Co-transfection with and via chitosan nanoparticles potentiates osteogenesis in human adipose-derived stromal cells .

Objective: To investigate if co-transfection of human bone morphogenetic protein 2 (BMP-2, ) and human fibroblast growth factor 2 (FGF2, ) via chitosan nanoparticles promotes osteogenesis in human adipose tissue-derived stem cells (ADSCs) .

Materials And Methods: Recombinant and/or expression vectors were constructed and packaged into chitosan nanoparticles. The chitosan nanoparticles were characterized by atomic force microscopy.

Physicochemical-property guided design of a highly sensitive probe to image nitrosative stress in the pathology of stroke.

real-time imaging of nitrosative stress in the pathology of stroke has long been a formidable challenge due to both the presence of the blood-brain barrier (BBB) and the elusive nature of reactive nitrogen species, while this task is also informative to gain a molecular level understanding of neurovascular injury caused by nitrosative stress during the stroke episode. Herein, using a physicochemical property-guided probe design strategy in combination with the reaction-based probe design rationale, we have developed an ultrasensitive probe for imaging nitrosative stress evolved in the pathology of stroke. This probe demonstrates an almost zero background fluorescence signal but a maximum 1000-fold fluorescence enhancement in response to peroxynitrite, the nitrosative stress marker.

Conformational restraint as a strategy for navigating towards lysosomes.

Using the conformational restraint strategy, we developed a hydrazonate-derived coumarin into a lysosome targeting probe for imaging native formaldehyde at the subcellular level. Using this probe, we observed the overproduction of formaldehyde in lysosomes when cells were treated with endoplasmic reticulum (ER) stress inducers, suggesting the involvement of formaldehyde in protein misfolding.

Myt1l induced direct reprogramming of pericytes into cholinergic neurons.

Objective: The cholinergic deficit is thought to underlie progressed cognitive decline in Alzheimer Disease. The lineage reprogramming of somatic cells into cholinergic neurons may provide strategies toward cell-based therapy of neurodegenerative diseases.

Methods And Results: Here, we found that a combination of neuronal transcription factors, including Ascl1, Myt1l, Brn2, Tlx3, and miR124 (5Fs) were capable of directly converting human brain vascular pericytes (HBVPs) into cholinergic neuronal cells.

A HO-Responsive Theranostic Probe for Endothelial Injury Imaging and Protection.

Overproduction of HO causes oxidative stress and is the hallmark of vascular diseases. Tracking native HO in the endothelium is therefore indispensable to gain fundamental insights into this pathogenesis. Previous fluorescent probes for HO imaging were generally arylboronates which were decomposed to emissive arylphenols in response to HO.

A Fluorogenic Probe for Ultrafast and Reversible Detection of Formaldehyde in Neurovascular Tissues.

Formaldehyde (FA) is endogenously produced in live systems and has been implicated in a diverse array of pathophysiological processes. To disentangle the detailed molecular mechanisms of FA biology, a reliable method for monitoring FA changes in live cells would be indispensable. Although there have been several fluorescent probes reported to detect FA, most are limited by the slow detection kinetics and the intrinsic disadvantage of detecting FA in an irreversible manner which may disturb endogenous FA homeostasis.

Stress-responsive heme oxygenase-1 isoenzyme participates in Toll-like receptor 4-induced inflammation during brain ischemia.

Toll-like receptors (TLRs) are involved in the progression of ischemic brain injury and hence vascular dementia; however, the underlying mechanisms are largely unknown. Here, we have investigated the interrelationship between stress-responsive heme oxygenase (HO)-1 isoenzyme and TLR4 during chronic brain hypoperfusion. The right unilateral common carotid artery occlusion was performed by ligation of the right common carotid artery in C57BL/6J mice.

Epirubicin-loaded superparamagnetic iron-oxide nanoparticles for transdermal delivery: cancer therapy by circumventing the skin barrier.

The transdermal administration of chemotherapeutic agents is a persistent challenge for tumor treatments. A model anticancer agent, epirubicin (EPI), is attached to functionalized superparamagnetic iron-oxide nanoparticles (SPION). The covalent modification of the SPION results in EPI-SPION, a potential drug delivery vector that uses magnetism for the targeted transdermal chemotherapy of skin tumors.

[Establishment of optimized neuronal differentiation-promoting model derived from P19 embryonic carcinoma cells].

Objective: To establish an optimized primary drug screen model of neuronal differentiation using P19 embryonal carcinoma cells.

Methods: The final concentration of retinoid acid (RA), days of suspension culture, manner of adherent culture, suitable cell density and adherent culture medium were tested, respectively. Two stages of neuronal differentiation were examined based on morphological changes and immunocytochemistry analysis of neuronal specific protein β-tubulin III.

[Expression of Junctophilin 1 during cardiogenesis of mouse embryonic stem cells and rat embryos].

Objective: To investigate the expression of Junctophilin 1 (JP1) in cardiogenesis of mammalian.

Methods: Cardiac differentiation of embryonic stem cells (ESCs) was generated by hanging drop method. Fetal heart was obtained from the rats aged d 14-20 of gestation.

Embryonic stem cell application in drug discovery.

Embryonic stem (ES) cells and their differentiated progeny offer tremendous potential for regenerative medicine, even in the field of drug discovery. There is an urgent need for clinically relevant assays that make use of ES cells because of their rich biological utility. Attention has been focused on small molecules that allow the precise manipulation of cells in vitro, which could allow researchers to obtain homogeneous cell types for cell-based therapies and discover drugs for stimulating the regeneration of endogenous cells.

Involvement of p38MAPK and reactive oxygen species in icariin-induced cardiomyocyte differentiation of murine embryonic stem cells in vitro.

We previously reported that treatment of icariin could significantly induce cardiomyocyte differentiation of murine embryonic stem (ES) cells in vitro. In the present study, the exact activity initiated by icariin was further confirmed and the underlying molecular mechanism was investigated. We found that cardiomyocyte differentiation was efficiently stimulated only if icariin was administrated between days 5 and 8 in differentiation course, which indicated with elevated percentage of embryoid bodies (EB) and with beating areas and up- regulated expression of alpha-actinin and troponin T.

Icariin promotes expression of PGC-1alpha, PPARalpha, and NRF-1 during cardiomyocyte differentiation of murine embryonic stem cells in vitro.

Aim: To investigate the effect of icariin on the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1alpha), peroxisome proliferator-activated receptor alpha (PPARalpha), and nuclear respiratory factor 1 (NRF-1) on cardiomyocyte differentiation of murine embryonic stem (ES) cells in vitro.

Methods: The cardiomyocytes derived from murine ES cells were verified by immunocytochemistry using confocal laser scanning microscopy. Cardiac-specific sarcomeric proteins (ie alpha-actinin, troponin T) were evaluated when embryoid bodies (EB) were treated with icariin or retinoid acid.

Time-dependence of cardiomyocyte differentiation disturbed by peroxisome proliferator-activated receptor alpha inhibitor GW6471 in murine embryonic stem cells in vitro.

Aim: To investigate the possible roles of peroxisome proliferator-activated receptor alpha(PPAR alpha) and the signal pathway regulating the transcription of PPAR alpha in the cardiomyocyte differentiation course of murine embryonic stem (ES) cells in vitro.

Methods: The expression of PPAR alpha during cardiomyocyte differentiation was analyzed using both Western blotting and immunofluorescence. Cardiac specific genes and sarcomeric proteins were evaluated when embryoid bodies were challenged with PPAR alpha specific inhibitor GW6471 at different time courses.