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Hyemin Kim, Won Ho Kong, Keum-Yong Seong, Dong Kyung Sung, Hyeonseon Jeong, Jin Kon Kim, Seung Yun Yang, Sei Kwang Hahn
Epidermal growth factor (EGF) has been recognized as an excellent wound healing agent due to its therapeutic function stimulating skin cell growth, proliferation and differentiation. However, the transdermal delivery of EGF poses a significant challenge due to its short half-life and lack of efficient formulation. Here, to improve the transdermal delivery efficiency, EGF was conjugated to hyaluronate (HA), which was formulated into a patch-type film for skin wound healing. HA-EGF conjugate was synthesized by coupling reaction between aldehyde-modified HA and N-terminal amine group of EGF to minimize the loss of biological activities...
October 24, 2016: Biomacromolecules
F Biscetti, G Straface, D Pitocco, F Angelini, G Tinelli, R Landolfi, A Flex
OBJECTIVE: Fibroblast growth factor 23 (FGF23) was demonstrated to be involved in the occurrence and development of cardiovascular disease (CVD). The aim of this study was to investigate the potential role of FGF23 on presence and severity of peripheral arterial disease (PAD) in type 2 diabetic patients. PATIENTS AND METHODS: In this study, we analyzed FGF23 serum levels in 413 type 2 diabetic patients with PAD and in 598 diabetic controls without lower limbs atherosclerosis...
October 2016: European Review for Medical and Pharmacological Sciences
Antonietta Franco, Richard N Kitsis, Julie A Fleischer, Evripidis Gavathiotis, Opher S Kornfeld, Guohua Gong, Nikolaos Biris, Ann Benz, Nir Qvit, Sara K Donnelly, Yun Chen, Steven Mennerick, Louis Hodgson, Daria Mochly-Rosen, Gerald W Dorn
Mitochondria are dynamic organelles, remodeling and exchanging contents during cyclic fusion and fission. Genetic mutations of mitofusin (Mfn) 2 interrupt mitochondrial fusion and cause the untreatable neurodegenerative condition, Charcot Marie Tooth disease type 2A (CMT2A). It has not been possible to directly modulate mitochondrial fusion, in part because the structural basis of mitofusin function is incompletely understood. Here we show that mitofusins adopt either a fusion-constrained or fusion-permissive molecular conformation directed by specific intramolecular binding interactions, and demonstrate that mitofusin-dependent mitochondrial fusion can be regulated by targeting these conformational transitions...
October 24, 2016: Nature
John Steven Torday
No abstract text is available yet for this article.
October 24, 2016: Pediatric Research
Satoshi Takasugi, Miho Shioyama, Masami Kitade, Masashi Nagata, Taketo Yamaji
The aim of this study was to investigate the effects of proton pump inhibitor (PPI), the most potent acid-suppressing drug, administration and intake of a combination of yogurt and galactooligosaccharides (YG) on bone and mineral metabolism in adult rats. Twelve-week-old male Wistar rats were divided into three groups: a control group fed the control diet with vehicle administration, a PPI group fed the control diet with PPI administration and a YG + PPI group fed the YG diet with PPI administration. All of the groups received their respective experimental diets and daily subcutaneous injection of the vehicle or PPI for 12 weeks...
October 21, 2016: Nutrients
Ingvild Aukrust, Ragnhild W Jansson, Cecilie Bredrup, Hilde E Rusaas, Siren Berland, Agnete Jørgensen, Marte G Haug, Eyvind Rødahl, Gunnar Houge, Per M Knappskog
PURPOSE: Despite being the third most common ABCA4 variant observed in patients with Stargardt disease, the functional effect of the intronic ABCA4 variant c.5461-10T>C is unknown. The purpose of this study was to investigate the molecular effect of this variant. METHODS: Fibroblast samples from patients carrying the ABCA4 variant c.5461-10T>C were analysed by isolating total RNA, followed by real-time polymerase chain reaction (RT-PCR) using specific primers spanning the variant...
October 24, 2016: Acta Ophthalmologica
Cong Wang, Yibo Gao, Xinghua Gao, Hua Wang, Jingxuan Tian, Li Wang, Bingpu Zhou, Ziran Ye, Jun Wan, Weijia Wen
A highly efficient photochromic hydrogel was successfully fabricated via casting precursor, which is based on amorphous tungsten oxide and poly (ethylene oxide)-block-poly (propylene oxide)-block-poly (ethylene oxide). Under simulated solar illumination, the hydrogel has a rapid and controlled temperature increasing ratio as its coloration degree. Localized electrons in the amorphous tungsten oxide play a vital role in absorption over a broad range of wavelengths from 400 nm to 1100 nm, encompassing the entire visible light and infrared regions in the solar spectrum...
October 24, 2016: Scientific Reports
Ruijuan Guan, Xia Wang, Xiaomei Zhao, Nana Song, Jimin Zhu, Jijiang Wang, Jin Wang, Chunmei Xia, Yonghua Chen, Danian Zhu, Linlin Shen
Aberrant activation of TGF-β1 is frequently encountered and promotes epithelial-mesenchymal transition (EMT) and fibroblast activation in pulmonary fibrosis. The present study investigated whether emodin mediates its effect via suppressing TGF-β1-induced EMT and fibroblast activation in bleomycin (BLM)-induced pulmonary fibrosis in rats. Here, we found that emodin induced apoptosis and inhibited cellular proliferation, migration and differentiation in TGF-β1-stimulated human embryonic lung fibroblasts (HELFs)...
October 24, 2016: Scientific Reports
Amal H Hamza, Widad M Al-Bishri, Laila A Damiati, Hanaa H Ahmed
BACKGROUND: The progresses made in stem cell therapy offer an innovative approach and exhibit great potential for the repair of damaged organs and tissues. This study was conducted with a view to find the mechanisms responsible for the effectiveness of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the suppression of diabetes and experimentally-induced diabetic nephropathy. METHODS: To realize this objective, diabetic and diabetic nephropathy subject groups that underwent MSC treatment were studied through numerous biochemistry and molecular genetics analyses...
October 23, 2016: Renal Failure
Viviana Anelli, Marina Mione
Cancer-associated fibroblasts (CAFs) are an activated sub-population of stromal fibroblast that have the ability to synthesize, deposit and remodel the extracellular matrix. They produce and secrete cytokines and growth factors that promote tumor growth, angiogenesis, inflammation and contribute to drug resistance (Micke and Ostman, 2005). CAFs are abundant constituents of many epithelial tumors. Less is known about CAFs in non-epithelial cancers, such as melanoma, but in vitro data suggest similar roles in tumor development and progression (Kim et al...
October 23, 2016: Pigment Cell & Melanoma Research
Khaled El Cheikh, Ilaria Basile, Afitz Da Silva, Coralie Bernon, Pierre Cérutti, Frédéric Salgues, Marc Perez, Marie Maynadier, Magali Gary-Bobo, Catherine Caillaud, Martine Cérutti, Marcel Garcia, Alain Morère
Improving therapeutics delivery in enzyme replacement therapy (ERT) for lysosomal storage disorders is a challenge. Herein, we present the synthesis of novel analogues of mannose 6-phosphate (M6P), known as AMFAs and functionalized at the anomeric position for enzyme grafting. AMFAs are non-phosphate serum-resistant derivatives that efficiently bind the cation-independent mannose 6-phosphate receptor (CI-M6PR), which is the main pathway to address enzymes to lysosomes. One of the AMFAs was used to improve the treatment of the lysosomal myopathy Pompe disease, in which acid α-glucosidase (GAA) is defective...
October 24, 2016: Angewandte Chemie
Nicole Y K Li-Jessen, Michael Powell, Ae-Jin Choi, Byung-Joo Lee, Susan L Thibeault
OBJECTIVES/HYPOTHESIS: High-mobility group box 1 (HMGB1) is a chromatin-binding protein located in the cell nucleus. Following injury, immunocompetent cells secrete HMGB1 to the extracellular milieu under the stimulation of proinflammatory cytokines. Extracellular HMGB1 acts a danger signal that instigates the innate immunity and tissue repair. We previously reported HMGB1 in the vocal fold extracellular compartment between day 3 and day 7 following surgical injury. In this study, we further investigated the cell source of HMGB1 and the relationship of proinflammatory cytokine expression and HMGB1 translocation in wounded vocal folds...
October 24, 2016: Laryngoscope
Zhaowei Kong, Shengyan Sun, Min Liu, Qingde Shi
This study was to determine the effects of five-week high-intensity interval training (HIIT) on cardiorespiratory fitness, body composition, blood glucose, and relevant systemic hormones when compared to moderate-intensity continuous training (MICT) in overweight and obese young women. Methods. Eighteen subjects completed 20 sessions of HIIT or MICT for five weeks. HIIT involved 60 × 8 s cycling at ~90% of peak oxygen consumption ([Formula: see text]) interspersed with 12 s recovery, whereas MICT involved 40-minute continuous cycling at 65% of [Formula: see text]...
2016: Journal of Diabetes Research
Anne S Bie, Paula Fernandez-Guerra, Rune I D Birkler, Shahar Nisemblat, Dita Pelnena, Xinping Lu, Joshua L Deignan, Hane Lee, Naghmeh Dorrani, Thomas J Corydon, Johan Palmfeldt, Liga Bivina, Abdussalam Azem, Kristin Herman, Peter Bross
We here report molecular investigations of a missense mutation in the HSPE1 gene encoding the HSP10 subunit of the HSP60/ HSP10 chaperonin complex that assists protein folding in the mitochondrial matrix. The mutation was identified in an infant who came to clinical attention due to infantile spasms at 3 months of age. Clinical exome sequencing revealed heterozygosity for a HSPE1 NM_002157.2:c.217C>T de novo mutation causing replacement of leucine with phenylalanine at position 73 of the HSP10 protein. This variation has never been observed in public exome sequencing databases or the literature...
2016: Frontiers in Molecular Biosciences
M Barandalla, S Colleoni, G Lazzari
Human Embryonic Stem Cells (hESCs) potentially offer a unique in vitro model to study how an adverse environment during the early developmental stages post-fertilization can affect the physiology of the undifferentiated embryonic stem cells existing in the early embryo and predispose to long term effects on the offspring, according to the Developmental Origins of Health and Disease (DOHaD) concept. A number of unfavourable conditions can affect the development of the early embryo inducing oxidative stress both in vivo, for instance in gestational diabetes and in vitro, when embryos are derived from Assisted Reproductive Technologies (ART)...
August 2016: Cell & Developmental Biology
S Thönes, L M Kutz, S Oehmichen, J Becher, K Heymann, A Saalbach, W Knolle, M Schnabelrauch, S Reichelt, U Anderegg
Cryogels made of components of natural extracellular matrix components are potent biomaterials for bioengineering and regenerative medicine. Human dermal fibroblasts are key cells for tissue replacement during wound healing. Thus, any biomaterial for wound healing applications should enable growth, differentiation and matrix synthesis by these cells. Cryogels are highly porous scaffolds consisting of a network of interconnected pores. Here, we used a novel group of cryogels generated from acrylated hyaluronan where the polymerization was initiated by accelerated electrons (E-beam)...
October 20, 2016: International Journal of Biological Macromolecules
Morgan S Schrock, Jenna R Karras, Matthew J Guggenbiller, Teresa Druck, Bahadir Batar, Kay Huebner
Expression of Fhit and Wwox protein is frequently lost or reduced in many human cancers. In this report, we provide data that further characterizes the molecular consequences of Fhit loss in the initiation of DNA double-strand breaks (DSBs), and of Wwox loss in altered repair of DSBs. We show that loss of Fhit initiates mild genome instability in early passage mouse kidney cells, confirming that DNA damage associated with Fhit-deficiency is not limited to cancer cells. We also demonstrate that the cause of Fhit-deficient DSBs: thymidine deficiency-induced replication stress, can be resolved with thymidine supplementation in early passage mouse kidney cells before extensive genome instability occurs...
September 26, 2016: Advances in Biological Regulation
Miho Nakamichi, Yuri Akishima-Fukasawa, Chie Fujisawa, Tetsuo Mikami, Kiyoshi Onishi, Yoshikiyo Akasaka
The precise role of fibrocytes in angiogenesis in wounds remains unclear. We therefore demonstrated the specific changes in fibrocyte accumulation for angiogesis in basic fibroblast growth factor (bFGF)-treated wounds. bFGF-treated wounds exhibited marked formation of arterioles and inhibition of podoplanin(+) lymph vessels that were lacking in vascular endothelial growth factor-A-treated wounds. Real-time PCR in bFGF-treated wounds manifested enhanced expression of CD34, CD31, and bFGF mRNA and reduced expression of podoplanin and collagen type I, III, and IV mRNA...
October 20, 2016: American Journal of Pathology
Yaara Cohen-Hadad, Gheona Altarescu, Talia Eldar-Geva, Ephrat Levi-Lahad, Ming Zhang, Ekaterina Rogaeva, Marc Gotkine, Osnat Bartok, Reut Ashwal-Fluss, Sebastian Kadener, Silvina Epsztejn-Litman, Rachel Eiges
We established two human embryonic stem cell (hESC) lines with a GGGGCC expansion in the C9orf72 gene (C9), and compared them with haploidentical and unrelated C9 induced pluripotent stem cells (iPSCs). We found a marked difference in C9 methylation between the cells. hESCs and parental fibroblasts are entirely unmethylated while the iPSCs are hypermethylated. In addition, we show that the expansion alters promoter usage and interferes with the proper splicing of intron 1, eventually leading to the accumulation of repeat-containing mRNA following neural differentiation...
October 17, 2016: Stem Cell Reports
Clara Bien Peek, Daniel C Levine, Jonathan Cedernaes, Akihiko Taguchi, Yumiko Kobayashi, Stacy J Tsai, Nicolle A Bonar, Maureen R McNulty, Kathryn Moynihan Ramsey, Joseph Bass
Circadian clocks are encoded by a transcription-translation feedback loop that aligns energetic processes with the solar cycle. We show that genetic disruption of the clock activator BMAL1 in skeletal myotubes and fibroblasts increased levels of the hypoxia-inducible factor 1α (HIF1α) under hypoxic conditions. Bmal1(-/-) myotubes displayed reduced anaerobic glycolysis, mitochondrial respiration with glycolytic fuel, and transcription of HIF1α targets Phd3, Vegfa, Mct4, Pk-m, and Ldha, whereas abrogation of the clock repressors CRY1/2 stabilized HIF1α in response to hypoxia...
October 19, 2016: Cell Metabolism
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