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101.
The silencing of specific oncogenes via RNA interference (RNAi) holds great promise for the future of cancer therapy. RNAi
is commonly carried out using small interfering RNA (siRNA) composed of a 19 bp duplex region with a 2-nucleotide overhang
at each 3′ end. This classical siRNA structure, however, can trigger non-specific effects, which has hampered the development
of specific and safe RNAi therapeutics. Previously, we developed a novel siRNA structure, called asymmetric shorter-duplex
siRNA (asiRNA), which did not cause the non-specific effects triggered by conventional siRNA, such as off-target gene silencing
mediated by the sense strand. In this study, we first screened potent asiRNA molecules targeting the human c-MET gene, a promising
anticancer target. Next, the activity of a selected asiRNA was further optimized by introducing a locked nucleic acid (LNA)
to maximize the gene silencing potency. The optimized asiRNA targeted to c-MET may have potential as a specific and safe anticancer
RNAi therapeutic. 相似文献
102.
Sung Mi Ju Su Jin Lee Dong Hyeon Sin Young-Hee Kang Moo-Ho Won Dong-Joo Kwon Soo Young Choi 《Biochemical and biophysical research communications》2009,387(1):115-1259
Keratinocytes, one of major cell types in the skin, can be induced by TNF-α and IFN-γ to express thymus- and activation-regulated chemokine (TARC/CCL17), which is considered to be a pivotal mediator in the inflammatory responses during the development of inflammatory skin diseases, such as atopic dermatitis (AD). In this study, we examined the effect of 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), isolated from the barks of Juglans mandshurica, on TNF-α/IFN-γ induced CCL17 expression in the human keratinocyte cell line HaCaT. Pretreatment of HaCaT cells with PGG suppressed TNF-α/IFN-γ-induced protein and mRNA expression of CCL17. PGG significantly inhibited TNF-α/IFN-γ-induced NF-κB activation as well as STAT1 activation. Furthermore, pretreatment with PGG resulted in significant reduction in expression of CXCL9, 10, and 11 in the HaCaT cells treated with IFN-γ. These results suggest that PGG may exert anti-inflammatory responses by suppressing TNF-α and/or IFN-γ-induced activation of NF-κB and STAT1 in the keratinocytes and might be a useful tool in therapy of skin inflammatory diseases. 相似文献
103.
Lee SK Lee JO Kim JH Kim SJ You GY Moon JW Jung JH Park SH Uhm KO Park JM Suh PG Kim HS 《Journal of cellular biochemistry》2011,112(5):1259-1267
Insulin resistance is the primary cause responsible for type 2 diabetes. Phosphatase and tensin homolog (PTEN) plays a negative role in insulin signaling and its inhibition improves insulin sensitivity. Metformin is a widely used insulin-sensitizing drug; however, the mechanism by which metformin acts is poorly understood. To gain insight into the role of PTEN, we examined the effect of metformin on PTEN expression. Metformin suppressed the expression of PTEN in an AMP-activated protein kinase (AMPK)-dependent manner in preadipocyte 3T3-L1 cells. Knock-down of PTEN potentiated the increase in insulin-mediated phosphorylation of Akt/ERK. Metformin also increased the phosphorylation of c-Jun N-terminal kinase (JNK)-c-Jun and mammalian target of rapamycin (mTOR)-p70S6 kinase pathways. Both pharmacologic inhibition and knock-down of AMPK blocked metformin-induced phosphorylation of JNK and mTOR. Knock-down of AMPK recovered the metformin-induced PTEN down-regulation, suggesting the involvement of AMPK in PTEN regulation. PTEN promoter activity was suppressed by metformin and inhibition of mTOR and JNK by pharmacologic inhibitors blocked metformin-induced PTEN promoter activity suppression. These findings provide evidence for a novel role of AMPK on PTEN expression and thus suggest a possible mechanism by which metformin may contribute to its beneficial effects on insulin signaling. 相似文献
104.
Chung Kwon Kim Ji-Yoon Hwang Tae Hee Hong Du Man Lee Kyunghoon Lee Hyun Nam Kyeung Min Joo 《BMB reports》2022,55(7):336
Narrowing of arteries supplying blood to the limbs provokes critical hindlimb ischemia (CLI). Although CLI results in irreversible sequelae, such as amputation, few therapeutic options induce the formation of new functional blood vessels. Based on the proangiogenic potentials of stem cells, in this study, it was examined whether a combination of dental pulp stem cells (DPSCs) and human umbilical vein endothelial cells (HUVECs) could result in enhanced therapeutic effects of stem cells for CLI compared with those of DPSCs or HUVECs alone. The DPSCs+ HUVECs combination therapy resulted in significantly higher blood flow and lower ischemia damage than DPSCs or HUVECs alone. The improved therapeutic effects in the DPSCs+ HUVECs group were accompanied by a significantly higher number of microvessels in the ischemic tissue than in the other groups. In vitro proliferation and tube formation assay showed that VEGF in the conditioned media of DPSCs induced proliferation and vessel-like tube formation of HUVECs. Altogether, our results demonstrated that the combination of DPSCs and HUVECs had significantly better therapeutic effects on CLI via VEGF-mediated crosstalk. This combinational strategy could be used to develop novel clinical protocols for CLI proangiogenic regenerative treatments. 相似文献
105.
106.
Kalthoum Tizaoui Jae Won Yang Keum Hwa Lee Ji Hong Kim Minseok Kim Sojung Yoon Yeonwoo Jung Joon Beom Park Kitae An Hyeok Choi Donggyu Song HyunTaek Jung Seongmin Ahn Taeho Yuh Hee Min Choi Jae Ha Ahn Younjuong Kim Sanghyun Jee Hyeongsun Lee Soohwa Jin Jun-Gu Kang Bohyun Koo Joo Yeop Lee Kyoung Min Min Wonseok Yoo Hyeong Jun Rhyu Yeonjung Yoon Min Ho Lee Sung Eun Kim Jimin Hwang Ai Koyanagi Louis Jacob Seoyeon Park Jae Il Shin Lee Smith 《International journal of biological sciences》2022,18(9):3731
YKL-40, a chitinase-3-like protein 1 (CHI3L1) or human cartilage glycoprotein 39 (HC gp-39), is expressed and secreted by various cell-types including macrophages, chondrocytes, fibroblast-like synovial cells and vascular smooth muscle cells. Its biological function is not well elucidated, but it is speculated to have some connection with inflammatory reactions and autoimmune diseases. Although having important biological roles in autoimmunity, there were only attempts to elucidate relationships of YKL-40 with a single or couple of diseases in the literature. Therefore, in order to analyze the relationship between YKL-40 and the overall diseases, we reviewed 51 articles that discussed the association of YKL-40 with rheumatoid arthritis, psoriasis, systemic lupus erythematosus, Behçet disease and inflammatory bowel disease. Several studies showed that YKL-40 could be assumed as a marker for disease diagnosis, prognosis, disease activity and severity. It is also shown to be involved in response to disease treatment. However, other studies showed controversial results particularly in the case of Behçet disease activity. Therefore, further studies are needed to elucidate the exact role of YKL-40 in autoimmunity and to investigate its potential in therapeutics. 相似文献
107.
Rocío Joo Andrea Snchez-Tapia Sara Mortara Yanina Bellini Saibene Heather Turner Dorothea Hug Peter Natalia Soledad Morandeira Matt Bannert Batool Almazrouq Elizabeth Hare Laura Acin Juan Pablo Narvez-Gmez Marcela Alfaro Crdoba Federico Marini Rita Giordano Silvia Caneln Anicet Ebou Adithi R. Upadhya Joselyn Chvez Janani Ravi 《PLoS computational biology》2022,18(7)
Conferences are spaces to meet and network within and across academic and technical fields, learn about new advances, and share our work. They can help define career paths and create long-lasting collaborations and opportunities. However, these opportunities are not equal for all. This article introduces 10 simple rules to host an inclusive conference based on the authors’ recent experience organizing the 2021 edition of the useR! statistical computing conference, which attracted a broad range of participants from academia, industry, government, and the nonprofit sector. Coming from different backgrounds, career stages, and even continents, we embraced the challenge of organizing a high-quality virtual conference in the context of the Coronavirus Disease 2019 (COVID-19) pandemic and making it a kind, inclusive, and accessible experience for as many people as possible. The rules result from our lessons learned before, during, and after the organization of the conference. They have been written mainly for potential organizers and selection committees of conferences and contain multiple practical tips to help a variety of events become more accessible and inclusive. We see this as a starting point for conversations and efforts towards building more inclusive conferences across the world. * Translated versions of the English abstract and the list of rules are available in 10 languages in S1 Text: Arabic, French, German, Italian, Japanese, Korean, Portuguese, Spanish, Tamil, and Thai. 相似文献
108.
109.
This paper examines recent developments and applications of Hidden Markov Models (HMMs) to various problems in computational biology, including multiple sequence alignment, homology detection, protein sequences classification, and genomic annotation. 相似文献
110.