Abeliophyllum distichum Nakai is a Korean endemic plant of the Oleaceae family that contains acteoside, a glycosylated caffeic acid, with neuroprotective, anti‑inflammatory and antibacterial properties. Previous studies, involving Accelerated Chromatographic Isolation, a high‑performance liquid chromatography‑photodiode array detector and a liquid chromatograph‑mass selective detector, isolated and identified acteoside in A. distichum (AAD) and documented its antioxidant and anti‑inflammatory activities. The aim of the present study was to determine whether AAD could protect from DNA damage by reducing oxidative stress. AAD treatment protected plasmid DNA against damage to DNA double‑strands induced by reactive oxygen species (ROS) and decreased the levels of phosphorylated p53 and γ‑H2AX in ROS‑treated NIH 3T3 cells. These findings suggested that AAD could reduce ROS‑mediated cellular damage and may represent an effective, natural antioxidant with the ability to protect genetic material.
Abeliophyllum distichum Nakai is the only species in Abeliophyllum genus, which is Korean endemic. Ok Hwang 1ho, the first official cultivar of A. distichum., displays that colour of corolla is light yellow (8D and 9D). Here, we completed chloroplast genome of A. distichum cultivar Ok Hwang 1ho to understand genetic diversity of A. distichum cultivar. Its length is 156,008 bp long and has four subregions: 86,773 bp of large single copy (LSC) and 17,827 bp of small single copy (SSC) regions are separated by 25,704 bp of inverted repeat (IR) regions including 133 genes (88 protein-coding genes, eight rRNAs, and 37 tRNAs). The overall GC contents of this chloroplast genome are 37.8% and in the LSC, SSC, and IR regions are 35.8%, 31.9%, and 43.2%, respectively. Ninety-three single nucleotide polymorphisms (SNPs) and 56 insertion and deletions (INDELs) are identified against previous A. distichum chloroplast genome. Phylogenetic trees show that A. distichum is clustered with two Forsythia species and many cultivars of Olea europaea subspecies present shorter branches than that of A. distichum. Our chloroplast genome will be a fundamental data to understand morphological diversity of A. distuichum.
11 January 2019 in International Journal of Molecular Medicine
Temozolomide (TMZ) is an alkylating agent commonly used as a first-line treatment for high-grade glioblastoma. However, TMZ has short half-life and frequently induces tumor resistance, which can limit its therapeutic efficiency. In the present study, it was hypothesized that combined treatment with TMZ and acteoside has synergistic effects in glioblastoma therapy. Using cell viability and wound-healing assays, it was determined that this treatment regimen reduced cell viability and migration to a greater extent than either TMZ or acteoside alone. Following previous reports that TMZ affected autophagy in glioma cells, the present study examined the effects of TMZ + acteoside combination treatment on apoptosis and autophagy. The TMZ + acteoside combination treatment increased the cleavage of caspase-3 and levels of B-cell lymphoma 2 (Bcl-2)-associated X protein and phosphorylated p53, and decreased the level of Bcl-2. The combination treatment increased microtubule-associated protein 1 light chain 3 and apoptosis-related gene expression. It was also determined that TMZ + acteoside induced apoptosis and autophagy through the mitogen-activated protein kinase signaling pathway. These findings suggest that acteoside has beneficial effects on TMZ-based glioblastoma therapy.
RNA interference (RNAi) is a posttranscriptional gene silencing mechanism acting as an antiviral defense in eukaryotes. During viral replication, intermediate double-stranded RNAs are processed into virus-derived small interfering RNAs (vsiRNAs) by the host enzyme, DICER. These vsiRNAs are incorporated into the RNA-induced silencing complex (RISC), where AGO2 cleaves viral genomic RNAs. However, viruses have evolved mechanisms to suppress this pathway. Here, we report that the nonstructural protein (NSs) of severe fever with thrombocytopenia syndrome virus (SFTSV) interacts with RISC to suppress the RNAi pathway. NSs forms a ternary complex by interacting with both DICER and AGO2 of the RNAi pathway. The interaction between NSs and DICER, facilitated by the two RNase III domains of DICER, is disrupted in the absence of AGO2 or the DICER-interacting domain (PIWI) of AGO2, indicating a direct interaction between NSs and AGO2. Functional assays using shRNA- and siRNA-mediated silencing of GFP signal, along with co-localization studies, demonstrated that NSs competes with siRNA to interact with AGO2, thereby abolishing RNAi activity. Mutational analysis identified an NSs-A26 mutant that no longer interacts with AGO2 and is unable to suppress RNAi activity, suggesting that NSs acts as a viral suppressor of RNAi (VSR) for SFTSV. Viral infection led to the generation of vsiRNA and showed higher replication in AGO2-/- cells compared to wild-type (WT) cells, confirming the antiviral role of the RNAi pathway against SFTSV infection. These data suggest that the NSs–AGO2 interaction suppresses RNAi, counteracting the antiviral RNAi pathway, thereby facilitating SFTSV infection and pathogenesis. IMPORTANCE: RNA interference (RNAi) is the main antiviral defense pathway in plants and insects but is not predominant in mammals. While RNAi’s role in countering severe fever with thrombocytopenia syndrome virus (SFTSV) infection has been studied in ticks, its role in humans is unknown. The SFTSV nonstructural protein (NSs) forms inclusion bodies (IBs) in the host, sequestering multiple antiviral proteins and facilitating pathogenesis, contributing to SFTSV’s high mortality rate. Our study found that SFTSV NSs directly interacts with AGO2, a key RNAi protein, hindering its function. A novel NSs mutant failed to interact with AGO2 and lost its RNAi suppression ability, highlighting NSs as a viral suppressor of RNAi (VSR). Infection studies confirmed the RNAi pathway’s critical role in combating SFTSV infection. This study demonstrates NSs’s role in viral infection and suggests potential therapeutic approaches.
8 November 2022 in Experimental and Therapeutic Medicine
Malignant melanoma is responsible for 3.0 and 1.7% of cases of tumor incidence and tumor‑associated mortality, respectively, in the Caucasian population. Melanoma is a type of skin cancer that occurs when melanocytes mutate and divide uncontrollably. Nypa fruticans Wurmb (NF) is abundant in phytochemicals (polyphenols and flavonoids) and is traditionally used to treat diseases of the respiratory tract. The present study investigated the inhibitory effect of the ethyl acetate fraction of NF (ENF) on melanogenesis‑related factors in isobutylmethylxanthine‑treated B16F10 melanoma cells. Phenolics and flavonoids (caffeic acid, catechin, epicatechin and hirsutine) in ENF were analyzed via liquid chromatography‑mass spectrometry. In addition, the main factors involved in melanogenesis were identified using immunoblotting, reverse transcription‑polymerase chain reaction (RT‑PCR), RT‑quantitative PCR and immunofluorescence. ENF significantly suppressed the expression of tyrosinase (TYR) and TYR‑related proteins 1 and 2 (TYRP‑1/2), which are the main factors involved in melanogenesis. ENF also inhibited the expression of microphthalmia‑associated transcription factor (MITF) by phosphorylating the related cell signaling proteins (protein kinase B, mammalian target of rapamycin, phosphoinositide 3‑kinase and cAMP response element‑binding protein). Furthermore, ENF inhibited the phosphorylation of extracellular signal‑regulated kinase and thereby downregulated melanogenesis. In conclusion, ENF inhibited melanogenesis by suppressing MITF, which controls TYRP‑1/2 and TYR. These results suggested that ENF may be a natural resource that can inhibit excessive melanin expression by regulating various melanogenesis pathways.
Chloroplast genome of Sang Jae, new candidate cultivar of Abeliophyllum distichum Nakai, has been sequenced to reveal infraspecific relationship of wildtypes and cultivars. Its length is 156,008 bp long (GC ratio is 37.8%) and has four subregions: 86,773 bp of large single copy (35.8%) and 17,827 bp of small single copy (31.9%) regions are separated by 25,704 bp of inverted repeat (43.2%) regions including 133 genes (87 protein-coding genes, eight rRNAs, and 37 tRNAs). Phylogenetic trees show that A. distichum is clustered with twelve Forsythia species and intraspecies variations level is similar to Olea europaea.