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Effective Antiviral Activity of the Tyrosine Kinase Inhibitor Sunitinib Malate against Zika Virus
Lin Chen-Sheng,Huang Su-Hua,Yan Bo-Yu,Lai Hsueh-Chou,Lin Cheng-Wen 대한감염학회 2021 Infection and Chemotherapy Vol.53 No.4
Introduction: Zika virus (ZIKV), a mosquito-borne flavivirus, causes the outbreaks of Latin America in 2015 - 2016, with the incidence of neurological complications. Sunitinib malate, an orally bioavailable malate salt of the tyrosine kinase inhibitor, is suggested as a broadspectrum antiviral agent against emerging viruses like severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. Materials and Methods: This study investigated the antiviral efficacy and antiviral mechanisms of sunitinib malate against ZIKV infection using cytopathic effect reduction, virus yield, and time-of-addition assays. Results: Sunitinib malate concentration-dependently reduced ZIKV-induced cytopathic effect, the expression of viral proteins, and ZIKV yield in supernatant with 50% inhibitory concentration (IC50) value of 0.015 μM, and the selectivity index of greater than 100 against ZIKV infection, respectively. Sunitinib malate had multiple antiviral actions during entry and post-entry stages of ZIKV replication. Sunitinib malate treatment at entry stage significantly reduced the levels of ZIKV RNA replication with the reduction of (+) RNA to (-) RNA ratio and the production of new intracellular infectious particles in infected cells. The treatment at post-entry stage caused a concentration-dependent increase in the levels of ZIKV (+) RNA and (-) RNA in infected cells, along with enlarging the ratio of (+) RNA to (-) RNA, but caused a pointed increase in the titer of intracellular infectious particles by 0.01 and 0.1 μM, and a substantial decrease in the titer of intracellular infectious particles by 1 μM. Conclusion: The study discovered the antiviral actions of sunitinib malate against ZIKV infection, demonstrating a repurposed, host-targeted approach to identify potential antiviral drugs for treating emerging and global viral diseases.
Lin Huang,Iwan Sugihartono,Djati Handoko,양동석,Candra Kurniawan,Erfan Handoko,김동현 한국물리학회 2019 Current Applied Physics Vol.19 No.3
We have investigated the correlation between structural and magnetic properties of M-type BaFe12O19 thin films (∼1.4 μm) with Co-Ti (magnetic/non-magnetic) and Co-Ni(magnetic/magnetic) substitution, as BaFe12- 2xCoxTixO19 and BaFe12-2xCoxNixO19 (0≤x≤1). With structural properties sensitively related to the magnetic properties, where ferro-ferri phase transition is involved, it has been found that magnetic properties can be substantially controlled by substitution concentration.
Combining Ultrasound-Mediated Intracellular Delivery with Microfluidics in Various Applications
Huang Guangyong,Lin Lin,Wu Shixiong,Dang Haojie,Cheng Xuesong,Liu Ying,You Hui 한국바이오칩학회 2024 BioChip Journal Vol.18 No.1
Ultrasound-mediated intracellular delivery is one of the popular technologies based on membrane rupture at present. To date, ultrasound directly acts on a large number of cells to achieve cargo delivery and has been widely used in drug deliv-ery, disease therapy and other fields. However, the existing macroscopic methods can no longer meet the requirements of accurate tracking and analysis and are prone to extensive cell damage and even death. With the rapid advancements in microfl uidic technologies, the combination of ultrasound and microfluidics (CUM) technology can effectively improve the delivery efficiency and cell survival rates. This new technology has rapidly become a new direction and focus of research. Thus, we analysed the mechanism of sonoporation and the effect of acoustic waves in a microfluidic channel. In addition, we reviewed the application of these new technologies in terms of structure and fabrication of ultrasound transducers and microfl uidic devices. As regards our main objective, we hope to help researchers better understand the future developments and the challenges of new technologies. With this review, researchers can promote the development of new technologies to solve the current challenges of intracellular delivery and advance clinical applications.
Lin Huang,Tingwen Guo,Yongjian Zhou,Dong Han,Yu Gu,Cheng Song,Feng Pan 한국자기학회 2022 Journal of Magnetics Vol.27 No.4
The casting process of Fe-Ni Invar alloy could drastically affect magnetic properties and thermal expansion. We have observed analogous trends of saturation magnetization and thermal expansion coefficient in two distinct types of casted samples, as we perform post-annealing at different temperatures. X-ray diffraction measurements show that all the alloys remain in the same face-centered cubic structure after different heat treatments without phase transformation. With the help of X-ray diffraction and differential thermal analysis, we have inferred that these changes in properties might be induced by magnetic lattice transitions and analyzed the possible reason for property differences in samples. This work delivers a perspective on the relationships between thermal expansion, magnetic properties, and heat treatments, which could help to improve the industrial assembly line design.
Lin Wang,Jingjing Miao,Huageng Huang,Boyu Chen,Xiao Xiao,Manyi Zhu,Yingshan Liang,Weiwei Xiao,Shaomin Huang,Yinglin Peng,Xiaowu Deng,Xing Lv,Weixiong Xia,Yanqun Xiang,Xiang Guo,Fei Han,Chong Zhao 대한암학회 2022 Cancer Research and Treatment Vol.54 No.1
Purpose This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients. Materials and Methods Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010. Results With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group. Conclusion Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.
Streptomyces Telomeres Contain a Promoter
Lin, Yuh-ru,Hahn, Mi-Young,Roe, Jung-Hye,Huang, Tzu-Wen,Tsai, Hsiu-Hui,Lin, Yung-Feng,Su, Tsung-Sheng,Chan, Yu-Jiun,Chen, Carton W. American Society for Microbiology 2009 Journal of Bacteriology Vol.191 No.3
<B>ABSTRACT</B><P>Bidirectional replication of the linear chromosomes and plasmids of <I>Streptomyces</I> spp. results in single-strand overhangs at their 3′ ends, which contain extensive complex palindromic sequences. The overhangs are believed to be patched by DNA synthesis primed by a terminal protein that remains covalently bound to the 5′ ends of the telomeres. We discovered that in vitro a conserved 167-bp telomere DNA binds strongly to RNA polymerase holoenzyme and exhibits promoter activities stronger than those of an rRNA operon. In vivo, the telomere DNA exhibited promoter activity in both orientations on a circular plasmid in <I>Streptomyces</I>. The telomere promoter is also active on a linear plasmid during exponential growth. Such promoter activity in a telomere has not hitherto been observed in eukaryotic or prokaryotic replicons. <I>Streptomyces</I> telomere promoters may be involved in priming the terminal Okazaki fragment (during replication) replicative transfer (during conjugation), or expression of downstream genes (including a conserved <I>ttrA</I> helicase-like gene involved in conjugal transfer). Interestingly, the <I>Streptomyces</I> telomeres also function as a promoter in <I>Escherichia coli</I> and as a transcription enhancer in yeast.</P>