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https://www.readbyqxmd.com/read/28813052/mixed-ligand-iridium-iii-complexes-as-photodynamic-anticancer-agents
#1
Yue Zheng, Liang He, Dong-Yang Zhang, Cai-Ping Tan, Liang-Nian Ji, Zong-Wan Mao
Many phosphorescent iridium complexes are potent candidates as photodynamic therapeutic agents. In this work, a series of mixed-ligand phosphorescent iridium complexes (Ir1: [Ir(L1)(bpy)Cl](PF6)2; Ir2: [Ir(L1)(ppy)Cl](PF6); Ir3: [Ir(L2)(bpy)Cl](PF6)2; Ir4: [Ir(L2)(ppy)Cl](PF6). L1 = 2,6-bis(2-benzimidazolyl)pyridine; bpy = 2,2'-bipyridine; L2 = 2,6-bis(1-methyl-benzimidazol-2-yl)pyridine; ppy = 2-phenylpyridine) have been synthesized and characterized. These complexes display high luminescence quantum yields and long phosphorescence lifetimes...
August 16, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28812582/control-of-intestinal-stem-cell-function-and-proliferation-by-mitochondrial-pyruvate-metabolism
#2
John C Schell, Dona R Wisidagama, Claire Bensard, Helong Zhao, Peng Wei, Jason Tanner, Aimee Flores, Jeffrey Mohlman, Lise K Sorensen, Christian S Earl, Kristofor A Olson, Ren Miao, T Cameron Waller, Don Delker, Priyanka Kanth, Lei Jiang, Ralph J DeBerardinis, Mary P Bronner, Dean Y Li, James E Cox, Heather R Christofk, William E Lowry, Carl S Thummel, Jared Rutter
Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation...
August 14, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28812394/the-use-of-sustained-low-efficiency-dialysis-sled-in-massive-paracetamol-overdose
#3
Anselm Wong, Roger L K Tong, Liam Ryan, Tim Crozier, Andis Graudins
CONTEXT: Massive paracetamol ingestion causing mitochondrial dysfunction is uncommon. Use of sustained low-efficiency dialysis (SLED) to improve acidaemia and enhance paracetamol elimination has not been previously described. CASE DETAILS: A 44-year-old male presented to the emergency department 2.5 hours post overdose of 200 g (2.5 g/kg) of paracetamol. Examination revealed a BP 85/60 mmHg, pulse 112 bpm, temperature 33.9 °C and blood glucose of 13...
August 16, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28810700/a-single-mini-barcode-test-to-screen-for-australian-mammalian-predators-from-environmental-samples
#4
Elodie Modave, Anna J MacDonald, Stephen D Sarre
Identification of species from trace samples is now possible through the comparison of diagnostic DNA fragments against reference DNA sequence databases. DNA detection of animals from non-invasive samples, such as predator faeces (scats) that contain traces of DNA from their species of origin, has proved to be a valuable tool for the management of elusive wildlife. However, application of this approach can be limited by the availability of appropriate genetic markers. Scat DNA is often degraded, meaning that longer DNA sequences, including standard DNA barcoding markers, are difficult to recover...
August 1, 2017: GigaScience
https://www.readbyqxmd.com/read/28806519/pluronic-p85-f68-micelles-of-baicalein-could-interfere-with-mitochondria-to-overcome-mrp2-mediated-efflux-and-offer-improved-anti-parkinsonian-activity
#5
Tongkai Chen, Ye Li, Chuwen Li, Xiang Yi, Ruibing Wang, Simon Ming Yuen Lee, Ying Zheng
Overexpression of the drug efflux transporter multidrug resistance-associated protein 2 (MRP2) in the gastrointestinal tract and blood-brain barrier compromises the oral delivery of drugs to the circulation system and brain in the treatment of Parkinson's disease (PD). In this study, we aim to develop small-sized Pluronic P85/F68 micelles loaded with baicalein (B-MCs) to overcome MRP2-mediated efflux and to investigate related mechanism, as well as the anti-Parkinsonian efficacy. Spherical and sustained-release B-MCs have a mean particle size of 40...
August 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28803790/utility-of-the-cytochrome-c-oxidase-subunit-i-gene-for-the-diagnosis-of-toxoplasmosis-using-pcr
#6
Xue Feng, Kazumi Norose, Kexin Li, Kenji Hikosaka
Toxoplasmosis is caused by the protozoan parasite Toxoplasma gondii, which belongs to the phylum Apicomplexa. Since this parasite causes severe clinical symptoms in immunocompromised patients, early diagnosis of toxoplasmosis is essential. PCR is currently used for early diagnosis, but there is no consensus regarding the most effective method for amplifying Toxoplasma DNA. In this study, we considered the utility of the cytochrome c subunit I (cox1) gene, which is encoded in the mitochondrial DNA of this parasite, as a novel target of PCR for the diagnosis of toxoplasmosis...
August 10, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28794642/overexpression-of-mitochondrial-serine-hydroxyl-methyltransferase-2-is-associated-with-poor-prognosis-and-promotes-cell-proliferation-and-invasion-in-gliomas
#7
Ming Wu, Siyi Wanggou, Xuejun Li, Qing Liu, Yuanyang Xie
Mitochondrial serine hydroxyl-methyltransferase 2 (SHMT2), participating in the synthesis of mitochondrial thymidine monophosphate, has been reported to drive glioma cell survival in ischemia. However, its clinical relevance in gliomas remains unclear. In the current study, immunohistochemistry was performed to examine subcellular localization and expression levels of SHMT2 protein in glioma and non-neoplastic brain tissue specimens. Then, the associations of SHMT2 expression with various clinicopathological features and patients' prognosis were statistically evaluated...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28792756/design-synthesis-and-biological-evaluation-of-novel-selenium-containing-isocombretastatins-and-phenstatins-as-antitumor-agents
#8
Yanqing Pang, Baijiao An, Lanlan Lou, Junsheng Zhang, Jun Yan, Ling Huang, Xingshu Li, Sheng Yin
Two series of structurally-related organoselenium compounds designed by fusing the anticancer agent methyl(phenyl)selane into the tubulin polymerization inhibitors isocombretastatins or phenstatins were synthesized and evaluated for antiproliferative activity. Most of these selenium containing hybrids exhibited potent cytotoxicity against a panel of cancel cell lines, with IC50 values in the submicromolar concentration range. Among them, 11a, the 3-methylseleno derivative of isocombretastatin A-4 (isoCA-4), represented the most active compound with IC50 values of 2-34 nM against twelve cancer cell lines, including two drug-resistant cell lines...
August 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28790391/deficiency-of-cox7rp-a-mitochondrial-supercomplex-assembly-promoting-factor-lowers-blood-glucose-level-in-mice
#9
Sachiko Shiba, Kazuhiro Ikeda, Kuniko Horie-Inoue, Akitoshi Nakayama, Tomoaki Tanaka, Satoshi Inoue
Mitochondria are essential organelles to efficiently produce ATP by ATP-synthase, which uses a proton-gradient generated by respiratory chain complexes. We previously demonstrated that COX7RP/COX7A2L/SCAF1 is a key molecule that promotes respiratory supercomplex assembly and regulates energy generation. The contribution of COX7RP to metabolic homeostasis, however, remains to be clarified. In the present study, we showed a metabolic phenotype of Cox7rp knockout (Cox7rpKO) mice, which exhibit lower blood glucose levels after insulin or pyruvate injection...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28789971/the-use-of-high-throughput-screening-techniques-to-evaluate-mitochondrial-toxicity
#10
Lauren P Wills
Toxicologists and chemical regulators depend on accurate and effective methods to evaluate and predict the toxicity of thousands of current and future compounds. Robust high-throughput screening (HTS) experiments have the potential to efficiently test large numbers of chemical compounds for effects on biological pathways. HTS assays can be utilized to examine chemical toxicity across multiple mechanisms of action, experimental models, concentrations, and lengths of exposure. Many agricultural, industrial, and pharmaceutical chemicals classified as harmful to human and environmental health exert their effects through the mechanism of mitochondrial toxicity...
August 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28782592/resveratrol-loaded-solid-lipid-nanoparticles-attenuate-mitochondrial-oxidative-stress-in-vascular-dementia-by-activating-nrf2-ho1-pathway
#11
Aarti Yadav, Aditya Sunkaria, Nitin Singhal, Rajat Sandhir
Vascular dementia (VaD) is the leading cause of cognitive decline resulting from vascular lesions. Recent studies have shown that mitochondrial dysfunctions and oxidative stress are involved in cognitive decline. The aim of the present study was to evaluate the beneficial effects of resveratrol-loaded solid lipid nanoparticles (R-SLNs) in permanent bilateral common carotid artery occlusion (BCCAO) induced model of VaD. R-SLNs prepared were 286 nm in size and had 91.25% drug encapsulation efficiency with sustained release...
August 4, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28780348/integration-of-in-silico-approaches-to-determination-of-endocrine-disrupting-perfluorinated-chemicals-binding-potency-with-steroidogenic-acute-regulatory-protein
#12
K Kranthi Kumar, B Uma Devi, P Neeraja
A myriad of perfluorinated compounds (PFCs) have the ability to interfere with steroidogenic acute regulatory (StAR) protein. Consequently, PFCs breaches cholesterol biotransformation in mitochondria and cause fatal consequences in steroidogenesis however, these were poorly characterized. In the present study, we have evaluated toxic potencies, nuclear mediated probabilities and interaction profiles with StAR of PFCs using computational system biology tools. Toxicity endpoints revealed that PFCs contain high carcinogenicity, developmental toxicity, skin sensitization effects with low mutagenic activity...
August 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28777375/inhibition-of-bcl-xl-prevents-pro-death-actions-of-%C3%AE-n-bcl-xl-at-the-mitochondrial-inner-membrane-during-glutamate-excitotoxicity
#13
Han-A Park, Pawel Licznerski, Nelli Mnatsakanyan, Yulong Niu, Silvio Sacchetti, Jing Wu, Brian M Polster, Kambiz N Alavian, Elizabeth A Jonas
ABT-737 is a pharmacological inhibitor of the anti-apoptotic activity of B-cell lymphoma-extra large (Bcl-xL) protein; it promotes apoptosis of cancer cells by occupying the BH3-binding pocket. We have shown previously that ABT-737 lowers cell metabolic efficiency by inhibiting ATP synthase activity. However, we also found that ABT-737 protects rodent brain from ischemic injury in vivo by inhibiting formation of the pro-apoptotic, cleaved form of Bcl-xL, ΔN-Bcl-xL. We now report that a high concentration of ABT-737 (1 μM), or a more selective Bcl-xL inhibitor WEHI-539 (5 μM) enhances glutamate-induced neurotoxicity while a low concentration of ABT-737 (10 nM) or WEHI-539 (10 nM) is neuroprotective...
August 4, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28776290/synthesis-characterization-and-evaluation-of-cd-l-proline-2-a-novel-histone-deacetylase-inhibitor-that-induces-epigenetic-modification-of-histone-deacetylase-isoforms-in-a549-cells
#14
Anusha Chidambaram, Arunachalam Sekar, Kavya S H, Ramesh Kumar Chidambaram, Kalaiarasi Arunachalam, Senthilkumar G P, Ravikumar Vilwanathan
Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression through their effects on the compact chromatin structure. In clinical studies, several classes of histone deacetylase inhibitors (HDACi) have demonstrated potent anticancer activities with metal complexes. Hence, we synthesized cadmium-proline complexes using both the D- and L-isomers of proline and evaluated their biological activities by observing the efficiency of their inhibition of HDAC activity, ability to reduce the expression of HDAC isoforms in A549 cells and effect on apoptosis...
August 3, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28774846/inhibited-fatty-acid-%C3%AE-oxidation-impairs-stress-resistance-ability-in-nile-tilapia-oreochromis-niloticus
#15
Han Pan, Ling-Yu Li, Jia-Min Li, Wei-Li Wang, Samwel Mchele Limbu, Pascal Degrace, Dong-Liang Li, Zhen-Yu Du
Energy metabolism plays important roles in stress resistance and immunity in mammals, however, such functions have not been established in fish. In the present study, Nile tilapia (Oreochromis niloticus) was fed with mildronate, an inhibitor of mitochondrial fatty acid (FA) β-oxidation, for six weeks subsequently challenged with Aeromonas hydrophila and ammonia nitrogen exposure. Mildronate treatment reduced significantly l-carnitine concentration and mitochondrial FA β-oxidation efficiency, while it increased lipid accumulation in liver...
July 31, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28774815/antioxidant-defense-in-quiescent-cells-determines-selectivity-of-electron-transport-chain-inhibition-induced-cell-death
#16
Jan Blecha, Silvia Magalhaes Novais, Katerina Rohlenova, Eliska Novotna, Sandra Lettlova, Sabine Schmitt, Hans Zischka, Jiri Neuzil, Jakub Rohlena
Mitochondrial electron transport chain (ETC) targeting shows a great promise in cancer therapy. It is particularly effective in tumors with high ETC activity where ETC-derived reactive oxygen species (ROS) are efficiently induced. Why modern ETC-targeted compounds are tolerated on the organismal level remains unclear. As most somatic cells are in non-proliferative state, the features associated with the ETC in quiescence could account for some of the specificity observed. Here we report that quiescent cells, despite increased utilization of the ETC and enhanced supercomplex assembly, are less susceptible to cell death induced by ETC disruption when glucose is not limiting...
July 31, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28772255/salt-responsive-physiological-photosynthetic-and-biochemical-attributes-at-early-seedling-stage-for-screening-soybean-genotypes
#17
D B Shelke, M Pandey, G C Nikalje, B N Zaware, P Suprasanna, T D Nikam
Salt stress affects all the stages of plant growth however seed germination and early seedling growth phases are more sensitive and can be used for screening of crop germplasm. In this study, we aimed to find the most effective indicators of salt tolerance for screening ten genotypes of soybean (SL-295, Gujosoya-2, PS-1042, PK-1029, ADT-1, RKS-18, KDS-344, MAUS-47, Bragg and PK-416). The principal component analysis (PCA) resulted in the formation of three different clusters, salt sensitive (SL-295, Gujosoya-2, PS-1042 and ADT-1), salt tolerant (MAUS-47, Bragg and PK-416) and moderately tolerant/sensitive (RKS-18, PK-1029 and KDS-344) suggesting that there was considerable genetic variability for salt tolerance in the soybean genotypes...
July 16, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28769029/loss-of-succinyl-coa-synthase-adp-forming-%C3%AE-subunit-disrupts-mtdna-stability-and-mitochondrial-dynamics-in-neurons
#18
Yujun Zhao, Jing Tian, Shaomei Sui, Xiaodong Yuan, Hao Chen, Chuanqiang Qu, Yifeng Du, Lan Guo, Heng Du
Succinyl Coenzyme A synthetase (SCS) is a key mitochondrial enzyme. Defected SCS ADP-forming β subunit (SCS A-β) is linked to lethal infantile Leigh or leigh-like syndrome. However, the impacts of SCS A-β deficiency on mitochondria specifically in neurons have not yet been comprehensively investigated. Here, by down-regulating the expression levels of SCS A-β in cultured mouse neurons, we have found that SCS A-β deficiency induces severe mitochondrial dysfunction including lowered oxidative phosphorylation (OXPHOS) efficiency, increased mitochondrial superoxide production, and mtDNA depletion as well as aberrations of mitochondrial fusion and fission proteins, which eventually leads to neuronal stress...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768180/increased-total-mtdna-copy-number-cures-male-infertility-despite-unaltered-mtdna-mutation-load
#19
Min Jiang, Timo Eino Sakari Kauppila, Elisa Motori, Xinping Li, Ilian Atanassov, Kat Folz-Donahue, Nina Anna Bonekamp, Sara Albarran-Gutierrez, James Bruce Stewart, Nils-Göran Larsson
Mutations of mtDNA cause mitochondrial diseases and are implicated in age-associated diseases and aging. Pathogenic mtDNA mutations are often present in a fraction of all mtDNA copies, and it has been widely debated whether the proportion of mutant genomes or the absolute number of wild-type molecules determines if oxidative phosphorylation (OXPHOS) will be impaired. Here, we have studied the male infertility phenotype of mtDNA mutator mice and demonstrate that decreasing mtDNA copy number worsens mitochondrial aberrations of spermatocytes and spermatids in testes, whereas an increase in mtDNA copy number rescues the fertility phenotype and normalizes testes morphology as well as spermatocyte proteome changes...
August 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28767741/antioxidant-effect-of-xanthan-gum-on-ram-sperm-after-freezing-and-thawing
#20
G DA Gastal, E F Silva, B Mion, A S Varela Junior, C E Rosa, C D Corcini, R G Mondadori, A D Vieira, I Bianchi, T Lucia
BACKGROUND: Xanthan gum is used as thickener in media to preserve food products, having cryoprotectant and antioxidant properties that may be relevant for sperm cryopreservation. OBJECTIVE: To evaluate the effects of adding xanthan gum to freezing extenders on post-thawing quality and oxidant activity of ram sperm. METHODS: Ejaculates from seven rams extended TRIS-egg yolk-glycerol were split in three treatments including xanthan gum (0.15%; 0...
May 2017: Cryo Letters
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