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https://www.readbyqxmd.com/read/28717398/preclinical-evaluation-of-nf-%C3%AE%C2%BAb-triggered-dendritic-cells-expressing-the-viral-oncogenic-driver-of-merkel-cell-carcinoma-for-therapeutic-vaccination
#1
Kerstin F Gerer, Michael Erdmann, Sine R Hadrup, Rikke Lyngaa, Lena-Marie Martin, Reinhard E Voll, Beatrice Schuler-Thurner, Gerold Schuler, Niels Schaft, Stefanie Hoyer, Jan Dörrie
BACKGROUND: Merkel cell carcinoma (MCC) is a rare but very aggressive skin tumor that develops after integration of a truncated form of the large T-antigen (truncLT) of the Merkel cell polyomavirus (MCV) into the host's genome. Therapeutic vaccination with dendritic cells (DCs) loaded with tumor antigens is an active form of immunotherapy, which intends to direct the immune system towards tumors which express the respective vaccination antigens. METHODS: Cytokine-matured monocyte-derived DCs of healthy donors and MCC patients were electroporated with mRNA encoding the truncLT...
July 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28716662/lgtf-effects-of-haemophilus-parasuis-los-induced-inflammation-through-regulation-of-nf-%C3%AE%C2%BAb-and-mapks-signaling-pathways
#2
Ze Zeng, Bin Zhang, Huan He, Xinnuo Chen, Yupeng Ren, Hua Yue, Cheng Tang
The lgtF gene encodes a glucosyltransferase responsible for adding a glucose to the first sugar of heptose I in the synthesis of lipooligosaccharides (LOS). To study the function of lgtF, we constructed an lgtF mutant (ΔlgtF) from Haemophilus parasuis SC096 using a natural transformation system. A highly purified preparation of LOS from ΔlgtF (ΔlgtF-LOS) exhibited an obvious truncation in structure compared to the LOS of the wild-type SC096 strain (WT-LOS). The ΔlgtF-LOS also displayed a significantly reduced ability to induce inflammatory cytokine mRNA expression of tumor necrosis factor alpha (TNF-α), interleukin-1α (IL-1α), IL-1β, IL-6 and IL-8 in porcine alveolar macrophages (PAMs) in comparison with the WT-LOS...
July 14, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28716597/cells-isolated-from-cryopreserved-dental-follicle-display-similar-characteristics-to-cryopreserved-dental-follicle-cells
#3
Hefeng Yang, Jie Li, JingJing Sun, Weihua Guo, Hui Li, Jinglong Chen, Yu Hu, Weidong Tian, Song Li
Dental follicle tissue is a promising resource of mesenchymal stem cells for cytotherapeutic approaches and tissue engineering applications. There are two procedures for banking of human dental follicle stem cells have been reported. Conventional method requires cell isolation, expansion and immediate cryopreservation. Whereas dental follicle stem cells can be isolated from cryopreserved dental follicle fragments. The aim of this study was to compare the characteristics of dental follicle cells isolated from cryopreserved fragments (DFCs-CF) with dental follicle cells recovered from cryopreserved cells (DFCs-CC)...
July 14, 2017: Cryobiology
https://www.readbyqxmd.com/read/28715234/is-cardiovascular-disease-in-patients-with-diabetes-associated-with-serum-levels-of-mmp-2-lox-and-the-elastin-degradation-products-elm-and-elm-2
#4
Simone Andrea Rørdam Preil, Anne-Sofie Faarvang Thorsen, Anne Lindegaard Christiansen, Mikael Kjær Poulsen, Morten Asser Karsdal, Diana Julie Leeming, Lars Melholt Rasmussen
BACKGROUND: Diabetes mellitus type 2 (T2DM) is a significant risk factor for the development of cardiovascular diseases (CVDs). In a previous microarray study of internal mammary arteries from patients with and without T2DM, we observed several elastin-related genes with altered mRNA-expression in diabetic patients, namely matrix metalloproteinase 2 (MMP-2), lysyl oxidase (LOX) and elastin itself. In this study we investigate whether the serum concentrations of elastin-related proteins correlate to signs of CVD in patients with T2DM...
July 17, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28714989/correction-of-a-splicing-defect-in-a-mouse-model-of-congenital-muscular-dystrophy-type-1a-using-a-homology-directed-repair-independent-mechanism
#5
Dwi U Kemaladewi, Eleonora Maino, Elzbieta Hyatt, Huayun Hou, Maylynn Ding, Kara M Place, Xinyi Zhu, Prabhpreet Bassi, Zahra Baghestani, Amit G Deshwar, Daniele Merico, Hui Y Xiong, Brendan J Frey, Michael D Wilson, Evgueni A Ivakine, Ronald D Cohn
Splice-site defects account for about 10% of pathogenic mutations that cause Mendelian diseases. Prevalence is higher in neuromuscular disorders (NMDs), owing to the unusually large size and multi-exonic nature of genes encoding muscle structural proteins. Therapeutic genome editing to correct disease-causing splice-site mutations has been accomplished only through the homology-directed repair pathway, which is extremely inefficient in postmitotic tissues such as skeletal muscle. Here we describe a strategy using nonhomologous end-joining (NHEJ) to correct a pathogenic splice-site mutation...
July 17, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28714570/human-osteoarthritic-chondrons-outnumber-patient-and-joint-matched-chondrocytes-in-hydrogel-culture-future-application-in-autologous-cell-based-oa-cartilage-repair
#6
Miriam Rothdiener, Tatiana Uynuk-Ool, Norbert Südkamp, Matthias Aurich, Alan J Grodzinsky, Bodo Kurz, Bernd Rolauffs
Autologous chondrocyte implantation (ACI) is used in 34-60% for osteoarthritic (OA) cartilage defects, although ACI is neither recommended nor designed for OA. Envisioning a hydrogel-based ACI for OA that uses chondrons instead of classically used chondrocytes, we hypothesized that human OA-chondrons may outperform OA-chondrocytes. We compared patient- and joint surface-matched human OA-chondrons vs. OA-chondrocytes cultured for the first time in a hydrogel, using a self-assembling peptide system. We determined yield, viability, cell numbers, mRNA expression, GAPDH mRNA enzyme activity, collagen II synthesis (CPII) and degradation (C2C), and sGAG...
July 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28714520/genomic-profiling-of-long-non-coding-rna-and-mrna-expression-associated-with-acquired-temozolomide-resistance-in-glioblastoma-cells
#7
Huijun Zeng, Ningbo Xu, Yanting Liu, Boyang Liu, Zhao Yang, Zhao Fu, Changlin Lian, Hongbo Guo
Temozolomide (TMZ) is an alkylating chemotherapeutic agent widely used in anti-glioma treatment. However, acquired TMZ resistance represents a major clinical challenge that leads to tumor relapse or progress. This study investigated the genomic profiles including long non-coding RNA (lncRNA) and mRNA expression associated with acquired TMZ resistance in glioblastoma (GBM) cells in vitro. The TMZ-resistant (TR) of GBM sub-cell lines were established through repetitive exposure to increasing TMZ concentrations in vitro...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28713985/microarray-expression-profiles-of-long-non-coding-rnas-in-germinal-center-like-diffuse-large-b-cell-lymphoma
#8
Hong-Yu Gao, Bin Wu, Wei Yan, Zi-Mu Gong, Qi Sun, Hui-Han Wang, Wei Yang
Long non-coding RNAs (lncRNAs) are continuously transcribed and are involved in various cellular activities. However, their contributions to the occurrence and development of germinal center B-cell (GCB)-like diffuse large B-cell lymphoma (DLBCL) remain largely unknown. We applied microarray technology to profile the expression of lncRNAs in two different GCB-DLBCL cell lines (OCI-ly1 and OCI-ly19) and normal B lymphocytes. We demonstrated that 21,539 lncRNAs were expressed in all of the samples analyzed...
July 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28708539/ppar-expression-throughout-the-oestrous-cycle-in-the-bovine-endometrium
#9
B M Socha, M Łupicka, A A Szczepańska, A J Korzekwa
Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that is composed of three isoforms: PPARα, PPARβ/δ and PPARγ. The ratio of two isoforms of PPARγ (1 and 2) varies among both species and tissues. The activity of PPARs can be modified by a number of endogenous compounds, including arachidonic acid (AA), its eicosanoid metabolites and synthetic ligands. Many studies have revealed that PPARs are important in reproduction. We hypothesized that the profiles of PPARs expression vary in the bovine endometrium during certain days of the oestrous cycle...
June 8, 2017: Theriogenology
https://www.readbyqxmd.com/read/28705935/forkhead-box-o3-foxo3-regulates-kidney-tubular-autophagy-following-urinary-tract-obstruction
#10
Ling Li, Ronald Zviti, Catherine Ha, Zhao V Wang, Joseph A Hill, Fangming Lin
Autophagy has been shown to be important for normal homeostasis and adaptation to stress in the kidney. Yet, the molecular mechanisms regulating renal epithelial autophagy are not fully understood. Here, we explored the role of the stress-responsive transcription factor forkhead box O3 (FoxO3) in mediating injury-induced proximal tubular autophagy in mice with unilateral ureteral obstruction (UUO). We show that following UUO, FoxO3 is activated and displays nuclear expression in the hypoxic proximal tubules exhibiting high levels of autophagy...
July 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28701922/bone-marrow-mesenchymal-stem-cell-transplantation-promotes-functional-improvement-associated-with-cntf-stat3-activation-after-hemi-sectioned-spinal-cord-injury-in-tree-shrews
#11
Liu-Lin Xiong, Fei Liu, Bing-Tuan Lu, Wen-Ling Zhao, Xiu-Juan Dong, Jia Liu, Rong-Ping Zhang, Piao Zhang, Ting-Hua Wang
Hemi-sectioned spinal cord injury (hSCI) can lead to spastic paralysis on the injured side, as well as flaccid paralysis on the contralateral side, which can negatively affect a patient's daily life. Stem-cell therapy may offer an effective treatment option for individuals with hSCI. To examine the role of bone marrow mesenchymal stem cells (BMSCs) transplantation on hSCI and explore related mechanisms in the tree shrews, here, we created a model of hSCI by inducing injury at the tenth thoracic vertebra (T10)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28701510/immunomodulatory-molecule-irak-m-balances-macrophage-polarization-and-determines-macrophage-responses-during-renal-fibrosis
#12
Stefanie Steiger, Santhosh V Kumar, Mohsen Honarpisheh, Georg Lorenz, Roman Günthner, Simone Romoli, Regina Gröbmayr, Heni-Eka Susanti, Jan Potempa, Joanna Koziel, Maciej Lech
Activation of various innate immune receptors results in IL-1 receptor-associated kinase (IRAK)-1/IRAK-4-mediated signaling and secretion of proinflammatory cytokines such as IL-12, IL-6, or TNF-α, all of which are implicated in tissue injury and elevated during tissue remodeling processes. IRAK-M, also known as IRAK-3, is an inhibitor of proinflammatory cytokine and chemokine expression in intrarenal macrophages. Innate immune activation contributes to both acute kidney injury and tissue remodeling that is associated with chronic kidney disease (CKD)...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28698120/effectiveness-of-formalin-killed-vaccines-containing-cpg-oligodeoxynucleotide-1668-adjuvants-against-vibrio-harveyi-in-orange-spotted-grouper
#13
Hai Trong Nguyen, Thuy Thi Thu Nguyen, Yi-Ting Wang, Pei-Chyi Wang, Shih-Chu Chen
Vibrio harveyi is a major bacterial pathogen that causes serious vibriosis in cultured groupers, leading to massive deaths. In this study, we evaluated the immune responses and protective efficacy of vaccines containing V. harveyi formalin-killed cells (FKC) formulated with CpG ODN 1668-enriched plasmids (p30CpG and p60CpG) in the orange-spotted grouper. Results indicated that antibody titres were remarkably increased in vaccinated fish 2 weeks post-immunisation. Expression level of major histocompatibility complex (MHC) class II, CD 8, and toll-like receptor 9 was significantly upregulated in the spleen of fish immunised with CpG ODN 1668-adjuvanted vaccines, as recorded at 6 weeks after immunisation...
July 8, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28696012/inhibition-of-snk-spar-signaling-pathway-promotes-the-restoration-of-motor-function-in-a-rat-model-of-ischemic-stroke
#14
Qing-Yu Fan, Jing-Jie Liu, Gui-Lian Zhang, Hai-Qin Wu, Ru Zhang, Shu-Qin Zhan, Na Liu
This study aimed to investigate the effects of SPAR signaling pathway on the restoration of motor function in ischemic stroke (IS). Sprague-Dawley male rats were separated into the control and sham groups, as well as the group for middle cerebral artery occlusion (MCAO) model establishment. Successfully established rat ischemic models were randomly divided into model, SNK(MCAO-del) and pcDNA3.1-SNK groups. The evaluation of motor function among the rats in each group was assessed using a balance beam, a screen test and the Garcia scoring method...
July 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28695966/dyrk2-displays-muscle-fiber-type-specific-function-during-zebrafish-early-somitogenesis
#15
Wei Sun, Shuang Jiao, Xungang Tan, Peijun Zhang, Feng You
Dual specificity tyrosine-phosphorylation regulated kinase 2 (DYRK2) is a serine/threonine kinase. In zebrafish, DYRK2 is expressed in the lateral somites and adaxial cells at the early stage of embryo development. However, its role in early myogenesis had not been elucidated yet. Here, we report that DYRK2 mRNA and MyoD mRNA were colocalized in the muscle progenitor cells in somites, including both the posterior compartment of the lateral somites and adaxial cells. Knockdown of DYRK2 reduced the levels of MyoD transcripts in the muscle progenitor cells in somites...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28694325/tcr-cxcr4-signaling-stabilizes-cytokine-mrna-transcripts-via-a-prex1-rac1-pathway-implications-for-ctcl
#16
Kimberly N Kremer, Brittney A Dinkel, Rosalie M Sterner, Douglas G Osborne, Dragan Jevremovic, Karen E Hedin
As with many immunopathologically-driven diseases, the malignant T cells of cutaneous T cell lymphomas (CTCL), such as Sezary Syndrome, display aberrant cytokine secretion patterns that contribute to pathology and disease progression. Targeting this disordered release of cytokines is complicated by the changing cytokine milieu that drives the phenotypic changes of CTCL. Here, we characterize a novel signaling pathway that can be targeted to inhibit the secretion of cytokines by modulating either CXCR4 or CXCR4-mediated signaling...
July 10, 2017: Blood
https://www.readbyqxmd.com/read/28692647/the-effects-of-kisspeptin-10-on-serum-metabolism-and-myocardium-in-rats
#17
Ying Zhang, Yuanlong Hou, Xiaoyan Wang, Jihui Ping, Zhiyu Ma, Chuan Suo, Zhihai Lei, Xiang Li, Zheng Zhang, Cuicui Jia, Juan Su
Kisspeptin is a peptide encoded by the Kiss 1 gene and is also called metastin. Previous studies have generally focused on several functions of this peptide, including metastasis, puberty, vasoconstriction and reproduction. However, few studies have focused on the cardiac functions of kisspeptin. In the present study, cardiac histomorphology was observed via TEM (transmission electron microscope) and HE and Masson staining to observe instinctive changes. Serum metabolites levels were also measured and analyzed using GC/TOF-MS after injection with kisspeptin-10...
2017: PloS One
https://www.readbyqxmd.com/read/28688895/differential-requirement-of-sufu-in-tissue-development-discovered-in-a-hypomorphic-mouse-model
#18
Maria A Hoelzl, Karin Heby-Henricson, Marco Gerling, José M Dias, Raoul V Kuiper, Cornelius Trünkle, Åsa Bergström, Johan Ericson, Rune Toftgård, Stephan Teglund
Suppressor of Fused (SUFU) is an essential negative regulator of the Hedgehog (HH) pathway and involved in GLI transcription factor regulation. Due to early embryonic lethality of Sufu(-/-) mice, investigations of SUFU's role later in development are limited to conditional, tissue-specific knockout models. In this study we developed a mouse model (Sufu(Ex456(fl)/Ex456(fl))) with hypomorphic features where embryos were viable up to E18.5, although with a spectrum of developmental defects of varying severity, including polydactyly, exencephaly and omphalocele...
July 5, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28688852/cdkl5-controls-postsynaptic-localization-of-glun2b-containing-nmda-receptors-in-the-hippocampus-and-regulates-seizure-susceptibility
#19
Kosuke Okuda, Shizuka Kobayashi, Masahiro Fukaya, Aya Watanabe, Takuto Murakami, Mai Hagiwara, Tempei Sato, Hiroe Ueno, Narumi Ogonuki, Sayaka Komano-Inoue, Hiroyuki Manabe, Masahiro Yamaguchi, Atsuo Ogura, Hiroshi Asahara, Hiroyuki Sakagami, Masashi Mizuguchi, Toshiya Manabe, Teruyuki Tanaka
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders accompanied by intractable epilepsies, i.e. West syndrome or atypical Rett syndrome. Here we report generation of the Cdkl5 knockout mouse and show that CDKL5 controls postsynaptic localization of GluN2B-containing N-methyl-d-aspartate (NMDA) receptors in the hippocampus and regulates seizure susceptibility. Cdkl5 -/Y mice showed normal sensitivity to kainic acid; however, they displayed significant hyperexcitability to NMDA...
July 6, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28688003/increased-training-intensity-induces-proper-membrane-localization-of-actin-remodeling-proteins-in-the-hippocampus-preventing-cognitive-deficits-implications-for-fragile-x-syndrome
#20
L A Martinez, Maria Victoria Tejada-Simon
Behavioral intervention therapy has proven beneficial in the treatment of autism and intellectual disabilities (ID), raising the possibility of certain changes in molecular mechanisms activated by these interventions that may promote learning. Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by autistic features and intellectual disability and can serve as a model to examine mechanisms that promote learning. FXS results from mutations in the fragile X mental retardation 1 gene (Fmr1) that prevents expression of the Fmr1 protein (FMRP), a messenger RNA (mRNA) translation regulator at synapses...
July 8, 2017: Molecular Neurobiology
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