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Si Houn Hahn, David Kronn, Nancy D Leslie, Loren D M Pena, Pranoot Tanpaiboon, Michael J Gambello, James B Gibson, Richard Hillman, David W Stockton, John W Day, Raymond Y Wang, Kristina An Haack, Raheel Shafi, Susan Sparks, Yang Zhao, Catherine Wilson, Priya S Kishnani
PurposePompe disease results from lysosomal acid α-glucosidase (GAA) deficiency and its associated glycogen accumulation and muscle damage. Alglucosidase alfa (recombinant human GAA (rhGAA)) received approval in 2006 as a treatment for Pompe disease at the 160 L production scale. In 2010, larger-scale rhGAA was approved for patients up to 8 years old without cardiomyopathy. NCT01526785 evaluated 4,000 L rhGAA efficacy/safety in US infantile- or late-onset Pompe disease (IOPD, LOPD) patients up to 1 year old transitioned from 160 L rhGAA...
March 22, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
José Luis Martínez-Rodríguez, Rosalinda Gutiérrez-Hernández, Claudia Araceli Reyes-Estrada, Angelica Judith Granados-López, Tatiana Arcos-Ortega, Jesús Adrián López
The metabolism of aromatic hydrocarbons by the organism forms products that cause cell death depending on the type of exposure. Benzene exposure has been linked to oxidative stress, hepatic damage, aplastic anemia and hematopoietic cancer as lymphoid and myeloid leukemia. However, there are not fast methods to evaluate chronically benzene exposure in human blood. The objective of this work was the evaluation of the correlation between oxidative damage with benzene exposure and the level of Cellular Plasma Membrane Stability (CPMS) in erythrocytes to use it as a future indicator to determine the grade of benzene intoxications...
March 22, 2018: Toxicology Mechanisms and Methods
Emiko Niiro, Sachiko Morioka, Kana Iwai, Yuki Yamada, Kenji Ogawa, Naoki Kawahara, Hiroshi Kobayashi
Cases of mucinous ovarian cancer are predominantly resistant to chemotherapies. The present review summarizes current knowledge of the therapeutic potential of targeting the Wingless (WNT) pathway, with particular emphasis on preclinical and clinical studies, for improving the chemoresistance and treatment of mucinous ovarian cancer. A review was conducted of English language literature published between January 2000 and October 2017 that concerned potential signaling pathways associated with the chemoresistance of mucinous ovarian cancer...
March 2018: Biomedical Reports
Shengbing Wang, Vidya Venkatraman, Erin L Crowgey, Ting Liu, Zongming Fu, Ronald J Holewinski, Mark J J Ranek, David A Kass, Brian O'Rourke, Jennifer E Van Eyk
<u>Rationale:</u> Glycogen synthase kinase 3β (GSK3β) is a multifunctional and constitutively active kinase known to regulate a myriad of cellular processes. The primary mechanism to regulate its function is through phosphorylation-dependent inhibition at serine-9 residue. Emerging evidence indicates that there may be alternative mechanisms that control GSK3β for certain functions. <u>Objective:</u> Here we sought to understand the role of protein S-nitrosylation (SNO) on the function of GSK3β...
March 21, 2018: Circulation Research
Zhong-Xin Zhou, Zu-Ping Zhang, Ze-Zhang Tao, Ting-Zhao Tan
Laryngeal cancer, one of the most common head and neck malignancies, is an aggressive neoplasm. Increasing evidence hasdemonstrated that microRNAs (miRNAs) exert important roles in oncogenesis and progression of diverse types of human cancers. MiR-632, a tumor-related miRNA, has been reported to be dysregulated and implicated in human malignancies; however, its biological role in laryngeal carcinoma remains to be elucidated. The present study aimed at exploring the role of miR-632 in laryngeal cancer and clarifying the potential molecular mechanisms involved...
March 21, 2018: Oncology Research
Norimichi Shirafuji, Tadanori Hamano, Shu-Hui Yen, Nicholas M Kanaan, Hirotaka Yoshida, Kouji Hayashi, Masamichi Ikawa, Osamu Yamamura, Masaru Kuriyama, Yasunari Nakamoto
Increased plasma homocysteinemia is considered a risk factor of dementia, including Alzheimer's disease (AD) and vascular dementia. However, the reason elevated plasma homocysteinemia increases the risk of dementia remains unknown. A pathological hallmark of AD is neurofibrillary tangles (NFTs) that consist of pathologically phosphorylated tau proteins. The effect of homocysteine (Hcy) on tau aggregation was explored using human neuroblastoma M1C cells that constitutively express human wild-type tau (4R0N) under the control of a tetracycline off system, primary mouse cultured neurons, and by inducing hyperhomocysteinemia in a mouse model of tauopathy (HHCy mice)...
March 17, 2018: International Journal of Molecular Sciences
Daniela Hulcová, Kateřina Breiterová, Tomáš Siatka, Kamila Klímová, Lara Davani, Marcela Šafratová, Anna Hošťálková, Angela De Simone, Vincenza Andrisano, Lucie Cahlíková
Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine protein kinase that was originally identified as an enzyme involved in the control of glycogen metabolism. It plays a key role in diverse physiological processes including metabolism, the cell cycle, and gene expression by regulating a wide variety of well-known substances like glycogen synthase, tau-protein, and β-catenin. Recent studies have identified GSK-3β as a potential therapeutic target in Alzheimer´s disease, bipolar disorder, stroke, more than 15 types of cancer, and diabetes...
March 21, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Tina Stopp, Michael Feichtinger, Wolfgang Eppel, Thomas M Stulnig, Peter Husslein, Christian Göbl
McArdle disease or glycogen storage disease (GSD) type V is a rare autosomal recessive inherited disorder in skeletal muscle metabolism leading to exercise intolerance, muscle cramps and in some cases to rhabdomyolysis and acute renal failure due to elevated serum myoglobin levels. Albeit the uterine smooth muscle is not affected, pregnancy and delivery can be physically strenuous and may require specific anesthesiologic care. However, data on pregnancy progress and outcome and on special implications linked to anesthesia in women with McArdle's disease is scarce, thus posing a challenge to pre- and peripartal management...
March 21, 2018: Gynecological Endocrinology
Yawei Xu, Yan Zhou, Rui Yin, Cheng Wang, Haijiao Chu, Junling Wang
The balance of oxidation and reduction in the body requires the synergistic effect of various antioxidant enzymes. Therefore, the construction of enzyme mimics with multiple antioxidant activities is important and beneficial for further research on the synergistic effects of antioxidant enzymes and their mechanism of action. To explore the synergistic effect of superoxide dismutase (SOD) and glutathione peroxidase (GPx), a 76-mer selenium-containing peptide (Se-76P) mimic containing the active SOD and GPx centers was designed...
March 20, 2018: In Vitro Cellular & Developmental Biology. Animal
Jian Weng, Yan-Hua Wang, Ming Li, Dian-Ying Zhang, Bao-Guo Jiang
Delay of axon regeneration after peripheral nerve injury usually leads to progressive muscle atrophy and poor functional recovery. The Wnt/β-catenin signaling pathway is considered to be one of the main molecular mechanisms that lead to skeletal muscle atrophy in the elderly. We hold the hypothesis that the innervation of target muscle can be promoted by accelerating axon regeneration and decelerating muscle cell degeneration so as to improve functional recovery of skeletal muscle following peripheral nerve injury...
February 2018: Neural Regeneration Research
Jun Liu, Lei Huang, Pengxiao Su, Tao Song, Wentao Zhang, Jinzhu Fan, Yang Liu
A number of studies have attempted to elucidate the association between mircoRNAs (miRNAs/miRs) and cancer-associated processes. The aim of the present study was to determine how miR-499a-5p intervenes in human osteosarcoma cell proliferation and differentiation. The cancerous tissues and adjacent non-cancerous tissues of 62 patients with osteosarcoma (OS) were collected. miRNA microarray analysis revealed that 29 miRNAs were upregulated while 26 were downregulated, among which miR-499a-5p expression was the most decreased...
April 2018: Oncology Letters
Sandra G Gonzalez Malagon, Anna M Lopez Muñoz, Daniel Doro, Triòna G Bolger, Evon Poon, Elizabeth R Tucker, Hadeel Adel Al-Lami, Matthias Krause, Christopher J Phiel, Louis Chesler, Karen J Liu
Neural crest migration is critical to its physiological function. Mechanisms controlling mammalian neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here we report requirements of glycogen synthase kinase 3 (GSK3) in regulating the neural crest in Xenopus and mouse models. We demonstrate that GSK3 is tyrosine phosphorylated (pY) in mouse neural crest cells and that loss of GSK3 leads to increased pFAK and misregulation of Rac1 and lamellipodin, key regulators of cell migration...
March 19, 2018: Nature Communications
Hua Rong, Yini Liang, Yingcai Niu
Oxidative stress is an important pathogenic factor in Alzheimer's disease (AD). Recently, nuclear factor E2-related factor 2 (Nrf2) has emerged as a master regulator for the endogenous antioxidant response, and thus represents an attractive therapeutic target against AD. The aim of this study is to test the hypothesis that rosmarinic acid (RosA) attenuates amyloid-β (Aβ)-evoked oxidative stress through activating Nrf2-inducible cellular antioxidant defense system. Here, we reported that RosA attenuated Aβ-induced cellular reactive oxygen species (ROS) generation and lipid hydroperoxides (LPO)...
March 16, 2018: Free Radical Biology & Medicine
Joanne Thomson, Laura Hargrove, Lindsey Kennedy, Jennifer Demieville, Heather Francis
The functions of the liver are very diverse. From detoxifying blood to storing glucose in the form of glycogen and producing bile to facilitate fat digestion, the liver is a very active and important organ. The liver is comprised of many varied cell types whose functions are equally diverse. Cholangiocytes line the biliary tree and aid in transporting and adjusting the composition of bile as it travels to the gallbladder. Hepatic stellate cells and portal fibroblasts are located in different areas within the liver architecture, but both contribute to the development of fibrosis upon activation after liver injury...
June 2017: Liver Research
Aifang Li, Yue Gu, Xueru Li, Hui Sun, He Zha, Jiaqing Xie, Jiali Zhao, Mao Huang, Lu Chen, Qi Peng, Yan Zhang, Yaguang Weng, Lan Zhou
Cervical cancer is the second most common gynecological cancer worldwide and remains one of the leading causes of cancer-associated mortality among women. S100A6 has been reported to be associated with the development of many types of cancer. The aim of the present study was to investigate the effect of S100A6 on the proliferation, apoptosis and migration of cervical cancer cells and its underlying molecular mechanisms. Quantative polymerase chain reaction (qPCR) was used to detect the basic mRNA level of S100A6 in HeLa, SiHa and CaSki cells...
April 2018: Oncology Letters
M Clara F do Amaral, James Frisbie, David L Goldstein, Carissa M Krane
Cope's gray treefrog (Dryophytes chrysoscelis) is one of few freeze-tolerant frogs that mobilize glycerol as a cryoprotectant, yet cold and freezing-induced accumulation of this and other osmolytes has received little attention in this species. This study investigated the development of freeze tolerance in D. chrysoscelis, analyzing the response of the cryoprotectant system to cold acclimation, freezing, and thawing. Glycerol production was low and unresponsive to acclimation temperature, or duration of acclimation to 5 °C, except for one cold-acclimated frog that presented elevated glycerol in plasma, liver, and skeletal muscle...
March 17, 2018: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
Wenqian Zhang, Ying Cui, Junling Gao, Ran Li, Xiaohua Jiang, Yanxia Tian, Kaijie Wang, Jianzhong Cui
BACKGROUND This study aimed to investigate the potential neuroprotective effect of recombinant osteopontin (r-OPN) on apoptotic changes via modulating phosphoinositide-3-kinase/Akt/glycogen synthase kinase 3 beta (PI3K/Akt/GSK-3β) signaling in a rat model of intracerebral hemorrhage (ICH). MATERIAL AND METHODS We subjected 10-12-week-old Sprague-Dawley male rats (n=120) to injection of autologous blood into the right basal ganglia to induce ICH or sham surgery. ICH animals received vehicle administration, r-OPN (4 μL/pup), or r-OPN combined with phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (86 ng/pup) at 30 min after injury...
March 18, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Ricardo Marques, Anna Ribera-Guardia, Jorge Santos, Gilda Carvalho, Maria A M Reis, Maite Pijuan, Adrian Oehmen
Denitrifying enhanced biological phosphorus removal (EBPR) systems can be an efficient means of removing phosphate (P) and nitrate (NO3 - ) with low carbon source and oxygen requirements. Tetrasphaera is one of the most abundant polyphosphate accumulating organisms present in EBPR systems, but their capacity to achieve denitrifying EBPR has not previously been determined. An enriched Tetrasphaera culture, comprising over 80% of the bacterial biovolume was obtained in this work. Despite the denitrification capacity of Tetrasphaera, this culture achieved only low levels of anoxic P-uptake...
March 7, 2018: Water Research
Connor M Pettem, Jennifer M Briens, David M Janz, Lynn P Weber
Selenium (Se) is considered an essential trace element, involved in important physiological and metabolic functions for all vertebrate species. Fish require dietary concentrations of 0.1-0.5 μg Se/g dry mass (d.m.) to maintain normal physiological and selenoprotein function, however concentrations exceeding 3 μg/g d.m. have been shown to cause toxicity. As Se is reported to have a narrow margin between essentiality and toxicity, there is growing concern surrounding the adverse effects of elevated Se exposure caused by anthropogenic activities...
March 8, 2018: Aquatic Toxicology
Xiaoqin Zhang, Yiping Zhang, Songqi Tang, Lishuang Yu, Youqin Zhao, Qiangqiang Ren, Xiaoqiang Huang, Wen Xu, Mingqing Huang, Jun Peng
ETHNOPHARMACOLOGICAL RELEVANCE: Pien-Tze-Huang (PZH) is a famous formula of traditional Chinese medicine used to treating stroke. However, the protective effect of PZH and its mechanisms in acute ischemic stroke remain to be explored. AIM OF THE STUDY: To investigate the protective effect of PZH on neuronal apoptosis in acute cerebral ischemic injury rats and explore its underlying mechanisms. MATERIALS AND METHODS: The effects of PZH were studied in acute ischemic stroke rats induced by transient middle cerebral artery occlusion, and the mitochondria-mediated apoptotic proteins including cytochrome C (Cyt C), Bax, Bcl-xl, P53, caspase-3, and caspase-9 as well as AKT and glycogen synthase kinase-3 beta (GSK-3β) were assessed...
March 14, 2018: Journal of Ethnopharmacology
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