Epithelial-Mesenchymal Transformation Promotes the Progression of Hepatocellular Carcinoma through NF-κB/MMP9 Axis.

BACKGROUND: Primary liver cancer (PHC) stands as one of the most prevalent malignant diseases in clinical settings. Studies have indicated that transcatheter arterial chemoembolization (TACE) treatment exhibits superior clinical outcomes, potentially increasing the complete necrosis rate in patients with PHC. A correlation exists between the clinical outcomes of TACE surgery and the process of epithelial-mesenchymal transition (EMT), yet the underlying mechanism remains a mystery. Hence, it is crucial to investigate the impact and mechanism of EMT on hepatocellular carcinoma (HCC). METHODS: Retrospectively, patients with advanced liver cancer who underwent TACE were selected and categorized into two groups based on the assessment of clinical efficacy: the effective group and the ineffective group. The expression levels of nuclear factor-kappa B (NF-κB), matrix metalloproteinase 9 (MMP9), Ki-67, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), Vimentin, E-cadherin, and N-cadherin in tumor tissues were evaluated using reverse transcription-polymerase chain reaction (RT-PCR). In vitro, Huh7 cells were cultured, and lentivirus infections were utilized to inhibit the overexpression of NF-κB and MMP9. The determination of EMT and cell viability was conducted through Cell Counting Kit-8 (CCK-8) assays, RT-PCR, and Western blot. RESULTS: Sixty patients diagnosed with advanced liver cancer were selected for the study. Based on their clinical outcomes, 30 patients with advanced hepatocellular carcinoma were categorized into the effective group, while the remaining 30 patients were categorized into the ineffective group. The results of the Western blot analysis indicated that, in comparison to the effective group, the expression levels of NF-κB, MMP9, Ki-67, Bcl-2, Vimentin, and N-cadherin were significantly higher in the tumor tissues of the ineffective group. Conversely, the expression of Bax and E-cadherin was notably lower in the effective group. Following the individual knockdown of NF-κB and MMP9, the cell experiments revealed a remarkable decrease in the expression levels of Ki-67, Bcl-2, Vimentin, and N-cadherin, whereas the expression of Bax and E-cadherin showed significant elevation (p < 0.05). Furthermore, there was a significant increase in cell viability and a decrease in cell apoptosis after the knockdown of NF-κB and MMP9. CONCLUSIONS: The NF-κB/MMP9 signaling axis serves as a pivotal regulator that fosters proliferation and impedes apoptosis in Huh7 cells by modulating the process of EMT.

A recognition of exosomes as regulators of epigenetic mechanisms in central nervous system diseases.

Exosomes, vesicular structures originating from cells, participate in the conveyance of proteins and nucleic acids. Presently, the centrality of epigenetic modifications in neurological disorders is widely acknowledged. Exosomes exert influence over various epigenetic phenomena, thereby modulating post-transcriptional regulatory processes contingent upon their constituent makeup. Consequently, the heightened attention directed toward exosomes as instigators of epigenetic alterations has burgeoned in recent years. Notably, exosomes serve as vehicles for delivering methyltransferases to recipient cells. More significantly, non-coding RNAs, particularly microRNAs (miRNAs), represent pivotal contents within exosomes, wielding the capacity to influence the expression of diverse factors within the cerebral milieu. The transfer of these exosomal contents amidst brain cells, encompassing neuronal cells and microglia, assumes a critical role in the genesis and progression of neurological disorders, also, this role is not limited to neurological disorders, it may deal with any human disease, such as cancer, and cardiovascular diseases. This review will concentrate on elucidating the regulation of exosome-induced epigenetic events and its subsequent ramifications for neurological diseases. A more profound comprehension of the involvement of exosome-mediated epigenetic regulation in neurological disorders contributes to a heightened awareness of the etiology and advancement of cerebral afflictions.

Sources, bioaccumulation, and toxicity mechanisms of cadmium in Chlamys farreri.

The Potentially toxic elements (PTEs) cadmium (Cd) is one of the most serious stressors polluting the marine environment. Marine bivalves have specific high enrichment capacity for Cd. Previous studies have investigated the tissue distribution changes and toxic effects of Cd in bivalves, but the sources of Cd enrichment, migration regulation during growth, and toxicity mechanisms in bivalves have not been fully explained. Here, we used stable-isotope labeling to investigate the contributions of Cd from different sources to scallop tissues. We sampled the entire growth cycle of Chlamys farreri, which is widely cultured in northern China, from juveniles to adult scallops. We found tissue variability in the bioconcentration-metabolism pattern of Cd in different bound states, with Cd in the aqueous accounting for a significant contribution. The accumulation pattern of Cd in all tissues during growth was more significant in the viscera and gills. Additionally, we combined a multi-omics approach to reveal a network of oxidative stress-induced toxicity mechanisms of Cd in scallops, identifying differentially expressed genes and proteins involved in metal ion binding, oxidative stress, energy metabolism, and apoptosis. Our findings have important implications for both ecotoxicology and aquaculture. They also provide new insights into marine environmental assessment and mariculture development.

Aptamer-mediated hollow MnO2 for targeting the delivery of sorafenib.

Sorafenib (SRF) presents undesirable effects in clinical treatment, due to the lack of targeting, poor water solubility, and obvious side effects. In this study, we constructed a novel nanodrug carrier system for accurate and efficient delivery of SRF, improving its therapeutic effects and achieving tumor-specific imaging. The hollow mesoporous MnO2 (H-MnO2) nanoparticles equipped with target substance aptamers (APT) on the surface were used to load SRF for the first time. The resulting H-MnO2-SRF-APT could specifically bound to glypican-3 (GPC3) receptors on the surface of hepatocellular carcinoma (HCC), rapidly undergoing subsequent degradation under decreased pH conditions in the tumor microenvironment (TME) and releasing the loaded SRF. In this process, Mn2+ ions were used for T1-weighted magnetic resonance imaging simultaneously. The in vitro cell experiments indicated that H-MnO2-SRF-APT showed much more effects on the inhibition in the proliferation of Huh7 and HepG2 HCC cells than that of the non-targeted H-MnO2-SRF and free SRF. Besides, the in vivo results further confirmed that H-MnO2-SRF-APT could effectively inhibit the growth of xenograft tumors Huh7 in the naked mouse with good biosafety. In conclusion, H-MnO2-SRF-APT could significantly enhance the therapeutic effect of SRF and is expected to be a new way of diagnosis and treatment of HCC.