin and the herb-drug interactions between wogonin and docetaxel after the combined administration in rats with mammary tumors...
April 21, 2018: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29679417/a-probiotic-modulates-the-microbiome-and-immunity-in-multiple-sclerosis
#20
Stephanie K Tankou, Keren Regev, Brian C Healy, Emily Tjon, Luca Laghi, Laura M Cox, Pia Kivisäkk, Isabelle V Pierre, Hrishikesh Lokhande, Roopali Gandhi, Sandra Cook, Bonnie Glanz, James Stankiewicz, Howard L Weiner
OBJECTIVE: Effect of a probiotic on the gut microbiome and peripheral immune function in healthy controls and relapsing-remitting multiple sclerosis (RRMS) patients. METHODS: MS patients (N=9) and controls (N=13) were orally administered a probiotic containing Lactobacillus, Bifidobacterium and Streptococcus twice daily for two months. Blood and stool specimens were collected at baseline, after completion of the 2-month treatment, and 3 months after discontinuation of therapy...
April 20, 2018: Annals of Neurology
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