Embelia ribes, a member of the subfamily Myrsinoideae within the family Primulaceae, is a widely distributed medicinally important plant and the primary source of embelin. Despite its wide distribution across South and Southeast Asia, and its medicinal importance, the genomics of E. ribes and the genus Embelia remain unexplored. In this study, the complete plastome sequence of E. ribes was determined and compared with those of 14 other plastomes from the families Primulaceae and Ebenaceae. The plastome of E. ribes spans 1,57,186 bp, and exhibits a quadripartite structure with a large single-copy region (86,681 bp), a small single-copy region (SSC; 18,248 bp), and a pair of inverted repeat (IR) regions (26,093 bp). The plastome comprises 134 genes, including 89 protein-coding genes, 8 rRNA genes, and 37 tRNA genes, of which 19 are duplicated in the IR region. The comparative plastome analysis revealed a conserved structure and gene content across the family, with minor IR boundary shifts. Six hypervariable regions and 61 simple sequence repeats were identified and can be used as potential tools for species identification and population genetic studies. Phylogenomics supports a close relationship of Embelia with Aegiceras and Myrsine. The study provides the complete plastome data of E. ribes, contributing to species delineation, evolutionary relationship studies, population genetics, and conservation.
Quinoline-based ionic liquids (ILs) are being evaluated for their potential antifungal activity, making them promising alternatives to traditional antifungal therapies. The peculiar properties, characteristic of the utilization of ILs, including their solvation effect, greatly influence their broad-spectrum activity against a wide range of fungal species. Thus, in this study, for the first time, to the best of our knowledge, we aim at exploring the mechanistic action of the previously synthesized quinoline-based IL, 1-hexadecylquinolin-1-ium bromide, [C16quin]Br, against the pathogenesis of the critical pathogenic fungus, Candida albicans. The impact of this compound was evaluated on C. albicans growth and biofilm formation using various biological assays. The antifungal activity and prevention of the yeast-to-hyphae transition, which is essential for virulence and biofilm formation, were demonstrated using light microscopy studies. Ultraviolet absorbance at 260 and 280 nm showed that when fungal cells were treated with IL, nucleic acid and proteinaceous material leaked out, suggesting a physically damaged cell membrane, which was further validated by scanning electron microscopy. By evaluating the solubility of fluconazole, a commercially available antifungal medication, and contrasting it with traditional solvents such as dimethyl sulfoxide, the study also stipulates the potential of [C16quin]Br as a drug carrier, contributing to replenishing the otherwise dry antifungal pipeline.
Newcastle disease virus (NDV) is an avian paramyxovirus that has a significant impact on the global poultry industry. The accessory W protein (W) of NDV is generated by RNA editing of the phosphoprotein (P) gene; however, its precise function remains elusive. Consequently, we conducted an in-silico analysis of the W sequences from 1,011 NDV strains, utilizing the data from GenBank. Our investigation revealed 24 W-length variants ranging between 135 and 231 amino acids (aa), with variant 227 aa being the most prevalent. Further, the W-length variants were distinct for class I and class II NDV strains. We observed no apparent correlation between W lengths and genotype or pathogenicity of NDV. However, a nuclear localization signal (NLS) in the W seemed to be associated with virulence, with 55.9% of virulent strains having an NLS, compared to 38.9% of avirulent strains. Geographical analysis indicated region-specific evolutionary factors, with Asia showing the most W diversity. The lengths of W were more specific to the bird species from which they were isolated/sequenced, suggesting possible adaptation to the host. Molecular clock analysis showed varied evolutionary rates among W types, with variant 185 aa evolving the fastest. Selection pressure analysis indicated that most types are under negative selection, but some presented signs of relaxed or positive selection. Our study provides a broad view of W diversity in NDV, highlighting its complex evolutionary history and possible implications for host adaptation and virulence.
Sorafenib, an established multi-kinase inhibitor, is a cornerstone of treatment for advanced hepatocellular carcinoma (HCC). This study explores the efficacy of combining sorafenib with cilostazol, a phosphodiesterase-3 inhibitor with emerging anticancer properties, using the HepG2 cell line. We assessed the effects on cell proliferation, apoptosis, and the expression levels of key regulatory proteins and genes, including VEGF, SMAD4, Bcl-2, TGF-β, Bax, and caspase-3. The combination treatment resulted in a significant reduction in the IC50 of sorafenib. Colony formation assays demonstrated that both cilostazol and sorafenib individually inhibited HepG2 cell growth, with combination therapy leading to a further decrease in colony numbers compared to individual treatments. Enhanced apoptosis was observed with the combination, as evidenced by increased Bax and caspase-3 levels and decreased Bcl-2 expression. Additionally, the combination therapy exhibited potent anti-angiogenic effects, significantly reducing VEGF and TGF-β levels. These findings suggest a synergistic interaction between sorafenib and cilostazol, offering promising insights for optimizing therapeutic strategies in HCC management.
