Screening of Candidate Inflammatory Markers of Epithelial Cells in Hepatocellular Carcinoma Based on Integration Analysis of TCGA/ICGC Databases and Single-cell Sequencing.

BACKGROUND: Hepatocellular Carcinoma (HCC) is closely linked to inflammatory reactions, with chronic liver diseases acting as major risk factors. In the inflammatory microenvironment, repeated damage and repair of liver cells lead to genetic mutations, abnormal proliferation, and tumorigenesis. OBJECTIVE: This study aimed to investigate the expression profile of specific cell clusters under inflammatory stimulation in HCC and identify potential therapeutic drugs. METHODS: Comprehensive analysis of HCC transcriptome data and single-cell sequencing data from TCGA, ICGC, and GEO databases was conducted to explore the specific molecular mechanisms of epithelial cells. Virtual screening of natural compounds in the ZINC database and in vitro cell experiments were performed to identify drugs that regulate the expression of inflammatory factors in epithelial cells. RESULTS: Analysis of the single-cell dataset revealed cell clusters closely associated with HCC, notably Epithelial cells, Hepatocytes, MSC, and iPS cells, with Epithelial cells playing a pivotal role in HCC development. Further investigation of TCGA data unveiled 83 differentially expressed genes (DEGs) related to inflammatory responses in HCC. Intersection analysis of DEGs in epithelial cells and HCC DEGs identified 12 common DEGs, including ADRM1, ATP2B1, FZD5, GPC3, KIF1B, KLF6, LY6E, MET, NAMPT, SERPINE1, SPHK1, and SRI. Prognostic analysis revealed that CCL7, GPR132, ITGB8, PTAFR, SELL, and VIP were influential in the survival prognosis of HCC. A prognostic model based on the expression levels of these genes demonstrated an increased risk of HCC associated with higher differential expression of inflammatory response genes. Additionally, molecular dynamics simulations indicated that compounds NADH and Deferoxamine formed stable docking models with the inflammatory protein VIP, suggesting their potential as candidates for targeted therapy. CONCLUSION: Inflammatory factors CCL7, GPR132, ITGB8, PTAFR, SELL, and VIP influence the inflammatory cascade response in HCC epithelial cells, and their expression correlates with the survival prognosis of HCC patients. Interfering with VIP expression effectively suppresses proliferation, migration, and invasion of HCC cells, as well as inhibiting the occurrence of inflammatory cascade reactions, thus slowing down the progression of hepatocellular carcinoma. Furthermore, compounds NADH and Deferoxamine have the potential to target and bind to the inflammatory protein VIP, highlighting their relevance in potential HCC treatment.

EMP1 as a Potential Biomarker in Liver Fibrosis: A Bioinformatics Analysis.

Liver fibrosis is a wound-healing response to chronic injury, which may result in cirrhosis and liver failure. Studies have been carried on the mechanisms and pathogenesis of liver fibrosis. However, the potential cell-specific expressed marker genes involved in fibrotic processes remain unknown. In this study, we combined a publicly accessible single-cell transcriptome of human liver with microarray datasets to evaluate the cell-specific expression patterns of differentially expressed genes in the liver. We noticed that EMP1 (epithelial membrane protein 1) is significantly active not only in CCl4 (carbon tetrachloride)-treated mouse liver fibrosis but also in BDL (bile duct ligation)-induced liver fibrosis and even in human fibrotic liver tissues such as alcoholic hepatitis, NASH (nonalcoholic steatohepatitis), and advanced stage liver fibrosis. Furthermore, we demonstrated that EMP1 is a specific fibrotic gene expressed in HSCs (hepatic stellate cells) and endothelial cells using the Protein Atlas single-cell transcriptome RNA-sequencing clustering. Its expression was significantly elevated in fibrotic HSCs or CCl4 and NASH-induced fibroblasts. Previous research revealed that EMP1 plays a role in proliferation, migration, metastasis, and tumorigeneses in different cancers via a variety of mechanisms. Because HSC activation and proliferation are two important steps following liver injury, it would be interesting to investigate the role of EMP1 in these processes. All of this information suggested that EMP1 could be used as a novel fibrotic liver marker and a possible target in the future.

Repeated bacteremia and hepatic cyst infection lasting 3 years following pancreatoduodenectomy: A case report.

BACKGROUND: Simple hepatic cysts are commonly occurring lesions that are usually asymptomatic and require no treatment. Hepatic cyst infection, however, is considered a severe complication. We report a case of hepatic cyst infection following pancreatoduodenectomy with repeated fever lasting for almost 3 years, and two cysts were infected successively. CASE SUMMARY: A 72-year-old woman diagnosed with adenocarcinoma of duodenal papilla underwent pancreatoduodenectomy with Child reconstruction. She then suffered repeated occurrences of bacteremia and hepatic cyst infection for 3 years. Blood cultures were positive for Klebsiella pneumoniae and Escherichia coli a total of 7 times and 4 times, respectively. During the early stage, we suspected that postoperative reflux cholangitis was the cause of fever and bacteremia. Multiple cysts were observed, so it was difficult to determine which cyst was infected. Through repeat examination, we found the focus of infection, and we treated the patient with antimicrobials and performed percutaneous cyst drainage. The patient did not experience another cyst infection for more than 4 years. CONCLUSION: Biliary reconstruction inducing hepatic cyst infection is easily misdiagnosed as biliary reflux infection, Repeated imaging examination is a method for identifying the infected focus.

Identification of Therapeutic Targets and Prognostic Biomarkers among Genes from the Mediator Complex Family in the Hepatocellular Carcinoma Tumour-Immune Microenvironment.

BACKGROUND: Hepatocellular carcinoma (HCC) is predominant among all types of primary liver cancers characterised by high morbidity and mortality. Genes in the mediator complex (MED) family are engaged in the tumour-immune microenvironment and function as regulatory hubs mediating carcinogenesis and progression across diverse cancer types. Whereas research studies have been conducted to examine the mechanisms in several cancers, studies that systematically focused on the therapeutic and prognostic values of MED in patients with HCC are limited. METHODS: The online databases ONCOMINE, GEPIA, UALCAN, GeneMANIA, cBioPortal, OmicStudio, STING, Metascape, and TIMER were used in this study. RESULTS: The transcriptional levels of all members of the MED family in HCC presented an aberrant high expression pattern. Significant correlations were found between the MED1, MED6, MED8, MED10, MED12, MED15, MED17, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, and MED27 expression levels and the pathological stage in the patients with HCC. The patients with high expression levels of MED6, MED8, MED10, MED17, MED19, MED20, MED21, MED22, MED24, and MED25 were significantly associated with poor prognosis. Functional enrichment analysis revealed that the members of the MED family were mainly enriched in the nucleobase-containing compound catabolic process, regulation of chromosome organisation, and transcriptional regulation by TP53. Significant correlations were found between the MED6, MED8, MED10, MED17, MED19, MED20, MED21, MED22, MED24, and MED25 expression levels and all types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). B cells and MED8 were independent predictors of overall survival. We found significant correlations between the somatic copy number alterations of the MED6, MED8, MED10, MED20, MED21, MED22, MED24, and MED25 molecules and the abundance of immune infiltrates. CONCLUSIONS: Our study delineated a thorough landscape to investigate the therapeutic and prognostic potentials of the MED family for HCC cases, which yielded promising results for the development of immunotherapeutic drugs and construction of a prognostic stratification model.

MiR-20b-5p promotes hepatocellular carcinoma cell proliferation, migration and invasion by down-regulating CPEB3.

INTRODUCTION AND OBJECTIVES: This study aimed to explore the functional mechanism of the miRNA-20b-5p/cytoplasmic polyadenylation element binding protein 3 (miR-20b-5p/CPEB3) axis in hepatocellular carcinoma (HCC) so as to provide a new idea for targeted therapy of HCC. MATERIALS AND METHODS: Bioinformatics analysis was employed to obtain markedly differentially expressed miRNAs and mRNAs in The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset, so as to find target miRNA and its target mRNA. Real-time quantitative PCR was conducted to detect miR-20b-5p and CPEB3 mRNA expression. Western blot was performed to determine CPEB3 protein expression. Dual-luciferase reporter assay was carried out to verify the targeting relationship between miR-20b-5p and CPEB3. Cell counting kit-8 assay, wound healing assay, Transwell invasion assay and flow cytometry were conducted to evaluate the proliferation, migration, invasion and apoptosis of HCC cells. RESULTS: Bioinformatics analysis suggested that miR-20b-5p and CPEB3 were markedly highly and lowly expressed, respectively, in HCC tissue in TCGA-LIHC dataset. Over-expressing miR-20b-5p facilitated the proliferation, migration and invasion, and suppressed the apoptosis of HCC cells. Dual-luciferase reporter assay validated that there was a targeting relationship between miR-20b-5p and CPEB3. The inhibitory effect of CPEB3 over-expression on HCC cell proliferation, migration and invasion was reversed by over-expressing miR-20b-5p. CONCLUSIONS: The present study proved that miR-20b-5p promotes HCC cell proliferation, migration and invasion by inhibiting CPEB3 expression, which may provide a theoretical basis for the prognosis and treatment of HCC patients.

Exosomes function as nanoparticles to transfer miR-199a-3p to reverse chemoresistance to cisplatin in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a frequently seen malignant tumor globally. The occurrence of cisplatin (DDP) resistance is one of the main reasons for the high mortality of HCC patients. Therefore, it is of great theoretical significance and application value to explore the mechanism of chemotherapy resistance. Drug resistance can be modulated by exosomes containing mRNAs, micro RNAs (miRNAs) and other non-coding RNA (ncRNAs). Exosomal miR-199a-3p (Exo-miR-199a-3p) was subjected to extraction and verification. Whether exo-miR-199a-3p could make HCC cells sensitive to DDP in vitro was verified via flow cytometry, Cell Counting Kit-8 (CCK-8) assay, immunofluorescence assay and Transwell assay. Intravenous injection of exo-miR-199a-3p and intraperitoneal injection of DDP were carried out in vivo. Moreover, the possible targets of miR-199a-3p were screened through bioinformatics analysis, which were ascertained by Western blotting (WB). Then, miR-199a-3p levels in human normal liver epithelial cell line HL-7702 and HCC cell lines HuH7 and HuH7/DDP were elevated in a concentration-dependent manner. Exo-miR-199a-3p has abilities to adjust underlying targets and conjugate cells, to repress cells to invade, stimulate their apoptosis and abate their ability. Additionally, the caudal injection of exo-miR-199a-3p reversed the chemoresistance of tumors and slowed down their growth in the body owing to the up-regulation of miR-199a-3p and down-regulation of underlying target proteins in tumors. Finally, exo-miR-199a-3p was found to overturn the HCC's resistance to DDP, and it may function in DDP-refractory HCC therapy as an underlying option in the future.

Abdominal distension and diarrhea as the main symptoms of primary amyloidosis: A case report and literature review.

Amyloidosis is a systemic disease caused by the accumulation of extracellular protein into amyloid deposits. Due to the involvement of a variety of organs and tissues, the disease has no specific clinical features and a high rate of misdiagnosis. The present study describes one case of primary amyloidosis, as confirmed by biopsies of rectal and renal tissues using Congo red staining, demonstrating that abdominal distension and diarrhea were the main symptoms of disease. The current case is also discussed within the context of a review of the associated literature.