Melatonin alleviates endoplasmic reticulum stress and follicular granulosa cell apoptosis by regulating ATF4 to activate mTOR signaling pathway in chickens.

Follicular atresia in chickens reduces the number of follicles that can further develop, leading to decrease egg laying. Endoplasmic reticulum stress (ERS) can initiate a unique pathway inducing the apoptosis of follicular granulosa cells, thus reducing egg laying. Melatonin (MEL) is involved in the regulation of follicle development, ovulation, and oocyte maturation, and is closely related to follicle fate. Mammalian target of Rapamycin (mTOR) signaling pathway plays an important role in cell growth regulation, and that there is a possible crosstalk between melatonin and mTOR activity in granular cells maturation and ovulation. This study aimed to investigate whether MEL inhibits ERS and follicular granulosa cell apoptosis by regulating ATF4 to activate mTOR signaling pathway in chickens. Frist, we established an in vitro ERS cell model using tunicamycin (TM). The results showed that different concentrations of TM exhibited dose-dependent inhibition of cell activity and induction of granulosa cells (P<0.01). Therefore, we chose 5 µg/mL of TM and a treatment time for 6 h as the optimal concentration for the following experiments. Then we investigate whether melatonin can inhibit ERS. TM treatment decreased the cell viability and Bcl-2 expression, increasing ROS levels and the mRNA expression of Grp78, ATF4, CHOP, PERK, eIF-2α, and BAX (P<0.01), whereas TM+MEL treatment significantly inhibited these changes (P<0.01). Then we explored whether melatonin protects follicular granulosa cells from ERS-induced apoptosis through the mammalian target of rapamycin (mTOR) signaling pathway by regulating ATF4, we found that ATF4 knockdown inhibited ERS by decreasing the expression of ERS-related genes and proteins and activating mTOR signaling pathway by increasing the protein expression of p4E-BP1 and pT389-S6K (P<0.001), while these changes were promoted by TM+si-ATF4+MEL treatment (P<0.01). These results indicate that MEL could alleviate TM-induced ERS by regulating ATF4 to activate mTOR signaling pathway in follicular granulosa cells, thus providing a new perspective for prolonging the laying cycle in chickens.

[The comparison of clinical features in children with different control levels of asthma].

OBJECTIVE: To compare the clinical features in children with different control levels of asthma and to explore the factors influencing asthma control. METHODS: A cross-sectional study was performed on 115 children diagnosed with asthma between October 2013 and February 2014. All the patients were classified into two groups: fully controlled group (n=65) and non-fully controlled group (n=55), according to the Children Bronchial Asthma Prevention and Treatment Guideline (2008 version) and the asthma control test results. The differences of clinical features between the two groups were compared. The quality of life was evaluated by an asthma-related quality of life questionnaire. The main factors influencing asthma control were analyzed by the logistic regression method. RESULTS: There were significant differences in the frequencies of respiratory tract infection and acute asthma attacks within the 3 months, and unplanned hospital visits due to acute asthma attacks between the fully controlled and non-fully controlled groups (P<0.05). The scores of asthma-related quality of life in the fully controlled group were significantly lower than in the non-fully controlled group in children under 7 years old. In contrast, the scores of asthma-related quality of life in the fully controlled group were significantly higher than in the non-fully controlled group in children at the age of 7-16 years (P<0.05). The logistic regression analysis showed that the patients without experiencing regular hospital visits (OR=7.715) and with allergic rhinitis (OR=5.531) had increased risks for poor asthma control and that the patients with other allergic diseases (eg. eczema, food allergy) had decreased risks for poor asthma control (OR=0.299). CONCLUSIONS: The appearance of some clinical features suggests that the asthmatic children may be in the status of poor asthma control and need an active intervention. A poor asthma control status can result in a decreased quality of life. To improve the asthma control level, the incidence of allergic rhinitis should be reduced and a regular hospital visit should be performed in the children.

[Survey on knowledge, attitude and practices in asthmatic children's parents in Beijing].

OBJECTIVES: To study the knowledge, attitude and practice (KAP) concerning asthma in parents of children with asthma and the related factors. METHOD: Questionnaire survey was conducted by using the multi-center research methods in twenty hospitals with asthmatic clinic or pediatric clinic in Beijing from August to October in 2008. The investigation focused on Beijing permanent residents with children who have been diagnosed as asthma for more than 6 months. RESULT: Totally 390 parents of asthmatic children were investigated among whom 351 provided valid questionnaires, the response rate reached 90.0%; 75.2% of the parents knew that the nature of asthma is a chronic allergic airway inflammatory disease; 54.4% of parents think that even if the child is in a state of asthma control he/she can participate in only mild exercise; 88.4% of parents consider that the long-term use of inhaled corticosteroid would have a mild effect on growth and development of children. Of the asthmatic children, 32.5% adhered to use inhaled corticosteroid prescription; 47.2% adhered to use leukotriene receptor modulator; 45.3% of parents of children with acute asthma attack will add antibiotics; 18.1% of parents would choose short-acting beta2-agonist. The multi-factors Logistic regression suggested that the parents' educational background and the frequency of referral in children with asthma under control may have an influences on the parents' KAP (P < 0.05, OR > 1). CONCLUSION: The general understanding of asthma in asthmatic children's parents in Beijing area is good, the higher the parents' educational background and revisit frequency of asthmatic children whose disease is under control, the better the Parents' KAP.