Application of 3D Hepatic Plate-Like Liver Model for Statin-Induced Hepatotoxicity Evaluation.

Drug-induced liver injury is one of the main reasons of withdrawals of drugs in postmarketing stages. However, an experimental model(s) which can accurately recapitulates liver functions and reflects the level of drug hepatotoxicity is lack. In this study, we assessed drug hepatotoxicity using a novel three-dimensional hepatic plate-like hydrogel fiber (3D-P) co-culture system.

Therapeutic Potential of CUDC-907 (Fimepinostat) for Hepatocarcinoma Treatment Revealed by Tumor Spheroids-Based Drug Screening.

Cancer is the second leading cause of death globally. However, most of the new anti-cancer agents screened by traditional drug screening methods fail in the clinic because of lack of efficacy. Choosing an appropriate tumor model is crucial for preclinical drug screening.

New Anti-Cancer Strategy to Suppress Colorectal Cancer Growth Through Inhibition of ATG4B and Lysosome Function.

Autophagy inhibition has been proposed to be a potential therapeutic strategy for cancer, however, few autophagy inhibitors have been developed. Recent studies have indicated that lysosome and autophagy related 4B cysteine peptidase (ATG4B) are two promising targets in autophagy for cancer therapy. Although some inhibitors of either lysosome or ATG4B were reported, there are limitations in the use of these single target compounds.

3D Culture System for Liver Tissue Mimicking Hepatic Plates for Improvement of Human Hepatocyte (C3A) Function and Polarity.

3D hepatocyte culture constitutes a core aspect of liver tissue engineering. However, conventional 3D cultures are unable to maintain hepatocyte polarity, functional phenotype, or viability. Here, we employed microfluidic chip technology combined with natural alginate hydrogels to construct 3D liver tissues mimicking hepatic plates.

Efficient synthesis of cyclic amidine-based fluorophores 6π-electrocyclic ring closure.

Novel 10π-electron cyclic amidines with excellent fluorescence properties were synthesized by a general and efficient 6π-electrocyclic ring closure of ketenimine and imine starting from -sulfonyl triazoles and arylamines. The photophysical properties of cyclic amidine fluorophores have been studied in detail and have shown good properties of a large Stokes shift, pH insensitivity, low cytotoxicity and higher photostability, which have great potential for biological imaging. Furthermore, this novel fluorophore was successfully applied to the localization of the NK-1 receptor in living systems.

High-throughput three-dimensional spheroid tumor model using a novel stamp-like tool.

Spheroid culture is a widely used three-dimensional culture technology that simulates the three-dimensional structure of tumors in vivo and has been considered a good model for tumor research. However, current commercialized spheroid culture tools have the shortcomings of high cost or relatively poor spheroid-forming results for some special cells. To solve such problems, we designed a 3D printed, reusable, stamp-like resin mold that could shape microstructures for spheroid culture of tumor cells on the surface of agarose substrate in a 96-well plate.

Switchable Skeletal Rearrangement of Dihydroisobenzofuran Acetals with Indoles.

The switchable skeletal rearrangement for the construction of amino indanones and tetrahydroisoquinolones frameworks had been developed. In the presence of a chiral phosphoric acid catalyst, the reaction gave the amino indanones in high yields and good to excellent ee (85-98%), while the methoxyl substituent at the 5-position of dihydroisobenzofuran acetal selectively gave isoquinolinones products in good to excellent ee (46-98%). Furthermore, DFT calculations were performed to explain the regioselectivity of the switchable transformation pathways.

Discovery of a small molecule targeting autophagy via ATG4B inhibition and cell death of colorectal cancer cells in vitro and in vivo.

Human Atg4 homologs are cysteine proteases, which play key roles in the macroautophagy/autophagy process by cleaving Atg8 homologs for conjugation to lipid membranes and for deconjugation of Atg8 homologs from membranes. Expression of ATG4B is significantly increased in colorectal cancer cells compared to normal cells, suggesting that ATG4B may be important for cancer biology. Inhibition of ATG4B may reduce the autophagy activity, thereby sensitizing cancer cells to therapeutic agents.

ATG4B inhibitor FMK-9a induces autophagy independent on its enzyme inhibition.

Atg4 is essential for autophagosome formation and Atg8 recycle with the function of processing the precursor and the lipidated Atg8-family proteins. Abnormal autophagic activity is involved in a variety of pathophysiological diseases and ATG4B is of interest as a potential therapeutic target due to its key roles in autophagy process. So ATG4B inhibitors are highly needed.