Minsheng Chen

In situ enzymatic formation of supramolecular nanofibers for efficiently killing cancer cells

We report a strategy of in situ forming supramolecular nanofibers of taxol-phosphorylated peptide conjugates catalyzed by phosphatase for efficiently killing cancer cells.

Resveratrol ameliorates cardiac dysfunction by inhibiting apoptosis via the PI3K/Akt/FoxO3a pathway in a rat model of diabetic cardiomyopathy.

Abstract: The aim of this study was to explore the effect and mechanism of action of resveratrol (RSV) on cardiac function in diabetic cardiomyopathy (DCM). Hyperglycemia-induced apoptosis contributes to the pathogenic changes in DCM. RSV treatment inhibited high glucose–induced apoptosis of neonatal rat ventricular myocytes. Additionally, high glucose decreased cell viability, prevented serine–threonine kinase (Akt) and FoxO3a phosphorylation, and suppressed cytoplasmic translocation of FoxO3a. However, these effects of apoptosis were reversed by 10 &mgr;M of RSV. The PI3K inhibitor LY294002 abolished the RSV protective effect in vitro. RSV (5 or 50 mg·kg−1·d−1 orally for 8 weeks) prevented the deterioration of cardiac function and structural cardiomyopathy in a streptozotocin-induced rat model of diabetes and reduced apoptosis in diabetic myocardium. Furthermore, it restored streptozotocin-impaired phosphorylation of Akt and FoxO3a (p-Akt and p-FoxO3a) and suppressed nuclear translocation of FoxO3a in vivo. Together, these data indicate that RSV has therapeutic potential against DCM by inhibiting apoptosis via the PI3K/Akt/FoxO3a pathway.

A Promising Therapeutic Target for Metabolic Diseases: Neuropeptide Y Receptors in Humans

Human neuropeptide Y (hNPY) is one of the most widely expressed neurotransmitters in the human central and peripheral nervous systems. It consists of 36 highly conserved amino acid residues, and was first isolated from the porcine hypothalamus in 1982. While it is the most recently discovered member of the pancreatic polypeptide family (which includes neuropeptide Y, gut-derived hormone peptide YY, and pancreatic polypeptide), NPY is the most abundant peptide found in the mammalian brain. In order to exert particular functions, NPY needs to bind to the NPY receptor to activate specific signaling pathways. NPY receptors belong to the class A or rhodopsin-like G-protein coupled receptor (GPCR) family and signal via cell-surface receptors. By binding to GPCRs, NPY plays a crucial role in various biological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. Abnormal regulation of NPY is involved in the development of a wide range of diseases, including obesity, hypertension, atherosclerosis, epilepsy, metabolic disorders, and many cancers. Thus far, five receptors have been cloned from mammals (Y1, Y2, Y4, Y5, and y6), but only four of these (hY1, hY2, hY4, and hY5) are functional in humans. In this review, we summarize the structural characteristics of human NPY receptors and their role in metabolic diseases.

D-amino acid doping peptide hydrogel for the production of a cell colony

We report on a rationally designed D-amino acid doping peptide that can form hydrogels under neutral conditions and can be applied to form a cell colony of HeLa cells.

A releasable disulfide carbonate linker for molecular hydrogelations

We used a releasable disulfide carbonate linker to construct precursors of gelators and form stable gels.

Treatment of Myocardial Infarction with Gene-modified Mesenchymal Stem Cells in a Small Molecular Hydrogel

The effect of transplanted rat mesenchymal stem cells (MSCs) can be reduced by extracellular microenvironment in myocardial infarction (MI). We tested a novel small-molecular hydrogel (SMH) on whether it could provide a scaffold for hepatocyte growth factor (HGF)-modified MSCs and alleviate ventricular remodeling while preserving cardiac function after MI. Overexpression of HGF in MSCs increased Bcl-2 and reduced Bax and caspase-3 levels in response to hypoxia in vitro. Immunocytochemistry demonstrated that cardiac troponin (cTnT), desmin and connexin 43 expression were significantly enhanced in the 5-azacytidine (5-aza) with SMH group compared with the 5-aza only group in vitro and in vivo. Bioluminescent imaging indicated that retention and survival of transplanted cells was highest when MSCs transfected with adenovirus (ad-HGF) were injected with SMH. Heart function and structure improvement were confirmed by echocardiography and histology in the Ad-HGF-SMHs-MSCs group compared to other groups. Our study showed that: HGF alleviated cell apoptosis and promoted MSC growth. SMHs improved stem cell adhesion, survival and myocardial cell differentiation after MSC transplantation. SMHs combined with modified MSCs significantly decreased the scar area and improved cardiac function.

Lentiviral vector-mediated co-overexpression of VEGF and Bcl-2 improves mesenchymal stem cell survival and enhances paracrine effects in vitro

Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy for ischemic heart disease; however, the low survival rate of transplanted cells limits their therapeutic efficacy. The aim of this study was to investigate whether the dual genetic modification of vascular endothelial growth factor (VEGF) and B-cell lymphoma-2 (Bcl-2) confers a higher expression level of the target genes, better survival and a stronger paracrine effect in MSCs in an adverse environment than the modification of the individual genes. For this purpse, a lentiviral vector was constructed by using a self-cleaving T2A peptide sequence to link and achieve the co-overexpression of VEGF and Bcl-2. Rat MSCs were transfected to obtain cell lines that exhibited a stable overexpression. An in vitro model of oxygen glucose deprivation (OGD) was applied to mimic the ischemic microenvironment, and cell apoptosis, autophagy and the paracrine effects were then determined. Compared with the MSCs in which individual genes were modified and the control MSCs, the MSCs which were subjected to dual genetic modification had a higher expression level of the target genes, a more rapid proliferation, reduced apoptosis, decreased autophagy and an enhanced paracrine effect. Furthermore, the suppression of autophagy was found to contribute to the inhibition of apoptosis in this in vitro OGD model. On the whole, these data indicate that the co-overexpression of VEGF and Bcl-2 protects MSCs in an ischemic environment by inhibiting apoptosis, suppressing autophagy and enhancing the paracrine effects.

Supramolecular nanofibers of self-assembling peptides and DDP to inhibit cancer cell growth

We report in this paper a molecular hydrogel formed by adding cis-dichlorodiamineplatinum(II) (DDP) to a self-assembling taxol-peptide amphiphile. Our study provides a novel self-assembling nanomedicine and hydrogel to deliver two anti-cancer drugs simultaneously.

Redox-controllable self-assembly and anti-bacterial activity of a vancomycin derivative

We report a selenium containing vancomycin derivative with redox-controllable self-assembly property and anti-bacterial activity.

Bifunctional Supramolecular Hydrogel Alleviates Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy and Apoptosis

Generally, nitric oxide (NO) is an important multi-functional cardioprotective soluble gas molecule. However, it may be detrimental when in excessive levels or combined with O2- a kind of reactive oxygen species (ROS)-to form ONOO-. The latter will rapidly decompose to highly reactive oxidant components. ROS will be abundantly produced during the ischemia/reperfusion (I/R) procedure. Therefore, an NO donor coupled with another antioxidant would be a more promising strategy for I/R treatment. In this study, we report on a novel self-assembly supramolecular hydrogel capable of constantly releasing both NO and curcumin (Cur) simultaneously, and we found that the combinational treatment of Cur and NO from the gel could efficiently reduce I/R injuries. The underlining mechanism revealed that the hydrogel could reduce the ROS level and thus inhibit the expression of the ROS-associated p38 MAPK/NF-κB signaling pathway. Moreover, the hydrogel also significantly suppressed over-stimulated autophagy and apoptosis during I/R treatment which was responsible for mediating severe post-ischemia myocardial cell death. The results indicated that our supramolecular hydrogel was a promising biomaterial for the treatment of myocardial I/R injuries.