Radiopaque, Self-Immolative Poly(benzyl ether) as a Functional X-ray Contrast Agent: Synthesis, Prolonged Visibility, and Controlled Degradation.

A self-immolative radiocontrast polymer agent has been newly designed for this study. The polymer agent is composed of a degradable poly(benzyl ether)-based backbone that enables complete and spontaneous depolymerization upon exposure to a specific stimulus, with iodophenyl pendant groups that confer a radiodensity comparable to that of commercial agents. In particular, when incorporated into a biodegradable polycaprolactone matrix, the agent not only reinforces the matrix and provides prolonged radiopacity without leaching but also governs the overall degradation kinetics of the composite under basic aqueous conditions, allowing for X-ray tracking and exhibiting a predictable degradation until the end of its lifespan. Our design would be advanced with various other components to produce synergistic functions and extended for applications in implantable biodegradable devices and theragnostic systems.

Cytoprotective and anti-inflammatory effects of melatonin in hydrogen peroxide-stimulated CHON-001 human chondrocyte cell line and rabbit model of osteoarthritis via the SIRT1 pathway.

Melatonin has potent antioxidant, analgesic, and antinociceptive properties. However, the effects of melatonin against oxidative stress-induced cytotoxicity and inflammatory mediators in human chondrocytes remain poorly understood. This study examined the effects and underlying mechanism of melatonin in hydrogen peroxide (H(2) O(2) )-stimulated human chondrocytes and rabbit osteoarthritis (OA) model. Melatonin markedly inhibited hydrogen peroxide (H(2) O(2) )-stimulated cytotoxicity, iNOS, and COX-2 protein and mRNA expression, as well as the downstream products, NO and PGE(2) . Incubation of cells with melatonin decreased H(2) O(2) -induced Sirtuin 1 (SIRT1) mRNA and protein expression. SIRT1 inhibition by sirtinol or Sirt1 siRNA reversed the effects of melatonin on H(2) O(2) -mediated induction of pro-inflammatory cytokines (NO, PGE(2) , TNF-α, IL-1ß, and IL-8) and the expression of iNOS, COX-2, and cartilage destruction molecules. Melatonin blocked H(2) O(2) -induced phosphorylation of PI3K/Akt, p38, ERK, JNK, and MAPK, as well as activation of NF-κB, which was reversed by sirtinol and SIRT1 siRNA. In rabbit with OA, intra-articular injection of melatonin significantly reduced cartilage degradation, which was reversed by sirtinol. Taken together, this study shows that melatonin exerts cytoprotective and anti-inflammatory effects in an oxidative stress-stimulated chondrocyte model and rabbit OA model, and that the SIRT1 pathway is strongly involved in this effect.

Mechanism of sappanchalcone-induced growth inhibition and apoptosis in human oral cancer cells.

Sappanchalcone, a flavonoid extracted from Caesalpinia sappan, exhibits cytoprotective activity, but the molecular basis for the anticancer effect of sappanchalcone has not been reported. In this study, we examined whether sappanchalcone could inhibit the growth of human primary and metastatic oral cancer cells, and we analyzed the signaling pathway underlying the apoptotic effects of the compound in this process using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assays, fluorescence microscopy, flow cytometry, and Western blotting. Sappanchalcone-treated oral cancer cells showed an increased cytosolic level of cytochrome c, downregulated Bcl-2 expression, upregulated Bax and p53 expression, caspase-3 and -9 activation, and poly (ADP-ribose) polymerase cleavage. Furthermore, sappanchalcone induced activation of p38, extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), and Nuclear factor k B (NF-κB), as demonstrated by the phosphorylation of each mitogen-activated protein kinases (MAPKs), the degradation of inhibitor of NF-κα (IκB-α), increased expression of nuclear p65, and NF-κB-DNA binding. Inhibition of the expression of p38, ERK, JNK, and NF-κB by pharmacological inhibitors reversed sappanchalcone-induced growth inhibition and apoptosis. These results provide the first evidence that sappanchalcone suppresses oral cancer cell growth and induces apoptosis through the activation of p53-dependent mitochondrial, p38, ERK, JNK, and NF-κB signaling. Thus, it has potential as a chemotherapeutic agent for oral cancer.