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https://www.readbyqxmd.com/read/29232702/adipose-tissue-deficiency-of-hormone-sensitive-lipase-causes-fatty-liver-in-mice
#1
Bo Xia, Guo He Cai, Hao Yang, Shu Pei Wang, Grant A Mitchell, Jiang Wei Wu
Fatty liver is a major health problem worldwide. People with hereditary deficiency of hormone-sensitive lipase (HSL) are reported to develop fatty liver. In this study, systemic and tissue-specific HSL-deficient mice were used as models to explore the underlying mechanism of this association. We found that systemic HSL deficient mice developed fatty liver in an age-dependent fashion between 3 and 8 months of age. To further explore the mechanism of fatty liver in HSL deficiency, liver-specific HSL knockout mice were created...
December 12, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29232699/cxcr4-blockade-decreases-cd4-t-cell-exhaustion-and-improves-survival-in-a-murine-model-of-polymicrobial-sepsis
#2
Kimberly M Ramonell, Wenxiao Zhang, Annette Hadley, Ching-Wen Chen, Katherine T Fay, John D Lyons, Nathan J Klingensmith, Kevin W McConnell, Craig M Coopersmith, Mandy L Ford
Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis...
2017: PloS One
https://www.readbyqxmd.com/read/29232661/downregulation-of-long-noncoding-rna-gas5-affects-cell-cycle-and-insulin-secretion-in-mouse-pancreatic-%C3%AE-cells
#3
Feiyan Jin, Ning Wang, Yanan Zhu, Lianghui You, Lintao Wang, Wei De, Wei Tang
BACKGROUND: Evidence shows that long non-coding RNAs (lncRNAs) are involved in individual development, cell differentiation, cell cycle processes and other important life processes and are closely related to major human diseases, including diabetes. Recent studies have reported that lncRNAs are involved in β cell functions and that lncRNA Gas5 levels decreased in T2DM patients' serum. The purpose of this study was to clarify the role of lncRNA Gas5 in mouse β cell functions in vitro and in vivo...
October 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29232626/targeted-isolation-and-identification-of-bioactive-compounds-lowering-cholesterol-in-the-crude-extracts-of-crabapples-using-uplc-dad-ms-spe-nmr-based-on-pharmacology-guided-pls-da
#4
Chao Wen, Dongshan Wang, Xing Li, Tao Huang, Cheng Huang, Kaifeng Hu
The anti-hyperlipidemic effects of crude crabapple extracts derived from Malus 'Red jade', Malus hupehensis (Pamp.) Rehd. and Malus prunifolia (Willd.) Borkh. were evaluated on high-fat diet induced obese (HF DIO) mice. The results revealed that some of these extracts could lower serum cholesterol levels in HF DIO mice. The same extracts were also parallelly analyzed by LC-MS in both positive and negative ionization modes. Based on the pharmacological results, 22 LC-MS variables were identified to be correlated with the anti-hyperlipidemic effects using partial least square discriminant analysis (PLS-DA) and independent samples t-test...
December 2, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29232607/simultaneous-uplc-ms-ms-analysis-of-two-stable-isotope-labeled-versions-of-sucrose-in-mouse-plasma-and-brain-samples-as-markers-of-blood-brain-barrier-permeability-and-brain-vascular-space
#5
Ekram Ahmed Chowdhury, Faleh Alqahtani, Raktima Bhattacharya, Reza Mehvar, Ulrich Bickel
Blood Brain Barrier (BBB) permeability is frequently compromised in the course of diseases affecting the central nervous system (CNS). Sucrose is a low molecular weight, hydrophilic marker with slow permeability at the naive BBB and therefore one of the widely used indicators of barrier integrity. Our laboratory recently developed a highly sensitive UPLC-MS/MS method for stable isotope labeled [13C12]sucrose in biological matrices. Correction of total brain concentration for contribution of intravascular space is required in such experiments in order to accurately measure BBB permeability, and it is often accomplished by vascular perfusion with buffer solutions prior to brain sampling...
December 6, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29232583/development-of-novel-bis-pyrazole-derivatives-as-antitumor-agents-with-potent-apoptosis-induction-effects-and-dna-damage
#6
Hong Dai, Shushan Ge, Jing Guo, Shi Chen, Meiling Huang, Jiaying Yang, Siyu Sun, Yong Ling, Yujun Shi
A series of bis-pyrazole derivatives were designed and synthesized, and their antitumor effects in vitro and in vivo were investigated. Several compounds displayed good antiproliferative activity with IC50 values in low-micromolar range against three human cancer cell lines in vitro, superior to 5-FU. The most potent compound 10M selectively inhibited human hepatocellular carcinoma cells but not non-tumor liver cell proliferation in vitro, and significantly triggered SMMC-7721 cell apoptosis by cleavage of both PARP and caspase-3 in a concentration-dependent manner...
December 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29232573/radioprotective-effects-of-silymarin-on-the-sperm-parameters-of-nmri-mice-irradiated-with-%C3%AE-rays
#7
Daryoush Fatehi, Mohsen Mohammadi, Babak Shekarchi, Arash Shabani, Mohammad Seify, Ayoob Rostamzadeh
Free radicals and reactive oxygen species (ROS) are generated using various endogenous systems or from external sources such as exposure to different physiochemicals. Ionizing radiation damage to the cell can be caused by the direct or indirect effects of radiotherapy processes. Silymarin (SM), a flavanolignan compound, has been identified as a natural potent antioxidant with cytoprotection activities due to scavenging free radicals. The aim of the present study was to evaluate the radioprotective effect of SM on sperm parameters of mice induced by γ-rays...
December 6, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29232562/tm6sf2-a-novel-target-for-plasma-lipid-regulation
#8
REVIEW
Ting-Ting Li, Tao-Hua Li, Juan Peng, Bei He, Lu-Shan Liu, Dang-Heng Wei, Zhi-Sheng Jiang, Xi-Long Zheng, Zhi-Han Tang
Transmembrane 6 superfamily 2 (TM6SF2), a gene identified at the locus 19p12, has been recognized to regulate plasma lipids. Here, we provide an overview of the roles of TM6SF2 as a novel target for plasma lipid regulation. We first review the association of TM6SF2 variant with plasma lipid traits, cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Then, we present an overview about the in vivo validation of TM6SF2 as a regulator of plasma lipid levels using mice, with overexpression or knockdown/knockout of TM6SF2...
December 1, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29232559/cilostazol-a-phosphodiesterase-3-inhibitor-activates-proteasome-proteolysis-and-attenuates-tauopathy-and-cognitive-decline
#9
Ari W Schaler, Natura Myeku
Alzheimer's disease and several variants of frontotemporal degeneration including progressive supranuclear palsy and corticobasal degeneration are characterized by the accumulation of abnormal tau protein into aggregates. Most proteins, including tau, are degraded via the ubiquitin proteasome system, but when abnormal tau accumulates, the function of 26S proteasomes is downregulated. The negative effect of tau aggregates on the function of the proteasome can have deleterious consequences on protein homeostasis and disease progression...
November 23, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29232556/mst4-phosphorylation-of-atg4b-regulates-autophagic-activity-tumorigenicity-and-radioresistance-in-glioblastoma
#10
Tianzhi Huang, Chung Kwon Kim, Angel A Alvarez, Rajendra P Pangeni, Xuechao Wan, Xiao Song, Taiping Shi, Yongyong Yang, Namratha Sastry, Craig M Horbinski, Songjian Lu, Roger Stupp, John A Kessler, Ryo Nishikawa, Ichiro Nakano, Erik P Sulman, Xinghua Lu, Charles David James, Xiao-Ming Yin, Bo Hu, Shi-Yuan Cheng
ATG4B stimulates autophagy by promoting autophagosome formation through reversible modification of ATG8. We identify ATG4B as a substrate of mammalian sterile20-like kinase (STK) 26/MST4. MST4 phosphorylates ATG4B at serine residue 383, which stimulates ATG4B activity and increases autophagic flux. Inhibition of MST4 or ATG4B activities using genetic approaches or an inhibitor of ATG4B suppresses autophagy and the tumorigenicity of glioblastoma (GBM) cells. Furthermore, radiation induces MST4 expression, ATG4B phosphorylation, and autophagy...
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29232523/exercise-training-differentially-alters-axial-and-appendicular-marrow-cellularity-in-old-mice
#11
Jeff Baker, Joshua P Nederveen, George Ibrahim, Victoria Ivankovic, Sophie Joanisse, Gianni Parise
Aging gradually renders bone marrow hematopoietically inactive. Endurance exercise reverses this phenotype in young mice. Here, we determine the effects in aged mice. Twenty-two month old mice (n=6) underwent a progressive exercise training protocol. In appendicular bones, marrow cellularity increased by 51% (p<0.05) and marrow CFU, CFU-GM, and CAFC increased by 12%, 71%, and 86%, respectively (p<0.05). Vertebral cellularity remained unchanged. The mechanical forces associated with treadmill exercise training may be responsible for these observations...
December 12, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29232521/an-immunoglobulin-fc-fused-peptide-without-c-terminal-arg-or-lys-residue-augments-neuropilin-1-dependent-tumor-vascular-permeability
#12
Du-San Baek, Jeong-Ho Kim, Ye-Jin Kim, Yong-Sung Kim
Neuropilin-1 (NRP1), which functions as a co-receptor for vascular endothelial growth factor (VEGF) and is implicated in vascular permeability and tumorigenesis, has been targeted by peptides that specifically bind to the VEGF-binding region on NRP1. Like natural VEGF ligands, all known peptides with NRP1-binding activity bind only through a carboxy (C)-terminal R/K-x-x-R/K sequence motif (x stands for any amino acids); this strict requirement is called the C-end rule (CendR). Here, we report immunoglobulin Fc-fused NRP1-specific peptides deviating from CendR...
December 12, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29232493/-carboxyl-11c-labeling-of-four-high-affinity-cpla2a-inhibitors-and-their-evaluation-as-radioligands-in-mice-with-positron-emission-tomography
#13
Martin J Fisher, Lindsay McMurray, Shuiyu Lu, Cheryl L Morse, Jeih-San Liow, Sami S Zoghbi, Aneta Kowalski, Geroge L Tye, Robert B Innis, Franklin I Aigbirhio, Victor W Pike
Cytosolic phospholipase A2α (cPLA2α) may play a critical role in neuropsychiatric and neurodegenerative disorders associated with oxidative stress and neuroinflammation. An effective PET radioligand for imaging cPLA2α in living brain might prove useful for biomedical research, especially on neuroinflammation. We selected four high-affinity (IC50 2.1 to 12 nM) indole-5-carboxylic acid-based inhibitors of cPLA2α (1-4), for labelling in carboxyl position with carbon-11 (t1/2 = 20.4 min) to provide candidate PET radioligands for imaging brain cPLA2α...
December 12, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29232419/mycobacterium-marinum-remains-an-unrecognized-cause-of-indolent-skin-infections
#14
Julie Steinbrink, Molara Alexis, Daniella Angulo-Thompson, Mayur Ramesh, George Alangaden, Marisa H Miceli
We identified 5 patients who had cutaneous lesions with cultures that yielded Mycobacterium marinum. It was discovered that all 5 patients had a home aquarium, and infection was preceded by trauma to the hand. However, the association between the development of the infection and exposure of the trauma site to the aquarium was not initially established until repeated questioning was performed. Skin biopsies or incision and drainage were performed for all patients, and the diagnosis was established by culture of the specimens...
November 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/29232411/rev-erb-agonist-improves-adverse-cardiac-remodeling-and-survival-in-myocardial-infarction-through-an-anti-inflammatory-mechanism
#15
Endin Nokik Stujanna, Nobuyuki Murakoshi, Kazuko Tajiri, DongZhu Xu, Taizo Kimura, Rujie Qin, Duo Feng, Saori Yonebayashi, Yukino Ogura, Fumi Yamagami, Akira Sato, Akihiko Nogami, Kazutaka Aonuma
Rev-erb α, known as nuclear receptor 1D1 (NR1D1), regulates circadian rhythm, modulates glucose and lipid metabolism, and inflammatory response. However, little is known about the effect of Rev-erb agonist on the progression of myocardial infarction (MI) and heart failure. To investigate it, wild-type male mice underwent sham-operation or permanent ligation of the left anterior descending coronary artery to create MI model. Rev-erb agonist SR9009 (100 mg/kg/day) or vehicle was intraperitoneally administered...
2017: PloS One
https://www.readbyqxmd.com/read/29232409/lupeol-and-stigmasterol-suppress-tumor-angiogenesis-and-inhibit-cholangiocarcinoma-growth-in-mice-via-downregulation-of-tumor-necrosis-factor-%C3%AE
#16
Thaned Kangsamaksin, Supattra Chaithongyot, Chanida Wootthichairangsan, Rattanavinan Hanchaina, Chayada Tangshewinsirikul, Jisnuson Svasti
Lupeol and stigmasterol, major phytosterols in various herbal plants, possess anti-inflammatory activities and have been proposed as candidates for anti-cancer agents, but their molecular mechanisms are still unclear. Here, we investigated the effects of lupeol and stigmasterol on tumor and endothelial cells in vitro and their anti-cancer activities in vivo. Our results demonstrated that lupeol and stigmasterol suppressed cell viability, migration, and morphogenesis of human umbilical vein endothelial cells (HUVECs) but not cholangiocarcinoma (CCA) cells...
2017: PloS One
https://www.readbyqxmd.com/read/29232383/low-doses-of-oxygen-ion-irradiation-cause-long-term-damage-to-bone-marrow-hematopoietic-progenitor-and-stem-cells-in-mice
#17
Yingying Wang, Jianhui Chang, Xin Li, Rupak Pathak, Vijayalakshmi Sridharan, Tamako Jones, Xiao Wen Mao, Gregory Nelson, Marjan Boerma, Martin Hauer-Jensen, Daohong Zhou, Lijian Shao
During deep space missions, astronauts will be exposed to low doses of charged particle irradiation. The long-term health effects of these exposures are largely unknown. We previously showed that low doses of oxygen ion (16O) irradiation induced acute damage to the hematopoietic system, including hematopoietic progenitor and stem cells in a mouse model. However, the chronic effects of low dose 16O irradiation remain undefined. In the current study, we investigated the long-term effects of low dose 16O irradiation on the mouse hematopoietic system...
2017: PloS One
https://www.readbyqxmd.com/read/29232382/charting-the-transcriptional-landscape-of-cells-of-renin-lineage-following-podocyte-depletion
#18
Aaron D McClelland, Julia Lichtnekert, Diana G Eng, Jeffrey W Pippin, Kenneth W Gross, Sina A Gharib, Stuart J Shankland
Renin producing cells of the juxtaglomerulus, herein called cells of renin lineage (CoRL), have garnered recent interest for their propensity to act as a progenitor source for various kidney cell types including podocytes. Despite recent advances, the process of transdifferentiation of CoRL to podocytes is poorly understood. In this study, we employed a transgenic reporter mouse line which permanently labels CoRL with ZsGreen fluorescent protein, allowing for isolation by fluorescence-activated cell sorting...
2017: PloS One
https://www.readbyqxmd.com/read/29232372/attenuated-expression-of-mtr-in-both-prenatally-androgenized-mice-and-women-with-the-hyperandrogenic-phenotype-of-pcos
#19
Lei Lei, Lijun Ding, Jing Su, Mengyuan Liu, Qingqing Shi, Jianjun Zhou, Haixiang Sun, Guijun Yan
Polycystic ovary syndrome (PCOS) is a common endocrine, metabolic and heterogeneous disorder in women of reproductive age, the exact etiology of which remains unknown. To unravel the molecular mechanisms underlying the hyperandrogenic phenotype of PCOS, prenatally androgenized (PNA) mice were used to mimic this phenotype in women with PCOS. Using microarray analysis, 1188 differentially expressed genes, including 671 upregulated and 517 downregulated genes, were identified in ovaries from PNA mice. Five differentially expressed genes (Aldh1a7, Bhmt, Mtr, Nrcam, Ptprg) were validated, and decreased MTR expression was shown in ovaries of PNA mice...
2017: PloS One
https://www.readbyqxmd.com/read/29232196/mechanisms-of-action-of-intravenous-immunoglobulin-in-septic-encephalopathy
#20
Figen Esen, Perihan Ergin Ozcan, Erdem Tuzun, M Dustin Boone
Acute brain dysfunction associated with sepsis is a serious complication that results in morbidity and mortality. Intravenous immunoglobulin (IVIg) treatment is known to alleviate behavioral deficits in the experimentally induced model of sepsis. To delineate the mechanisms by which IVIg treatment prevents neuronal dysfunction, an array of immunological and apoptosis markers was investigated. Our results suggest that IVIgG and IgGAM administration ameliorates neuronal dysfunction and behavioral deficits by reducing apoptotic cell death and glial cell proliferation...
December 12, 2017: Reviews in the Neurosciences
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