ABSTRACT
OBJECTIVE@#To investigate the inhibitory effect of ketogenic diet (KD) on growth of neuroblastoma in mice.@*METHODS@#BALB/c-nu mouse models bearing neuroblastoma xenografts were established by subcutaneous injection of human neuroblastoma cell line (SH-SY5Y). When the tumor volume reached 250 mm3, the mice were randomized into SD group with standard diet and PBS treatment, KD group with ketogenic diet and PBS treatment, and CP+KD group with ketogenic diet and cyclophosphamide (60 mg·kg·day) treatment, =8. The tumor volume, body weight, blood glucose, ketone body (β-Hydroxybutyrate) levels, and hepatic steatosis in the mice were assessed. The expressions of caspase-3 and caspase-8 were detected by Western blotting, and Ki67 expresison was detected using immunohistochemistry (IHC). Transmission electron microscopy (TEM) was employed for the autophagosomes, and the autophagic protein Beclin1, LC3A/B and P62 were detected by IHC and Western blotting.@*RESULTS@#On day 28 post tumor cell injection, the mice in KD and CP+KD groups could prolong the overall survival rates than that in SD group ( < 0.001). On day 22 post the injection, the tumor volume in KD group was smaller than that in SD group ( < 0.05); on 16, 19, and 22 day post the injection, the tumor volume in CP+KD group was smaller than that in SD group ( < 0.01). The mice in SD group showed greater body weight on day 19 and higher blood glucose level on day 13 post the injection than those in the other two groups ( < 0.05). Blood ketone level and hepatic steatosis score were higher and glucose ketone index (GKI) was lower in KD and CP+KD groups than those in SD group (all < 0.05). The expressions of Ki67 and apoptotic proteins were detected in the tumor tissues of all groups. TEM revealed more autophagosomes in the tumor tissues of KD group than that of SD group. P62 expression was lowered ( < 0.01) and Beclin1 and LC3A/B expressions were up-regulated in the tumor tissues of KD group ( < 0.05), which is consisitent with IHC.@*CONCLUSIONS@#KD has a strong anti-tumor effect in the xenograft mouse model possibly by regulating cell autophagy.
Subject(s)
Animals , Humans , Mice , 3-Hydroxybutyric Acid , Blood Glucose , Cell Line, Tumor , Diet, Ketogenic , Mice, Inbred BALB C , NeuroblastomaABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is the result of the interaction between many factors, and “second hit” focusing on oxidative stress is a key factor for the progression of NAFLD. Autophagy has been a research hotspot in recent years, and more and more studies have shown that autophagy plays an important role in lipid metabolism in hepatocytes, inflammatory response, and liver fibrosis and is closely associated with oxidative stress. With reference to the latest research findings in China and foreign countries, this article analyzes the interrelation between autophagy and oxidative stress in the pathogenesis of NAFLD from the aspects of the association between autophagy and NAFLD and the association between oxidative stress and NAFLD. It is pointed out that the molecular mechanism of the regulation of oxidative stress by autophagy in the pathogenesis of NAFLD may be a research hotspot in future, and blockade or activation of a key pathway involved in the regulation of oxidative stress by autophagy may provide a new method for the treatment of NAFLD.
ABSTRACT
Treatment of H.pylor(Hp)-relatedgastropathy with traditional Chinese medicine(TCM) therapy has prominent advantages. Integration of traditional and western medicine can remarkably increase negative conversion ratio, reduce drug resistance rate and effectively decrease adverse reactions and recurrence rate. This paper summarized the research progress of the treatment for Hp-related gastropathy and related mechanism with TCM recently. The content included the aspects of theory, treatment and anti-Hp mechanism of Hp-related gastropathy in TCM, in order to provide relevant reference for clinical medication and scientific research direction in future .