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https://www.readbyqxmd.com/read/29691495/mechanisms-and-treatment-of-organ-failure-in-sepsis
#1
REVIEW
Christophe Lelubre, Jean-Louis Vincent
Sepsis is a dysregulated immune response to an infection that leads to organ dysfunction. Knowledge of the pathophysiology of organ failure in sepsis is crucial for optimizing the management and treatment of patients and for the development of potential new therapies. In clinical practice, six major organ systems - the cardiovascular (including the microcirculation), respiratory, renal, neurological, haematological and hepatic systems - can be assessed and monitored, whereas others, such as the gut, are less accessible...
April 24, 2018: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29691292/phenformin-induced-mitochondrial-dysfunction-sensitizes-hepatocellular-carcinoma-for-dual-inhibition-of-mtor
#2
Sonia Rosa Veiga, Xuemei Ge, Carol A Mercer, María Isabel Hernández-Alvarez, Hala Elnakat Thomas, Javier Hernández-Losa, Santiago Ramón Y Cajal, Antonio Zorzano, George Thomas, Sara C Kozma
PURPOSE: Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited therapeutic options. We recently described the synergistic effect of allosteric and ATP-site competitive inhibitors against the mammalian target of rapamycin (mTOR) for the treatment of HCC. However, such inhibitors induce glycemia and increase mitochondrial efficiency. Here we determined whether the mitochondrial complex I inhibitor Phenformin could reverse both side effects, impose an energetic-stress on cancer cells and suppress the growth of HCC...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29689442/ameliorating-mitochondrial-dysfunction-restores-carbon-ion-induced-cognitive-deficits-via-co-activation-of-nrf2-and-pink1-signaling-pathway
#3
Yang Liu, Jiawei Yan, Cao Sun, Guo Li, Sirui Li, Luwei Zhang, Cuixia Di, Lu Gan, Yupei Wang, Rong Zhou, Jing Si, Hong Zhang
Carbon ion therapy is a promising modality in radiotherapy to treat tumors, however, a potential risk of induction of late normal tissue damage should still be investigated and protected. The aim of the present study was to explore the long-term cognitive deficits provoked by a high-linear energy transfer (high-LET) carbon ions in mice by targeting to hippocampus which plays a crucial role in memory and learning. Our data showed that, one month after 4 Gy carbon ion exposure, carbon ion irradiation conspicuously resulted in the impaired cognitive performance, neurodegeneration and neuronal cell death, as well as the reduced mitochondrial integrity, the disrupted activities of tricarboxylic acid cycle flux and electron transport chain, and the depressed antioxidant defense system, consequently leading to a decline of ATP production and persistent oxidative damage in the hippocampus region...
April 14, 2018: Redox Biology
https://www.readbyqxmd.com/read/29689339/mitochondrial-dysfunction-is-implicated-in-retinoic-acid-induced-spina-bifida-aperta-in-rat-fetuses
#4
Jia Xue, Hui Gu, Dan Liu, Wei Ma, Xiaowei Wei, Lianshuai Zhao, Yusi Liu, Chaonan Zhang, Zhengwei Yuan
Neural tube defects (NTDs) are the most common and severe congenital malformations, which result from failure of the neural tube to close during embryonic development. The etiology of NTDs is complex, caused by interactions between genetic defects and environmental factors, but the exact mechanisms of this disease are still not fully understood. We herein employ a Seahorse Bioscience microplate-based extracellular flux (XF) analyzer to determine mitochondrial function and quantify respiratory coupling to various bioenergetic functions using specific pharmacological inhibitors of bioenergetic pathways...
April 21, 2018: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/29688820/elucidating-differential-nano-bio-interactions-of-multi-walled-andsingle-walled-carbon-nanotubes-using-subcellular-proteomics
#5
Joseph D T Ndika, Jukka Sund, Harri Alenius, Anne Puustinen
Understanding the relationship between adverse exposure events and specific material properties will facilitate predictive classification of carbon nanotubes (CNTs) according to their mechanisms of action, and a safe-by-design approach for the next generation of CNTs. Mass-spectrometry-based proteomics is a reliable tool to uncover the molecular dynamics of hazardous exposures, yet challenges persist with regards to its limited dynamic range when sampling whole organisms, tissues or cell lysates. Here, the simplicity of the sub-cellular proteome was harnessed to unravel distinctive adverse exposure outcomes at the molecular level, between two CNT subtypes...
April 24, 2018: Nanotoxicology
https://www.readbyqxmd.com/read/29688484/effect-of-the-catechol-o-methyltransferase-inhibitors-tolcapone-and-entacapone-on-fatty-acid-metabolism-in-heparg-cells
#6
David Grünig, Andrea Felser, Urs Duthaler, Jamal Bouitbir, Stephan Krähenbühl
Tolcapone and entacapone are catechol-O-methyltransferase (COMT) inhibitors used in patients with Parkinson's disease. For tolcapone, patients with liver failure have been reported with microvesicular steatosis observed in the liver biopsy of one patient. We therefore investigated the impact of tolcapone and entacapone on fatty acid metabolism in HepaRG cells exposed for 24 hours and on acutely exposed mouse liver mitochondria. In HepaRG cells, tolcapone induced lipid accumulation starting at 100µM, whereas entacapone was ineffective up to 200µM...
April 23, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29686775/beneficial-effects-of-cynaroside-on-cisplatin-induced-kidney-injury-in-vitro-and-in-vivo
#7
Jong-Hyun Nho, Ho-Kyung Jung, Mu-Jin Lee, Ji-Hun Jang, Mi-Ok Sim, Da-Eun Jeong, Hyun-Woo Cho, Jong-Choon Kim
Anti-cancer drugs such as cisplatin and doxorubicin are effectively used more than radiotherapy. Cisplatin is a chemotherapeutic drug, used for treatment of various forms of cancer. However, it has side effects such as ototoxicity and nephrotoxicity. Cisplatin-induced nephrotoxicity increases tubular damage and renal dysfunction. Consequently, we investigated the beneficial effect of cynaroside on cisplatin-induced kidney injury using HK-2 cell (human proximal tubule cell line) and an animal model. Results indicated that 10 μM cynaroside diminished cisplatin-induced apoptosis, mitochondrial dysfunction and caspase-3 activation, cisplatin-induced upregulation of caspase-3/MST-1 pathway decreased by treatment of cynaroside in HK-2 cells...
April 2018: Toxicological Research
https://www.readbyqxmd.com/read/29686303/mitochondrial-dna-induces-foley-catheter-related-bladder-inflammation-via-toll-like-receptor-9-activation
#8
Carlos A Puyo, Alexander Earhart, Nicholas Staten, Yuan Huang, Alana Desai, Henry Lai, Ramakrishna Venkatesh
Bladder instrumentation engages the innate immune system via neutrophil activation, promoting inflammation and pain. Elevated levels of mitochondrial DNA (mtDNA) have been associated with tissue damage and organ dysfunction. We hypothesized that local bladder trauma induced by a Foley catheter (FC) will result in mtDNA release, migration of neutrophils into the bladder lumen, and activation of the Toll-like receptor 9 (TLR9) and nuclear factor kappa B (NF-κB) pathway leading to bladder tissue damage. We randomized 10 swine into two groups receiving uncoated, or chloroquine/N-Acetylcysteine (CQ/NAC)-coated FCs...
April 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29686083/unexpected-metabolic-disorders-induced-by-endocrine-disruptors-in-xenopus-tropicalis-provide-new-lead-for-understanding-amphibian-decline
#9
Christophe Regnault, Marie Usal, Sylvie Veyrenc, Karine Couturier, Cécile Batandier, Anne-Laure Bulteau, David Lejon, Alexandre Sapin, Bruno Combourieu, Maud Chetiveaux, Cédric Le May, Thomas Lafond, Muriel Raveton, Stéphane Reynaud
Despite numerous studies suggesting that amphibians are highly sensitive to endocrine disruptors (EDs), both their role in the decline of populations and the underlying mechanisms remain unclear. This study showed that frogs exposed throughout their life cycle to ED concentrations low enough to be considered safe for drinking water, developed a prediabetes phenotype and, more commonly, a metabolic syndrome. Female Xenopus tropicalis exposed from tadpole stage to benzo( a )pyrene or triclosan at concentrations of 50 ng⋅L-1 displayed glucose intolerance syndrome, liver steatosis, liver mitochondrial dysfunction, liver transcriptomic signature, and pancreatic insulin hypersecretion, all typical of a prediabetes state...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29685148/recurrent-inhibition-of-mitochondrial-complex-iii-induces-chronic-pulmonary-vasoconstriction-and-glycolytic-switch-in-the-rat-lung
#10
Olga Rafikova, Anup Srivastava, Ankit A Desai, Ruslan Rafikov, Stevan P Tofovic
BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease; however, the mechanisms directly involved in triggering and the progression of PAH are not clear. Based on previous studies that demonstrated a possible role of mitochondrial dysfunction in the pathogenesis of PAH, we investigated the effects of chronic inhibition of mitochondrial function in vivo in healthy rodents. METHODS: Right ventricle systolic pressure (RVSP) was measured in female rats at baseline and up to 24 days after inhibition of mitochondrial respiratory Complex III, induced by Antimycin A (AA, 0...
April 23, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29684997/protective-effect-of-erythropoietin-against-lipopolysaccharide-induced-inflammation-and-mitochondrial-damage-in-liver
#11
G X Zhang, Y D Du, X H Li, Z T Feng, H Zhao, Y Sun, J J Jin, X J Li
Recent studies have shown that liver dysfunction is an early event in sepsis. Pre-existing liver dysfunction is a risk factor for progression of infection to sepsis. However, the mechanism of the liver immune response in promoting sepsis and the importance of liver function are not completely understood. In the present study, we investigated the protective effect of erythropoietin (EPO) against mitochondrial dysfunction in a lipopolysaccharide (LPS)-induced sepsis model, and examined the underlying signaling mechanisms...
March 2018: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/29684508/methylene-blue-ameliorates-olfactory-dysfunction-and-motor-deficits-in-a-chronic-mptp-probenecid-mouse-model-of-parkinson-s-disease
#12
K C Biju, Robert C Evans, Kripa Shrestha, Daniel C B Carlisle, Jonathan Gelfond, Robert A Clark
Mitochondrial dysfunction and oxidative stress are very prominent and early features in Parkinson's disease (PD) and in animal models of PD. Thus, antioxidant therapy for PD has been proposed, but in clinical trials such strategies have met with very limited success. Methylene blue (MB), a small-molecule synthetic heterocyclic organic compound that acts as a renewable electron cycler in the mitochondrial electron transport chain, manifesting robust antioxidant and cell energetics-enhancing properties, has recently been shown to have significant beneficial effects in reducing nigrostriatal dopaminergic loss and motor impairment in acute toxin models of PD...
April 20, 2018: Neuroscience
https://www.readbyqxmd.com/read/29684467/vitamin-c-for-the-treatment-of-sepsis-the-scientific-rationale
#13
REVIEW
Paul E Marik
Most vertebrates can synthesize vitamin C with synthesis increasing during stress. Humans, however, have lost the ability to synthesize vitamin C. Vitamin C is an important anti-oxidant and an enzyme cofactor for many important biological reactions. Sepsis results in the overwhelming production of reactive oxygen species with widespread endothelial, cellular and mitochondrial injury leading to progressive organ failure. Sepsis is associated with an acute deficiency of vitamin C. In experimental sepsis models, intravenous vitamin C reduces organ injury and improves survival...
April 20, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29684426/mitochondria-targeting-nanomedicine-an-effective-and-potent-strategy-against-aminoglycosides-induced-ototoxicity
#14
Shuang Zhou, Yanhui Sun, Xiao Kuang, Shanshan Hou, YinXian Yang, Zhenjie Wang, Hongzhuo Liu
We report a proof-of-concept for the development of mitochondria-targeting nanoparticles (NPs) loaded with geranylgeranylacetone (GGA) to protect against a wide range of gentamicin-induced ototoxicity symptoms in a zebrafish model. The polymeric NPs were functionalized with a mitochondrial-homing peptide (d‑Arg‑Dmt‑Orn‑Phe‑NH2 ) and exhibited greater mitochondrial uptake and lower gentamicin uptake in hair cells via mechanotransduction (MET) channels and tuned machinery in the hair bundle than the ordinary NPs did...
April 20, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29684334/the-mkk7-inhibitor-peptide-gadd45%C3%AE-i-attenuates-er-stress-induced-mitochondrial-dysfunction-in-ht22-cells-involvement-of-jnk-wnt-pathway
#15
Guang-Hua Xu, Bing-Jun Song, Dan Liu, Yu-Hua Chen, Yuan Zhou, Wen-Bo Liu, Hua Li, Tian-Lin Long, Rui Zhang, Wei Liu
JNK, a member of the mitogen activated protein kinases (MAPKs) superfamily, plays a key role in cell death in many neurological disorders, but systemic inhibition of JNK has detrimental side effects. JNK can be regulated by two direct upstream kinases: MAPK kinase 4 (MKK4) and MAPK kinase 7 (MKK7). Here, we investigated the effect of GADD45β-I, a recently designed cell-permeable inhibitor peptide for MKK7, on endoplasmic reticulum (ER) stress-induced cytotoxicity in neuronal HT22 cells. We found that treatment with the ER stress inducer tunicamycin (TM) increased the phosphorylation of JNK and MKK7 in HT22 cells, which was nullified by GADD45β-I...
April 20, 2018: Brain Research
https://www.readbyqxmd.com/read/29684109/mitochondria-associated-endoplasmic-reticulum-membranes-mams-involve-in-the-regulation-of-mitochondrial-dysfunction-and-heart-failure
#16
Kai Zhang, Qionglin Zhou, Yu Guo, Linxi Chen, Lanfang Li
No abstract text is available yet for this article.
April 19, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29683756/de-novo-expression-of-transfected-sirtuin-3-enhances-susceptibility-of-human-mcf-7-breast-cancer-cells-to-hyperoxia-treatment
#17
Marija Pinterić, Iva I Podgorski, Sandra Sobočanec, Marijana Popović Hadžija, Mladen Paradžik, Ana Dekanić, Maja Marinović, Mirna Halasz, Robert Belužić, Grazia Davidović, Andreja Ambriović Ristov, Tihomir Balog
Sirtuin 3 (Sirt3) has a promising role in cancer tumourigenesis and treatment, but there have been controversies about its role as oncogene or tumour suppressor in different types of cancer. Changes in its expression are associated with the excessive production of reactive oxygen species (ROS), thus contributing to mitochondrial dysfunction and age-related pathologies. Hyperoxic treatment (i.e. generator of ROS) was shown to support some tumourigenic properties, but finally suppresses growth of certain mammary carcinoma cells...
April 23, 2018: Free Radical Research
https://www.readbyqxmd.com/read/29683083/indoxyl-sulfate-induces-apoptosis-and-hypertrophy-in-human-kidney-proximal-tubular-cells
#18
Robert J Ellis, David M Small, Keng Lim Ng, David A Vesey, Luis Vitetta, Ross S Francis, Glenda C Gobe, Christudas Morais
Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with declining kidney function. Although generally thought of as a consequence of declining kidney function, emerging evidence demonstrates direct cytotoxic role of IS on endothelial cells and cardiomyocytes, largely through the expression of pro-inflammatory and pro-fibrotic factors. The direct toxicity of IS on human kidney proximal tubular epithelial cells (PTECs) remains a matter of debate. The current study explored the effect of IS on primary cultures of human PTECs and HK-2, an immortalized human PTEC line...
January 1, 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/29682638/resveratrol-reverses-the-adverse-effects-of-a-diet-induced-obese-murine-model-on-oocyte-quality-and-zona-pellucida-softening
#19
Zhenzhen Jia, Zeyang Feng, Lining Wang, Hao Li, Hongyu Wang, Dingqi Xu, Xin Zhao, Daofu Feng, Xizeng Feng
Reproductive dysfunction associated with obesity is increasing among women of reproductive age, including infertility and increasing risk of miscarriage. In females, reproductive disorders are linked to declining quality of oocytes. Using a model of diet-induced obesity, we have investigated the possible effects of obesity on oocyte quality, including metabolism, lipid accumulation, ROS levels, meiosis and changes in spindle structure in Metaphase II. Our study showed that obesity induced by a high fat diet can impair oocyte meiosis, destroy spindle assembly, and promote oxidative stress and abnormal mitochondrial distribution...
April 23, 2018: Food & Function
https://www.readbyqxmd.com/read/29682501/vdac1-as-pharmacological-target-in-cancer-and-neurodegeneration-focus-on-its-role-in-apoptosis
#20
REVIEW
Andrea Magrì, Simona Reina, Vito De Pinto
Cancer and neurodegeneration are different classes of diseases that share the involvement of mitochondria in their pathogenesis. Whereas the high glycolytic rate (the so-called Warburg metabolism) and the suppression of apoptosis are key elements for the establishment and maintenance of cancer cells, mitochondrial dysfunction and increased cell death mark neurodegeneration. As a main actor in the regulation of cell metabolism and apoptosis, VDAC may represent the common point between these two broad families of pathologies...
2018: Frontiers in Chemistry
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