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Matrine and glycyrrhizin are representative active ingredients of traditional Chinese medicine (TCM) used in clinical practice. Studies have demonstrated that matrine has antitumor pharmacological effects and that glycyrrhizin protects liver function. However, the potential bioactive compounds and mechanisms remain unknown, as well as whether they have synergistic effects in killing cancer cells and protecting liver cells. To investigate the synergistic effects and mechanism of matrine combined with glycyrrhizin in hepatocellular carcinoma (HCC) treatment, we used both network pharmacology and bioinformatics analyses. First, the chemical gene interaction information of matrine and glycyrrhizin was obtained from the PubChem database. The pathogenic genes of HCC were accessed from five public databases. The RNA sequencing data and clinical information of HCC patients were downloaded from The Cancer Genome Atlas (TCGA). Next, the overlapping genes among the potential targets of matrine and glycyrrhizin and HCC-related targets were determined using bioinformatics analysis. We constructed the drug-target interaction network. Prognosis-associated genes were acquired through the univariate Cox regression model and Lasso-Cox regression model. The results were verified by the International Cancer Genome Consortium (ICGC) database. Finally, we predicted the immune function of the samples. The drug-target interaction network consisted of 10 matrine and glycyrrhizin targets. We selected a Lasso-Cox regression model consisting of 3 differentially expressed genes (DEGs) to predict the efficacy of the combination in HCC. Subsequently, we successfully predicted the overall survival of HCC patients using the constructed prognostic model and investigated the correlation of the immune response. Matrine and glycyrrhizin have synergistic effects on HCC. The model we obtained consisted of three drug-target genes by Lasso-Cox regression analysis. The model independently predicted the combined effect of matrine and glycyrrhizin in HCC treatment and OS, which will be helpful for guiding clinical treatment. The prognostic model was correlated with the immune cells and immune checkpoints of patients, which had an adjuvant effect on HCC immunotherapy. Matrine and glycyrrhizin can have therapeutic effects on HCC by promoting the production or enhancing the core gene activity in the drug network and improving the immune system function of patients.

Hepatocellular carcinoma (HCC) is currently the second leading cause of cancer-related deaths worldwide, with high morbidity and mortality. The clinical diagnosis of HCC mainly depends on imaging technology, such as ultrasound and computed tomography, and serum biomarkers, such as alpha-fetoprotein (AFP). However, HCC is still hard to diagnose at an early stage due to the low sensitivity of the above mentioned traditional methods. Typically, HCC is diagnosed at an advanced stage when limited treatment options are available. It is urgent to identify effective biomarkers for the early diagnosis of HCC. Increasing evidence uncovered ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), could be used in HCC diagnosis. The aim of this review is to summarize our understanding of circulating miRNAs, lncRNAs and circRNAs as fluid-based non-invasive biomarkers, and aiming at providing new insights into the diagnosis of HCC.

Background With the advancement of hepatocellular carcinoma (HCC) treatment technology, the treatment options for HCC patients have increased. However, due to high heterogeneity, among other reasons, the five-year survival rate of patients is still very low. Currently, gene expression prognostic models can suggest more appropriate strategies for the treatment of HCC. This study investigates the role of FAT10 in hepatocarcinogenesis and its underlying mechanism. Methods The expression of FAT10 was detected by immunohistochemical method using tissue arrays containing 4 specimens of patients with digestive cancer. The expression of FAT10 was determined by a tissue microarray which included 286 pairs of HCC samples and corresponding normal mucosae and was further confirmed by real-time polymerase chain reaction (PCR) and western blot. The Kaplan-Meier survival curve was used to determine the correlation of FAT10 expression with patients' recurrence and overall survival (OS) rate. In vivo, liver fibrosis, cirrhosis, and HCC models were established to assess the FAT10 expression. Moreover, FAT10 over-expressing cell lines were used to determine the molecular mechanism underlying the FAT10-induced cell proliferation and hepatocarcinogenesis by reporter gene measure, real-time PCR, and western blot. Based on TCGA database, signal pathways associated with FAT10 and HCC invasion and metastasis were analyzed by KEGG enrichment analyze. Results Overexpression of FAT10 in HCC was observed in this study compared with its expression in other digestive tumors. Clinicopathological analysis revealed that FAT10 expression levels were closely associated with tumor diameters and poor prognosis of HCC. This study also confirmed through in vivo experiments that the expression of FAT10 in liver fibrosis, cirrhosis, and HCC gradually increases. Further study revealed that forced FAT10 expression enhanced the growth ability of HCC cells and mediated the degradation of the critical anti-cancer protein p53, which led to carcinogenesis. Finally, 9 signal pathways related to HCC metastasis were obtained through bioinformatics analysis. Conclusions FAT10 may act as a proto-oncogene that facilitates HCC carcinogenesis by mediating p53 degradation, and the expression of FAT10 is negatively correlated with the prognosis of HCC patients. FAT10 is expected to become a potential combined target and prognostic warning marker for HCC treatment.

Background:There is a great controversy about lethal effect of Omicron Variant on vulnerable populations and the measure of full-open or zero community transmission policy. Thus, we designed an observational study to evaluate the outcomes of Omicron-infected patients with pancreatic & biliary cancer (the so-called “King of Cancer”) in order to provide potential evidence for the most appropriate strategy to counter Omicron transmission in Shanghai.Methods: Omicron infected patients with advanced pancreatic & biliary cancer were enrolled from April 15 to May 31, 2022. Four groups were set in this study: Group 1, Omicron-infected cancer patients (N=4); Group 2, non-infected cancer patients (N=4); Group 3, infected non-cancer-afflicted subjects (N=4); Group 4, non-infected non-cancer-afflicted subjects (N=4). On Day 0, 7 and 14 after infection, the blood samples were dynamically collected from all subjects. The primary endpoints were disease severity and survival. Results:By the endpoints in this observational study, Patients No. 2, 3 and 4 died separately at Day 11, 25 and 13 after viral infection, all of whom were patients with advanced cancer, with the death rate up to 75%. Group 1 presented an overall T cell exhaustion status compared with other groups with obviously lower T cell populations and higher B cell% and CD4+T/CD8+T ratio (PConclusions:For patients with advanced pancreatic & biliary cancer, the strict & comprehensive control strategy for COVID-19 epidemic in Shanghai provided a guarantee of low infection and death rate. Conclusively, this policy shall be persisted upon the consideration of the welfare of vulnerable populations.

Cholangiocarcinoma (CCA) is one of the most common hepatic and biliary malignancies. The overall five-year survival rate for cholangiocarcinoma is less than 15%. miR-28-5p has been reported to participate the development of various human cancer types. But whether miR-28-5p is associated with the clinical course of CCA patients has not been clarified. Herein, we observed that miR-28-5p was reduced in CCA tissues and predicts the poor prognosis of CCA patients. Treatment with the demethylating agent 5-aza-2’-deoxycytidine (5-AZA) restored miR-28-5p expression in CCA cell lines. Furthermore, up-regulated miR-28-5p inhibited CCA cells growth and metastasis. Mechanistically, miR-28-5p suppressed CCA cells growth and metastasis via directly targeting CD44 molecular. Specific CD44 special siRNA abrogated the discrepancy of the proliferation and metastasis capacity between miR-28-5p-overexpression CCA cells and their control cells, which further confirmed that CD44 was required in miR-28-5p-inhibited CCA cell growth and metastasis.

MicroRNAs (miRNAs) are involved in tumorigenesis, progression, recurrence, and drug resistance of hepatocellular carcinoma (HCC). However, few miRNAs have been identified and entered clinical practice. Herein, we report that microRNA (miR)-552 is upregulated in HCC tissues and has an important function in liver tumor-initiating cells (T-ICs). Functional studies revealed that a forced expression of miR-552 promotes liver T-IC self-renewal and tumorigenesis. Conversely, miR-552 knockdown inhibits liver T-IC self-renewal and tumorigenesis. Mechanistically, miR-552 downregulates phosphatase and tensin homolog (PTEN) via its mRNA 3′ UTR and activates protein kinase B (AKT) phosphorylation. Our clinical investigations elucidated the prognostic value of miR-552 in HCC patients. Furthermore, miR-552 expression determines the responses of hepatoma cells to sorafenib treatment. The analysis of patient cohorts and patient-derived xenografts (PDXs) further demonstrated that miR-552 may predict sorafenib benefits in HCC patients. In conclusion, our findings revealed the crucial role of the miR-552 in liver T-IC expansion and sorafenib response, rendering miR-552 an optimal target for the prevention and intervention in HCC.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide. MiR-371 has recently emerged as an important regulator in tumorigenesis, and may serve as a biomarker for malignant tumors. We transfected miR-371 or its inhibitor in two human HCC cell lines, then used 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, soft agar colony formation, and transwell migration assays to evaluate the effects on cell proliferation, migration, and invasion. We found that miR-371 was positively correlated with HCC metastasis and poor prognosis in the inflicted patients, and the high expression of miR-371 was promoted, whereas a low level of miR-371 depressed cell proliferation and invasion. We found PTEN to be a direct target of miR-371. The overexpression or knockdown of PTEN exhibited the opposite effects from those of miR-371 on cell proliferation and migration. Our study demonstrates that miR-371 promotes proliferation and metastasis in HCC by targeting PTEN. [BMB Reports 2019; 52(5): 312-317].

Background The effective evaluation of cholangiocarcinoma (CCA) is challenging due to a lack of accurate screening tools. Consequently, there is an urgent need to screen out effective biomarkers. Bioinformatics analysis on a substantial amount of transcriptomic data to screen biomolecules allows for the verification of histological samples, and can provide a new method for CCA biomolecule screening in diagnosis and prognosis. Methods EdgeR model was used to analyze The Cancer Genome Atlas (TCGA)-extracted CCA data set, and to determine the differential expression of mRNAs. Based on this, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to perform functional and pathway enrichment analysis. Subsequently, a protein interaction network was also established to identify the key differential node genes. Then, the previously determined differential genes were analyzed to establish a link between these genes and clinical prognosis. Finally, we used tissue samples to realize our results via IHC, Western blot and qRT-PCR. Results A total of 5,561 differential mRNAs were screened, including 3,473 upregulated genes and 2,088 downregulated genes. GO and KEGG enrichment analysis showed that the upregulated genes had significantly enriched cell adhesion, concentrated chromosomal motility, and microtubule motility. Downregulated genes were significantly enriched in heterologous metabolism and exosomes. Furthermore, we found upregulated genes were significantly enriched in the cancer pathways and cell cycle. Downregulated genes were enriched in the metabolic pathways and biosynthesis of antibiotics. Ten hub genes were screened out through the protein interaction network; among these, the AURKB and PLK1 genes were closely related to the clinical prognosis of patients. Results of the immunohistochemical staining, Western blot and qRT-PCR all showed that the expression of AURKB and PLK1 in cancer tissues was higher than that in the adjacent tissues, and this difference was statistically significant (P

Hepatocellular carcinoma (HCC) and primary pancreatic cancer are common malignant tumors of the digestive system. However, there are significant differences in treatment methods, medication types, and survival prognoses. For patients whose imaging findings suggest there to be a significant pancreatic mass and multiple masses in the liver, it can be easily misdiagnosed as a primary pancreatic cancer with liver metastasis in the clinic instead. Therefore, patients with a high likelihood of primary pancreatic cancer based on their clinical data, the pathological diagnosis should be confirmed through a needle biopsy as early as possible to avoid a misdiagnosis and possible mistreatment. In this study, our department admitted a patient with HCC that was characterized by a pancreatic occupation. The clinical data originally highly suggested primary pancreatic cancer with liver metastasis, but the final pathological puncture results had confirmed pancreatic metastasis of HCC. This case reminds us that a pathological biopsy should still be used as the final means of definite diagnosis and should be widely popularized for pancreatic nodules.

Transcatheter arterial chemoembolization (TACE) plays an important role in the treatment of unresectable liver cancer. We conducted this meta-analysis to compare the clinical safety and efficacy of conventional TACE (C-TACE) and drug-eluting beads (DEB)-TACE. A search for those procedures was performed using the PubMed, EMBASE, and Cochrane Library databases. A meta-analysis of patients who underwent C-TACE or DEB-TACE was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Of 334 studies, 30 were analyzed. The complete response rate, disease control rate, objective response rate, 3-year survival rate, and non-response rate were significantly higher in patients who underwent DEB-TACE than those in patients who underwent C-TACE. The 1-year survival rate, 2-year survival rate, 30-day mortality rate, complete response rate, disease control rate, complete necrosis rate, non-response rate, objective response rate, progressive disease rate, and recurrence did not differ significantly between patients who underwent C-TACE and patients who underwent DEB-TACE. Patients who undergo DEB-TACE might have a higher complete response rate, disease control rate, and 3-year survival rate than patients who undergo C-TACE. Safety did not differ significantly between C-TACE and DEB-TACE.

The encode-and-forward mechanism of network coding (NC) system, not only could provide increased network throughput, but also might get seriously vulnerable to pollution attacks. It has been an interesting and challenging topic how to design a secure, efficient and publicly verifiable homomorphic NC scheme. The existing cryptography-based NC schemes are grouped in either public key cryptosystem (PKC), or symmetric key cryptosystem (SKC). NC schemes in PKC naturally have public verifiability, but imply much more computation cost and longer operation delay. NC schemes in SKC have cheaper computations cost, but are dilemma about how to share the secret key to those intermediate nodes who might be malicious. Therefore, in this paper, we provide a new NC scheme that based on null-space HMAC with hierarchically sharing keys. The inner sharing keys are for the destination nodes to verify the integrity of the messages; the outer sharing keys are for the intermediate nodes to verify the integrity of the received packets. Our scheme shows a way how to balance the computation efficiency and the public verifiability for the NC system with a SKC scheme.