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Ji-Eun Im, Sun-Hwa Song, Wonhee Suh
PURPOSE: Stem cell factor (SCF) has been recently acknowledged as a novel endothelial permeability factor. However, the mechanisms by which SCF-induced activation of the SCF cognate receptor, cKit, enhances endothelial permeability have not been fully elucidated. This study aimed to investigate the role of Src in SCF-induced breakdown of the blood-retinal barrier (BRB). METHODS: In vitro endothelial permeability and in vivo retinal vascular permeability assays were performed to investigate the role of Src in SCF-induced breakdown of the BRB...
2016: Molecular Vision
Zhenping Wang, Nicholas Mascarenhas, Lars Eckmann, Yukiko Miyamoto, Xiaojun Sun, Toshiaki Kawakami, Anna Di Nardo
BACKGROUND: Mast cell (MC) progenitors leave the bone marrow, enter the circulation, and settle in the skin and other tissues. Their maturation in tissues is influenced by the surrounding microenvironment. OBJECTIVE: We tested the hypothesis that environmental factors play a role in MC maturation in the skin. METHODS: MCs were numerically, phenotypically, and functionally compared between germ-free (GF), SPF, and GF mice reconstituted with microbiota...
October 13, 2016: Journal of Allergy and Clinical Immunology
Seyyed Mohammad Reza Hashemnia, Somayeh Atari-Hajipirloo, Shiva Roshan-Milani, Nasim Valizadeh, Sonya Mahabadi, Fatemeh Kheradmand
BACKGROUND: The anticancer agent imatinib (IM) is a small molecular analog of ATP that inhibits tyrosine kinase activity of platelet derived growth factors (PDGFs) and stem cell factor (SCF) receptor in cancer cells. However these factors have a key role in regulating growth and development of normal Sertoli, Leydig and germ cells. OBJECTIVE: The aim of this study was to determine cell viability, PDGF and SCF levels in mouse normal Sertoli cells exposed to IM. MATERIALS AND METHODS: In this experimental study, the mouse TM4 Sertoli cells were treated with 0, 2...
September 2016: International Journal of Reproductive Biomedicine (Yazd, Iran)
Yuya Yamagishi, Marc Tessier-Lavigne
Axon degeneration is a tightly regulated, self-destructive program that is a critical feature of many neurodegenerative diseases, but the molecular mechanisms regulating this program remain poorly understood. Here, we identify S-phase kinase-associated protein 1A (Skp1a), a core component of a Skp/Cullin/F-box (SCF)-type E3 ubiquitin ligase complex, as a critical regulator of axon degeneration after injury in mammalian neurons. Depletion of Skp1a prolongs survival of injured axons in vitro and in the optic nerve in vivo...
October 11, 2016: Cell Reports
Yilun Wu, Xicheng Lu, Jinshu Su, Peixin Chen
Preserving the privacy of electronic medical records (EMRs) is extremely important especially when medical systems adopt cloud services to store patients' electronic medical records. Considering both the privacy and the utilization of EMRs, some medical systems apply searchable encryption to encrypt EMRs and enable authorized users to search over these encrypted records. Since individuals would like to share their EMRs with multiple persons, how to design an efficient searchable encryption for sharable EMRs is still a very challenge work...
December 2016: Journal of Medical Systems
Haichen Li, David J Yaron
A least-squares commutator in the iterative subspace (LCIIS) approach is explored for accelerating self-consistent field (SCF) calculations. LCIIS is similar to direct inversion of the iterative subspace (DIIS) methods in that the next iterate of the density matrix is obtained as a linear combination of past iterates. However, whereas DIIS methods find the linear combination by minimizing a sum of error vectors, LCIIS minimizes the Frobenius norm of the commutator between the density matrix and the Fock matrix...
October 6, 2016: Journal of Chemical Theory and Computation
Qin Qin, Jianrong Liu, Yuehong Ma, Yimin Wang, Fang Zhang, Songdan Gao, Lina Dong
BACKGROUND/PURPOSE: Varicocele (VC) is considered by the World Health Organization as the main cause of male infertility. Studies have shown that VC can affect spermatogenesis and then result in male infertility. But the exact mechanism by which VC affects spermatogenesis is still unclear. Stem cell factor (SCF) and c-KIT receptor are crucial molecules during spermatogenesis in testis. This study aims to investigate whether SCF/c-KIT signaling is involved in the pathophysiology of VC on spermatogenesis...
October 2, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Kiran Jyoti, Richa Kaur Bhatia, Elvis A F Martis, Evans C Coutinho, Upendra Kumar Jain, Ramesh Chandra, Jitender Madan
In present investigation, initially curcumin was complexed with 2-HP-β-CD (curcumin-2-HP-β-CD-complex) in 1:1 ratio and later amalgamated with chitosan microspheres (curcumin-2-HP-β-CD-CMs) for selective delivery in colon only through oral route of administration. Various analytical, spectral and in-silico docking techniques revealed that the curcumin was deeply inserted in the 2-HP-β-CD cavity with apparent stability constant of 3.35×10(-3)M. Furthermore, the mean particle size of 6.8±2.6μm and +39...
September 28, 2016: Colloids and Surfaces. B, Biointerfaces
Mark Wunderlich, Courtney Stockman, Mahima Devarajan, Navin Ravishankar, Christina Sexton, Ashish R Kumar, Benjamin Mizukawa, James C Mulloy
Transgenic expression of key myelosupportive human cytokines in immune-deficient mice corrects for the lack of cross-species activities of stem cell factor (SCF), IL-3, and GM-CSF. When engrafted with human umbilical cord blood (UCB), these triple-transgenic mice produce BM and spleen grafts with much higher myeloid composition, relative to nontransgenic controls. Shortly after engraftment with UCB, these mice develop a severe, fatal macrophage activation syndrome (MAS) characterized by a progressive drop in rbc numbers, increased reticulocyte counts, decreased rbc half-life, progressive cytopenias, and evidence of chronic inflammation, including elevated human IL-6...
September 22, 2016: JCI Insight
Risa Mukai, Takayuki Ohshima
Human T-cell leukemia virus type1 (HTLV-1) is an oncogenic retrovirus that is the etiological agent of adult T-cell leukemia (ATL). The HTLV-1 basic leucine-zipper factor (HBZ), which is encoded by the minus strand of the provirus, is constitutively expressed in all ATL patient cells and likely contributes to the development and maintenance of ATL. Furthermore, the overexpression of myeloid cell leukemia-1 (MCL1) is frequently observed in hematological cancers as well as several other types of cancers. Here, we found that the expression of HBZ in cells stabilized MCL1 protein expression and suppressed MCL-mediated release of cytochrome c from the mitochondria...
October 3, 2016: Molecular and Cellular Biology
Yassmin O Samak, Magda El Massik, Allan G A Coombes
Alginate microparticles incorporating hydrocortisone hemisuccinate were produced by aerosolization and homogenization methods to investigate their potential for colonic drug delivery. Microparticle stabilization was achieved by CaCl2 crosslinking solution (0.5 M and 1 M), and drug loading was accomplished by diffusion into blank microparticles or by direct encapsulation. Homogenization method produced smaller microparticles (45-50 μm), compared to aerosolization (65-90 μm). High drug loadings (40% wt/wt) were obtained for diffusion-loaded aerosolized microparticles...
September 29, 2016: Journal of Pharmaceutical Sciences
A L Márquez-Aguirre, R M Camacho-Ruíz, Y K Gutiérrez-Mercado, E Padilla-Camberos, M González-Ávila, F J Gálvez-Gastélum, N E Díaz-Martínez, D Ortuño-Sahagún
Fructans from agave have received specific attention because of their highly branched fructan content. We have previously reported that the degree of polymerization (dp) influences their biological activity. Therefore, the aim of this study was to investigate the effect of unfractionated and fractionated fructans (higher and lower dps) from Agave tequilana in high-fat diet-induced (HFD) obese mice. Fructans with a lower dp (HFD+ScF) decreased weight gain by 30 %, body fat mass by 51 %, hyperglycemia by 25 % and liver steatosis by 40 %...
September 27, 2016: Plant Foods for Human Nutrition
E Malek, M A Y Abdel-Malek, S Jagannathan, N Vad, R Karns, A G Jegga, A Broyl, M van Duin, P Sonneveld, F Cottini, K C Anderson, J J Driscoll
While clinical benefit of the proteasome inhibitor (PI) bortezomib for multiple myeloma (MM) patients remains unchallenged, dose-limiting toxicities and drug resistance limit the long-term utility. The E3 ubiquitin (Ub) ligase Skp1-Cullin-1-Skp2 (SCF(Skp2)) promotes proteasomal degradation of the cell cycle inhibitor p27 to enhance tumor growth. Increased SKP2 expression and reduced p27 levels are frequent in human cancers and are associated with therapeutic resistance. SCF(Skp2) activity is increased by the Cullin-1-binding protein Commd1 and the Skp2-binding protein Cks1B...
September 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Neta Soffer-Tsur, Dan Peer, Tal Dvir
The success of hematopoietic stem cells (HSCs) transplantation is limited due to the low number of HSCs received from donors. In vivo, HSCs reside within a specialized niche inside the 3D porous spongy bone. The natural environment in the niche is composed of structural proteins, glycosaminoglycans (GAGs) and soluble factors that control cells fate. However, the designed scaffolds for in vitro culture do not fairly recapitulate this microenvironment and cannot efficiently control HSCs fate. Here we report on the development of new omental ECM-based 3D macroporous sponges for hematopoietic cell culture...
September 23, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
F L Cheng, Q T Li, C Q Zhao, Y F An, X P Qi
Objective: To investigate the effect of interleukin-4 (IL-4) stimulation on the expression of FcεRⅠα and NK-1R on mature mast cells(MC) cultured and differentiated from mouse bone marrow stem cells, and then to study if these MC also respond to substance P (SP) both in FcεRⅠα and NK-1R dependent manners. Methods: Bone marrow cells were aseptically flushed from BALB/c mouse femurs into complete RPMI 1640, followed by culture with stem cell factor (SCF 100 μg/L), IL-3 (15 μg/L) and IL-4 (0, 10, 15, 20 and 25 μg/L, respectively)...
September 7, 2016: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
Sandhya Anand, Deepa Bhartiya, Kalpana Sriraman, Alpna Mallick
Very small embryonic-like stem cells (VSELs) exist among spermatogonial stem cells and survive chemotherapy in both mice and human testes because of their relatively quiescent nature. Our earlier study revealed that inter-tubular transplantation of niche (Sertoli or bone marrow derived mesenchymal) cells can restore spermatogenesis from endogenous surviving VSELs. Present study was undertaken to delineate the effect of busulphan on testicular stem/germ/Sertoli cells and to comprehend the underlying mechanisms of how transplanted niche cells restore spermatogenesis...
September 23, 2016: Stem Cell Reviews
Loic Lebellec, François Bertucci, Emmanuelle Tresch-Bruneel, Emmanuelle Bompas, Yves Toiron, Luc Camoin, Olivier Mir, Valerie Laurence, Stephanie Clisant, Emilie Decoupigny, Jean-Yves Blay, Anthony Goncalves, Nicolas Penel
BACKGROUND: Patients with advanced chordoma are often treated with tyrosine kinase inhibitors without any predictive factor to guide decision. We report herein an ancillary analysis of the the Angionext phase II trial (NCT 00874874). RESULTS: From May 2011 to January 2014, 26 were sampled. The 9-month PFS rate was 72.9% (95%-CI: 45.9-87.9). During sorafenib treatment, a significant increase in PlGF (18.4 vs 43.8 pg/mL, p<0.001) was noted along with a non-significant increase in VEGF (0...
September 21, 2016: Oncotarget
Szilamér Ferenczi, Krisztián Szegi, Zsuzsanna Winkler, Teréz Barna, Krisztina J Kovács
Inflammatory bowel disease shows increasing prevalence, however its pathomechanism and treatment is not fully resolved. Prebiotics are non-digestible carbohydrates which might provide an alternative to treat inflammatory conditions in the gut due to their positive effects either on the microbiome or through their direct effect on macrophages and mucosa. To test the protective effects of an oligomannan prebiotic, yeast cell wall mannooligosaccharide (MOS) was administered in dextran-sulphate-sodium (DSS)-induced mouse model of acute colitis...
2016: Scientific Reports
Nana Zheng, Xiangpeng Dai, Zhiwei Wang, Wenyi Wei
Set8 is critically involved in transcription regulation, cell cycle progression and genomic stability. Emerging evidence has revealed that E3 ubiquitin ligases such as CRL4(cdt2) and SCF(Skp2) regulate Set8 protein abundance. However, it is unclear whether other E3 ligase(s) could govern Set8 level for proper cell cycle progression in response to genotoxic stress such as UV irradiation. Recently, we report that the SCF(β-TRCP) complex regulates Set8 protein stability by targeting it for ubiquitination and subsequent degradation...
September 20, 2016: Cell Cycle
Bastian Jöhnk, Özgür Bayram, Anja Abelmann, Thorsten Heinekamp, Derek J Mattern, Axel A Brakhage, Ilse D Jacobsen, Oliver Valerius, Gerhard H Braus
F-box proteins share the F-box domain to connect substrates of E3 SCF ubiquitin RING ligases through the adaptor Skp1/A to Cul1/A scaffolds. F-box protein Fbx15 is part of the general stress response of the human pathogenic mold Aspergillus fumigatus. Oxidative stress induces a transient peak of fbx15 expression, resulting in 3x elevated Fbx15 protein levels. During non-stress conditions Fbx15 is phosphorylated and F-box mediated interaction with SkpA preferentially happens in smaller subpopulations in the cytoplasm...
September 2016: PLoS Pathogens
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