ABSTRACT
Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and is characterized by high mortality rates and a lack of effective therapeutic options. HCC cells undergo extensive metabolic reprogramming, including alterations in glycolytic, lipid, and amino acid metabolism, among other processes. These metabolic changes are often accompanied by widespread alterations in the epigenetic landscape, including DNA methylation, post-transcriptional modifications, non-coding RNA dysregulation, and histone modifications. A thorough understanding of how epigenetic modifications and metabolic reprogramming interact in HCC is critical for elucidating the mechanisms underlying hepatocarcinogenesis and developing new treatment approaches against HCC. In this review, we systematically introduce the molecular biological basis of each epigenetic modification and then summarize the latest research progress on the epigenetic regulation of metabolism in HCC, with the goal of linking these two frontier fields to provide novel insights into the treatment of HCC.
Yicheng Pu, Yue Lv, Zhen Wang et al.· Chinese Medical Journal· 0 citations
Abstract Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the destruction of pancreatic β cells, leading to lifelong insulin dependence and an increased risk of severe complications. Three-dimensional stem cells (3D SCs) culture systems have emerged as a superior alternative by more accurately mimicking the in vivo microenvironment and enhancing stemness maintenance, regenerative efficiency, and paracrine secretion. However, studies exploring the application of 3D SCs in T1D remain limited. Here, we developed a novel serum- and cytokine-free orbital-shaking system. It enables efficient and large-scale reprogramming of somatic cells into 3D embryonic-like stem cell spheroids (Sph-Es) characterized by robust pluripotency and improved safety. To enhance therapeutic utility, Sph-Es were irradiated and transduced with INS-expressing adenoviral vectors to generate Sph-R-Ins, allowing transient insulin production without permanent genomic modification. In STZ-induced T1D mice, Sph-R-Ins improved glycemic control and glucose tolerance and increased mouse insulin and C-peptide responses, indicating improved endogenous islet function. Donor-cell tracking analyses showed no pancreatic engraftment, supporting an indirect mode of action. Additional transcriptomic, immunological, and ex vivo studies indicated that the therapeutic benefit was accompanied by ECM-related signaling changes, reduced inflammatory infiltration, enhanced M2 macrophage polarization and Treg-associated immune regulation, improved metabolic signaling, and spheroid-derived paracrine support of islet function. Together, these findings establish a mechanically guided 3D stem cell–gene therapy platform with both endocrine and immunometabolic benefits in T1D.
