Ligand-activated liver X receptor α (LXRα) upregulates the expression of hepatic lipogenic genes, which leads to triglyceride (TG) accumulation, resulting in nonalcoholic fatty liver disease (NAFLD). Thus, LXRα regulation may provide a novel therapeutic target against NAFLD. However, histone methylation-mediated epigenetic regulation involved in LXRα-dependent lipogenesis is poorly understood. In this study, we investigated the functional role of the histone demethylase Jumonji domain-containing protein 2B (JMJD2B) in LXRα-dependent lipogenesis. JMJD2B expression level was upregulated in HepG2 cells treated with LXRα agonist T0901317 or palmitate and the liver of mice administered with T0901317 or fed a high-fat diet. Knockdown of JMJD2B using siRNA abrogated T0901317-induced LXRα-dependent lipogenic gene expression and lowered intracellular TG accumulation. Conversely, overexpression of JMJD2B in HepG2 cells upregulated the expression of LXRα-dependent lipogenic genes, in line with increased intracellular TG levels. JMJD2B overexpression or T0901317 treatment induced the recruitment of JMJD2B and LXRα to LXR response elements (LXRE) in the promoter region of LXRα-target gene and reduced the enrichment of H3K9me2 and H3K9me3 in the vicinity of the LXRE. Furthermore, JMJD2B enhanced T0901317 or LXRα-induced transcriptional activities of reporters containing LXRE. A co-immunoprecipitation assay revealed that JMJD2B interacted with activated LXRα. Moreover, overexpression of JMJD2B in mice resulted in upregulation of hepatic LXRα-dependent lipogenic genes, consistent with development of hepatic steatosis. Taken together, these results indicate that JMJD2B plays a role in LXRα-mediated lipogenesis via removing the repressive histone marks, H3K9me2 and H3K9me3, at LXRE, which might contribute to hepatic steatosis.

Correct temporal and spatial control of actin dynamics is essential for the cytotoxic T cell effector function against tumor cells. However, little is known whether actin engineering in tumor-targeted T cells can enhance their antitumor responses, thereby potentiating the adoptive T cell therapy. Here, we report that TAGLN2, a 22-KDa actin-stabilizing protein which is physically associated with lymphocyte function-associated antigen-1 (LFA-1), potentiates the OTI TCR CD8⁺ T cells to kill the intercellular adhesion molecule-1 (ICAM-1)-positive/OVA-presenting E0771 cells, but not ICAM-1-negative OVA-B16F10 cells, suggesting an ‘inside-out’ activation of LFA-1, which causes more efficient immunological synapse formation between T cells and tumor cells. Notably, recombinant TAGLN2 fused with the protein transduction domain (TG2P) overcame the disadvantages of viral gene delivery, leading to a significant reduction in tumor growth in mice. TG2P also potentiated the CD19-targeted, chimeric antigen receptor (CAR)-modified T cells to kill Raji B-lymphoma cells. Our findings indicate that activating the TAGLN2–actin–LFA-1 axis is an effective strategy to potentiate the adoptive T-cell immunotherapy.

Porcine circovirus type 2 (PCV2) is the causative agent of postweaning multisystemic wasting syndrome (PMWS) in pigs. Replicase (Rep) proteins are considered essential for viral replication. Capsid (Cap) protein is the primary immunogenic protein that induces protective immunity. Little is known about comparison on the immunogenicity of PCV2 Rep and Cap fusion protein and Cap protein. In the present study, recombinant baculoviruses expressing the Rep-Cap fusion protein (Bac-Rep-Cap) and the Cap protein (Bac-Cap) of PCV2 were constructed and confirmed with western blot and indirect fluorescence assay. Immunogenicities of the two recombinant proteins were tested in mice. The titers of antibodies were determined with a PCV2-specific enzyme-linked immunosorbent assay (ELISA) and a serum neutralization assay. The IFN-γ response of immunized mice was measured by ELISA. The mice immunized with the Bac-Rep-Cap and Bac-Cap successfully produced Cap-specific immunoreaction. The mice immunized with the Bac-Cap developed higher PCV2-specific neutralizing antibody titers than mice injected with the Bac-Rep-Cap. IFN-γ in the Bac-Rep-Cap group was increased compared to those in the Bac-Cap group. Vaccination of mice with the Bac-Rep-Cap showed significantly decreased protective efficacy compared to the Bac-Cap. Our findings will indubitably not only lead to a better understanding of the immunogenicity of PCV2, but also improved vaccines.

Sargassum horneri (SH) and Ulva australis (UA) are marine waste resources that cause environmental and economic problems when entering or multiplying the coastal waters of Jeju Island. We analyzed their anti-diabetic efficacy to assess their reusability as functional additives. The alpha-glucosidase inhibitory activity of SH and UA extracts was confirmed, and the effect of UA extract was higher than that of SH. After the induction of insulin-resistant HepG2 cells, the effects of the two marine extracts on oxidative stress, intracellular glucose uptake, and glycogen content were compared to the positive control, metformin. Treatment of insulin-resistant HepG2 cells with SH and UA resulted in a concentration-dependent decrease in oxidative stress and increased intracellular glucose uptake and glycogen content. Moreover, SH and UA treatment upregulated the expression of IRS-1, AKT, and GLUT4, which are suppressed in insulin resistance, to a similar degree to metformin, and suppressed the expression of FoxO1, PEPCK involved in gluconeogenesis, and GSK-3β involved in glycogen metabolism. The oral administration of these extracts to rats with streptozotocin-induced diabetes led to a higher weight gain than that in the diabetic group. Insulin resistance and oral glucose tolerance are alleviated by the regulation of blood glucose. Thus, the SH and UA extracts may be used in the development of therapeutic agents or supplements to improve insulin resistance.

Current research highlights the use of natural products or phytochemicals as drugs and functional additives to treat obesity with few side effects. Sargassum horneri (SH) and Ulva australis (UA) are marine waste resources on Jeju Island, Republic of Korea. In this study, we analyzed their antioxidant and anti-obesity efficacies to confirm their potential as functional additives. We prepared SH and UA extracts using 80% ethanol and observed that free radical scavenging activity and total phenol content were high in SH extracts, and total flavonoid content was elevated in UA extracts. Additionally, 3T3-L1 cells were treated with SH and UA extracts, and the ability of the extracts to inhibit adipocyte differentiation was examined using Oil Red O staining and analysis of neutral fat content. We confirmed that the mRNA expression of the C/EBPα, PPARγ, and SREBP1c genes that act on adipocyte differentiation, and of FAS, a fatty acid synthase, was suppressed. Experiments in a mouse model of obesity showed that 12-week administration of a high-fat diet with 1% extract added to drinking water resulted in lower weight gain compared to the high-fat diet alone. These results suggest that SH and UA extracts have antioxidant properties and are effective in obesity prevention. Therefore, the two marine waste resources are potential functional additive candidates for preventing obesity.