Liver cancer is a significant contributor to the cancer burden, and its incidence rates have recently increased in almost all countries. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is the second leading cause of cancer-related deaths worldwide. Because of the late diagnosis and lack of efficient therapeutic modality for advanced stages of HCC, the death rate continues to increase by ~2–3% per year. Circulating tumor cells (CTCs) are promising tools for early diagnosis, precise prognosis, and follow-up of therapeutic responses. They can be considered to be an innovative biomarker for the early detection of tumors and targeted molecular therapy. In this review, we briefly discuss the novel materials and technologies applied for the practical isolation and detection of CTCs in HCC. Also, the clinical value of CTC detection in HCC is highlighted.

Recurrence in hepatocellular carcinoma (HCC) after conventional treatments is a crucial challenge. Despite the promising progress in advanced targeted therapies, HCC is the fourth leading cause of cancer death worldwide. Radionuclide therapy can potentially be a practical targeted approach to address this concern. Rhenium-188 (¹⁸⁸Re) is a β-emitting radionuclide used in the clinic to induce apoptosis and inhibit cell proliferation. Although adherent cell cultures are efficient and reliable, appropriate cell-cell and cell-extracellular matrix (ECM) contact is still lacking. Thus, we herein aimed to assess ¹⁸⁸Re as a potential therapeutic component for HCC in 2D and 3D models. The death rate in treated Huh7 and HepG2 lines was significantly higher than in untreated control groups using viability assay. After treatment with ¹⁸⁸ReO₄, Annexin/PI data indicated considerable apoptosis induction in HepG2 cells after 48 h but not Huh7 cells. Quantitative RT-PCR and western blotting data also showed increased apoptosis in response to ¹⁸⁸ReO₄ treatment. In Huh7 cells, exposure to an effective dose of ¹⁸⁸ReO₄ led to cell cycle arrest in the G2 phase. Moreover, colony formation assay confirmed post-exposure growth suppression in Huh7 and HepG2 cells. Then, the immunostaining displayed proliferation inhibition in the ¹⁸⁸ReO₄-treated cells on 3D scaffolds of liver ECM. The PI3-AKT signaling pathway was activated in 3D culture but not in 2D culture. In nude mice, Huh7 cells treated with an effective dose of ¹⁸⁸ReO₄ lost their tumor formation ability compared to the control group. These findings suggest that ¹⁸⁸ReO₄ can be a potential new therapeutic agent against HCC through induction of apoptosis and cell cycle arrest and inhibition of tumor formation. This approach can be effectively combined with antibodies and peptides for more selective and personalized therapy.

The majority of monogenic liver diseases are autosomal recessive disorders, with few being sex-related or co-dominant. Although orthotopic liver transplantation (LT) is currently the sole therapeutic option for end-stage patients, such an invasive surgical approach is severely restricted by the lack of donors and post-transplant complications, mainly associated with life-long immunosuppressive regimens. Therefore, the last decade has witnessed efforts for innovative cellular or gene-based therapeutic strategies. Gene therapy is a promising approach for treatment of many hereditary disorders, such as monogenic inborn errors. The liver is an organ characterized by unique features, making it an attractive target for in vivo and ex vivo gene transfer. The current genetic approaches for hereditary liver diseases are mediated by viral or non-viral vectors, with promising results generated by gene-editing tools, such as CRISPR-Cas9 technology. Despite massive progress in experimental gene-correction technologies, limitations in validated approaches for monogenic liver disorders have encouraged researchers to refine promising gene therapy protocols. Herein, we highlighted the most common monogenetic liver disorders, followed by proposed genetic engineering approaches, offered as promising therapeutic modalities.

Background: The venoms of some scorpions are rich in bioactive components that may be used in the development and discovery of new antibacterial drugs. The venoms have many components, such as neurotoxins, salts, proteins and peptides with therapeutic properties, and can rapidly eliminate a broad range of bacteria. This study evaluated the anti-bacterial activity of Odontobuthus bidentatus’ crude venom against typical Gram-positive and negative bacteria, such as Staphylococcus aureus, Bacillus subtilis, and Escherichia coli. Methods: The antibacterial effects of the crude venom were evaluated using Minimal Inhibitory Concentration (MIC) and MTT assays and its IC50 value was determined, using GraphPad software. Results: The crude venom significantly inhibited the growth of both Gram-positive and negative bacteria. Also the MTT results showed that the crude venom significantly reduced the viability of E. Coli, S. Aureus, and B. Subtilis bacteria compared with that for the controls. The IC50 values of the venom for E.coli, S.aureus, and B.subtilis were 30.19, 17.64, and 24.13 µM, respectively. Conclusion: The findings suggest that the venom of O. bidentatus scorpion has antibacterial properties. Also, our results offer preliminary clues toward the development of new antibacterial agents and new drugs with high therapeutic potentials for use in animals and humans.

Background Hepatocellular carcinoma (HCC) is a deadly form of liver cancer with limited treatment options. Natural compounds, such as venom-derived peptides, have emerged as potential sources of anticancer agents. 3D cell models, which closely resemble the architectural characteristics of natural tumors, serve as an appropriate system for investigating the cytotoxic and apoptotic effects of scorpion venom on cancer cells. In this study, we investigated the apoptotic effects of low molecular weight peptides isolated from the venom of Odontobuthus bidentatus on HepG2 cells in a 3D cell culture model. Methods and Results The O. bidentatus venom was subjected to high-performance liquid chromatography (HPLC) for fractionation and purification of the low molecular weight peptides. Subsequently, the isolated peptides were evaluated for their impact on cell viability and apoptosis induction in HepG2 cells within a 3D cell culture system and were compared to crude venom. To create a 3D cell culture, HepG2 cells were enclosed within alginate hydrogel. Subsequently, the cytotoxic effects of scorpion venom were evaluated using MTT and neutral red uptake assays. Changes in the redox potential of HepG2 cells were assessed by measuring accumulated nitric oxide (NO) in the cell culture media, as well as levels of glutathione (GSH) and catalase activity. To determine the induction of apoptosis in cells treated with scorpion venom, various assays including alkaline comet assay, caspase-3 enzyme activity, and cytochrome c release were employed. Additionally, the expression of the pro-apoptotic gene BAX and the anti-apoptotic gene BCL-2 was evaluated using qRT-PCR. The results obtained from the MTT and neutral red uptake assays demonstrated that O. bidentatus crude venom and isolated fractions (5, 6, and 10) had cytotoxic effects on HepG2 cells in the 3D cell culture. The concentration of NO released into the culture media increased, while the levels of reduced glutathione and catalase decreased in a dose-dependent manner within the 3D culture. The findings from the caspase-3 enzyme activity, cytochrome c release assay, comet assay, and Bax/Bcl-2 gene expression ratio supported the conclusion that O. bidentatus scorpion venom induces apoptosis through the mitochondrial pathway. Conclusion This finding highlights the potential of scorpion venom-derived peptides as novel therapeutic agents for hepatocellular carcinoma.