Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different ...mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.
Background
Myocardial infarction is one of the most common causes of death, and the number of individuals at risk is increasing. A rapid and accurate differential diagnosis of myocardial infarction ...is crucial for timely interventions and for improvement of the prognosis. However, it is difficult to achieve using current methods. To better manage this condition, improved tools for risk prediction, including more accurate biomarkers, are needed.
Methods
We studied the expression of microRNA-539 (miR-539) and of MEK protein using a rat model of myocardial infarction.
Results
The results of our experiments demonstrated an increase in the expression of miR-539 and a decrease in the expression of MEK. Furthermore, we observed that miR-539 inhibited the expression of MEK through targeting of the 3’UTR of MEK; this led not only to suppressed proliferation but also to apoptosis and autophagy of H9C2 cells.
Conclusion
Overexpression of miR-539 plays a role in the degree of myocardial infarction. On the basis of our results, we conclude that miR-539 may be a potential therapeutic target for myocardial infarction.
The aim of the study was to investigate whether functional changes and structural remodeling occurs in the microvascular bed of the pulmonary circulation under nonpulsatile flow perfusion.
An animal ...model of unilateral nonpulsatile flow in the right lung was established in dogs. Streptavidin-biotin enzyme complex (SP method) was used to detect the expression of endothelial nitric oxide synthase (eNOS) in vascular endothelial cells and the apoptosis-related protein Fas in smooth muscle cells of the pulmonary artery of both lungs, and structural changes of the arterioles in the capillary bed of both lungs were observed under light microscope.
eNOS expression in right lung arterioles with nonpulsatile flow perfusion was significantly lower than in the left lung (10,846.7 ± 177.8 vs. 13,136.1 ± 189.6; T = 2.24, P < 0.05). Expression of the apoptosis-related protein Fas in smooth muscle cells of the arteriole of the right lung was significantly higher than in the left lung (14,254.1 ± 217.1 vs. 11,976.7 ± 195.7; T = 2.16, P < 0.05). Image analysis of pulmonary arterioles showed that the ratio of vascular wall thickness and the external vessel diameter (13.64% ± 12.8% vs. 14.96% ± 13.1%) and the ratio of vascular wall area and the total vessel area (46.4% ± 11.7% vs. 47.8% ± 12.2%) of the right lung were significantly lower than in the left lung.
Long-term nonpulsatile flow perfusion of the Fontan circulation can decrease the synthesis of eNOS in endothelial cells of the pulmonary vessels, increase the apoptosis of smooth muscle cells of the arteriole wall, and lead to arterial venous conversion and pulmonary vessel remodeling.
Study on Preference of Shuso Japanese Paper HU, Hongguang; TAKAI, Yuka; GOTO, Akihiko
International Journal of Affective Engineering,
2014, Letnik:
13, Številka:
1
Journal Article
Odprti dostop
Japanese paper made in Saijo City is called shuso, and its making is a traditional Japanese craft. One of the main characteristics of shuso paper is a crepe structure called shibo. The shibo ...structure is made by hand; it is fabricated by bending the edge of the shuso paper toward the front. The shibo structure is affected by the bending angle. In recent years, the demand for shuso paper has stagnated. Shuso paper requires the creation of new products. However, the preferred type of shuso paper is unclear. The shibo structure of shuso paper can easily be changed to prepare many types of shibo structures. This study quantified shibo structures of shuso paper under various fabrication conditions. The preferences of subjects from different countries for shuso paper with various shibo structures were clarified.
Purpose
: Cystine knot (knottin) peptides, engineered to bind with high affinity to integrin receptors, have shown promise as molecular imaging agents in living subjects. The aim of the current study ...was to evaluate tumor uptake and
in vivo
biodistribution of
18
F-labeled knottins in a U87MG glioblastoma model.
Procedures
: Engineered knottin mutants 2.5D and 2.5F were synthesized using solid phase peptide synthesis and were folded
in vitro
, followed by radiolabeling with 4-nitrophenyl 2-
18
F-fluoropropionate (
18
F-NFP). The resulting probes,
18
F-FP-2.5D and
18
F-FP-2.5F, were evaluated in nude mice bearing U87MG tumor xenografts using microPET and biodistribution studies.
Results
: MicroPET imaging studies with
18
F-FP-2.5D and
18
F-FP-2.5F demonstrated high tumor uptake in U87MG xenograft mouse models. The probes exhibited rapid clearance from the blood and kidneys, thus leading to excellent tumor-to-normal tissue contrast. Specificity studies confirmed that
18
F-FP-2.5D and
18
F-FP-2.5F had reduced tumor uptake when co-injected with a large excess of the peptidomimetic c(RGDyK) as a blocking agent.
Conclusions
:
18
F-FP-2.5D and
18
F-FP-2.5F showed reduced gallbladder uptake compared with previously published
18
F-FB-2.5D.
18
F-FP-2.5D and
18
F-FP-2.5F enabled integrin-specific PET imaging of U87MG tumors with good imaging contrasts.
18
F-FP-2.5D demonstrated more desirable pharmacokinetics compared to
18
F-FP-2.5F, and thus has greater potential for clinical translation.
Study on Preference of Shuso Japanese Paper Hu, Hongguang; Takai, Yuka; Goto, Akihiko
International Journal of Affective Engineering,
2014, Letnik:
13, Številka:
1
Journal Article
Odprti dostop
Japanese paper made in Saijo City is called shuso, and its making is a traditional Japanese craft. One of the main characteristics of shuso paper is a crepe structure called shibo. The shibo ...structure is made by hand; it is fabricated by bending the edge of the shuso paper toward the front. The shibo structure is affected by the bending angle. In recent years, the demand for shuso paper has stagnated. Shuso paper requires the creation of new products. However, the preferred type of shuso paper is unclear. The shibo structure of shuso paper can easily be changed to prepare many types of shibo structures. This study quantified shibo structures of shuso paper under various fabrication conditions. The preferences of subjects from different countries for shuso paper with various shibo structures were clarified.
Fractional calculus has been used to model various hydrologic processes for 15years. Yet, there are still major gaps between real-world hydrologic dynamics and fractional-order partial differential ...equations (fPDEs). In addition, the applicability of fPDEs in the broad field of Earth dynamics remains obscure. This study first reviews previous applications and then identifies new research directions for fPDEs simulating non-Fickian transport in both surface and subsurface hydrology. We then explore the applicability of fractional calculus in various anomalous dynamics with a wide range of spatiotemporal scales observed in the solid Earth, including internal dynamics (such as inner core rotation, outer core flow, mantle convection, and crustal deformation), large-scale surface dynamics (in fluvial, Aeolian, and glacial systems), and small vertical-scale surface kinetics (in crystal growth, rock/mineral weathering, and pedogenesis), where driven forces, previous modeling approaches, and the details of anomalous dynamics are analyzed. Results show that the solid Earth can provide an ideal and diverse base for the application of fractional calculus and fPDEs. Complex dynamics within and across spatiotemporal scales, multi-scale intrinsic heterogeneity, and intertwined controlling factors for dynamic processes in the solid Earth can motivate the application of fPDEs. Challenges for the future application of fPDEs in Earth systems are also discussed, including poor parameter predictability, the lack of mathematical specification of bounded fractional diffusion, lack of intermediate-scale geologic information in parsimonious and upscaling models, and a lack of models for multi-phase and coupled processes. Substantial extension of fPDE models is needed for the development of next-generation, solid Earth dynamic models, where potential solutions are discussed based on our experience gained in the development and application of fractional calculus and fPDEs over the last decade. Therefore, the current bottleneck in the application of fractional calculus in hydrologic sciences should not be the end of a promising stochastic approach, but could be the early stage of a decade-long effort filled with multiple new research and application directions in geology. This conclusion may shed light on the bottleneck challenging stochastic hydrogeology, where the advanced stochastic models (with more than 3500 journal publications in the last three decades) have not significantly impacted the practice of groundwater flow and transport modeling.
We compared bona fide human induced pluripotent stem cells (iPSCs) derived from umbilical cord blood (CB) cells and neonatal keratinocytes (K). As a consequence of both incomplete erasure of ...tissue-specific methylation and aberrant de novo methylation, CB-iPSCs and K-iPSCs were distinct in genome-wide DNA methylation profiles and differentiation potential. Extended passage of some iPSC clones in culture did not improve their epigenetic resemblance to embryonic stem cells, implying that some human iPSCs retain a residual 'epigenetic memory' of their tissue of origin.
Abstract Background: Oxidative and cytotoxic damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Curcumin is proved to elicit a vanity of ...biological effects through its antioxidant and anti-inflammatory properties. But the mechanisms underlying are poorly understood. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates expression of genes required for free radical scavenging, detoxification of xenobiotics, and maintenance of redox potential. This study evaluated the time course expression regularity of Nrf2, HO-1 and the curcumin's role in cerebral ischemia and its potential mechanism. Methods: Male, Sprague–Dawley rats were subjected to permanent focal cerebral ischemia by right MCA occlusion. Experiment 1 was used to evaluate the expression of Nrf2 and HO-1 in the cerebral ischemia, 6 time points was included. Experiment 2 was used to detect curcumin's neuroprotection in cerebral ischemia. At 24 h neurological deficit was evaluated using a modified six point scale; brain water content was measured; infarct size was analysed with 2, 3, 5-triphenyltetrazolium chloride (TTC). Immunohistochemistry, RT-PCR, Western blot, and confocal microscope were used to analyse the expression of Nrf2 and HO-1. Results: Compared with sham-operated, Nrf2 and HO-1 were upregulated at gene and protein level in ischemic brain, beginning at 3 h and peaking at 24 h after MCAO ( P < 0.05). Curcumin high dose (100 mg/kg) upregulated Nrf2 and HO-1 in MCAO-affected brain tissue and reduced infarct volume ( P < 0.05), brain water content ( P < 0.05) and behavioral deficits ( P < 0.05) caused by MCAO. Conclusions: Nrf2 and HO-1 were induced at the early stage after MCAO. Curcumin protected the brain from damage caused by MCAO, this effect may be through upregulation of the transcription factor Nrf2 expression. Nrf2 may be one of the strategic targets for cerebral ischemic therapies.
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