Search

Background: Oncolytic viral therapy is a promising method for tumor treatment. Currently, several oncolytic viruses (OVs) have been used as tumor therapy at different phases of research and clinical trials. OVs not only directly lyse tumor cells due to viral replication but also initiate host antitumor immune responses. Previous studies have primarily focused on how OVs activate adaptive immune responses in immune cells. However, the role of innate immune responses in tumors induced by OVs remains unclear. Methods: To determine the innate immune responses induced by vesicular stomatitis virus (VSV), the mutant VSVΔM51 strain was used for the infection and quantitative polymerase chain reaction (qPCR) was employed to measure the transcriptional levels of antiviral genes. The knockdown efficiency of RIG‐I was examined by qPCR. Viral titers were measured by plaque assays. Tumor models were established by intradermally implanting RIG‐I‐knockdown and control LLC cells into the flank of wild type C57BL/6J mice. When the tumors reached approximately 50mm3, they were infected with VSVΔM51 via intratumoral injections to examine its therapeutic effect. Results: Infection with VSVΔM51 triggered remarkable innate immune responses in several tumor cell lines through the cytoplasmic RIG‐I sensing pathway. Moreover, we found that intratumoral injection of VSVΔM51 effectively reduced tumor growth in murine LCC lung cancer model. Importantly, VSVΔM51‐induced antitumor therapy was more effective in murine LLC tumor model established using Rig‐I‐knockdown cells compared with the tumor model established using control cells. Conclusion: RIG‐I‐mediated innate immune signaling in tumor cells plays a negative role in regulating antitumor therapy with VSVΔM51 virus. [ABSTRACT FROM AUTHOR]

Efforts to develop disease-modifying treatments for Parkinson's disease (PD) have been hindered by the lack of animal models replicating all hallmarks of PD and the insufficient attention to extra-nigrostriatal regions pathologically critical for the prodromal appearance of non-motor symptoms. Among PD models, 6-hydroxydopamine (6-OHDA) infusion in mice has gained prominence since 2012, primarily focusing on the nigrostriatal region. This study characterized widespread tyrosine hydroxylase-positive neuron and fiber loss across the brain following a unilateral 6-OHDA (20 µg) infusion into the dorsal striatum. Our analysis integrates immunolabeling, brain clearing (iDISCO+), light sheet microscopy, and computational methods, including fMRI and machine learning tools. We also examined sex differences, disease progression, neuroinflammatory responses, and pro-apoptotic signaling in nigrostriatal regions of C57BL/6 mice exposed to varying 6-OHDA dosages (5, 10, or 20 µg). This comprehensive, spatiotemporal analysis of 6-OHDA-induced pathology may guide the future design of experimental PD studies and neurotherapeutic development.

MicroRNAs are small endogenously expressed RNA molecules which are involved in the process of silencing gene expression through translational regulation. The polycistronic miR-17-92 cluster is the first microRNA cluster shown to play a role in tumorigenesis. It has two other paralogs in the human genome, the miR-106b-25 cluster and the miR-106a-363 cluster. Collectively, the microRNAs encoded by these clusters can be further grouped based on the seed sequences into four families, namely the miR-17, the miR-92, the miR-18 and the miR-19 families. Over-expression of the miR-106b-25 and miR-17-92 clusters has been reported not only during the development of cirrhosis but also subsequently during the development of hepatocellular carcinoma. Members of these clusters have also been shown to affect the replication of hepatitis B and hepatitis C viruses. Various targets of these microRNAs have been identified, and these targets are involved in tumor growth, cell survival and metastasis. In this review, we first describe the regulation of these clusters by c-Myc and E2F1, and how the members of these clusters in turn regulate E2F1 expression forming an auto-regulatory loop. In addition, the roles of the various members of the clusters in affecting relevant target gene expression in the pathogenesis of hepatocellular carcinoma will also be discussed.