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Carol H Miao
Current treatment of hemophilia A (HemA) patients with repeated infusions of factor VIII (FVIII; abbreviated as F8 in constructs) is costly, inconvenient, and incompletely effective. In addition, approximately 25 % of treated patients develop anti-factor VIII immune responses. Gene therapy that can achieve long-term phenotypic correction without the complication of anti-factor VIII antibody formation is highly desired. Lentiviral vector (LV)-mediated gene transfer into hematopoietic stem cells (HSCs) results in stable integration of FVIII gene into the host genome, leading to persistent therapeutic effect...
2016: Thrombosis Journal
Nirali N Shah, Theresa M Watson, Bonnie Yates, David J Liewehr, Seth M Steinberg, David Jacobsohn, Terry J Fry
BACKGROUND: Diagnosis of engraftment syndrome (ES) following allogeneic hematopoietic stem cell transplantation (HSCT) can be a challenge due to the systemic presentation and alternative etiologies. With a goal of establishing biomarkers to more accurately distinguish ES, we prospectively analyzed levels of cytokines during HSCT. PROCEDURES: We performed a prospective study of children ≤21 years who underwent allogeneic HSCT. Blood samples for interleukin (IL)-6, IL-8, IL-10, IL-1b, IL-12p70, interferon-γ, tumor necrosis factor alpha (TNF-α) and procalcitonin were obtained from each subject prior to conditioning, at day 0, and then biweekly through engraftment and at days 30, 60 and 100...
October 20, 2016: Pediatric Blood & Cancer
Feng Zhou, Ying Zhang, Jing Chen, Xuemei Hu, Yancheng Xu
Liraglutide, an effective drug for the treatment of diabetes, has been proven to demonstrate anti-inflammatory and immunomodulatory effects. Hence, this study explored the effects and mechanism of action of liraglutide on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Male BALB/c mice were pre-conditioned with liraglutide or saline prior to intraperitoneal LPS or saline administration. Histopathological examination of lung, the wet/dry (W/D)weight ratio, protein content, inflammatory cell numbers and pro-inflammatory cytokine levels in broncho-alveolar lavage fluid (BAL fluid) were conducted...
October 15, 2016: European Journal of Pharmacology
Takashi Ishida, Sachie Suzuki, Chen-Yi Lai, Satoshi Yamazaki, Shigeru Kakuta, Yoichiro Iwakura, Masanori Nojima, Yasuo Takeuchi, Masaaki Higashihara, Hiromitsu Nakauchi, Makoto Otsu
Hematopoietic stem cell (HSC) transplantation (HSCT) for malignancy requires toxic pre-conditioning to maximize anti-tumor effects and donor-HSC engraftment. While this induces bone marrow (BM)-localized inflammation, how this BM environmental change affects transplanted HSCs in vivo remains largely unknown. We here report that, depending on interval between irradiation and HSCT, residence within lethally irradiated recipient BM compromises donor-HSC reconstitution ability. Both in vivo and in vitro we demonstrate that, among inflammatory cytokines, TNF-α plays a role in HSC damage: TNF-α stimulation leads to accumulation of reactive oxygen species (ROS) in highly purified hematopoietic stem/progenitor cells (HSCs/HSPCs)...
October 18, 2016: Stem Cells
Daniel Pelaez, Zenith Acosta Torres, Tsz Kin Ng, Kwong Wai Choy, Chi Pui Pang, Herman S Cheung
Cellular therapies for the treatment of myocardial infarction have proven to be an invaluable tool in recent years and provide encouraging evidence for the possibility to restore normal heart function. However, questions still remain as to the optimal cell source, pre-conditioning methods and delivery techniques for such an application. This study explores the use of a population of stem cells arising from the neural crest and isolated from adult human periodontal ligament along with short-term mechanical strain as an inducer of cardiomyogenesis and possibly pre-conditioning stimulus for cellular cardiomyoplasty...
October 17, 2016: Cell and Tissue Research
Thangavelu Soundara Rajan, Sabrina Giacoppo, Oriana Trubiani, Francesca Diomede, Adriano Piattelli, Placido Bramanti, Emanuela Mazzon
Conditioned medium derived from mesenchymal stem cells (MSCs) shows immunomodulatory and neuroprotective effects in preclinical models. Given the difficulty to harvest MSCs from bone marrow and adipose tissues, research has been focused to find alternative resources for MSCs, such as oral-derived tissues. Recently, we have demonstrated the protective effects of MSCs obtained from healthy human periodontal ligament tissue (hPDLSCs) in murine experimental autoimmune encephalomyelitis model. In the present in vitro study, we have investigated the immunomodulatory and neuroprotective effects of conditioned medium obtained from hPDLSCs of Relapsing Remitting- Multiple sclerosis (RR-MS) patients on NSC34 mouse motoneurons stimulated with lipopolysaccharide (LPS)...
October 11, 2016: Experimental Cell Research
Nicholas V Skladnev, Varshika Ganeshan, Ji Yeon Kim, Thomas J Burton, John Mitrofanis, Jonathan Stone, Daniel M Johnstone
Dietary saffron has shown promise as a neuroprotective intervention in clinical trials of retinal degeneration and dementia and in animal models of multiple CNS disorders, including Parkinson's disease. This therapeutic potential makes it important to define the relationship between dose and protection and the mechanisms involved. To explore these two issues, mice were pre-conditioned by providing an aqueous extract of saffron (0.01% w/v) as their drinking water for 2, 5 or 10 days before administration of the parkinsonian neurotoxin MPTP (50 mg/kg)...
October 1, 2016: Journal of Neurochemistry
Ladda Kajeechiwa, May Myo Thwin, Paw Wah Shee, Nan Lin Yee, Elvina Elvina, Peapah Peapah, Kyawt Kyawt, Poe Thit Oo, William PoWah, Jacqueline Roger Min, Jacher Wiladphaingern, Lorenz von Seidlein, Suphak Nosten, Francois Nosten
BACKGROUND: A targeted malaria elimination project, including mass drug administrations (MDA) of dihydroartemisinin/piperaquine plus a single low dose primaquine is underway in villages along the Thailand Myanmar border. The intervention has multiple components but the success of the project will depend on the participation of the entire communities. Quantitative surveys were conducted to study reasons for participation or non-participation in the campaign with the aim to identify factors associated with the acceptance and participation in the mass drug administrations...
September 27, 2016: Malaria Journal
Carolyn W Snyder
Reconstructions of Earth's past climate strongly influence our understanding of the dynamics and sensitivity of the climate system. Yet global temperature has been reconstructed for only a few isolated windows of time, and continuous reconstructions across glacial cycles remain elusive. Here I present a spatially weighted proxy reconstruction of global temperature over the past 2 million years estimated from a multi-proxy database of over 20,000 sea surface temperature point reconstructions. Global temperature gradually cooled until roughly 1...
September 26, 2016: Nature
Heike A Hildebrandt, Vincent Kreienkamp, Sabine Gent, Philipp Kahlert, Gerd Heusch, Petra Kleinbongard
Although remote ischemic pre-conditioning (RIPC) reduced infarct size in animal experiments and proof-of-concept clinical trials, recent phase III trials failed to confirm cardioprotection during cardiac surgery. Here, we characterized the kinetic properties of humoral factors that are released after RIPC, as well as the signal transduction pathways that were responsible for cardioprotection in an ex vivo model of global ischemia reperfusion injury. Venous blood from 20 healthy volunteers was collected at baseline and 5 min, 30 min, 1 h, 6 h, and daily from 1 to 7 days after RIPC (3 × 5/5 min upper-limb ischemia/reperfusion)...
January 2016: JACC. Basic to Translational Science
Sailaja Ghanta, Konstantin Tsoyi, Xiaoli Liu, Kiichi Nakahira, Bonna Ith, Anna A Coronata, Laura E Fredenburgh, Joshua A Englert, Claude A Piantadosi, Augustine M K Choi, Mark A Perrella
Oxidative stress resulting from inflammatory responses that occur during acute lung injury and sepsis can initiate changes in mitochondrial function. Autophagy regulates cellular processes in the setting of acute lung injury, sepsis, and oxidative stress by modulating the immune response and facilitating turnover of damaged cellular components. We have shown that mesenchymal stromal cells (MSCs) improve survival in murine models of sepsis by also regulating the immune response. However, the effect of autophagy on MSC and MSC mitochondrial function during oxidative stress is unknown...
September 16, 2016: American Journal of Respiratory Cell and Molecular Biology
Christian Heim, Benjamin Motsch, Sabina Jalilova, Wanja Bernhard, Martina Ramsperger-Gleixner, Nicolai Burzlaff, Michael Weyand, Kai-Uwe Eckardt, Stephan M Ensminger
BACKGROUND: Obliterative bronchiolitis (OB) is the major limiting factor for long-term survival after lung transplantation. As previously shown, donor treatment with a PHD-inhibitor activating hypoxia-inducible transcription factors (HIFs) prevents graft injury both in an allogenic kidney and aortic allograft transplant model. The aim of this study was to investigate the effect of HIF activation with a PHD-inhibitor on the development of OB. METHODS: Fully MHC-mismatched C57BL/6 (H-2(b)) donor tracheas were orthotopically transplanted into CBA/J (H-2(k)) recipients...
August 30, 2016: Transplant Immunology
Ao Zhou, Meng Li, Bo He, Weixing Feng, Fei Huang, Bing Xu, A Keith Dunker, Curt Balch, Baiyan Li, Yunlong Liu, Yue Wang
BACKGROUND: Lipopolysaccharide (LPS) is a gram-negative bacterial antigen that triggers a series of cellular responses. LPS pre-conditioning was previously shown to improve the therapeutic efficacy of bone marrow stromal cells/bone-marrow derived mesenchymal stem cells (BMSCs) for repairing ischemic, injured tissue. RESULTS: In this study, we systematically evaluated the effects of LPS treatment on genome-wide splicing pattern changes in mouse BMSCs by comparing transcriptome sequencing data from control vs...
2016: BMC Genomics
Sofia Halin Bergström, Christina Hägglöf, Elin Thysell, Anders Bergh, Pernilla Wikström, Marie Lundholm
Accumulating data indicates that tumor-derived extracellular vesicles (EVs) are responsible for tumor-promoting effects. However, if tumor EVs also prepare the tumor-bearing organ for subsequent tumor growth, and if this effect is different in low and high malignant tumors is not thoroughly explored. Here we used orthotopic rat Dunning R-3327 prostate tumors to compare the role of EVs from fast growing and metastatic MatLyLu (MLL) tumors with EVs from more indolent and non-metastatic Dunning G (G) tumors. Prostate tissue pre-conditioned with MLL-EVs in vivo facilitated G tumor establishment compared to G-EVs...
2016: Scientific Reports
Amar Bhide, Olli Vuolteenaho, Mervi Haapsamo, Tiina Erkinaro, Juha Rasanen, Ganesh Acharya
Myocardial performance index (MPI) is increased in growth-restricted fetuses with placental insufficiency, but it is unknown if this is due to fetal hypoxemia or increased placental vascular resistance (Rplac). We used chronically instrumented sheep fetuses (n = 24). In 12 fetuses, placental embolization was performed 24 h before experiments. On the day of the experiment, left (LV) and right (RV) ventricular MPIs were obtained by pulsed Doppler at baseline and in the hypoxemia and recovery phases. At baseline, Rplac was greater and fetal pO2 lower in the placental embolization group, but RV and LV MPIs were comparable to those of the control group...
November 2016: Ultrasound in Medicine & Biology
C Paul Buckley, S T Samuel Salisbury, Amy B Zavatsky
Tendons are highly anisotropic and also viscoelastic. For understanding and modeling their 3D deformation, information is needed on their viscoelastic response under off-axis loading. A study was made, therefore, of creep and recovery of bovine digital extensor tendons when subjected to transverse compressive stress of up to ca. 100 kPa. Preconditioned tendons were compression tested between glass plates at increasing creep loads. The creep response was anomalous: the relative rate of creep reduced with the increasing stress...
October 1, 2016: Journal of Biomechanical Engineering
Jingkai Wang, Yiqing Tao, Xiaopeng Zhou, Hao Li, Chengzhen Liang, Fangcai Li, Qi-Xin Chen
Recent studies indicated that cell-based therapy could be a promising approach to treat intervertebral disc degeneration. Though the harsh microenvironment in disc is still challenging to implanted cells, it could be overcome by pre-conditioning graft cells before transplantation, suggested by previous literatures. Therefore, we designed this study to identify the potential effect of chondrogenic pre-differentiation on adipose-derived mesenchymal stem cells in intervertebral disc-like microenvironment, characterized by limited nutrition, acidic, and high osmosis in vitro...
August 3, 2016: Experimental Biology and Medicine
Eleonora Aricò, Paola Sestili, Giulia Carpinelli, Rossella Canese, Serena Cecchetti, Giovanna Schiavoni, Maria Teresa D'Urso, Filippo Belardelli, Enrico Proietti
Tumor-specific immune tolerance represents an obstacle for the development of effective anti-tumor immune responses through cancer vaccines. We here evaluated the efficacy of chemo-immunotherapy in breaking tumor-specific immune tolerance in an almost incurable mouse model of spontaneous carcinogenesis.Transgenic HER-2/neu mice bearing large mammary tumors received the adoptive transfer of splenocytes and serum isolated from immune donors, with or without pre-conditioning with cyclophosphamide. Treatment efficacy was assessed by monitoring tumor growth by manual inspection and by magnetic resonance imaging...
July 28, 2016: Oncotarget
Zijiang Yang, John Concannon, Kelvin S Ng, Kathleen Seyb, Luke J Mortensen, Sudhir Ranganath, Fangqi Gu, Oren Levy, Zhixiang Tong, Keir Martyn, Weian Zhao, Charles P Lin, Marcie A Glicksman, Jeffrey M Karp
Pre-treatment or priming of mesenchymal stem cells (MSC) prior to transplantation can significantly augment the immunosuppressive effect of MSC-based therapies. In this study, we screened a library of 1402 FDA-approved bioactive compounds to prime MSC. We identified tetrandrine as a potential hit that activates the secretion of prostaglandin E2 (PGE2), a potent immunosuppressive agent, by MSC. Tetrandrine increased MSC PGE2 secretion through the NF-κB/COX-2 signaling pathway. When co-cultured with mouse macrophages (RAW264...
2016: Scientific Reports
Mattia Fabbri, Edoardo Monaco, Riccardo Maria Lanzetti, Dario Perugia, Matteo Guzzini, Luca Labianca, Andrea Ferretti
BACKGROUND: The all-inside graft-link technique for anterior cruciate ligament reconstruction is performed with two cortical suspension devices with adjustable loops on both femur and tibia. This technique requires meticulous graft preparation. The aim of this study was to biomechanically test three different graft configurations resulting from differences in initial graft length. MATERIALS AND METHODS: Thirty bovine digital extensor tendons were arranged in three different ways: "half-quadrupled", "tripled" and "quadrupled"...
July 19, 2016: Journal of Orthopaedics and Traumatology: Official Journal of the Italian Society of Orthopaedics and Traumatology
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