75 results on '"Yueh-Hsin Ping"'
Search Results
2. Glycosylation and S-palmitoylation regulate SARS-CoV-2 spike protein intracellular trafficking
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Chih-Feng Tien, Wan-Ting Tsai, Chun Hwa Chen, Hui-Ju Chou, Mingzi M. Zhang, Jhe-Jhih Lin, En-Ju Lin, Shih-Syong Dai, Yueh-Hsin Ping, Chia-Yi Yu, Yi-Ping Kuo, Wei-Hsiang Tsai, Hsin-Wei Chen, and Guann-Yi Yu
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Biochemistry ,Virology ,Cell biology ,Science - Abstract
Summary: Post-translational modifications (PTMs), such as glycosylation and palmitoylation, are critical to protein folding, stability, intracellular trafficking, and function. Understanding regulation of PTMs of SARS-CoV-2 spike (S) protein could help the therapeutic drug design. Herein, the VSV vector was used to produce SARS-CoV-2 S pseudoviruses to examine the roles of the 611LYQD614 and cysteine-rich motifs in S protein maturation and virus infectivity. Our results show that 611LY612 mutation alters S protein intracellular trafficking and reduces cell surface expression level. It also changes S protein glycosylation pattern and decreases pseudovirus infectivity. The S protein contains four cysteine-rich clusters with clusters I and II as the main palmitoylation sites. Mutations of clusters I and II disrupt S protein trafficking from ER-to-Golgi, suppress pseudovirus production, and reduce spike-mediated membrane fusion activity. Taken together, glycosylation and palmitoylation orchestrate the S protein maturation processing and are critical for S protein-mediated membrane fusion and infection.
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- 2022
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3. Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2
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Ly Hien Doan, Li-Wei Chu, Zi-Yi Huang, Anh Thuc Nguyen, Chia-Yin Lee, Chien-Ling Huang, Yu-Fen Chang, Wen-Yu Hsieh, Trang Thi Huyen Nguyen, Chao-Hsiung Lin, Chun-Li Su, Tsung-Hsien Chuang, Jin-Mei Lai, Feng-Sheng Wang, Chia-Jui Yang, Hui-Kang Liu, Yueh-Hsin Ping, and Chi-Ying F. Huang
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COVID-19 ,SARS-CoV-2 variants ,Omicron variant (SARS-CoV-2) ,Delta variant (B.1.617.2) ,ACE2 (angiotensin-converting enzyme 2) ,miRNA ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Coronavirus disease 2019 (COVID-19) remains a threat with the emergence of new variants, especially Delta and Omicron, without specific effective therapeutic drugs. The infection causes dysregulation of the immune system with a cytokine storm that eventually leads to fatal acute respiratory distress syndrome (ARDS) and further irreversible pulmonary fibrosis. Therefore, the promising way to inhibit infection is to disrupt the binding and fusion between the viral spike and the host ACE2 receptor. A transcriptome-based drug screening platform has been developed for COVID-19 to explore the possibility and potential of the long-established drugs or herbal medicines to reverse the unique genetic signature of COVID-19. In silico analysis showed that Virofree, an herbal medicine, reversed the genetic signature of COVID-19 and ARDS. Biochemical validations showed that Virofree could disrupt the binding of wild-type and Delta-variant spike proteins to ACE2 and its syncytial formation via cell-based pseudo-typed viral assays, as well as suppress binding between several variant recombinant spikes to ACE2, especially Delta and Omicron. Additionally, Virofree elevated miR-148b-5p levels, inhibited the main protease of SARS-CoV-2 (Mpro), and reduced LPS-induced TNF-α release. Virofree also prevented cellular iron accumulation leading to ferroptosis which occurs in SARS-CoV-2 patients. Furthermore, Virofree was able to reduce pulmonary fibrosis-related protein expression levels in vitro. In conclusion, Virofree was repurposed as a potential herbal medicine to combat COVID-19. This study highlights the inhibitory effect of Virofree on the entry of Delta and Omicron variants of SARS-CoV-2, which have not had any effective treatments during the emergence of the new variants spreading.
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- 2022
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4. Repurposing Astragalus Polysaccharide PG2 for Inhibiting ACE2 and SARS-CoV-2 Spike Syncytial Formation and Anti-Inflammatory Effects
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Chia-Yin Lee, Anh Thuc Nguyen, Ly Hien Doan, Li-Wei Chu, Chih-Hung Chang, Hui-Kang Liu, I-Lin Lee, Teng-Hsu Wang, Jin-Mei Lai, Shih-Ming Tsao, Hsiu-Jung Liao, Yueh-Hsin Ping, and Chi-Ying F. Huang
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COVID-19 ,microRNAs ,macrophages ,cytokine storm ,viral entry ,Microbiology ,QR1-502 - Abstract
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health. In an effort to develop novel anti-coronavirus therapeutics and achieve prophylactics, we used gene set enrichment analysis (GSEA) for drug screening and identified that Astragalus polysaccharide (PG2), a mixture of polysaccharides purified from Astragalus membranaceus, could effectively reverse COVID-19 signature genes. Further biological assays revealed that PG2 could prevent the fusion of BHK21-expressing wild-type (WT) viral spike (S) protein and Calu-3-expressing ACE2. Additionally, it specifically prevents the binding of recombinant viral S of WT, alpha, and beta strains to ACE2 receptor in our non-cell-based system. In addition, PG2 enhances let-7a, miR-146a, and miR-148b expression levels in the lung epithelial cells. These findings speculate that PG2 has the potential to reduce viral replication in lung and cytokine storm via these PG2-induced miRNAs. Furthermore, macrophage activation is one of the primary issues leading to the complicated condition of COVID-19 patients, and our results revealed that PG2 could regulate the activation of macrophages by promoting the polarization of THP-1-derived macrophages into an anti-inflammatory phenotype. In this study, PG2 stimulated M2 macrophage activation and increased the expression levels of anti-inflammatory cytokines IL-10 and IL-1RN. Additionally, PG2 was recently used to treat patients with severe COVID-19 symptoms by reducing the neutrophil-to-lymphocyte ratio (NLR). Therefore, our data suggest that PG2, a repurposed drug, possesses the potential to prevent WT SARS-CoV-2 S-mediated syncytia formation with the host cells; it also inhibits the binding of S proteins of WT, alpha, and beta strains to the recombinant ACE2 and halts severe COVID-19 development by regulating the polarization of macrophages to M2 cells.
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- 2023
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5. The Traditional Chinese Medicine Formula Jing Guan Fang for Preventing SARS-CoV-2 Infection: From Clinical Observation to Basic Research
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Yueh-Hsin Ping, Hsin Yeh, Li-Wei Chu, Zhi-Hu Lin, Yin-Chieh Hsu, Lie-Chwen Lin, Chung-Hua Hsu, Shu-Ling Fu, and Tung-Yi Lin
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Chinese medicine decoction ,Jing Guan Fang ,ACE2 ,TMPRSS2 ,COVID-19 ,prevention ,Therapeutics. Pharmacology ,RM1-950 - Abstract
COVID-19 is a global epidemic. Developing adjuvant therapies which could prevent the virus from binding to cells may impair viral infection. This study produces a traditional Chinese medicine formula, Jing Guan Fang (JGF), based on ancient medical texts, and examines the efficacy and the mechanism by which JGF prevents viral infections. JGF reduces COVID-19 like symptoms. Functional studies show that JGF inhibits the formation of syncytium and reduces the formation of viral plaque. JGF is not toxic in vitro and in vivo. Mechanistically, JGF induces lysosomal-dependent ACE2 degradation and suppresses mRNA and the protein levels of TMPRSS2 in human lung WI-38 and MRC-5 cells. Mice that inhale JGF exhibit reduced ACE2 and TMPRSS2 protein levels in lung tissues. Together, these findings suggest that JGF may improve the COVID-19 like symptoms and inhibit viral infection. Moreover, JGF may be applicable as an adjuvant preventive strategy against SARS-CoV-2 infection in addition to the use of vaccines.
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- 2022
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6. Honeysuckle (Lonicera japonica) and Huangqi (Astragalus membranaceus) Suppress SARS-CoV-2 Entry and COVID-19 Related Cytokine Storm in Vitro
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Yuan-Chieh Yeh, Ly Hien Doan, Zi-Yi Huang, Li-Wei Chu, Tzu-Hau Shi, Ying-Ray Lee, Cheng-Tao Wu, Chao-Hsiung Lin, Shu-Tuan Chiang, Hui-Kang Liu, Tsung-Hsien Chuang, Yueh-Hsin Ping, Hsiao-Sheng Liu, and Chi-Ying F. Huang
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honeysuckle ,Huangqi ,COVID-19 ,SARS-CoV-2 ,microRNA ,let-7a ,Therapeutics. Pharmacology ,RM1-950 - Abstract
COVID-19 is threatening human health worldwide but no effective treatment currently exists for this disease. Current therapeutic strategies focus on the inhibition of viral replication or using anti-inflammatory/immunomodulatory compounds to improve host immunity, but not both. Traditional Chinese medicine (TCM) compounds could be promising candidates due to their safety and minimal toxicity. In this study, we have developed a novel in silico bioinformatics workflow that integrates multiple databases to predict the use of honeysuckle (Lonicera japonica) and Huangqi (Astragalus membranaceus) as potential anti-SARS-CoV-2 agents. Using extracts from honeysuckle and Huangqi, these two herbs upregulated a group of microRNAs including let-7a, miR-148b, and miR-146a, which are critical to reduce the pathogenesis of SARS-CoV-2. Moreover, these herbs suppressed pro-inflammatory cytokines including IL-6 or TNF-α, which were both identified in the cytokine storm of acute respiratory distress syndrome, a major cause of COVID-19 death. Furthermore, both herbs partially inhibited the fusion of SARS-CoV-2 spike protein-transfected BHK-21 cells with the human lung cancer cell line Calu-3 that was expressing ACE2 receptors. These herbs inhibited SARS-CoV-2 Mpro activity, thereby alleviating viral entry as well as replication. In conclusion, our findings demonstrate that honeysuckle and Huangqi have the potential to be used as an inhibitor of SARS-CoV-2 virus entry that warrants further in vivo analysis and functional assessment of miRNAs to confirm their clinical importance. This fast-screening platform can also be applied to other drug discovery studies for other infectious diseases.
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- 2022
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7. Development of Fluorescence-Tagged SARS-CoV-2 Virus-like Particles by a Tri-Cistronic Vector Expression System for Investigating the Cellular Entry of SARS-CoV-2
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Young-Sheng Chang, Li-Wei Chu, Zan-Yu Chen, Joh-Sin Wu, Wen-Chi Su, Chia-Jui Yang, Yueh-Hsin Ping, and Cheng-Wen Lin
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SARS-CoV-2 ,virus-like particle ,fluorescence labeling ,cell entry ,ACE2 ,fusion ,Microbiology ,QR1-502 - Abstract
Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has caused the pandemic that began late December 2019. The co-expression of SARS-CoV-2 structural proteins in cells could assemble into several types of virus-like particles (VLPs) without a viral RNA genome. VLPs containing S proteins with the structural and functional properties of authentic virions are safe materials to exploit for virus-cell entry and vaccine development. In this study, to generate SARS-CoV-2 VLPs (SCoV2-SEM VLPs) composed of three structural proteins including spike (S), envelop (E) protein and membrane (M) protein, a tri-cistronic vector expression system was established in a cell line co-expressing SARS-CoV-2 S, E and M proteins. The SCoV2-SEM VLPs were harvested from the cultured medium, and three structure proteins were confirmed by Western blot assay. A negative-stain TEM assay demonstrated the size of the SCoV2-SEM VLPs with a diameter of about 90 nm. To further characterize the infectious properties of SCoV2-SEM VLPs, the VLPs (atto647N-SCoV2-SEM VLPs) were fluorescence-labeled by conjugation with atto-647N and visualized under confocal microscopy at a single-particle resolution. The results of the infection assay revealed that atto647N-SCoV2-SEM VLPs attached to the surface of the HEK293T cells at the pre-binding phase in a ACE2-dependent manner. At the post-infection phase, atto647N-SCoV2-SEM VLPs either fused with the cellular membrane or internalized into the cytoplasm with mCherry-rab5-positive early endosomes. Moreover, fusion with the cellular membrane and the internalization with early endosomes could be inhibited by the treatment of camostat (a pharmacological inhibitor of TMPRSS2) and chlorpromazine (an endocytosis inhibitor), respectively. These results elucidated that SCoV2-SEM VLPs behave similarly to the authentic live SARS-CoV-2 virus, suggesting that the development of SCoV2-SEM VLPs provide a realistic and safe experimental model for studying the infectious mechanism of SARS-CoV-2.
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- 2022
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8. The Mechanism of the Zika Virus Crossing the Placental Barrier and the Blood-Brain Barrier
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Chi-Fen Chiu, Li-Wei Chu, I-Chen Liao, Yogy Simanjuntak, Yi-Ling Lin, Chi-Chang Juan, and Yueh-Hsin Ping
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Zika virus ,placental barrier ,blood-brain barrier ,tight junction ,transcytosis ,single-virus imaging ,Microbiology ,QR1-502 - Abstract
Zika virus (ZIKV) infection causes severe neurological symptoms in adults and fetal microcephaly and the virus is detected in the brain of microcephaly and meningoencephalitis patient. However, the mechanism of ZIKV crossing the physiological barrier to the central nervous systems (CNS) remains elusive. The placental barrier and the blood brain barrier (BBB) protect the fetus from pathogens and ensure healthy brain development during pregnancy. In this study, we used human placenta trophoblasts cells (JEG-3) and human brain-derived endothelial cells (hCMEC/D3) as in vitro models of the physiological barriers. Results showed that ZIKV could infect JEG-3 cells effectively and reduce the amounts of ZO-1 and occludin between adjacent cells by the proteasomal degradation pathway, suggesting that the permeability of the barrier differentially changed in response to ZIKV infection, allowing the virus particle to cross the host barrier. In contrast, ZIKV could infect hCMEC/D3 cells without disrupting the BBB barrier permeability and tight junction protein expression. Although no disruption to the BBB was observed during ZIKV infection, ZIKV particles were released on the basal side of the BBB model and infected underlying cells. In addition, we observed that fluorescence-labeled ZIKV particles could cross the in vitro placenta barrier and BBB model by transcytosis and the action of transcytosis could be blocked by either low temperature or pharmacological inhibitors of endocytosis. In summary, the ZIKV uses a cell-type specific paracellular pathway to cross the placenta monolayer barrier by disrupting cellular tight junction. In addition, the ZIKV can also cross both the placenta barrier and the BBB by transcytosis. Our study provided new insights into on the mechanism of the cellular barrier penetration of ZIKV particles.
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- 2020
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9. Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression
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I-Han Wang, Tzu-Ting Huang, Ji-Lin Chen, Li-Wei Chu, Yueh-Hsin Ping, Kai-Wen Hsu, Kuo-Hung Huang, Wen-Liang Fang, Hsin-Chen Lee, Chian-Feng Chen, Chen-Chung Liao, Rong-Hong Hsieh, and Tien-Shun Yeh
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HMGCS1 ,mevalonate pathway ,gastric cancer progression ,integrated stress response ,pluripotency ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a potential regulatory node in the mevalonate pathway that is frequently dysregulated in tumors. This study found that HMGCS1 expression is upregulated in stomach adenocarcinoma samples of patients and tumorspheres of gastric cancer cells. HMGCS1 elevates the expression levels of the pluripotency genes Oct4 and SOX-2 and contributes to tumorsphere formation ability in gastric cancer cells. HMGCS1 also promotes in vitro cell growth and progression and the in vivo tumor growth and lung metastasis of gastric cancer cells. After blocking the mevalonate pathway by statin and dipyridamole, HMGCS1 exerts nonmetabolic functions in enhancing gastric cancer progression. Furthermore, the level and nuclear translocation of HMGCS1 in gastric cancer cells are induced by serum deprivation. HMGCS1 binds to and activates Oct4 and SOX-2 promoters. HMGCS1 also enhances the integrated stress response (ISR) and interacts with the endoplasmic reticulum (ER) stress transducer protein kinase RNA-like endoplasmic reticulum kinase (PERK). Our results reveal that HMGCS1 contributes to gastric cancer progression in both metabolic and nonmetabolic manners.
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- 2020
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10. TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy
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Li-Wei Chu, Chia-Jui Yang, Kuan-Jen Peng, Pei-Ling Chen, Shuu-Jiun Wang, and Yueh-Hsin Ping
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dengue virus ,autophagy ,tim-1 ,p85 ,rab5 ,early endosome ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Dengue virus (DENV) infection triggers the activation of autophagy to facilitate the viral replication cycle from various aspects. Although a number of stimulators are proposed to activate autophagy, none of them appears prior to the uncoating process. Given that T-cell immunoglobulin and mucin domain 1 (TIM-1) receptor is a putative DENV receptor and promotes apoptotic body clearance by autophagy induction, it raises the possibility that TIM-1 may participate in the activation of DENV-induced autophagy. In this study, confocal images first revealed the co-localization of TIM-1 with autophagosomes in DENV-induced autophagy rather than rapamycin-induced autophagy, suggesting the co-transportation of TIM-1 with DENV during infection. The treatment of siRNA to knockdown TIM-1 expression in DENV-infected GFP-microtubule-associated protein light chain 3 (LC3)-Huh7.5 cells revealed that TIM-1 is required not only for DENV cellular internalization but also for autophagy activation. Furthermore, knockdown p85, a subunit of phosphoinositide 3-kinases (PI3Ks), which is co-localized with TIM-1 at rab5-positive endosomes caused the reduction of autophagy, indicating that TIM-1-mediated DENV-induced autophagy requires p85. Taken together, the current study uncovered TIM-1 as a novel factor for triggering autophagy in DENV infection through TIM-1-p85 axis, in addition to serving as a DENV receptor.
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- 2019
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11. Honokiol, a Lignan Biphenol Derived from the Magnolia Tree, Inhibits Dengue Virus Type 2 Infection
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Chih-Yeu Fang, Siang-Jyun Chen, Huey-Nan Wu, Yueh-Hsin Ping, Ching-Yen Lin, David Shiuan, Chi-Long Chen, Ying-Ray Lee, and Kao-Jean Huang
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antiviral ,honokiol ,dengue virus ,Magnolia ,Microbiology ,QR1-502 - Abstract
Dengue is the most widespread arbovirus infection and poses a serious health and economic issue in tropical and subtropical countries. Currently no licensed vaccine or compounds can be used to prevent or manage the severity of dengue virus (DENV) infection. Honokiol, a lignan biphenol derived from the Magnolia tree, is commonly used in Eastern medicine. Here we report that honokiol has profound antiviral activity against serotype 2 DENV (DENV-2). In addition to inhibiting the intracellular DENV-2 replicon, honokiol was shown to suppress the replication of DENV-2 in baby hamster kidney (BHK) and human hepatocarcinoma Huh7 cells. At the maximum non-toxic dose of honokiol treatment, the production of infectious DENV particles was reduced >90% in BHK and Huh7 cells. The underlying mechanisms revealed that the expression of DENV-2 nonstructural protein NS1/NS3 and its replicating intermediate, double-strand RNA, was dramatically reduced by honokiol treatment. Honokiol has no effect on the expression of DENV putative receptors, but may interfere with the endocytosis of DENV-2 by abrogating the co-localization of DENV envelope glycoprotein and the early endosomes. These results indicate that honokiol inhibits the replication, viral gene expression, and endocytotic process of DENV-2, making it a promising agent for chemotherapy of DENV infection.
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- 2015
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12. Gene expression profiling of peripheral blood leukocytes identifies and validates ABCB1 as a novel biomarker for Alzheimer's disease
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Kuang-Den Chen, Po-Tsung Chang, Yueh-Hsin Ping, Hsin-Chen Lee, Chin-Wei Yeh, and Pei-Ning Wang
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Gene expression profile ,ABCB1 ,Peripheral blood leukocytes ,Microarray ,Alzheimer's disease ,Mild cognitive impairment ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Increasing evidence has shown that the immunological reaction of leukocytes plays a crucial role in the development of neurodegenerative disorders. We conducted transcriptome analysis of leukocytes from patients of mild cognitive impairment (MCI), Alzheimer's disease (AD), as well as normal controls (NC) by oligonucleotide microarray. The differentially expressed genes of interest were selected by pathway-based functional enrichment and were then validated in 60 subjects (17 NC, 20 MCI and 23 AD) by quantitative PCR (QRT-PCR). Thirty-four differentially expressed genes between NC and AD were enriched in ATP-binding cassette (ABC) transporters, ascorbate and aldarate metabolism, Gly/Ser/Thr metabolism, transforming growth factor-β signaling, and extracellular matrix (ECM)-receptor interaction pathways (Welch t-test; p
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- 2011
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13. Effect of heated tobacco products and traditional cigarettes on pulmonary toxicity and SARS-CoV-2-induced lung injury
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Han-Hsing Tsou, Ping-Huai Wang, Tzu-Hsin Ting, Yueh-Hsin Ping, Tsung-Yun Liu, Hsiao-Wei Cheng, and Hsiang-Tsui Wang
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Lung Diseases ,Angiotensins ,Tight Junction Proteins ,SARS-CoV-2 ,NF-kappa B ,COVID-19 ,Lung Injury ,Tobacco Products ,Toxicology ,Cadherins ,Pulmonary Disease, Chronic Obstructive ,Claudin-1 ,Spike Glycoprotein, Coronavirus ,Tobacco ,Cytokines ,Angiotensin-Converting Enzyme 2 - Abstract
Cigarette smoke (CS) significantly contributes to the development of chronic obstructive pulmonary disease (COPD). Heated tobacco products (HTPs), newly developed cigarette products, have been proposed as an alternative for safe cigarette smoking. Although it is plausible to think that replacing traditional cigarettes with HTPs would lower the risks of COPD, this notion requires confirmation by further investigations from sources independent of the tobacco industry. COPD is characterized by an ongoing inflammatory process in the lungs, and the renin-angiotensin system (RAS) has been implicated in the pathogenesis of COPD. Angiotensin-converting enzyme-2 (ACE2) functions as a negative regulator of RAS and has been suggested as a cellular receptor for the causative agent of SARS-CoV-2. It has been shown that smoking is most likely associated with the negative progression and adverse outcomes of SARS-CoV-2. In this study, we found that cigarette smoke extracts from traditional cigarettes (CSE) caused higher cytotoxicity and higher oxidative stress levels than extracts from HTPs (HTPE) in two lung cell lines (Calu-3 and Beas-2B). CSE and HTPE induced RAS activation, MAPK activation, and NF-kB inflammatory pathway activation, resulting in the production of inflammatory cytokines. Furthermore, CSE and a high dose of HTPE reduced tight junction proteins, including claudin 1, E-cadherin, and ZO-1, and disrupted lung epidermal tight junctions at the air-liquid interface (ALI). Finally, CSE and HTPE enhanced the spike protein S1-induced lung injury response. Together, these results suggest that HTPE induced similar lung pathogenesis relevant to COPD and SARS-CoV-2-induced lung injury caused by CSE.
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- 2022
14. A Houttuynia cordata-based Chinese herbal formula improved symptoms of allergic rhinitis during the COVID-19 pandemic
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Kai-Wei Chang, Tung-Yi Lin, Shu-Ling Fu, Yueh-Hsin Ping, Fang-pey Chen, and Yen-Ying Kung
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Adult ,Lipopolysaccharides ,China ,Interleukin-6 ,Anosmia ,COVID-19 ,General Medicine ,Middle Aged ,Rhinitis, Allergic ,Young Adult ,Quality of Life ,Humans ,Houttuynia ,Pandemics ,Drugs, Chinese Herbal - Abstract
The symptoms of coronavirus disease 2019 (COVID-19) such as hyposmia, rhinorrhea, nasal obstruction, and cough are similar to those of chronic allergic rhinitis (AR). Such symptoms can easily lead AR patients to unnecessary anxiety, misdiagnosis, and invasive diagnostic tests in the COVID-19 pandemic. Interleukin-6 (IL-6) is an important mediator for chronic AR and plays a crucial role in the inflammation of COVID-19. Houttuynia cordata (HC) has been shown to reduce nasal congestion and swelling by suppressing the activation of IL-6 and is used to fight COVID-19. A novel HC-based Chinese herbal formula, Zheng-Yi-Fang (ZYF), was developed to test effects on nasal symptoms of patients with AR in the COVID-19 pandemic.Participants aged between 20 and 60 years with at least a 2-year history of moderate to severe perennial AR were enrolled. Eligible participants were randomly allocated to either the intervention group (taking ZYF) or the control group (using regular western medicine) for 4 weeks. The Chinese version of the Rhinosinusitis Outcome Measures was used to evaluate impacts on quality of life and nasal symptoms of participants with AR. In addition, the effect of ZYF on lipopolysaccharide (LPS)-induced IL-6 was investigated.Participants with AR taking ZYF improved their symptoms of nasal obstruction, nasal secretion, hyposmia, and postnasal drip in comparison with those of the control group. Meanwhile, ZYF exhibited inhibition of IL-6 secretion in the LPS-induced inflammatory model.ZYF has potential effects to relieve nasal symptoms for AR during the COVID-19 pandemic.
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- 2022
15. Benzenesulfonamide Derivatives as Calcium/Calmodulin-Dependent Protein Kinase Inhibitors and Antiviral Agents against Dengue and Zika Virus Infections
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Li Wei Chu, Yi Ling Lee, Yueh Hsin Ping, Wen-Shan Li, Yi-Ling Lin, Wei Chia Chen, and Yogy Simanjuntak
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Viremia ,Dengue virus ,medicine.disease_cause ,Antiviral Agents ,01 natural sciences ,Dengue fever ,Zika virus ,Dengue ,Mice ,Structure-Activity Relationship ,03 medical and health sciences ,Catalytic Domain ,Ca2+/calmodulin-dependent protein kinase ,Drug Discovery ,medicine ,Animals ,Humans ,Protein kinase A ,Protein Kinase Inhibitors ,030304 developmental biology ,Sulfonamides ,0303 health sciences ,Molecular Structure ,biology ,Zika Virus Infection ,Chemistry ,Kinase ,Proteins ,Outbreak ,Zika Virus ,Dengue Virus ,medicine.disease ,biology.organism_classification ,Virology ,0104 chemical sciences ,Molecular Docking Simulation ,010404 medicinal & biomolecular chemistry ,Drug Design ,Molecular Medicine ,Protein Binding - Abstract
Emerging and resurging mosquito-borne flaviviruses are an important public health challenge. The increased prevalence of dengue virus (DENV) infection has had a significant socioeconomic impact on epidemic countries. The recent outbreak of Zika virus (ZIKV) has created an international public health emergency because ZIKV infection has been linked to congenital defects and Guillain-Barre syndrome. To develop potentially prophylactic antiviral drugs for combating these acute infectious diseases, we have targeted the host calcium/calmodulin-dependent kinase II (CaMKII) for inhibition. By using CaMKII structure-guided inhibitor design, we generated four families of benzenesulfonamide (BSA) derivatives for SAR analysis. Among these substances, N-(4-cycloheptyl-4-oxobutyl)-4-methoxy-N-phenylbenzenesulfonamide (9) showed superior properties as a lead CaMKII inhibitor and antiviral agent. BSA 9 inhibited CaMKII activity with an IC50 value of 0.79 μM and displayed EC50 values of 1.52 μM and 1.91 μM against DENV and ZIKV infections of human neuronal BE(2)C cells, respectively. Notably, 9 significantly reduced the viremia level and increased animal survival time in mouse-challenge models.
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- 2020
16. Honeysuckle (
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Yuan-Chieh, Yeh, Ly Hien, Doan, Zi-Yi, Huang, Li-Wei, Chu, Tzu-Hau, Shi, Ying-Ray, Lee, Cheng-Tao, Wu, Chao-Hsiung, Lin, Shu-Tuan, Chiang, Hui-Kang, Liu, Tsung-Hsien, Chuang, Yueh-Hsin, Ping, Hsiao-Sheng, Liu, and Chi-Ying F, Huang
- Abstract
COVID-19 is threatening human health worldwide but no effective treatment currently exists for this disease. Current therapeutic strategies focus on the inhibition of viral replication or using anti-inflammatory/immunomodulatory compounds to improve host immunity, but not both. Traditional Chinese medicine (TCM) compounds could be promising candidates due to their safety and minimal toxicity. In this study, we have developed a novel
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- 2021
17. Mechanism of site-specific psoralen photoadducts formation in triplex DNA directed by psoralen-conjugated oligonucleotides
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Yueh-Hsin Ping and Rana, Tariq M.
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Binding sites (Biochemistry) -- Research ,DNA microarrays -- Research ,Psoralens -- Research ,Biological sciences ,Chemistry - Abstract
Triplex structures were generated by targeting a DNA duplex with photoreactive psoralen molecule (psoTFO), where TFO is triplex-formation oligonucleotides, of different lengths in order to investigate the mechanism of photoadduct-formation by psoralen photo-cross-linking. Results demonstrated that UV radiation of triplexes formed between a psoTFO and a DNA duplex generated two distinct groups of psoralen photoadducts, monoadducts and psoralen interstand cross-link products.
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- 2005
18. Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression
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Ji-Lin Chen, Yueh Hsin Ping, Li-Wei Chu, Rong-Hong Hsieh, Chian-Feng Chen, Kuo Hung Huang, Tzu Ting Huang, Wen-Liang Fang, Kai-Wen Hsu, I-Han Wang, Chen-Chung Liao, Tien Shun Yeh, and Hsin Chen Lee
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0301 basic medicine ,Cancer Research ,Statin ,medicine.drug_class ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Integrated stress response ,gastric cancer progression ,Cell growth ,Kinase ,Chemistry ,Endoplasmic reticulum ,mevalonate pathway ,Cancer ,integrated stress response ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,pluripotency ,medicine.disease ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,HMGCS1 ,Mevalonate pathway - Abstract
The 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a potential regulatory node in the mevalonate pathway that is frequently dysregulated in tumors. This study found that HMGCS1 expression is upregulated in stomach adenocarcinoma samples of patients and tumorspheres of gastric cancer cells. HMGCS1 elevates the expression levels of the pluripotency genes Oct4 and SOX-2 and contributes to tumorsphere formation ability in gastric cancer cells. HMGCS1 also promotes in vitro cell growth and progression and the in vivo tumor growth and lung metastasis of gastric cancer cells. After blocking the mevalonate pathway by statin and dipyridamole, HMGCS1 exerts nonmetabolic functions in enhancing gastric cancer progression. Furthermore, the level and nuclear translocation of HMGCS1 in gastric cancer cells are induced by serum deprivation. HMGCS1 binds to and activates Oct4 and SOX-2 promoters. HMGCS1 also enhances the integrated stress response (ISR) and interacts with the endoplasmic reticulum (ER) stress transducer protein kinase RNA-like endoplasmic reticulum kinase (PERK). Our results reveal that HMGCS1 contributes to gastric cancer progression in both metabolic and nonmetabolic manners.
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- 2020
19. TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy
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Yueh Hsin Ping, Kuan Jen Peng, Chia Jui Yang, Li Wei Chu, Shuu Jiun Wang, and Pei Ling Chen
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early endosome ,0301 basic medicine ,viruses ,Dengue virus ,Virus Replication ,medicine.disease_cause ,lcsh:Chemistry ,Dengue ,0302 clinical medicine ,Hepatitis A Virus Cellular Receptor 1 ,Receptor ,Internalization ,lcsh:QH301-705.5 ,Spectroscopy ,media_common ,Gene knockdown ,virus diseases ,General Medicine ,Apoptotic body ,Computer Science Applications ,Cell biology ,Gene Knockdown Techniques ,030220 oncology & carcinogenesis ,Signal Transduction ,autophagy ,TIM-1 ,Endosome ,media_common.quotation_subject ,Biology ,rab5 ,Models, Biological ,Article ,Catalysis ,Cell Line ,Inorganic Chemistry ,03 medical and health sciences ,medicine ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,p85 ,dengue virus ,Organic Chemistry ,Autophagy ,Autophagosomes ,biochemical phenomena, metabolism, and nutrition ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Viral replication ,Biomarkers - Abstract
Dengue virus (DENV) infection triggers the activation of autophagy to facilitate the viral replication cycle from various aspects. Although a number of stimulators are proposed to activate autophagy, none of them appears prior to the uncoating process. Given that T-cell immunoglobulin and mucin domain 1 (TIM-1) receptor is a putative DENV receptor and promotes apoptotic body clearance by autophagy induction, it raises the possibility that TIM-1 may participate in the activation of DENV-induced autophagy. In this study, confocal images first revealed the co-localization of TIM-1 with autophagosomes in DENV-induced autophagy rather than rapamycin-induced autophagy, suggesting the co-transportation of TIM-1 with DENV during infection. The treatment of siRNA to knockdown TIM-1 expression in DENV-infected GFP-microtubule-associated protein light chain 3 (LC3)-Huh7.5 cells revealed that TIM-1 is required not only for DENV cellular internalization but also for autophagy activation. Furthermore, knockdown p85, a subunit of phosphoinositide 3-kinases (PI3Ks), which is co-localized with TIM-1 at rab5-positive endosomes caused the reduction of autophagy, indicating that TIM-1-mediated DENV-induced autophagy requires p85. Taken together, the current study uncovered TIM-1 as a novel factor for triggering autophagy in DENV infection through TIM-1-p85 axis, in addition to serving as a DENV receptor.
- Published
- 2019
20. MicroRNA‑23a/27a/24‑2 cluster promotes gastric cancer cell proliferation synergistically
- Author
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Hsin Chen Lee, Chin-Wen Chi, Kate Hua, Yu‑Ting Chen, Ming Ta Hsu, Ya‑Syuan Tang, Tien Shun Yeh, Chi Hung Lin, Kuo Hung Huang, Yueh Hsin Ping, Tzu Ting Huang, Chian Feng Chen, Chew Wun Wu, and Yu‑Cheng Lin
- Subjects
0301 basic medicine ,Cancer Research ,Oncogene ,Chemistry ,gastric cancer ,Cell ,Cancer ,Articles ,Cell cycle ,medicine.disease ,Molecular medicine ,03 medical and health sciences ,microRNA-23a/27a/24-2 cluster ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,suppressor of cytokine-induced signaling 6 ,Cancer cell ,microRNA ,medicine ,Cancer research ,SOCS6 - Abstract
Previous studies have indicated that certain microRNAs (miRNAs/miRs) function as either tumor suppressors or oncogenes in human cancer. The present study identified the miR-23a/27a/24-2 cluster, containing miR-23, miR-27a and miR-24, as an oncogene in gastric cancer. The expression of the miR-23a/27a/24-2 cluster was upregulated in clinical gastric cancer tissues. Transfection with inhibitors of miR-23a, miR-27a, or miR-24, either independently or together, repressed in vitro colony formation and in vivo tumor formation. The miR23a/27a/24-2 cluster inhibitors repressed the growth of gastric cancer cells in a synergistic manner. In addition, treatment with lower doses of the miRNA inhibitor mixture induced the formation of apoptotic bodies. According to computational predictions using TargetScan, suppressor of cytokine-induced signaling 6 (SOCS6) was identified as one of the downstream target genes of the miR-23a/27a/24-2 cluster. The expression of SOCS6 was significantly lower in tumor tissues than in matched normal tissues (P
- Published
- 2018
21. Notch1-promoted TRPA1 expression in erythroleukemic cells suppresses erythroid but enhances megakaryocyte differentiation
- Author
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Tien Shun Yeh, Yuan I. Chang, Yueh Hsin Ping, Hsin Chen Lee, Rong Hong Hsieh, Min-Jen Tseng, and Ji Lin Chen
- Subjects
0301 basic medicine ,Transcriptional Activation ,Megakaryocyte differentiation ,Cellular differentiation ,Article ,Proto-Oncogene Protein c-ets-1 ,03 medical and health sciences ,Transactivation ,Erythroid Cells ,hemic and lymphatic diseases ,Cell Line, Tumor ,Humans ,DNA (Cytosine-5-)-Methyltransferases ,RNA, Small Interfering ,Receptor, Notch1 ,Promoter Regions, Genetic ,TRPA1 Cation Channel ,Gene knockdown ,Multidisciplinary ,Oncogene ,Chemistry ,food and beverages ,Cell Differentiation ,DNA Methylation ,Cell biology ,030104 developmental biology ,Cell culture ,DNA methylation ,embryonic structures ,RNA Interference ,K562 Cells ,Megakaryocytes ,psychological phenomena and processes ,K562 cells ,Naphthoquinones - Abstract
The Notch1 pathway plays important roles in modulating erythroid and megakaryocyte differentiation. To screen the Notch1-related genes that regulate differentiation fate of K562 and HEL cells, the expression of transient receptor potential ankyrin 1 (TRPA1) was induced by Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor. N1IC and v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1) bound to TRPA1 promoter region to regulate transcription in K562 cells. Transactivation of TRPA1 promoter by N1IC depended on the methylation status of TRPA1 promoter. N1IC and Ets-1 suppressed the DNA methyltransferase 3B (DNMT3B) level in K562 cells. Inhibition of TRPA1 expression after Notch1 knockdown could be attenuated by nanaomycin A, an inhibitor of DNMT3B, in K562 and HEL cells. Functionally, hemin-induced erythroid differentiation could be suppressed by TRPA1, and the reduction of erythroid differentiation of both cells by N1IC and Ets-1 occurred via TRPA1. However, PMA-induced megakaryocyte differentiation could be enhanced by TRPA1, and the surface markers of megakaryocytes could be elevated by nanaomycin A. Megakaryocyte differentiation could be reduced by Notch1 or Ets-1 knockdown and relieved by TRPA1 overexpression. The results suggest that Notch1 and TRPA1 might be critical modulators that control the fate of erythroid and megakaryocyte differentiation.
- Published
- 2017
22. Downregulation of tumor suppressor MBP-1 by microRNA-363 in gastric carcinogenesis
- Author
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Hsin Chen Lee, Tzu Ting Huang, An-Ming Wang, Yueh Hsin Ping, Chin-Wen Chi, Kai-Wen Hsu, Su Shun Lo, Tien Shun Yeh, and Kuo Hung Huang
- Subjects
Cancer Research ,Epithelial-Mesenchymal Transition ,Lung Neoplasms ,Down-Regulation ,Mice, Nude ,Mice, SCID ,Biology ,medicine.disease_cause ,Downregulation and upregulation ,Stomach Neoplasms ,Cell Line, Tumor ,microRNA ,medicine ,Animals ,Humans ,Epithelial–mesenchymal transition ,3' Untranslated Regions ,Regulation of gene expression ,Three prime untranslated region ,Cancer ,General Medicine ,medicine.disease ,Xenograft Model Antitumor Assays ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Gene Knockdown Techniques ,Phosphopyruvate Hydratase ,Cancer cell ,Cancer research ,Female ,Carcinogenesis - Abstract
Gastric carcinoma is one of the most common malignancies and the second most lethal cancer worldwide. The mechanisms underlying aggressiveness of gastric cancer still remain obscure. c-Myc promoter binding protein 1 (MBP-1) is a negative regulator of c-myc expression and ubiquitously expressed in normal human tissues. It is produced by alternative translation initiation of α-enolase gene. Both MBP-1 and α-enolase are involved in the control of tumorigenesis including gastric cancer. MicroRNAs (miRNAs) are involved in tumorigenesis and could have diagnostic, prognostic and therapeutic potential. In this study, whether miRNAs modulate tumorigenesis of gastric cancer cells through targeting MBP-1 was evaluated. We found that miR-363 targets 3'-untranslated region of human MBP-1/α-enolase messenger RNA. The exogenous miR-363 promotes growth, viability, progression, epithelial-mesenchymal transition and tumorsphere formation of SC-M1 gastric cancer cells through downregulation of MBP-1, whereas the knockdown of endogenous miR-363 suppresses tumorigenesis and progression of SC-M1 cells via upregulation of MBP-1. The miR-363/MBP-1 axis is also involved in the control of carcinogenesis in KATO III and SNU-16 gastric cancer cells. Furthermore, miR-363 induces the xenografted tumor growth and lung metastasis of SC-M1 cells through MBP-1 in vivo. Taken together, these results suggest that miR-363 plays an important role in the increment of gastric carcinogenesis via targeting MBP-1.
- Published
- 2013
23. Identification of novel cancer fusion genes using chromosome breakpoint screening
- Author
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Ya Lun Chen, Yuh-Shan Jou, Chian Feng Chen, Yueh Hsin Ping, Chin Hui Lin, Kate Hua, and Chi Hung Lin
- Subjects
0301 basic medicine ,Cancer Research ,Oncogene Proteins ,Oncogene Proteins, Fusion ,Chromosome Breakpoints ,Chromosomal translocation ,Chromosomal rearrangement ,Biology ,Polymorphism, Single Nucleotide ,Translocation, Genetic ,Fusion gene ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Humans ,Gene ,Protein Kinase C ,Oligonucleotide Array Sequence Analysis ,Sequence Deletion ,Genetics ,Breakpoint ,General Medicine ,Hep G2 Cells ,Amplicon ,Fibronectins ,Isoenzymes ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Genome-Wide Association Study - Abstract
Gene fusion due to rearrangement or translocation of chromosomes is a powerful mutational mechanism during tumorigenesis. Several new high-resolution technologies have recently been developed to evaluate large numbers of small aberrations as candidate loci for fusion gene screening. In our previous whole-genome screening study using 500K SNP arrays, we identified more than 700 homozygous deletions (HDs) and amplicons in 23 cancer cell lines. To explore novel fusion genes in cancer, we established stringent criteria for defining HD and amplicon breakpoints. Then genomic PCR and sequencing analyses identified a fusion gene, FNDC3B-PRKCI, that resulted from chromosome intra-rearrangement. Western blotting and 3'-RACE analyses revealed that the chimeric transcript was an in-frame fusion between FNDC3B and PRKCI. Finally, cell migration and colony formation assays suggested that FNDC3B-PRKCI is a potential oncogene.
- Published
- 2016
24. Positive transcription elongation factor b (P-TEFb) contributes to dengue virus-stimulated induction of interleukin-8 (IL-8)
- Author
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Hsing Hui Lee, Shiau Ting Hu, Shao Hung Wang, Li li Li, Yen Ting Wang, and Yueh Hsin Ping
- Subjects
Cyclin T1 ,viruses ,Immunology ,virus diseases ,Promoter ,RNA polymerase II ,biochemical phenomena, metabolism, and nutrition ,Biology ,Microbiology ,Virology ,Molecular biology ,Transcription (biology) ,Gene expression ,biology.protein ,Viral structural protein ,P-TEFb ,Transcription factor - Abstract
Summary Dengue virus (DENV) is one of the most common infectious pathogens worldwide. One major clinical and pathogenic feature of DENV infection is the elevation of interleukin-8 (IL-8) expression; however, little is known about the molecular mechanism of DENV-induced chemokine production. The positive transcription elongation factor b (P-TEFb) composed of CDK9 and cyclin T1 stimulates gene expression by enhancing RNA polymerase II (RNA pol II) processivity. This study examined the possibility that P-TEFb mediates DENV-induced IL-8 expression. The treatment of either a pharmacological inhibitor of P-TEFb, 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB) or cyclin T1 siRNA prior to DENV infection abolished the elevation of IL-8, indicating that P-TEFb is essential for IL-8 induction. Moreover, DENV core protein participated in the activation of IL-8 promoter in a P-TEFb-dependent manner. Immunostaining and co-immunoprecipitation assays demonstrated the association between P-TEFb and DENV core protein. Finally, chromatin immunoprecipitation (ChIP) results indicated that P-TEFb and DENV core protein were recruited to the transcriptionally active IL-8 gene promoter. Taken together, this study showed that P-TEFb and DENV core protein work in concert to enhance IL-8 gene expression by DENV infection. This is the first demonstration of P-TEFb being directly involved in virus-induced host gene expression by interacting with a viral structural protein.
- Published
- 2010
25. Resveratrol inhibits human lung adenocarcinoma cell metastasis by suppressing heme oxygenase 1-mediated nuclear factor-κB pathway and subsequently downregulating expression of matrix metalloproteinases
- Author
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Feng Yen Lin, Po Len Liu, Albert Linton Charles, Wen Chi Chen, Yueh Hsin Ping, Shah Hwa Chou, Inn Wen Chong, Jhi Jhu Hwang, Jong Rung Tsai, Yung-Hsiang Chen, Yuh-Lien Chen, and Chun Ying Hung
- Subjects
Lung Neoplasms ,Cell Survival ,Angiogenesis ,Down-Regulation ,Adenocarcinoma ,Matrix metalloproteinase ,Biology ,Resveratrol ,Metastasis ,chemistry.chemical_compound ,Cell Movement ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Stilbenes ,medicine ,Humans ,Neoplasm Invasiveness ,Gene Silencing ,RNA, Small Interfering ,Lung cancer ,A549 cell ,Osmolar Concentration ,NF-kappa B ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Matrix Metalloproteinases ,Heme oxygenase ,Matrix Metalloproteinase 9 ,Biochemistry ,chemistry ,Cell culture ,Cancer research ,Matrix Metalloproteinase 2 ,Heme Oxygenase-1 ,Signal Transduction ,Food Science ,Biotechnology - Abstract
Resveratrol exhibits potential anti-carcinogenic activities. Heme oxygenase-1 (HO-1) is involved in angiogenesis and tumor metastasis. Matrix metalloproteinases (MMPs) are key enzymes in the degradation of extracellular matrix, and their expression may be dysregulated in lung cancer metastasis. In this study, we investigated the anti-invasive mechanism of resveratrol in lung cancer cells. HO-1 was shown to be elevated (approximately 4.7-fold) in lung cancer tumor samples as compared with matched normal tissues. After treatment of lung adenocarcinoma cell line A549 cells with resveratrol (50 microM) for 24 h, the migratory and invasive abilities (38 and 30% inhibition, respectively) of A549 cells were significantly reduced. Resveratrol significantly inhibited HO-1-mediated MMP-9 (35% inhibition) and MMP-2 (28% inhibition) expression in lung cancer cells. Nuclear factor (NF)-kappaB inhibitor induced a marked reduction in MMP-9 and MMP-2 expression, suggesting NF-kappaB pathway could play an important role. Furthermore, HO-1 inhibition and silencing significantly suppressed MMPs and invasion of lung cancer cells. Our results suggest that resveratrol inhibited HO-1 and subsequently MMP-9 and MMP-2 expression in lung cancer cells. The inhibitory effects of resveratrol on MMP expression and invasion of lung cancer cells are, in part, associated with the HO-1-mediated NF-kappaB pathway.
- Published
- 2010
26. Open Reading Frame 8a of the Human Severe Acute Respiratory Syndrome Coronavirus Not Only Promotes Viral Replication but Also Induces Apoptosis
- Author
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Te Cheng Lien, Yu Juin Chan, Lung Sen Kao, Chi Hung Lin, Yi Ming Arthur Chen, Kuan Hsuan Chen, Hsin Chen Lee, Yuan Ming Lee, Tjin Shing Jap, Chia Yen Chen, and Yueh Hsin Ping
- Subjects
Programmed cell death ,Small interfering RNA ,Time Factors ,Apoptosis ,Severe Acute Respiratory Syndrome ,Virus Replication ,medicine.disease_cause ,Virus ,Major Articles ,Cell Line ,Major Articles and Brief Reports ,Open Reading Frames ,Oxygen Consumption ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Immunology and Allergy ,Coronaviridae ,RNA, Small Interfering ,Coronavirus ,biology ,Caspase 3 ,Transfection ,biology.organism_classification ,Virology ,Open reading frame ,Infectious Diseases ,Severe acute respiratory syndrome-related coronavirus ,Viral replication ,Viruses ,Reactive Oxygen Species - Abstract
Background A unique genomic difference between human and civet severe acute respiratory syndrome coronaviruses (SARS-CoVs) is that the former has a deletion of 29 nucleotides from open reading frame (orf) 8d that results in the generation of orf8a and orf8b. The objectives of the present study were to analyze antibody reactivity to ORF8a in patients with SARS and to elucidate the function of ORF8a. Methods Western-blot and immunofluorescent antibody assays were used to detect anti-ORF8a antibody. SARS-CoV HKU39849 was used to infect stable clones expressing ORF8a and cells transfected with small interfering RNA (siRNA). The virus loads (VLs) and cytopathic effects (CPEs) were recorded. Confocal microscopy and several mitochondria-related tests were used to study the function of ORF8a. Results Two (5.4%) of 37 patients with SARS had anti-ORF8a antibodies. The VLs in the stable clones expressing ORF8a were significantly higher than those in control subjects 5 days after infection. siRNA against orf8a significantly reduced VLs and interrupted the CPE. ORF8a was found to be localized in mitochondria, and overexpression resulted in increases in mitochondrial transmembrane potential, reactive oxygen species production, caspase 3 activity, and cellular apoptosis. Conclusions ORF8a not only enhances viral replication but also induces apoptosis through a mitochondria-dependent pathway.
- Published
- 2007
27. Enhanced oxidative stress and aberrant mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells during methamphetamine induced apoptosis
- Author
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Chin-Wen Chi, Jiin Cherng Yen, Sheng Fan Wang, Chia Yu Chang, Chi-Wei Wu, Yueh Hsin Ping, Hsin Chen Lee, and Chiao Ling Yeh
- Subjects
Programmed cell death ,Mitochondrial DNA ,Time Factors ,SH-SY5Y ,Gene Dosage ,Apoptosis ,Mitochondrion ,Biology ,Toxicology ,medicine.disease_cause ,DNA, Mitochondrial ,Resting Phase, Cell Cycle ,Antioxidants ,Methamphetamine ,Mitochondrial Proteins ,chemistry.chemical_compound ,Cell Line, Tumor ,medicine ,Humans ,Vitamin E ,Cycloheximide ,Membrane Potential, Mitochondrial ,Protein Synthesis Inhibitors ,Pharmacology ,Dose-Response Relationship, Drug ,G1 Phase ,Meth ,Flow Cytometry ,Fluoresceins ,Mitochondria ,Cell biology ,Oxidative Stress ,Biochemistry ,chemistry ,Mitochondrial biogenesis ,Central Nervous System Stimulants ,Mitochondrial Size ,Reactive Oxygen Species ,Intracellular ,Oxidative stress - Abstract
Methamphetamine (METH) is an abused drug that may cause psychiatric and neurotoxic damage, including degeneration of monoaminergic terminals and apoptosis of non-monoaminergic cells in the brain. The cellular and molecular mechanisms underlying these METH-induced neurotoxic effects remain to be clarified. In this study, we performed a time course assessment to investigate the effects of METH on intracellular oxidative stress and mitochondrial alterations in a human dopaminergic neuroblastoma SH-SY5Y cell line. We characterized that METH induces a temporal sequence of several cellular events including, firstly, a decrease in mitochondrial membrane potential within 1 h of the METH treatment, secondly, an extensive decline in mitochondrial membrane potential and increase in the level of reactive oxygen species (ROS) after 8 h of the treatment, thirdly, an increase in mitochondrial mass after the drug treatment for 24 h, and finally, a decrease in mtDNA copy number and mitochondrial proteins per mitochondrion as well as the occurrence of apoptosis after 48 h of the treatment. Importantly, vitamin E attenuated the METH-induced increases in intracellular ROS level and mitochondrial mass, and prevented METH-induced cell death. Our observations suggest that enhanced oxidative stress and aberrant mitochondrial biogenesis may play critical roles in METH-induced neurotoxic effects.
- Published
- 2007
28. The reciprocal regulation loop of Notch2 pathway and miR-23b in controlling gastric carcinogenesis
- Author
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Chia Chi Ke, Chin-Wen Chi, Hsin Chen Lee, Wen Liang Fang, Tzu Ting Huang, An Ming Wang, Tien Shun Yeh, Yueh Hsin Ping, and Kuo Hung Huang
- Subjects
Male ,Pathology ,Lung Neoplasms ,Time Factors ,Ets1 ,Mice, SCID ,medicine.disease_cause ,Cell Movement ,Mice, Inbred NOD ,Receptor, Notch2 ,3' Untranslated Regions ,miR-23b ,Mice, Inbred BALB C ,notch2 receptor ,Gene Expression Regulation, Neoplastic ,Oncology ,gastric carcinogenesis ,Neoplastic Stem Cells ,Adenocarcinoma ,Signal transduction ,Signal Transduction ,Research Paper ,Pluripotent Stem Cells ,medicine.medical_specialty ,endocrine system ,Epithelial-Mesenchymal Transition ,Mice, Nude ,Transfection ,Proto-Oncogene Protein c-ets-1 ,Stomach Neoplasms ,Cell Line, Tumor ,microRNA ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Epithelial–mesenchymal transition ,Cell Proliferation ,Binding Sites ,Oncogene ,business.industry ,Genetic Therapy ,medicine.disease ,Xenograft Model Antitumor Assays ,MicroRNAs ,E2F1 ,Tumor progression ,Cancer cell ,Cancer research ,business ,Carcinogenesis ,E2F1 Transcription Factor - Abstract
Gastric carcinoma is one of the most common malignancies and the third highest cause of global cancer-related death. Notch2 receptor intracellular domain (N2IC), the activated form of Notch2 receptor, enhances gastric carcinogenesis. MicroRNAs (miRNAs) act as either oncogenes or tumor suppressors in tumorigenesis and cross-talk with Notch pathways. Herein, microRNA-23b (miR-23b) was identified as a Notch2 receptor-related miRNA and its role in gastric carcinogenesis was investigated. Levels of miR-23b in stomach adenocarcinoma samples were down-regulated, whereas those of Notch2 receptor, v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets1), and E2F1 transcripts were up-regulated. Results also showed that N2IC down-regulated miR-23b expression in gastric cancer cells through up-regulating E2F1. The miR-23b inhibited gastric tumorigenesis including growth, viability, epithelial-mesenchymal transition, and abilities of colony formation, migration, invasion, and tumorsphere formation. Mechanistically, miR-23b suppressed tumor progression and pluripotency gene expression and affected tumorsphere ultra-structure in gastric cancer cells via targeting Notch2 receptor or Ets1. Furthermore, miR-23b diminished the xenografted tumor growth and lung metastasis of SC-M1 gastric cancer cells through Notch2 pathway. Our results suggest that Notch2 pathway and miR-23b interplay in a reciprocal regulation loop in gastric cancer cells and this axis plays an important role in gastric carcinogenesis.
- Published
- 2015
29. Intracellular Transport of Vaccinia Virus in HeLa Cells Requires WASH-VPEF/FAM21-Retromer Complexes and Recycling Molecules Rab11 and Rab22
- Author
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Cheng Yen Huang, Yueh Hsin Ping, Wen Chang, Jye Chian Hsiao, Sue Ping Lee, Li Wei Chu, Tzu Jung Chen, and Yung Tsun Lo
- Subjects
Retromer ,Endosome ,viruses ,Immunology ,Genetic Vectors ,Vesicular Transport Proteins ,Vaccinia virus ,Endocytosis ,Microbiology ,Virus ,Fluorescence ,chemistry.chemical_compound ,Virology ,Humans ,Orthopoxvirus ,RNA, Small Interfering ,DNA Primers ,Microscopy, Confocal ,biology ,Cellular Vesicle ,Microfilament Proteins ,Virion ,Lipid bilayer fusion ,Biological Transport ,biology.organism_classification ,Cell biology ,Virus-Cell Interactions ,chemistry ,Mutagenesis ,rab GTP-Binding Proteins ,Insect Science ,Multiprotein Complexes ,Vaccinia ,Carrier Proteins ,HeLa Cells - Abstract
Vaccinia virus, the prototype of the Orthopoxvirus genus in the family Poxviridae , infects a wide range of cell lines and animals. Vaccinia mature virus particles of the WR strain reportedly enter HeLa cells through fluid-phase endocytosis. However, the intracellular trafficking process of the vaccinia mature virus between cellular uptake and membrane fusion remains unknown. We used live imaging of single virus particles with a combination of various cellular vesicle markers, to track fluorescent vaccinia mature virus particle movement in cells. Furthermore, we performed functional interference assays to perturb distinct vesicle trafficking processes in order to delineate the specific route undertaken by vaccinia mature virus prior to membrane fusion and virus core uncoating in cells. Our results showed that vaccinia virus traffics to early endosomes, where recycling endosome markers Rab11 and Rab22 are recruited to participate in subsequent virus trafficking prior to virus core uncoating in the cytoplasm. Furthermore, we identified WASH-VPEF/FAM21-retromer complexes that mediate endosome fission and sorting of virus-containing vesicles prior to virus core uncoating in the cytoplasm. IMPORTANCE Vaccinia mature virions of the WR strain enter HeLa cells through fluid phase endocytosis. We previously demonstrated that virus-containing vesicles are internalized into phosphatidylinositol 3-phosphate positive macropinosomes, which are then fused with Rab5-positive early endosomes. However, the subsequent process of sorting the virion-containing vesicles prior to membrane fusion remains unclear. We dissected the intracellular trafficking pathway of vaccinia mature virions in cells up to virus core uncoating in cytoplasm. We show that vaccinia mature virions first travel to early endosomes. Subsequent trafficking events require the important endosome-tethered protein VPEF/FAM21, which recruits WASH and retromer protein complexes to the endosome. There, the complex executes endosomal membrane fission and cargo sorting to the Rab11-positive and Rab22-positive recycling pathway, resulting in membrane fusion and virus core uncoating in the cytoplasm.
- Published
- 2015
30. DSIF and NELF Interact with RNA Polymerase II Elongation Complex and HIV-1 Tat Stimulates P-TEFb-mediated Phosphorylation of RNA Polymerase II and DSIF during Transcription Elongation
- Author
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Tariq M. Rana and Yueh Hsin Ping
- Subjects
Transcription, Genetic ,RNA polymerase II ,Protein Serine-Threonine Kinases ,Biology ,Biochemistry ,Transcription (biology) ,Humans ,Positive Transcriptional Elongation Factor B ,Phosphorylation ,Negative elongation factor ,Promoter Regions, Genetic ,P-TEFb ,Molecular Biology ,RNA polymerase II holoenzyme ,HIV Long Terminal Repeat ,Cell Nucleus ,Models, Genetic ,Nuclear Proteins ,Templates, Genetic ,Cell Biology ,DSIF ,Molecular biology ,Recombinant Proteins ,Repressor Proteins ,Elongation factor ,Gene Products, tat ,HIV-1 ,biology.protein ,tat Gene Products, Human Immunodeficiency Virus ,RNA Polymerase II ,Transcriptional Elongation Factors ,Transcription factor II D ,HeLa Cells ,Transcription Factors - Abstract
Control of transcription elongation requires a complex interplay between the recently discovered positive transcription elongation factor b (P-TEFb) and negative transcription elongation factors, 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB) sensitivity inducing factors (DSIF) and the negative elongation factor (NELF). Activation of HIV-1 gene expression is regulated by a nascent RNA structure, termed TAR RNA, in concert with HIV-1 Tat protein and these positive and negative elongation factors. We have used a stepwise RNA pol II walking approach and Western blotting to determine the dynamics of interactions between HIV-1 Tat, DSIF/NELF, and the transcription complexes actively engaged in elongation. In addition, we developed an in vitro kinase assay to determine the phosphorylation status of proteins during elongation stages. Our results demonstrate that DSIF/NELF associates with RNA pol II complexes during early transcription elongation and travels with elongation complexes as the nascent RNA is synthesized. Our results also show that HIV-1 Tat protein stimulated DSIF and RNA pol II phosphorylation by P-TEFb during elongation. These findings reveal a molecular mechanism for the negative and positive regulation of transcriptional elongation at the HIV-1 promoter.
- Published
- 2001
31. The effect of Lp3 enlargement on the folding and catalysis of hepatitis delta viruscis-cleaving ribozyme
- Author
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Jing Yu Lee, Chen Nai Wang, Yueh Hsin Ping, and Huey-Nan Wu
- Subjects
Mutant ,Oligonucleotides ,Biophysics ,Biochemistry ,Catalysis ,Virus ,Ribozyme folding ,Structural Biology ,Genetics ,RNA, Catalytic ,Molecular Biology ,biology ,Chemistry ,Oligonucleotide ,Ribozyme ,Cell Biology ,Molecular biology ,Hepatitis delta virus ribozyme ,Folding (chemistry) ,Mutagenesis, Insertional ,biology.protein ,Nucleic Acid Conformation ,RNA, Viral ,Mammalian CPEB3 ribozyme ,Hepatitis Delta Virus ,Hairpin ribozyme ,Ribozyme catalysis ,VS ribozyme - Abstract
Oligonucleotides were inserted into the Lp3 region of a hepatitis delta virus (HDV) cis-cleaving ribozyme and the effect of Lp3 enlargement on ribozyme folding was examined by assaying the activity of each mutant. The location of insertion and the sequence of the inserted oligonucleotide had distinct effects on ribozyme activity, and the HDV ribozyme was capable of adopting the active structure for cis-cleavage when a pentanucleotide was inserted into the 3′ portion of Lp3. Furthermore, whether the insertion mutant cis-cleaved or not, the structure of Lp3 was altered by the inserted oligonucleotide. These findings disclose that the 5′ rather than the 3′ portion of Lp3 is critical for ribozyme folding and catalysis.
- Published
- 1998
32. Application of FRET microscopy for visualizing the uncoating process of a single Dengue virus in living cells
- Author
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Chau-Hwang Lee, Li-Wei Chu, Yueh Hsin Ping, and Ya-Hsuan Lin
- Subjects
Förster resonance energy transfer ,Chemistry ,Scientific method ,Microscopy ,medicine ,Biophysics ,Dengue virus ,medicine.disease_cause ,Instrumentation - Published
- 2015
33. Using Optical Tweezers to Quantify the Interaction Force of Dengue Virus with Host Cellular Receptors
- Author
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Bo-Ying Tsai, Arthur Chiou, Yueh-Hsin Ping, and Jyun-Yu Chen
- Subjects
Materials science ,Optical tweezers ,Host (biology) ,medicine ,Nanotechnology ,Dengue virus ,medicine.disease_cause ,Receptor ,Instrumentation ,Cell biology - Published
- 2015
34. An AU at the first base pair of helix 3 elevates the catalytic activity of hepatitis delta virus ribozymes
- Author
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Zhi Shun Huang, Yueh Hsin Ping, and Huey-Nan Wu
- Subjects
Hepatitis delta virus (HDV) ribozyme ,Stereochemistry ,Base pair ,viruses ,Molecular Sequence Data ,trans-Cleavage ,Biophysics ,Cleavage (embryo) ,Biochemistry ,Virus ,Catalysis ,Ribozyme ,Structural Biology ,Genetics ,RNA, Catalytic ,Molecular Biology ,Base Sequence ,biology ,RNA ,Cell Biology ,Hydrogen-Ion Concentration ,biochemical phenomena, metabolism, and nutrition ,Mutation ,Helix ,biology.protein ,Nucleic Acid Conformation ,RNA, Viral ,cis-Cleavage ,Mammalian CPEB3 ribozyme ,Hepatitis Delta Virus - Abstract
A mutational analysis of the helix 3 (H3) region of hepatitis delta virus (HDV) ribozymes disclosed that an AU at the first base pair of H3 elevates the catalytic activity of various cis- and trans-acting HDV ribozymes. A GC to AU substitution at this position of H3, which is located at the junction of three of the four helices of the pseudoknot-like structure model, altered the structure of HDV ribozymes. This substitution in the H3 did not change the independence of the cleavage rate to pH nor the sensitivity to formamide treatment of the ribozymes.
- Published
- 1997
35. Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection
- Author
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Li-Wei, Chu, Yi-Lung, Huang, Jin-Hui, Lee, Long-Ying, Huang, Wei-Jun, Chen, Ya-Hsuan, Lin, Jyun-Yu, Chen, Rui, Xiang, Chau-Hwang, Lee, and Yueh-Hsin, Ping
- Subjects
Dengue ,Sirolimus ,Adenine ,Cell Line, Tumor ,Phagosomes ,Host-Pathogen Interactions ,Autophagy ,Virion ,Humans ,Dengue Virus ,Molecular Imaging - Abstract
Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.
- Published
- 2013
36. The Importance of the Helix 2 Region for the cis-Cleaving and trans-Cleaving Activities of Hepatitis Delta Virus Ribozymes
- Author
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Yen Chein Lai, Zhi Shun Huang, Chuan Bin Lee, Jung Yaw Lin, Huey-Nan Wu, and Yueh Hsin Ping
- Subjects
Base pair ,Stereochemistry ,Molecular Sequence Data ,Mutant ,Nucleic Acid Denaturation ,Cleavage (embryo) ,Polymerase Chain Reaction ,Biochemistry ,Virus ,Hepatitis B virus PRE beta ,Ribonucleases ,RNA, Catalytic ,Protein secondary structure ,Base Sequence ,Formamides ,biology ,Chemistry ,HEPATITIS DELTA ,Ribozyme ,Virology ,Kinetics ,Mutagenesis ,biology.protein ,Nucleic Acid Conformation ,Electrophoresis, Polyacrylamide Gel ,Hepatitis Delta Virus - Abstract
The sequence, secondary structure, and size requirements of the helix 2 region (H2) of a cis-acting hepatitis delta virus ribozyme Rz 1 were examined in this study. Mutational analysis was performed, and the cleavage rate of each H2 mutant of Rz 1 was assayed. We found that H2 could be elongated to twice its original size without affecting ribozyme folding while the shortening of H2 by one base pair severely decreased autolytic activity. In addition, the maintenance of the Watson-Crick base-pairing interactions of the last base pair of H2 (A16U58) was not critical for cis-cleavage reaction. Nevertheless, mutants with an AA, an AG, an AC, or a GG pair at the bottom of H2 were less active, and the sequence of the H2/H3 interface might affect the stability of the catalytic core. The negative effects on ribozyme folding, such as the destabilization of H2, the unfavorable sequences at the last base pair of H2 as well as the disruption of the continuity of H2 and H3, could be compensated for by elongating the H2 region of the corresponding mutants. The extension of H2 may alter the conformation of ribozyme molecules; in addition, it stabilized the catalytic core and enhanced the resistance to formamide. Finally, for a trans-acting ribozyme and its substrate that require the formation of H1, H2, and H4 to reconstitute the autocatalytic domain of HDV RNA, the extension of H2 stabilized the substrate/ribozyme complex and speeded up the cleavage rate but hindered the product release process.
- Published
- 1996
37. Neuroprotective effect of oral S/B remedy (Scutellaria baicalensis Georgi and Bupleurum scorzonerifolfium Willd) on iron-induced neurodegeneration in the nigrostriatal dopaminergic system of rat brain
- Author
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J.Y. Wang, C.D. Kuo, C.W. Chi, Yueh Hsin Ping, Anya M.Y. Lin, Jen-Hwey Chiu, and G.F. Chang
- Subjects
Male ,Dopamine ,Iron ,Substantia nigra ,Apoptosis ,Pharmacology ,Neuroprotection ,Antioxidants ,Lipid peroxidation ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Electrochemistry ,Animals ,Chromatography, High Pressure Liquid ,Ferrous citrate ,biology ,Traditional medicine ,Plant Extracts ,Dopaminergic ,biology.organism_classification ,Corpus Striatum ,Bupleurum ,Rats ,Substantia Nigra ,Oxidative Stress ,Neuroprotective Agents ,Spectrometry, Fluorescence ,chemistry ,Scutellaria baicalensis ,Trolox ,Lipid Peroxidation ,medicine.drug - Abstract
Aim of the study S/B remedy prepared from Scutellaria baicalensis Georgi and Bupleurum scorzonerifolfium Willd, two herbals of Xiao-Tsai-Hu-Tang or Sho-Saiko-To (TJ-9), contains active flavonoids. In this study, the protective effect of S/B remedy on iron-induced neurodegeneration was investigated in the nigrostriatal dopaminergic system of rat brain. Materials and methods The antioxidative activity of S/B remedy was studied using brain homogenates incubated with ferrous citrate (iron, 1 M), S/B remedy, Trolox and melatonin. Furthermore, a Parkinsonian animal model by an intranigral infusion of iron in the anesthetized rats was employed to investigate the protective effect of S/B remedy in the nigrostriatal dopaminergic system. Results Our in vitro studies showed that S/B remedy was more potent than melatonin and equal to trolox in inhibiting iron-induced lipid peroxidation of brain homogenates. Our in vivo studies found that oral administration of S/B remedy dose-dependently attenuated iron-elevated lipid peroxidation in the infused substantia nigra (SN) and iron-depleted dopamine levels in the ipsilateral striatum. Furthermore, iron-induced reductions in glutathione (GSH) content and increases in GSSG (oxidized GSH)/GSH ratio in the infused SN were inhibited in S/B remedy-treated rats. Systemic S/B remedy attenuated the iron-induced increases in heme-oxygenase-1 levels and α-synuclein aggregation in the infused SN. Moreover, S/B remedy reduced iron-induced apoptosis via attenuating mitochondrial and endoplasmic reticulum stress. In addition, S/B remedy was anti-inflammatory as indicated by the attenuation of iron-induced elevations in inducible nitric oxide synthase and cyclo-oxygenase II levels as well as glial fibrillary acidic protein (a biological marker of astrocytes) and ED-1 (a protein indicative of activated microglia) levels in the infused SN of S/B remedy-treated rats. Conclusions These findings suggest that oral administration of S/B remedy is protective against iron-induced neurodegeneration in the nigrostriatal dopaminergic system of rat brain. Therefore, S/B remedy may be therapeutically useful for the treatment of CNS neurodegenerative diseases.
- Published
- 2010
38. Mesenchymal Stem Cells for Liver Regeneration
- Author
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Yueh Hsin Ping, Tom K. Kuo, and Oscar K. Lee
- Subjects
Cell therapy ,Mesenchymal stem cell ,Liver Stem Cell ,Amniotic stem cells ,Stem cell ,Biology ,Liver regeneration ,Stem cell transplantation for articular cartilage repair ,Adult stem cell ,Cell biology - Abstract
The liver is an extraordinary organ that retains its regenerative power throughout life. The precise molecular mechanisms regulating liver regeneration are unknown, but a number of cell types have been postulated to be involved in the process, including (1) resident liver stem cells, (2) differentiated hepatocytes, and (3) extrahepatic stem cells. This chapter will discuss liver regeneration from the context of extrahepatic stem cells. Recent research findings have challenged the dogma of limited lineage commitment potency of somatic stem cells. This chapter reviews the hepatic lineage plasticity of mesenchymal stem cells in vitro and in. In addition, it discusses developments in the application of mesenchymal stem cells for the treatment of liver diseases in preclinical and clinical studies, as well as in possible signaling pathways and mechanisms, including microRNAs, which are involved in the regulatory control of hepatic fate specification.
- Published
- 2010
39. Positive transcription elongation factor b (P-TEFb) contributes to dengue virus-stimulated induction of interleukin-8 (IL-8)
- Author
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Li-li, Li, Shiau-Ting, Hu, Shao-Hung, Wang, Hsing-Hui, Lee, Yen-Ting, Wang, and Yueh-Hsin, Ping
- Subjects
Cell Nucleus ,Chromatin Immunoprecipitation ,Transcription, Genetic ,Cyclin T ,Viral Core Proteins ,Interleukin-8 ,NF-kappa B ,Dengue Virus ,Cyclin-Dependent Kinase 9 ,Polymerase Chain Reaction ,Gene Expression Regulation ,Cell Line, Tumor ,Mutation ,Humans ,Positive Transcriptional Elongation Factor B ,RNA Polymerase II ,RNA, Small Interfering ,Promoter Regions, Genetic ,Dichlororibofuranosylbenzimidazole - Abstract
Dengue virus (DENV) is one of the most common infectious pathogens worldwide. One major clinical and pathogenic feature of DENV infection is the elevation of interleukin-8 (IL-8) expression; however, little is known about the molecular mechanism of DENV-induced chemokine production. The positive transcription elongation factor b (P-TEFb) composed of CDK9 and cyclin T1 stimulates gene expression by enhancing RNA polymerase II (RNA pol II) processivity. This study examined the possibility that P-TEFb mediates DENV-induced IL-8 expression. The treatment of either a pharmacological inhibitor of P-TEFb, 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) or cyclin T1 siRNA prior to DENV infection abolished the elevation of IL-8, indicating that P-TEFb is essential for IL-8 induction. Moreover, DENV core protein participated in the activation of IL-8 promoter in a P-TEFb-dependent manner. Immunostaining and co-immunoprecipitation assays demonstrated the association between P-TEFb and DENV core protein. Finally, chromatin immunoprecipitation (ChIP) results indicated that P-TEFb and DENV core protein were recruited to the transcriptionally active IL-8 gene promoter. Taken together, this study showed that P-TEFb and DENV core protein work in concert to enhance IL-8 gene expression by DENV infection. This is the first demonstration of P-TEFb being directly involved in virus-induced host gene expression by interacting with a viral structural protein.
- Published
- 2010
40. Heteroplasmy of mitochondrial D310 mononucleotide repeat region in the blood of patients with Alzheimer's disease
- Author
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Pei Ning Wang, Chun Hui Wang, Hsin Chen Lee, Yueh Hsin Ping, Tsung-Yun Liu, Hsu Chih Liu, Ker Nen Lin, and Chin-Wen Chi
- Subjects
Adult ,Male ,Mitochondrial DNA ,Somatic cell ,DNA Mutational Analysis ,Physiology ,Disease ,medicine.disease_cause ,DNA, Mitochondrial ,Oxidative damage ,chemistry.chemical_compound ,Young Adult ,Alzheimer Disease ,Medicine ,Humans ,Aged ,Retrospective Studies ,Aged, 80 and over ,Aspartic Acid ,Blood Cells ,business.industry ,General Neuroscience ,General Medicine ,Middle Aged ,Molecular biology ,Heteroplasmy ,Peripheral ,Psychiatry and Mental health ,Clinical Psychology ,chemistry ,Female ,Geriatrics and Gerontology ,business ,Cognition Disorders ,Oxidative stress ,Cytosine ,Microsatellite Repeats - Abstract
There is increasing evidence of oxidative stress in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Because mitochondrial DNA (mtDNA) is susceptible to oxidative damage, somatic mtDNA mutations may be induced by oxidative stress. Most of the studies examining mitochondrial mutations have been performed on postmortem brain tissues of AD patients. This study examined peripheral blood samples of AD and MCI patients to determine if peripheral mtDNA mutations are associated with these two conditions. A total of 236 subjects, including 71 AD patients, 84 amnestic MCI patients, 41 cognitively normal aging controls, and 40 young controls, were recruited. There was heteroplasmy of the mtDNA D310 polycytosine repeat region in 37 of 71 (52.1%) AD patients and this was significantly more frequent than in MCI patients (31.0%), normal aging (31.7%), and young controls (27.5%). However, subjects with amnestic MCI did not have a significantly higher rate of heteroplasmy in D310 than cognitively normal elderly subjects. The heteroplasmic alterations of D310 were more frequently in subjects with a larger number of polycytosine repetitions. Insertion of cytosine was the most common mutation type. The results suggest that mutations of mtDNA 310 region are frequently present in the peripheral blood of AD patients. Further prospective investigations to determine if MCI subjects with D310 mutations develop AD is warranted.
- Published
- 2009
41. Mitochondria are an essential mediator of nitric oxide/cyclic guanosine 3',5'-monophosphate blocking of glucose depletion induced cytotoxicity in human HepG2 cells
- Author
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Wing Yiu Lui, Yueh Hsin Ping, Hsin Chen Lee, Yi Chiung Hsu, Chin-Wen Chi, and Tsung-Yun Liu
- Subjects
Cancer Research ,Carcinoma, Hepatocellular ,Cell Survival ,Guanosine ,Mitochondria, Liver ,Antimycin A ,Mitochondrion ,Nitric Oxide ,DNA, Mitochondrial ,Polymorphism, Single Nucleotide ,Nitric oxide ,Cell Line ,chemistry.chemical_compound ,Humans ,Molecular Biology ,Cyclic GMP ,DNA Primers ,biology ,Cytochrome c ,Liver Neoplasms ,Cytoprotection ,Cell biology ,Gene Expression Regulation, Neoplastic ,Kinetics ,Glucose ,Oncology ,chemistry ,Biochemistry ,Coenzyme Q – cytochrome c reductase ,biology.protein ,Energy source - Abstract
It is well known that glucose is a major energy source in tumors and that mitochondria are specialized organelles required for energy metabolism. Previous studies have revealed that nitric oxide (NO) protects against glucose depletion–induced cytotoxicity in mouse liver cells and in rat hepatocytes, but the detailed mechanism is not well understood. Therefore, we investigated the involvement of mitochondria in the NO protective effect in human hepatoma HepG2 cells. In this study, we showed that glucose depletion resulted in a time-dependent decrease in intracellular NO and in the protein expression of NO synthases. This glucose depletion–induced decrease in NO was blocked by NO donors. Next, we showed that the cytoprotective effect of NO is via a cyclic guanosine 3′,5′-monophosphate–dependent pathway. Additionally, SNP blocked a glucose depletion–induced decrease in mitochondrial mass, mitochondrial DNA copies, and ATP level in HepG2 cells. Moreover, glucose depletion decreased the expression of various mitochondrial proteins, including cytochrome c, complex I (NADH dehydrogenase), complex III (cytochrome c reductase), and heat shock protein 60; these glucose depletion–induced effects were blocked by SNP. Furthermore, we found that rotenone and antimycin A (mitochondria complex I and III inhibitors, respectively) blocked SNP cytoprotection against glucose depletion–induced cytotoxicity. Taken together, our results indicated that the mitochondria serve as an important cellular mediator of NO during protection against glucose deprivation–induced damage. (Mol Cancer Res 2007;5(9):923–32)
- Published
- 2007
42. Anticancer effects of low-dose 10-hydroxycamptothecin in human colon cancer
- Author
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Hsin Chen Lee, Chin-Wen Chi, Jen Yi Lee, Jane Jen Wang, Pin Ho Wu, Li Kang Ho, Ming Fong Lu, and Yueh Hsin Ping
- Subjects
G2 Phase ,Cancer Research ,Colorectal cancer ,Blotting, Western ,Administration, Oral ,Mice, Nude ,Pharmacology ,Mice ,In vivo ,Oral administration ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Cell Proliferation ,Mice, Inbred BALB C ,Dose-Response Relationship, Drug ,biology ,Caspase 3 ,business.industry ,Topoisomerase ,Cancer ,General Medicine ,Flow Cytometry ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Xenograft Model Antitumor Assays ,Acute toxicity ,Oncology ,Apoptosis ,Caspases ,Colonic Neoplasms ,Immunology ,Toxicity ,biology.protein ,Camptothecin ,business - Abstract
10-Hydroxycamptothecin (10-HCPT), an indole alkaloid isolated from a Chinese tree, Camptotheca acuminate, inhibits the activity of topoisomerase I and has a broad spectrum of anticancer activity in vitro and in vivo. However, its use has been limited due to its water-insolubility and toxicity with i.v. administration. The purpose of this study was to investigate the efficacy, toxicity and proper dosage of 10-HCPT as a single agent by oral administration in the treatment of human colon cancer. 10-HCPT significantly repressed the proliferation of Colo 205 cells at a relatively low concentration (5-20 nM). Flow cytometry analysis and western blot and apoptosis assays demonstrated that low-dose 10-HCPT arrested Colo 205 cells in the G2 phase of the cell cycle and triggered apoptosis through a caspase-3-dependent pathway. Moreover, following oral administration at doses of 2.5-7.5 mg/kg/2 days, significant suppression of tumor growth by 10-HCPT was observed in mouse xenografts. No acute toxicity was observed after an oral challenge of 10-HCPT in BALB/c-nude mice every 2 days. The results of this study suggest that a relatively low dose of 10-HCPT (p.o.) is able to inhibit the growth of colon cancer, facilitating the development of a new protocol of human trials with this anticancer drug.
- Published
- 2006
43. Identification of novel cancer fusion genes using chromosome breakpoint screening.
- Author
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KATE HUA, CHIN-HUI LIN, YA-LUN CHEN, CHI-HUNG LIN, YUEH-HSIN PING, YUH-SHAN JOU, and CHIAN-FENG CHEN
- Published
- 2017
- Full Text
- View/download PDF
44. Modulating HIV-1 replication by RNA interference directed against human transcription elongation factor SPT5
- Author
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Yueh-Hsin, Ping, Chia-Ying, Chu, Hong, Cao, Jean-Marc, Jacque, Mario, Stevenson, and Tariq M, Rana
- Subjects
Gene Expression Regulation, Viral ,Transcriptional Activation ,lcsh:Immunologic diseases. Allergy ,Research ,Terminal Repeat Sequences ,Nuclear Proteins ,Virus Replication ,Gene Products, tat ,HIV-1 ,Humans ,RNA Interference ,tat Gene Products, Human Immunodeficiency Virus ,RNA, Messenger ,Transcriptional Elongation Factors ,lcsh:RC581-607 - Abstract
Background Several cellular positive and negative elongation factors are involved in regulating RNA polymerase II processivity during transcription elongation in human cells. In recruiting several of these regulatory factors to the 5' long terminal repeat (LTR) promoter during transcription elongation, HIV-1 modulates replication of its genome in a process mediated by the virus-encoded transactivator Tat. One particular cellular regulatory factor, DSIF subunit human SPT5 (hSpt5), has been implicated in both positively and negatively regulating transcriptional elongation but its role in Tat transactivation in vivo and in HIV-1 replication has not been completely elucidated. Results To understand the in vivo function of hSpt5 and define its role in Tat transactivation and HIV-1 replication, we used RNA interference (RNAi) to specifically knockdown hSpt5 expression by degrading hSpt5 mRNA. Short-interfering RNA (siRNA) designed to target hSpt5 for RNAi successfully resulted in knockdown of both hSpt5 mRNA and protein levels, and did not significantly affect cell viability. In contrast to hSpt5 knockdown, siRNA-mediated silencing of human mRNA capping enzyme, a functionally important hSpt5-interacting cellular protein, was lethal and showed a significant increase in cell death over the course of the knockdown experiment. In addition, hSpt5 knockdown led to significant decreases in Tat transactivation and inhibited HIV-1 replication, indicating that hSpt5 was required for mediating Tat transactivation and HIV-1 replication. Conclusions The findings presented here showed that hSpt5 is a bona fide positive regulator of Tat transactivation and HIV-1 replication in vivo. These results also suggest that hSpt5 function in transcription regulation and mRNA capping is essential for a subset of cellular and viral genes and may not be required for global gene expression.
- Published
- 2004
45. Discovery of a small molecule Tat-trans-activation-responsive RNA antagonist that potently inhibits human immunodeficiency virus-1 replication
- Author
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Akbar Ali, Karen V. Kibler, Natarajan Tamilarasu, Kuan-Teh Jeang, Hong Cao, Tariq M. Rana, Seongwoo Hwang, and Yueh Hsin Ping
- Subjects
Transcriptional Activation ,Chromatography, Gas ,Biology ,Ligands ,Biochemistry ,Antiviral Agents ,Models, Biological ,Automation ,Mice ,Structure-Activity Relationship ,In vivo ,Peptide Library ,Fluorescence Resonance Energy Transfer ,Animals ,Humans ,Molecular Biology ,Cells, Cultured ,Regulation of gene expression ,chemistry.chemical_classification ,Models, Statistical ,Dose-Response Relationship, Drug ,RNA ,RNA-Directed DNA Polymerase ,Cell Biology ,Virology ,Small molecule ,In vitro ,Reverse transcriptase ,Enzyme ,chemistry ,Viral replication ,Models, Chemical ,Gene Products, tat ,HIV-1 ,Nucleic Acid Conformation ,tat Gene Products, Human Immunodeficiency Virus ,Carbamates ,Oligopeptides ,HeLa Cells ,Protein Binding - Abstract
Antiretroviral therapy to treat AIDS uses molecules that target the reverse transcriptase and protease enzymes of human immunodeficiency virus, type 1 (HIV-1). A major problem associated with these treatments, however, is the emergence of drug-resistant strains. Thus, there is a compelling need to find drugs against other viral targets. One such target is the interaction between Tat, an HIV-1 regulatory protein essential for viral replication, and trans-activation-responsive (TAR) RNA. Here we describe the design and synthesis of an encoded combinatorial library containing 39,304 unnatural small molecules. Using a rapid high through-put screening technology, we identified 59 compounds. Structure-activity relationship studies led to the synthesis of 19 compounds that bind TAR RNA with high affinities. In the presence of a representative Tat-TAR inhibitor (5 μm TR87), we observed potent and sustained suppression of HIV replication in cultured cells over 24 days. The same concentration of this inhibitor did not exhibit any toxicity in cell cultures or in mice. TR87 was also shown to specifically disrupt Tat-TAR binding in vitro and inhibit Tat-mediated transcriptional activation in vitro and in vivo, providing a strong correlation between its activities and inhibition of HIV-1 replication. These results provide a structural scaffold for further development of new drugs, alone or in combination with other drugs, for treatment of HIV-1-infected individuals. Our results also suggest a general strategy for discovering pharmacophores targeting RNA structures that are essential in progression of other infectious, inflammatory, and genetic diseases.
- Published
- 2003
46. TAR RNA LOOP: A SCAFFOLD FOR THE ASSEMBLY OF A REGULATORY SWITCH IN HIV REPLICATION
- Author
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Yueh Hsin Ping, Tariq M. Rana, and Sara N. Richter
- Subjects
Transcriptional Activation ,Cyclin T1 ,RNA-induced transcriptional silencing ,RNA-dependent RNA polymerase ,RNA polymerase II ,Biology ,Virus Replication ,Tat protein ,Transcription (biology) ,Cyclins ,7SK RNA ,Transcription elongation factor complex ,TAR RNA ,Binding Sites ,Multidisciplinary ,Base Sequence ,Chromosome Mapping ,RNA ,HIV ,Biological Sciences ,Molecular biology ,Cell biology ,Gene Products, tat ,HIV-1 ,Trans-Activators ,biology.protein ,Nucleic Acid Conformation ,RNA, Viral ,tat Gene Products, Human Immunodeficiency Virus - Abstract
Replication of HIV requires the Tat protein, which activates elongation of RNA polymerase II transcription at the HIV-1 promoter by interacting with the cyclin T1 (CycT1) subunit of the positive transcription elongation factor complex b (P-TEFb). The transactivation domain of Tat binds directly to the CycT1 subunit of P-TEFb and induces loop sequence-specific binding of P-TEFb onto nascent HIV-1 trans-activation responsive region (TAR) RNA. We used systematic RNA–protein photocross-linking, Western blot analysis, and protein footprinting to show that residues 252–260 of CycT1 interact with one side of the TAR RNA loop and enhance interaction of Tat residue K50 to the other side of the loop. Our results show that TAR RNA provides a scaffold for two protein partners to bind and assemble a regulatory switch in HIV replication. RNA-mediated assembly of RNA–protein complexes could be a general mechanism for stable ribonucleoprotein complex formation and a key step in regulating other cellular processes and viral replication.
- Published
- 2002
47. Controlling human immunodeficiency virus type 1 gene expression by unnatural peptides
- Author
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Yueh Hsin Ping, Tariq M. Rana, Ikramul Huq, and Natarajan Tamilarasu
- Subjects
Gene Expression Regulation, Viral ,Transcriptional Activation ,Molecular Sequence Data ,Biochemistry ,Binding, Competitive ,Transcription (biology) ,Gene expression ,Humans ,Protein Isoforms ,Amino Acid Sequence ,Gene ,Peptide sequence ,HIV Long Terminal Repeat ,Regulation of gene expression ,Cell-Free System ,Chemistry ,RNA ,Translation (biology) ,Stereoisomerism ,Virology ,Cell biology ,RNA splicing ,Gene Products, tat ,HIV-1 ,RNA, Viral ,tat Gene Products, Human Immunodeficiency Virus ,Peptides ,HeLa Cells - Abstract
Small unnatural peptides that target specific RNA structures have the potential to control biological processes. RNA-protein interactions are important in many cellular functions, including transcription, RNA splicing, and translation. One example of such interactions is the mechanism of trans-activation of human immunodeficiency virus type 1 (HIV-1) gene expression that requires the interaction of Tat protein with the trans-activation responsive region (TAR) RNA, a 59-base stem-loop structure located at the 5'-end of all nascent HIV-1 transcripts. We report here a synthetic peptide derived from Tat sequence (37-72), containing all D-amino acids, that binds in the major groove of TAR RNA and interferes with transcriptional activation by Tat protein in vitro and in HeLa cells. Our results indicate that unnatural peptides can inhibit the transcription of specific genes regulated by RNA-protein interactions.
- Published
- 1999
48. Tat-associated kinase (P-TEFb): a component of transcription preinitiation and elongation complexes
- Author
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Tariq M. Rana and Yueh Hsin Ping
- Subjects
biology ,Transcription, Genetic ,Cell Biology ,Protein Serine-Threonine Kinases ,Peptide Elongation Factors ,Biochemistry ,Molecular biology ,Transcription Factors, TFII ,Transcription Factor TFIIH ,Transcription preinitiation complex ,Gene Products, tat ,biology.protein ,Humans ,Transcription factor II F ,Positive Transcriptional Elongation Factor B ,Transcription factor II E ,RNA Polymerase II ,P-TEFb ,Molecular Biology ,RNA polymerase II holoenzyme ,Transcription factor II B ,Transcription factor II A ,HeLa Cells ,Transcription Factors - Abstract
Human immunodeficiency virus, type 1 (HIV-1) Tat protein activates transcription from the HIV-1 long terminal repeat. Tat interacts with TFIIH and Tat-associated kinase (a transcription elongation factor P-TEFb) and requires the carboxyl-terminal domain of the largest subunit of RNA polymerase II (pol II) for transactivation. We developed a stepwise RNA pol II walking approach and used Western blotting to determine the role of TFIIH and P-TEFb in HIV-1 transcription elongation. Our results demonstrate the new findings that P-TEFb is a component of the preinitiation complex and travels with the elongating RNA pol II, whereas TFIIH is released from the elongation complexes before the trans-activation responsive region RNA is synthesized. Our results suggest that TFIIH and P-TEFb are involved in the clearance of promoter-proximal pausing of RNA pol II on the HIV-1 long terminal repeat at different stages.
- Published
- 1999
49. Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection.
- Author
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Li-Wei Chu, Yi-Lung Huang, Jin-Hui Lee, Long-Ying Huang, Wei-Jun Chen, Ya-Hsuan Lin, Jyun-Yu Chen, Rui Xiang, Chau-Hwang Lee, and Yueh-Hsin Ping
- Subjects
DENGUE viruses ,MICROTUBULE-associated protein kinase ,CONFOCAL microscopy ,IMAGE analysis ,AUTOPHAGY - Abstract
Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
50. Open Reading Frame 8a of the Human Severe Acute Respiratory Syndrome Coronavirus Not Only Promotes Viral Replication but Also Induces Apoptosis.
- Author
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Chia-Yen Chen, Yueh-Hsin Ping, Hsin-Chen Lee, Kuan-Hsuan Chen, Yuan-Ming Lee, Yu-Juin Chan, Te-Cheng Lien, Tjin-Shing Jap, Chi-Hung Lin, Lung-Sen Kao, and Yi-Ming Arthur Chen
- Subjects
- *
SARS disease , *VIRAL replication , *APOPTOSIS , *RNA , *CELL death , *COMMUNICABLE diseases , *CORONAVIRUS diseases , *CONFOCAL microscopy - Abstract
Background. A unique genomic difference between human and civet severe acute respiratory syndrome coronaviruses (SARS-CoVs) is that the former has a deletion of 29 nucleotides from open reading frame (orf) 8d that results in the generation of orf8a and orf8b. The objectives of the present study were to analyze antibody reactivity to ORF8a in patients with SARS and to elucidate the function of ORF8a. Methods. Western-blot and immunofluorescent antibody assays were used to detect anti-ORF8a antibody. SARS-CoV HKU39849 was used to infect stable clones expressing ORF8a and cells transfected with small interfering RNA (siRNA). The virus loads (VLs) and cytopathic effects (CPEs) were recorded. Confocal microscopy and several mitochondria-related tests were used to study the function of ORF8a. Results. Two (5.4%) of 37 patients with SARS had anti-ORF8a antibodies. The VLs in the stable clones expressing ORF8a were significantly higher than those in control subjects 5 days after infection. siRNA against orf8a significantly reduced VLs and interrupted the CPE. ORF8a was found to be localized in mitochondria, and overexpression resulted in increases in mitochondrial transmembrane potential, reactive oxygen species production, caspase 3 activity, and cellular apoptosis. Conclusions. ORF8a not only enhances viral replication but also induces apoptosis through a mitochondriadependent pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
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