A deeper mechanistic understanding of tumour angiogenesis regulation is needed to improve current anti-angiogenic therapies. Here we present evidence from systems-based miRNA analyses of large-scale patient data sets along with in vitro and in vivo experiments that miR-192 is a key regulator of angiogenesis. The potent anti-angiogenic effect of miR-192 stems from its ability to globally downregulate angiogenic pathways in cancer cells through regulation of EGR1 and HOXB9. Low miR-192 expression in human tumours is predictive of poor clinical outcome in several cancer types. Using 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) nanoliposomes, we show that miR-192 delivery leads to inhibition of tumour angiogenesis in multiple ovarian and renal tumour models, resulting in tumour regression and growth inhibition. This anti-angiogenic and anti-tumour effect is more robust than that observed with an anti-VEGF antibody. Collectively, these data identify miR-192 as a central node in tumour angiogenesis and support the use of miR-192 in an anti-angiogenesis therapy.

The global burden of hepatitis B virus (HBV) infection is profound, and represents a public health threat as chronic infection can lead to liver cirrhosis, hepatocellular carcinoma, and death. The risk factors for chronic hepatitis B-related liver disease differ according to HBV endemicity, hepatitis B e-antigen seropositivity, and viral load. It is important to identify these risk factors and start antiviral treatment at an appropriate time according to current guidelines. The most crucial step in reducing HBV infection is prevention in infancy or early childhood, as infection at an early stage may lead to chronicity. South Korea was formerly an HBV-endemic area, but the epidemiology of HBV infection was changed by the introduction of vaccination in 1983 and nationwide immunization in 1995. The government and the private sector made efforts to reduce the prevalence of HBV infection, and Korea is on target to meet the World Health Organization goal of eliminating viral hepatitis by 2030. To eliminate hepatitis worldwide, the costs of antiviral treatment to prevent perinatal HBV transmission in pregnant women with high viremia should be covered by a national program, and strategies to reduce the prevalence of HBV infection in immigrant populations are needed.

Han Ah Lee, Joon Young Jung, Young-Sun Lee, Young Kul Jung, Ji Hoon Kim, Hyonggin An, Hyung Joon Yim, Yoon Tae Jeen, Jong Eun Yeon, Kwan Soo Byun, Soon Ho Um, and Yeon Seok Seo. Gut and Liver 2021;15:599-605. https://doi.org/10.5009/gnl20171

The expression of chemokine receptor CX₃CR1 is related to migration and signaling in cells of the monocyte-macrophage lineage. The precise roles of CX₃CR1 in the liver have been investigated but not clearly elucidated. Here, we investigated the roles of CX₃CR1 in hepatic macrophages and liver injury. Hepatic and splenic CX₃CR1^lowF4/80^low monocytes and CX₃CR1^lowCD16⁻ monocytes were differentiated into CX₃CR1^highF4/80^high or CX₃CR1^highCD16⁺ macrophages by co-culture with endothelial cells. Moreover, CX₃CL1 deficiency in human umbilical vein endothelial cells (HUVECs) attenuated the expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), whereas recombinant CX₃CL1 treatment reversed this expression in co-cultured monocytes. Upon treatment with clodronate liposome, hepatic F4/80^high macrophages were successfully depleted at day 2 and recovered similarly in CX₃CR1^+/GFP and CX₃CR1^GFP/GFP mice at week 4, suggesting a CX₃CR1-independent replacement. However, F4/80^high macrophages of CX₃CR1^+/GFP showed a stronger pro-inflammatory phenotype than CX₃CR1^GFP/GFP mice. In clodronate-treated chimeric CX₃CR1^+/GFP and CX₃CR1^GFP/GFP mice, CX₃CR1⁺F4/80^high macrophages showed higher expression of IL-1β and TNF-α than CX₃CR1⁻F4/80^high macrophages. In alcoholic liver injury, despite the similar frequency of hepatic F4/80^high macrophages, CX₃CR1^GFP/GFP mice showed reduced liver injury, hepatic fat accumulation, and inflammatory responses than CX₃CR1^+/GFP mice. Thus, CX₃CR1 could be a novel therapeutic target for pro-inflammatory macrophage-mediated liver injury.