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Metabolic response to injury

Mary S McCarthy, Evelyn B Elshaw, Barbara M Szekely, Dheeraj Raju
PURPOSE: To explore response to vitamin D supplementation in active duty (AD) warfighters and translate findings into evidence-based health policy. BACKGROUND: Soldiers are at risk for musculoskeletal injuries and metabolic dysfunction that impact physical performance and military readiness; the link with low vitamin D status is unclear. METHODS: This prospective trial enrolled 152 soldiers; baseline 25 hydroxyvitamin (OH) D level determined assignment to a no-treatment control (CG) or treatment group (TG) receiving a vitamin D3 supplement for 90 days...
March 1, 2019: Military Medicine
Barbara Scelsa, Serena Gasperini, Andrea Righini, Maria Iascone, Valeria G Brazzoduro, Pierangelo Veggiotti
BACKGROUND: Molybdenum cofactor deficiency (MoCD) is a rare autosomal-recessive disorder that results in the combined deficiency of molybdenum-dependent enzymes. Four different genes are involved in Molybdenum cofactor biosynthesis: MOCS1, MOCS2, MOCS3, and GEPH. The classical form manifests in the neonatal period with severe encephalopathy, including intractable seizures, MRI changes that resemble hypoxic-ischemic injury, microcephaly, and early death. To date, an atypical phenotype with late-onset has been reported in the literature in 13 patients...
March 21, 2019: Molecular Genetics & Genomic Medicine
Zhimeng Lv, Ming Guo, Chenghua Li, Yina Shao, Xuelin Zhao, Weiwei Zhang
Skin ulceration syndrome (SUS) of sea cucumber is a common and serious disease that affects the stable development of Apostichopus japonicus in the culture industry. The part of sea cucumber that suffers from major injury and is directly observed is the body wall, in which protein variations should be the most direct evidence of the disease. To understand the response mechanisms of A. japonicus in SUS progression, we investigated protein changes in the body wall of diseased A. japonicus induced by Vibrio splendidus and individuals with natural diseases by isobaric tags for relative and absolute quantification (iTRAQ)...
March 13, 2019: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
Mitchell C Lock, Jack R T Darby, Jia Yin Soo, Doug A Brooks, Sunthara Rajan Perumal, Joseph B Selvanayagam, Mike Seed, Christopher K Macgowan, Enzo R Porrello, Ross L Tellam, Janna L Morrison
Aim: Characterizing the response to myocardial infarction (MI) in the regenerative sheep fetus heart compared to the post-natal non-regenerative adolescent heart may reveal key morphological and molecular differences that equate to the response to MI in humans. We hypothesized that the immediate response to injury in (a) infarct compared with sham, and (b) infarct, border, and remote tissue, in the fetal sheep heart would be fundamentally different to the adolescent, allowing for repair after damage. Methods: We used a sheep model of MI induced by ligating the left anterior descending coronary artery...
2019: Frontiers in Physiology
Muhammad Naveed, Qi-Gang Zhou, Feng Han
The cerebrovascular system is not only inert bystandard that support the metabolic demands of the brain but also elicit the barrier functions against risk factors mediated neurovascular injury. The onsets of cerebrovascular inflammation are considered as stimuli that can provoke the host defense system and trigger the development of neurological disorders. Homeostasis of the brain function is regulated by the movement of endothelial, glial, and neuronal cells within the neurovascular unit (NVU), which acts as a "platform" for the coordinated action of anti- and pro-inflammatory mechanisms...
March 16, 2019: Neurochemistry International
Blanca I Aldana
The high energetic demand of the brain deems this organ rather sensitive to changes in energy supply. Therefore, even minor alterations in energy metabolism may underlie detrimental disturbances in brain function, contributing to the generation and progression of neurodegenerative diseases. Considerable evidence supports the key role of deficits in cerebral energy metabolism, particularly hypometabolism of glucose and mitochondrial dysfunction, in the pathophysiology of brain disorders. Major breakthroughs in the field of bioenergetics and neurodegeneration have been achieved through the use of in vitro and in vivo models of disease as well as sophisticated neuroimaging techniques in patients, yet these have been mainly focused on neuron and astrocyte function...
March 13, 2019: Journal of Molecular Biology
Dan Wu, Ming Zhou, Liang Li, Xiangfeng Leng, Zheng Zhang, Ning Wang, Yanwei Sun
Patients with severe burns are susceptible to infectious complications including burn-site infections and sepsis. The purpose of this study was to explore the pathologic development of burn injury in a mouse model and to screen genes dysregulated at different time points on the basis of gene expression microarrays. Differential expression analysis identified a total 223 genes that related to only time progression independent of burn injury and 214 genes with aberrant expression due to burn injury. Weighted gene co-expression network analysis (WGCNA) of the 214 genes obtained seven gene modules which named as red, blue, turquoise, green, brown, yellow, and gray module, and the blue module was found to be significantly associated with severe burn injury progression, and in which several genes were previously reported being associated with inflammation and immune response, such as interleukin IL-6, IL-8, and IL-1b...
March 16, 2019: Inflammation
Yun Fang, David Wu, Konstantin G Birukov
Vascular endothelial cells (ECs) form a semiselective barrier for macromolecules and cell elements regulated by dynamic interactions between cytoskeletal elements and cell adhesion complexes. ECs also participate in many other vital processes including innate immune reactions, vascular repair, secretion, and metabolism of bioactive molecules. Moreover, vascular ECs represent a unique cell type exposed to continuous, time-dependent mechanical forces: different patterns of shear stress imposed by blood flow in macrovasculature and by rolling blood cells in the microvasculature; circumferential cyclic stretch experienced by the arterial vascular bed caused by heart propulsions; mechanical stretch of lung microvascular endothelium at different magnitudes due to spontaneous respiration or mechanical ventilation in critically ill patients...
March 15, 2019: Comprehensive Physiology
Anup Ramachandran, Ruben G J Visschers, Luqi Duan, Jephte Y Akakpo, Hartmut Jaeschke
Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids...
May 28, 2018: Journal of Clinical and Translational Research
Wen-Fa Zhang, Ze-Hao Gong, Meng-Bo Wu, Helen Chan, Yu-Jin Yuan, Ning Tang, Qiang Zhang, Ming-Jun Miao, Wei Chang, Zhi Li, Zheng-Guo Li, Liang Jin, Wei Deng
Tomato fruit are especially susceptible to chilling injury (CI) when continuously exposed to temperatures below 12 °C. In this study, integrative comparative analyses of transcriptomics and metabolomics data were performed to uncover the regulatory network in CI tomato fruit. Metabolite profiling analysis found that 7 amino acids, 27 organic acids, 16 of sugars and 22 other compounds had a significantly different content while transcriptomics data showed 1735 differentially expressed genes (DEGs) were down-regulated and 1369 were up-regulated in cold-stored fruit...
March 14, 2019: Scientific Reports
Sashi Kant, Gangarao Davuluri, Khaled A Alchirazi, Nicole Welch, Claire Heit, Avinash Kumar, Mahesha Gangadhariah, Adam Kim, Megan R McMullen, Belinda Willard, Donal S Luse, Laura E Nagy, Vasilis Vasiliou, Anna Maria Marini, David Weiner, Srinivasan Dasarathy
Ethanol causes dysregulated muscle protein homeostasis while simultaneously causing hepatocyte injury. Since hepatocytes are the primary site for physiological disposal of ammonia, a cytotoxic cellular metabolite generated during a number of metabolic processes, we determined if hyperammonemia aggravates ethanol-induced muscle loss. Differentiated murine C2C12 myotubes, skeletal muscle from pair-fed or ethanol-treated mice and human patients with alcoholic cirrhosis and healthy controls were used to quantify protein synthesis, mTORC1 signaling and autophagy makers...
March 14, 2019: Journal of Biological Chemistry
Marco Aurelio M Freire, Luana Nazaré S Santana, Leonardo Oliveira Bittencourt, Priscila Cunha Nascimento, Rafael Monteiro Fernandes, Luana Ketlen R Leão, Luanna Melo P Fernandes, Marcia Cristina F Silva, Lílian Lund Amado, Walace Gomes-Leal, Maria Elena Crespo-Lopez, Cristiane do Socorro F Maia, Rafael Rodrigues Lima
Stroke is one of the main causes of human disability worldwide. Ischemic stroke is mostly characterized by metabolic collapse and fast tissue damage, followed by secondary damage in adjacent regions not previously affected. Heavy metals intoxication can be associated with stroke incidence, because of their damaging action in the vascular system. Mercury, in particular, possesses a high tropism by metabolically active regions, such as the brain. In the present study we sought to evaluate whether methylmercury (MeHg) intoxication can aggravate the tissue damage caused by an ischemic stroke induced by microinjections of endothelin-1 (ET-1) into the motor cortex of adult rats...
March 9, 2019: Ecotoxicology and Environmental Safety
Luthfiyyah Mutsnaini, Chu-Sook Kim, Jiye Kim, Yeonsoo Joe, Hun Taeg Chung, Hye-Seon Choi, Eun Roh, Min-Seon Kim, Rina Yu
OBJECTIVE AND DESIGN: Hypothalamic inflammation is closely associated with metabolic dysregulation. Fibroblast growth factor 21 (FGF21) is known to be an important metabolic regulator with anti-inflammatory properties. In this study, we investigated the effects of FGF21 deficiency on obesity-induced hypothalamic inflammation and thermogenic responses. MATERIALS AND METHODS: FGF21-deficient mice and/or wild-type (WT) mice were fed a high-fat diet (HFD) for 12 weeks...
March 12, 2019: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Ke Shang, Yingying Wei, Qun Su, Bing Yu, Ying Tao, Yan He, Youlian Wang, Guixiu Shi, Lihua Duan
Interleukin-33 (IL-33), a member of the IL-1 superfamily, has been shown to play a critical role in many diseases through regulating the immune cell responses, including myeloid-derived suppressor cells (MDSCs). Our previous study demonstrated that IL-33 might play a protective role in kidney injury in gout patients by regulating the lipid metabolism. However, the role of IL-33in the development of MSU-induced inflammation remains elusive. In this study, an increased IL-33 expression was observed in gout patients, which was positively correlated with inflammatory marker CRP...
2019: Frontiers in Endocrinology
Sarah P Short, Caitlyn W Barrett, Kristy R Stengel, Frank L Revetta, Yash A Choksi, Lori A Coburn, Mary K Lintel, Elizabeth M McDonough, M Kay Washington, Keith T Wilson, Egor Prokhortchouk, Xi Chen, Scott W Hiebert, Albert B Reynolds, Christopher S Williams
The myeloid translocation gene family member MTG16 is a transcriptional corepressor that relies on the DNA-binding ability of other proteins to determine specificity. One such protein is the ZBTB family member Kaiso, and the MTG16:Kaiso interaction is necessary for repression of Kaiso target genes, such as matrix metalloproteinase-7. Using the azoxymethane and dextran sodium sulfate (AOM/DSS) murine model of colitis-associated carcinoma, we previously determined that MTG16 loss accelerates tumorigenesis and inflammation...
March 11, 2019: Oncogene
Sanjit K Dhar, Ines Batinic-Haberle, Daret K St Clair
Mitochondria are major sites of energy metabolism that influence numerous cellular events including immunity and cancer development. Previously, we reported that the mitochondrion specific antioxidant enzyme, manganese containing superoxide dismutase (MnSOD), has dual roles in early- and late- carcinogenesis stages. However, how defective MnSOD impacts the chain of events that leads to cell transformation in pathologically normal epidermal cells that have been exposed to carcinogens is unknown. Here, we show that UVB radiation causes nitration and inactivation of MnSOD leading to mitochondrial injury and mitophagy...
March 11, 2019: Journal of Biological Chemistry
Cheng Fang, Hai Du, Xiaojiao Zheng, Aihua Zhao, Wei Jia, Yan Xu
Alcoholic beverages, which are consumed widely in most parts of the world, have long been identified as a major risk factor for all liver diseases, particularly alcoholic liver disease (ALD). Recent compositional analyses suggest that Chinese Baijiu (CB), a clear alcoholic liquid distilled from fermented grains, contains large amounts of small molecule bioactive compounds in addition to a significant amount of ethanol (EtOH). Here, in an experimental mouse model, we show that CB caused lower degrees of liver injury than pure EtOH by protecting against the decrease of the relative abundance of Akkermansia and increase of the relative abundance of Prevotella in the gut, thereby preventing the destruction of the intestinal barrier...
March 11, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
T Greco, L Ferguson, C Giza, M L Prins
Traumatic brain injury (TBI) has drawn national attention for its high incidence and mechanistic complexity. The majority of TBI cases are "mild" in nature including concussions and mild TBI (mTBI). Concussions are a distinct form of mTBI where diagnosis is difficult, quantification of the incidence is challenging and there is greater risk for subsequent injuries. While concussions occur in the general population, it has become a hallmark injury consistently observed among adolescent and young adult athletes and the risks for repeat TBI (rTBI) is significant...
March 7, 2019: Experimental Neurology
Sreenivasa C Ramaiahgari, Scott S Auerbach, Trey O Saddler, Julie R Rice, Paul E Dunlap, Nisha S Sipes, Michael J DeVito, Ruchir R Shah, Pierre R Bushel, B Alex Merrick, Richard S Paules, Stephen S Ferguson
Prediction of human response to chemical exposures is a major challenge in both pharmaceutical and toxicological research. Transcriptomics has been a powerful tool to explore chemical-biological interactions, however, limited throughput, high-costs and complexity of transcriptomic interpretations have yielded numerous studies lacking sufficient experimental context for predictive application. To address these challenges, we have utilized a novel high-throughput transcriptomics (HTT) platform, TempO-Seq, to apply the interpretive power of concentration-response modeling with exposures to 24 reference compounds in both differentiated and non-differentiated human HepaRG cell cultures...
March 8, 2019: Toxicological Sciences: An Official Journal of the Society of Toxicology
Abdulnaser Alkhalil, Bonnie C Carney, Taryn E Travis, Seid Muhie, Stacy Ann Miller, Jessica C Ramella-Roman, Pejhman Ghassemi, Rasha Hammamieh, Marti Jett, Lauren T Moffatt, Jeffrey W Shupp
Although pigment synthesis is well understood, relevant mechanisms of psychologically debilitating dyspigmentation in nascent tissue after cutaneous injuries are still unknown. Here, differences in genomic transcription of hyper- and hypopigmented tissue relative to uninjured skin were investigated using a red Duroc swine scar model. Transcription profiles differed based on pigmentation phenotypes with a trend of more upregulation or downregulation in hyper- or hypopigmented scars, respectively. Ingenuity Pathway Analysis (IPA) of significantly modulated genes in both pigmentation phenotypes showed pathways related to redox, metabolic, and inflammatory responses were more present in hypopigmented samples, while those related to stem cell development differentiation were found mainly in hyperpigmented samples...
March 8, 2019: Pigment Cell & Melanoma Research
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