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https://www.readbyqxmd.com/read/28098432/a-multi-mitochondrial-anticancer-agent-that-selectively-kills-cancer-cells-and-overcomes-drug-resistance
#1
Yong Bo Peng, Zi Long Zhao, Teng Liu, Guo Jian Xie, Cheng Jin, Tang Gang Deng, Yang Sun, Xiong Li, Xiao Xiao Hu, Xiao Bing Zhang, Mao Ye, Wei Hong Tan
Mitochondria are double-membrane-bound organelles involved mainly in supplying cellular energy, but also play roles in signaling, cell differentiation, and cell death. Mitochondria are implicated in carcinogenesis, and therefore dozens of lethal signal transduction pathways converge on these organelles. Accordingly, mitochondria provide an alternative target for cancer management. In this study, F16, a drug that targets mitochondria, and chlorambucil (CBL), which is indicated for the treatment of selected human neoplastic diseases, were covalently linked, resulting in the synthesis of a multi-mitochondrial anticancer agent, FCBL...
January 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28097102/mechanisms-of-accelerated-liver-fibrosis-progression-during-hiv-infection
#2
REVIEW
Jose D Debes, Paul R Bohjanen, Andre Boonstra
With the introduction of antiretroviral therapy (ART), a dramatic reduction in HIV-related morbidity and mortality has been observed. However, it is now becoming increasingly clear that liver-related complications, particularly rapid fibrosis development from ART as well as from the chronic HIV infection itself, are of serious concern to HIV patients. The pathophysiology of liver fibrosis in patients with HIV is a multifactorial process whereby persistent viral replication, and bacterial translocation lead to chronic immune activation and inflammation, which ART is unable to fully suppress, promoting production of fibrinogenic mediators and fibrosis...
December 28, 2016: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28096195/the-multifunctional-mitochondrial-epac1-controls-myocardial-cell-death
#3
Loubina Fazal, Marion Laudette, Sílvia Paula-Gomes, Sandrine Pons, Caroline Conte, Florence Tortosa, Pierre Sicard, Yannis Sainte-Marie, Malik Bisserier, Olivier Lairez, Alexandre Lucas, Jérôme Roy, Bijan Ghaleh, Jeremy Fauconnier, Jeanne Mialet-Perez, Frank Lezoualc'h
RATIONALE: Although the second messenger cyclic AMP (cAMP) is physiologically beneficial in the heart, it largely contributes to cardiac disease progression when dysregulated. Current evidence suggests that cAMP is produced within mitochondria. However, mitochondrial cAMP signaling and its involvement in cardiac pathophysiology are far from being understood. OBJECTIVE: To investigate the role of mitochondrial exchange protein directly activated by cAMP 1 (MitEpac1) in ischemia/reperfusion (I/R) injury...
January 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28095860/mouse-models-of-atherosclerosis-a-historical-perspective-and-recent-advances
#4
REVIEW
Yee Ting Lee, Hiu Yu Lin, Yin Wah Fiona Chan, Ka Hou Christien Li, Olivia Tsz Ling To, Bryan P Yan, Tong Liu, Guangping Li, Wing Tak Wong, Wendy Keung, Gary Tse
Atherosclerosis represents a significant cause of morbidity and mortality in both the developed and developing countries. Animal models of atherosclerosis have served as valuable tools for providing insights on its aetiology, pathophysiology and complications. They can be used for invasive interrogation of physiological function and provide a platform for testing the efficacy and safety of different pharmacological therapies. Compared to studies using human subjects, animal models have the advantages of being easier to manage, with controllable diet and environmental risk factors...
January 17, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28095363/curcumin-confers-neuroprotection-against-alcohol-induced-hippocampal-neurodegeneration-via-creb-bdnf-pathway-in-rats
#5
Majid Motaghinejad, Manijeh Motevalian, Sulail Fatima, Hajar Hashemi, Mina Gholami
BACKGROUND: Alcohol abuse causes severe damage to the brain neurons. Studies have reported the neuroprotective effects of curcumin against alcohol-induced neurodegeneration. However, the precise mechanism of action remains unclear. METHODS: Seventy rats were equally divided into 7 groups (10 rats per group). Group 1 received normal saline (0.7ml/rat) and group 2 received alcohol (2g/kg/day) for 21days. Groups 3, 4, 5 and 6 concurrently received alcohol (2g/kg/day) and curcumin (10, 20, 40 and 60mg/kg, respectively) for 21days...
January 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28094894/transmission-electron-microscopy-method-providing-high-resolution-in-the-cell-section-without-radiation-damage
#6
Jarmil Prachař
Several new features of mitochondrial nucleoid and its surroundings in mammalian cells were described previously (Prachař, 2016). Very small details were observed using the improved transmission electron microscopy method, as described in the article. In the meantime, the method has again been improved to 2 Å resolutions in the cell section. The method described in detail in the present work is documented on the same records that were published in lower resolution in the work Prachař (2016), enabling comparison of the achieved resolution with the previous one...
January 17, 2017: Microscopy Research and Technique
https://www.readbyqxmd.com/read/28094349/proteomic-and-carbonylation-profile-analysis-at-the-critical-node-of-seed-ageing-in-oryza-sativa
#7
Guangkun Yin, Xia Xin, Shenzao Fu, Mengni An, Shuhua Wu, Xiaoling Chen, Jinmei Zhang, Juanjuan He, James Whelan, Xinxiong Lu
The critical node (CN), which is the transition from the plateau phase to the rapid decreasing phase of seed ageing, is extremely important for seed conservation. Although numerous studies have investigated the oxidative stress during seed ageing, information on the changes in protein abundance at the CN is limited. In this study, we aimed to investigate the abundance and carbonylation patterns of proteins at the CN of seed ageing in rice. The results showed that the germination rate of seeds decreased by less than 20% at the CN; however, the abundance of 112 proteins and the carbonylation levels of 68 proteins markedly changed, indicating oxidative damage...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094012/mammalian-mitochondria-and-aging-an-update
#8
REVIEW
Timo E S Kauppila, Johanna H K Kauppila, Nils-Göran Larsson
Mitochondria were first postulated to contribute to aging more than 40 years ago. During the following decades, multiple lines of evidence in model organisms and humans showed that impaired mitochondrial function can contribute to age-associated disease phenotypes and aging. However, in contrast to the original theory favoring oxidative damage as a cause for mtDNA mutations, there are now strong data arguing that most mammalian mtDNA mutations originate as replication errors made by the mtDNA polymerase. Currently, a substantial amount of mitochondrial research is focused on finding ways to either remove or counteract the effects of mtDNA mutations with the hope of extending the human health- and lifespan...
January 10, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28093935/new-methods-for-monitoring-mitochondrial-biogenesis-and-mitophagy-in%C3%A2-vitro-and-in%C3%A2-vivo
#9
Jessica A Williams, Katrina Zhao, Shengkan Jin, Wen-Xing Ding
Removal of damaged mitochondria through mitophagy is critical for maintaining cellular homeostasis and functions. Increasing evidence implicates mitophagy in red blood cell differentiation, neurodegeneration, macrophage-mediated inflammation, ischemia, adipogenesis, drug-induced tissue injury, and cancer. Considerable progress has been made toward understanding the biochemical mechanisms involved in mitophagy regulation. However, few reliable assays to monitor and quantify mitophagy have been developed, particularly in vivo...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28093764/pre-ischemic-mitochondrial-substrate-constraint-by-inhibition-of-malate-aspartate-shuttle-preserves-mitochondrial-function-after-ischemia-reperfusion
#10
Nichlas Riise Jespersen, Takashi Yokota, Nicolaj Brejnholt Støttrup, Andreas Bergdahl, Kim Bolther Paelestik, Jonas Agerlund Povlsen, Flemming Dela, Hans Erik Bøtker
Mitochondrial dysfunction plays a central role in ischemia-reperfusion (IR) injury. The pre-ischemic administration of aminooxyacetate (AOA), an inhibitor of the malate-aspartate shuttle (MAS), provides cardioprotection against IR injury, but the underlying mechanism remains unknown. We hypothesized that a transient inhibition of the MAS during ischemia and early reperfusion could preserve mitochondrial function at later phase of reperfusion in IR-injured heart to the same extent as ischemic preconditioning (IPC), which is a well-validated cardioprotective strategy against IR injury...
January 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28093214/the-upr-reduces-glucose-metabolism-via-ire1-signaling
#11
Judith M van der Harg, Jessica C van Heest, Fabian N Bangel, Sanne Patiwael, Jan R T van Weering, Wiep Scheper
Neurons are highly dependent on glucose. A disturbance in glucose homeostasis therefore poses a severe risk that is counteracted by activation of stress responses to limit damage and restore the energy balance. A major stress response that is activated under conditions of glucose deprivation is the unfolded protein response (UPR) that is aimed to restore proteostasis in the endoplasmic reticulum. The key signaling of the UPR involves the transient activation of a transcriptional program and an overall reduction of protein synthesis...
January 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28093052/erk-nrf2-ho-1-pathway-mediated-mitophagy-alleviates-traumatic-brain-injury-induced-intestinal-mucosa-damage-and-epithelial-barrier-dysfunction
#12
Yinlong Liu, Zhongyuan Bao, Xiupeng Xu, Honglu Chao, Chao Lin, Zheng Li, Yan Liu, Xiaoming Wang, Yongping You, Ning Liu, Jing Ji
Gastrointestinal dysfunction is one of several physiologic complications in patients with traumatic brain injury (TBI). TBI can result in increased intestinal permeability due to apoptosis of intestinal epithelial cells, which contain a large number of mitochondria for persisting barrier function. Autophagy of damaged mitochondria (mitophagy) controls the quality of the mitochondria and regulates cellular homeostasis. However, the exact mechanism of mitophagy that underlies the pathological changes induced by TBI is unknown...
January 16, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28091991/trophic-transfer-and-effects-of-gold-nanoparticles-aunps-in-gammarus-fossarum-from-contaminated-periphytic-biofilm
#13
Magalie Baudrimont, Jennifer Andrei, Stéphane Mornet, Patrice Gonzalez, Nathalie Mesmer-Dudons, Pierre-Yves Gourves, Ali Jaffal, Odile Dedourge-Geffard, Alain Geffard, Olivier Geffard, Jeanne Garric, Agnès Feurtet-Mazel
This work addressed the trophic transfer and effects of functionalized gold nanoparticles (AuNPs) from periphytic biofilms to the crustacean Gammarus fossarum. Biofilms were exposed for 48 h to 10 nm positively charged functionalized AuNPs at two concentrations, 4.6 and 46 mg/L, and crustaceans G. fossarum grazed on these for 7 days, with daily biofilm renewal. Gold bioaccumulation in biofilm and crustacean were measured to estimate the trophic transfer ratio of these AuNP, and, for the first time, a transcriptomic approach and transmission electron microscopy observations in the crustacean were made...
January 13, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28091959/genetic-variation-in-mitochondrial-genes-of-the-tick-haemaphysalis-flava-collected-from-wild-hedgehogs-in-china
#14
Zhong-Bo Li, Tian-Yin Cheng, Xing-Li Xu, Lu-Lin Song, Guo-Hua Liu
The tick Haemaphysalis flava (Acari: Ixodidae) is an important ectoparasite, which causes direct damage to their hosts and also acts as a vector of various infectious disease agents in China. Despite its significance, the epidemiology, genetics and biology of H. flava has not been studied in detail. In the present study, the genetic variation in three mitochondrial (mt) DNA regions, namely cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 and 4 (nad1 and nad4), was examined in H. flava ticks collected from wild hedgehogs in China...
January 16, 2017: Experimental & Applied Acarology
https://www.readbyqxmd.com/read/28091829/inhibition-of-dpp-4-activity-and-neuronal-atrophy-with-genistein-attenuates-neurological-deficits-induced-by-transient-global-cerebral-ischemia-and-reperfusion-in-streptozotocin-induced-diabetic-mice
#15
Mithun Singh Rajput, Purnima Dey Sarkar, Nilesh Prakash Nirmal
Genistein, an isoflavonoid phytoestrogen, has been known for its potential pharmacological properties especially for neuroprotection and treating diabetes. The present study aims to determine the neuroprotective efficacy of genistein against global cerebral ischemia-reperfusion-induced neuronal injury in streptozotocin-induced diabetic mice and explore the underlying mechanisms. Streptozotocin-induced diabetic mice were subjected to transient cerebral ischemia by occluding both common carotid arteries for 30 min followed by 24 h reperfusion to induce neuronal injury...
January 16, 2017: Inflammation
https://www.readbyqxmd.com/read/28089824/mitochondrial-uncoupling-protein-2-in-human-cumulus-cells-is-associated-with-regulating-autophagy-and-apoptosis-maintaining-gap-junction-integrity-and-progesterone-synthesis
#16
Hongshan Ge, Fan Zhang, Duan Ping, Nan Zhu, Jiayan Zhang, Feijun Ye, Dan Shan, Hua Chen, XiaoSheng Lu, ChunFang Zhu, Renshan Ge, Zhenkun Lin
To explore the roles of mitochondrial Uncoupling Protein 2 (UCP2) in cumulus cells (CCs), human CCs were cultured in vitro, and the UCP2 was inhibited by treatment with Genipin, a special UCP inhibitor, or by RNA interference targeting UCP2. No significant differences in adenosine triphosphate levels and the ratio of ADP/ATP were observed after UCP2 inhibition. UCP2 inhibition caused a significant increase in cellular oxidative damage, which was reflected in alterations to several key parameters, including reactive oxygen species (ROS) and lipid peroxidation levels and the ratio of reduced GSH to GSSG...
January 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28089782/hepatic-co-cultures-in-vitro-reveal-suitable-to-detect-nrf2-mediated-oxidative-stress-responses-on-the-bladder-carcinogen-o-anisidine
#17
Franziska Wewering, Florent Jouy, Sükran Caliskan, Stefan Kalkhof, Martin von Bergen, Andreas Luch, Sebastian Zellmer
The azo dye o-anisidine is known as an industrial and environmental pollutant. Metabolites of o-anisidine remain in the liver for >24h. However, the toxicological impact of o-anisidine on the liver and its individual cell types, e.g., hepatocytes and immune cells, is currently poorly understood. A novel co-culture system, composed of HepG2 or Huh-7 cells, and differentiated THP-1 cells was used to study the metabolic capacity towards o-anisidine, and compared to primary murine hepatocytes which express high enzyme activities...
January 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28089781/genotoxic-effect-and-rat-hepatocyte-death-occurred-after-oxidative-stress-induction-and-antioxidant-gene-downregulation-caused-by-long-term-fluoride-exposure
#18
F D Campos-Pereira, L Lopes-Aguiar, F L Renosto, G A S Nogueira, E F D Costa, R Barbieri Pulz, E C M Silva-Zacarin, C A Oliveira, A A Pigoso, G D C Severi-Aguiar
Studies focusing on possible genotoxic effects of excess fluoride are contradictory and inconclusive. Currently, studies have reported a probable link to oxidative stress, DNA damage and apoptosis induced by fluoride in rat hepatocytes. We developed an in vivo study administering three doses of fluoride by gavage given to rats for 60 day. Micronucleus test was applied to investigate genotoxic potential of fluoride. The TUNEL method determined DNA fragmentation and apoptosis. Biochemical parameters to investigate mitochondrial swelling and oxidative stress...
January 12, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28089741/inflammatory-myopathy-in-a-patient-with-aicardi-gouti%C3%A3-res-syndrome
#19
Birutė Tumienė, Norine Voisin, Eglė Preikšaitienė, Donatas Petroška, Jurgita Grikinienė, Rūta Samaitienė, Algirdas Utkus, Alexandre Reymond, Vaidutis Kučinskas
Aicardi-Goutières syndrome (AGS) is an inflammatory disorder belonging to the recently characterized group of type I interferonopathies. The most consistently affected tissues in AGS are the central nervous system and skin, but various organ systems and tissues have been reported to be affected, pointing to the systemic nature of the disease. Here we describe a patient with AGS due to a homozygous p.Arg114His mutation in the TREX1 gene. The histologically proven inflammatory myopathy in our patient expands the range of clinical features of AGS...
January 9, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28089588/discovery-of-a-novel-series-of-n-hydroxypyridone-derivatives-protecting-astrocytes-against-hydrogen-peroxide-induced-toxicity-via-improved-mitochondrial-functionality
#20
Sarbjit Singh, Ja-Il Goo, Hyojin Noh, Sung Jae Lee, Myoung Woo Kim, Hyejun Park, Hitesh B Jalani, Kyeong Lee, Chunsook Kim, Won-Ki Kim, Chung Ju, Yongseok Choi
Astrocytes play a key role in brain homeostasis, protecting neurons against neurotoxic stimuli such as oxidative stress. Therefore, the neuroprotective therapeutics that enhance astrocytic functionality has been regarded as a promising strategy to reduce brain damage. We previously reported that ciclopirox, a well-known antifungal N-hydroxypyridone compound, protects astrocytes from oxidative stress by enhancing mitochondrial function. Using the N-hydroxypyridone scaffold, we have synthesized a series of cytoprotective derivatives...
January 3, 2017: Bioorganic & Medicinal Chemistry
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