Nitrite/nitrate levels in patients after stem cell transplant

published_or_final_versio

Pharmacologically blocking p53-dependent apoptosis protects intestinal stem cells and mice from radiation.

Exposure to high levels of ionizing radiation (IR) leads to debilitating and dose-limiting gastrointestinal (GI) toxicity. Using three-dimensional mouse crypt culture, we demonstrated that p53 target PUMA mediates radiation-induced apoptosis via a cell-intrinsic mechanism, and identified the GSK-3 inhibitor CHIR99021 as a potent radioprotector. CHIR99021 treatment improved Lgr5+ cell survival and crypt regeneration after radiation in culture and mice. CHIR99021 treatment specifically blocked apoptosis and PUMA induction and K120 acetylation of p53 mediated by acetyl-transferase Tip60, while it had no effect on p53 stabilization, phosphorylation or p21 induction. CHIR99021 also protected human intestinal cultures from radiation by PUMA but not p21 suppression. These results demonstrate that p53 posttranslational modifications play a key role in the pathological and apoptotic response of the intestinal stem cells to radiation and can be targeted pharmacologically

Improved Cell Survival and Paracrine Capacity of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells Promote Therapeutic Potential for Pulmonary Arterial Hypertension.

Although transplantation of adult bone marrow mesenchymal stem cells (BM-MSCs) holds promise in the treatment for pulmonary arterial hypertension (PAH), the poor survival and differentiation potential of adult BM-MSCs have limited their therapeutic efficiency. Here, we compared the therapeutic efficacy of human embryonic stem cell-derived MSCs (hESC-MSCs) with adult BM-MSCs for the treatment of PAH in an animal model. One week following monocrotaline (MCT)-induced PAH, mice were randomly assigned to receive phosphate-buffered saline (MCT group); 3.0×106 human BM-derived MSCs (BM-MSCs group) or 3.0 ×106 hESC-derived MSCs (hESC-MSCs group) via tail vein injection. At 3 weeks posttransplantation, the right ventricular systolic pressure (RVSP), degree of RV hypertrophy, and medial wall thickening of pulmonary arteries were lower=, and pulmonary capillary density was higher in the hESC-MSC group as compared with BM-MSC and MCT groups (all p < 0.05). At 1 week posttransplantation, the number of engrafted MSCs in the lungs was found significantly higher in the hESC-MSC group than in the BM-MSC group (all p < 0.01). At 3 weeks posttransplantation, implanted BM-MSCs were undetectable whereas hESC-MSCs were not only engrafted in injured pulmonary arteries but had also undergone endothelial differentiation. In addition, protein profiling of hESC-MSC- and BM-MSC-conditioned medium revealed a differential paracrine capacity. Classification of these factors into bioprocesses revealed that secreted factors from hESC-MSCs were preferentially involved in early embryonic development and tissue differentiation, especially blood vessel morphogenesis. We concluded that improved cell survival and paracrine capacity of hESC-MSCs provide better therapeutic efficacy than BM-MSCs in the treatment for PAH. © 2012 Cognizant Comm. Corp.published_or_final_versio

Improved Cell Survival and Paracrine Capacity of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells Promote Therapeutic Potential for Pulmonary Arterial Hypertension.

Although transplantation of adult bone marrow mesenchymal stem cells (BM-MSCs) holds promise in the treatment for pulmonary arterial hypertension (PAH), the poor survival and differentiation potential of adult BM-MSCs have limited their therapeutic efficiency. Here, we compared the therapeutic efficacy of human embryonic stem cell-derived MSCs (hESC-MSCs) with adult BM-MSCs for the treatment of PAH in an animal model. One week following monocrotaline (MCT)-induced PAH, mice were randomly assigned to receive phosphate-buffered saline (MCT group); 3.0×106 human BM-derived MSCs (BM-MSCs group) or 3.0 ×106 hESC-derived MSCs (hESC-MSCs group) via tail vein injection. At 3 weeks posttransplantation, the right ventricular systolic pressure (RVSP), degree of RV hypertrophy, and medial wall thickening of pulmonary arteries were lower=, and pulmonary capillary density was higher in the hESC-MSC group as compared with BM-MSC and MCT groups (all p < 0.05). At 1 week posttransplantation, the number of engrafted MSCs in the lungs was found significantly higher in the hESC-MSC group than in the BM-MSC group (all p < 0.01). At 3 weeks posttransplantation, implanted BM-MSCs were undetectable whereas hESC-MSCs were not only engrafted in injured pulmonary arteries but had also undergone endothelial differentiation. In addition, protein profiling of hESC-MSC- and BM-MSC-conditioned medium revealed a differential paracrine capacity. Classification of these factors into bioprocesses revealed that secreted factors from hESC-MSCs were preferentially involved in early embryonic development and tissue differentiation, especially blood vessel morphogenesis. We concluded that improved cell survival and paracrine capacity of hESC-MSCs provide better therapeutic efficacy than BM-MSCs in the treatment for PAH. © 2012 Cognizant Comm. Corp.published_or_final_versio

Numerical simulations of nonequilibrium flows over rounded models at reentry speeds

2012-2013 > Academic research: refereed > Refereed conference paperOther VersionPublishe

Crystallisation route map

A route map for the assessment of crystallisation processes is presented. A theoretical background on solubility, meta-stable zone width, nucleation and crystal growth kinetics is presented with practical examples. The concepts of crystallisation hydrodynamics and the application of population balances and computational fluid dynamics for modelling crystallisation processes and their scaling up are also covered

Novel Tunable Fiber Optic Edge Filter Based on Modulating Chirp Rate of pi-Phase-Shifted Fiber Bragg Grating

We propose and experimentally demonstrate a novel tunable fiber optic edge filter based on modulating the chirp rate of a pi-phase-shifted fiber Bragg grating (FBG) operated in reflection mode. The phase shift induced notch in the reflection spectrum is utilized as the edge filter. The dependence of the pi-phase-shifted FBG's spectral response on the chirp rate has been numerically studied in detail and experimentally confirmed for the first time. The linear wavelength range of this edge filter can be tuned by changing the chirp rate of FBG. A fiber optic edge filter is further obtained experimentally and tested as a wavelength interrogator, which is in a good agreement with numerical results. The proposed edge filter has advantages of simple-structure, cost-effectiveness, high sensitivity, and flexible tunable, thus opening up some applications, especially as wavelength interrogator in small wavelength range

Biodegradable Thermosensitive Hydrogel for SAHA and DDP Delivery: Therapeutic Effects on Oral Squamous Cell Carcinoma Xenografts

Background: OSCC is one of the most common malignancies and numerous clinical agents currently applied in combinative chemotherapy. Here we reported a novel therapeutic strategy, SAHA and DDP-loaded PECE (SAHA-DDP/PECE), can improve the therapeutic effects of intratumorally chemotherapy on OSCC cell xenografts. Objective/Purpose: The objective of this study was to evaluate the therapeutic efficacy of the SAHA-DDP/PECE in situ controlled drug delivery system on OSCC cell xenografts. Methods: A biodegradable and thermosensitive hydrogel was successfully developed to load SAHA and DDP. Tumorbeared mice were intratumorally administered with SAHA-DDP/PECE at 50 mg/kg (SAHA) +2 mg/kg (DDP) in 100 ul PECE hydrogel every two weeks, SAHA-DDP at 50 mg/kg(SAHA) +2 mg/kg(DDP) in NS, 2 mg/kg DDP solution, 50 mg/kg SAHA solution, equal volume of PECE hydrogel, or equal volume of NS on the same schedule, respectively. The antineoplastic actions of SAHA and DDP alone and in combination were evaluated using the determination of tumor volume, immunohistochemistry, western blot, and TUNEL analysis. Results: The hydrogel system was a free-flowing sol at 10uC, become gel at body temperature, and could sustain more than 14 days in situ. SAHA-DDP/PECE was subsequently injected into tumor OSCC tumor-beared mice. The results demonstrated that such a strategy as this allows the carrier system to show a sustained release of SAHA and DDP in vivo, and coul

Analysis of the genomic homologous recombination in Theilovirus based on complete genomes

At present, Theilovirus is considered to comprise four distinct serotypes, including Theiler's murine encephalomyelitis virus, Vilyuisk human encephalomyelitis virus, Thera virus, and Saffold virus. So far, there is no systematical study that investigated the genomic recombination of Theilovirus. The present study performed the phylogenetic and recombination analysis of Theilovirus over the complete genomes. Seven potentially significant recombination events were identified. However, according to the strains information and references related to the recombinants and their parental strains, four of the recombination events might happen non-naturally. These results will provide valuable hints for future research on evolution and antigenic variability of Theilovirus