These results implicated YAP1 R331W as an allele predisposed for lung adenocarcinoma with high familial penetrance. Low-dose computed tomography scans may be recommended to this subpopulation, which is at high risk for lung cancer, for personalized prevention and health management.

Depression is associated with behavioral disturbances and serotonergic and neuroendocrinological disfunctions.1,2) The brain serotonergic system is a very complicated control system playing an important role in the response to depression. 3)A number of factors have been proposed to account for a reduced functionality of serotonergic system in depression. Investigations based on this system have formed into currently available antidepressants.2) On the other hand, neuroendocrinological abnormality in depressed patients is hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypersecretion of corticotropin-releasing factor (CRF), which stimulates corticosterone release. 4,5) Successful antidepressant treatment could attenuate these alterations in clinical trials and animal experiments. [6][7][8][9] In addition, there is a close relationship between the serotonergic and HPA axis systems in major depression. [10][11][12][13] The impact of stress on the HPA axis is reviewed and evidence present that CRF is the stress neurotransmitter which plays an important role in the activation of serotonergic systems. 11,14) Psoralen (Fig. 1) is a main furocoumarin isolated from the seeds of Psoralea corylifolia, 15) which is a traditional Chinese medicine used to treat a wide range of diseases and conditions. Our previous studies demonstrated that the total furocoumarins extracts of P. corylifolia possessed the potent antidepressant properties by employing the forced swimming test (FST), a well-established animal model of depression. 7)These furocoumarins extracts depressed the hyperactive HPA axis induced by swim stress in mice.7) Furthermore, the total furocoumarins extracts and psoralen exhibited inhibitory actions on monoamine oxidase (MAO) A and B activities. 16,17) Per-orally administered psoralen increased the daytime levels of melatonin via the competitive inhibition of hepatic melatonin metabolism, indicating that psoralen might affect seasonal affective disorder patients under a low level of illumination.18) However, there is no study on antidepressant-like effects and related possible mechanisms of actions by psoralen. The aim of the current study was to investigate the effects of psoralen on the durations of immobility, climbing and swimming in the mouse FST after administrations for 1, 3, 7 and 14 d, respectively. We also examined the effects of 14-d psoralen treatment on serotonergic neurotransmitters serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) levels in frontal cortex and hippocampus of the mouse brain regions. The regulation of psoralen on the HPA axis including CRF and corticosterone concentrations was simultaneously studied in the mouse FST. MATERIALS AND METHODS MaterialsPsoralen was isolated and purified from the seeds of P. corylifolia as described in our previous reports. 19)The purity of the chemical was determined to beyond 98% by HPLC analysis. Amitriptyline was obtained from Changzhou Siyao Pharmaceuticals Co., Ltd. (P. R. China). All other chemical...

Lung cancer is the leading cause of cancer death worldwide and cancer relapse accounts for the majority of cancer mortality. The mechanism is still unknown, especially in hereditary lung cancer without known actionable mutations. To identify genetic alternations involved in hereditary lung cancer and relapse is urgently needed. We collected genetic materials from a unique hereditary lung cancer patient's blood, first cancer tissue (T1), adjacent normal tissue (N1), relapse cancer tissue (T2), and adjacent normal tissue (N2) for whole genome sequencing. We identified specific mutations in T1 and T2, and attributed them to tumorigenesis and recurrence. These tumor specific variants were enriched in antigen presentation pathway. In addition, a lung adenocarcinoma cohort from the TCGA dataset was used to confirm our findings. Patients with high mutation burdens in tumor specific genes had decreased relapse‐free survival ( P = 0.017, n = 186). Our study may provide important insight for designing immunotherapeutic treatment for hereditary lung cancer.

Risk factors including genetic effects are still being investigated in lung adenocarcinoma (LUAD). Mitochondria play an important role in controlling imperative cellular parameters, and anomalies in mitochondrial function might be crucial for cancer development. The mitochondrial genomic aberrations found in lung adenocarcinoma and their associations with cancer development and progression are not yet clearly characterized. Here, we identified a spectrum of mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with prognosis and clinical outcomes. Next-generation sequencing was used to reveal the mitochondrial genomes of tumor and conditionally normal adjacent tissues from 61 Stage 1 LUADs. Mitochondrial somatic mutations and clinical outcomes including relapse-free survival (RFS) were analyzed. Patients with somatic mutations in the D-loop region had longer RFS (adjusted hazard ratio, adjHR = 0.18, p = 0.027), whereas somatic mutations in mitochondrial Complex IV and Complex V genes were associated with shorter RFS (adjHR = 3.69, p = 0.012, and adjHR = 6.63, p = 0.002, respectively). The risk scores derived from mitochondrial somatic mutations were predictive of RFS (adjHR = 9.10, 95%CI: 2.93–28.32, p < 0.001). Our findings demonstrated the vulnerability of the mitochondrial genome to mutations and the potential prediction ability of somatic mutations. This research may contribute to improving molecular guidance for patient treatment in precision medicine.