Gastrointestinal cancer is a disease that affects the population worldwide with high morbidity and mortality. Melatonin, an endogenously produced molecule, may provide a defense against a variety of cancer types. In particular, the ability of melatonin to inhibit gastrointestinal cancer is substantial. In this review, we first clarify the relationship between the disruption of the melatonin rhythm and gastrointestinal cancer (based on epidemiologic surveys and animal and human studies) and summarize the preventive effect of melatonin on carcinogenesis. Thereafter, the mechanisms through which melatonin exerts its anti‐gastrointestinal cancer actions are explained, including inhibition of proliferation, invasion, metastasis, and angiogenesis, and promotion of apoptosis and cancer immunity. Moreover, we discuss the drug synergy effects and the role of melatonin receptors involved in the growth‐inhibitory effects on gastrointestinal cancer. Taken together, the information compiled here serves as a comprehensive reference for the anti‐gastrointestinal cancer actions of melatonin that have been identified to date and will hopefully aid in the design of further experimental and clinical studies and increase the awareness of melatonin as a therapeutic agent in cancers of the gastrointestinal tract.

Introduction: High altitude (HA) exposure leads to cognitive impairment while the underlying mechanism is still unclear. Brain functional network is crucial for advanced functions, and its alteration is implicated in cognitive decline in multiple diseases. The aim of current study was to investigate the topological changes in HA‐exposed brain functional network.Methods: Based on Shaanxi‐Tibet immigrant cohort, neuropsychological tests and resting‐state functional MRI were applied to evaluate the participants' cognitive function and functional connection (FC) changes, respectively. GRETNA toolbox was used to construct the brain functional network. The gray matter was parcellated into 116 anatomically defined regions according to Automated Anatomical Labeling atlas. Subsequently, the mean time series for each of the 116 regions were extracted and computed for Pearson's correlation coefficients. The relation matrix was further processed and seen as brain functional network. Correlation between functional network changes and neuropsychological results was also examined.Results: The cognitive performance was impaired by HA exposure as indicated by neuropsychological test. HA exposure led to alterations of degree centrality and nodal efficiency in multiple brain regions. Moreover, two subnetworks were extracted in which the FCs significantly decreased after exposure. In addition, the alterations in FCs within above two subnetworks were significantly correlated with changes of memory and reaction time.Conclusions: Our results suggest that HA exposure modulates the topological property of functional network and FCs of some important regions, which may impair the attention, perception, memory, motion ignition, and modulation processes, finally decreasing cognitive performance in neuropsychological tests.

Necroptosis is a new type of programmed cell death and involves the occurrence and development of various cancers. Moreover, the aberrantly expressed lncRNA can also affect tumorigenesis, migration, and invasion. However, there are few types of research on the necroptosis-related lncRNA (NRL), especially in kidney renal clear cell carcinoma (KIRC). In this study, we analyzed the sequencing data obtained from the TGCA-KIRC dataset, then applied the LASSO and COX analysis to identify 6 NRLs (AC124854.1, AL117336.1, DLGAP1-AS2, EPB41L4A-DT, HOXA-AS2, and LINC02100) to construct a risk model. Patients suffering from KIRC were divided into high- and low-risk groups according to the risk score, and the patients in the low-risk group had a longer OS. This signature can be used as an indicator to predict the prognosis of KIRC independent of other clinicopathological features. In addition, the gene set enrichment analysis showed that some tumor and immune-associated pathways were more enriched in a high-risk group. We also found significant differences between the high and low-risk groups in the infiltrating immune cells, immune functions, and expression of immune checkpoint molecules. Finally, we use the “pRRophetic” package to complete the drug sensitivity prediction, and the risk score could reflect patients’ response to 8 small molecule compounds. In general, NRLs divided KIRC into two subtypes with different risk scores. Furthermore, this signature based on the 6 NRLs could provide a promising method to predict the prognosis and immune response of KIRC patients. To some extent, our findings helped give a reference for further research between NRLs and KIRC and find more effective therapeutic drugs for KIRC.