Licorice, a natural medicine derived from the roots and rhizomes of Glycyrrhiza species, possesses a wide range of therapeutic applications, including antiviral properties. Glycyrrhizic acid (GL) and glycyrrhetinic acid (GA) are the most important active ingredients in licorice. Glycyrrhetinic acid 3-O-mono-β-d-glucuronide (GAMG) is the active metabolite of GL. GL and its metabolites have a wide range of antiviral activities against viruses, such as, the hepatitis virus, herpes virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and so on. Although their antiviral activity has been widely reported, the specific mechanism of action involving multiple links such as the virus itself, cells, and immunity are not clearly established. In this review, we will give an update on the role of GL and its metabolites as antiviral agents, and detail relevant evidence on the potential use and mechanisms of actions. Analyzing antivirals, their signaling, and the impacts of tissue and autoimmune protection may provide promising new therapeutic strategies.

Although ALYREF has been demonstrated to have a role in a number of malignancies, its role in hepatocellular carcinoma (HCC) has received little attention. Our objective was to research at the prognostic value, biological role and relevance of ALYREF to the immune system in HCC. The expression of ALYREF and its relationship with clinical parameters of HCC patients were analyzed by liver cancer cohort (LIHC) of The Cancer Genome Atlas. The expression and prognosis were verified by immunohistochemistry experiments. Gene transfection, CCK-8, scratch healing, transwell invasion and flow cytometry were used to assess the molecular function of ALYREF in vitro. The TIMER and TISIDB online data portals were used to assess the relevance of ALYREF to immunization. Stepwise regression analysis of ALYREF-related immune genes in the LIHC training set was used to construct a prognostic risk prediction model. Also, construct a nomogram to predict patient survival. The testing set for internal verification. Knockdown of ALYREF changed the biological phenotypes of HCC cells, such as proliferation, apoptosis, and invasion. In addition, the expression of ALYREF in HCC affected the level of immune cell infiltration and correlated with the overall survival time of patients. The constructed immune prognostic model allows for a valid assessment of patients. ALYREF is increased in HCC, has an impact on cellular function and the immune system, and might be used as a prognostic marker.

Propensity score matching study of 325 patients with spontaneous rupture of hepatocellular carcinoma Wei Wang, Tao Meng, Ying Chen, Ye-Chan Xu, Yi-Jun Zhao, Yan Zhang, Ming-Ya Yang, Zhi-Hua Zhang, Fan Huang, Hong-Chuan Zhao, Xiao-Ping Geng, Li-Xin Zhu

FAM83D has been demonstrated to contribute to tumorigenesis. However, its immune effects in hepatocellular carcinoma (HCC) have not been reported. This study aimed to identify the immune role of FAM83D in HCC. FAM83D was over-expressed in HCC and contributed to poor prognosis according to the results of data analysis based on The Cancer Genome Atlas (TCGA). Afterward, the levels of immune cells infiltration were found to be correlated with the expression level of FAM83D in HCC. Through TISIDB and cBioPortal network tools, a total of 82 FAM83D-associated genes were screened out, including 12 immunoinhibitors, 20 immunostimulators and 50 tightly co-expressed genes. TCGA cohort was divided into train set and test set on the basis of the proportion of 7:3. According to FAM83D-associated immunomodulators, a four gene predicted model was established using train set via the Cox regression analysis. Survival analysis demonstrated that the overall survival (OS) of high-risk HCC patients was poor compared with the patients in low-risk group. The reliability and predicted power of the risk-score model were identified by a receiver operating characteristic (ROC) curve. A risk-score based nomogram as well as a calibration curve, which were created could be used to anticipate patient’s 1-year, 3-year and 5-year survival probabilities. The test set was used to validate these results. Our findings showed that the FAM83D gene was related with HCC immunity. The immune marker chosen could be a promising biomarker for HCC prognosis.

A member of the short-chain dehydrogenase/reductase superfamily (DHRS1, SDR19C1) is a member of the short-chain dehydrogenase/reductase superfamily and a potential predictor of hepatocellular carcinoma (HCC). However, the role of DHRS1 in HCC immunity remains unclear. We systematically analyzed the association between DHRS1 and HCC immunity with transcriptional and clinical data from the Tumor Immune Estimation Resource, an integrated repository portal for tumor immune system interactions, and cBioPortal databases. Six DHRS1-associated immunomodulators strongly correlated with survival and were uncovered by exploiting univariate and multivariate Cox analyses. We created a risk score for each patient by adding the points from each immunomodulator and then classified them into high and low risk categories. Survival analysis were used to compare the overall survival between the 2 groups, and the receiver operating characteristic curve was applied to assess the accuracy of the risk score. Data from our center were adopted as the external validation set, the risk score was calculated using the risk coefficient of the 6 genes in the training cohort, and survival analysis were executed to verify the experimental group results. A nomogram was ultimately constructed with the R package. Our data revealed a correlation between the levels of immune cell infiltration and either the DHRS1 gene copy numbers or mRNA levels in HCC. Second, we generated a signature based on the 6 DHRS1-related immunomodulators (KDR, TNFRSF4, CD276, TNFSF4, SLAMF6, and SIGLEC9). We postulate that the generated risk scores would serve as an independent indicator of HCC prognosis, with an area under the receiver operating characteristic curve for the risk score of 0.743. We further established external validation sets to reconfirm the predictive validity of the risk score. Finally, a prognostic nomogram and calibration curve were created. The DHRS1 gene may exert an impact on HCC immunity. We posit that the nominated immune signature based on DHRS1-associated immunomodulators could constitute a promising prognostic biomarker in HCC.