Effect of Fenton oxidized lignin support on immobilized ß-glucosidase activity.

In this study, the Fenton oxidized lignin was prepared to investigate the effect of Fenton oxidation modification on the activity of lignin immobilized ß-glucosidase (ß-GL). The results demonstrated that Fenton oxidation could significantly improve the activity and stability of immobilized ß-GL. This is because the Fenton oxidation increased the electrostatic, hydrogen bonding, and hydrophobic forces between lignin and ß-GL, resulting in increased lignin adsorption onto ß-GL. The Fenton oxidation also changed the chemical structure of lignin, altering the lignin-ß-GL binding site and reducing the negative effect of lignin on the ß-GL catalytic domain. This research will improve understanding of the effect of Fenton lignin oxidation on immobilized ß-GL activity and expand the use of lignin in enzyme immobilization.

A multi-hit therapeutic nanoplatform for hepatocellular carcinoma: Dual stimuli-responsive drug release, dual-modal imaging, and in situ oxygen supply to enhance synergistic therapy.

Nanomedicine has been widely studied for the diagnosis and treatment of hepatocellular carcinoma (HCC). How to synthesize a nanoplatform possessing a high synergistic therapeutic efficacy remains a challenge in this emerging research field. In this study, a convenient all-in-one therapeutic nanoplatform (FTY720@AM/T7-TL) is designed for HCC. This advanced nanoplatform consists of multiple functional elements, including gold-manganese dioxide nanoparticles (AM), tetraphenylethylene (T), fingolimod (FTY720), hybrid-liposome (L), and T7 peptides (T7). The nanoplatform is negatively charged at physiological pH and can transit to a positively charged state once moving to acidic pH environments. The specially designed pH-responsive charge-reversal nanocarrier prolongs the half-life of nanodrugs in blood and improves cellular uptake efficiency. The platform achieves a sustained and controllable drug release through dual stimulus-response, with pH as the endogenous stimulus and near-infrared as the exogenous stimulus. Furthermore, the nanoplatform realizes in situ O2 generation by catalyzing tumor over-expressed H2O2, which alleviates tumor microenvironment hypoxia and improves photodynamic therapy. Both in vitro and in vivo studies show the prepared nanoplatform has good photothermal conversion, cellular uptake efficiency, fluorescence/magnetic resonance imaging capabilities, and synergistic anti-tumor effects. These results suggest that the prepared all-in-one nanoplatform has great potential for dual-modal imaging-guided synergistic therapy of HCC.

Immune checkpoint inhibitor therapy for malignant tumors in liver transplantation recipients: A systematic review of the literature.

BACKGROUND: Treatment for de novo or recurrent tumors of liver transplantation (LT) recipients is challenging and immune checkpoint inhibitor (ICI) is recently well developed and could be a potentially effective option for this population. There remains limited evidence on the safety and efficacy of ICI therapy in LT recipients. METHODS: A systematic literature search was conducted on PubMed database through April 1, 2022, to identify publications reporting ICI treatment for malignant tumors in LT recipients. We summarized the allograft rejection, mortality, and tumor response of ICI treatment. RESULTS: 24 articles with 41 LT recipients were identified. The age of LT recipients ranged from 14 to 78, 76.2% were male, 56.1% had recurrent HCC, and 87.8% received anti-PD-1 therapy. Allograft rejection occurred in 31.7% of patients, death was reported in 46.3% and 6 cases died secondary to allograft rejection. Progressive disease rate of this population was 48.8% and 10 patients responded to immunotherapy. Half of recipients with positive PD-L1 staining (4/8) experienced allograft rejection. CONCLUSIONS: ICI therapy has potential therapeutic value on malignant tumors for LT recipients, accompanied by a high rate of allograft rejection and mortality. PD-L1 expression, type of ICI, and immunosuppression agent should be taken into consideration before initiation of immunotherapy. Further studies are needed to optimize this anticancer treatment approach in these patients.

Obg-like ATPase 1 (OLA1) overexpression predicts poor prognosis and promotes tumor progression by regulating P21/CDK2 in hepatocellular carcinoma.

BACKGROUND: Obg-like ATPase 1 (OLA1) has been found to have a dual role in cancers. However, the relationship between OLA1 and hepatocellular carcinoma (HCC) remains unclear. RESULTS: High expression of OLA1 in HCC was detected in public datasets and clinical samples, and correlated with poor prognosis. Downregulation of OLA1 significantly inhibited the proliferation, migration, invasion and tumorigenicity of HCC cells. Mechanistically, GSEA showed that OLA1 might promote tumor progression by regulating the cell cycle and apoptosis. In addition, OLA1 knockdown resulted in G0/G1 phase arrest and high levels of apoptosis. OLA1 could bind with P21 and upregulate CDK2 expression to promote HCC progression. CONCLUSIONS: Overall, these findings uncover a role for OLA1 in regulating the proliferation and apoptosis of HCC cells. MATERIALS AND METHODS: The Cancer Genome Atlas and Gene Expression Omnibus datasets were analyzed to identify gene expression. Immunohistochemistry staining, western blot and real-time polymerase chain reaction were performed to evaluate OLA1 expression in samples. Cell count Kit-8, wound-healing, transwell and flow cytometry assays were used to analyze HCC cell progression. Subcutaneous xenotransplantation models were used to investigate the role of OLA1 in vivo. Coimmunoprecipitation was used to analyze protein interactions.

SKA3 Promotes tumor growth by regulating CDK2/P53 phosphorylation in hepatocellular carcinoma.

Spindle and kinetochore-related complex subunit 3 (SKA3) is a component of the spindle and kinetochore-related complexes and is essential for accurate timing of late mitosis. However, the relationship between SKA3 and hepatocellular carcinoma (HCC) has not yet been fully elucidated. Gene expression omnibus (GEO) (GSE62232, GSE45436, GSE6764, and GSE36376) and The Cancer Atlas (TCGA) datasets were analyzed to identify differential expression genes. Cell proliferation ability was analyzed using Cell Counting Kit-8 (CCK8) assay and plate clone formation assay, while scratch wound healing assay and transwell assay were used to analyze cell invasion. The role of SKA3 in vivo was explored using subcutaneous xenotransplantation model and lung metastasis model. Bioinformatics analysis found that hepatocellular carcinoma patients with high levels of expression of SKA3 have a poor prognosis. Similarly, immunohistochemical staining of 236 samples of tumors also found higher SKA3 expression in them, than in adjacent normal liver tissues. Significant levels of inhibition of in vivo and in vitro tumor proliferation and invasion result from the downregulation of SKA3. Mechanistically, SKA3 was found to affect tumor progression through the cell cycle and P53 signaling pathway as shown by the gene enrichment analysis (GSEA). G2/M phase arrest and severe apoptosis was also found to result from SKA3 knockdown, as shown by the inhibition of CDK2/p53 phosphorylation together with downregulation of BAX/Bcl-2 expression in HCC cells. Overall, these findings uncover the role of SKA3 in regulating the apoptosis and proliferation of hepatocellular carcinoma cells. This study was able to uncover new information on the tumorigenesis mechanism in hepatocellular carcinoma.

Exportin-T promotes tumor proliferation and invasion in hepatocellular carcinoma.

Exportin-T (XPOT) belongs to the RAN-GTPase exportin family that mediates export of tRNA from the nucleus to the cytoplasm. Up-regulation of XPOT indicates poor prognosis in breast cancer patients. However, the correlation between XPOT and hepatocellular carcinoma (HCC) remains unclear. Here, we found that high expression of XPOT in HCC indicated worse prognosis via bioinformatics analysis. Consistently, immunohistochemical staining of 95 pairs of tumors and adjacent normal liver tissues (ANLT) also showed up-regulation of XPOT. Small interfering (si) RNA transfection was used to down-regulate XPOT in HepG2 and 7721 cell lines. Cell Counting Kit-8 (CCK8) assays were performed to analyze cell proliferation. Cell migration and invasion were measured by scratch wound healing assays and migration assays. Subcutaneous xenograft models were using to explore the role of XPOT in tumor formation in vivo. Down-regulation of XPOT significantly inhibited tumor proliferation and invasion in vitro and vivo. Gene set enrichment analysis (GSEA) results indicated that XPOT may affect tumor progression through cell cycle and ubiquitin-mediated proteolysis. Furthermore, knockdown of XPOT caused a block in G0/G1 phase as evidenced by down-regulation of cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), CyclinA1 (CCNA1), CyclinB1 (CCNB1), CyclinB2 (CCNB2), and CyclinE2 (CCNE2) in HCC cells. In conclusion, our findings indicate that XPOT could serve as a novel biomarker for prognoses and a potential therapeutic target for patients with HCC.

Uridine-cytidine kinase 2 upregulation predicts poor prognosis of hepatocellular carcinoma and is associated with cancer aggressiveness.

Patients with advanced hepatocellular carcinoma (HCC) continue to have a dismal prognosis. Potential biomarkers to determine prognosis and select targeted therapies are urgently needed for patients with HCC. This study aimed to elucidate the role of UCK2 in HCC prognosis and tumor progression. We performed a screen of public databases to identify functional genes associated with HCC tumorigenesis, progression, and outcome. We identified uridine-cytidine kinase 2 (UCK2) as a gene of interest for further study. UCK2 promoting HCC aggressiveness was demonstrated by evaluation of clinical samples, in vitro experiments, in vivo tumorigenicity, and transcript analysis. UCK2 expression was generally elevated in HCC and was significantly correlated with poor survival and inferior clinicopathological characteristics of HCC patients. A multivariate analysis revealed that high UCK2 expression was an independent factor for poor prognosis. In HCC cell lines, UCK2 knockdown suppressed cell migration and invasion and inhibited cell proliferation, while UCK2 overexpression had an opposite effect. Animal model experiments confirmed that knockdown of UCK2 suppressed tumor growth in vivo. The bioinformatics analysis demonstrated that UCK2 might associated with metabolsim, splicesome, and adherens junction. UCK2 is highly associated with HCC malignant behavior and is a potential prognostic predictor for HCC patients in the clinic.

Exosome-related lncRNAs as predictors of HCC patient survival: a prognostic model.

OBJECTIVES: Accumulating evidence suggests that long non-coding RNA (lncRNA) may affect hepatocellular carcinoma (HCC) progression. However, the mechanism remains unclear. Previous studies have shown that exosomes may promote tumor progression by transporting proteins. Our study aimed to determine the prognostic value of lncRNAs in HCC and the underlying mechanism. METHODS: A dataset comprising a HCC cohort of 364 patients from The Cancer Genome Atlas (TCGA) was analyzed to identify lncRNAs with prognostic value. Co-expression and competing endogenous RNA (ceRNA) networks were constructed to investigate the mechanism of exosome-related lncRNAs. To confirm the bioinformatics analysis results, 95 pairs of clinical samples were evaluated by digoxigenin-labeled chromogenic in situ hybridization (CISH). RESULTS: Five lncRNAs (CTD-2116N20.1, AC012074.2, RP11-538D16.2, LINC00501 and RP11-136I14.5) with significant differences were identified (P<0.001). A prognostic nomogram was constructed with a C-index of 0.701. The co-expression and ceRNA networks showed possible mechanisms for CTD-2116N20.1 and RP11-538D16.2. The CISH results confirmed that CTD-2116N20.1 and RP11-538D16.2 were correlated with a poor prognosis for HCC patients. CONCLUSION: Our findings provide an independent and effective prognostic model to predict the survival rate of HCC patients. RP11-538D16.2 and CTD-2116N20.1 are highlighted as important exosome-related lncRNAs.