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Safa Alqudah, Mark Chertoff, Dianne Durham, Jackob Moskovitz, Hinrich Staecker, Marcello Peppi
Methionine sulfoxide reductases (MsrA and MsrB) protect the biological activity of proteins from oxidative modifications to methionine residues and are important for protecting against the pathological effects of neurodegenerative diseases. In the current study, we characterized the auditory phenotype of the MsrA knockout mouse. Young MsrA knockout mice showed small high-frequency threshold elevations for auditory brainstem response and distortion product otoacoustic emission compared to those of wild-type mice, which progressively worsened in older MsrA knockout mice...
June 21, 2018: Audiology & Neuro-otology
Yu Zhang, Weida Gao, Kongbin Yang, Haiquan Tao, Haicheng Yang
BACKGROUND/AIMS: Alcohol consumption has been shown to cause neuroinflammation and increase a variety of immune-related signaling processes. Microglia are a crucial part of alcohol-induced neuroinflammation and undergo apoptosis. Even though the importance of these inflammatory processes in the effects of alcohol-related neurodegeneration have been established, the mechanism of alcohol-induced microglia apoptosis is unknown. In prior research, we discovered that alcohol increases expression of salt-inducible kinase 1 (SIK1) in rodent brain tissue...
June 19, 2018: Cellular Physiology and Biochemistry
Jing Tong, Yan Lai, Yi-An Yao, Xue-Jun Wang, Yu-Shuang Shi, Han-Jin Hou, Jian-Yun Gu, Fei Chen, Xue-Bo Liu
BACKGROUND/AIMS: To explore the potential role of qiliqiangxin (QLQX) A traditional Chinese medicine and the involvement of angiotensin II receptor type 1 (AGTR1) and transient receptor potential vanilloid 1 (TRPV1) in diabetic mouse cardiac function. METHODS: Intragastric QLQX was administered for 5 weeks after streptozotocin (STZ) treatment. Additionally, Intraperitoneal injections of angiotensin II (Ang II) or intragastric losartan (Los) were administered to assess the activities of AGTR1 and TRPV1...
June 19, 2018: Cellular Physiology and Biochemistry
Krutika Joshi, Lily Shen, Feng Cao, Susan Dong, Zhengping Jia, Miguel A Cortez, O Carter Snead
OBJECTIVE: Infantile spasms (IS) is a catastrophic childhood seizure disorder that is characterized by extensor and/or flexor spasms, cognitive deterioration and a characteristic EEG abnormality. The latter consists of a pattern of a spike-wave followed by an electrodecremental response (EDR), which is a flattening of the EEG waveform amplitude. The mechanism/circuitry that underpins IS is unknown. Children with Down Syndrome (DS) are particularly vulnerable to IS. The standard mouse model of DS is the Ts65Dn mutant mouse (Ts)...
June 12, 2018: Epilepsy Research
Didem Dagdeviren, Zana Kalajzic, Douglas J Adams, Ivo Kalajzic, Alan Lurie, Maija I Mednieks, Arthur R Hand
OBJECTIVE: To determine if spaceflight and microgravity affect non-weight bearing bones and development and mineralization of teeth, reasoning that combining an organ and a cellular level approach can lead to greater insights about these effects. DESIGN: Mandibles and incisors of mice flown on the US STS-135 space shuttle mission and the Russian Bion-M1 satellite were studied using micro-computed tomography and immunohistochemistry. Ground controls were mice housed in standard vivarium cages and flight habitats...
June 7, 2018: Archives of Oral Biology
Eleonora Palagano, Giulia Zuccarini, Paolo Prontera, Renato Borgatti, Gabriela Stangoni, Sandro Elisei, Stefano Mantero, Ciro Menale, Antonella Forlino, Paolo Uva, Manuela Oppo, Paolo Vezzoni, Anna Villa, Giorgio R Merlo, Cristina Sobacchi
Acrofrontofacionasal Dysostosis type 1 (AFFND1) is an extremely rare, autosomal recessive syndrome, comprising facial and skeletal abnormalities, short stature and intellectual disability. We analyzed an Indian family with two affected siblings by exome sequencing and identified a novel homozygous truncating mutation in the Neuroblastoma-Amplified Sequence (NBAS) gene in the patients' genome. Mutations in the NBAS gene have recently been associated with different phenotypes mainly involving skeletal formation, liver and cognitive development...
June 18, 2018: Bone
Jiancheng Yang, Xiaofeng Meng, Dandan Dong, Yanru Xue, Xin Chen, Shenghang Wang, Ying Shen, Gejing Zhang, Peng Shang
During deep-space exploration missions, astronauts will be exposed to abnormal space environments including microgravity and hypomagnetic field (HyMF) that is 10,000 times weaker than geomagnetic field (GMF). It is well known that microgravity in space can induce bone loss; however, it is ill-defined whether HyMF involved in this process. Herein, we aimed to investigate the combined effects of HyMF and microgravity on bone loss. A mouse model of hindlimb suspension (HLU) was adopted to simulate microgravity-induced bone loss, that was exposed to a hypomagnetic field of <300 nanotesla (nT) generated by a geomagnetic field-shielding chamber...
June 18, 2018: Bone
Rachit Bakshi, Yuehang Xu, Kaly A Mueller, Xiqun Chen, Eric Granucci, Sabrina Paganoni, Ghazaleh Sadri-Vakili, Michael A Schwarzschild
Dominant mutations in an antioxidant enzyme superoxide dismutase-1 (SOD1) cause amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease characterized by loss of motor neurons. Oxidative stress has also been linked to many of the neurodegenerative diseases and is likely a central mechanism of motor neuron death in ALS. Astrocytes derived from mutant SOD1G93A mouse models or patients play a significant role in the degeneration of spinal motor neurons in ALS through a non-cell-autonomous process...
June 18, 2018: Molecular and Cellular Neurosciences
Toru Komatsu, Masahiro Shimoda, Yukiko Kawamura, Yasuteru Urano, Tetsuo Nagano
Diced electrophoresis gel (DEG) assay is a methodology to identify enzymes with a specified activity in complex cell or tissue lysates by means of two-dimensional separation using isoelectric focusing and native PAGE, followed by dicing of the gel into small pieces that are assayed separately, and digestion and peptide fingerprinting to identify the protein(s) of interest in positive wells. The existing hand-made system has some disadvantages, and here we describe the development and validation of an improved cutter-plate system that enables simple, reliable and reproducible DEG assay in a 384-well plate-based format with signal readout using fluorometric or LC-MS-based reaction monitoring...
June 18, 2018: Biochimica et Biophysica Acta
Yongfeng Wang, Meiling Duan, Lijiang Zhao, Ping Ma
Guajadial, one of natural dialdehyde meroterpenoids, demonstrated significant antineoplasmic activity. The present research was to investigate the inhibitory effects of guajadial by using two NSCLC cells (A549 and H1650) proliferation and migration. Western blotting was employed to explore the underlying mechanisms of VEGF receptor (VEGFR)2-mediated. This research indicated that guajadial not only inhibited endothelial cell proliferation and migration but also suppress tumor growth in human NSCLC xenograft mouse models...
June 18, 2018: Fitoterapia
Kei Kawaguchi, Kentaro Miyake, Qinghong Han, Shukuan Li, Yuying Tan, Kentaro Igarashi, Tasuku Kiyuna, Masuyo Miyake, Takashi Higuchi, Hiromichi Oshiro, Zhiying Zhang, Sahar Razmjooei, Sintawat Wangsiricharoen, Michael Bouvet, Shree Ram Singh, Michiaki Unno, Robert M Hoffman
Recombinant methioninase (rMETase) was administered as an injectable drug to target methionine dependence of cancer. Recently, we observed that rMETase could be administered orally (o-rMETase) in a patient-derived orthotopic xenograft (PDOX) mouse model of melanoma. Here, we determined the efficacy of o-rMETase on a pancreatic cancer PDOX model. Forty pancreatic cancer PDOX mouse models were randomized into four groups of 10 mice each. o-rMETase was significantly more effective than i.p.-rMETase, but combination of both was significantly more effective...
June 18, 2018: Cancer Letters
Eun Hye Kim, Daiha Shin, Jaewang Lee, Ah Ra Jung, Jong-Lyel Roh
Sulfasalazine has been repurposed to induce ferroptotic cancer cell death via inhibition of xc - -cystine/glutamate antiporter (xCT). However, cancer cells are capable of developing mechanisms to evade cell death. Therefore, we sought to determine the molecular mechanisms underlying resistance to sulfasalazine-induced ferroptosis in head and neck cancer (HNC). The effects of sulfasalazine and pioglitazone were tested in various HNC cell lines. The effects of these drugs and inhibition and overexpression of CISD2 gene were determined by evaluating viability, cell death, lipid ROS production, mitochondrial iron, and mouse tumor xenograft models...
June 18, 2018: Cancer Letters
Gregory Simchick, Amelia Yin, Hang Yin, Qun Zhao
PURPOSE: To explore, at a high field strength of 7T, the performance of various fat spectral models on the quantification of triglyceride composition and proton density fat fraction (PDFF) using chemical-shift encoded MRI (CSE-MRI). METHODS: MR data was acquired from CSE-MRI experiments for various fatty materials, including oil and butter samples and in vivo brown and white adipose mouse tissues. Triglyceride composition and PDFF were estimated using various a priori 6- or 9-peak fat spectral models...
June 18, 2018: Magnetic Resonance Imaging
Marie-Cécile Valéra, Emmanuelle Noirrit-Esclassan, Marion Dupuis, Coralie Fontaine, Françoise Lenfant, Anne Briaux, Cendrine Cabou, Cedric Garcia, Olivier Lairez, Jean-Michel Foidart, Bernard Payrastre, Jean-François Arnal
Estetrol (E4) is a natural estrogen synthesized exclusively during pregnancy by the human fetal liver, and the physiological role of this hormone is unknown. Interestingly, E4 was recently evaluated in preclinical and phase II-III clinical studies in combination with a progestin, with the advantage to not increase the circulating level of coagulation factors, at variance to oral estradiol or ethinylestradiol. Here, we evaluated the effect of E4 on hemostasis and thrombosis in mouse. Following chronic E4 treatment, mice exhibited a prolonged tail-bleeding time and were protected from arterial and also venous thrombosis in vivo...
June 18, 2018: Molecular and Cellular Endocrinology
Li Wen, Tanveer A Javed, Dean Yimlamai, Amitava Mukherjee, Xiangwei Xiao, Sohail Z Husain
BACKGROUND AND AIMS: Pancreatitis following endoscopic retrograde cholangiopancreatography (PEP) is thought to be provoked by pancreatic ductal hypertension, via unknown mechanisms. We investigated the effects of hydrostatic pressures on the development of pancreatitis in mice. METHODS: We performed studies with Swiss Webster mice, B6129 mice (controls), and B6129 mice with disruption of the protein phosphatase 3, catalytic subunit, beta isoform gene (Cnab-/- mice)...
June 18, 2018: Gastroenterology
Viviana Vastolo, Immacolata Cristina Nettore, Marco Ciccarelli, Luigi Albano, Gregory Alexander Raciti, Michele Longo, Francesco Beguinot, Paola Ungaro
BACKGROUND: The impact of nutrition on the evolution towards type 2 diabetes has recently received increasing attention because of the effect on chromatin structure and gene expression. PURPOSE: Evaluate the effect of high-fat diet on chromatin remodelling and expression of Ped/Pea-15, a gene commonly overexpressed in individuals at risk of type 2 diabetes. METHODS: We used mouse and cell models to investigate Ped/Pea-15 transcriptional regulation by high-fat diet and glucose, respectively...
June 18, 2018: Metabolism: Clinical and Experimental
Denise M Hilton, Rey M Aguilar, Adam B Johnston, Bruce L Goode
Twinfilin is a highly conserved member of the actin depolymerization factor homology (ADF-H) protein superfamily, which also includes ADF/Cofilin, Abp1/Drebrin, GMF, and Coactosin. Twinfilin has a unique molecular architecture consisting of two ADF-H domains joined by a linker and followed by a C-terminal tail. Yeast Twinfilin, in conjunction with yeast cyclase-associated protein (Srv2/CAP), increases the rate of depolymerization at both the barbed and pointed ends of actin filaments. However, it has remained unclear whether these activities extend to Twinfilin homologs in other species...
June 18, 2018: Journal of Molecular Biology
Young Hun Kim, Minsung Kim, Miyoun Yoo, Ji Eun Kim, Heung Kyoung Lee, Jung-Nyoung Heo, Chong Ock Lee, Minjin Yoo, Kwan-Young Jung, Chang-Soo Yun, Sung Woong Moon, Hye Kyung Chang, Chul-Woong Chung, Suhkneung Pyo, Sang Un Choi, Chi Hoon Park
Bromodomain-containing protein 4 (Brd4) is known to play a key role in tumorigenesis. It binds acetylated histones to regulate the expression of numerous genes. Because of the importance of brd4 in tumorigenesis, much research has been undertaken to develop brd4 inhibitors with therapeutic potential. As a result, various scaffolds for bromodomain inhibitors have been identified. To discover new scaffolds, we performed mid-throughput screening using two different enzyme assays, alpha-screen and ELISA. We found a novel bromodomain inhibitor with a unique scaffold, aristoyagonine...
June 18, 2018: Biochemical and Biophysical Research Communications
Omi Nagata, Masayuki Nakamura, Hitoshi Sakimoto, Yuka Urata, Natsuki Sasaki, Nari Shiokawa, Akira Sano
Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disease characterized by neurodegeneration in the striatum and acanthocytosis caused by loss-of-function mutations in the Vacuolar Protein Sorting 13 Homolog A (VPS13A) gene, which encodes chorein. We previously produced a ChAc-model mouse with a homozygous deletion of exons 60-61 in Vps13a, which corresponded to the human disease mutation. We found that male ChAc-model mice exhibited complete infertility as a result of severely diminished sperm motility...
June 18, 2018: Biochemical and Biophysical Research Communications
J L Brown, L Campbell, J Malcolm, A Adrados Planell, J P Butcher, S Culshaw
Innate lymphoid cells (ILCs) are a population of lymphocytes that act as the first line of immunologic defense at mucosal surfaces. The ILC family in the skin, lungs, and gastrointestinal tissues has been investigated, and there are reports of individual subsets of ILCs in the oral tissues. We sought to investigate the whole ILC population (group 1, 2, and 3 subsets) in the murine gingivae and the lymph nodes draining the oral cavity. We show that ILCs made up a greater proportion of the whole CD45+ lymphocyte population in the murine gingivae (0...
June 1, 2018: Journal of Dental Research
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