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Ferroptosis is an iron- and lipotoxicity-dependent form of regulated cell death (RCD). It is morphologically and biochemically distinct from characteristics of other cell death. This modality has been intensively investigated in recent years due to its involvement in a wide array of pathologies, including cancer, neurodegenerative diseases, and acute kidney injury. Dysregulation of ferroptosis has also been linked to various liver diseases and its modification may provide a hopeful and attractive therapeutic concept. Indeed, targeting ferroptosis may prevent the pathophysiological progression of several liver diseases, such as hemochromatosis, nonalcoholic steatohepatitis, and ethanol-induced liver injury. On the contrary, enhancing ferroptosis may promote sorafenib-induced ferroptosis and pave the way for combination therapy in hepatocellular carcinoma. Glutathione peroxidase 4 (GPx4) and system xc− have been identified as key players to mediate ferroptosis pathway. More recently diverse signaling pathways have also been observed. The connection between ferroptosis and other forms of RCD is intricate and compelling, where discoveries in this field advance our understanding of cell survival and fate. In this review, we summarize the central molecular machinery of ferroptosis, describe the role of ferroptosis in non-cancer hepatic disease conditions and discuss the potential to manipulate ferroptosis as a therapeutic strategy.

Objective:Endothelial dysfunction was widely regarded as the initial lesion in the multifactorial pathogenesis of cardiovascular disease (CVD). Serum endocan, a novel endothelial dysfunction biochemical marker, is involved in the development of CVD. Here, we fulfilled a meta-analysis to evaluate the association between CVD and serum endocan levels.Method:The relevant published literature was searched through large literature databases, including PubMed, Embase, Cochrane Library, SinoMed, and Web of Science, up to June 1, 2018. The data were extracted from the studies. Stata software was used to perform a meta-analysis.Result:Fifteen original studies with a total of 1839 patients and 1258 controls fulfilled the inclusion criteria and were included in the study dataset. Meta-analysis showed that the levels of serum endocan in patients with hypertension, coronary artery disease, and coronary slow flow were higher than those in the control group. The pooled standardized mean differences and 95% confidence intervals of endocan concentrations in those 3 groups were 0.53 [0.19–0.86], P < .01; 0.99 [0.51–1.39], P < .01; and 0.62 [0.45–0.78], P < .01, respectively. Further analysis showed that the level of serum endocan in hypertension patients with coronary artery disease was higher than that in patients with hypertension (0.61 [0.30–0.92], P < .01). Sensitivity analysis and subgroup analysis were use to confirm the above results.Conclusions:In this meta-analysis, we further confirmed that serum endocan level was significantly increased in the CVD population. The high serum endocan level may be one of the risk factors for CVD.

To survive, cancer cells are subjected to various internal and external adverse factors, including genetic mutations, hypoxia, nutritional deficiencies, and drug toxicity. All of these factors result in the accumulation of unfolded proteins in the endoplasmic reticulum, which leads to a condition termed endoplasmic reticulum stress (ER stress) and triggers the unfolded protein response (UPR). UPR downstream components strictly control transcription and translation reprogramming to ensure selective gene expression, including that of non-coding RNA (ncRNAs), to adapt to adverse environments. NcRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play important roles in regulating target gene expression and protein translation, and their aberrant expression is related to tumor development. Dysregulation of ncRNAs is involved in the regulation of various cellular characteristics of cancer cells, including growth, apoptosis, metastasis, angiogenesis, drug sensitivity, and tumor stem cell properties. Notably, ncRNAs and ER stress can regulate each other and collaborate to determine the fate of tumor cells. Therefore, investigating the interaction between ER stress and ncRNAs is crucial for developing effective cancer treatment and prevention strategies. In this review, we summarize the ER stress-triggered UPR signaling pathways involved in carcinogenesis followed by the mutual regulation of ER stress and ncRNAs in cancer, which provide further insights into the understanding of tumorigenesis and therapeutic strategies.

Background Alterations in body compositions are related to poor outcomes and the presence of complications in cirrhosis. However, no predictive tools combining all these anthropometric parameters are applicable in the clinical setting. We aimed to clarify the potential utility of body compositions and develop a nomogram incorporating any independent factor for prognosticating long‐term mortality in cirrhosis. Methods A total of 414 patients were randomized into primary (n = 274) and validation (n = 140) cohorts. X‐tile was performed to identify optimal cut points for stratifying participants. Multivariate Cox regression was performed, and nomogram incorporating body compositions were generated. The utility of developed models was evaluated by Harrell concordance index (C‐index), calibration curve, and decision curve analysis (DCA). Results Stratifying by X‐tilederived cut points, low skeletal muscle index (myopenia), high intramuscular adipose tissue content (myosteatosis), and the ratio of high visceral to subcutaneous adipose tissue area (adiposity) was independently associated with 3‐year mortality. A sex‐stratified nomogram incorporating anthropometric indices and clinical factors resulted in moderate discriminative accuracy, with a C‐index of 0.787 (95% CI, 0.736–0.838) and 0.789 (95% CI, 0.727–0.851) in males and females, respectively. The calibration curve showed predictive survival corresponding optimally with the actual outcomes. Our models were feasible in the clinical settings based on DCA. Similar results were observed in the validation cohort. Additionally, participants could be classified into 3 distinct risk groups by the nomogram. Conclusions Our proposed nomogram embedding body compositions rendered an individualized predictive tool for long‐term mortality in cirrhosis.