Esophageal cancer (ESCA) is among the most prevalent and lethal tumors globally. While nitric oxide synthase 1 (NOS1) is recognized for its important involvement in various cancers, its specific function in ESCA remains unclear.

To explore the potential role and underlying mechanisms of NOS1 in ESCA.

Survival rates were analyzed using GeneCards and Gene Expression Profiling Interactive Analysis. The effects and mechanisms of NOS1 on ESCA cells were evaluated via the Cell Counting Kit-8 assay, scratch assay, Transwell assay, flow cytometry, quantitative polymerase chain reaction, western blotting, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining. The protein interaction network was used to screen the interacting proteins of NOS1 and validate these interactions through co-immunoprecipitation and dual luciferase assays. Additionally, a nude mouse xenograft model was established to evaluate the effect of NOS1 in vivo.

The survival rate of patients with ESCA with high NOS1 expression was higher than that of patients with low NOS1 expression. NOS1 expression in ESCA cell lines was lower than that in normal esophageal epithelial cells. Overexpression of NOS1 (oe-NOS1) inhibited proliferation, invasion, and migration abilities in ESCA cell lines, resulting in decreased autophagy levels and increased apoptosis, pyroptosis, and ferroptosis. Protein interaction studies confirmed the interaction between NOS1 and NOS1 adaptor protein (NOS1AP). Following oe-NOS1 and the silencing of NOS1AP, levels of P62 and microtubule-associated protein 1 light chain 3 beta increased both in vitro and in vivo. Furthermore, the expression levels of E-cadherin, along with the activation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT), were inhibited in ESCA cell lines.

NOS1 and NOS1 proteins interact to suppress autophagy, activate the PI3K/AKT pathway, and exert anti-cancer effects in ESCA.

Shikonin is a plant medicine extracted from Lithospermum, which dominate influential antioxidant and antitumor effect. Here, we report that shikonin was capable of inducing human esophageal cancer EC9706 cell apoptosis and autophagy, in a time- and dose-dependent manner. Shikonin exposure repressed cell viability and migration and invasion capabilities and caused EC9706 cell autophagy and apoptosis by activating the AMPK/mTOR/ULK axis. Autophagy inhibition secured EC9706 cells against shikonin-induced autophagy and apoptosis and reversed the upregulation of AMPK and ULK phosphorylation and downregulation of mTOR phosphorylation provoked by shikonin. In summary, shikonin instigates EC9706 cell apoptosis and autophagy using the target AMPK/mTOR/ULK signal pathway axis, which provides a potential new target to treat human esophageal cancer.

Gastrointestinal disorders encompass a spectrum of conditions affecting various organs within the digestive system, such as the esophagus, stomach, colon, rectum, pancreas, liver, small intestine, and bile ducts. The role of autophagy in the etiology and progression of gastrointestinal diseases has garnered significant attention. This paper seeks to evaluate the impact and mechanisms of autophagy in gastrointestinal disorders by synthesizing recent research findings. Specifically, we delve into inflammation-related gastrointestinal conditions, including ul-cerative colitis, Crohn's disease, and pancreatitis, as well as gastrointestinal cancers such as esophageal, gastric, and colorectal cancers. Additionally, we provide commentary on a recent publication by Chang et al in the World Journal of Gastroenterology. Our objective is to offer fresh perspectives on the mechanisms and therapeutic approaches for these gastrointestinal ailments. This review aims to offer new perspectives on the mechanisms and therapeutic strategies for gastrointestinal disorders by critically analyzing relevant publications. As discussed, the role of autophagy in gastrointestinal diseases is complex and, at times, contentious. To harness the full therapeutic potential of autophagy in treating these conditions, more in-depth research is imperative.

With the increasing severity of the malignant tumors situation worldwide, the impacts of climate on them are receiving increasing attention. In this study, for the first time, all-malignant tumors were used as the dependent variable and absolute humidity (AH) was innovatively introduced into the independent variable to investigate the relationship between all-malignant tumors and meteorological factors. A total of 42,188 cases of malignant tumor deaths and meteorological factors in Wuhu City were collected over a 7-year (2014-2020) period. The analysis method combines distributed lagged nonlinear modeling (DLNM) as well as generalized additive modeling (GAM), with prior pre-analysis using structural equation modeling (SEM). The results showed that AH, temperature mean (T mean) and diurnal temperature range (DTR) all increased the malignant tumors mortality risk. Exposure to low and exceedingly low AH increases the malignant tumors mortality risk with maximum RR values of 1.008 (95% CI: 1.001, 1.015, lag 3) and 1.016 (95% CI: 1.001, 1.032, lag 1), respectively. In addition, low and exceedingly low T mean exposures also increased the risk of malignant tumors mortality, the maximum RR was 1.020 (95% CI: 1.006, 1.034) for low T mean and 1.035 (95% CI: 1.014, 1.058) for exceedingly low T mean. As for DTR, all four levels (exceedingly low, low, high, exceedingly high, from low to high) of exposure increased the risk of death from malignant tumors, from exceedingly low to exceedingly high maximum RR values of 1.018 (95% CI: 1.004, 1.032), 1.011 (95% CI: 1.005, 1.017), 1.006 (95% CI: 1.001, 1.012) and 1.019 (95% CI: 1.007, 1.031), respectively. The results of the stratified analysis suggested that female appear to be more sensitive to humidity, while male require additional attention to reduce exposure to high level of DTR.

Gastrointestinal cancers are a group of cancers occurred in gastrointestinal tissues with high morbidity and mortality rate. Although numerous studies were conducted on the investigation of gastrointestinal cancers, the real mechanisms haven't been discovered, and no effective methods of prevention and treatment of gastrointestinal cancers have been developed. Autophagy, a vital catabolic process in organisms, have been proven to participate in various mechanisms and signaling pathways, thus producing a regulatory effect on various diseases. The role of autophagy in gastrointestinal cancers remains unclear due to its high complexity. In this review, firstly, the biological features of autophagy will be introduced. Secondly, the role of autophagy in three popular gastrointestinal cancers, namely esophageal cancer, gastric cancer, and colorectal cancer will be described and discussed by reviewing the related literature. We aimed to bring novel insights in exploring the real mechanisms for gastrointestinal cancers and developing effective and efficient therapeutic methods to treat gastrointestinal cancers.