MRPL48 is a novel prognostic and predictive biomarker of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent forms of cancer and poses a threat to the health and survival of humans. Mitochondrial ribosomal protein L48 (MRPL48) belongs to the mitochondrial ribosomal protein family, which participates in energy production. Studies have shown that MRPL48 can predict osteosarcoma incidence and prognosis, as well as promotes colorectal cancer progression. However, the role of MRPL48 in HCC remains unknown. METHODS: TCGA, GEO, HCCDB, CPTAC, SMART, UALCAN, Kaplan-Meier plotter, cBioPortal, and MethSurv were performed for bioinformatics purposes. Quantitative RT-PCR, immunoblotting, and functional studies were conducted to validate the methodology in vitro. RESULTS: MRPL48 was greatly overexpressed in HCC tissues, compared with healthy tissue, which was subsequently demonstrated in vitro as well. The survival and regression analyses showed that MRPL48 expression is of significant clinical prognostic value in HCC. The ROC curve and nomogram analysis indicated that MRPL48 is a powerful predictor of HCC. MRPL48 methylation was adversely associated with the expression of MRPL48, and patients with a low level of methylation had poorer overall survival than those with a high level of methylation. GSEA showed that the expression of the MRPL48 was correlated with Resolution of Sister Chromatid Cohesion, Mitotic Prometaphase, Retinoblastoma Gene in Cancer, RHO Gtpases Activate Formins, Mitotic Metaphase and Anaphase, and Cell Cycle Checkpoints. An analysis of immune cell infiltration showed a significant association between MRPL48 and immune cell infiltration subsets, which impacted the survival of HCC patients. Additionally, MRPL48 knockdown reduced HCC cell proliferation, migration, and invasion in vitro. CONCLUSIONS: We demonstrated that MRPL48 expression may be associated with HCC development and prognosis. These findings may open up new research directions and opportunities for the development of HCC treatments.

Isolated traumatic gallbladder injury: A case report.

BACKGROUND: Isolated gallbladder injury (GI) (IGI) directly induced by abdominal trauma is rare. Symptoms, indications, and imaging examinations of IGI are frequently non-specific, posing tremendous diagnostic challenges, which are simple to overlook and may have severe implications. Improving doctors' understanding of gallbladder injury (GI) facilitates early detection and decreases the likelihood of severe consequences, including death. CASE SUMMARY: We report a case of IGI caused by blunt violence (after falling from three meters with the umbilicus as the stress point) and performed laparoscopic repair of the gallbladder rupture, which helps clinicians understand IGI and reduce the severe consequences of delayed diagnosis. Through extensive medical history and dynamic abdominal ultrasound evaluation, doctors can identify GI early and begin surgery, thereby decreasing the devastating repercussions of delayed diagnosis. CONCLUSION: This article aims to improve clinicians' understanding of IGI and propose a method for the diagnosis and treatment of GI.

Receptor-Interacting Protein Kinase 1 Promotes Cholangiocarcinoma Proliferation And Lymphangiogenesis Through The Activation Protein 1 Pathway.

PURPOSE: Receptor-interacting protein kinase 1 (RIPK1) is an important upstream regulator of multiple cell signaling pathways including inflammatory signals. RIPK1 is reported to be closely associated with the prognostic implications of cancer, especially epithelial tumors. But its role in proliferation and lymphangiogenesis in cholangiocarcinoma (CCA) remains unclear and requires further investigation. PATIENTS AND METHODS: Expression of RIPK1 in human CCA tissues and CCA cell lines (QBC939, HUH28 and CCPL-1) was measured using qPCR, immunoblotting and immunohistochemistry. Silencing of RIPK1 was achieved by transduction of CCA cells via lentiviral plasmids (LV3-H1/GFP&Puro) encapsulating RIPK1 shRNA (LV-shRIPK1) or negative control shRNA (LV-shNC), and puromycin was used to select stable colonies. Proliferation and lymphangiogenesis were assessed in vitro by CCK-8 and matrigel-based tube formation assays, respectively. Activity of the activation protein-1 (AP-1) was evaluated by double-luciferase reporter gene assay. Protein expression of JNK, P38MAPK, ERK1/2, AP-1, P-AP-1, E-cadherin, N-cadherin and vascular endothelial growth factor-C (VEGF-C) was measured by immunoblotting or ELISA. An orthotopic CCA model in null mice was generated by transplanting QBC939 LV-shRIPK1, LV-shNC and control cells to further evaluate the role of RIPK1 on lymphangiogenesis in vivo. Immunohistochemistry was utilized to evaluate the expression of RIPK1 and VEGF-C, and tumor lymphatic vessels in the CCA model mice. RESULTS: Upregulated expression of RIPK1 in CCA tissues was closely related to tumor size, lymph node metastasis and poor prognosis. RIPK1 promoted proliferation and lymphangiogenesis in CCA cells, and regulated the activation of JNK and P38MAPK-mediated AP-1/VEGF-C pathway. Finally, in vivo animal experiments in the orthotopic CCA mouse model further confirmed the function of RIPK1 in lymphangiogenesis. CONCLUSION: This is the first report demonstrating the role of RIPK1 in proliferation and lymphangiogenesis through the MAPK (JNK and P38MAPK)- AP-1 pathway in CCA.

HBx inhibits HMGB1 expression and active oxygen production in LO2 cells through the NF-κB signaling pathway.

Hepatitis B virus (HBV) infection is one of major causes of various kinds of liver diseases. Among the four open reading frames (ORFs) of the HBV genome, the X region of HBV encodes HBx protein, which plays an important regulatory role in HBV infection. NF-κB and high-mobility group protein box1 (HMGB1) are potentially able to enhance the scavenging activity of host cells against foreign microorganisms. The present study focuses on the effect of HBx on the expression of HMGB1 in vitro. First, the lentiviral vector was used to induce the overexpression of HBx protein in LO2 cells (a normal hepatocyte cell line). Then, NF-κB activity, HMGB1 expression and the production of ROS were detected by Western blot and DCFH-DA (ROS detector) staining. Afterward, rotenone and LPS, which are activors of ROS and NF-κB, respectively, were used to stimulate HBx-overexpressing cells. Then, the expression differentiation of HMGB1 and ROS or the activity alternation of NF-κB was detected again. HBx inhibited the activity of NF-κB, inhibited the expression of HMGB1 and inhibited the production of ROS. The stimulation study with retenone or LPS suggested that there were mutual regulations between NF-κB and HMGB1. HBx inhibits the expression of HMGB1 and the generation of ROS via the NF-κB signaling pathway.