Evolution of DS-1-like G8P[8] rotavirus A strains from Vietnamese children with acute gastroenteritis (2014-21): Adaptation and loss of animal rotavirus-derived genes during human-to-human spread.

Animal rotaviruses A (RVAs) are considered the source of emerging, novel RVA strains that have the potential to cause global spread in humans. A case in point was the emergence of G8 bovine RVA consisting of the P[8] VP4 gene and the DS-1-like backbone genes that appeared to have jumped into humans recently. However, it was not well documented what evolutionary changes occurred on the animal RVA-derived genes during circulation in humans. Rotavirus surveillance in Vietnam found that DS-1-like G8P[8] strains emerged in 2014, circulated in two prevalent waves, and disappeared in 2021. This surveillance provided us with a unique opportunity to investigate the whole process of evolutionary changes, which occurred in an animal RVA that had jumped the host species barrier. Of the 843 G8P[8] samples collected from children with acute diarrhoea in Vietnam between 2014 and 2021, fifty-eight strains were selected based on their distinctive electropherotypes of the genomic RNA identified using polyacrylamide gel electrophoresis. Whole-genome sequence analysis of those fifty-eight strains showed that the strains dominant during the first wave of prevalence (2014-17) carried animal RVA-derived VP1, NSP2, and NSP4 genes. However, the strains from the second wave of prevalence (2018-21) lost these genes, which were replaced with cognate human RVA-derived genes, thus creating strain with G8P[8] on a fully DS-1-like human RVA gene backbone. The G8 VP7 and P[8] VP4 genes underwent some point mutations but the phylogenetic lineages to which they belonged remained unchanged. We, therefore, propose a hypothesis regarding the tendency for the animal RVA-derived genes to be expelled from the backbone genes of the progeny strains after crossing the host species barrier. This study underlines the importance of long-term surveillance of circulating wild-type strains in order to better understand the adaptation process and the fate of newly emerging, animal-derived RVA among the human population. Further studies are warranted to disclose the molecular mechanisms by which spillover animal RVAs become readily transmissible among humans, and the roles played by the expulsion of animal-derived genes and herd immunity formed in the local population.

Detection of three independently-generated DS-1-like G9P[8] reassortant rotavirus A strains during the G9P[8] dominance in Vietnam, 2016-2018.

A rapid increase and dominance of G9P[8] Rotavirus A strains occurred in northern Vietnam between 2016 and 2018, during which period there appeared three G9P[8] strains possessing short RNA patterns. To understand how the first-ever G9P[8] strains possessing short RNA patterns were formed, next generation sequencing technology was used to examine the whole genomes of the three strains, i.e., RVA/Human-wt/VNM/RVN16.1024/2016/G9P[8], RVA/Human-wt/VNM/RVN17.0879/2017/G9P[8], and RVA/Human-wt/VNM/RVN18.0197/2018/G9P[8], and those of seven representative G9P[8] strains possessing long RNA patterns. The VP7 genes of the short and long G9P[8] strains were > 99% identical, indicating that the origin was in the co-circulating, dominant, long G9P[8] strains. On the other hand, the VP4 genes likely derived from recently-emerging G1/G3/G8P[8] strains possessing the DS-1 backbone. At the lineage level, however, the backbone genes of any one strain differed from that of the other two in the VP1, VP3 or NSP4 gene. Moreover, even at the nucleotide sequence level of the backbone genes belonging to the same lineage, the identities between the three strains were lower than those expected for the strains deriving from an immediate, common ancestor. Thus, the three strains were likely formed by independent reassortment events in which the VP7 gene of the currently dominant G9P[8] strains was incorporated into co-circulating G1/G3/G8P[8] strains possessing similar yet distinct DS-1-like backbone genes. The observation that all of the three reassortant G9P[8] strains were detected only once among the prevalent, ordinary G9P[8] strains suggests that acquisition of the DS-1-like backbone genes unlikely provided selective advantage over the parental Wa-like G9P[8] strains.

Anticancer Activity of Ramalin, a Secondary Metabolite from the Antarctic Lichen Ramalina terebrata, against Colorectal Cancer Cells.

Colorectal cancer is a leading cause of death worldwide and occurs through the highly complex coordination of multiple cellular pathways, resulting in carcinogenesis. Recent studies have increasingly revealed that constituents of lichen extracts exhibit potent pharmaceutical activities, including anticancer activity against various cancer cells, making them promising candidates for new anticancer therapeutic drugs. The main objective of this study was to evaluate the anticancer capacities of ramalin, a secondary metabolite from the Antarctic lichen Ramalina terebrata, in the human colorectal cancer cell line HCT116. In this study, ramalin displayed concentration-dependent anticancer activity against HCT116 cells, significantly suppressing proliferation and inducing apoptosis. Furthermore, ramalin induced cell cycle arrest in the gap 2/mitosis (G2/M) phase through the modulation of hallmark genes involved in the G2/M phase transition, such as tumour protein p53 (TP53), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase 1 (CDK1) and cyclin B1 (CCNB1). At both the transcriptional and translational level, ramalin caused a gradual increase in the expression of TP53 and its downstream gene CDKN1A, while decreasing the expression of CDK1 and CCNB1 in a concentration-dependent manner. In addition, ramalin significantly inhibited the migration and invasion of colorectal cancer cells in a concentration-dependent manner. Taken together, these data suggest that ramalin may be a therapeutic candidate for the targeted therapy of colorectal cancer.