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https://www.readbyqxmd.com/read/28437863/sirt3-acts-as-a-negative-regulator-of-autophagy-dictating-hepatocyte-susceptibility-to-lipotoxicity
#1
Songtao Li, Xiaobing Dou, Hua Ning, Qing Song, Wei Wei, Ximei Zhang, Chen Shen, Jiaxin Li, Changhao Sun, Zhenyuan Song
Lipotoxicity induced by saturated fatty acids (SFAs) plays a central role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD); however, the exact mechanism(s) remain to be fully elucidated. SIRT3 is an NAD(+) -dependent deacetylase primarily located inside mitochondria. In this study, we demonstrated that a SFAs-rich high-fat diet (HFD) was more detrimental to the liver than an isocaloric unsaturated FAs-rich HFD. Unexpectedly, SIRT3 expression/activity were significantly elevated in the livers of mice exposed to the SFAs-rich HFD...
April 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28437835/pten-downregulation-promotes-%C3%AE-oxidation-to-fuel-hypertrophic-liver-growth-after-hepatectomy-in-mice
#2
Ekaterina Kachaylo, Christoph Tschuor, Nicolas Calo, Nathalie Borgeaud, Perparim Limani, Anne-Christine Piguet, Jean-Francois Dufour, Michelangelo Foti, Rolf Graf, Pierre A Clavien, Bostjan Humar
In regenerating liver, hepatocytes accumulate lipids before the major wave of parenchymal growth. This transient, regeneration-associated steatosis (TRAS) is required for liver recovery, but its purpose is unclear. The tumor suppressor PTEN is a key inhibitor of the AKT-mTOR axis that regulates growth and metabolic adaptations after hepatectomy. In quiescent liver, PTEN causes pathological steatosis when lost, while its role in regenerating liver remains unknown. Here, we show that PTEN downregulation promotes liver growth in a TRAS-dependent way...
April 24, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28437736/murine-diet-induced-obesity-remodels-cardiac-and-liver-mitochondrial-phospholipid-acyl-chains-with-differential-effects-on-respiratory-enzyme-activity
#3
E Madison Sullivan, Amy Fix, Miranda J Crouch, Genevieve C Sparagna, Tonya N Zeczycki, David A Brown, Saame Raza Shaikh
Cardiac phospholipids, notably cardiolipin, undergo acyl chain remodeling and/or loss of content in aging and cardiovascular diseases, which is postulated to mechanistically impair mitochondrial function. Less is known about how diet-induced obesity influences cardiac phospholipid acyl chain composition and thus mitochondrial responses. Here we first tested if a high fat diet remodeled murine cardiac mitochondrial phospholipid acyl chain composition and consequently disrupted membrane packing, supercomplex formation and respiratory enzyme activity...
April 12, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28437633/microrna-500a-promotes-migration-and-invasion-in-hepatocellular-carcinoma-by-activating-the-wnt-%C3%AE-catenin-signaling-pathway
#4
Yuntao Guo, Liwen Chen, Chengyi Sun, Chao Yu
Increased expression of microRNA-500a (miR-500a) has been reported in the serum of hepatocellular carcinoma (HCC) patients. However, the biological effects and mechanisms of miR-500a in hepatoma cells remain unclear. In this study, we found that miR-500a expression was up-regulated in HCC cell lines and tissues, and that high levels of miR-500a was associated with poor prognosis. We found that miR-500a upregulation promoted migration and invasion in two hepatoma cell lines, HCCLM3 and SMMC7721, while miR-500a downregulation had the opposite effect...
April 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28437605/aqueously-released-graphene-oxide-embedded-in-epoxy-resin-exhibits-different-characteristics-and-phytotoxicity-of-chlorella-vulgaris-from-the-pristine-form
#5
Xiangang Hu, Weilu Kang, Li Mu
The environmental release of nanoparticles is attracting increasing attention. Graphene oxide (GO) embedded in epoxy resin (ER) is a popular composite that has been used in various fields, but the environmental release of GO-ER composites and the effects on organisms in the environment remain unknown. The present work found that GO-ER composites in water for 2-7 days resulted in the release of 0.3-2.1% GO-ER at nanoscale (2-3 nm thickness and approximately 70-130 nm lateral length). Interestingly, pristine GO quenched 30-45% hydroxyl and 12% nitroxide free radicals, whereas this capacity was not observed for the released particles from GO-ER...
April 24, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28437576/irisin-and-musculoskeletal-health
#6
Graziana Colaianni, Saverio Cinti, Silvia Colucci, Maria Grano
Irisin is a hormone-like myokine produced in abundance by skeletal muscle in response to exercise, both in mice and humans. Once released into the circulation, irisin acts on white adipocytes to induce the browning response and subsequently activates nonshivering thermogenesis. We have examined the premise that irisin produced during exercise may subserve further functions in the musculoskeletal system. We review evidence for its possible skeletal effects, including the central role that irisin plays in the control of bone mass, with positive effects on cortical mineral density and geometry in mice...
April 24, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28437526/prominin-1-is-a-novel-regulator-of-autophagy-in-the-human-retinal-pigment-epithelium
#7
Sujoy Bhattacharya, Jinggang Yin, Christina S Winborn, Qiuhua Zhang, Junming Yue, Edward Chaum
Purpose: Prominin-1 (Prom1) is a transmembrane glycoprotein, which is expressed in stem cell lineages, and has recently been implicated in cancer stem cell survival. Mutations in the Prom1 gene have been shown to disrupt photoreceptor disk morphogenesis and cause an autosomal dominant form of Stargardt-like macular dystrophy (STGD4). Despite the apparent structural role of Prom1 in photoreceptors, its role in other cells of the retina is unknown. The purpose of this study is to investigate the role of Prom1 in the highly metabolically active cells of the retinal pigment epithelium (RPE)...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28437481/firemaster%C3%A2-550-and-its-components-isopropylated-triphenyl-phosphate-and-triphenyl-phosphate-enhance-adipogenesis-and-transcriptional-activity-of-peroxisome-proliferator-activated-receptor-ppar%C3%AE-on-the-adipocyte-protein-2-ap2-promoter
#8
Emily W Y Tung, Shaimaa Ahmed, Vian Peshdary, Ella Atlas
Firemaster® 550 (FM550) is a chemical mixture currently used as an additive flame retardant in commercial products, and is comprised of 2-ethylhexyl-2,3,4,5-tertrabromobenzoate (TBB), bis(2-ethylhexyl) tetrabromophthalate (TBPH), triphenyl phosphate (TPP), and isopropylated triphenyl phosphate (IPTP). Animal and in vitro studies suggest that FM550, TPP and IPTP may have adipogenic effects and may exert these effects through PPARγ activation. Using murine 3T3-L1 preadipocytes, we investigated the detailed expression of transcription factors and adipogenic markers in response to FM550 and its components...
2017: PloS One
https://www.readbyqxmd.com/read/28437463/relationship-of-the-crebc-two-component-regulatory-system-and-inner-membrane-protein-cred-with-swimming-motility-in-stenotrophomonas-maltophilia
#9
Hsin-Hui Huang, Wei-Ching Chen, Cheng-Wen Lin, Yi-Tsung Lin, Hsiao-Chen Ning, Yi-Chih Chang, Tsuey-Ching Yang
The CreBC two-component system (TCS) is a conserved regulatory system found in Escherichia coli, Aeromonas spp., Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. In this study, we determined how CreBC TCS regulates secreted protease activities and swimming motility using creB, creC, and creBC in-frame deletion mutants (KJΔCreB, KJΔCreC, and KJΔBC) of S. maltophilia KJ. Compared to wild-type KJ, KJΔCreB had a comparable secreted protease activity; however, the secreted protease activities were obviously reduced in KJΔCreC and KJΔBC, suggesting that CreC works together with another unidentified response regulator (not CreB) to regulate secreted protease activity...
2017: PloS One
https://www.readbyqxmd.com/read/28437395/global-survey-of-the-immunomodulatory-potential-of-common-drugs
#10
Gregory I Vladimer, Berend Snijder, Nikolaus Krall, Johannes W Bigenzahn, Kilian V M Huber, Charles-Hugues Lardeau, Kumar Sanjiv, Anna Ringler, Ulrika Warpman Berglund, Monika Sabler, Oscar Lopez de la Fuente, Paul Knöbl, Stefan Kubicek, Thomas Helleday, Ulrich Jäger, Giulio Superti-Furga
Small-molecule drugs may complement antibody-based therapies in an immune-oncology setting, yet systematic methods for the identification and characterization of the immunomodulatory properties of these entities are lacking. We surveyed the immumomodulatory potential of 1,402 small chemical molecules, as defined by their ability to alter the cell-cell interactions among peripheral mononuclear leukocytes ex vivo, using automated microscopy and population-wide single-cell image analysis. Unexpectedly, ∼10% of the agents tested affected these cell-cell interactions differentially...
April 24, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28437178/a-novel-injectable-recombinant-collagen-i-peptide-based-macroporous-microcarrier-allows-superior-expansion-of-c2c12-and-human-bone-marrow-derived-mesenchymal-stromal-cells-and-supports-deposition-of-mineralized-matrix
#11
Davide Confalonieri, Margherita La Marca, Elisabeth Marianna Wilhelmina Maria van Dongen, Heike Walles, Franziska Ehlicke
The development of scaffold formulations based on extracellular matrix-inspired synthetic materials constitutes an important resource for the advance of cell-based therapies in bone tissue engineering approaches, where both cell and scaffold implantation are often needed. Culturing cells on porous microcarriers (MCs) allows cell expansion in a three-dimensional microenvironment and constitutes a possible solution for minimally invasive cell and scaffold simultaneous delivery, but the reduced pore dimension and pore interconnection diameter of several commercially available microcarriers limits de facto cell ingrowth, and ultimately their suitability for in vivo cell delivery...
March 3, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28436968/metabolic-control-of-primed-human-pluripotent-stem-cell-fate-and-function-by-the-mir-200c-sirt2-axis
#12
Young Cha, Min-Joon Han, Hyuk-Jin Cha, Janet Zoldan, Alison Burkart, Jin Hyuk Jung, Yongwoo Jang, Chun-Hyung Kim, Ho-Chang Jeong, Byung-Gyu Kim, Robert Langer, C Ronald Kahn, Leonard Guarente, Kwang-Soo Kim
A hallmark of cancer cells is the metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon referred to as the 'Warburg effect', which is also observed in primed human pluripotent stem cells (hPSCs). Here, we report that downregulation of SIRT2 and upregulation of SIRT1 is a molecular signature of primed hPSCs and that SIRT2 critically regulates metabolic reprogramming during induced pluripotency by targeting glycolytic enzymes including aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase...
April 24, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28436957/pyruvate-kinase-m2-activation-may-protect-against-the-progression-of-diabetic-glomerular-pathology-and-mitochondrial-dysfunction
#13
Weier Qi, Hillary A Keenan, Qian Li, Atsushi Ishikado, Aimo Kannt, Thorsten Sadowski, Mark A Yorek, I-Hsien Wu, Samuel Lockhart, Lawrence J Coppey, Anja Pfenninger, Chong Wee Liew, Guifen Qiang, Alison M Burkart, Stephanie Hastings, David Pober, Christopher Cahill, Monika A Niewczas, William J Israelsen, Liane Tinsley, Isaac E Stillman, Peter S Amenta, Edward P Feener, Matthew G Vander Heiden, Robert C Stanton, George L King
Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and therapeutic options for preventing its progression are limited. To identify novel therapeutic strategies, we studied protective factors for DN using proteomics on glomeruli from individuals with extreme duration of diabetes (ł50 years) without DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol, methylglyoxal and mitochondrial pathways were elevated in individuals without DN. In particular, pyruvate kinase M2 (PKM2) expression and activity were upregulated...
April 24, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28436951/hypoxic-lung-cancer-secreted-exosomal-mir-23a-increased-angiogenesis-and-vascular-permeability-by-targeting-prolyl-hydroxylase-and-tight-junction-protein-zo-1
#14
Y-L Hsu, J-Y Hung, W-A Chang, Y-S Lin, Y-C Pan, P-H Tsai, C-Y Wu, P-L Kuo
Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28436724/circulating-proprotein-convertase-subtilisin-kexin-type-9-all-cause-mortality-and-cardiovascular-mortality-the-ludwigshafen-risk-and-cardiovascular-health-study
#15
Günther Silbernagel, Hubert Scharnagl, Marcus E Kleber, Tatjana Stojakovic, Winfried März
Background It is unclear whether proprotein convertase subtilisin-kexin type 9 (PCSK9) concentrations may be useful for cardiovascular risk stratification. Design The LUdwigshafen RIsk and Cardiovascular health (LURIC) study is a prospective observational registry of patients who were referred for coronary angiography. Methods Circulating PCSK9 was measured in 2139 participants of the LURIC study. There was a follow-up for all-cause and cardiovascular mortality with a median (interquartile range) duration of 10...
January 1, 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28436711/mir-33b-5p-sensitizes-gastric-cancer-cells-to-chemotherapy-drugs-via-inhibiting-hmga2-expression
#16
Xiaoyan Yang, Qian Zhao, Huali Yin, Xiaoyong Lei, Runliang Gan
MicroRNAs (miRNAs) are internal, noncoding, and ∼22 nt small RNAs that display cell- and tissue-specific expression. They play important regulatory roles in cell proliferation and chemo-sensitivity. This study focused on tumor-suppressive miR-33b-5p expression as well as its role in gastric cancer. MiR-33b-5p was found low expression in gastric cancer cell lines. Functionally, western blots and the luciferase reporter assay were used to confirme that HMGA2 was the potential target of miR-33b-5p. Next, we used CCK-8 kits to analyze the effect of miR-33b-5p combined chemotherapy drugs on cell inhibition rate, and flow cytometry to analyze cells apoptosis...
April 24, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28436683/dexmedetomidine-protects-pc12-cells-from-lidocaine-induced-cytotoxicity-through-downregulation-of-col3a1-mediated-by-mir-let-7b
#17
Qiong Wang, Yingjun She, Xiaobao Bi, Baisong Zhao, Xiangcai Ruan, Yonghong Tan
Safety concerns of some local anesthetics, such as lidocaine, have been raised in recent years due to potential neurological impairment. Dexmedetomidine may protect humans from neurotoxicity, and miR-let-7b is activated by nerve injury; however, the roles of miR-let-7b and its target gene in lidocaine-induced cytotoxicity are not well known. Through bioinformatics and a luciferase reporter assay, COL3A1 was suggested as a direct target gene of miR-let-7b. Here, we confirmed by measuring mRNA and protein levels that miR-let-7b was downregulated and COL3A1 was upregulated in lidocaine-treated cells, an observation that was reversed by dexmedetomidine...
April 24, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28436570/bre-enhances-osteoblastic-differentiation-by-promoting-the-mdm2-mediated-degradation-of-p53
#18
Fujun Jin, Yiliang Wang, Xiaojing Wang, Yanting Wu, Xiaoyan Wang, Qiuying Liu, Yexuan Zhu, Enqi Liu, Jianglin Fan, Yifei Wang
Bre is a conserved cellular protein expressed in various tissues. Its major function includes DNA damage repair and anti-apoptosis. Recent studies indicate that Bre is potentially involved in stem cell differentiation although pathophysiological significance along with the molecular mechanisms is still unclear. Here, we report that Bre protein was substantially expressed in the bone tissue and its expression was highly upregulated during the osteogenic differentiation. To test a hypothesis that Bre plays functional roles in the process of osteogenic differentiation, we examined the expression of Bre in an osteoporosis mouse model...
April 24, 2017: Stem Cells
https://www.readbyqxmd.com/read/28436420/key-role-of-15-lo-15-hete-in-angiogenesis-and-functional-recovery-in-later-stages-of-post-stroke-mice
#19
Di Wang, Yu Liu, Li Chen, Pengyan Li, Youyang Qu, Yanmei Zhu, Yulan Zhu
This study sought to clarify the effects of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in angiogenesis and neurological functional recovery after cerebral ischaemic stroke in mice. In vivo, we performed behavioural tests to determine functional recovery after stroke. Double immunofluorescence staining of CD31 and Ki67/PCNA was performed to evaluate the effects of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid on angiogenesis in an MCAO mouse model. In vitro, we investigated the effects of 15-hydroxyeicosatetraenoic acid on BMVEC proliferation and migration...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436337/molecular-cloning-expression-and-characterization-of-e2f-transcription-factor-4-from-antheraea-pernyi
#20
M N Abbas, S Kausar, Y-X Sun, Y Sun, L Wang, C Qian, G-Q Wei, B-J Zhu, C-L Liu
The E2F transcription factor family is distributed widely in eukaryotes and has been well studied among mammals. In the present study, the E2F transcription factor 4 (E2F4) gene was isolated from fat bodies of Antheraea pernyi and sequenced. E2F4 comprised a 795 bp open reading frame encoding a deduced amino acid sequence of 264 amino acid residues. The recombinant protein was expressed in Escherichia coli (Transetta DE3), and anti-E2F4 antibodies were prepared. The deduced amino acid sequence displayed significant homology to an E2F4-like protein from Bombyx mori L...
April 24, 2017: Bulletin of Entomological Research
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