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    Complete genome sequence of Amazon lily mosaic virus isolated from amaryllis (Hippeastrum hybridum Hort.)

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    [[abstract]]In April 2011, a virus was isolated by single-lesion isolation on Chenopodium quinoa leaves from an amaryllis plant with chlorotic ringspots in a private garden in Changhua County, Taiwan. An Illumina MiSeq sequencing system was used to determine the genomic nucleotide (nt) sequence of the virus. A de novo-assembled contig with 9377 nt, containing an open reading frame encoding a putative potyviral polyprotein, was annotated as the potyvirus Amazon lily mosaic virus (ALiMV), sharing 95.5% nt sequence identity with a partial genomic sequence of ALiMV available in the GenBank database. Therefore, the amaryllis virus was designated as ALiMV-TW. Through 5? and 3? rapid amplification of cDNA ends (RACE), the complete 9618-nt genome sequence of ALiMV-TW was determined. Sequence comparisons indicated that the genome and polyprotein of ALiMV-TW share 52.3–65.1% nt and 30.1–64.2% aa sequence identity, respectively, with those of other potyviruses. This is the first report of a complete genome sequence of ALiMV

    Estimating the incidence rate ratio of common cold among patients with non-apnea sleep disorders: a retrospective cohort study

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    [[abstract]]The purpose was to explore the potential effects of nonapnea sleep disorders (NSDs) and hypnotic use on the incidence of common cold. This study adapted population-based retrospective cohort study designed. We used the data from the Taiwan National Health Insurance Research Database between 1998 and 2011. In total, 59,476 patients with NSDs were included in the study cohort, and the reference cohort comprised 59,476 propensity score-matched patients. We conducted a Poisson regression analysis to assess the incidence of common cold. The overall incidence of common cold was significantly higher than that in the reference cohort. Compared with the patients of the reference cohort without hypnotic use, those of the NSDs cohort with benzodiazepines and zolpidem use had higher incidence of common cold. In conclusion, study cohort had a higher incidence of developing common cold, and particularly pronounced in NSDs with hypnotic use

    Glycyrrhizic Acid Derivatives Bearing Amino Acid Residues in the Carbohydrate Part as Dengue Virus E Protein Inhibitors: Synthesis and Antiviral Activity

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    [[abstract]]Dengue virus (DENV) is one of the most geographically distributed mosquito-borne flaviviruses, like Japanese encephalitis virus (JEV), and Zika virus (ZIKV). In this study, a library of the known and novel Glycyrrhizic acid (GL) derivatives bearing amino acid residues or their methyl/ethyl esters in the carbohydrate part were synthesized and studied as DENV inhibitors in vitro using the cytopathic effect (CPE), viral infectivity and virus yield assays with DENV1 and DENV-2 in Vero E6 and A549 cells. Among the GL conjugates tested, compound hits GL-D-ValOMe 3, GL-TyrOMe 6, GL-PheOEt 11, and GL-LysOMe 21 were discovered to have better antiviral activity than GL, with IC50 values ranging from <0.1 to 5.98 μM on the in vitro infectivity of DENV1 and DENV2 in Vero E6 and A549 cells. Compound hits 3, 6, 11, and 21 had a concentration-dependent inhibition on the virus yield in Vero E6, in which GL-D-ValOMe 3 and GL-PheOEt 11 were the most active inhibitors of DENV2 yield. Meanwhile, the time-of-addition assay indicated that conjugates GL-D-ValOMe 3 and GL-PheOEt 11 exhibited a substantial decrease in the DENV2 attachment stage. Subsequently, chimeric single-round infectious particles (SRIPs) of DENV2 C-prM-E protein/JEV replicon and DENV2 prM-E/ZIKV replicon were utilized for the DENV envelope I protein-mediated attachment assay. GL conjugates 3 and 11 significantly reduced the attachment of chimeric DENV2 C-prM-E/JEV and DENV2 prM-E/ZIKV SRIPs onto Vero E6 cells in a concentration-dependent manner but did not impede the attachment of wild-type JEV CprME/JEV and ZIKV prM-E/ZIKV SRIPs, indicating the inhibition of Compounds 3 and 11 on DENV2 E-mediated attachment. Molecular docking data revealed that Compounds 3 and 11 have hydrophobic interactions within a hydrophobic pocket among the interfaces of Domains I, II, and the stem region of the DENV2 envelope (E) protein. These results displayed that Compounds 3 and 11 were the lead compounds targeting the DENV E protein. Altogether, our findings provide new insights into the structure-activity relationship of GL derivatives conjugated with amino acid residues and can be the new fundamental basis for the search and development of novel flavivirus inhibitors based on natural compounds

    Test-retest reliabilities and minimal detectable changes of 5 versions of the Alzheimer's Disease Assessment Scale-Cognitive Subscale in people with dementia

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    [[abstract]]Purpose: To compare the test-retest reliability and minimal detectable change (MDC) of the commonly used versions of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) (the ADAS-Cog-11 (11 items), ADAS-Cog-3 (three items), ADAS-Cog-5-Subset (five items), ADAS-Cog-6-Subset (six items), and ADAS-Rasch (11 items)) in people with dementia. Materials and methods: A repeated-assessments design (2 weeks apart) was used to examine the ADAS-Cog-11, ADAS-Cog-3, ADAS-Cog-5-Subset, ADAS-Cog-6-Subset, and ADAS-Rasch. Participants with dementia were recruited from one hospital, one elder care center, and two day-care centers using convenience sampling. Results: Fifty-two participants finished the assessments twice in two weeks. All versions showed high intraclass correlation coefficients (ICCs) (0.82-0.96), minimal standardized response means (-0.07 to 0.08) and low to acceptable MDC% (9.2-28.6%). The ADAS-Rasch had the highest ICC (0.96) and the lowest MDC%. The ADAS-Cog-3 had an ICC lower than 0.90 (0.82) and the highest MDC% (28.6%). Conclusions: The ADAS-Rasch seems to be the most reliable version of the ADAS-Cog for group- and individual-level comparisons. The ADAS-Cog-3 may be a better choice for researchers for group-level comparisons because it requires fewer items to achieve acceptable reliability. The ADAS-Cog-11, ADAS-Cog-5-Subset, ADAS-Cog-6-Subset, and ADAS-Rasch could be considered for clinical usage for individual-level comparisons.Implications for rehabilitationThe ADAS-Rasch is the most reliable version of the ADAS-Cog for group- and individual-level comparisons due to its excellent test-retest reliability, lowest random measurement error and absence of a practice effect.The ADAS-Cog-5-Subset and ADAS-Cog-6-Subset might be good substitutes for the ADAS-Rasch in clinical settings because of their comparable reliability features and superior administration efficiency

    How mycobacterium tuberculosis infection could lead to the increasing risks of chronic fatigue syndrome and the potential immunological effects: a population?based retrospective cohort study

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    [[abstract]]Background: Chronic fatigue syndrome (CFS) has been shown to be associated with infections. Tuberculosis (TB) is a highly prevalent infectious disease. Patients with chronic fatigue syndrome and post-tuberculosis experience similar symptoms. Furthermore, chronic fatigue syndrome and tuberculosis share similar plasma immunosignatures. This study aimed to clarify the risk of chronic fatigue syndrome following the diagnosis of Mycobacterium tuberculosis infection (MTI), by analyzing the National Health Insurance Research Database of Taiwan. Methods: 7666 patients aged 20 years or older with newly diagnosed Mycobacterium tuberculosis infection during 2000-2011 and 30,663 participants without Mycobacterium tuberculosis infection were identified. Both groups were followed up until the diagnoses of chronic fatigue syndrome were made at the end of 2011. Results: The relationship between Mycobacterium tuberculosis infection and the subsequent risk of chronic fatigue syndrome was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 3.04 and 3.69 per 1000 person-years among the non-Mycobacterium tuberculosis infection and Mycobacterium tuberculosis infection populations, respectively (adjusted hazard ratio [HR] = 1.23, with 95% confidence interval [CI] 1.03-1.47). In the stratified analysis, the Mycobacterium tuberculosis infection group were consistently associated with a higher risk of chronic fatigue syndrome in the male sex (HR = 1.27, 95% CI 1.02-1.58) and age group of ? 65 years old (HR = 2.50, 95% CI 1.86-3.38). Conclusions: The data from this population-based retrospective cohort study revealed that Mycobacterium tuberculosis infection is associated with an elevated risk of subsequent chronic fatigue syndrome

    Protective effects of CHIP overexpression and Wharton's jelly mesenchymal-derived stem cell treatment against streptozotocin-induced neurotoxicity in rats

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    [[abstract]]Diabetic neuropathy is a common complication of diabetes mellitus, posing a challenge in treatment. Previous studies have indicated the protective role of mesenchymal stem cells against several disorders. Although they can repair nerve injury, their key limitation is that they reduce viability under stress conditions. We recently observed that overactivation of the carboxyl terminus of heat shock protein 70 (Hsp70) interacting protein (CHIP) considerably rescued cell viability under hyperglycemic stress and played an essential role in promoting the beneficial effects of Wharton's jelly-derived mesenchymal stem cells (WJMSCs). Thus, the present study was designed to unveil the protective effects of CHIP-overexpressing WJMSCs against neurodegeneration using in vivo animal model based study. In this study, western blotting observed that CHIP-overexpressing WJMSCs could rescue nerve damage observed in streptozotocin-induced diabetic rats by activating the AMPKα/AKT and PGC1α/SIRT1 signaling pathway. In contrast, these signaling pathways were downregulated upon silencing CHIP. Furthermore, CHIP-overexpressing WJMSCs inhibited inflammation induced in the brains of diabetic rats by suppressing the NF-κB, its downstream iNOS and cytokines signaling nexus and enhancing the antioxidant enzyme system. Moreover, TUNEL assay demonstrated that CHIP carrying WJMSCs suppressed the apoptotic cell death induced in STZ-induced diabetic group. Collectively, our findings suggests that CHIP-overexpressing WJMSCs might exerts beneficial effects, which may be considered as a therapeutic strategy against diabetic neuropathy complications

    Regulatory Effects of Quercetin on M1/M2 Macrophage Polarization and Oxidative/Antioxidative Balance

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    [[abstract]]Macrophage polarization plays essential and diverse roles in most diseases, such as atherosclerosis, adipose tissue inflammation, and insulin resistance. Homeostasis dysfunction in M1/M2 macrophage polarization causes pathological conditions and inflammation. Neuroinflammation is characterized by microglial activation and the concomitant production of pro-inflammatory cytokines, leading to numerous neurodegenerative diseases and psychiatric disorders. Decreased neuroinflammation can be obtained by using natural compounds, including flavonoids, which are known to ameliorate inflammatory responses. Among flavonoids, quercetin possesses multiple pharmacological applications and regulates several biological activities. In the present study, we found that quercetin effectively inhibited the expression of lipocalin-2 in both macrophages and microglial cells stimulated by lipopolysaccharides (LPS). The production of nitric oxide (NO) and expression levels of the pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, were also attenuated by quercetin treatment. Our results also showed that quercetin significantly reduced the expression levels of the M1 markers, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β, in the macrophages and microglia. The M1 polarization-associated chemokines, C-C motif chemokine ligand (CCL)-2 and C-X-C motif chemokine ligand (CXCL)-10, were also effectively reduced by the quercetin treatment. In addition, quercetin markedly reduced the production of various reactive oxygen species (ROS) in the microglia. The microglial phagocytic ability induced by the LPS was also effectively reduced by the quercetin treatment. Importantly, the quercetin increased the expression levels of the M2 marker, IL-10, and the endogenous antioxidants, heme oxygenase (HO)-1, glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone oxidoreductase-1 (NQO1). The enhancement of the M2 markers and endogenous antioxidants by quercetin was activated by the AMP-activated protein kinase (AMPK) and Akt signaling pathways. Together, our study reported that the quercetin inhibited the effects of M1 polarization, including neuroinflammatory responses, ROS production, and phagocytosis. Moreover, the quercetin enhanced the M2 macrophage polarization and endogenous antioxidant expression in both macrophages and microglia. Our findings provide valuable information that quercetin may act as a potential drug for the treatment of diseases related to inflammatory disorders in the central nervous system

    Driving decision-making among older adults with dementia in Taiwan: A longitudinal study

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    [[abstract]]Background Driving is a complex skill that requires the integration of cognition and motor functions. However, these functions are all impacted by dementia. Aim We investigated the driving status among persons with dementia and the effects of a Dementia and Driving Decision Aid (DDDA) on changes in driving decisions, depressive symptoms and anxiety. Methods A longitudinal study with a 6-month observation was undertaken. Participants were clients in an Integrated Dementia Care Center (IDCC) who were diagnosed with a mild dementia. The primary outcome was changes in driving decisions; secondary outcomes included depressive symptoms, anxiety, and views on the booklet. Data were collected at four time points: baseline (T0), and 1 month (T1), 3 months (T2), 6 months (T3) after implementing DDDA. A logistic regression was used to examine changes in driving decisions, and a repeated-measures ANOVA was adopted to compare changes in secondary outcomes across time. Findings The number of participants who decided to continue driving significantly decreased (p < 0.001), while those who decided to drive less significantly increased (p < 0.001). A significant improvement in depressive symptoms was found in participants over time (F = 9.192; p < 0.001), the mean scores at all post-test time points were lower compared to the baseline measure. Discussion We report successful implementation of a DDDA booklet in an IDCC in Taiwan. In addition, participants’ satisfaction level toward the booklet was high. Conclusion We suggest the DDDA booklet can be widely utilised in community-based dementia care centres

    比較新型與傳統型神經肌肉逆轉劑 於老年膝關節置換術患者麻醉安全之回溯調查

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    [[abstract]]背景:全球老年人口逐年增加,高齡手術麻醉及甦醒成為重要議題。新型逆轉劑Sugammadex能加速逆轉神經肌肉阻斷並促使一般患者盡早脫離呼吸器,對於老年患者麻醉安全指標缺乏相關研究。 目的:比較使用新型與傳統型神經肌肉逆轉劑對於老年膝關節置換術患者麻醉恢復成效調查。 方法:病歷回溯法自2018年1月1日至2018年8月31日期間,採立意取樣65歲以上行膝關節置換術且接受神經肌肉逆轉劑老年患者,自擬結構式問卷「神經肌肉逆轉劑麻醉恢復病歷回溯表」進行登錄,共收案214例。 結果:不論新型或傳統組皆以女性居多(p<0.05),其他基本性質未達顯著差異。麻醉照護指標方面,新型組術中接受較多次神經肌肉阻斷劑(Rocuronium)(p<0.05),但在拔管前吐氣二氧化碳監測(ETCO2)兩組雖達顯著差異但皆於正常範圍內(p<0.05)。新型組不論在麻醉與手術時間 (p<0.05)、給藥至拔管時間(p=0.02),皆有低於傳統組的趨勢,且新型組在拔管後平均神經肌肉阻斷程度(TOF)為98%,達拔管安全指標。恢復期照護指標方面,新型組意識恢復優於傳統組(p<0.05)。在恢復期合併症方面兩組無論在延遲拔管、低血氧、高血壓、頭暈、嘔吐及喉嚨痛,皆未達顯著差異;新型組在術後整體滿意度得分高於傳統組,呈顯著差異(p<0.05)。 結論:接受新型阻斷劑老年病患能縮短手術麻醉時間、意識恢復及自主呼吸,達到麻醉安全指標。恢復期合併症及術後品質分析與傳統組相近,本研究結果可提供醫護人員在麻醉安全及提升照護品質。 關鍵字:麻醉恢復、神經肌肉逆轉劑、Sugammadex、麻醉安全、老人[[abstract]]Background: The pace of population ageing is much faster than in the past and aging increases the probability of a person to undergo surgery. Elderly patients take more time to recover from general anesthesia therefore generation of muscle reversal agent is important in facilitating anesthesia safety issue. Objective: To compare the effects of new and traditional neuromuscular reversal agents on anesthesia recovery in elderly patients undergoing knee arthroplasty. Methods: From January 1, 2018 to August 31, 2018, the medical records were retrospectively sampled for elderly patients over 65 years old who underwent knee arthroplasty and received neuromuscular reversal. Self-made structural questionnaire &quot;neuromuscular reversal&quot; The agent's anesthesia recovery medical record retrospective table was registered, and a total of 214 cases were received. Results: Population of the new or traditional reversal agents were predominantly female (p < 0.05), and there were no significant differences in the baseline characteristics. In terms of anesthesia care indicators, the new reversal agents received more than one neuromuscular blocker (Rocuronium) (p<0.05), but the two groups of exhaled carbon dioxide monitoring (ETCO2) before extubation showed significant differences but were within the normal range ( p<0.05). The new reversal agents had a lower trend than the traditional group in the time of anesthesia and surgery (p<0.05), and the time of administration to extubation (p=0.02), and the average neuromuscular blockade after extubation in the new reversal agents (TOF) is 98%. In terms of recovery period care indicators, the recovery of new reversal agents consciousness was better than that of the traditional group (p<0.05). There were no significant differences between the two groups in terms of delayed complication, delayed extubation, hypoxemia, hypertension, dizziness, vomiting, and sore throat.. The overall satisfaction score of the new group was higher than that of the traditional group (p<0.05). Conclusion: Elderly patients receiving new reversal agents can recover consciousness and spontaneous breathing in a short time, and achieve anesthesia safety indicators

    HO-1 Upregulation by Kaempferol via ROS-Dependent Nrf2-ARE Cascade Attenuates Lipopolysaccharide-Mediated Intercellular Cell Adhesion Molecule-1 Expression in Human Pulmonary Alveolar Epithelial Cells

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    [[abstract]]Lung inflammation is a pivotal event in the pathogenesis of acute lung injury. Heme oxygenase-1 (HO-1) is a key antioxidant enzyme that could be induced by kaempferol (KPR) and exerts anti-inflammatory effects. However, the molecular mechanisms of KPR-mediated HO-1 expression and its effects on inflammatory responses remain unknown in human pulmonary alveolar epithelial cells (HPAEpiCs). This study aimed to verify the relationship between HO-1 expression and KPR treatment in both in vitro and in vivo models. HO-1 expression was determined by real time-PCR, Western blotting, and promoter reporter analyses. The signaling components were investigated by using pharmacological inhibitors or specific siRNAs. Chromatin immunoprecipitation (ChIP) assay was performed to investigate the interaction between nuclear factor erythroid-2-related factor (Nrf2) and antioxidant response elements (ARE) binding site of HO-1 promoter. The effect of KPR on monocytes (THP-1) binding to HPAEpiCs challenged with lipopolysaccharides (LPS) was determined by adhesion assay. We found that KPR-induced HO-1 level attenuated the LPS-induced intercellular cell adhesion protein 1 (ICAM-1) expression in HPAEpiCs. KPR-induced HO-1 mRNA and protein expression also attenuated ICAM-1 expression in mice. Tin protoporphyrin (SnPP)IX reversed the inhibitory effects of KPR in HPAEpiCs. In addition, in HPAEpiCs, KPR-induced HO-1 expression was abolished by both pretreating with the inhibitor of NADPH oxidase (NOX, apocynin (APO)), reactive oxygen species (ROS) (N-acetyl-L-cysteine (NAC)), Src (Src kinase inhibitor II (Srci II)), Pyk2 (PF431396), protein kinase C (PKC)α (G?6976), p38 mitogen-activated protein kinase (MAPK) inhibitor (p38i) VIII, or c-Jun N-terminal kinases (JNK)1/2 (SP600125) and transfection with their respective siRNAs. The transcription of the homx1 gene was enhanced by Nrf2 activated by JNK1/2 and p38α MAPK. The binding activity between Nrf2 and HO-1 promoter was attenuated by APO, NAC, Srci II, PF431396, or G?6983. KPR-mediated NOX/ROS/c-Src/Pyk2/PKCα/p38α MAPK and JNK1/2 activate Nrf2 to bind with ARE on the HO-1 promoter and induce HO-1 expression, which further suppresses the LPS-mediated inflammation in HPAEpiCs. Thus, KPR exerts a potential strategy to protect against pulmonary inflammation via upregulation of the HO-1

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