Cytoskeleton remodeling mediated by circRNA-YBX1 phase separation suppresses the metastasis of liver cancer.

Metastasis, especially intrahepatic, is a major challenge for hepatocellular carcinoma (HCC) treatment. Cytoskeleton remodeling has been identified as a vital process mediating intrahepatic spreading. Previously, we reported that HCC tumor adhesion and invasion were modulated by circular RNA (circRNA), which has emerged as an important regulator of various cellular processes and has been implicated in cancer progression. Here, we uncovered a nuclear circRNA, circASH2, which is preferentially lost in HCC tissues and inhibits HCC metastasis by altering tumor cytoskeleton structure. Tropomyosin 4 (TPM4), a critical binding protein of actin, turned out to be the major target of circASH2 and was posttranscriptionally suppressed. Such regulation is based on messenger RNA (mRNA)/precursormRNA splicing and degradation process. Furthermore, liquid-liquid phase separation of nuclear Y-box binding protein 1 (YBX1) enhanced by circASH2 augments TPM4 transcripts decay. Together, our data have revealed a tumor-suppressive circRNA and, more importantly, uncovered a fine regulation mechanism for HCC progression.

Global trends in research of mitophagy in liver diseases over past two decades: A bibliometric analysis.

Increasing evidence indicated that mitophagy might play a crucial role in the occurrence and progression of liver diseases. In order to enhance our understanding of the intricate relationship between mitophagy and liver diseases, a comprehensive bibliometric analysis of the existing literature in this field was conducted. This analysis aimed to identify key trends, potential areas of future research, and forecast the development of this specific field. We systematically searched the Web of Science Core Collection (WoSCC) for publications related to mitophagy in liver diseases from 2000 to 2022. We conducted the bibliometric analysis and data visualization through VOSviewer and CiteSpace. The analysis of publication growth revealed a substantial increase in articles published in this field over the past years, indicating mitophagy's growing interest and significance in liver diseases. China and USA emerged as the leading contributors in the number of papers, with 294 and 194 independent papers, respectively. Exploring the mechanism of mitophagy in the initiation and procession of liver diseases was the main content of studies in this field, and Parkin-independent mediated mitophagy has attracted much attention recently. "Lipid metabolism," "cell death," "liver fibrosis" and "oxidative stress" were the primary keywords clusters. Additionally, "nlrp3 inflammasome", "toxicity" and "nonalcoholic steatohepatitis" were emerging research hotspots in this area and have the potential to continue to be focal areas of investigation in the future. This study represents the first systematic bibliometric analysis of research on mitophagy in liver diseases conducted over the past 20 years. By providing an overview of the existing literature and identifying current research trends, this analysis sheds light on the critical areas of investigation and paves the way for future studies in this field.

Reversal of liver failure using a bioartificial liver device implanted with clinical-grade human-induced hepatocytes.

Liver resection is the first-line treatment for primary liver cancers, providing the potential for a cure. However, concerns about post-hepatectomy liver failure (PHLF), a leading cause of death following extended liver resection, have restricted the population of eligible patients. Here, we engineered a clinical-grade bioartificial liver (BAL) device employing human-induced hepatocytes (hiHeps) manufactured under GMP conditions. In a porcine PHLF model, the hiHep-BAL treatment showed a remarkable survival benefit. On top of the supportive function, hiHep-BAL treatment restored functions, specifically ammonia detoxification, of the remnant liver and facilitated liver regeneration. Notably, an investigator-initiated study in seven patients with extended liver resection demonstrated that hiHep-BAL treatment was well tolerated and associated with improved liver function and liver regeneration, meeting the primary outcome of safety and feasibility. These encouraging results warrant further testing of hiHep-BAL for PHLF, the success of which would broaden the population of patients eligible for liver resection.

Cause of Death Among Patients With Thyroid Cancer: A Population-Based Study.

Background: Over the last decades, the number of patients diagnosed with thyroid carcinoma has been increasing, highlighting the importance of comprehensively evaluating causes of death among these patients. This study aimed to comprehensively characterize the risk of death and causes of death in patients with thyroid carcinoma. Methods: A total of 183,641 patients diagnosed with an index thyroid tumor were identified from the Surveillance, Epidemiology, and End Result database (1975-2016). Standardized mortality rates (SMRs) for non-cancer deaths were calculated to evaluate mortality risk and to compare mortality risks with the cancer-free US population. Cumulative mortality rates were calculated to explore the factors associated with higher risk of deaths. Results: There were 22,386 deaths recorded during follow-up, of which only 31.0% were due to thyroid cancer and 46.4% due to non-cancer causes. Non-cancer mortality risk among patients with thyroid cancer was nearly 1.6-fold (SMR=1.59) that of the general population. Cardiovascular diseases were the leading cause of non-cancer deaths, accounting for 21.3% of all deaths in thyroid cancer patients. Non-cancer causes were the dominant cause of death in thyroid cancer survivors as of the third year post-diagnosis. We found that males with thyroid cancer had a higher risk of all-cause mortality compared with females. The risk of suicide was highest in the first post-diagnostic year (<1 year: SMR=1.51). The long-term risk of Alzheimer's disease was notably increased in thyroid cancer patients (>5 years: SMR=8.27). Conclusion: Non-cancer comorbidities have become the major risks of death in patients with thyroid tumor in the US, as opposed to death from the tumor itself. Clinicians and researchers should be aware of these risk trends in order to conduct timely intervention strategies.

CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma.

BACKGROUND: The physiological regulatory functions of circRNAs have become a topic of intensive research in recent years. Increasing evidence supports a significant role of circRNAs during cancer initiation and progression, including hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A bioinformatics analysis from three independent Gene Expression Omnibus (GEO) databases was performed to profile and screen the dysregulated circRNAs in HCC. RT-qPCR was used to examine the expression level of circUBAP2 in HCC and adjacent non-tumor tissues. Then, proliferation assays (CCK8 and colony formation) and migration assays (transwell and wound healing) were performed to examine effect of circUBAP2 in vitro. Immunoprecipitation, RNA pulldown, FISH, and dual-luciferase reporter assay was conducted to explore the circUBAP2-related mechanism for regulating HCC progression. Moreover, a mouse xenograft model and a mouse lung metastasis model confirmed the effect of circUBAP2 in vivo. RESULTS: In this study, we found a novel circRNA: circUBAP2, which was identified by bioinformatics analysis. Among 91 HCC patients, circUBAP2 was significantly upregulated in HCC tissues, and negatively correlated with aggressive clinical characteristics and prognosis. Functional assays demonstrated that circUBAP2 promoted cell proliferation, colony formation, migration, and invasion in vitro. Moreover, circUBAP2 enhanced tumor growth and pulmonary metastasis in vivo. Mechanistically, circUBAP2 acts as a competing endogenous RNA (ceRNA) for miR-194-3p, a tumor suppressor in HCC. We confirmed that MMP9 was direct target for miR-194-3p, which was regulated by circUBAP2. CONCLUSION: CircUBAP2 plays a significant role in promoting HCC via the miR-194-3p/MMP9 pathway and could serve as a promising prognostic biomarker and novel therapeutic target for HCC patients.

Laparoscopic versus open hemihepatectomy: a 1:1 matched analysis.

BACKGROUND: Laparoscopic liver resection has increased rapidly and procedure has almost extended to all the types of liver resection. Major liver resections, such as hemihepatectomies, were still innovative procedures in the exploration phase and continued cautious introduction of major laparoscopic liver resections was recommended by experts. The study aims to evaluate the safety of laparoscopic hemihepatectomy (LH) by the comparing with open hemihepatectomy (OH). METHODS: Patients who underwent hemihepatectomy in Sir Run Run Shaw Hospital from January 2012 to December 2017 were reviewed. A 1:1 matched study was performed between LH group and OH group. Patients who fail to be matched were excluded. Perioperative outcomes, complications and cost were compared between LH group and OH group. RESULTS: One hundred and thirty-eight exact matches for all matching variables were found between LH patients and OH patients. The length of postoperative hospital stay of LH group was significant shorter than the OH group (P=0.031). Intraoperative blood loss (P=0.005) and transfusion rate (P=0.001) in the LH group were significantly lower than the OH group. There was no mortality in either group. Twenty-six patients in LH group and 31 patients in OH group had complications and all of them recovered uneventfully after immediate treatments. The hospital expense of LH group was significantly higher than OH group (P<0.001). CONCLUSIONS: These results lead us to believe that LH is a safe procedure and it could be performed routinely in experienced laparoscopic centers.

Scientometric analysis of mTOR signaling pathway in liver disease.

BACKGROUND: The mTOR pathway is vital for homeostasis, metabolism, cancer transplantation and regeneration in the liver. The aim of this study is to use a bibliometric method to reveal current research hotspots and promising future trends in mTOR signaling in liver diseases. METHODS: Publications were searched and downloaded from the Web of Science Core Collection (WOSCC) Database. CiteSpace, Carrot2, and VOSviewer programs were utilized to analyze the contribution of various countries/regions, institutes, and authors; and to reveal research hotspots and promising future trends in this research area. RESULTS: Until May 21, 2019, a total of 2,232 papers regarding mTOR signaling pathway in liver disease were included, and each paper was cited 23.21 times on average. The most active country was the USA. 5 landmark articles with centrality and burstiness were determined by co-citation analysis. Research hotspots included "liver transplantation" "hepatic stellate cell proliferation" "NAFLD" "therapy of HCC". Moreover, six key clusters were discovered during the procedure of "clustering", including "liver transplantation" "protein synthesis" "mTOR inhibitor" "following early cyclosporine withdrawal" "srebp-1 activation", and "hepatocellular cancer". CONCLUSIONS: Various scientific methods were applied to reveal scientific productivity, collaboration, and research hotspots in the mTOR signaling pathway in liver disease. Liver transplantation, hepatic stellate cell proliferation, non-alcoholic fatty liver disease (NAFLD), therapy of hepatocellular carcinoma (HCC), cell growth and autophagy, are research hotspots and are likely to be promising in the next few years. Further studies in this field are needed.