The role of interleukin-20 in liver disease: Functions, mechanisms and clinical applications.

Liver disease is a severe public health concern worldwide. There is a close relationship between the liver and cytokines, and liver inflammation from a variety of causes leads to the release and activation of cytokines. The functions of cytokines are complex and variable, and are closely related to their cellular origin, target molecules and mode of action. Interleukin (IL)-20 has been studied as a pro-inflammatory cytokine that is expressed and regulated in some diseases. Furthermore, accumulating evidences has shown that IL-20 is highly expressed in clinical samples from patients with liver disease, promoting the production of pro-inflammatory molecules involved in liver disease progression, and antagonists of IL-20 can effectively inhibit liver injury and produce protective effects. This review highlights the potential of targeting IL-20 in liver diseases, elucidates the potential mechanisms of IL-20 inducing liver injury, and suggests multiple viable strategies to mitigate the pro-inflammatory response to IL-20. Genomic CRISPR/Cas9-based screens may be a feasible way to further explore the signaling pathways and regulation of IL-20 in liver diseases. Nanovector systems targeting IL-20 offer new possibilities for the treatment and prevention of liver diseases.

NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro, AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.

Early-onset locally advanced rectal cancer characteristics, a practical nomogram and risk stratification system: a population-based study.

Background: The purpose of this study is to construct a novel and practical nomogram and risk stratification system to accurately predict cancer-specific survival (CSS) of early-onset locally advanced rectal cancer (EO-LARC) patients. Methods: A total of 2440 patients diagnosed with EO-LARC between 2010 and 2019 were screened from the Surveillance, Epidemiology, and End Results (SEER) database. The pool of potentially eligible patients was randomly divided into two groups: a training cohort (N=1708) and a validation cohort (N=732). The nomogram was developed and calibrated using various methods, including the coherence index (C-index), receiver operating characteristic curve (ROC), calibration curves, and decision curves (DCA). A new risk classification system was established based on the nomogram. To compare the performance of this nomogram to that of the American Joint Committee on Cancer (AJCC) staging system, DCA, net reclassification index (NRI), and integrated discrimination improvement (IDI) were employed. Result: Seven variables were included in the model. The area under the ROC curve (AUC) for the training cohort was 0.766, 0.736, and 0.731 at 3, 6, and 9 years, respectively. Calibration plots displayed good consistency between actual observations and the nomogram's predictions. The DCA curve further demonstrated the validity of the nomination form in clinical practice. Based on the scores of the nomogram, all patients were divided into a low-risk group, a middle-risk group, and a high-risk group. NRI for the 3-, 6-, and 9-year CSS(training cohort: 0.48, 0.45, 0.52; validation cohort: 0.42, 0.37, 0.37), IDI for the 3-, 6-, and 9-year CSS (training cohort: 0.09, 0.10, 0.11; validation cohort: 0.07, 0.08, 0.08). The Kaplan-Meier curve revealed that the new risk classification system possesses a more extraordinary ability to identify patients in different risk groups than the AJCC staging. Conclusion: A practical prognostic nomogram and novel risk classification system have been developed to efficiently predict the prognosis of EO-LARC. These tools can serve as a guide to individualize patient treatment and improve clinical decision-making.

The role of acetaldehyde dehydrogenase 2 in the pathogenesis of liver diseases.

Common liver tissue damage is mainly due to the accumulation of toxic aldehydes in lipid peroxidation under oxidative stress. Cumulative toxic aldehydes in the liver can be effectively metabolized by acetaldehyde dehydrogenase 2 (ALDH2), thereby alleviating various liver diseases. Notably, gene mutation of ALDH2 leads to impaired ALDH2 enzyme activity, thus aggravating the progress of liver diseases. However, the relationship and specific mechanism between ALDH2 and liver diseases are not clear. Consequently, the review explains the relationship between ALDH2 and liver diseases such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), liver fibrosis and hepatocellular carcinoma (HCC). In addition, this review also discusses ALDH2 as a potential therapeutic target for various liver diseases,and focuses on summarizing the regulatory mechanism of ALDH2 in these liver diseases.