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https://www.readbyqxmd.com/read/27933294/branched-chain-amino-acid-levels-are-related-with-surrogates-of-disturbed-lipid-metabolism-among-older-men
#1
Urho M Kujala, Markku Peltonen, Merja K Laine, Jaakko Kaprio, Olli J Heinonen, Jouko Sundvall, Johan G Eriksson, Antti Jula, Seppo Sarna, Heikki Kainulainen
AIMS/HYPOTHESIS: Existing studies suggest that decreased branched-chain amino acid (BCAA) catabolism and thus elevated levels in blood are associated with metabolic disturbances. Based on such information, we have developed a hypothesis how BCAA degradation mechanistically connects to tricarboxylic acid cycle, intramyocellular lipid storage, and oxidation, thus allowing more efficient mitochondrial energy production from lipids as well as providing better metabolic health. We analyzed whether data from aged Finnish men are in line with our mechanistic hypothesis linking BCAA catabolism and metabolic disturbances...
2016: Frontiers in Medicine
https://www.readbyqxmd.com/read/27928970/effect-of-transfection-and-co-incubation-of-bovine-sperm-with-exogenous-dna-on-sperm-quality-and-functional-parameters-for-its-use-in-sperm-mediated-gene-transfer
#2
María Elena Arias, Esther Sánchez-Villalba, Andrea Delgado, Ricardo Felmer
Sperm-mediated gene transfer (SMGT) is based on the capacity of sperm to bind exogenous DNA and transfer it into the oocyte during fertilization. In bovines, the progress of this technology has been slow due to the poor reproducibility and efficiency of the production of transgenic embryos. The aim of the present study was to evaluate the effects of different sperm transfection systems on the quality and functional parameters of sperm. Additionally, the ability of sperm to bind and incorporate exogenous DNA was assessed...
December 8, 2016: Zygote: the Biology of Gametes and Early Embryos
https://www.readbyqxmd.com/read/27923139/plga-peg-plga-triblock-copolymeric-micelles-as-oral-drug-delivery-system-in-vitro-drug-release-and-in-vivo-pharmacokinetics-assessment
#3
Xiufen Chen, Jianzhong Chen, Bowen Li, Xiang Yang, Rongjie Zeng, Yajun Liu, Tao Li, Rodney J Y Ho, Jingwei Shao
Poly (d,l-lactide-co-glycolide)-poly (ethylene glycol)-poly (d,l-lactide-co-glycolide) triblock copolymers (PLGA-PEG-PLGA) has been proven to be desirable for anti-cancer drug delivery by intravenous administration. But till now there is no report of developing this micelle as a sustained oral formulation for cancer therapy. 3β-acetoxy-urs-12-en-28-oic acid hexamethylenediamine (US597), a derivative of natural product ursolic acid has been developed as a novel cancer metastasis chemopreventive agent by us...
November 26, 2016: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/27922186/characterization-of-the-pro-inflammatory-cytokine-il-1%C3%AE-on-butyrate-oxidation-in-colorectal-cancer-cells
#4
Megan Johnstone, Natalie Bennett, Cynthia Standifer, Alexis Smith, Anna Han, Ahmed Bettaieb, Jay Whelan, Dallas R Donohoe
Cancer, in part, is driven, by alterations in cellular metabolism that promote cell survival and cell proliferation. Identifying factors that influence this shift in cellular metabolism in cancer cells is important. Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that has been reported to be elevated in colorectal cancer patients. While much is known towards the effect of dietary nutrients on regulating inflammation and the inflammatory response, which includes cytokines such as IL-1β, far less is understood how cytokines impact nutrient fate to alter cancer cell metabolism...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27919073/mitochondrial-replacement-in-human-oocytes-carrying-pathogenic-mitochondrial-dna-mutations
#5
Eunju Kang, Jun Wu, Nuria Marti Gutierrez, Amy Koski, Rebecca Tippner-Hedges, Karen Agaronyan, Aida Platero-Luengo, Paloma Martinez-Redondo, Hong Ma, Yeonmi Lee, Tomonari Hayama, Crystal Van Dyken, Xinjian Wang, Shiyu Luo, Riffat Ahmed, Ying Li, Dongmei Ji, Refik Kayali, Cengiz Cinnioglu, Susan Olson, Jeffrey Jensen, David Battaglia, David Lee, Diana Wu, Taosheng Huang, Don P Wolf, Dmitry Temiakov, Juan Carlos Izpisua Belmonte, Paula Amato, Shoukhrat Mitalipov
Maternally inherited mitochondrial (mt)DNA mutations can cause fatal or severely debilitating syndromes in children, with disease severity dependent on the specific gene mutation and the ratio of mutant to wild-type mtDNA (heteroplasmy) in each cell and tissue. Pathogenic mtDNA mutations are relatively common, with an estimated 778 affected children born each year in the United States. Mitochondrial replacement therapies or techniques (MRT) circumventing mother-to-child mtDNA disease transmission involve replacement of oocyte maternal mtDNA...
December 8, 2016: Nature
https://www.readbyqxmd.com/read/27916644/targeted-mitochondrial-uncoupling-beyond-ucp1-the-fine-line-between-death-and-metabolic-health
#6
REVIEW
Mario Ost, Susanne Keipert, Susanne Klaus
In the early 1930s, the chemical uncoupling agent 2,4-dinitrophenol (DNP) was promoted for the very first time as a powerful and effective weight loss pill but quickly withdrawn from the market due to its lack of tissue-selectivity with resulting dangerous side effects, including hyperthermia and death. Today, novel mitochondria- or tissue-targeted chemical uncouplers with higher safety and therapeutic values are under investigation in order to tackle obesity, diabetes and fatty liver disease. Moreover, in the past 20 years, transgenic mouse models were generated to understand the molecular and metabolic consequences of targeted uncoupling, expressing functional uncoupling protein 1 (UCP1) ectopically in white adipose tissue or skeletal muscle...
December 1, 2016: Biochimie
https://www.readbyqxmd.com/read/27916642/magnetic-hyperthermia-and-ph-responsive-effective-drug-delivery-to-the-sub-cellular-level-of-human-breast-cancer-cells-by-modified-cofe2o4-nanoparticles
#7
Yunok Oh, Madhappan Santha Moorthy, Panchanathan Manivasagan, Subramaniyan Bharathiraja, Junghwan Oh
Magnetic iron oxide nanoparticles (MNPs) have been extensively utilized in a wide range of biomedical applications including magnetic hyperthermia agent. To improve the efficiency of the MNPs in therapeutic applications, in this study, we have synthesized CoFe2O4 nanoparticles and its surface was further functionalized with meso-2,3-dimercaptosuccinic acid (DMSA). The anticancer agent, Doxorubucin (DOX) was conjugated with CoFe2O4@DMSA nanoparticle to evaluate the combined effects of thermotherapy and chemotherapy...
December 1, 2016: Biochimie
https://www.readbyqxmd.com/read/27916505/cyclophilin-d-over-expression-increases-mitochondrial-complex-iii-activity-and-accelerates-supercomplex-formation
#8
Julie C Etzler, Mariana Bollo, Deborah Holstein, Janice Jianhong Deng, Viviana Perez, Da-Ting Lin, Arlan Richardson, Yidong Bai, James D Lechleiter
Cyclophilin D (CyPD), a mitochondrial matrix protein, has been widely studied for its role in mitochondrial-mediated cell death. Unexpectedly, we previously discovered that overexpression of CyPD in a stable cell line, increased mitochondrial membrane potentials and enhanced cell survival under conditions of oxidative stress. Here, we investigated the underlying mechanisms responsible for these findings. Spectrophotometric measurements in isolated mitochondria revealed that overexpression of CyPD in HEK293 cells increased respiratory chain activity, but only for Complex III (CIII)...
December 1, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27913682/translational-regulation-of-mitochondrial-biogenesis
#9
REVIEW
Yi Zhang, Hong Xu
Mitochondria are generated by the expression of genes on both nuclear and mitochondrial genome. Mitochondrial biogenesis is highly plastic in response to cellular energy demand, developmental signals and environmental stimuli. Mechanistic target of rapamycin (mTOR) pathway regulates mitochondrial biogenesis to co-ordinate energy homeostasis with cell growth. The local translation of mitochondrial proteins on the outer membrane facilitates their efficient import and thereby allows prodigious mitochondrial biogenesis during rapid cell growth and proliferation...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27907193/phylogenetic-lineages-and-postglacial-dispersal-dynamics-characterize-the-genetic-structure-of-the-tick-ixodes-ricinus-in-northwest-europe
#10
Knut H Røed, Kjersti S Kvie, Gunnar Hasle, Lucy Gilbert, Hans Petter Leinaas
Dispersal and gene flow are important mechanisms affecting the dynamics of vectors and their pathogens. Here, patterns of genetic diversity were analyzed in many North European populations of the tick, Ixodes ricinus. Population sites were selected within and between areas separated by geographical barriers in order to evaluate the importance of tick transportation by birds in producing genetic connectivity across open sea and mountain ranges. The phylogenetic analyses of the mitochondrial control region and the cytochrome b gene revealed two distinct clades with supported sub-clades, with three genetic lineages: GB and WNo associated with Great Britain and western Norway respectively, and Eu with a wider distribution across continental Europe in agreement with much lower efficiency of tick dispersal by birds than by large mammals...
2016: PloS One
https://www.readbyqxmd.com/read/27907123/mice-hemizygous-for-a-pathogenic-mitofusin-2-allele-exhibit-hind-limb-foot-gait-deficits-and-phenotypic-perturbations-in-nerve-and-muscle
#11
Peter Bannerman, Travis Burns, Jie Xu, Laird Miers, David Pleasure
Charcot-Marie-Tooth disease type 2A (CMT2A), the most common axonal form of hereditary sensory motor neuropathy, is caused by mutations of mitofusin-2 (MFN2). Mitofusin-2 is a GTPase required for fusion of mitochondrial outer membranes, repair of damaged mitochondria, efficient mitochondrial energetics, regulation of mitochondrial-endoplasmic reticulum calcium coupling and axonal transport of mitochondria. We knocked T105M MFN2 preceded by a loxP-flanked STOP sequence into the mouse Rosa26 locus to permit cell type-specific expression of this pathogenic allele...
2016: PloS One
https://www.readbyqxmd.com/read/27903899/human-mitochondrial-transcription-factors-tfam-and-tfb2m-work-synergistically-in-promoter-melting-during-transcription-initiation
#12
Aparna Ramachandran, Urmimala Basu, Shemaila Sultana, Divya Nandakumar, Smita S Patel
Human mitochondrial DNA is transcribed by POLRMT with the help of two initiation factors, TFAM and TFB2M. The current model postulates that the role of TFAM is to recruit POLRMT and TFB2M to melt the promoter. However, we show that TFAM has 'post-recruitment' roles in promoter melting and RNA synthesis, which were revealed by studying the pre-initiation steps of promoter binding, bending and melting, and abortive RNA synthesis. Our 2-aminopurine mapping studies show that the LSP (Light Strand Promoter) is melted from -4 to +1 in the open complex with all three proteins and from -4 to +3 with addition of ATP...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27902774/intravenous-treatment-with-a-long-chain-omega-3-lipid-emulsion-provides-neuroprotection-in-a-murine-model-of-ischemic-stroke-a-pilot-study
#13
Dirk Berressem, Konrad Koch, Nicole Franke, Jochen Klein, Gunter P Eckert
Single long-chain omega-3 fatty acids (e.g. docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA)) are known for their neuroprotective properties associated with ischemic stroke. This pilot study aimed to test the effectiveness of an acute treatment with a long-chain omega-3 lipid emulsion (Omegaven 10%®, OGV) that contains fish oil (DHA 18 mg/ml; EPA 21 mg/ml) and α-tocopherol (0.2 mg/ml) in a transient middle cerebral artery occlusion (MCAO) model of ischemic stroke in mice. For this purpose, female CD-1 mice were anesthetized and subjected to 90 minutes of MCAO...
2016: PloS One
https://www.readbyqxmd.com/read/27900024/acute-effect-of-lactic-acid-on-tumor-endothelial-cell-metabolic-coupling-in-the-tumor-microenvironment
#14
Guanqun Zhu, Degui Wang, Shenqian Li, Xuecheng Yang, Yanwei Cao, Yonghua Wang, Haitao Niu
The present study aimed to systematically analyze alterations in the expression of mitochondrial-associated proteins in human bladder cancer T24 cells co-cultured with tumor-associated human umbilical vein endothelial cells (HUVECs), and to investigate the characteristics of bladder cancer cell energy metabolism. The present study used the following techniques: A co-culture system of T24 cells and HUVECs was constructed using a microfluidic chip as a 3D co-culture system; the concentration of lactic acid in the medium of the cells was determined using an automatic microplate reader; a qualitative analysis of mitochondria-associated protein expression was performed by immunofluorescent staining; and a quantitative analysis of mitochondrial-associated protein expression was conducted using western blotting...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27898923/growth-and-development-symposium-adenosine-monophosphate-activated-protein-kinase-and-mitochondria-in-rendement-napole-pig-growth
#15
T L Scheffler, D E Gerrard
The Rendement Napole mutation (RN-), which is well known to influence pork quality, also has a profound impact on metabolic characteristics of muscle. Pigs with RN- possess a SNP in the γ3 subunit of adenosine monophosphate (AMP)-activated protein kinase (AMPK); AMPK, a key energy sensor in skeletal muscle, modulates energy producing and energy consuming pathways to maintain cellular homeostasis. Importantly, AMPK regulates not only acute response to energy stress but also facilitates long-term adaptation via changes in gene and protein expression...
September 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/27892499/recognition-of-extremophilic-archaeal-viruses-by-eukaryotic-cells-a-promising-nanoplatform-from-the-third-domain-of-life
#16
Kristine Buch Uldahl, Linping Wu, Arnaldur Hall, Pavlos Papathanasiou, Xu Peng, Seyed Moein Moghimi
Viruses from the third domain of life, Archaea, exhibit unusual features including extreme stability that allow their survival in harsh environments. In addition, these species have never been reported to integrate into human or any other eukaryotic genomes, and could thus serve for exploration of novel medical nanoplatforms. Here, we selected two archaeal viruses Sulfolobus monocaudavirus 1 (SMV1) and Sulfolobus spindle shaped virus 2 (SSV2) owing to their unique spindle shape, hyperthermostable and acid-resistant nature and studied their interaction with mammalian cells...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27886551/reconsidering-azobenzene-as-a-component-of-small-molecule-hypoxia-mediated-cancer-drugs-a-theranostic-case-study
#17
Peter Verwilst, Jiyou Han, Jiyeong Lee, Sora Mun, Hee-Gyoo Kang, Jong Seung Kim
An azobenzene scaffold serves as both a fluorescence quencher and nitrogen mustard deactivator in a mitochondrial targeting unit bearing theranostic drug delivery system (DDS). The DDS exhibited a tissue selectivity for tumors with aggressive phenotypes, and the efficient in vitro and in vivo azoreduction under hypoxia conditions resulted in bright fluorescence at the tumor site as well as the in situ activation of the prodrug. In vivo therapeutic experiments demonstrated a significant reduction in tumor growth versus number of controls and ex vivo tissue analysis confirmed tissue normalization with strongly reduced angiogenic markers and suppressed cell proliferation...
January 2017: Biomaterials
https://www.readbyqxmd.com/read/27885628/bcaa-metabolism-and-nh3-homeostasis
#18
M E Conway, S M Hutson
The branched chain amino acids (BCAA) are essential amino acids required not only for growth and development, but also as nutrient signals and as nitrogen donors to neurotransmitter synthesis and glutamate/glutamine cycling. Transamination and oxidative decarboxylation of the BCAAs are catalysed by the branched-chain aminotransferase proteins (BCATm, mitochondrial and BCATc, cytosolic) and the branched-chain α-keto acid dehydrogenase enzyme complex (BCKDC), respectively. These proteins show tissue, cell compartmentation, and protein-protein interactions, which call for substrate shuttling or channelling and nitrogen transfer for oxidation to occur...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27877138/a-ketogenic-diet-in-rodents-elicits-improved-mitochondrial-adaptations-in-response-to-resistance-exercise-training-compared-to-an-isocaloric-western-diet
#19
Hayden W Hyatt, Wesley C Kephart, A Maleah Holland, Petey Mumford, C Brooks Mobley, Ryan P Lowery, Michael D Roberts, Jacob M Wilson, Andreas N Kavazis
Purpose: Ketogenic diets (KD) can facilitate weight loss, but their effects on skeletal muscle remain equivocal. In this experiment we investigated the effects of two diets on skeletal muscle mitochondrial coupling, mitochondrial complex activity, markers of oxidative stress, and gene expression in sedentary and resistance exercised rats. Methods: Male Sprague-Dawley rats (9-10 weeks of age, 300-325 g) were fed isocaloric amounts of either a KD (17 g/day, 5.2 kcal/g, 20.2% protein, 10.3% CHO, 69.5% fat, n = 16) or a Western diet (WD) (20 g/day, 4...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27875779/novel-pyrimidine-2-4-dione-1-2-3-triazole-and-furo-2-3-d-pyrimidine-2-one-1-2-3-triazole-hybrids-as-potential-anti-cancer-agents-synthesis-computational-and-x-ray-analysis-and-biological-evaluation
#20
Tomislav Gregorić, Mirela Sedić, Petra Grbčić, Andrea Tomljenović Paravić, Sandra Kraljević Pavelić, Mario Cetina, Robert Vianello, Silvana Raić-Malić
Regioselective 1,4-disubstituted 1,2,3-triazole tethered pyrimidine-2,4-dione derivatives (5-23) were successfully prepared by the copper(I)-catalyzed click chemistry. While known palladium/copper-cocatalyzed method based on Sonogashira cross-coupling followed by the intramolecular 5-endo-dig ring closure generated novel 6-alkylfuro[2,3-d]pyrimidine-2-one-1,2,3-triazole hybrids (24b-37b), a small library of their 5-alkylethynyl analogs (24a-37a) was synthesized and described for the first time by tandem terminal alkyne dimerization and subsequent 5-endo-trig cyclization, which was additionally corroborated with computational and X-ray crystal structure analyses...
January 5, 2017: European Journal of Medicinal Chemistry
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