• Title/Summary/Keyword: $\xi-potential$

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BCR/ABL mRNA Targeting Small Interfering RNA Effects on Proliferation and Apoptosis in Chronic Myeloid Leukemia

  • Zhu, Xi-Shan;Lin, Zi-Ying;Du, Jing;Cao, Guang-Xin;Liu, Gang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4773-4780
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    • 2014
  • Background: To investigate the effects of small interference RNA (siRNA) targeting BCR/ABL mRNA on proliferation and apoptosis in the K562 human chronic myeloid leukemia (CML) cell line and to provide a theoretical rationale and experimental evidence for its potential clinical application for anti-CML treatment. Materials and Methods: The gene sequence for BCR/ABL mRNA was found from the GeneBank. The target gene site on the BCR/ABL mRNA were selected according to Max-Planck-Institute (MPI) and rational siRNA design rules, the secondary structure of the candidate targeted mRNA was predicted, the relevant thermodynamic parameters were analyzed, and the targeted gene sequences were compared with BLAST to eliminate any sequences with significant homology. Inhibition of proliferation was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry (FCM) and the morphology of apoptotic cells was identified by Giemsa-Wright staining. Western blotting was used to analyze the expression of BCR/ABL fusion protein in K562 cells after siRNA treatment. Results: The mRNA local secondary structure calculated by RNA structure software, and the optimal design of specific siRNA were contributed by bioinformatics rules. Five sequences of BCR/ABL siRNAs were designed and synthesized in vitro. Three sequences, siRNA1384, siRNA1276 and siRNA1786, which showed the most effective inhibition of K562 cell growth, were identified among the five candidate siRNAs, with a cell proliferative inhibitory rate nearly 50% after exposure to 12.5nmol/L~50nmol/L siRNA1384 for 24,48 and 72 hours. The 50% inhibitory concentrations ($IC_{50}$) of siRNA1384, siRNA1276 and siRNA1786 for 24hours were 46.6 nmol/L, 59.3 nmol/L and 62.6 nmol/L, respectively, and 65.668 nmol/L, 76.6 nmol/L, 74.4 nmol/L for 72 hours. The colony-formation inhibiting test also indicated that, compared with control, cell growth of siRNA treated group was inhibited. FCM results showed that the rate of cell apoptosis increased 24 hours after transfecting siRNA. The results of annexinV/PI staining indicated that the rate of apoptosis imcreased (1.53%, 15.3%, 64.5%, 57.5% and 21.5%) following treamtne with siRNAs (siRNA34, siRNA372, siRNA1384, siRNA1276 and siRNA1786). Morphological analysis showed td typical morphologic changes of apoptosis such as shrunken, fragmentation nucleus as well as "apoptotic bodies" after K562 cell exposure to siRNA. Western blot analysis showed that BCR/ABL protein was reduced sharply after a single dose of 50nmol/L siRNA transfection. Conclusions: Proliferation of K562 cells was remarkbly inhibited by siRNAs (siRNA1384, siRNA1276 and siRNA1786) in a concentration-dependent manner in vitro, with effective induction of apoptosis at a concentration of 50 nmol/L. One anti-leukemia mechanism in K562 cells appeared that BCR/ABL targeted protein was highly down-regulated. The siRNAs (siRNA1384, siRNA1276 and siRNA1786) may prove valuable in the treatment of CML.

Eurasian Naval Power on Display: Sino-Russian Naval Exercises under Presidents Xi and Putin (유라시아 지역의 해군 전력 과시: 시진핑 주석과 푸틴 대통령 체제 하에 펼쳐지는 중러 해상합동훈련)

  • Richard Weitz
    • Maritime Security
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    • v.5 no.1
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    • pp.1-53
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    • 2022
  • One manifestation of the contemporary era of renewed great power competition has been the deepening relationship between China and Russia. Their strengthening military ties, notwithstanding their lack of a formal defense alliance, have been especially striking. Since China and Russia deploy two of the world's most powerful navies, their growing maritime cooperation has been one of the most significant international security developments of recent years. The Sino-Russian naval exercises, involving varying platforms and locations, have built on years of high-level personnel exchanges, large Russian weapons sales to China, the Sino-Russia Treaty of Friendship, and other forms of cooperation. Though the joint Sino-Russian naval drills began soon after Beijing and Moscow ended their Cold War confrontation, these exercises have become much more important during the last decade, essentially becoming a core pillar of their expanding defense partnership. China and Russia now conduct more naval exercises in more places and with more types of weapons systems than ever before. In the future, Chinese and Russian maritime drills will likely encompass new locations, capabilities, and partners-including possibly the Arctic, hypersonic delivery systems, and novel African, Asian, and Middle East partners-as well as continue such recent innovations as conducting joint naval patrols and combined arms maritime drills. China and Russia pursue several objectives through their bilateral naval cooperation. The Treaty of Good-Neighborliness and Friendly Cooperation Between the People's Republic of China and the Russian Federation lacks a mutual defense clause, but does provide for consultations about common threats. The naval exercises, which rehearse non-traditional along with traditional missions (e.g., counter-piracy and humanitarian relief as well as with high-end warfighting), provide a means to enhance their response to such mutual challenges through coordinated military activities. Though the exercises may not realize substantial interoperability gains regarding combat capabilities, the drills do highlight to foreign audiences the Sino-Russian capacity to project coordinated naval power globally. This messaging is important given the reliance of China and Russia on the world's oceans for trade and the two countries' maritime territorial disputes with other countries. The exercises can also improve their national military capabilities as well as help them learn more about the tactics, techniques, and procedures of each other. The rising Chinese Navy especially benefits from working with the Russian armed forces, which have more experience conducting maritime missions, particularly in combat operations involving multiple combat arms, than the People's Liberation Army (PLA). On the negative side, these exercises, by enhancing their combat capabilities, may make Chinese and Russian policymakers more willing to employ military force or run escalatory risks in confrontations with other states. All these impacts are amplified in Northeast Asia, where the Chinese and Russian navies conduct most of their joint exercises. Northeast Asia has become an area of intensifying maritime confrontations involving China and Russia against the United States and Japan, with South Korea situated uneasily between them. The growing ties between the Chinese and Russian navies have complicated South Korean-U.S. military planning, diverted resources from concentrating against North Korea, and worsened the regional security environment. Naval planners in the United States, South Korea, and Japan will increasingly need to consider scenarios involving both the Chinese and Russian navies. For example, South Korean and U.S. policymakers need to prepare for situations in which coordinated Chinese and Russian military aggression overtaxes the Pentagon, obligating the South Korean Navy to rapidly backfill for any U.S.-allied security gaps that arise on the Korean Peninsula. Potentially reinforcing Chinese and Russian naval support to North Korea in a maritime confrontation with South Korea and its allies would present another serious challenge. Building on the commitment of Japan and South Korea to strengthen security ties, future exercises involving Japan, South Korea, and the United States should expand to consider these potential contingencies.

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