Genetically modified macrophage infusion has been proven to be a novel treatment for cancer. One of the most important processes in macrophage-based therapy is the efficient transfer of genes. HIV-1-derived lentiviruses were widely used as delivery vectors in chimeric antigen receptor T and NK cell construction. While macrophages are relatively refractory to this lentiviral vector transduction as a result of the myeloid-specific restriction factor SAMHD1, which inhibited the virion cycle through exhausting the dNTPs pool and degradating RNAs. An efficient macrophage transduction strategy has been developed via packaging the HIV-2 accessory protein Vpx into the virion. Vpx counteracts SAMHD1 through CRL4 (DCAF1) E3 ubiquitin ligase mediated SAMHD1 degradation, yet the influence by the introduction of Vpx on macrophage has not been fully evaluated. Here, we constructed the chimeric lentiviral vector HIV-1-Vpx and systematically analyzed the infection efficiency of this vector in time-dependent manner. Our results showed that the simplified chimeric virus exhibited dramatically enhanced infection in human macrophages compared to normal lentivirus. Moreover, transcriptome sequencing was performed to evaluate the cellular status after chimeric virus infection. The sequencing results indicated that Vpx introduction promoted macrophage remodeling towards a proinflammatory phenotype, without affecting classic M1/M2 cell surface markers. Our results suggest that the Vpx-containing lentivirus could be used as an ideal tool for the generation of genetically engineered macrophages with high gene transfer efficiency and poised proinflammatory gene sets, especially for solid tumor treatment.

Non-canonical nuclear factor kappa B (NF-κB) signaling pathway regulates many physiological and pathological processes, including liver homeostasis and diseases. Recent studies demonstrate that non-canonical NF-κB signaling pathway plays an essential role in hyperglycemia, non-alcoholic fatty liver disease, alcoholic liver disease, liver regeneration, liver injury, autoimmune liver disease, viral hepatitis, and hepatocellular carcinoma. Small-molecule inhibitors targeting to non-canonical NF-κB signaling pathway have been developed and shown promising results in the treatment of liver injuries. Here, the recent advances and future prospects in understanding the roles of the non-canonical NF-κB signaling pathways in the regulation of liver diseases are discussed.

The chronic liver diseases will slowly develop into liver fibrosis, cirrhosis, and even liver cancer if no proper control is performed with high efficiency. Up to now, the most effective treatment for end-stage liver diseases is liver transplantation. However, liver transplantation has the problems of donor deficiency, low matching rate, surgical complications, high cost, and immune rejection. These problems indicate that novel therapeutic strategies are urgently required. Mesenchymal stem cells (MSCs) are somatic stem cells with multidirectional differentiation potential and self-renewal ability. MSCs can secrete a large number of cytokines, chemokines, immunomodulatory molecules, and hepatotrophic factors, as well as produce extracellular vesicles. They alleviate liver diseases by differentiating to hepatocyte-like cells, immunomodulation, homing to the injured site, regulating cell ferroptosis, regulating cell autophagy, paracrine effects, and MSC-mitochondrial transfer. In this review, we focus on the main resources of MSCs, underlying therapeutic mechanisms, clinical applications, and efforts made to improve MSC-based cell therapy efficiency.