Browsing by Author "Chen, Wen-Liang"

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AgriTalk: IoT for Precision Soil Farming of Turmeric Cultivation
(2019-06-01)
Chen, Wen-Liang
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Lin, Yi-Bing
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Lin, Yun-Wei
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Chen, Robert
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Liao, Jyun-Kai
This paper proposes AgriTalk, an inexpensive Internet of Things (IoT) platform for precision farming of soil cultivation. We conduct experiments on turmeric cultivation, which indicates that the turmeric quality is significantly enhanced through AgriTalk. Specifically, the curcumin concentration is up to 4500-5500 mg/100 g, which is five times more than existing products. We demonstrate how to intuitively configure the connections between the sensors and the actuators with the desired farming intelligence, and to effectively maintain AgriTalk for precision farming. We conduct measurement, analytic analysis, and simulation experiments to investigate the IoT message delays of AgriTalk. This paper indicates that the delays for automatic control and automatic-manual control switching with long distances (more than 30 km) are very short (less than 0.2 s) and AgriTalk can easily respond to quick and dynamic change of the field environment conditions in soil cultivation.
Anchor-based classification and type-C inhibitors for tyrosine kinases
(2015-06-16)
Hsu, Kai-Cheng
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Sung, Tzu-Ying
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Lin, Chih-Ta
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Chiu, Yi-Yuan
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Hsu, John T. -A.
Tyrosine kinases regulate various biological processes and are drug targets for cancers. At present, the design of selective and anti-resistant inhibitors of kinases is an emergent task. Here, we inferred specific site-moiety maps containing two specific anchors to uncover a new binding pocket in the C-terminal hinge region by docking 4,680 kinase inhibitors into 51 protein kinases, and this finding provides an opportunity for the development of kinase inhibitors with high selectivity and anti-drug resistance. We present an anchor-based classification for tyrosine kinases and discover two type-C inhibitors, namely rosmarinic acid (RA) and EGCG, which occupy two and one specific anchors, respectively, by screening 118,759 natural compounds. Our profiling reveals that RA and EGCG selectively inhibit 3% (EGFR and SYK) and 14% of 64 kinases, respectively. According to the guide of our anchor model, we synthesized three RA derivatives with better potency. These type-C inhibitors are able to maintain activities for drug-resistant EGFR and decrease the invasion ability of breast cancer cells. Our results show that the type-C inhibitors occupying a new pocket are promising for cancer treatments due to their kinase selectivity and anti-drug resistance.
Antibodies against Helicobacter pylori heat shock protein 60 aggravate HSP60-mediated proinflammatory responses
(2011-08-01)
Liao, Kuang-Wen
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Lin, Chen-Si
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Chen, Wen-Liang
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Yang, Chu-Ting
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Lin, Ching-Min
Anti-Helicobacter pylori heat shock protein 60 (HpHSP60) antibodies are Usually found in H. pylori-infected patients and are known to be associated with the progression of gastric diseases. However, the effects of these antibodies on the functions of HpHSP60 have not been identified. This study aims to investigate the effects of the interaction between anti-HSP60 antibodies and HpHSP60 on inflammatory responses. Anti-HpHSP60 polyclonal sera and monoclonal antibodies (mAbs) were produced to evaluate their effects on HpHSP60-induced IL-8 and TNF-alpha activity. The results indicated that anti-HpHSP60 polyclonal sera collected from patients infected with H. pylori or from rabbit and mice immunized with HpHSP60 could significantly enhance HpHSP60-mediated IL-8 and TNF-alpha secretion from monocytic THP-1 cells. Similar effects were also found with anti-HpHSP60 mAbs. Further analysis revealed that this phenomenon was only carried out by anti-HpHSP60 antibody but not by other non-specific mAbs. Moreover, the non-specific mAbs decreased the synergism of HpHSP60 and anti-HpHSP60 mAbs in proinflammatory cytokine induction. Herein, we have examined the role of anti-HpHSP60 antibody in host immune responses for the first time. This study demonstrated that H. pylori HSP60/mAbs could modulate helico-bacterial pathogenesis by increasing IL-8 and TNF-alpha production. The pathogen-specific antibodies may execute potential immune functions rather than recognize or neutralize microbes. (C) 2011 Elsevier Ltd. All rights reserved.
Bacterial alterations in salivary microbiota and their association in oral cancer
(2017-11-28)
Lee, Wei-Hsiang
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Chen, Hui-Mei
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Yang, Shun-Fa
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Liang, Chao
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Peng, Chih-Yu
Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity and the fourth leading malignancy and cause of cancer-related death in the male population of Taiwan. Most cases are detected at advanced stages, resulting in poor prognosis. Therefore, improved detection of early oral health disorders is indispensable. The involvement of oral bacteria in inflammation and their association with OSCC progression provide a feasible target for diagnosis. Due to the nature of oral neoplasms, the diagnosis of epithelial precursor lesions is relatively easy compared with that of other types of cancer. However, the transition from an epithelial precursor lesion to cancer is slow and requires further and continuous follow-up. In this study, we investigated microbiota differences between normal individuals, epithelial precursor lesion patients, and cancer patients with different lifestyle habits, such as betel chewing and smoking, using next-generation sequencing. Overall, the oral microbiome compositions of five genera, Bacillus, Enterococcus, Parvimonas, Peptostreptococcus, and Slackia, revealed significant differences between epithelial precursor lesion and cancer patients and correlated with their classification into two clusters. These composition changes might have the potential to constitute a biomarker to help in monitoring the oral carcinogenesis transition from epithelial precursor lesion to cancer.
Bronchial asthma is associated with increased risk of chronic kidney disease
(2014-05-08)
Huang, Hui-Ling
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Ho, Shinn-Ying
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Li, Chien-Hsun
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Chu, Fang-Ying
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Ciou, Li-Ping
Background: Bronchial asthma influences some chronic diseases such as coronary heart disease, diabetes mellitus, and hypertension, but the impact of asthma on vital diseases such as chronic kidney disease is not yet verified. This study aims to clarify the association between bronchial asthma and the risk of developing chronic kidney disease. Methods: The National Health Research Institute provided a database of one million random subjects for the study. A random sample of 141 064 patients aged >= 18 years without a history of kidney disease was obtained from the database. Among them, there were 35 086 with bronchial asthma and 105 258 without asthma matched for sex and age for a ration of 1:3. After adjusting for confounding risk factors, a Cox proportional hazards model was used to compare the risk of developing chronic kidney disease during a three-year follow-up period. Results: Of the subjects with asthma, 2 196 (6.26%) developed chronic kidney disease compared to 4 120 (3.91%) of the control subjects. Cox proportional hazards regression analysis revealed that subjects with asthma were more likely to develop chronic kidney disease (hazard ratio [HR]: 1.56; 95% CI: 1.48-1.64; p < 0.001). After adjusting for sex, age, monthly income, urbanization level, geographic region, diabetes mellitus, hypertension, hyperlipidemia, and steroid use, the HR for asthma patients was 1.40 (95% CI: 1.33-1.48; p = 0.040). There was decreased HRs in steroid use (HR: 0.56; 95% CI: 0.62-0.61; p < 0.001) in the development of chronic kidney disease. Expectorants, bronchodilators, anti-muscarinic agents, airway smooth muscle relaxants, and leukotriene receptor antagonists may also be beneficial in attenuating the risk of chronic kidney disease. Conclusions: Patients with bronchial asthma may have increased risk of developing chronic kidney disease. The use of steroids or non-steroidal drugs in the treatment of asthma may attenuate this risk.
Crystal structure of a secondary vitamin D(3) binding site of milk beta-lactoglobulin
(2008-05-15)
Yang, Ming-Chi
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Guan, Hong-Hsiang
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Liu, Ming-Yih
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Lin, Yih-Hung
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Yang, Jinn-Moon
beta-lactoglobulin (beta-LG), one of the most investigated proteins, is a major bovine milk protein with a predominantly beta structure. The structural function of the only alpha-helix with three turns at the C-terminus is unknown. Vitamin D(3) binds to the central calyx formed by the beta-strands. Whether there are two vitamin D binding-sites in each beta-LG molecule has been a subject of controversy. Here, we report a second vitamin D(3) binding site identified by synchrotron X-ray diffraction (at 2.4 angstrom resolution). In the central calyx binding mode, the aliphatic tail of vitamin D(3) clearly inserts into the binding cavity, where the 3-OH group of vitamin D(3) binds externally. The electron density map suggests that the 3-OH group interacts with the carbonyl of Lys-60 forming a hydrogen bond (2.97 angstrom). The second binding site, however, is near the surface at the C-terminus (residues 136-149) containing part of an a-helix and a beta-strand I with 17.91 angstrom in length, while the span of vitamin D(3) is about 12.51 angstrom. A remarkable feature of the second exosite is that it combines an amphipathic alpha-helix providing nonpolar residues (Phe-136, Ala-139, and Leu-140) and a beta-strand providing a nonpolar (Ile-147) and a buried polar residue (Arg-148). They are linked by a hydrophobic loop (Ala-142, Leu-143, Pro-144, and Met-145). Thus, the binding pocket furnishes strong hydrophobic force to stabilize vitamin D(3) binding. This finding provides a new insight into the interaction between vitamin D(3) and beta-LG, in which the exosite may provide another route for the transport of vitamin D(3) in vitamin D(3) fortified dairy products. Atomic coordinates for the crystal structure Of beta-LG-vitamin D(3) complex described in this work have been deposited in the PDB (access code 2GJ5).
Demographics of Pediatric OHCA Survivors With Postdischarge Diseases: A National Population-Based Follow-Up Study
(2020-01-24)
Lee, Tsung-Han
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Juan, I-Cheng
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Hsu, Hsiu-Ying
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Chen, Wen-Liang
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Huang, Cheng-Chieh
Background: Postdischarge diseases (PDDs) have been reported for adult survivors of out-of-hospital cardiac arrest (OHCA). However, the detailed demographics of pediatric OHCA survivors with PDDs are not well-documented, and information regarding functional survivors is particularly limited. We aimed to report detailed information on the PDDs of survivors of traumatic and non-traumatic pediatric OHCA using a national healthcare database. Methods: We retrospectively obtained data from the Taiwan government healthcare database (2011-2015). Information on the demographics of traumatic and non-traumatic pediatric OHCA survivors (<20 years) was obtained and reported. The patients who survived to discharge (survivors) and those classified as functional survivors were followed up for 1 year for the analysis of newly diagnosed PDDs. The time from discharge to PDD diagnosis was also reported. Results: A total of 2,178 non-traumatic and 288 traumatic OHCA pediatric cases were included. Among the non-traumatic OHCA survivors (n = 374, survival rate = 17.2%), respiratory tract (n = 270, 72.2%), gastrointestinal (n = 187, 50.0%), and neurological diseases (n = 167, 49.1%) were the three most common PDD categories, and in these three categories, the majority of PDDs were atypical/influenza pneumonia, non-infective acute gastroenteritis, and generalized/status epilepsy, respectively. Among the traumatic OHCA survivors (n = 21, survival rate = 7.3%), respiratory tract diseases (n = 17, 81.0%) were the most common, followed by skin or soft tissue (n = 14, 66.7%) diseases. Most functional survivors still suffered from neurological and respiratory tract diseases. Most PDDs, except for skin or soft tissue diseases, were newly diagnosed within the first 3 months after discharge. Conclusions: Respiratory tract (pneumonia), neurological (epilepsy), and skin or soft tissue (dermatitis) diseases were very common among both non-traumatic and traumatic OHCA survivors. More importantly, most PDDs, except for skin or soft tissue diseases, were newly diagnosed within the first 3 months after discharge.
Discovery of prognostic biomarkers for predicting lung cancer metastasis using microarray and survival data
(2015-02-21)
Huang, Hui-Ling
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Wu, Yu-Chung
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Su, Li-Jen
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Huang, Yun-Ju
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Charoenkwan, Phasit
Background: Few studies have investigated prognostic biomarkers of distant metastases of lung cancer. One of the central difficulties in identifying biomarkers from microarray data is the availability of only a small number of samples, which results overtraining. Recently obtained evidence reveals that epithelial-mesenchymal transition (EMT) of tumor cells causes metastasis, which is detrimental to patients' survival. Results: This work proposes a novel optimization approach to discovering EMT-related prognostic biomarkers to predict the distant metastasis of lung cancer using both microarray and survival data. This weighted objective function maximizes both the accuracy of prediction of distant metastasis and the area between the disease-free survival curves of the non-distant and distant metastases. Seventy-eight patients with lung cancer and a follow-up time of 120 months are used to identify a set of gene markers and an independent cohort of 26 patients is used to evaluate the identified biomarkers. The medical records of the 78 patients show a significant difference between the disease-free survival times of the 37 non-distant-and the 41 distant-metastasis patients. The experimental results thus obtained are as follows. 1) The use of disease-free survival curves can compensate for the shortcoming of insufficient samples and greatly increase the test accuracy by 11.10%; and 2) the support vector machine with a set of 17 transcripts, such as CCL16 and CDKN2AIP, can yield a leave-one-out cross-validation accuracy of 93.59%, a test accuracy of 76.92%, a large disease-free survival area of 74.81%, and a mean survival prediction error of 3.99 months. The identified putative biomarkers are examined using related studies and signaling pathways to reveal the potential effectiveness of the biomarkers in prospective confirmatory studies. Conclusions: The proposed new optimization approach to identifying prognostic biomarkers by combining multiple sources of data (microarray and survival) can facilitate the accurate selection of biomarkers that are most relevant to the disease while solving the problem of insufficient samples.
Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis
(2016-01-01)
Lin, Yan-Ren
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Li, Chao-Jui
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Syu, Shih-Han
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Wen, Cheng-Hao
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Buddhakosai, Waradee
Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2) were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n = 20) and control (normal saline,n = 20) groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5) or to culture medium (control). Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group (n < 0.05). In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53) and apoptosis (caspase-3, Bcl-xL) markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR). L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5). More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells' beating function at a low pH level.
Early Epinephrine Improves the Stabilization of Initial Post-resuscitation Hemodynamics in Children With Non-shockable Out-of-Hospital Cardiac Arrest
(2019-06-06)
Lin, Yan-Ren
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Li, Chao-Jui
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Huang, Cheng-Chieh
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Lee, Tsung-Han
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Chen, Tren-Yi
Background: In children with non-shockable out-of-hospital cardiac arrest, early epinephrine (EE) might help to establish the return of spontaneous circulation (ROSC) and be associated with survival. In the present study, we aimed to analyze the effects of EE on outcomes and post-resuscitation hemodynamics in children with non-shockable OHCA. Methods: This was a retrospective analysis of data from 216 children (<19 years) who had suffered non-traumatic and non-shockable OHCA and received epinephrine for resuscitation (Jan 1, 2006-Dec 31, 2014). Demographics, pre-/in-hospital information, and the time to the first dose of epinephrine were recorded. Early post-resuscitation hemodynamics (the first hour after sustained ROSC), survival and good neurological outcomes (Pediatric Cerebral Performance Category Scales 1 or 2) were analyzed by the time to epinephrine-classified as early (EE): <15 min, intermediate (IE): 15-30 min, or late (LE): >30 min. Results: Twenty-eight (13.0%) children survived to discharge, but only 17 (7.9%) had good neurological outcomes. In all, 41 (18.9%) children received EE; in comparison to IE and LE, this was significantly associated with tachycardia (73.9%) in the post-resuscitation period (p < 0.05). Tachycardia (OR: 7.41, 95% CI: 1.96-29.31) and hypertension (OR: 6.03, 95% CI: 1.85-13.77) were significantly associated with EE after adjusting for confounding factors. EE was also significantly associated with better overall outcomes than ME and LE (any ROSC, sustained ROSC, survival to the intensive care unit, admission, survival to discharge and good neurological outcomes, all p < 0.05). Conclusions: EE helped to establish ROSC but was also associated with more tachycardia and hypertension in the early post-resuscitation period. In children with non-traumatic and non-shockable OHCA, EE was associated with a higher survival rate and better neurological outcomes than were ME and LE.
Elastin-like Polypeptide-based Hydrogel Actuator for Cardiac Tissue Engineering
(2017-01-01)
Lo, Yu-Chih
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Chiang, Min-Yu
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Chen, Wen-Liang
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Chen, San-Yuan
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材料科學與工程學系
Cardiac tissue engineering aims to reconstruct functional construction with resembling native tissue to replace damaged myocardium. To mimic native myocardium, cells with phenotypes of mature cardiomyocytes and scaffolds with elastic, electro-conductive, highly porous, and biodegradable plays two major roles. So far, although a number of cell types have been evaluated in the reports of cardiac repair, most of them cannot form functional cardiomyocytes with mature cardiac phenotypes including the formation of the myocytic syncytium with surrounding cardiomyocytes, and expression of cardiac specific proteins in completely organized pattern. The maturation of cardiomyocytes can be achieved by multiple stimuli such as electrical stimulation, mechanical stretching, and chemical stimulation. Therefore, in this study, we aimed to develop a conductive hydrogel actuator based on elastin-like polypeptide (ELP) consisting of repeating elastin-derived sequences Val-Pro-Gly-Ile-Gly (VPGIG), combining near-infrared light (NIR)-induced mechanical stretching and electrical stimulation for the simulation of immature cardiomyocytes. The hydrogel actuator can be fabricated by rapidly crosslinking by tetrakis(hydroxymethyl) phosphonium chloride (THPC) to form a high density porous structure, providing cardiac muscle cell an extracellular matrix (ECM)-like nanostructure with bioactive Arg-Gly-Asp (RGD) peptide. It showed appropriate mechanical strength and sufficient electroactivity, which is suitable for myocardial cell culture system. In addition, the actuation leads a specific and efficient way to regulate activity in cardiac muscle cell by physical cue of the hydrogel. In the future, we expect the ELP-baesd hydrogel actuator to show great potential to be used in the differentiation and maturation of cardiomyocytes.
Enterotype-based Analysis of Gut Microbiota along the Conventional Adenoma-Carcinoma Colorectal Cancer Pathway
(2019-07-29)
Yang, Tzu-Wei
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Lee, Wei-Hsiang
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Tu, Siang-Jyun
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Huang, Wei-Chih
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Chen, Hui-Mei
The dysbiosis of human gut microbiota is strongly associated with the development of colorectal cancer (CRC). The dysbiotic features of the transition from advanced polyp to early-stage CRC are largely unknown. We performed a 16S rRNA gene sequencing and enterotype-based gut microbiota analysis study. In addition to Bacteroides-and Prevotella-dominated enterotypes, we identified an Escherichia-dominated enterotype. We found that the dysbiotic features of CRC were dissimilar in overall samples and especially Escherichia-dominated enterotype. Besides a higher abundance of Fusobacterium, Enterococcus, and Aeromonas in all CRC faecal microbiota, we found that the most notable characteristic of CRC faecal microbiota was a decreased abundance of potential beneficial butyrate-producing bacteria. Notably, Oscillospira was depleted in the transition from advanced adenoma to stage 0 CRC, whereas Haemophilus was depleted in the transition from stage 0 to early-stage CRC. We further identified 7 different CAGs by analysing bacterial clusters. The abundance of microbiota in cluster 3 significantly increased in the CRC group, whereas that of cluster 5 decreased. The abundance of both cluster 5 and cluster 7 decreased in the Escherichia-dominated enterotype of the CRC group. We present the first enterotype-based faecal microbiota analysis. The gut microbiota of colorectal neoplasms can be influenced by its enterotype.
Impact of Different Initial Epinephrine Treatment Time Points on the Early Postresuscitative Hemodynamic Status of Children With Traumatic Out-of-hospital Cardiac Arrest
(2016-03-01)
Lin, Yan-Ren
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Syue, Yuan-Jhen
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Buddhakosai, Waradee
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Lu, Huai-En
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Chang, Chin-Fu
The postresuscitative hemodynamic status of children with traumatic out-of-hospital cardiac arrest (OHCA) might be impacted by the early administration of epinephrine, but this topic has not been well addressed. The aim of this study was to analyze the early postresuscitative hemodynamics, survival, and neurologic outcome according to different time points of first epinephrine treatment among children with traumatic OHCA.Information on 388 children who presented to the emergency departments of 3 medical centers and who were treated with epinephrine for traumatic OHCA during the study period (2003-2012) was retrospectively collected. The early postresuscitative hemodynamic features (cardiac functions, end-organ perfusion, and consciousness), survival, and neurologic outcome according to different time points of first epinephrine treatment (early: <15, intermediate: 15-30, and late: >30minutes after collapse) were analyzed.Among 165 children who achieved sustained return of spontaneous circulation, 38 children (9.8%) survived to discharge and 12 children (3.1%) had good neurologic outcomes. Early epinephrine increased the postresuscitative heart rate and blood pressure in the first 30minutes, but ultimately impaired end-organ perfusion (decreased urine output and initial creatinine clearance) (all P<0.05). Early epinephrine treatment increased the chance of achieving sustained return of spontaneous circulation, but did not increase the rates of survival and good neurologic outcome.Early epinephrine temporarily increased heart rate and blood pressure in the first 30minutes of the postresuscitative period, but impaired end-organ perfusion. Most importantly, the rates of survival and good neurologic outcome were not significantly increased by early epinephrine administration.
Increased Risk of Major Depression in the Three Years following a Femoral Neck Fracture-A National Population-Based Follow-Up Study
(2014-03-13)
Chang, Chih-Yu
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Chen, Wen-Liang
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Liou, Yi-Fan
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Ke, Chih-Chi
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Lee, Hua-Chin
Femoral neck fracture is common in the elderly, and its impact has increased in aging societies. Comorbidities, poor levels of activity and pain may contribute to the development of depression, but these factors have not been well addressed. This study aims to investigate the frequency and risk of major depression after a femoral neck fracture using a nationwide population-based study. The Taiwan Longitudinal Health Insurance Database was used in this study. A total of 4,547 patients who were hospitalized for femoral neck fracture within 2003 to 2007 were recruited as a study group; 13,641 matched non-fracture participants were enrolled as a comparison group. Each patient was prospectively followed for 3 years to monitor the occurrence of major depression. Cox proportional-hazards models were used to compute the risk of major depression between members of the study and comparison group after adjusting for residence and sociodemographic characteristics. The most common physical comorbidities that were present after the fracture were also analyzed. The incidences of major depression were 1.2% (n = 55) and 0.7% (n = 95) in the study and comparison groups, respectively. The stratified Cox proportional analysis showed a covariate-adjusted hazard ratio of major depression among patients with femoral neck fracture that was 1.82 times greater (95% CI, 1.30-2.53) than that of the comparison group. Most major depressive episodes (34.5%) presented within the first 200 days following the fracture. In conclusion, patients with a femoral neck fracture are at an increased risk of subsequent major depression. Most importantly, major depressive episodes mainly occurred within the first 200 days following the fracture.
Increased risk of major depression subsequent to a first-attack and non-infection caused urticaria in adolescence: a nationwide population-based study
(2014-07-11)
Kuo, Chia-Lun
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Chen, Chi-Yen
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Huang, Hui-Ling
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Chen, Wen-Liang
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Lee, Hua-Chin
Background: Non-infection caused urticaria is a common ailment in adolescents. Its symptoms (e.g., unusual rash appearance, limitation of daily activities, and recurrent itching) may contribute to the development of depressive stress in adolescents; the potential link has not been well studied. This study aimed to investigate the risk of major depression after a first-attack and non-infection caused urticaria. Methods: This study used the Taiwan Longitudinal Health Insurance Database. A total of 5,755 adolescents hospitalized for a first-attack and non-infection caused urticaria from 2005 to 2009 were recruited as the study group, together with 17,265 matched non-urticarial enrollees who comprised the control group. Patients who had any history of urticaria or depression prior to the evaluation period were excluded. Each patient was followed for one year to identify the occurrence of depression. Cox proportional hazards models were generated to compute the risk of major depression, adjusting for the subjects\' sociodemographic characteristics. Depression-free survival curves were also analyzed. Results: Thirty-four (0.6%) adolescents with non-infection caused urticaria and 59 (0.3%) non-urticarial control subjects suffered a new-onset episode of major depression during the study period. The stratified Cox proportional analysis showed that the crude hazard ratio (HR) of depression among adolescents with urticaria was 1.73 times (95% CI, 1.13-2.64) than that of the control subjects without urticaria. Moreover, the HR were higher in physical (HR: 3.39, 95% CI 2.77-11.52) and allergy chronic urticaria (HR: 2.43, 95% CI 3.18-9.78). Conclusion: Individuals who have a non-infection caused urticaria during adolescence are at a higher risk of developing major depression.
Integrated MicroRNA-mRNA Analysis Reveals miR-204 Inhibits Cell Proliferation in Gastric Cancer by Targeting CKS1B, CXCL1 and GPRC5A
(2018-01-01)
Shrestha, Sirjana
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Yang, Chi-Dung
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Hong, Hsiao-Chin
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Chou, Chih-Hung
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Tai, Chun-San
Gastric cancer (GC) is the second most frequent cause of cancer-related deaths worldwide. MicroRNAs are single-stranded RNA molecules of 21-23 nucleotides that regulate target gene expression through specific base-pairing interactions between miRNA and untranslated regions of targeted mRNAs. In this study, we generated a multistep approach for the integrated analysis of miRNA and mRNA expression. First, both miRNA and mRNA expression profiling datasets in gastric cancer from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) identified 79 and 1042 differentially expressed miRNAs and mRNAs, respectively, in gastric cancer. Second, inverse correlations between miRNA and mRNA expression levels identified 3206 miRNA-mRNA pairs combined with 79 dysregulated miRNAs and their 774 target mRNAs predicted by three prediction tools, miRanda, PITA, and RNAhybrid. Additionally, miR-204, which was found to be down-regulated in gastric cancer, was ectopically over-expressed in the AGS gastric cancer cell line and all down-regulated targets were identified by RNA sequencing (RNA-seq) analysis. Over-expression of miR-204 reduced the gastric cancer cell proliferation and suppressed the expression of three targets which were validated by qRT-PCR and luciferase assays. For the first time, we identified that CKS1B, CXCL1, and GPRC5A are putative targets of miR-204 and elucidated that miR-204 acted as potential tumor suppressor and, therefore, are useful as a promising therapeutic target for gastric cancer.
Is schizophrenia associated with an increased risk of chronic kidney disease? A nationwide matched-cohort study
(2015-01-01)
Tzeng, Nian-Sheng
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Hsu, Yung-Ho
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Ho, Shinn-Ying
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Kuo, Yu-Ching
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Lee, Hua-Chin
Objective: The impact of schizophrenia on vital diseases, such as chronic kidney disease (CKD), has not as yet been verified. This study aims to establish whether there is an association between schizophrenia and CKD. Design: A nationwide matched cohort study. Setting: Taiwan's National Health Insurance Research Database. Participants: A total of 2338 patients with schizophrenia, and 7014 controls without schizophrenia (1: 3), matched cohort for sex, age group, geography, urbanisation and monthly income, between 1 January 2003 and 31 December 2007, based on the International Classifications of Disease Ninth Edition (ICD-9), Clinical Modification codes. Primary and secondary outcome measures: After making adjustments for confounding risk factors, a Cox proportional hazards model was used to compare the risk of developing CKD during a 3-year follow-up period from the index date. Results: Of the 2338-subject case cohort, 163 (6.97%) developed a CKD, as did 365 (5.20%) of the 7014 control participants. Cox proportional hazards regression analysis revealed that patients with schizophrenia were more likely to develop CKD (HR = 1.36, 95% CI 1.13 to 1.63; p < 0.001). After adjusting for gender, age group, hypertension, diabetes mellitus, hyperlipidaemia, heart disease and nonsteroid anti-inflammatory drugs (NSAIDs) usage, the HR for patients with schizophrenia was 1.25 (95% CI 1.04 to 1.50; p < 0.05). Neither typical nor atypical antipsychotics was associated an increased risk of CKD in patients with schizophrenia. Conclusions: The findings from this population-based retrospective cohort study suggest that schizophrenia is associated with a 25% increase in the risk of developing CKD within only a 3-year follow-up period.
miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database
(2016-01-04)
Chou, Chih-Hung
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Chang, Nai-Wen
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Shrestha, Sirjana
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Hsu, Sheng-Da
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Lin, Yu-Ling
MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides, which negatively regulate the gene expression at the post-transcriptional level. This study describes an update of the miRTarBase (http://miRTarBase.mbc.nctu.edu.tw/) that provides information about experimentally validated miRNA-target interactions (MTIs). The latest update of the miRTarBase expanded it to identify systematically Argonaute-miRNA-RNA interactions from 138 crosslinking and immunoprecipitation sequencing (CLIP-seq) data sets that were generated by 21 independent studies. The database contains 4966 articles, 7439 strongly validated MTIs (using reporter assays or western blots) and 348 007 MTIs from CLIP-seq. The number of MTIs in the miRTarBase has increased around 7-fold since the 2014 miRTarBase update. The miRNA and gene expression profiles from The Cancer Genome Atlas (TCGA) are integrated to provide an effective overview of this exponential growth in the miRNA experimental data. These improvements make the miRTarBase one of the more comprehensively annotated, experimentally validated miRNA-target interactions databases and motivate additional miRNA research efforts.
miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions
(2018-01-04)
Chou, Chih-Hung
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Shrestha, Sirjana
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Yang, Chi-Dung
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Chang, Nai-Wen
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Lin, Yu-Ling
MicroRNAs (miRNAs) are small non-coding RNAs of similar to 22 nucleotides that are involved in negative regulation of mRNA at the post-transcriptional level. Previously, we developed miRTarBase which provides information about experimentally validated miRNA-target interactions (MTIs). Here, we describe an updated database containing 422 517 curated MTIs from 4076 miRNAs and 23 054 target genes collected from over 8500 articles. The number of MTIs curated by strong evidence has increased similar to 1.4-fold since the last update in 2016. In this updated version, target sites validated by reporter assay that are available in the literature can be downloaded. The target site sequence can extract new features for analysis via a machine learning approach which can help to evaluate the performance of miRNA-target prediction tools. Furthermore, different ways of browsing enhance user browsing specific MTIs. With these improvements, miRTarBase serves as more comprehensively annotated, experimentally validated miRNA-target interactions databases in the field of miRNA related research. miRTarBase is available at http://miRTarBase.mbc.nctu.edu.tw/.
Prediction and analysis of protein solubility using a novel scoring card method with dipeptide composition
(2012-12-13)
Huang, Hui-Ling
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Charoenkwan, Phasit
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Kao, Te-Fen
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Lee, Hua-Chin
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Chang, Fang-Lin
Background: Existing methods for predicting protein solubility on overexpression in Escherichia coli advance performance by using ensemble classifiers such as two-stage support vector machine (SVM) based classifiers and a number of feature types such as physicochemical properties, amino acid and dipeptide composition, accompanied with feature selection. It is desirable to develop a simple and easily interpretable method for predicting protein solubility, compared to existing complex SVM-based methods. Results: This study proposes a novel scoring card method (SCM) by using dipeptide composition only to estimate solubility scores of sequences for predicting protein solubility. SCM calculates the propensities of 400 individual dipeptides to be soluble using statistic discrimination between soluble and insoluble proteins of a training data set. Consequently, the propensity scores of all dipeptides are further optimized using an intelligent genetic algorithm. The solubility score of a sequence is determined by the weighted sum of all propensity scores and dipeptide composition. To evaluate SCM by performance comparisons, four data sets with different sizes and variation degrees of experimental conditions were used. The results show that the simple method SCM with interpretable propensities of dipeptides has promising performance, compared with existing SVM-based ensemble methods with a number of feature types. Furthermore, the propensities of dipeptides and solubility scores of sequences can provide insights to protein solubility. For example, the analysis of dipeptide scores shows high propensity of a-helix structure and thermophilic proteins to be soluble. Conclusions: The propensities of individual dipeptides to be soluble are varied for proteins under altered experimental conditions. For accurately predicting protein solubility using SCM, it is better to customize the score card of dipeptide propensities by using a training data set under the same specified experimental conditions. The proposed method SCM with solubility scores and dipeptide propensities can be easily applied to the protein function prediction problems that dipeptide composition features play an important role. Availability: The used datasets, source codes of SCM, and supplementary files are available at http://iclab.life.nctu.edu.tw/SCM/.