Shuai Deng

1. Diabetic foot ulcer (DFU) is one of the most common and severe chronic complications of diabetes and is a major contributor to the increased risks of amputation, disability, and mortality in aff...

A bilayer hydrogel, combining a GelMA-ALG-nZnO protective film and a COL1-PRP regenerative hydrogel, offers protection against bacterial infection and promotes wound healing function, addressing the complexities of diabetic foot treatment.

Efficient and mild synthetic routes for bioactive natural product derivatives are of current interest for drug discovery. Herein, on the basis of the pharmacophore hybrid strategy, we report a two-step protocol to obtain a series of structurally novel oleanolic acid (OA)-dithiocarbamate conjugates in mild conditions with high yields. Moreover, biological evaluations indicated that representative compound 3e exhibited the most potent and broad-spectrum antiproliferative effects against Panc1, A549, Hep3B, Huh-7, HT-29, and Hela cells with low cytotoxicity on normal cells. In terms of the IC₅₀ values, these OA-dithiocarbamate conjugates were up to 30-fold more potent than the natural product OA. These compounds may be promising hit compounds for the development of novel anti-cancer drugs.

Zinc oxide nanoparticles (Nano-ZnO) have been widely used in the food, cosmetics, and biomedical fields due to their excellent antibacterial and antioxidant properties. However, with the widespread application of Nano-ZnO, Nano-ZnO inevitably enters the environment and living organisms, causing harm to human health and ecosystem safety. Therefore, the biosafety and toxicological issues of Nano-ZnO are gradually being emphasized. Our study found that Nano-ZnO has superior antibacterial properties compared to ofloxacin in the fight against Staphylococcus aureus (S. aureus). Given that ofloxacin can inhibit bacterial-induced inflammation, we constructed a model of bacterial inflammation using S. aureus in zebrafish. We found that Nano-ZnO inhibited the NF-κB-mediated inflammatory signaling pathway. However, in the process, we found that Nano-ZnO caused hepatic steatosis in zebrafish. This suggested that Nano-ZnO had a certain hepatotoxicity, but did not affect liver development. Subsequently, we investigated the mechanism of hepatotoxicity produced by Nano-ZnO. Nano-ZnO triggered oxidative stress in the liver by generating ROS, which then induced endoplasmic reticulum stress to occur. It further activated srebp and its downstream genes fasn and acc1, which promoted the accumulation of fatty acid synthesis and the development of steatosis, leading to the development of nonalcoholic fatty liver disease (NAFLD). To address the hepatotoxicity of Nano-ZnO, we added carbon dots for the treatment of NAFLD. The carbon dots were found to normalize the steatotic liver. This provided a new strategy to address the hepatotoxicity caused by Nano-ZnO. In this work, we systematically analyzed the antibacterial advantages of Nano-ZnO in vivo and in vitro, explored the mechanism of Nano-ZnO hepatotoxicity, and proposed a new method to treat Nano-ZnO hepatotoxicity.

Three-dimensional (3D) culture techniques, such as spheroid and organoid cultures, have gained increasing interest in biomedical research. However, the understanding and control of extracellular matrix (ECM) effect in spheroid and organoid culture has been limited. Here, we report a biofabrication approach to efficiently form uniform-sized 3D hepatocyte spheroids and encapsulate them in a hybrid hydrogel composed of alginate and various ECM molecules. Cells were seeded in a microwell platform to form spheroid before being encapsulated directly in a hybrid hydrogel containing various ECM molecules, including collagen type I (COL1), collagen type IV (COL4), fibronectin (FN), and laminin (LM). A systematic analysis of the effect of ECM molecules on the primary mouse hepatocyte phenotype was then performed. Our results showed that hydrogel encapsulation of hepatocyte spheroid promoted hepatic marker expression and secretory functions. In addition, different ECM molecules elicited distinct effects on hepatic functions in 3D encapsulated hepatocyte spheroids, but not in 2D hepatocyte and 3D non-encapsulated spheroids. When encapsulated in hybrid hydrogel containing LM alone or COL1 alone, hepatocyte spheroids exhibited improved hepatic functions overall. Analysis of gene and protein expression showed an upregulation of integrin α 1 and integrin α 6 when LM was introduced in the hybrid hydrogel, suggesting a possible role of integrin signaling involved in the ECM effect. Finally, a combinatorial screening was performed to demonstrate the potential to screen a multitude of 3D microenvironments of varying ECM combinations that exhibited synergistic influence, indicating a strong positive effect of COL1 and a negative interaction effect of COL1·LM on both albumin and urea secretion. These findings illustrate the broad application potential of this biofabrication approach in identifying optimal ECM composition(s) for engineering 3D tissue, and elucidating defined ECM cues for tissue engineering and regenerative medicine.