Exosomes derived from mesenchymal stem cells in diabetes and diabetic complications.

Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.

SNS-032 attenuates liver fibrosis by anti-active hepatic stellate cells via inhibition of cyclin dependent kinase 9.

Liver fibrosis is a common pathological process of all chronic liver diseases. Hepatic stellate cells (HSCs) play a central role in the development of liver fibrosis. Cyclin-dependent kinase 9 (CDK9) is a cell cycle kinase that regulates mRNA transcription and elongation. A CDK9 inhibitor SNS-032 has been reported to have good effects in anti-tumor. However, the role of SNS-032 in the development of liver fibrosis is unclear. In this study, SNS-032 was found to alleviate hepatic fibrosis by inhibiting the activation and inducing the apoptosis of active HSCs in carbon tetrachloride-induced model mice. In vitro, SNS-032 inhibited the activation and proliferation of active HSCs and induced the apoptosis of active HSCs by downregulating the expression of CDK9 and its downstream signal transductors, such phosphorylated RNA polymerase II and Bcl-2. CDK9 short hairpin RNA was transfected into active HSCs to further elucidate the mechanism of the above effects. Similar results were observed in active HSCs after CDK9 knockdown. In active HSCs with CDK9 knockdown, the expression levels of CDK9, phosphorylated RNA polymerase II, XIAP, Bcl-2, Mcl-1, and ɑ-SMA significantly decreased, whereas those of cleaved-PARP1 and Bax decreased prominently. These results indicated that SNS-032 is a potential drug and CDK9 might be a new prospective target for the treatment of liver fibrosis.

An NIR-light-responsive surface molecularly imprinted polymer for photoregulated drug release in aqueous solution through porcine tissue.

The application of photoresponsive surface molecularly imprinted polymers based on azobenzene is limited by the UV light source required and their poor water solubility. Reducing the phototoxicity and solvent toxicity of the polymers therefore presents a challenge. In this work, an NIR-light-responsive surface molecularly imprinted polymer was fabricated by atom transfer radical polymerization using up-conversion nanoparticles as the core, a hydrophilic green-light-responsive azobenzene derivative as the functional monomer, and a drug as the template. The up-conversion nanoparticles core emitted green fluorescence in the range of 520-550 nm upon NIR irradiation (980 nm, 5 W cm-2), which was absorbed by the azobenzene containing molecularly imprinted polymers layer on the up-conversion nanoparticles surface. This caused the azobenzene chromophores to undergo trans→cis isomerization in phosphate buffered solution (pH = 7.4), thus resulting in NIR-light-induced drug release. The up-conversion fluorescence spectra were used to study the interaction mechanism between the azobenzene monomer and NIR light. Compared with structural analogues of the template (antifebrin and phenacetin), the NIR-light-responsive surface molecularly imprinted polymer showed excellent specificity of recognition for the template drug (paracetamol). The maximum adsorption capacity of the NIR-light-responsive surface molecularly imprinted polymer for loading of paracetamol was 16.80 µmol g-1. The NIR-light-responsive surface molecularly imprinted polymer was applied for NIR-light-induced paracetamol release in phosphate buffered solution (pH = 7.4) through porcine tissue. This work demonstrates the potential of drug delivery systems based on molecularly imprinted polymers for application in deep tissue delivery.