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Metabolic response to injury

Rehab S Abdelrahman, Noha Abdel-Rahman
Drug-induced liver toxicity is the most frequent cause of acute liver failure worldwide. Hepatotoxicity caused by acetaminophen (ACT) overdose is mediated by its metabolic product promoting oxidative stress and activation of inflammatory mediators. Nuclear factor erythroid-related factor-2 (Nrf-2) induces the release of cytoprotective enzymes in response to electrophilic or oxidative stress and is considered a promising therapeutic target. Dimethyl fumarate (DMF) is a potent activator of (Nrf-2), its anti-inflammatory and antioxidant properties of DMF have been highlighted recently...
December 11, 2018: Life Sciences
Frederick A Zeiler, Eric P Thelin, Joseph Donnelly, Andrew R Stevens, Peter Smielewski, Marek Czosnyka, Peter J Hutchinson, David K Menon
Cerebral autoregulatory dysfunction after traumatic brain injury (TBI) is strongly linked to poor global outcome in patients at 6 months after injury. However, our understanding of the drivers of this dysfunction is limited. Genetic variation among individuals within a population gives rise to single-nucleotide polymorphisms (SNPs) that have the potential to influence a given patient's cerebrovascular response to an injury. Associations have been reported between a variety of genetic polymorphisms and global outcome in patients with TBI, but few studies have explored the association between genetic variants and cerebrovascular function after injury...
December 13, 2018: Nature Reviews. Neurology
Marco Moscarelli, Francesca Fiorentino, M-Saadeh Suleiman, Costanza Emanueli, Barnaby C Reeves, Prakash P Punjabi, Gianni D Angelini
OBJECTIVES: This trial was designed and patients were recruited at a time when the benefits of remote ischaemic preconditioning during open-heart surgery were still controversial. We focused on a homogeneous patient population undergoing either isolated aortic valve replacement or coronary artery bypass grafting (CABG) surgery by investigating cardiac injury, metabolic stress and inflammatory response. METHODS: A 2-centre randomized controlled trial recruited a total of 124 patients between February 2013 and April 2015...
December 12, 2018: European Journal of Cardio-thoracic Surgery
Lucija Tudor, Marcela Konjevod, Matea Nikolac Perkovic, Dubravka Svob Strac, Gordana Nedic Erjavec, Suzana Uzun, Oliver Kozumplik, Marina Sagud, Zrnka Kovacic Petrovic, Nela Pivac
Posttraumatic stress disorder (PTSD) is a trauma and stressor related disorder that may develop after exposure to an event that involved the actual or possible threat of death, violence or serious injury. Its molecular underpinning is still not clear. Brain-derived neurotrophic factor (BDNF) modulates neuronal processes such as the response to stress, but also weight control, energy and glucose homeostasis. Plasma BDNF levels and a functional BDNF Val66Met (rs6265) polymorphism were reported to be associated with PTSD, as well as with increased body mass index (BMI) and dyslipidaemia in healthy subjects and patients with cardio-metabolic diseases, but these results are controversial...
2018: Frontiers in Psychiatry
Ashraf S Gorgey, Oksana Witt, Laura O'Brien, Christopher Cardozo, Qun Chen, Edward J Lesnefsky, Zachary A Graham
Mitochondria are responsible for aerobic respiration and large-scale ATP production in almost all cells of the body. Their function is decreased in many neurodegenerative and cardiovascular disease states, in metabolic disorders such as type II diabetes and obesity, and as a normal component of aging. Disuse of skeletal muscle from immobilization or unloading triggers alterations of mitochondrial density and activity. Resultant mitochondrial dysfunction after paralysis, which precedes muscle atrophy, may augment subsequent release of reactive oxygen species leading to protein ubiquitination and degradation...
December 11, 2018: European Journal of Applied Physiology
Liang Liu, Qinling Hu, Huihui Wu, Xiujing Wang, Chao Gao, Guoxun Chen, Ping Yao, Zhiyong Gong
Diets containing various docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) ratios protect against liver damage in mice fed with a high-fat diet (HFD). However, it is unclear whether these beneficial roles of DHA and EPA are associated with alterations of fatty acid (FA) composition in the liver. This study evaluated the positive impacts of n-6/n-3 polyunsaturated fatty acids (PUFAs) containing different DHA/EPA ratios on HFD-induced liver disease and alterations of the hepatic FA composition. ApoE-/- mice were fed with HFDs with various ratios of DHA/EPA (2 : 1, 1 : 1, and 1 : 2) and an n-6/n-3 ratio of 4 : 1 for 12 weeks...
2018: Oxidative Medicine and Cellular Longevity
Xun Li, Zhanwen Lin, Lei Wang, Qin Liu, Zhi Cao, Zhujuan Huang, Mingtian Zhong, Shuxian Peng, Yingheng Zhang, Yong Li, Xiaodong Ma
BACKGROUND/AIMS: Our previous study demonstrated that a deficiency of microRNA 21 (miR-21) protects mice from acute pancreatitis, yet the underlying molecular networks associated with miR-21 in pancreatitis and pancreatitis-associated lung injury remain unexplored. METHODS: We used next generation sequencing to analyze gene expression profiles of pancreatic tissues from wild-type (WT) and miR-21 knockout (KO) mice treated with caerulein by using a 1-day treatment protocol...
2018: Cellular Physiology and Biochemistry
David J Orlicky, Andrew E Libby, Elise S Bales, Rachel H McMahan, Jenifer Monks, Francisco G La Rosa, James L McManaman
KEY POINTS: Wild type mice as well as mice with hepatocyte-specific or whole-body deletions of perilipin-2 (Plin2) were used to define hepatocyte and extra-hepatocyte effects of altered cellular lipid storage on obesity and non-alcoholic fatty liver disease (NAFLD) pathophysiology in a western-diet (WD) model of these disorders. Extra-hepatocyte actions of Plin2 are responsible for obesity, adipose inflammation, and glucose clearance abnormalities in WD-fed mice. Hepatocyte and extra-hepatic actions of Plin2 mediate fatty liver formation in WD-fed mice through distinct mechanisms...
December 8, 2018: Journal of Physiology
Eliana Baez-Jurado, Gina Guio-Vega, Oscar Hidalgo-Lanussa, Janneth González, Valentina Echeverria, Ghulam Md Ashraf, Amirhossein Sahebkar, George E Barreto
Astrocytes are specialized cells capable of regulating inflammatory responses in neurodegenerative diseases or traumatic brain injury. In addition to playing an important role in neuroinflammation, these cells regulate essential functions for the preservation of brain tissue. Therefore, the search for therapeutic alternatives to preserve these cells and maintain their functions contributes in some way to counteract the progress of the injury and maintain neuronal survival in various brain pathologies. Among these strategies, the conditioned medium from human adipose-derived mesenchymal stem cells (CM-hMSCA) has been reported with a potential beneficial effect against several neuropathologies...
December 8, 2018: Molecular Neurobiology
Antonella Calzone, Alessandra Podda, Giacomo Lorenzini, Bianca Elena Maserti, Elisa Carrari, Elena Deleanu, Yasutomo Hoshika, Matthew Haworth, Cristina Nali, Ovidiu Badea, Elisa Pellegrini, Silvano Fares, Elena Paoletti
Plants are exposed to a broad range of environmental stresses, such as salinity and ozone (O3 ), and survive due to their ability to adjust their metabolism. The aim of this study was to evaluate the physiological and biochemical adjustments adopted by pomegranate (Punica granatum L. cv. Dente di cavallo) under realistic field conditions. One-year-old saplings were exposed to O3 [two levels denoted as ambient (AO) and elevated (EO) O3 concentrations] and salinity [S (salt, 50 mM NaCl)] for three consecutive months...
November 28, 2018: Science of the Total Environment
Hye-Youn Cho, Laura Miller-DeGraff, Terry Blankenship-Paris, Xuting Wang, Douglas A Bell, Fred Lih, Leesa Deterding, Vijayalakshmi Panduri, Daniel L Morgan, Masayuki Yamamoto, Anita J Reddy, Paul Talalay, Steven R Kleeberger
Nrf2 is essential to antioxidant response element (ARE)-mediated host defense. Sulforaphane (SFN) is a phytochemical antioxidant known to affect multiple cellular targets including Nrf2-ARE pathway in chemoprevention. However, the role of SFN in non-malignant airway disorders remain unclear. To test if pre-activation of Nrf2-ARE signaling protects lungs from oxidant-induced acute injury, wild-type (Nrf2+/+ ) and Nrf2-deficient (Nrf2-/- ) mice were given SFN orally or as standardized broccoli sprout extract diet (SBE) before hyperoxia or air exposure...
December 5, 2018: Toxicology and Applied Pharmacology
Prangmalee Leurcharusmee, Passakorn Sawaddiruk, Yodying Punjasawadwong, Nipon Chattipakorn, Siriporn C Chattipakorn
Ischemia and reperfusion (I/R) injury induced by tourniquet (TQ) application leads to the release of both oxygen free radicals and inflammatory cytokines. The skeletal muscle I/R may contribute to local skeletal muscle and remote organ damage affecting outcomes after total knee arthroplasty (TKA). The aim of the study is to summarize the current findings associated with I/R injury following TKA using a thigh TQ, which include cellular alterations and protective therapeutic interventions. The PubMed database was searched using the keywords "ischemia reperfusion injury," "oxidative stress," "tourniquet," and "knee arthroplasty...
2018: Oxidative Medicine and Cellular Longevity
William J Pearce
The human cerebral vasculature originates in the fourth week of gestation and continues to expand and diversify well into the first few years of postnatal life. A key feature of this growth is smooth muscle differentiation, whereby smooth muscle cells within cerebral arteries transform from migratory to proliferative to synthetic and finally to contractile phenotypes. These phenotypic transformations can be reversed by pathophysiological perturbations such as hypoxia, which causes loss of contractile capacity in immature cerebral arteries...
December 2018: Seminars in Pediatric Neurology
Anja Beckmann, Alexander Grißmer, Sandra Wolf, Johanna Recktenwald, Carola Meier
In the intact brain, astrocytes play an important role in a number of physiological functions like spatial buffering of potassium, maintenance of calcium homeostasis, neurotransmitter release, regulation of the cerebral blood flow, and many more. As pathophysiological events upon hypoxic-ischemic brain injury include excitotoxicity by glutamate release as well as oxidative stress, astrocytes and their gap junction-based syncytium are of major relevance for regulating the extent of resulting brain damage. The gap junction protein Connexin 43 (Cx43) contributes mainly to the astrocytic intercellular communication...
December 1, 2018: Neuroscience
Jana Schleicher, Uta Dahmen
Question: Donor liver organs with moderate to high fat content (i.e. steatosis) suffer from an enhanced susceptibility to ischemia/reperfusion injury (IRI) during liver transplantation. Responsible for the cellular injury is an increased level of oxidative stress, however the underlying mechanistic network is still not fully understood. Method: We developed a phenomenological mathematical model of key processes of hepatic lipid metabolism linked to pathways of oxidative stress...
2018: Computational and Structural Biotechnology Journal
Yunfang Zhang, Junxia Feng, Qi Wang, Shili Zhao, Shen Yang, Lu Tian, Ping Meng, Jingchun Li, Hongyan Li
BACKGROUND/AIMS: Hyperglycaemia stress-induced renal injury is closely associated with mitochondrial dysfunction through poorly understood mechanisms. The aim of our study is to explore the upstream trigger and the downstream effector driving diabetic nephropathy via modulating mitochondrial homeostasis. METHODS: A diabetic nephropathy model was generated in wild-type (WT) mice and MAP Kinase phosphatase 1 transgenic (MKP1-TG) mice using STZ injection. Cell experiments were conducted via high-glucose treatment in the human renal mesangial cell line (HRMC)...
November 30, 2018: Cellular Physiology and Biochemistry
Rui Cao, Chenchu Zhang, Vladimir Mitkin, Miles Lankford, Jun Li, Zhiyi Zuo, Craig Meyer, Christopher Goyne, Stephen Ahlers, James R Stone, Song Hu
Blast traumatic brain injury (bTBI) is a leading contributor to combat-related injuries and death. Although substantial emphasis has been placed on blast-induced neuronal and axonal injuries, co-existing dysfunctions in the cerebral vasculature, particularly the microvasculature, remain poorly understood. Here, we studied blast-induced cerebrovascular dysfunctions in a rat model of bTBI (blast overpressure: 187.8±18.3 kPa). Using photoacoustic microscopy, we quantified changes in cerebral hemodynamics and metabolism-including blood perfusion, oxygenation, flow, oxygen extraction fraction, and the metabolic rate of oxygen-4 hours post-injury...
December 1, 2018: Journal of Neurotrauma
Lisa M Mangus, Rachel L Weinberg, Audrey C Knight, Suzanne E Queen, Robert J Adams, Joseph L Mankowski
Human immunodeficiency virus-associated sensory neuropathy (HIV-SN) remains a frequent neurologic complication of HIV infection. Little is known about alterations in the peripheral nervous system during the early stages of HIV, a time when neuroprotective interventions may be most beneficial. We performed Nanostring gene expression analysis on lumbar dorsal root ganglia (DRG) from 6 simian immunodeficiency virus (SIV)-infected pigtailed macaques killed at 7 days post-inoculation and 8 uninfected controls. We found significant upregulation of many genes involved in immune signaling and activation in the DRG...
November 4, 2018: Journal of Neuropathology and Experimental Neurology
Xueting Yao, Chao Xu, Yurong Cao, Lin Lin, Hanxu Wu, Chang Wang
Radiation-induced brain injury contains acute, early delayed and late delayed damage based on the time-course and clinical manifestations. The acute symptoms are mostly transient and reversible, whereas the late delayed radiation-induced changes are progressive and irreversible. Therefore, evaluation of the organ specific early response to ionizing radiation exposure is necessary for improving treatment strategies and minimizing possible damages at early stage after radiation exposure. In current study, the gas chromatography-mass spectrometry technique (GC-MS) based on metabolomics coupled with metabolic correlation network was applied to investigate the early metabolic characterization of the rat brain tissues following irradiation...
November 30, 2018: Biomedical Chromatography: BMC
Ramires Alsamir Tibana, Nuno Manuel Frade de Sousa
Extreme conditioning programmes (ECPs, eg, CrossFit, Insanity and Gym Jones) are a growing fitness regimen characterised by functional movements performed at high-intensity and with constantly varying movements. While the popularity and number of practitioners of ECPs are growing, a debate has been established between what is observed in the scientific literature and anecdotal reports from athletes, coaches and physicians about safety (incidence and prevalence of injuries and rhabdomyolysis) and benefits (physical and mental health)...
2018: BMJ Open Sport & Exercise Medicine
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