Modification of chitosan nanofibers with CuS and fucoidan for antibacterial and bone tissue engineering applications.

Chitosan (CS) electrospun nanofiber (ENF) membranes were modified with fucoidan (Fu) and CuS NPs through polyelectrolyte complexation and genipin (GP)-involved cross-linking reaction. The formation of Fu/CS complex and cross-linking of CS with GP increased the acid resistance and reduced the swelling rate of CS ENF, while the covalent conjugation of CuS NPs provided CS ENF with durable Fenton-like catalytic activity. The CuS@ENF composite (ENFC) effectively adsorbed H2O2 and near-infrared (NIR) light, enabling it to kill bacteria by photothermal and photocatalytic bactericidal effects. Fu and copper ions were able to release from the ENFC in a pH-dependent manner, and promoted the alkaline phosphatase activity of osteoblast cells and capillary tube formation of endothelial cells. This study provides a new approach to modify CS ENF with antibacterial and osteoblast differentiation activities, which may be available for bone infection prevention and tissue regeneration.

Signal transducer and activator of transcription 3 mediates apoptosis inhibition through reducing mitochondrial ROS and activating Bcl-2 in gemcitabine-resistant lung cancer A549 cells.

Lung cancer is a leading cause of cancer-related death worldwide. In this study, we used lung adenocarcinoma cells as a model, as lung adenocarcinoma has the highest mortality rate among all lung cancers. For the past few years, medical treatments or lung cancer have been limited because of chemotherapy resistance. Therefore, understanding the pathogenesis of the development of drug resistance in lung cancer is urgent. Gemcitabine is widely prescribed in the chemotherapeutic treatment of lung cancers. In this study, we developed gemcitabine-resistant lung adenocarcinoma cells (A549-GR) from the A549 cell line. The results showed that apoptotic protein expression and reactive oxygen species (ROS) generation were reduced in A549-GR cells compared to A549 cells. Interestingly, we found that signal transducer and activator of transcription 3 (STAT3) translocated to the nucleus and mitochondria to affect the apoptotic pathway and ROS generation, respectively. Furthermore, treatment with STAT3 small interfering RNA diminished the increase in ROS production, proliferation and antiapoptotic proteins in A549-GR cells. Taken together, the study demonstrated that STAT3 acts as an essential regulator and moderates apoptosis through two major mechanisms to induce gemcitabine resistance in cells; and these findings provide a potential target for the treatment of gemcitabine-resistant lung cancer.

Plumbagin inhibits TPA-induced MMP-2 and u-PA expressions by reducing binding activities of NF-kappaB and AP-1 via ERK signaling pathway in A549 human lung cancer cells.

This study first investigates the anti-metastatic effect of plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMPs and u-PA expressions in human lung cancer cells, A549. First, the result demonstrated plumbagin could inhibit TPA induced the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and Boyden chamber assay. Data also showed plumbagin could inhibit the activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) involved in the down-regulating enzyme activities, protein and messenger RNA levels of matrix metalloproteinase-2 (MMP-2), and urokinase-type plasminogen activator (u-PA) induced by TPA. Next, plumbagin also strongly inhibited TPA-induced phosphorylation and degradation of inhibitor of kappaBalpha (IkappaBalpha), and the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, a dose-dependent inhibition on the binding abilities of NF-kappaB and activator protein-1 (AP-1) by plumbagin treatment was further observed. Further, the treatment of specific inhibitor for ERK (U0126) to A549 cells could inhibit TPA-induced MMP-2 and u-PA expressions along with an inhibition on cell invasion and migration. Presented data reveals that plumbagin is a novel, effective, anti-metastatic agent that functions by down-regulating MMP-2 and u-PA gene expressions.