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121.
Drug repositioning can identify new therapeutic applications for existing drugs, thus mitigating high R&D costs. The Protein kinase 2 (CK2) inhibitor CX-4945 regulates human cancer cell survival and angiogenesis. Here we found that CX-4945 significantly inhibited the RANKL-induced osteoclast differentiation, but enhanced the BMP2-induced osteoblast differentiation in a cell culture model. CX-4945 inhibited the RANKL-induced activation of TRAP and NFATc1 expression accompanied with suppression of Akt phosphorylation, but, in contrast, it enhanced the BMP2-mediated ALP induction and MAPK ERK1/2 phosphorylation. CX-4945 is thus a novel drug candidate for bone-related disorders such as osteoporosis. 相似文献
122.
Kim Ok-Hee Kang Gun-Hyung Noh Hyungjoon Cha Ji-Young Lee Ho-Jae Yoon Jeong-Hwan Mamura Mizuko Nam Jeong-Seok Lee Dae Ho Kim Young A. Park Young Joo Kim Hyeonjin Oh Byung-Chul 《Molecules and cells》2013,36(5):432-438
Tumor-associated macrophages (TAMs) accumulate in various cancers and promote tumor angiogenesis and metastasis, and thus may be ideal targets for the clinical diagnosis of tumor metastasis with high specificity. However, there are few specific markers to distinguish between TAMs and normal or inflammatory macrophages. Here, we show that TAMs localize in green fluorescent protein-labeled tumors of metastatic lymph nodes (MLNs) from B16F1 melanoma cells but not in necrotic tumor regions, suggesting that TAMs may promote the growth of tumor cells and the progression of tumor metastasis. Furthermore, we isolated pure populations of TAMs from MLNs and characterized their gene expression signatures compared to peritoneal macrophages (PMs), and found that TAMs significantly overexpress immunosuppressive cytokines such as IL-4, IL-10, and TGF-β as well as proangiogenic factors such as VEGF, TIE2, and CD31. Notably, immunological analysis revealed that TIE2+/CD31+ macrophages constitute the predominant population of TAMs that infiltrate MLNs, distinct from tissue or inflammatory macrophages. Importantly, these TIE2+/CD31+ macrophages also heavily infiltrated MLNs from human breast cancer biopsies but not reactive hyperplastic LNs. Thus, TIE2+/CD31+ macrophages may be a unique histopathological biomarker for detecting metastasis in clinical diagnosis, and a novel and promising target for TAM-specific cancer therapy. 相似文献
123.
Many solid tumor cells exhibit mitochondrial respiratory impairment; however, the mechanisms of such impairment in cancer development remain unclear. Here, we demonstrate that SNU human hepatoma cells with declined mitochondrial respiratory activity showed decreased expression of mitochondrial 8-oxoguanine DNA glycosylase/lyase (mtOGG1), a mitochondrial DNA repair enzyme; similar results were obtained with human hepatocellular carcinoma tissues. Among several OGG1-2 variants with a mitochondrial-targeting sequence (OGG1-2a, -2b, -2c, -2d, and -2e), OGG1-2a was the major mitochondrial isoform in all examined hepatoma cells. Interestingly, hepatoma cells with low mtOGG1 levels showed delayed cell growth and increased intracellular reactive oxygen species (ROS) levels. Knockdown of OGG1-2 isoforms in Chang-L cells, which have active mitochondrial respiration with high mtOGG1 levels, significantly decreased cellular respiration and cell growth, and increased intracellular ROS. Overexpression of OGG1-2a in SNU423 cells, which have low mtOGG1 levels, effectively recovered cellular respiration and cell growth activities, and decreased intracellular ROS. Taken together, our results suggest that mtOGG1 plays an important role in maintaining mitochondrial respiration, thereby contributing to cell growth of hepatoma cells. 相似文献
124.
Insu Jeon Ji-Yong Bae Jin-Hong Park Taek-Rim Yoon Mitsugu Todo Masaaki Mawatari 《Computer methods in biomechanics and biomedical engineering》2013,16(1):103-112
To investigate the biomechanical effect of collars, finite element analyses are carried out through two hip joints that are implanted using collared and collarless stems, respectively, and an intact hip joint model. For the analyses, the sacrum, coxal bone, and the cancellous and cortical bones of a femur are modelled using finite elements based on X-ray computed tomographic images taken from a 27-year-old woman. From the results, it is found that a collar with perfect calcar contact prevents stem subsidence and decreases the proximal–lateral gap and the lateral stem tilting. Therefore, it can impart reasonable biomechanical stability for total hip arthroplasty. However, its low load transmission ability and increased stem tilting effect due to the imperfect contact between the collar and the calcar are found to be serious problems that need to be solved. Results of clinical follow-up are presented for supporting the computational results. 相似文献
125.
Hee Kyoung Kang Jung Han Suh Jung Jin Lee Sun Hee Yoon Jin Won Hyun Seong Won Choi 《Free radical research》2013,47(7):773-779
The present study was undertaken to examine the effect of l-ascorbic acid (LAA) on the growth of HL-60 promyelocytic leukemia cells, besides induction of apoptosis. LAA (≥10-4?M) was found to markedly inhibit the proliferation of HL-60 in liquid culture and clonogenicity in semisolid culture. Moreover, LAA-treated HL-60 showed activity to produce chemiluminescence and expressed CD 66b cell surface antigens, indicating that LAA induces the differentiation of HL-60 mainly into granulocytes. The results are supported by morphological changes of LAA-treated HL-60 into segmented neutrophils. Therefore, the inhibitory effect of LAA on the growth of HL-60 cells seems to arise from the induction of differentiation. To assess the potential role of LAA, cells were exposed to oxygen radical scavengers in the absence or presence of LAA. Catalase abolished and superoxide dismutase promoted LAA-induced differentiation of HL-60. Thus, H2O2 produced as a result of LAA treatment seems to play a major role in induction of HL-60 differentiation. 相似文献
126.
127.
Jae-Jin Lee Hyun Ji Lee Gi Seon Jang Ja Myoung Yu Ji Yoon Cha Su Jeong Kim Eun Bit Lee Myung Kyum Kim 《Journal of microbiology (Seoul, Korea)》2013,51(3):305-311
Strain DY59T, a Gram-positive non-motile bacterium, was isolated from soil in South Korea, and was characterized to determine its taxonomic position. Phylogenetic analysis based on the 16S rRNA gene sequence of strain DY59T revealed that the strain DY59T belonged to the family Deinococcaceae in the class Deinococci. The highest degree of sequence similarities of strain DY59T were found with Deinococcus radiopugnans KACC 11999T (99.0%), Deinococcus marmoris KACC 12218T (97.9%), Deinococcus saxicola KACC 12240T (97.0%), Deinococcus aerolatus KACC 12745T (96.2%), and Deinococcus frigens KACC 12220T (96.1%). Chemotaxonomic data revealed that the predominant fatty acids were iso-C15:0 (19.0%), C16:1 ω7c (17.7%), C15:1 ω6c (12.6%), iso-C17:0 (10.3%), and iso-C17:1 ω9c (10.3%). A complex polar lipid profile consisted of a major unknown phosphoglycolipid. The predominant respiratory quinone is MK-8. The cell wall peptidoglycan contained D-alanine, L-glutamic acid, glycine, and L-ornithine (di-amino acid). The novel strain showed resistance to gamma radiation, with a D10 value (i.e. the dose required to reduce the bacterial population by 10-fold) in excess of 5 kGy. Based on the phylogenetic, chemotaxonomic, and phenotypic data, strain DY59T (=KCTC 33033T =JCM 18581T) should be classified as a type strain of a novel species, for which the name Deinococcus swuensis sp. nov. is proposed. 相似文献
128.
Byoung-Shik Shim Jung-ah Choi Ho-Hyun Song Sung-Moo Park In Su Cheon Ji-Eun Jang Sun Je Woo Chung Hwan Cho Min-Suk Song Hyemi Kim Kyung Joo Song Jae Myun Lee Suhng Wook Kim Dae Sub Song Young Ki Choi Jae-Ouk Kim Huan Huu Nguyen Dong Wook Kim Young Yil Bahk Cheol-Heui Yun Man Ki Song 《Journal of microbiology (Seoul, Korea)》2013,51(1):130-135
Influenza viruses are respiratory pathogens that continue to pose a significantly high risk of morbidity and mortality of humans worldwide. Vaccination is one of the most effective strategies for minimizing damages by influenza outbreaks. In addition, rapid development and production of efficient vaccine with convenient administration is required in case of influenza pandemic. In this study, we generated recombinant influenza virus hemagglutinin protein 1 (sHA1) of 2009 pandemic influenza virus as a vaccine candidate using a well-established bacterial expression system and administered it into mice via sublingual (s.l.) route. We found that s.l. immunization with the recombinant sHA1 plus cholera toxin (CT) induced mucosal antibodies as well as systemic antibodies including neutralizing Abs and provided complete protection against infection with pandemic influenza virus A/CA/04/09 (H1N1) in mice. Indeed, the protection efficacy was comparable with that induced by intramuscular (i.m.) immunization route utilized as general administration route of influenza vaccine. These results suggest that s.l. vaccination with the recombinant non-glycosylated HA1 protein offers an alternative strategy to control influenza outbreaks including pandemics. 相似文献
129.
Yochan Joung Haneul Kim Beom-Il Lee Heeyoung Kang Tae Yong Jang O-Seob Kwon Kiseong Joh 《Journal of microbiology (Seoul, Korea)》2013,51(4):531-535
A Gram-staining-negative, rod-shaped and red-pigmented bacterial strain, HMD3125T, was isolated from a solar saltern in Jeungdo, Republic of Korea. A phylogenetic tree based on 16S rRNA gene sequences showed that strain HMD3125T formed a lineage within the genus Pontibacter and was similar to Pontibacter salisaro (96.1%) and P. korlensis (95.3%). The major fatty acids of strain HMD3125T were summed feature 4 (comprising iso-C17:1 I and/or anteiso-C17:1 B; 30.4%), iso-C15:0 (20.4%) and iso-C17:0 3OH (17.2%). The polar lipid profile of HMD3125T consisted of the phosphatidylethanolamine, four unidentified polar lipids, unidentified phospholipid, unidentified aminolipid and unidentified aminophospholipid. Strain HMD3125T contained MK-7 as the predominant menaquinone and sym-homospermidine as the major polyamine. The DNA G+C content of strain HMD3125T was 45.6 mol%. Strain HMD3125T assigned as a novel species in the genus Pontibacter, for which the name Pontibacter jeungdoensis sp. nov. is proposed. The type strain is HMD3125T (=KCTC 23156T =CECT 7710T). 相似文献
130.
Seung Hyun Kim Sin-Duk Jang Ki Yong Lee Sang Hyun Sung 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):230-233
A methanolic extract of dried leaves of Polygala japonica Houtt (Polygalaceae) significantly attenuated nitric oxide production in lipopolysaccharide-simulated BV2 microglia. Five anthraquinones chrysophanol (1), emodin (2), aloe-emodin (3), emodin 8-O-β-D-glucopyranoside (4) and trihydroxy anthraquinone (5), and four flavonoids kaempferol (6), chrysoeriol (7), kaempferol 3-gentiobioside (8) and isorhamnetin (9) were isolated from the methanolic extract using bioactivity-guided fractionation. Among them, compounds 1–4, 6 and 7 showed significant inhibitory effect on lipopolysaccharide-induced nitric oxide production in BV2 microglia at the concentrations ranging from 1.0 to 100.0 μM. 相似文献