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Poor prognosis of hepatocellular carcinoma (HCC) patients is frequently associated with rapid tumor growth, recurrence and drug resistance. MT1G is a low-molecular weight protein with high affinity for zinc ions. In the present study, we investigated the expression of MT1G, analyzed clinical significance of MT1G, and we observed the effects of MT1G overexpression on proliferation and apoptosis of HCC cell lines in vitro and in vivo. Our results revealed that MT1G was significantly downregulated in tumor tissues, and could inhibit the proliferation as well as enhance the apoptosis of HCC cells. The mechanism study suggested that MT1G increased the stability of p53 by inhibiting the expression of its ubiquitination factor, MDM2. Furthermore, MT1G also could enhance the transcriptional activity of p53 through direct interacting with p53 and providing appropriate zinc ions to p53. The modulation of MT1G on p53 resulted in upregulation of p21 and Bax, which leads cell cycle arrest and apoptosis, respectively. Our in vivo assay further confirmed that MT1G could suppress HCC tumor growth in nude mice. Overall, this is the first report on the interaction between MT1G and p53, and adequately uncover a new HCC suppressor which might have therapeutic values by diminishing the aggressiveness of HCC cells.

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Single-wall carbon nanotubes (SWNTs) have attractive biochemical properties such as strong cell adhesion and protein absorption, which are very useful for a cell cultivation scaffold. In this study, collagen/SWNT-COOHs nanocomposite films composed of regenerated fish collagen and SWNT-COOHs (0, 0.5, 1.0 and 2.0 weight percent) were prepared by mixing solubilized pepsin-soluble collagen with solutions of SWNT-COOHs. Morphological observation by SEM indicated the homogenous dispersion of SWNT-COOHs in the collagen matrix. The application of FTIR confirmed that the process we applied to prepare the composites did not destroy the native structures of collagen and composites were crosslinked by D-ribose. The biocompatibility was evaluated in vitro using SD rat bone marrow stem cells (BMSCs). Compared with films without transforming growth factor beta 1 (TGF-β1), films with TGF-β1 had superior performance on promotion of cell growth. Compared with pure collagen film with TGF-β1, SWNT-containing films might promote cellular functions by adsorbing more growth factors. In conclusion, the study suggested that the collagen/SWNT-COOHs nanocomposite films with TGF-β1 were expected to be useful scaffolds in cartilage tissue engineering.

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The programmed death (PD) pathway is frequently present in the tumor microenvironment (TME) and suppresses tumor immunity by inhibiting the activity of tumor-infiltrating lymphocytes (TILs), particularly, CD8 + lymphocytes. PD immunotherapy involves stimulation of the immune response in the region surrounding the tumor but is insufficient to prevent tumor progression. Therefore, in this study, we examined the effects of combined PD immunotherapy with fractionated radiotherapy (RT) on antitumor immunity and tumor growth in lymphoma. The immune cell profiles of the TME, blood, and secondary lymphoid organs were determined 7 days after treatment. Four combination therapies were compared. The synergistic effects of αPD-1 mAb and fractionated RT on increased CD8 + lymphocytes in the TME, blood, and secondary lymphoid organs led to substantial tumor regression in mouse EL4 lymphoma, both locally and systemically. Fractionated RT for 4 days followed by αPD-1 mAb therapy was significantly superior to other schemes in terms of overall survival rates and curative rates in xenograft model mice. Our data indicated that substantial immune responses occurred following combination therapy with fractionated RT and αPD-1 mAb immunotherapy. Our findings provide important insights into the use of RT plus αPD-1 mAb as an efficacious combinatorial therapy.

Circular RNAs (circRNAs) are a class of highly stable and closed-loop noncoding RNA that are involved in the occurrence and development of hepatocellular carcinoma (HCC). However, little is known about the therapeutic role of circRNAs in HCC. We found that high circ_0058051 expression was negatively correlated with the prognosis of HCC patients. Circ_0058051 knockdown attenuated the proliferation and colony formation, meanwhile inhibited migration of HCC cells. Circ_0058051 may be used as a target for HCC gene therapy. We synthesized a novel small interfering RNA (siRNA) delivery system, PEG-PCL-PEI-C14-SPIONs (PPPCSs), based on superparamagnetic iron oxide nanoparticles (SPIONs). PPPCSs protected the siRNA of circ_0058051 from degradation in serum and effectively delivered siRNA into SMMC-7721 cells. Meanwhile, intravenous injection of the PPPCSs/siRNA complex could inhibit tumor growth in the subcutaneous tumor model. In addition, the nanocomposite is not toxic to the organs of nude mice. The above results show that PPPCSs/si-circ_0058051 complex may provide a novel and promising method of HCC treatment. Graphical abstract

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