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61.
Ahmed H.E. Hassan Min Chang Cho Hye In Kim Ji Seul Yang Kyung Tae Park Ji Young Hwang Choon-Gon Jang Ki Duk Park Yong Sup Lee 《Bioorganic & medicinal chemistry》2018,26(18):5069-5078
CRA13; a peripheral dual CB1R/CB2R agonist with clinically proven analgesic properties, infiltrates into CNS producing adverse effects due to central CB1R agonism. Such adverse effects might be circumvented by less lipophilic compounds with attenuated CB1R affinity. Metabolism produces less lipophilic metabolites that might be active metabolites. Some CRA13 oxidative metabolites and their analogues were synthesized as less lipophilic CRA13 analogues. Probing their CB1R and CB2R activity revealed the alcohol metabolite 8c as a more potent and more effective CB2R ligand with attenuated CB1R affinity relative to CRA13. Also, the alcohol analogue 8b and methyl ester 12a possessed enhanced CB2R affinity and reduced CB1R affinity. The CB2R binding affinity of alcohol analogue 8b was similar to CRA13 while that of methyl ester 12a was more potent. In silico study provided insights into the possible molecular interactions that might explain the difference in the elicited biological activity of these compounds. 相似文献
62.
Hemocytes of the last larva of the Japanese rhinoceros beetle A. dichotoma (Linnaeus) (Coleoptera: Scarabaeidae) were classified as granulocytes, plasmatocytes, oenocytoids, spherulocytes, prohemocytes, and adipohemocytes. Among these cell types, only the granulocytes became immunologically activated with obvious morphological changes, displaying large amoeba-like, lobopodia-like, and fan-like structures. In addition, their cytoplasmic granules became larger and greatly increased in number. To explore whether these granules could be immunologically generated as phagosomes, total hemocytes were stained with LysoTracker. Greater than 90% of the granulocytes retained the LysoTracker dye at 4 h post-bacterial infection. In flow cytometry analysis, the red fluorescent signal was highly increased at 4 h post-bacterial infection (60.36%) compared to controls (5.08%), as was confirmed by fluorescent microscopy. After 12 h post-infection, these signals returned to basal levels. The uptake of pathogens by granulocytes rapidly triggered the translocation of the microtubule-associated protein 1 light chain 3 alpha (LC3) to the phagosome, which may result in enhanced pathogen killing. 相似文献
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Hui‐Su Kim Bo‐Young Lee Jeonghoon Han Chang‐Bum Jeong Dae‐Sik Hwang Min‐Chul Lee Hye‐Min Kang Duck‐Hyun Kim Daehwan Lee Jaebum Kim Ik‐Young Choi Jae‐Seong Lee 《Molecular ecology resources》2018,18(3):656-665
Marine medaka (Oryzias melastigma) is considered to be a useful fish model for marine and estuarine ecotoxicology studies and has good potential for field‐based population genomics because of its geographical distribution in Asian estuarine and coastal areas. In this study, we present the first whole‐genome draft of O. melastigma. The genome assembly consists of 8,602 scaffolds (N50 = 23.737 Mb) and a total genome length of 779.4 Mb. A total of 23,528 genes were predicted, and 12,670 gene families shared with three teleost species (Japanese medaka, mangrove killifish and zebrafish) were identified. Genome analyses revealed that the O. melastigma genome is highly heterozygous and contains a large number of repeat sequences. This assembly represents a useful genomic resource for fish scientists. 相似文献
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Hye Ran Park Jae Meen Lee Gwanhee Ehm Hui-Jun Yang In Ho Song Yong Hoon Lim Mi-Ryoung Kim Keyoung Ran Kim Woong-Woo Lee Young Eun Kim Jae Ha Hwang Chae Won Shin Hyeyoung Park Jin Wook Kim Han-Joon Kim Cheolyoung Kim Dong Gyu Kim Beom Seok Jeon Sun Ha Paek 《PloS one》2016,11(1)
Background
GPi (Internal globus pallidus) DBS (deep brain stimulation) is recognized as a safe, reliable, reversible and adjustable treatment in patients with medically refractory dystonia.Objectives
This report describes the long-term clinical outcome of 36 patients implanted with GPi DBS at the Neurosurgery Department of Seoul National University Hospital.Methods
Nine patients with a known genetic cause, 12 patients with acquired dystonia, and 15 patients with isolated dystonia without a known genetic cause were included. When categorized by phenomenology, 29 patients had generalized, 5 patients had segmental, and 2 patients had multifocal dystonia. Patients were assessed preoperatively and at defined follow-up examinations postoperatively, using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) for movement and functional disability assessment. The mean follow-up duration was 47 months (range, 12–84)Results
The mean movement scores significantly decreased from 44.88 points preoperatively to 26.45 points at 60-month follow up (N = 19, P = 0.006). The mean disability score was also decreased over time, from 11.54 points preoperatively to 8.26 points at 60-month follow up, despite no statistical significance (N = 19, P = 0.073). When analyzed the movement and disability improvement rates at 12-month follow up point, no significant difference was noted according to etiology, disease duration, age at surgery, age of onset, and phenomenology. However, the patients with DYT-1 dystonia and isolated dystonia without a known genetic cause showed marked improvement.Conclusions
GPi DBS is a safe and efficient therapeutic method for treatment of dystonia patients to improve both movement and disability. However, this study has some limitations caused by the retrospective design with small sample size in a single-center. 相似文献69.
Dain Son Yi Rang Na Eung-Soo Hwang Seung Hyeok Seok 《The Journal of biological chemistry》2014,289(9):6225-6235
PDGF-C, which is abundant in the malignant breast tumor microenvironment, plays an important role in cell growth and survival. Because tumor-associated macrophages (TAMs) contribute to cancer malignancy, macrophage survival mechanisms are an attractive area of research into controlling tumor progression. In this study, we investigated PDGF-C-mediated signaling pathways involved in anti-apoptotic effects in macrophages. We found that the human malignant breast cancer cell line MDA-MB-231 produced high quantities of PDGF-C, whereas benign MCF-7 cells did not. Recombinant PDGF-C induced PDGF receptor α chain phosphorylation, followed by Akt and Bad phosphorylation in THP-1-derived macrophages. MDA-MB-231 culture supernatants also activated macrophage PDGF-Rα. PDGF-C prevented staurosporine-induced macrophage apoptosis by inhibiting the activation of caspase-3, -7, -8, and -9 and cleavage of poly(ADP-ribose) polymerase. Finally, TAMs isolated from the PDGF-C knockdown murine breast cancer cell line 4T1 and PDGF-C knockdown MDA-MB-231-derived tumor mass showed higher rates of apoptosis than the respective WT controls. Collectively, our results suggest that tumor cell-derived PDGF-C enhances TAM survival, promoting tumor malignancy. 相似文献
70.
The objective of the experiment was to use starch processing waste as an alternative growth medium for cultivation of mycelia of the mushroom Phellinus linteus and to find an optimum condition under solid-state cultivation. Response surface analysis along with a central composite design was successfully applied to approximate the simultaneous effects of the substrate concentration (16-36 g l(-1)), pH (4.5-6.5), and temperature (25-35 degrees C) on the mycelial growth rate. In the model, pH and temperature significantly affected the mycelial growth but substrate concentration did not. The optimal substrate concentration, pH, and temperature for maximizing growth rate of P. linteus mycelia were found to be 16.5 g l(-1), pH 6.0, and 29.7 degrees C, respectively. Subsequent verification of these levels agreed with model predictions and the maximum mycelial growth rate at these conditions was 6.1 +/- 0.8 mm day(-1). Therefore, the results of the experiments suggest that starch processing waste could be utilized as a growth substrate for the cultivation of the mushroom mycelia of P. linteus, enhancing the usefulness of this byproduct of the starch manufacturing industry. This approach is likely to be useful for establishing similar parameters for the cultivation of other fungi. 相似文献