Korea Research Institute of Bioscience and Biotechnology
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Impaired hand dexterity function in a non-human primate model with chronic Parkinson's disease
No full textSymptoms of Parkinson's disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.
Lipid composition of latex and rubber particles in Hevea brasiliensis and Taraxacum kok-saghyz
No full textNatural rubber is usually synthesized in the rubber particles present in the latex of rubber-producing plants such as the Para rubber tree (Hevea brasiliensis) and rubber dandelion (Taraxacum kok-saghyz). Since the detailed lipid compositions of fresh latex and rubber particles of the plants are poorly known, the present study reports detailed compound lipid composition, focusing on phospholipids and galactolipids in the latex and rubber particles of the plants. In the fresh latex and rubber particles of both plants, phospholipids were much more dominant (85-99%) compared to galactolipids. Among the nine classes of phospholipids, phosphatidylcholines (PCs) were most abundant, at ~80%, in both plants. Among PCs, PC (36:4) and PC (34:2) were most abundant in the rubber tree and rubber dandelion, respectively. Two classes of galactolipids, monogalactosyl diacylglycerol and digalactosyl diacylglycerol, were detected as 12% and 1%, respectively, of total compound lipids in rubber tree, whereas their percentages in the rubber dandelion were negligible (< 1%). Overall, the compound lipid composition differed only slightly between the fresh latex and the rubber particles of both rubber plants. These results provide fundamental data on the lipid composition of rubber particles in two rubber-producing plants, which can serve as a basis for artificial rubber particle production in the future.
DK-1108 exerts anti-inflammatory activity against phorbol 12-myristate 13-acetate-induced inflammation and protective effect against OVA-induced allergic asthma
No full textThere is an increasing interest in natural products and their derivatives with therapeutic benefits and less side effects compared to steroid therapy. Benzofuran derivatives display biological effects including anti-inflammatory effects. The present study aims to investigate whether (3-(7-methoxy-2-p-tolyl benzofuran-5-yl) propan-1-ol) (DK-1108), new synthetic benzofuran compound exerts anti-asthmatic effects in vitro and in vivo. DK-1108 strongly reduced the production of inflammatory mediators, cytokines and chemokines in RAW264.7 and A549 cells. DK-1108 significantly regulated the levels of AKT/MAPKs/c-Jun activation, AP-1 luciferase activity and ICAM-1 expression. Furthermore, DK-1108 effectively suppressed the adhesion of A549 and EOL-1 cells. In OVA-induced asthmatic mice, DK-1108 decreased the levels of IL-5/IL-13/IgE production, eosinophils/macrophages influx, ICAM-1/MCP-1 expression, mucus secretion and airway hyperresponsiveness (AHR). These effects of DK-1108 were accompanied by downregulation of MAPKs activation. Therefore, we suggest that DK-1108 exerts protective effect against airway inflammation and mucus overproduction, and therefore could be valuable therapeutic agent for treatment in asthma.
Cytoplasmic MYC is an anti-necroptotic protein
No full textCancer cells are often resistant to necroptosis as well as apotosis, but the underlying mechanisms are not fully understood. We recently revealed an important crosstalk between MYC, a potent oncogene, and receptor-interacting protein kinase 3 (RIPK3), a pivotal factor in inducing necroptosis. Mechanistically, cytoplasmic MYC directly binds to RIPK3, inhibiting initial necrosome complex formation.
Metabolic engineering of Escherichia coli for production of non-natural acetins from glycerol
No full textMono-, di- and triacetin are three glycerol esters which are usually synthesized via costly and environmentally unfriendly chemical synthesis methods. Here, Escherichia coli is metabolically engineered for the production of mono-, di- and triacetin using glycerol as a substrate. First, a novel biosynthetic route of mono- and diacetin is established by overexpression of a native enzyme, maltose O-acetyltransferase (MAA). Next, the biosynthetic pathway is extended to produce a mixture of mono-, di- and triacetin by overexpression of chloramphenicol-O-acetyltransferase (CAT). By successive strategies, including heterologous gene expression, metabolic engineering, and culture optimization, a recombinant E. coli is enabled to produce more than 27 g L？1 of a mixture of mono-, di- and triacetin in shake flask cultures, which is a >650-fold increase over the initial production of 0.04 g L？1. In vitro studies confirm the acetylation of glycerol to mono- and diacetin by MAA, and the additional acetylation to triacetin by CAT. When crude glycerol is used as a substrate, the engineered strain produced a total of 25.9 g L？1 of the acetin mixture, about the same as that achieved from pure glycerol. To our knowledge, this is the first successful report of microbial production of the artificial chemicals, acetins.
Tabrizicola algicola sp. nov. isolated from culture of microalga Ettlia sp.
No full textA novel Gram-stain-negative, aerobic, non-spore-forming, non-motile, and rod-shaped bacterium, strain ETT8T was isolated from a chemostat culture of microalga Ettlia sp. YC001. Optimal growth was with 0-2% NaCl and at 25-37 °C on R2A medium. Phylogenetic analysis based on the 16S rRNA gene and genome sequence showed that strain ETT8T belongs to the genus Tabrizicola, with the close neighbours being T. sediminis DRYC-M-16T (98.1 %), T. alkalilacus DJCT (97.6 %), T. fusiformis SY72T (96.9 %), T. piscis K13M18T (96.8 %), and T. aquatica RCRI19T (96.5 %). The genomic comparison of strain ETT8T with type species in the genus Tabrizicola was analysed using the genome-to-genome distance calculator (GGDC), average nucleotide identity (ANI), and average amino acid identity (AAI) (values indicated ≤17.7, ≤75.4 and ≤71.9 %, respectively). The genomic DNA G+C content of strain ETT8T was 64.4 %, plus C18 : 1 ω6c and C18 : 0-iso were the major fatty acids and Q-10 the major respiratory quinone. Strain ETT8T contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine aminolipid, and four unidentified lipids as the major polar lipids. Based on the chemotaxonomic, genotypic, and phenotype results, strain ETT8T was recognized as a novel species of the genus Tabrizicola for which the name Tabrizicola algicola sp. nov. is proposed. The type strain is ETT8T (=KCTC 72206T=JCM 31893T=MCC 4339T).
Development of a polo-like kinase-1 polo-box domain inhibitor as a tumor growth suppressor in mice models
No full textPolo-like kinase-1 (Plk1) plays a key role in mitosis and has been identified as an attractive anticancer drug target. Plk1 consists of two drug-targeting sites, namely, N-terminal kinase domain (KD) and C-terminal polo-box domain (PBD). As KD-targeting inhibitors are associated with severe side effects, here we report on the pyrazole-based Plk1 PBD inhibitor, KBJK557, which showed a remarkable in vitro anticancer effect by inducing Plk1 delocalization, mitotic arrest, and apoptosis in HeLa cells. Further, in vivo optical imaging analysis and antitumorigenic activities in mouse xenograft models demonstrate that KBJK557 preferentially accumulates in cancer cells and selectively inhibits cancer cell proliferation. Pharmacokinetic profiles and partition coefficients suggest that KBJK557 was exposed in the blood and circulated through the organs with an intermediate level of clearance (t1/2, 7.73 h). The present investigation offers a strategy for specifically targeting cancer using a newly identified small-molecule inhibitor that targets the Plk1 PBD.
Potential anti-wrinkle activity of Chlorella sp. HS1-derived oil components on human dermal fibroblasts
No full textPurpose: In this study, we investigated the effects of Chlorella sp. HS1-derived oils on collagen expressions in dermal fibroblasts.
Methods: We prepared the oil extracts from Chlorella sp . HS1 biomass, and high-performance liquid chromatography analysis was used in the identification and quantitation of components in the oil extracts. Using human dermal fibroblasts, cell viability and quantitative RT-PCR (qRTPCR)-mediated expression analysis of collagen and matrix metalloprotease (MMP ) genes after oil treatments. We further investigated whether the effect of the oil extracts on collagen expression was related to the major component, β-carotene, of the extracts. In addition, we analyzed the effect of photoprotective effect of β-carotene on ultraviolet (UV)-irradiated dermal fibroblasts.
Results: We found that under 50 μg/mL of the oil extracts had little cytotoxicity in skin cells including epidermal keratinocytes, melanocytes and dermal fibroblasts. The HPLC analysis revealed that β-carotene was identified as the major non-polar molecules. Next, we found that the oil-derived β-carotene was little cytotoxicity in dermal fibroblasts. Further experiments revealed that treatment with the oil extracts significantly upregulated collagen type 1 and 3 mRNAs and downregulated MMP1 and MMP3 mRNAs in dermal fibroblasts. Also, we found that these effects were showed in β-carotene-treated cells. In addition, β-carotene significantly attenuated UVA-induced downregulation of collagen type 1 and 3 expressions.
Conclusion: Therefore, our results suggested that the oil extracts had a potential anti-wrinkle agent via its major component, β-carotene.
Anomalous restoration of sp2 hybridization in graphene functionalization
No full textThe functionalization of nanocarbon materials such as graphene has attracted considerable attention over the past decades. In this work, we designed and synthesized a unique N-heterocyclic carbene compound with a pyrene tail group (NHCp) to investigate how carbene species can be used for the functionalization of graphene. Although the carbene moiety of NHCp has the ability to covalently bond to graphene, the pyrene tail can noncovalently interact with graphene and allows monitoring its surrounding microenvironment. The major characteristics of the resulting nanohybrids were highly dependent on the type of graphene and the NHCp-to-graphene weight ratio. Importantly, despite the covalent functionalization of graphene, an anomalous decrease in the intensity of the Raman D peak and improved conductivity were observed for the nanohybrids. It was found that the covalent bond of NHCp to the graphene edge may allow the hybridization of their orbitals, which affects electronic energy levels and alters the double resonance process that originates the D peak at the edge defect. Importantly, the NHCp compound can act as a π acceptor (not just as a σ donor) via the NHCp？graphene covalent bridge. This is the first report showing that the concept of π-backdonation can be realized in two-dimensional materials, such as graphene, and rationally designed carbene molecules can functionalize graphene without losing their beneficial sp2 hybridization characteristics.