Korea Research Institute of Bioscience and Biotechnology
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Detection of infectious white spot syndrome virus in red claw cray？sh (Cherax quadricarinatus) and red swamp cray？sh (Procambarus clarkii) imported into Korea
No full textWhite spot syndrome virus (WSSV) is one of the most virulent viruses in crustaceans, causing severe economic losses to aquaculture industry. In this study, we tested for the presence of WSSV in the commodity crayfish imported to Korea and also examined the potential infectivity of WSSV in the commodity WSSV-positive crayfish. For the sampling, two species of crayfish, Cherax quadricarinatus (320 red claw crayfish in eight batches) imported from Indonesia and Procambarus clarkii (40 red swamp crayfish in two batches) imported from China, were obtained from fishery markets in Korea. Five representative samples per batch (N = 50) were screened for WSSV using PCR assay, and the virus was detected in five C. quadricarinatus samples and one P. clarkii sample. Among the WSSV-positive samples, the highest virus titer (the copies ranged between 4.93 × 105 and 8.36 × 106 copies/μL) was detected in the P. clarkii sample (20？012) by qPCR, and a comparatively low titer was observed in the C. quadricarinatus sample (20？008) (the copies ranged between 5.94 × 101 and 3.86 × 105 copies/μL). Following the virus infectivity test, WSSV infection was confirmed after feeding WSSV-positive crayfish tissue (20？008, 3.46 × 107 WSSV copies/μL) to Penaeus vannamei (Pacific white shrimp, N = 42) at 5% shrimp biomass. This is the first report of confirmed infectivity of WSSV from the commodity crayfish imported into Korea, suggesting that virus-infected frozen crayfish may present a potential source of viral disease in Korean shrimp aquaculture. Therefore, accurate and strict monitoring of crustacean viruses is required for imported crayfish from foreign countries into Korea.
Receptor-mediated muscle homeostasis as a target for sarcopenia therapeutics
No full textSarcopenia is a disease characterized by age-related decline of skeletal muscle mass and function. The molecular mechanisms of the pathophysiology of sarcopenia form a complex network due to the involvement of multiple interconnected signaling pathways. Therefore, signaling receptors are major targets in pharmacological strategies in general. To provide a rationale for pharmacological interventions for sarcopenia, we herein describe several druggable signaling receptors based on their role in skeletal muscle homeostasis and changes in their activity with aging. A brief overview is presented of the efficacy of corresponding drug candidates under clinical trials. Strategies targeting the androgen receptor, vitamin D receptor, Insulin-like growth factor-1 receptor, and ghrelin receptor primarily focus on promoting anabolic action using natural ligands or mimetics. Strategies involving activin receptors and angiotensin receptors focus on inhibiting catabolic action. This review may help to select specific targets or combinations of targets in the future.
Development of high sensitivity diagnostic platform for non-invasive genetic diseases that can be used for liquid biopsy
No full text액상 생체 검사에 활용 가능한 비침습적 유전 질환의 고감도 진단 플랫폼 개발OGM441201
Tilianin attenuates HDM-induced allergic asthma by suppressing Th2-immune responses via downregulation of IRF4 in dendritic cells
No full textBackground
Acacetin 7-O-β-D-glucoside (tilianin) is a major constituent of Agastache rugosa, a traditional medicine that has long been used for the treatment of gastrointestinal disorders. Tilianin has a wide variety of pharmacological properties such as cardioprotective, neuroprotective, and anti-atherogenic activities. We recently discovered that tilianin has the ability to suppress MUC5AC expression in vitro. In addition, we have established an in vivo model of allergic asthma using house dust mite (HDM) that can be applied to tilianin.
Purpose
We investigated the effects of tilianin on airway inflammation in a HDM-induced asthma mouse model and associated mechanisms.
Methods
Tilianin was treated in splenocytes cultured in Th0 condition and HDM-stimulated bone marrow-derived dendritic cells (BMDCs), and their mRNA expression and cytokines production were determined by quantitative real-time PCR and ELISA. To evaluate the effects of tilianin in an allergic asthma model, mice were sensitized and challenged with HDM. Tilianin was administered prior to challenge by oral gavage and airway hyper-reactivity (AHR) to methacholine, inflammatory cell infiltration, cytokine levels, and airway remodeling were assessed.
Results
Tilianin inhibited the production of Th2-related cytokines in splenocytes, which play pivotal roles in allergic airway inflammation. When treated in HDM-stimulated BMDCs, tilianin decreased Th2-skewing cytokine IL-33 and transcription factor IRF4. On the contrary, tilianin increased Th1-skewing regulators, IL-12 and IRF1. In an HDM-induced asthmatic mouse model, tilianin attenuated AHR and airway inflammation. Tilianin suppressed the expression of Th2-related cytokines, IL-13 and IL-33 in lung tissues. As seen in HDM-stimulated BMDCs, tilianin also downregulated the expression of the transcription factor IRF4 but not IRF1.
Conclusion
Taken together, these results suggest that tilianin attenuates HDM-induced allergic airway inflammation by inhibiting Th2-mediated inflammation through the selective inhibition of the IRF4-IL-33 axis in dendritic cells.
VGLL1 phosphorylation and activation promotes gastric cancer malignancy via TGF-β/ERK/RSK2 signaling
No full textWe previously reported that vestigial-like 1 (VGLL1), a cofactor of transcriptional enhanced associate domain 4 (TEAD4), is transcriptionally regulated by PI3K and β-catenin signaling and is involved in gastric cancer malignancy. However, the precise mechanism underlying the regulation of VGLL1 activation remains unknown. Therefore, we aimed to investigate the molecular mechanism underlying the transforming growth factor-β (TGF-β)-mediated activation of VGLL1 and the VGLL1-TEAD4 interaction in gastric cancer cells. We showed that TGF-β enhanced VGLL1 phosphorylation and that this phosphorylated VGLL1 functioned as a transcription cofactor of TEAD4 in NUGC3 cells. TGF-β also increased the phosphorylation of ERK and ribosomal S6 kinase 2 (RSK2) in NUGC3 cells, thereby triggering the translocation of phosphorylated RSK2 to the nucleus. Site-directed mutagenesis and immunoprecipitation experiments revealed that RSK2 phosphorylated VGLL1 at S84 in the presence of TGF-β. Mutation of VGLL1 at S84 suppressed VGLL1-TEAD4 binding and the subsequent transcriptional activation of matrix metalloprotease 9 (MMP9). Moreover, VGLL1 peptide containing S84 suppressed the TGF-β-induced MMP9 expression and reduced the invasion and proliferation of gastric cancer cells, whereas VGLL1 peptide containing S84A did not. Furthermore, suppression of expression or activation of VGLL1 enhances the therapeutic effects of lapatinib. Collectively, these results indicate that VGLL1 phosphorylation via TGF-β/ERK/RSK2 signaling plays a crucial role in MMP9-mediated malignancy of gastric cancer. In addition, our study highlights the therapeutic potential of the peptide containing VGLL1 S84 for the treatment of gastric cancer.
Direct reprogramming of human fibroblasts into induced neural progenitor cells using suicide gene embodied episomal vectors for rapid selection of exogenous DNA-free cells
No full textDirect neural reprogramming involves a rapid conversion of somatic cells into neural cells without passing through the intermediate pluripotent stage. This phenomenon can be mediated in the starting somatic cells by the introduction of lineage-specific master transcription factors or by pluripotency factors routinely used in iPS cell generation. In the latter process known as Pluripotency factor-mediated Direct Reprogramming (PDR), the pluripotency factors are used to elicit epigenetic changes producing a permissive state in the starting cells which are then driven to the neural lineages by simple manipulations of the culture conditions. When genes are exogenously introduced to achieve such conversion, their persistent expression after completion of the reprogramming can affect the properties of the resulting cells. Here, we describe a robust method for direct neural reprogramming using the episomal vectors that incorporate a suicide gene scFCY1 (encoding cytosine deaminase) that allows rapid and efficient generation of a homogenous population of transgene-free human-induced neural progenitor cells (hiNPCs). The resulting NESTIN+/PAX6+/CDH2+ hiNPCs can be expanded and cryopreserved and can be further differentiated into neurons and glia.
Protective effects of Phlomis umbrosa extract on a monosodium iodoacetate-induced osteoarthritis model and prediction of molecular mechanisms using transcriptomics
No full textBackground: Phlomis umbrosa Turczaninow root has been traditionally used to treat fractures, rheumatoid arthritis, and arthralgia. However, the effects and mechanisms of P. umbrosa on osteoarthritis (OA) remain poorly understood and a functional genomic approach has not been investigated.
Aim: The purpose of this study was to investigate the effects and mechanisms of P. umbrosa extract (PUE) on OA using transcriptomic analysis.
Methods: We performed joint diameter measurements, micro computed tomography, and histopathological analysis of monosodium iodoacetate (MIA)-induced OA rats treated with PUE (200 mg/kg) for 3 weeks. Gene expression profiling in articular cartilage tissue was then performed using RNA sequencing (RNA-seq) followed by signaling pathway analysis of regulatory genes.
Results: PUE treatment improved OA based on decreased joint diameter, increased joint morphological parameters, and histopathological features. Many genes involved in multiple signal transduction pathway and collagen activation in OA were differentially regulated by PUE. These included genes related to Wnt/β-catenin, OA pathway, and sonic hedgehog signaling activity. Furthermore, PUE treatment downregulated cartilage damage factors (MMP-9, MMP-13, ADAMTs4, and ADMATs5) and upregulated chondrogenesis (COL2A1 and SOX-9) by regulating the transcription factors SOX-9, Ctnnb1, and Epas1.
Conclusion: Based on the results of gene expression profiling, this study highlighted the molecular mechanisms underlying the effects of PUE in MIA-induced OA rats. The findings provide novel insight into the mechanisms by which PUE treatment-induced gene expression changes may influence OA disease progression. Taken together, the results suggest that PUE may be used as a source of therapeutic agents for OA.
Crosstalk between YAP and TGFβ regulates SERPINE1 expression in mesenchymal lung cancer cells
No full textSerpin family E member 1 (SERPINE1), a serine proteinase inhibitor, serves as an important regulator of extracellular matrix remodeling. Emerging evidence suggests that SERPINE1 has diverse roles in cancer and is associated with poor prognosis. However, the mechanism via which SERPINE1 is induced in cancer has not been fully determined. In order to examine the molecular mechanism of SERPINE1 expression, the present study took advantage of the isogenic pair of lung cancer cells with epithelial or mesenchymal features. Using genetic perturbation and following biochemical analysis, the present study demonstrated that SERPINE1 expression was upregulated in mesenchymal lung cancer cells and promoted cellular invasiveness. Yes？associated protein (YAP)？dependent SERPINE1 expression was modulated by treatment with a Rho？associated protein kinase inhibitor, Y27632. Moreover, TGFβ treatment supported YAP？dependent SERPINE1 expression, and an enhanced TGFβ response in mesenchymal lung cancer cells promoted SERPINE1 expression. TGFβ？mediated SERPINE1 expression was significantly attenuated by knockdown of YAP or transcriptional co？activator with PDZ？binding motif, suggesting that crosstalk between the TGFβ and YAP pathways underlies SERPINE1 expression in mesenchymal cancer cells.
Evaluation of 13-week subchronic toxicity of Platycodon grandiflorus (Jacq.) A.DC. root extract in rats
No full textEthnopharmacological relevance: Platycodi radix is widely used in traditional herbal medicine for bronchitis, asthma, pulmonary tuberculosis, hypertension, hyperlipidemia, and diabetes. However, data on safety of Platycodi radix are insufficient.
Aim of the study: The present study was performed to evaluate the potential subchronic toxicity of Platycodi radix water extract through a 13-week repeated oral dose experiment in Sprague-Dawley rats.
Materials and methods: Forty male and 40 female rats were randomly assigned to four experimental groups: three treatment groups receiving 300, 1000, and 3000 mg/kg/day of Platycodi radix water extract and a vehicle control group receiving sterile distilled water for 13 weeks.
Results: Repeated oral administration of the Platycodi radix water extract to rats resulted in an increased incidence of centrilobular hepatocellular hypertrophy in the liver, diffuse follicular cell hypertrophy in the thyroid gland, and squamous hyperplasia of the limiting ridge in the stomach at dose levels of ≥500 mg/kg/day of both genders. However, these findings are considered be adaptive non-adverse changes because these findings were observed without organ weight change or clinical pathology alterations. No treatment-related effects on clinical signs, body weight, food and water consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, and organ weights were observed at any dose tested.
Conclusion: Under the present experimental conditions, the no-observed-adverse-effect level of the Platycodi radix water extract was considered to be ≥ 3000 mg/kg/day in rats, and no target organs were identified.
iCSDB: an integrated database of CRISPR screens
No full textHigh-throughput screening based on CRISPR-Cas9 libraries has become an attractive and powerful technique to identify target genes for functional studies. However, accessibility of public data is limited due to the lack of user-friendly utilities and up-to-date resources covering experiments from third parties. Here, we describe iCSDB, an integrated database of CRISPR screening experiments using human cell lines. We compiled two major sources of CRISPR-Cas9 screening: the DepMap portal and BioGRID ORCS. DepMap portal itself is an integrated database that includes three large-scale projects of CRISPR screening. We additionally aggregated CRISPR screens from BioGRID ORCS that is a collection of screening results from PubMed articles. Currently, iCSDB contains 1375 genome-wide screens across 976 human cell lines, covering 28 tissues and 70 cancer types. Importantly, the batch effects from different CRISPR libraries were removed and the screening scores were converted into a single metric to estimate the knockout efficiency. Clinical and molecular information were also integrated to help users to select cell lines of interest readily. Furthermore, we have implemented various interactive tools and viewers to facilitate users to choose, examine and compare the screen results both at the gene and guide RNA levels. iCSDB is available at https://www.kobic.re.kr/icsdb/.