ROS-mediated PERK-CHOP pathway plays an important role in cadmium-induced HepG2 cells apoptosis.

Cadmium (Cd) is a common heavy metal that is highly toxic to the liver, however, the exact mechanism underlying this damage accompanied by apoptosis has not been thoroughly demonstrated. In this study, we found that Cd exposure significantly reduced cell viability, including the increased populations of apoptotic cells and caspase-3/-7/-12 activation in HepG2 cells. Mechanistically, Cd initiated oxidative stress via elevating reactive oxygen species (ROS) levels, leading to oxidative damage in HepG2 cells. Simultaneously, Cd exposure induced endoplasmic reticulum (ER) stress via activating the protein kinase RNA-like ER kinase (PERK)-C/EBP homologous protein (CHOP) axis in HepG2 cells, and subsequently disturbed ER function as increased Ca2+ releasing from ER lumen. Intriguingly, further study revealed that oxidative stress is closely related with ER stress, as pretreatment with ROS scavenger, N-acetyl-l-cysteine (NAC) markedly reduced ER stress as well as protected ER function in Cd treated HepG2 cell. Collectively, these findings first revealed Cd exposure induced HepG2 cells death via a ROS-mediated PERK-CHOP-related apoptotic signaling pathway, which provides a novel insight into the mechanisms of Cd-induced hepatotoxicity. Furthermore, inhibitors for oxidative stress and ER stress might be considered as a new strategy to prevent or treat this disorder.

Analysis of Prognosis Influencing Factor of Children with Tourette Syndrome / 广州中医药大学学报

Objective To explore the related factors influencing the prognosis of children with Tourette syndrome ( TS) . Methods We collected 420 outpatient cases of TS children in the department of pediatrics of Guangdong Provincial Hospital of Traditional Chinese Medicine from January of 2007 to October of 2010 as the research objects. Using the unified survey questionnaire, we observed the influencing factors of TS prognosis such as sex, onset age, mother’s pregnancy situation, the perinatal period, partiality for food intake, family relationship, the first symptom, the severity of disease, underlying diseases, comorbidities ( such as attention deficit hyperactivity disorder, anxiety disorder, and obsessive-compulsive disorder) , family history of psychiatric or neurological diseases, trace elements levels, electroencephalogram (EEG), antistreptolycin O (ASO), course of disease, and maintenance treatment. The related factors of prognosis was analyzed with single factor and multiple factors Logistic regression analysis. Results Among the 420 cases of TS children, 396 cases were included into the final analysis, 24 were lost and the follow-up lost rate was 5.7%. The remission rate of TS was 78.3%, and the uncured rate was 21.7%. The results of preliminary screening of the influencing factors by single factor Logistic analysis showed that the related influencing factors for TS prognosis were 12, and they were course of diseases, abnormal birth history, father’s education level, mother’s education level, upbringing methods, family history of psychiatric or neurological diseases, underlying disease history, comorbidities history, abnormal ASO, the severity of disease, the frequency of disease relapse, and the medication history of western medicine (P<0.05) . And then the obtained 12 factors were analyzed by the multiple fac tors Lo gistic regression analysis, the results showed that upbringing methods, comorbidities history, the severity of disease, and the frequency of disease relapse were correlated with TS prognosis ( P < 0.05) . Conclusion TS children will have poor prognosis when their parents spoil, indiscipline, beat and scold, and dictate them, or when the children have severe illness state, frequent recurrence of the disease, and the history of comorbidities ( atten tion deficit hyperactivity disorder, anxiety disorder, obsessive-compulsive disorder, etc.) .