Publications by authors named "Chien-Sheng Chen"

89 Publications

YPIBP: A repository for phosphoinositide-binding proteins in yeast.

Comput Struct Biotechnol J 2021 24;19:3692-3707. Epub 2021 Jun 24.

Department of Electrical Engineering, College of Electrical Engineering and Computer Science, National Cheng Kung University, Tainan 701, Taiwan.

Phosphoinositides (PIs) are a family of eight lipids consisting of phosphatidylinositol (PtdIns) and its seven phosphorylated forms. PIs have important regulatory functions in the cell including lipid signaling, protein transport, and membrane trafficking. Yeast has been recognized as a eukaryotic model system to study lipid-protein interactions. Hundreds of yeast PI-binding proteins have been identified, but this research knowledge remains scattered. Besides, the complete PI-binding spectrum and potential PI-binding domains have not been interlinked. No comprehensive databases are available to support the lipid-protein interaction research on phosphoinositides. Here we constructed the first knowledgebase of Yeast Phosphoinositide-Binding Proteins (YPIBP), a repository consisting of 679 PI-binding proteins collected from high-throughput proteome-array and lipid-array studies, QuickGO, and a rigorous literature mining. The YPIBP also contains protein domain information in categories of lipid-binding domains, lipid-related domains and other domains. The YPIBP provides search and browse modes along with two enrichment analyses (PI-binding enrichment analysis and domain enrichment analysis). An interactive visualization is given to summarize the PI-domain-protein interactome. Finally, three case studies were given to demonstrate the utility of YPIBP. The YPIBP knowledgebase consolidates the present knowledge and provides new insights of the PI-binding proteins by bringing comprehensive and in-depth interaction network of the PI-binding proteins. YPIBP is available at http://cosbi7.ee.ncku.edu.tw/YPIBP/.
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http://dx.doi.org/10.1016/j.csbj.2021.06.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261538PMC
June 2021

Materials Engineering of Violin Soundboards by Stradivari and Guarneri.

Angew Chem Int Ed Engl 2021 Jun 1. Epub 2021 Jun 1.

Department of Chemistry, National Taiwan University, 1 Roosevelt Road Section 4, Taipei, 106, Taiwan.

We investigated the material properties of Cremonese soundboards using a wide range of spectroscopic, microscopic, and chemical techniques. We found similar types of spruce in Cremonese soundboards as in modern instruments, but Cremonese spruces exhibit unnatural elemental compositions and oxidation patterns that suggest artificial manipulation. Combining analytical data and historical information, we may deduce the minerals being added and their potential functions-borax and metal sulfates for fungal suppression, table salt for moisture control, alum for molecular crosslinking, and potash or quicklime for alkaline treatment. The overall purpose may have been wood preservation or acoustic tuning. Hemicellulose fragmentation and altered cellulose nanostructures are observed in heavily treated Stradivari specimens, which show diminished second-harmonic generation signals. Guarneri's practice of crosslinking wood fibers via aluminum coordination may also affect mechanical and acoustic properties. Our data suggest that old masters undertook materials engineering experiments to produce soundboards with unique properties.
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http://dx.doi.org/10.1002/anie.202105252DOI Listing
June 2021

Role of Trachway versus Conventional Modes of Intubation in Difficult Airway Management in COVID-19 Setups.

Emerg Med Int 2021 25;2021:6614523. Epub 2021 Feb 25.

Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 231 New Taipei, Taiwan.

Difficult airway management in critically ill patients remains a difficult task associated with high morbidity and mortality rates. In difficult airway populations, prompt effective intubation is more important to prevent hypoxia and neurological injury. During the ongoing COVID-19 pandemic, prolonged intubation time and repeated intubation can lead to an increase in the risk of infection. Therefore, digital devices can shorten intubation times and decrease the risk of infection among clinical staff. The advantages of the Trachway videolight intubating stylet suit these conditions. Trachway stylet intubation is an effective method for video laryngoscopy to enhance patient safety and improve the intubation success rate. However, a few studies have focused on the effect of stylet intubation by reducing repeated intubation and oxygen desaturation. In this study, we reviewed current data of Trachway intubation and shared our four major training scenarios in Taipei Tzu Chi Hospital via the Trachway videolight intubating stylet system for emergency intubation, comparing them with other modes of intubation.
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http://dx.doi.org/10.1155/2021/6614523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910513PMC
February 2021

Systematic Identification of Protein Targets of Sub5 Using Proteome Microarrays.

Int J Mol Sci 2021 Jan 13;22(2). Epub 2021 Jan 13.

Graduate Institute of Systems Biology and Bioinformatics, and Department of Biomedical Sciences and Engineering, College of Health Sciences and Technology, National Central University, Jhongli 32001, Taiwan.

Antimicrobial peptides (AMPs) are intensively studied in terms of alternative drugs. Sub5 is a synthetic 12-mer AMP with substitutions of five amino acids of bactenecin 2A (Bac2A), a linear-ized bactenecin variant of bovine. Sub5 is highly effective against fungi with an ability to trans-locate cell membrane, but its targets are unknown. Systematic analysis of Sub5 targets will facil-itate our understanding on its mechanism of action. In this study, we used high-throughput proteome microarrays to explore the potential protein targets of Sub5. The screening results showed 128 potential protein targets of Sub5. Bioinformatics analysis of protein targets of Sub5 revealed significant gene ontology (GO) enrichment in actin related pro-cess of "actin filament-based process", "actin filament organization", "actin cortical patch or-ganization", regulation of "actin filament bundle assembly". Moreover, the other enriched cat-egories in GO enrichment mostly contained actin associate proteins. In total, 11 actin-associated proteins were identified in the protein targets of Sub5. Protein family (PFAM) enrichment anal-ysis shows protein domain enriched in actin binding, i.e., "Cytoskeletal-regulatory complex EF hand (helix E-loop-helix F motif)". Being consistent with GO analysis, Search Tool for the Re-trieval of Interacting Genes/Proteins (STRING) analysis of the protein targets of Sub5 showed ac-tin network with involvement of 15 protein targets. Along with actin-network, STRING analysis showed protein-protein interaction network in ribonucleoprotein, transcription and translation, chromosome, histone, and ubiquitin related, DNA repair, and chaperone. Multiple Expression motifs for Motif Elicitation (MEME) suite provided a consensus binding motif of [ED][ED]EEE[ED][ED][ED][ED][ED], in total of 75 protein targets of Sub5. This motif was present in 9 out of 15 actin-related proteins identified among protein targets of Sub5.
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http://dx.doi.org/10.3390/ijms22020760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828587PMC
January 2021

Pediatric Spontaneous Pneumomediastinum after a Push-Up Exercise: An Uncommon Complication of a Common Exercise.

Children (Basel) 2020 Dec 11;7(12). Epub 2020 Dec 11.

Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.

Pediatric spontaneous pneumomediastinum is an uncommon condition associated with infection, trauma, or coexisting structural lung pathology. Exercise-related spontaneous subcutaneous emphysema and pneumomediastinum are rarely reported. However, severe pneumomediastinum may coexist with pneumothorax, pneumorrhachis, and subcutaneous emphysema, which can potentially lead to serious complications, including airway obstruction and pneumorrhachis. Therefore, early diagnosis and timely management are important for physicians to determine the etiology and prevent further damage. Here, we present a case of exercise-related spontaneous subcutaneous emphysema and pneumomediastinum to highlight the pathogenesis and suggest therapeutic strategies.
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http://dx.doi.org/10.3390/children7120287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763168PMC
December 2020

Systematic Analysis of Phosphatidylinositol-5-phosphate-Interacting Proteins Using Yeast Proteome Microarrays.

Anal Chem 2021 01 11;93(2):868-877. Epub 2020 Dec 11.

Department of Food Safety/Hygiene and Risk Management, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.

We used yeast proteome microarrays (∼5800 purified proteins) to conduct a high-throughput and systematic screening of PI5P-interacting proteins with PI5P-tagged fluorescent liposomal nanovesicles. Lissamine rhodamine B-dipalmitoyl phosphatidylethanol was incorporated into the liposome bilayer to provide the nanovesicles with fluorescence without any encapsulants, which not only made the liposome fabrication much easier without the need for purification but also improved the chip-probing quality. A special chip assay was washed very gently without the traditional spin-dry step. Forty-five PI5P-interacting proteins were identified in triplicate with this special chip assay. Subsequently, we used flow cytometry to validate these interactions, and a total of 41 PI5P-interacting proteins were confirmed. Enrichment analysis revealed that these proteins have significant functions associated with ribosome biogenesis, rRNA processing, ribosome binding, GTP binding, and hydrolase activity. Their component enrichment is located in the nucleolus. The InterPro domain analysis indicated that PI5P-interacting proteins are enriched in the P-loop containing nucleoside triphosphate hydrolases domain (P-loop). Additionally, using the MEME program, we identified a consensus motif (IVGPAGTGKSTLF) that contains the Walker A sequence, a well-known nucleotide-binding motif. Furthermore, using a quartz crystal microbalance, both the consensus motif and Walker A motif showed strong affinities to PI5P-containing liposomes but not to PI5P-deprived liposomes or PI-containing liposomes. Additionally, the glycine (G6) and lysine (K7) residues of the Walker A motif (-GPAGTGKS-) were found to be critical to the PI5P-binding ability. This study not only identified an additional set of PI5P-interacting proteins but also revealed the strong PI5P-binding affinity ( = 1.81 × 10 M) of the Walker A motif beyond the motif's nucleotide-binding characteristic.
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http://dx.doi.org/10.1021/acs.analchem.0c03463DOI Listing
January 2021

MS Location Estimation Based on the Artificial Bee Colony Algorithm.

Sensors (Basel) 2020 Sep 29;20(19). Epub 2020 Sep 29.

School of Electrical and Computer Engineering, Nanfang College of Sun Yat-Sen University, Guangzhou 510970, China.

With the mature technology of wireless communications, the function of estimating the mobile station (MS) position has become essential. Suppressing the bias resulting from non-line-of-sight (NLSO) scenarios is the main issue for a wireless location network. The artificial bee colony (ABC) algorithm, based on the depiction of bee swarm's foraging characteristics, is widely applied to solve optimization problems in several fields. Based on three measurements of time-of-arrival (TOA), an objective function is used to quantify the additional NLOS error on the MS positioning scheme. The ABC algorithm is adopted to locate the most precise MS location by minimizing the objective function value. The performance of the proposed positioning methods is verified under various error distributions through computer simulations. Meanwhile, the localization accuracy achieved by other existing methods is also investigated. According to the simulation results, accurate estimation of the MS position is derived and therefore the efficiency of the localization process is increased.
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http://dx.doi.org/10.3390/s20195597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582589PMC
September 2020

Identification of MltG as a Prc Protease Substrate Whose Dysregulation Contributes to the Conditional Growth Defect of Prc-Deficient .

Front Microbiol 2020 27;11:2000. Epub 2020 Aug 27.

Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Microbial proteases play pivotal roles in many aspects of bacterial physiological processes. Because a protease exerts its biological function by proteolytically regulating its substrates, the identification and characterization of the physiological substrates of a protease advance our understanding of the biological roles of the protease. Prc (also named Tsp) is an periplasmic protease thought to be indispensable for to survive under low osmolality at 42°C. The accumulation of the Prc substrate MepS due to Prc deficiency contributes to the conditional growth defect. Because preventing MepS accumulation only partially restored the growth of Prc-deficient , we hypothesized that other unidentified Prc substrates intracellularly accumulate due to Prc deficiency and contribute to the conditional growth defect. To identify previously undiscovered substrates, 85 proteins able to physically interact with Prc were identified using proteome arrays. Ten proteins were shown to be cleavable by Prc . Among these candidates, MltG was able to interact with Prc in . Prc regulated the intracellular level of MltG, indicating that MltG is a physiological substrate of Prc. Prc deficiency induced the accumulation of MltG in the bacteria. Blocking MltG accumulation by deleting partially restored the growth of Prc-deficient . In addition, Prc-deficient with blocked MltG and MepS expression exhibited higher growth levels than those with only the MltG or MepS expression blocked under low osmolality at 42°C, suggesting that these accumulated substrates additively contributed to the conditional growth defect. MltG is a lytic transglycosylase involved in the biogenesis of peptidoglycan (PG). In addition to MltG, the previously identified physiological Prc substrates MepS and PBP3 are involved in PG biogenesis, suggesting a potential role of Prc in regulating PG biogenesis.
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http://dx.doi.org/10.3389/fmicb.2020.02000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481392PMC
August 2020

Two-Thumb or Two-Finger Technique in Infant Cardiopulmonary Resuscitation by a Single Rescuer? A Meta-Analysis with GOSH Analysis.

Int J Environ Res Public Health 2020 07 19;17(14). Epub 2020 Jul 19.

Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan.

Out-of-hospital infant cardiopulmonary arrest is a fatal and uncommon event. High mortality rates and poor neurological outcomes may be improved by early cardiopulmonary resuscitation (CPR). The ongoing debate over two different infant CPR techniques, the two-thumb (TT) and the two-finger (TF) technique, has remained, especially in terms of the adequate compression depth, compression rate, and hands-off time. In this article, we searched three major databases, PubMed, EMBASE (Excerpta Medica database), and CENTRAL (Cochrane Central Register of Controlled Trials), for randomized control trials which compared the outcomes of interest between the TT and TF techniques in infant CPR. The results showed that the TT technique was associated with higher proportion of adequate compression depth (Mean difference (MD): 19.99%; 95%, Confidence interval (CI): 9.77 to 30.22; < 0.01) than the TF technique. There was no significant difference in compression rate and hands-off time. In our conclusion, the TT technique is better in terms of adequate compression depth than the TF technique, without significant differences in compression rate and hands-off time.
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http://dx.doi.org/10.3390/ijerph17145214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400494PMC
July 2020

Analysis of Chest-Compression Depth and Full Recoil in Two Infant Chest-Compression Techniques Performed by a Single Rescuer: Systematic Review and Meta-Analysis.

Int J Environ Res Public Health 2020 06 5;17(11). Epub 2020 Jun 5.

Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan.

Pediatric cardiac arrest is associated with high mortality and permanent neurological injury. We aimed to compare the effects of the two-thumb (TT) and two-finger (TF) techniques in infant cardiopulmonary resuscitation (CPR) performed by a single rescuer. We searched PubMed, EMBASE, and CENTRAL for randomized control trials published before December 2019. Studies comparing the TT and TF techniques in infant CPR were included for meta-analysis. Relevant information was extracted for methodological assessment. Twelve studies were included. The TT technique was associated with deeper chest-compression depth (mean difference: 4.71 mm; 95% confidence interval: 3.61 to 5.81; < 0.001) compared with the TF technique. The TF technique was better in terms of the proportion of complete chest recoil (mean difference: -11.73%; 95% confidence interval: -20.29 to -3.17; = 0.007). CPR was performed on a manikin model, and the application of the results to real human beings may be limited. The TT technique was superior to the TF technique in terms of chest-compression depth, but with inferior chest full recoil. Future investigations should focus on modifying the conventional TT technique to generate greater compression depth and achieve complete chest recoil.
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http://dx.doi.org/10.3390/ijerph17114018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312068PMC
June 2020

Nonthyroidal Illness Syndrome and Hypothyroidism in Ischemic Heart Disease Population: A Systematic Review and Meta-Analysis.

J Clin Endocrinol Metab 2020 08;105(8)

Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan.

Context: The association of non-thyroidal illness syndrome (NTIS) and hypothyroidism with the prognosis in ischemic heart disease (IHD) population is inconclusive.

Objective: We aimed to evaluate the influence of NTIS and hypothyroidism on all-cause mortality and major adverse cardiac events (MACE) in IHD population.

Data Sources: We searched PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library from inception through February 17, 2020.

Study Selection: Original articles enrolling IHD patients, comparing all-cause mortality and MACE of NTIS and hypothyroidism with those of euthyroidism, and providing sufficient information for meta-analysis were considered eligible.

Data Extraction: Relevant information and numerical data were extracted for methodological assessment and meta-analysis.

Data Synthesis: Twenty-three studies were included. The IHD population with NTIS was associated with higher risk of all-cause mortality (hazard ratio [HR] = 2.61; 95% confidence interval [CI] = 1.89-3.59) and MACE (HR = 2.22; 95% CI = 1.71-2.89) than that without. In addition, the IHD population with hypothyroidism was also associated with higher risk of all-cause mortality (HR = 1.47; 95% CI = 1.10-1.97) and MACE (HR = 1.53; 95% CI = 1.19-1.97) than that without. In the subgroup analysis, the acute coronary syndrome (ACS) subpopulation with NTIS was associated with higher risk of all-cause mortality (HR = 3.30; 95% CI = 2.43-4.48) and MACE (HR = 2.19; 95% CI = 1.45-3.30). The ACS subpopulation with hypothyroidism was also associated with higher risk of all-cause mortality (HR = 1.67; 95% CI = 1.17-2.39).

Conclusions: The IHD population with concomitant NTIS or hypothyroidism was associated with higher risk of all-cause mortality and MACE. Future research is required to provide evidence of the causal relationship and to elucidate whether normalizing thyroid function parameters can improve prognosis.
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http://dx.doi.org/10.1210/clinem/dgaa310DOI Listing
August 2020

Anti-cancer therapeutic benefit of red guava extracts as a potential therapy in combination with doxorubicin or targeted therapy for triple-negative breast cancer cells.

Int J Med Sci 2020 6;17(8):1015-1022. Epub 2020 Apr 6.

Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan.

Guava extracts purified from leaf and bark have many bio-active molecules with anti-cancer activities. In addition, lycopene-rich extracts obtained from red guava fruit can induce apoptosis in estrogen receptor-positive breast cancers. Triple-negative breast cancer (TNBC) lacks estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2 (HER2) and, therefore, hormone therapy and targeted therapy are not used in the clinic. The purpose of this study was to determine whether red guava fruit extracts can affect the proliferation of TNBC cells. In this study, cell viability was determined by using the MTT assay. Apoptosis and necrosis were analyzed using flow cytometry. Cleaved caspase-3 and PARP were analyzed by western blotting. We found that red guava extracts can, through caspase-3 activation and PARP cleavage signaling, induce apoptotic and necrotic death in TNBC cells. Our results thus show the therapeutic benefit of red guava extracts as a potential cancer treatment for TNBC in combination with doxorubicin or targeted therapy.
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http://dx.doi.org/10.7150/ijms.40131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211147PMC
March 2021

The Effects of Early Bispectral Index to Predict Poor Neurological Function in Cardiac Arrest Patients: A Systematic Review and Meta-Analysis.

Diagnostics (Basel) 2020 Apr 30;10(5). Epub 2020 Apr 30.

Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan.

The diagnostic performance of the bispectral index (BIS) to early predict neurological outcomes in patients achieving return of spontaneous circulation (ROSC) after cardiac arrest (CA) remained unclear. We searched PubMed, EMBASE, Scopus and CENTRAL for relevant studies through October 2019. Methodologic quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Meta-analysis was performed using a linear mixed-effects model to the log-transformed data with a logistic distribution assumption. Bivariate meta-regression was performed to explore heterogeneity. In total, 13 studies with 999 CA adult patients were included. At the optimal threshold of 32, BIS obtained within 72 h of ROSC elicits a pooled sensitivity of 84.9% (95% confidence interval (CI), 71.1% to 92.7%), a pooled specificity of 85.9% (95% CI, 71.2% to 93.8%) and an area under the curve of 0.92. Moreover, a BIS cutoff < 12 yielded a pooled specificity of 95.0% (95% CI, 77.8% to 99.0%). In bivariate meta-regression, the timing of neurological outcome assessment, the adoption of targeted temperature management, and the administration of sedative agents or neuromuscular blocking agents (NMBA) were not identified as the potential source of heterogeneity. BIS retains good diagnostic performance during targeted temperature management (TTM) and in the presence of administrated sedative agents and NMBA. In conclusion, BIS can predict poor neurological outcomes early in patients with ROSC after CA with good diagnostic performance and should be incorporated into the neuroprognostication strategy algorithm.
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http://dx.doi.org/10.3390/diagnostics10050271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277843PMC
April 2020

An Envenoming Syndrome from Massive Stings Induces Multiple Organ Failure.

Insects 2020 Apr 2;11(4). Epub 2020 Apr 2.

Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan.

Envenoming syndrome is a systemic reaction induced by inoculation of large volumes of Hymenoptera venom. The clinical manifestations range from skin allergic reactions to multiple organ failure. Vespid venom-induced toxic reactions and anaphylaxis are the most common lethal mechanism of death, involving acute respiratory failure, acute liver failure, rhabdomyolysis, acute kidney injury, and severe coagulopathy. Multiple organ failure as a consequence of severe venom toxicity is a rare but dangerous complication in victims. Delay of intervention to correct vespid venom-induced toxic reactions may cause catastrophic complications. Here, we describe a case presenting a rare vespid venom-induced multiple organ failure with systemic coagulopathy after massive attack.
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http://dx.doi.org/10.3390/insects11040219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240471PMC
April 2020

Valproic Acid-Induced Hyperammonemic Encephalopathy in a Patient with Bipolar Disorder: A Case Report.

Brain Sci 2020 Mar 24;10(3). Epub 2020 Mar 24.

Department of Psychiatry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.

Valproic acid (VPA) is widely used to control various seizure disorders and psychiatric disorders. Valproic acid-induced hyperammonemic encephalopathy (VHE) is a rare but dangerous complication of VPA-induced toxicity. For this case report, several risk factors were identified, including young age, polytherapy regimens, VPA overdose, poor liver function, and carnitine deficiency. The detailed mechanisms of VHE remained unclear. Hyperammonemia may be caused by hypocarnitinemia, leading to imbalanced VPA metabolism. VHE may initially cause gastrointestinal symptoms, followed by a decreased level of consciousness and seizure. Early diagnosis of VHE is important for physicians for the timely reversal of VHE by discontinuing administration of VPA and administering lactulose or levocarnitine. Here, we describe a patient with a bipolar disorder who presented with VHE after receiving a strict vegetarian diet in our hospital. We recommend that VHE be included in the differential diagnosis of patients with high serum VPA levels and strictly vegetarian diets, especially those presenting with acute gastrointestinal symptoms.
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http://dx.doi.org/10.3390/brainsci10030187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139302PMC
March 2020

Induced Fatal Waterhouse-Friderichsen Syndrome in a Patient Presenting With Disseminated Intravascular Coagulation and Multiple Organ Failure.

Brain Sci 2020 Mar 17;10(3). Epub 2020 Mar 17.

Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.

-induced acute systemic meningococcal disease is an emergency and a fatal condition that has a high mortality rate. In patients with a fulminant infection, a maculopapular petechial eruption, purpura fulminans, or an ecchymotic lesion are worrisome signs reflecting disseminated intravascular coagulation (DIC) and hint at Waterhouse-Friderichsen syndrome (WFS). Here, we describe a rare case of a patient with a fulminant induced acute systemic meningococcal disease presenting with high-grade fever without meningitis symptoms. Fatal septicemia with DIC and multiple organ failure was noted. WFS was chiefly suspected. We highlight the clinical features and pathogenesis of -induced meningococcemia and WFS. We propose that they should be kept in mind, especially in patients presenting with a petechial eruption and purpura fulminans.
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http://dx.doi.org/10.3390/brainsci10030171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139770PMC
March 2020

Improving the High-Frequency Response of PEI-Based Earphone with Sodium Copper Chlorophyllin.

Molecules 2020 Jan 5;25(1). Epub 2020 Jan 5.

Department of Chemistry, Fu-Jen Catholic University, New Taipei City 24205, Taiwan.

The polyetherimide diaphragm, sodium copper chlorophyllin (SCC), and copper ion coating composite used on earphones were observed to improve the high-frequency (10k-14k Hz) performance. This reinforcement phenomenon was expected to make the sound experience brighter and more diverse. By SEM observation, the mixed coating of SCC/Cu on the polyethylenimine (PEI) diaphragm exhibited a planar blocky structure and was tightly bonded to the surface of the PEI polymer without the aid of colloids. The endothermic process of SCC and metal ion complexation was analyzed by isothermal titration calorimetry. The association ratios of SCC/Cu and SCC/Ni were 4/1 and 6/1, respectively, and the SCC/Cu association yielded a stronger binding constant and more free energy. It was expected that the SCC/Cu(4/1) mixed liquid would be immobilized on the PEI polymer by multivalent interaction, including hydrogen-bonding networks between carboxyl groups of SCC and amine groups of PEI, and cross-linking of bridging copper ions. We used dimethylethylenediamine (DME) monomer instead of PEI polymer to analyze this multivalent interaction and observed a two-stage exothermic association of SCC/Cu(4/1) and DME with a total Gibbs free energy of 15.15 kcal/mol. We observed that the binding energy could be used to explain that the SCC/Cu mixed formulation could be fixed on the surface of the PEI polymer and could enhance the strength of the PEI film. Compared with graphene films, which can continuously improve the performance of high and ultrasonic frequencies, this study was devoted to and was initiated for the purpose of applying porphyrin compounds to improve music performance.
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http://dx.doi.org/10.3390/molecules25010219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983146PMC
January 2020

Spontaneous Splenic Rupture as a Rare Initial Presentation in an Acute Lymphoblastic Leukemia Patient.

Diagnostics (Basel) 2019 Oct 18;9(4). Epub 2019 Oct 18.

Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan.

A spontaneous rupture of the spleen is a rare but critical diagnosis of an acute abdomen, which may accompany unspecific symptoms mimicking acute pancreatitis, rupture of aortic aneurism, or acute coronary syndrome, delaying diagnosis and treatment. In patients that have experienced a severe spleen rupture, hypovolemic shock may cause catastrophic clinical outcomes. Therefore, early diagnosis is very important in order for physicians to declare the etiology for prevention and timely correction of the shock status. Several causes of spontaneous splenic rupture have been reported, including infection, vasculitis, pancreatitis, or hematological malignancies. Acute lymphoblastic leukemia (ALL) remains a rare but important cause of non-traumatic splenic rupture that physicians are required to assess for. Here, we describe a case presenting an acute abdomen due to spontaneous spleen rupture as the first manifestation. The purpose of this case report was to highlight the importance of considering spontaneous ruptures of the spleen as a rare but critical differential diagnosis of an acute abdomen, especially in patients with acute lymphoblastic leukemia.
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http://dx.doi.org/10.3390/diagnostics9040152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963524PMC
October 2019

Systematical Analysis of the Protein Targets of Lactoferricin B and Histatin-5 Using Yeast Proteome Microarrays.

Int J Mol Sci 2019 Aug 28;20(17). Epub 2019 Aug 28.

Graduate Institute of Systems Biology and Bioinformatics, National Central University, Jhongli 32001, Taiwan.

Antimicrobial peptides (AMPs) have potential antifungal activities; however, their intracellular protein targets are poorly reported. Proteome microarray is an effective tool with high-throughput and rapid platform that systematically identifies the protein targets. In this study, we have used yeast proteome microarrays for systematical identification of the yeast protein targets of Lactoferricin B (Lfcin B) and Histatin-5. A total of 140 and 137 protein targets were identified from the triplicate yeast proteome microarray assays for Lfcin B and Histatin-5, respectively. The Gene Ontology (GO) enrichment analysis showed that Lfcin B targeted more enrichment categories than Histatin-5 did in all GO biological processes, molecular functions, and cellular components. This might be one of the reasons that Lfcin B has a lower minimum inhibitory concentration (MIC) than Histatin-5. Moreover, pairwise essential proteins that have lethal effects on yeast were analyzed through synthetic lethality. A total of 11 synthetic lethal pairs were identified within the protein targets of Lfcin B. However, only three synthetic lethal pairs were identified within the protein targets of Histatin-5. The higher number of synthetic lethal pairs identified within the protein targets of Lfcin B might also be the reason for Lfcin B to have lower MIC than Histatin-5. Furthermore, two synthetic lethal pairs were identified between the unique protein targets of Lfcin B and Histatin-5. Both the identified synthetic lethal pairs proteins are part of the Spt-Ada-Gcn5 acetyltransferase (SAGA) protein complex that regulates gene expression via histone modification. Identification of synthetic lethal pairs between Lfcin B and Histatin-5 and their involvement in the same protein complex indicated synergistic combination between Lfcin B and Histatin-5. This hypothesis was experimentally confirmed by growth inhibition assay.
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http://dx.doi.org/10.3390/ijms20174218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747642PMC
August 2019

Protein interactome analysis of iduronic acid-containing glycosaminoglycans reveals a novel flagellar invasion factor MbhA.

J Proteomics 2019 09 14;208:103485. Epub 2019 Aug 14.

Department of Biomedical Science and Engineering, National Central University, Jongli District, Taoyuan City, Taiwan; Department of Food Safety/Hygiene and Risk Management, National Cheng Kung University, Tainan, Taiwan. Electronic address:

Pathogens are able to exploit specific glycosaminoglycans (GAGs), especially iduronic acid (IdoA)-containing GAGs, to invade the host. By analyzing Escherichia coli proteome chip data, we identified the interactomes of three IdoA-containing GAGs: heparin, heparin sulfate (HS), and chondroitin sulfate B (CSB). Using non-IdoA-containing GAG, chondroitin sulfate C, as a negative control, 157 proteins specifically binding with IdoA-containing GAGs were revealed in the present study. These proteins showed functional enrichment in protein synthesis and metabolism. Fifteen proteins which commonly interacts with three IdoA-containing GAGs were further examined. The regular expression for motif showed these common IdoA interactome shared a conserved sequence. Among them, we identified a second flagellar system outer membrane protein, MbhA. The MbhA has Kd values of 8.9 × 10 M, 5.3 × 10 M, and 1.79 × 10 M to interact with heparin, HS, and CSB, respectively. Using flow cytometry, we confirmed that the MbhA protein can bind to human epithelial cells HCT-8. Overexpression of mbhA increased the percentage of invasion in E. coli which lacks a second flagellar system. Moreover, pre-blocking of HCT-8 cells with MbhA inhibited the bacterial invasion, implying the importance of the direct interaction of MbhA and the host cell surface on bacterial invasion. SIGNIFICANCE: We analyzed the Escherichia coli proteomic data to elucidate the interactomes of three different IdoA-containing GAGs (heparin, HS, and CSB) because these IdoA-containing GAGs can mediate bacterial invasion to the host. Through proteomic and systematic analysis, a second flagellar system outer membrane protein, MbhA, was also identified in the present study. Affinity assay confirmed that MbhA can bind to three IdoA-containing GAGs heparin, HS, and CSB. The result of flow cytometry also showed MbhA can interact with human epithelial cells HCT-8. Results of bacteria invasion assay showed overexpression of mbhA promoted the bacterial invasion. Moreover, pre-blocking of HCT-8 cells with MbhA also reduced the percentage of bacterial invasion. These findings correspond well that MbhA is one of invasion factors.
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http://dx.doi.org/10.1016/j.jprot.2019.103485DOI Listing
September 2019

Protein Microarrays and Liposome: A Method for Studying Lipid-Protein Interactions.

Methods Mol Biol 2019 ;2003:191-199

Department of Pharmacology and Molecular Sciences/High-Throughput Biology Center, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

Interactions between specific lipids and proteins can provide important information regarding the functions of proteins and lipids. One of the novel and powerful methods to identify lipid-protein interactions is using protein microarrays and liposomes. Liposomes are spherical vesicles that are surrounded by phospholipid bilayers in which the lipid of interest can be incorporated. Thus, liposomes can be used to detect lipid-protein interactions and to analyze interactions between thousands of proteins and a small number of lipids with a single experiment. This chapter presents the methods and procedures for using protein microarray assays and liposome fabrication to analyze protein-lipid interactions. Up-to-date research reports are also reviewed briefly.
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http://dx.doi.org/10.1007/978-1-4939-9512-7_10DOI Listing
March 2020

Advanced Evolution of Pathogenesis Concepts in Cardiomyopathies.

J Clin Med 2019 Apr 16;8(4). Epub 2019 Apr 16.

Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan.

Cardiomyopathy is a group of heterogeneous cardiac diseases that impair systolic and diastolic function, and can induce chronic heart failure and sudden cardiac death. Cardiomyopathy is prevalent in the general population, with high morbidity and mortality rates, and contributes to nearly 20% of sudden cardiac deaths in younger individuals. Genetic mutations associated with cardiomyopathy play a key role in disease formation, especially the mutation of sarcomere encoding genes and ATP kinase genes, such as titin, lamin A/C, myosin heavy chain 7, and troponin T1. Pathogenesis of cardiomyopathy occurs by multiple complex steps involving several pathways, including the Ras-Raf-mitogen-activated protein kinase-extracellular signal-activated kinase pathway, G-protein signaling, mechanotransduction pathway, and protein kinase B/phosphoinositide 3-kinase signaling. Excess biomechanical stress induces apoptosis signaling in cardiomyocytes, leading to cell loss, which can induce myocardial fibrosis and remodeling. The clinical features and pathophysiology of cardiomyopathy are discussed. Although several basic and clinical studies have investigated the mechanism of cardiomyopathy, the detailed pathophysiology remains unclear. This review summarizes current concepts and focuses on the molecular mechanisms of cardiomyopathy, especially in the signaling from mutation to clinical phenotype, with the aim of informing the development of therapeutic interventions.
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http://dx.doi.org/10.3390/jcm8040520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518034PMC
April 2019

Nitride-Based Microarray Biochips: A New Route of Plasmonic Imaging.

ACS Appl Mater Interfaces 2018 Nov 12;10(46):39898-39903. Epub 2018 Nov 12.

Department of Food Safety/Hygiene and Risk Management, College of Medicine , National Cheng Kung University , Tainan 701 , Taiwan.

The desire to improve human lives has led to striking development in biosensing technologies. While the ongoing research efforts are mostly dedicated to enhancing speed and sensitivity of the sensor, a third consideration that has become increasingly important is compactness, which is strongly desired in emergency situations and personal health management. Surface plasmon resonance imaging (SPRi) is one of the few techniques that can potentially fulfill all the three goals, considering its multiplexed assay capability. However, miniaturizing SPRi biosensors remains elusive as it entails complicated optical gears. Here, we significantly slim the architecture of SPRi devices by visualizing the varied local density of states around analytes. The unusual detection scheme is realized by building a gain-assisted SPRi with InGaN quantum wells (QWs), where the QW-plasmon coupling efficiency hinges on localized refractive index variation. This new modality abolishes the prism, the polarizer, and the beam-tracking components in the most used Kretschmann configuration without compromising the performances.
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http://dx.doi.org/10.1021/acsami.8b14962DOI Listing
November 2018

The Emerging Role of Pathogenesis of IgA Nephropathy.

J Clin Med 2018 Aug 20;7(8). Epub 2018 Aug 20.

Research Assistant Center, Show Chwan Memorial Hospital, Changhua 500, Taiwan.

IgA nephropathy is an autoimmune disease induced by fthe ormation of galactose-deficient IgA1 and anti-glycans autoantibody. A multi-hit hypothesis was promoted to explain full expression of IgA nephropathy. The deposition of immune complex resulted in activation of the complement, increasing oxidative stress, promoting inflammatory cascade, and inducing cell apoptosis via mesangio-podocytic-tubular crosstalk. The interlinked signaling pathways of immune-complex-mediated inflammation can offer a novel target for therapeutic approaches. Treatments of IgA nephropathy are also summarized in our review article. In this article, we provide an overview of the recent basic and clinical studies in cell molecular regulation of IgAN for further treatment interventions.
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http://dx.doi.org/10.3390/jcm7080225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112037PMC
August 2018

High-Throughput Chip Assay for Investigating Escherichia coli Interaction with the Blood-Brain Barrier Using Microbial and Human Proteome Microarrays (Dual-Microarray Technology).

Anal Chem 2018 09 24;90(18):10958-10966. Epub 2018 Aug 24.

Department of Pharmacology and Molecular Sciences, School of Medicine , Johns Hopkins University , Baltimore , Maryland 21205 , United States.

Bacterial meningitis in neonates and infants is an acute lethal disease and occurs in response to microbial exploitation of the blood-brain barrier (BBB), resulting in the intracranial inflammation. Several pathogens, such as Escherichia coli ( E. coli), can cause this devastating disease; however, the underlying molecular mechanisms by which these pathogens exploit the BBB remain incompletely understood. To identify important players on both the pathogen and host sides that govern the E. coli-BBB cell interactions, we took advantage of the E. coli and human proteome microarrays (i.e., HuProt) as an unbiased, proteome-wide tool for identification of important players on both sides. Using the E. coli proteome microarrays, we developed a unique high throughput chip-based cell probing assay to probe with fluorescent live human brain microvascular endothelial cells (HBMEC, which constitute the BBB). We identified several transmembrane proteins, which effectively bound to live HBMEC. We focused on YojI protein for further study. By probing the HuProt arrays with YojI, interferon-alpha receptor (IFNAR2) was identified as one of its binding proteins. The importance of YojI and IFNAR2 involved in E. coli-HBMEC interactions was characterized using the YojI knockout bacteria and IFNAR2-knock down HBMEC and further confirmed by E. coli binding assay in HBMEC. This study represents a new paradigm (dual-microarray technology) that enables rapid, unbiased discovery of both pathogen and host players that are involved in pathogen-host interactions for human infectious diseases in a high throughput manner.
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http://dx.doi.org/10.1021/acs.analchem.8b02513DOI Listing
September 2018

New Insights into the Immune Molecular Regulation of the Pathogenesis of Acute Respiratory Distress Syndrome.

Int J Mol Sci 2018 Feb 16;19(2). Epub 2018 Feb 16.

Research Assistant Center, Show Chwan Memorial Hospital, Changhua 500, Taiwan.

Acute respiratory distress syndrome is an inflammatory disease characterized by dysfunction of pulmonary epithelial and capillary endothelial cells, infiltration of alveolar macrophages and neutrophils, cell apoptosis, necroptosis, NETosis, and fibrosis. Inflammatory responses have key effects on every phase of acute respiratory distress syndrome. The severe inflammatory cascades impaired the regulation of vascular endothelial barrier and vascular permeability. Therefore, understanding the relationship between the molecular regulation of immune cells and the pulmonary microenvironment is critical for disease management. This article reviews the current clinical and basic research on the pathogenesis of acute respiratory distress syndrome, including information on the microenvironment, vascular endothelial barrier and immune mechanisms, to offer a strong foundation for developing therapeutic interventions.
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http://dx.doi.org/10.3390/ijms19020588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855810PMC
February 2018

Antigen Analysis of Pre-Eclamptic Plasma Antibodies Using Proteome Chips.

Mol Cell Proteomics 2018 08 28;17(8):1457-1469. Epub 2017 Dec 28.

§Graduate Institute of Systems Biology and Bioinformatics, National Central University, Jhongli 32001, Taiwan;

Pre-eclampsia is one of the main causes of perinatal mortality and morbidity. Many biomarkers for diagnosing pre-eclampsia have been found but most have low accuracy. Therefore, a potential marker that can detect pre-eclampsia with high accuracy is required. Infection has been reported as a cause of pre-eclampsia. In recent years, protein microarray chips have been recognized as a strong and robust tool for profiling antibodies for infection diagnoses. The purpose of the present study was to profile antibodies in the human plasma of healthy and pre-eclamptic pregnancies to identify suitable biomarkers. In this study, an chip was probed with samples from 29 individuals (16 pre-eclamptic women and 13 healthy pregnant women) to profile plasma antibodies. Bioinformatics tools were used to analyze the results, discover conserved motifs, compare against the entire human proteome, and perform protein functional analysis. An antibody classifier was identified using -top scoring pairs and additional samples for a blinded test were collected. The findings indicated that compared with the healthy women, the pre-eclamptic women exhibited 108 and 130 differentially immunogenic proteins against human immunoglobulins G and M, respectively. In addition, pre-eclamptic women developed more immunoglobulin G but less immunoglobulin M against bacterial surface proteins compared with healthy women. The k-top scoring pairs identified five pairs of immunogenic proteins as classifiers with a high accuracy of 90% in the blind test. [AG] [ISV] GV [AE] L [LF] and [IV] [IV] RI [AG] [AD] E were the consensus motifs observed in immunogenic proteins in the immunoglobulin G and immunoglobulin M of pre-eclamptic women, respectively, whereas GA [AG] [AL] L [LF] and [SRY] [IQML] [ILV] [ILV] [ACG] GI [GH] [AEF] [AK] [ATY] [RG] N [IV] were observed in the immunoglobulins G and immunoglobulin M of healthy women, respectively.
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http://dx.doi.org/10.1074/mcp.RA117.000139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072543PMC
August 2018

Antibody Profiling of Kawasaki Disease Using Proteome Microarrays.

Mol Cell Proteomics 2018 03 15;17(3):472-481. Epub 2017 Dec 15.

§Graduate Institute of Systems Biology and Bioinformatics, National Central University, Taoyuan, Taiwan 32001;

Kawasaki disease (KD) is a form of systemic vasculitis that generally occurs in children under 5 years old. Currently, KD is still diagnosed according to its clinical symptoms, including prolonged fever, skin rash, conjunctivitis, neck lymphadenopathy, palm erythema, and oral mucosa changes. Because KD is a type of inflammation without specific marker for diagnosis, we plan to profile the plasma antibodies by using proteome microarray and analyze the differences between KD and healthy subjects. Plasmas were collected from KD patient before intravenous immunoglobulin treatment (KD1), at least 3 weeks after treatment (KD3), nonfever control (NC), and fever control (FC) children. The initial screening, which consisted of 20 KD1, 20 KD3, 20 NC, and 20 FC, were explored using proteome microarrays (∼4200 unique proteins). About ∼70 proteins were shown to have high accuracy, 0.78∼0.92, with regard to separating KD1, KD3, NC, and FC. Those proteins were then purified to fabricate KD focus arrays for training ( = 20 each) and blind-testing ( = 20 each). It only took 125 pl of plasma, less than a drop of blood, in the focus array assays. The AUC scores for blind tests of KD1 NC (17 protein markers), KD1 FC (20 protein markers), KD3 NC (9 protein markers), and KD1 KD3 (6 protein markers) were 0.84, 0.75, 0.99 and 0.98, respectively. This study is the first to profile plasma antibodies in KD and demonstrate that an proteome microarray can screen differences among patients with KD, nonfever controls, and fever controls.
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http://dx.doi.org/10.1074/mcp.RA117.000198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836372PMC
March 2018

Intestinal fungi contribute to development of alcoholic liver disease.

J Clin Invest 2017 Jun 22;127(7):2829-2841. Epub 2017 May 22.

Department of Medicine, UCSD, La Jolla, California, USA.

Chronic liver disease with cirrhosis is the 12th leading cause of death in the United States, and alcoholic liver disease accounts for approximately half of all cirrhosis deaths. Chronic alcohol consumption is associated with intestinal bacterial dysbiosis, yet we understand little about the contribution of intestinal fungi, or mycobiota, to alcoholic liver disease. Here we have demonstrated that chronic alcohol administration increases mycobiota populations and translocation of fungal β-glucan into systemic circulation in mice. Treating mice with antifungal agents reduced intestinal fungal overgrowth, decreased β-glucan translocation, and ameliorated ethanol-induced liver disease. Using bone marrow chimeric mice, we found that β-glucan induces liver inflammation via the C-type lectin-like receptor CLEC7A on Kupffer cells and possibly other bone marrow-derived cells. Subsequent increases in IL-1β expression and secretion contributed to hepatocyte damage and promoted development of ethanol-induced liver disease. We observed that alcohol-dependent patients displayed reduced intestinal fungal diversity and Candida overgrowth. Compared with healthy individuals and patients with non-alcohol-related cirrhosis, alcoholic cirrhosis patients had increased systemic exposure and immune response to mycobiota. Moreover, the levels of extraintestinal exposure and immune response correlated with mortality. Thus, chronic alcohol consumption is associated with an altered mycobiota and translocation of fungal products. Manipulating the intestinal mycobiome might be an effective strategy for attenuating alcohol-related liver disease.
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http://dx.doi.org/10.1172/JCI90562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490775PMC
June 2017

High-Throughput Screening of Sulfated Proteins by Using a Genome-Wide Proteome Microarray and Protein Tyrosine Sulfation System.

Anal Chem 2017 03 2;89(6):3278-3284. Epub 2017 Mar 2.

Department of Biological Science and Technology, National Chiao Tung University , 75 Boai Street, Hsinchu 300, Taiwan.

Protein tyrosine sulfation (PTS) is a widespread posttranslational modification that induces intercellular and extracellular responses by regulating protein-protein interactions and enzymatic activity. Although PTS affects numerous physiological and pathological processes, only a small fraction of the total predicted sulfated proteins has been identified to date. Here, we localized the potential sulfation sites of Escherichia coli proteins on a proteome microarray by using a 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase-coupled tyrosylprotein sulfotransferase (TPST) catalysis system that involves in situ PAPS generation and TPST catalysis. Among the 4256 E. coli K12 proteins, 875 sulfated proteins were identified using antisulfotyrosine primary and Cy3-labeled antimouse secondary antibodies. Our findings add considerably to the list of potential proteins subjected to tyrosine sulfation. Similar procedures can be applied to identify sulfated proteins in yeast and human proteome microarrays, and we expect such approaches to contribute substantially to the understanding of important human diseases.
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http://dx.doi.org/10.1021/acs.analchem.6b02853DOI Listing
March 2017