Browsing by Author "Tseng, Yu-Ting"

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AIDS-related opportunistic illnesses and early initiation of HIV care remain critical in the contemporary HAART era: a retrospective cohort study in Taiwan
(2018-07-28)
Lee, Chun-Yuan
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Tseng, Yu-Ting
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Lin, Wei-Ru
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Chen, Yen-Hsu
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Tsai, Jih-Jin
Background: No study has reported the epidemiology of AIDS-related opportunistic illnesses (AOIs) in patients with newly diagnosed HIV infection in Taiwan in the past decade. Understanding the current trends in AOI-related morbidity/mortality is essential in improving patient care and optimizing current public health strategies to further reduce AOIs in Taiwan in the era of contemporary highly active antiretroviral therapy (HAART). Methods: Eligible patients were evaluated at two referral centers between 2010 and 2015. The patients were stratified by date of diagnosis into three periods: 2010-2011, 2012-2013, and 2014-2015. The demographics, HIV stage at presentation according to the United States CDC 2014 case definition, laboratory variables, and the occurrence of AOIs and associated outcomes were compared among the patients. Logistic regression and Cox regression were respectively used to identify variables associated with the occurrence of AOIs within 90 days of HIV enrollment and all-cause mortality. Results: Over a mean observation period of 469 days, 1264 patients with newly diagnosed HIV with a mean age of 29 years and mean CD4 count of 275 cells/mu L experienced 394 AOI episodes in 290 events. At presentation, 37.7% of the patients had AIDS; the frequency did not significantly differ across groups. The overall proportion of AOIs within the study period was 21.0%, and no decline across groups was observed. The majority of AOls (91.7%) developed within 90 days of enrollment. All-cause and AOI-related mortality did not significantly differ across groups. Throughout the three study periods, AOIs remained the main cause of death (47/56, 83.9%), especially within 180 days of enrollment (40/42, 95.2%). A CD4 cell count of < 200 cells/mu L at presentation was associated with increased adjusted odds of an AOI within 90 days [adjusted odds ratio, 40.84; 95% confidence intervals (CI), 12. 59-132.49] and an elevated adjusted hazard of all-cause mortality (adjusted hazard ratio, 11.03; 95% CI, 1.51-80.64). Conclusions: Despite efforts toward HIV prevention and management, early HIV care in Taiwan continues to be critically affected by AOI-related morbidity and mortality in the era of contemporary HAART. Additional targeted interventions are required for the earlier diagnosis of patients with HIV.
Extension of C-elegans lifespan using the center dot NO-delivery dinitrosyl iron complexes
(2018-07-01)
Huang, Hsiao-Wen
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Lin, Yen-Hung
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Lin, Min-Hsuan
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Huang, Ya-Rong
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Chou, Chih-Hung
The ubiquitous and emerging physiology function of endogenous nitric oxide in vascular, myocardial, immune, and neuronal systems prompts chemists to develop a prodrug for the controlled delivery of center dot NO in vivo and for the translational biomedical application. Inspired by the discovery of natural [Fe(NO)(2)] motif, herein, we develop the synthetic dinitrosyl iron complexes (DNICs) [Fe-2(mu-SR)(2)(NO)(4)] (1) as a universal platform for the O-2-triggered release of center dot NO, for the regulation of center dot NO-release kinetics (half-life = 0.6-27.4 h), and for the activation of physiological function of center dot NO. Using C. elegans as a model organism, the center dot NO-delivery DNIC 1 regulates IIS signaling pathway, AMPK signaling pathway, and mitochondrial function pathway to extend the lifespan and to delay the aging process based on the lifespan analysis, SA-beta gal activity assay, and next-generation RNA sequencing analysis. This study unveils the anti-aging effect of center dot NO and develops DNICs as a chemical biology probe for the continued discovery of unprecedented NO physiology. [GRAPHICS] .
Loganin possesses neuroprotective properties, restores SMN protein and activates protein synthesis positive regulator Akt/mTOR in experimental models of spinal muscular atrophy
(2016-09)
Tseng, Yu-Ting
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Chen, Cheng-Sheng
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Jong, Yuh-Jyh
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Chang, Fang-Rong
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Lo, Yi-Ching
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease characterized by motor neurons degeneration and muscular atrophy. There is no effective SMA treatment. Loganin is a botanical candidate with anti-inflammatory, anti-oxidant, glucose-lowering and anti-diabetic nephropathy activities. The aim of this study is to investigate the potential protective effects of loganin on SMA using two cellular models, SMN-deficient NSC34 cells and SMA patient fibroblasts, and an animal disease model, SMA Delta 7 mice. In SMN-deficient NSC34 cells, loganin increased cell viability, neurite length, and expressions of SMN, Gemin2, SMN-Gemin2 complex, p-Akt, p-GSK-3 beta, p-CREB, BDNF and Bcl-2. However, both AG1024 (IGF-1 R antagonist) and IGF-1 R siRNA attenuated the protective effects of loganin on SMN level and cell viability in SMN-deficient NSC34 cells. In SMA patient fibroblasts, loganin up-regulated levels of SMN,FL-SMN2, and Gemins, increased numbers of SMN-containing nuclear gems, modulated splicing factors, and up-regulated p-Akt. Furthermore, in the brain, spinal cord and gastrocnemius muscle of SMA Delta 7 mice, loganin up-regulated the expressions of SMN and p-Akt. Results from righting reflex and hind limb suspension tests indicated loganin improved muscle strength of SMA Delta 7 mice; moreover, loganin activated Akt/mTOR signal and inhibited atrogin-1/MuRF-1 signal in gastrocnemius muscle of SMA Delta 7 mice. Loganin also increased body weight, but the average lifespan of loganin (20 mg/kg/day)-treated SMA mice was 16.80 +/- 0.73 days, while saline-treated SMA mice was 10.91 +/- 0.96 days. In conclusion, the present results demonstrate that loganin provides benefits to SMA therapeutics via improving SMN restoration, muscle strength and body weight. IGF-1 plays an important role in loganin neuroprotection. Loganin can be therefore a valuable complementary candidate for treatment of neuromuscular diseases via regulation of muscle protein synthesis and neuroprotection. (C) 2016 Elsevier Ltd. All rights reserved.
miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions
(2014-01-01)
Hsu, Sheng-Da
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Tseng, Yu-Ting
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Shrestha, Sirjana
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Lin, Yu-Ling
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Khaleel, Anas
MicroRNAs (miRNAs) are small non-coding RNA molecules capable of negatively regulating gene expression to control many cellular mechanisms. The miRTarBase database (http://mirtarbase.mbc.nctu.edu.tw/) provides the most current and comprehensive information of experimentally validated miRNA-target interactions. The database was launched in 2010 with data sources for >100 published studies in the identification of miRNA targets, molecular networks of miRNA targets and systems biology, and the current release (2013, version 4) includes significant expansions and enhancements over the initial release (2010, version 1). This article reports the current status of and recent improvements to the database, including (i) a 14-fold increase to miRNA-target interaction entries, (ii) a miRNA-target network, (iii) expression profile of miRNA and its target gene, (iv) miRNA target-associated diseases and (v) additional utilities including an upgrade reminder and an error reporting/user feedback system.
The water extract of Liuwei dihuang possesses multi-protective properties on neurons and muscle tissue against deficiency of survival motor neuron protein
(2017-10-15)
Tseng, Yu-Ting
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Jong, Yuh-Jyh
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Liang, Wei-Fang
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Chang, Fang-Rong
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Lo, Yi-Ching
Background: Deficiency of survival motor neuron (SMN) protein, which is encoded by the SMN1 and SMN2 genes, induces widespread splicing defects mainly in spinal motor neurons, and leads to spinal muscular atrophy (SMA). Currently, there is no effective treatment for SMA. Liuwei dihuang (LWDH), a traditional Chinese herbal formula, possesses multiple therapeutic benefits against various diseases via modulation of the nervous, immune and endocrine systems. Previously, we demonstrated water extract of LWDH (LWDH-WE) protects dopaminergic neurons and improves motor activity in models of Parkinson's disease. Purpose: This study aimed to investigate the potential protection of LWDH-WE on SMN deficiency-induced neurodegeneration and muscle weakness. Study design: The effects of LWDH-WE on SMN deficiency-induced neurotoxicity and muscle atrophy were examined by using SMN-deficient NSC34 motor neuron-like cells and SMA-like mice, respectively. Methods: Inducible SMN-knockdown NSC34 motor neuron-like cells were used to mimic SMN-deficient condition. Doxycycline (1 mu g/ml) was used to induce SMN deficiency in stable NSC34 cell line carrying SMN-specific shRNA. SMA.7 mice were used as a severe type of SMA mouse model. Cell viability was measured by 3-(4,5dimethylthiazol- 2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Apoptotic cells and neurite length were observed by inverted microscope. Protein expressions were examined by western blots. Muscle strength of animals was evaluated by hind-limb suspension test. Results: LWDH-WE significantly increased SMN protein level, mitochondrial membrane potential and cell viability of SMN-deficient NSC34 cells. LWDH-WE attenuated SMN deficiency-induced down-regulation of B-cell lymphoma-2 (Bcl-2) and up-regulation of cytosolic cytochrome c and cleaved caspase-3. Moreover, LWDH-WE prevented SMN deficiency-induced inhibition of neurite outgrowth and activation of Ras homolog gene family, member A (RhoA)/Rho-associated protein kinase (ROCK2)/phospho-LIM kinase (p-LIMK)/phospho-cofilin (pcofilin) pathway. Furthermore, in SMA-like mice, LWDH-WE improved muscle strength and body weight accompanied with up-regulation of SMN protein in spinal cord, brain, and gastrocnemius muscle tissues. Conclusion: The present study demonstrated that LWDH-WE protects motor neurons against SMN deficiencyinduced neurodegeneration, and it also improves the muscle strength of SMA-like mice, suggesting the potential benefits of LWDH-WE as a complementary prescription for SMN deficiency-related diseases.
Visceral obesity and cell cycle pathways serve as links in the association between bisphenol A exposure and breast cancer
(2020-07-01)
Wang, Tsu-Nai
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Yang, Pei-Jing
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Tseng, Yu-Ting
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Tsai, Yi-Shan
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Kuo, Po-Lin
It has been identified that bisphenol A (BPA) exposure causes developmental toxicity in breast cells. However, the exact molecular mechanisms underlying the association between exposure to BPA and breast cancer remain unclear. The aim of the present study was to investigate the BPA-regulated signaling pathways associated with the aggressiveness and the development of breast cancer. Microarray technology and functional gene set analyses were used to evaluate BPA and breast cancer-associated biomarkers and pathways in a discovery-driven manner. Using individual dataset analyses, it was indicated that two BPA-associated gene sets, the visceral obesity pathway, involved in visceral fat deposits and the metabolic syndrome, and the cell cycle pathway, involved in cyclins and cell cycle regulation, were significantly associated with a high grade of aggressiveness and the development of estrogen receptor (ER)-positive breast cancer (between P<0.05 and 0.0001). The pooled analysis indicated that the most significant pathway was G(1)/S checkpoint regulation, and the cyclin and cell cycle regulation pathway for BPA-associated ER-positive cancer. Cancer cell signaling pathways were associated with healthy breast cells developing into breast cancer. The visceral obesity and the cell cycle pathways were indicated to link BPA exposure to breast cancer. The results of the present study demonstrate a significant association between breast cancer and BPA-regulated gene pathways.