Background: Deposition and accumulation of silver nanoparticles (Ag-nps) in the liver have been shown to induce hepatotoxicity in animal studies. The hepatotoxicity may include oxidative stress, abnormalities in energy metabolism, and cell death. Studies have indicated that autophagy is an intracellular event involving balance of energy, nutrients, and turnover of subcellular organelles. The present study was undertaken to test the hypothesis that autophagy plays a role in mediating hepatotoxicity in animal after exposure to Ag-nps. Focus was placed on interrelationship between energy metabolism, autophagy, apoptosis and hepatic dysfunction. Methods: Sprague Dawley rats were intraperitoneally injected with Ag-nps (10–30 nm in diameter) at concentration of 500 mg kg^-1. All animals were sacrificed on days 1, 4, 7, 10 and 30 after exposure and blood and liver tissues were collected for further studies. Results: Uptake of Ag-nps was quite prompt and not proportional to the blood Ag concentration. Declination of ATP (-64% in days 1) and autophagy (determined by LC3-II protein expression and morphological evaluation) increased and peaked on the first day. The ATP content remained at low level even though the autophagy has been activated. Apoptosis (based on caspase-3 protein expression and TUNEL-positive cells staining) began to rise sigmoidally at days 1 and 4, reached a peak level at day 7, and remained at the same levels during days 7–30 post exposure. Meanwhile, autophagy exhibited a gradual decrease from days 1–10 and the decrease at day 30 was statistically significant as compared to day 0 (sham group). Inflammatory reaction (histopathological evaluation) was found at day 10 and preceded to an advanced degree at day 30 when liver function was impaired. Conclusions: These results indicate that following Ag-nps administration, autophagy was induced; however, failure to preserve autophagy compounded with energy reduction led to apoptosis and the eventual impairment of liver function. The study provides an in-vivo evidence of hepatotoxicity by continuous exposure of Ag-nps in rats.

The etiological factors of oral cancer are complex including drinking alcohol, smoking tobacco, betel quid chewing, human papillomavirus infection, and nutritional deficiencies. Understanding the molecular mechanism of oral cancer is vital. The traditional treatment for patients with oral squamous cell carcinoma (e.g., surgery, radiotherapy, and chemotherapy) and targeted molecular therapy still have numerous shortcomings. In recent years, the use of phytochemical factors to prevent or treat cancer has received increasing attention. These phytochemicals have little or no toxicity against healthy tissues and are thus ideal chemopreventive agents. However, phytochemicals usually have low water solubility, low bioavailability, and insufficient targeting which limit therapeutic use. Numerous studies have investigated the development of phytochemical delivery systems to address these problems. The present article provides an overview of oral cancer including the etiological factors, diagnosis, and traditional therapy. Furthermore, the classification, dietary sources, anticancer bioactivity, delivery system improvements, and molecular mechanisms against oral cancer of phytochemicals are also discussed in this review.

Accumulation of oxidative proteins within mitochondria leads to loss of mitochondrial function, which may lead to age‐related degenerative diseases. Mitochondrial antioxidant defense capacity reflects the expression of mitochondrial unfolded protein response (mtUPR)‐related proteins. Senescent cells are considered to be less resistant to cellular stress stimuli than exponentially growing cells. In this study, we aimed to investigate the ability of mitochondrial stress response in senescent cells to cope with the accumulation of mitochondrial unfolded proteins induced by hydrogen peroxide (H₂O₂) and to understand the relevant molecular mechanisms. We report here that senescence‐associated β‐galactosidase (SA‐β‐gal) and senescence marker protein‐30 (SMP‐30), commonly used replicative senescence biomarkers, changed remarkably between population doubling (PD) 25 (exponentially growing cells) and PD50 (senescent cells) of MRC‐5 fibroblasts. Mitochondrial unfolded proteins were significantly accumulated in H₂O₂‐treated senescent cells, whereas mtUPR‐related molecular chaperones (heat shock protein Hsp60 and Hsp10) and proteases (caseinolytic Clp protease) were not concomitantly elevated in senescent cells. In addition, decreased expression of stromal interacting molecule 1‐Orai1‐mediated store‐operated Ca²⁺ entry following an declined intracellular calcium level after 2 mM calcium treatment together with H₂O₂ addition, implying impairment of calcium influx in senescent MRC‐5 during H₂O₂‐induced injury. These findings suggest that senescent fibroblasts expressed higher vulnerability to H₂O₂‐induced injury involving the imbalance of calcium homeostasis and impaired mitochondrial nuclear communication. This may provide useful information for the future development of therapeutic agents to prevent the adverse effects of aging on cells and the potential for treatment of proteinopathies in the elderly.