University of Macau

About: University of Macau is a education organization based out in Macao, Macau, China. It is known for research contribution in the topics: Population & Control theory. The organization has 6636 authors who have published 18324 publications receiving 327384 citations. The organization is also known as: UM & UMAC.

Identification of a natural product-like STAT3 dimerization inhibitor by structure-based virtual screening.

Abstract: STAT3 regulates a variety of genes involved with cell proliferation, differentiation, apoptosis, angiogenesis, metastasis, inflammation, and immunity. The purpose of this study was to apply molecular docking techniques to identify STAT3 inhibitors from a database of over 90 000 natural product and natural product-like compounds. The virtual screening campaign furnished 14 hit compounds, from which compound 1 emerged as a top candidate. Compound 1 inhibited STAT3 DNA-binding activity in vitro and attenuated STAT3-directed transcription in cellulo with selectivity over STAT1 and with comparable potency to the well-known STAT3 inhibitor S3I-201. Furthermore, compound 1 inhibited STAT3 dimerization and decreased STAT3 phosphorylation in cells without affecting STAT1 dimerization and phosphorylation. Compound 1 also exhibited selective anti-proliferative activity against cancer cells over normal cells in vitro. Molecular docking analysis suggested that compound 1 might putatively function as an inhibitor of STAT3 dimerization by binding to the SH2 domain. This study also validates the use of in silico techniques to identify inhibitors of protein–protein interactions, which are typically considered difficult to target with small molecules.

Development of an Iridium(III) Complex as a G-Quadruplex Probe and Its Application for the G-Quadruplex-Based Luminescent Detection of Picomolar Insulin

Abstract: In this study, an unreported Ir(III) complex 1 was identified by screening as a versatile G-quadruplex probe. It exhibited highly selective response for different G-quadruplex DNA over double strand, single strand and triplex DNA. Compared with the organic G-quadruplex probe thioflavin T, complex 1 displays a longer lifetime, a larger Stokes shift, comparable G-quadruplex/ssDNA enhancement ratios, and higher G-quadruplex/triplex DNA enhancement ratios. In consideration of the encouraging G-quadruplex probe performance of complex 1, we employed 1 to develop a G-quadruplex-based detection system for the detection of insulin as a “proof-of-principle” concept. We also demonstrate an optimization process that enhanced the sensitivity of this sensing assay. Compared to previously reported methods, our “mix-and-detect” detection methodology is easy operated, quick, and cost-effective. A detection limit as low as 80 pM for insulin can be achieved by this sensing approach, with a linear relationship between lumine...

A Proresolving Peptide Nanotherapy for Site-Specific Treatment of Inflammatory Bowel Disease by Regulating Proinflammatory Microenvironment and Gut Microbiota.

Abstract: The incidence and prevalence of inflammatory bowel disease (IBD) increases steadily worldwide. There is an urgent need for effective and safe IBD therapies. Accelerated resolution of inflammation is a new strategy for the management of inflammatory diseases. For effective and safe IBD treatment, herein a smart nanotherapy (i.e. oxidation-responsive nanoparticles containing a proresolving annexin A1-mimetic peptide Ac2-26, defined as AON) is developed, which can release packaged Ac2-26, in response to highly expressed reactive oxygen species (ROS) at diseased sites. AON effectively protects Ac2-26 from degradation in the enzyme-rich environment of the gastrointestinal tract. By delivering this nanotherapy to the inflamed colons of mice with IBD, site-specific release and accumulation of Ac2-26 in response to high levels of ROS at the inflammatory sites are achieved. Mechanistically, the Ac2-26-containing, oxidation-labile nanotherapy AON effectively decreases the expression of proinflammatory mediators, attenuates trafficking and infiltration of inflammatory cells, promotes efferocytosis of apoptotic neutrophils, and increases phenotypic switching of macrophages. Therapeutically, AON reduces symptoms of inflammation, accelerates intestinal mucosal wound healing, reshapes the gut microbiota composition, and increases short-chain fatty acid production. Additionally, oral delivery of this nanomedicine shows excellent safety profile in a mouse model, conferring the confidence for further development of a targeted precision therapy for IBD and other inflammatory diseases.