Relationship between oily fish intake and breast cancer based on estrogen receptor status: a Mendelian randomization study.

OBJECTIVE: We used a Mendelian randomization (MR) method in our research to examine the relationship between genetically determined oily fish intake and breast cancer (BC) incidence. METHODS: The summary data pertaining to the oily fish intake were acquired from the UK Biobank, which consisted of a sample size of 460,443 people. Information on BC was received from the Breast Cancer Association Consortium (BCAC). We analyzed the causal connection between oily fish intake and BC incidence using various methods, including inverse variance weighting (IVW). Heterogeneity was investigated using Cochran's Q test. IVW, MR-Egger, and MR-PRESSO methods were used for sensitivity analysis. In addition, a multivariate MR adjusted for body mass index (BMI) and weight was used for further research. RESULTS: Two-sample MR results showed that oily fish intake was negatively associated with total breast cancer (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.39-0.87, IVW method), estrogen receptor-positive (ER +) breast cancer (OR 0.44, 95% CI 0.21-0.93, IVW method), and estrogen receptor-negative (ER-) breast cancer (OR 0.53, 95% CI 0.30-0.93, IVW method). The sensitivity analysis did not observe the presence of heterogeneity and horizontal pleiotropy. In multivariate MR analysis, the negative association between oily fish intake and total breast cancer (P = 0.03) and ER- breast cancer (P = 0.04) risk persisted after adjusting for BMI and body weight. However, no correlation was found in ER + breast cancer (P = 0.30). CONCLUSION: The oily fish intake has a negatively correlated with the incidence of total breast cancer, particularly in the cases of ER- breast cancer. There is a lack of substantial evidence supporting a link between the oily fish intake and the incidence of ER + breast cancer.

Applying ketamine to alleviate the PTSD-like effects by regulating the HCN1-related BDNF.

BACKGROUND: Post-traumatic stress disorder (PTSD) is commonly associated with concurrent anxiety and depression symptoms, and reduce the expression of the Brain-Derived Neurotrophic Factor (BDNF) which promotes the proliferation and survival of neurons. The hyperpolarization-activated cyclic nucleotide-gated channel 1(HCN1) could be inhibited by the ketamine, a drug to alleviate depression and anxiety, and regulated the BDNF expression, however, the effects of ketamine in alleviating PTSD symptoms by regulating the HCN1-related BDNF have been poorly perceived. METHODS: In the present study, the effects of ketamine were examined on the PTSD-like effects in a rat model of PTSD induced by SPS&S procedure. After the SPS&S procedure and model testing, PTSD rats were subjected to behavioral testing and biochemical assessments, followed by single treatment with certain doses of ketamine (5, 10, 15 and 20 mg/kg IP). RESULTS: The results showed that the SPS&S procedure induced severe PTSD-like behaviors, with lower levels of BDNF protein levels and higher level of the HCN1 protein in the prefrontal cortex (PFC). These were reversed by a single administration of ketamine. The ketamine with dose of 15 mg/kg significantly increased locomotor behavior in the open field test, aggrandized exploratory behavior in the elevated plus maze test, and decreased immobility time spent in the forced swim test. Meanwhile, ketamine with dose of 15 mg/kg could increase the BDNF protein level, while down-regulate the expression of the HCN1. Eventually, there was a negative correlation between the level of BDNF and HCN1 in the PFC. CONCLUSION: Ketamine affects the HCN1-related BDNF signaling pathways to alleviate PTSD-like effects in rat.