Background: hsa_circ_0001727 (circZKSCAN1) has been reported to be a tumor-associated circRNA by sponging microRNAs. Intriguingly, we found that circZKSCAN1 encoded a secretory peptide (circZKSaa) in the liver. The present study aims to elucidate the potential role and molecular mechanism of circZKSaa in the regulation of hepatocellular carcinoma (HCC) progression. Methods: The circRNA profiling datasets (RNA-seq data GSE143233 and GSE140202) were reanalyzed and circZKSCAN1 was selected for further study. Mass spectrometry, polysome fractionation assay, dual-luciferase reporter, and a series of experiments showed that circZKSCAN1 encodes circZKSaa. Cell proliferation, apoptosis, and tumorigenesis in nude mice were examined to investigate the functions of circZKSaa. Mechanistically, the relationship between the circZKSaa and mTOR in HCC was verified by immunoprecipitation analyses, mass spectrometry, and immunofluorescence staining analyses. Results: Receiver operating characteristic (ROC) analysis demonstrated that the secretory peptide circZKSaa encoded by circZKSCAN1 might be the potential biomarker for HCC tissues. Through a series of experiments, we found that circZKSaa inhibited HCC progression and sensitize HCC cells to sorafenib. Mechanistically, we found that the sponge function of circZKSCAN1 to microRNA is weak in HCC, while overexpression of circZKSaa promoted the interaction of FBXW7 with the mammalian target of rapamycin (mTOR) to promote the ubiquitination of mTOR, thereby inhibiting the PI3K/AKT/mTOR pathway. Furthermore, we found that the high expression of cicZKSCAN1 in sorafenib-treated HCC cells was regulated by QKI-5. Conclusions: These results reveal that a novel circZKSCAN1-encoded peptide acts as a tumor suppressor on PI3K/AKT/mTOR pathway, and sensitizes HCC cells to sorafenib via ubiquitination of mTOR. These findings demonstrated that circZKSaa has the potential to serve as a therapeutic target and biomarker for HCC treatment.

It is important to clarify the distinct contributions of estrogen/estrogen receptor (ER) and androgen/androgen receptor (AR) signaling and their reciprocal effects on the regulation of hepatic lipid homeostasis. We studied the molecular mechanisms underlying the preventive effects of estradiol (E2), dihydrotestosterone (DHT), or E2+DHT on high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) in an orchidectomized Sprague-Dawley (SD) rat model. E2 is shown to be associated with decreased fatty acid synthesis in hepatic zone 3-specific manner by increasing the phosphorylation of acetyl coenzyme-A carboxylase via an ERα-mediated pathway. DHT is shown to be associated with decreased lipid accumulation and cholesterol synthesis in a hepatic zone 1-specific manner by increasing expression of carnitine palmitotyltransferase1 and phosphorylation of 3-hydroxy-3-methyl-glutaryl-CoA reductase via an AR-mediated pathway. E2+DHT showed an additive positive effect and normalized all three impaired zones of the liver. Gene expression changes in human severe liver steatosis were similar to those of experimental rat NAFLD. Steroids reversed the histopathological NAFLD changes, likely by decreasing fatty acid and cholesterol synthesis and increasing β-oxidation. The diverse steroid effects (ER/AR) on NAFLD prevention in male rats indicate the potential applicability of ER/AR modulators for NAFLD treatment.

Atherosclerosis is a leading cause of death worldwide, and its mechanisms are still unclear. However, various animal models have significantly advanced our understanding of the mechanisms involved in atherosclerosis and have allowed the evaluation of therapeutic options. The aim of this paper is to review those animal models (i.e., rabbits, mice, rats, guinea pigs, hamsters, avian, carnivores, swine, and, non-human primates) that have been used to study atherosclerosis. Though there is no single perfect animal model that completely replicates the stages of human atherosclerosis, cholesterol feeding and mechanical endothelial injury are two common features shared by most models of atherosclerosis. Further, with the development of genetically modified animals, these models are significantly broadening our understanding of the pathogenesis of atherosclerosis.

Bleeding complications can cause significant morbidities and mortalities in both civilian and military conditions. The formation of stable blood clots or hemostasis is essential to prevent major blood loss and death from excessive bleeding. However, the body's self-coagulation process cannot accomplish timely hemostasis without the assistance of hemostatic agents under some conditions. In the past two decades, topical hemostatic materials and devices containing platelets, fibrin, and polysaccharides have been gradually developed and introduced to induce faster or more stable blood clot formation, updating or iterating traditional hemostatic materials. Despite the various forms and functions of topical hemostatic materials that have been developed for different clinical conditions, uncontrolled hemorrhage still causes over 30% of trauma deaths across the world. Therefore, it is important to fabricate fast, efficient, safe, and ready-to-use novel hemostatic materials. It is necessary to understand the coagulation process and the hemostatic mechanism of different materials to develop novel topical hemostatic agents, such as tissue adhesives and sealants from various natural and synthetic materials. This review discusses the structural features of topical hemostatic materials related to the stimulation of hemostasis, summarizes the commercially available products and their applications, and reviews the ongoing clinical trials and recent studies concerning the development of different hemostatic materials.