Alpha-fetoprotein/endoplasmic reticulum stress signaling mitigates injury in hepatoma cells.

Alpha-fetoprotein (AFP) and endoplasmic reticulum (ER) stress play multiple roles in hepatocellular carcinoma. Here, we analyzed the crosstalk between AFP and ER stress in human hepatoma cells. We induced ER stress in human hepatoma cell lines (HepG2 and SK-Hep1 cells) with thapsigargin (TG, an ER stress inducer), and mitigated ER stress with 4-phenylbutyrate acid (4-PBA, an ER stress inhibitor). AFP expression was knocked down by AFP short hairpin RNA and rescued by the pCI-AFP vector. AFP expression and ER stress were examined, and their roles in apoptosis, necroptosis, and proliferation were analyzed. TG significantly induced ER stress, apoptosis, necroptosis, and intracellular AFP protein levels, and reduced proliferation and AFP mRNA expression as well as supernatant AFP protein levels in HepG2 and SK-Hep1 cells. 4-PBA pretreatment partially reversed those changes in HepG2 cells. By contrast to AFP overexpression, knockdown of AFP significantly exacerbated TG-induced ER stress, apoptosis, and necroptosis, and decreased proliferation and the expression of activating transcription factor 6 alpha. In conclusion, ER stress causes the accumulation of AFP protein, which may be related to the reduction of AFP secretion. Accumulated AFP mitigates apoptosis and necroptosis and restores the proliferation of hepatoma cells by reducing ER stress.

Failure analysis: enamel fracture after debonding orthodontic brackets.

OBJECTIVE: To determine the location and size of enamel fracture (EF) when debonding a bracket. MATERIALS AND METHODS: Tests on actual EF situations were conducted in different debonding load modes (tension, shear, and torsion) via mechanical testing, finite element model (FEM) analysis, and scanning electronic microscopy (SEM). Through these simultaneous analyses of the relationships among debonding load modes, value/distribution of stress, and actual enamel fracture location/size, an investigation was undertaken to explore the complex failure mode during enamel fracture after debonding of an orthodontic bracket. RESULTS: The EF usually was located in the area where the force was exerted during various loading modes. The tensile, shear, and torsion debonding modes produce EF sizes and incidences with no significant differences. Findings on FEM matched the mechanical testing and SEM results. CONCLUSIONS: The EF locations coincided with the areas where the tensile, shear, or torsion force was exerted. Therefore, the dentist should give extra care and attention to these specific areas of enamel after debonding. The sizes and incidences of EF produced by these three debonding modes showed no significant difference. Thus, clinically, when the sizes and incidences of produced EF are considered, it should not matter which of these three exerting forces is used to debond a bracket.