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Wei-Yi Lei,Tso-Tsai Liu,Wei-Chuan Chang,Chih-Hsun Yi,Jui-Sheng Hung,Ming-Wun Wong,Shu-Wei Liang,Lin Lin,Chien-Lin Chen 대한소화기 기능성질환∙운동학회 2024 Journal of Neurogastroenterology and Motility (JNM Vol.30 No.1
Background/AimsThis study aims to evaluate the effects of acute codeine administration on primary and secondary esophageal peristalsis in patients with ineffective esophageal motility (IEM). MethodsEighteen IEM patients (8 women; mean age 37.8 years, range 23-64 years) were enrolled in the study. The patients underwent high-resolution manometry exams, consisting of 10 single wet swallows, multiple rapid swallows, and ten 20 mL rapid air injections to trigger secondary peristalsis. All participants completed 2 separate sessions, including acute administration of codeine (60 mg) and placebo, in a randomized order. ResultsCodeine significantly increased the distal contractile integral (566 ± 81 mmHg∙s∙cm vs 247 ± 36 mmHg∙s∙cm, P = 0.001) and shortened distal latency (5.7 ± 0.2 seconds vs 6.5 ± 0.1 seconds, P < 0.001) for primary peristalsis compared with these parameters after placebo treatment. The mean total break length decreased significantly after codeine treatment compared with the length after placebo (P = 0.003). Codeine significantly increased esophagogastric junction-contractile integral (P = 0.028) but did not change the 4-second integrated relaxation pressure (P = 0.794). Codeine significantly decreased the frequency of weak (P = 0.039) and failed contractions (P = 0.009), resulting in increased frequency of normal primary peristalsis (P < 0.136). No significant differences in the ratio of impaired multiple rapid swallows inhibition and parameters of secondary peristalsis were detected. ConclusionsIn IEM patients, acute administration of codeine increases contraction vigor and reduces distal latency of primary esophageal peristalsis, but has no effect on secondary peristalsis. Future studies are required to further elucidate clinical relevance of these findings, especially in the setting of gastroesophageal reflux disease with IEM.
Wei-Che Hsieh,Yu-Nong Lin,Ting-Chien Lin,Chun-Hung Hans Lin 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1
Fucosyltransferases (FucTs) usually catalyze the final step of glycosylation and are critical to many biological processes. High levels of specific FucT activities are often associated with various cancers. Here we report the development of a chemoenzymatic method for synthesizing a library of GDP-L-fucose derivatives, followed by in situ screening for inhibitory activity against bacterial and human -1,3-FucTs (4). Several compounds incorporating appropriate hydrophobic moieties were identified from the initial screening. These were individually synthesized, purified and characterized in detail for their inhibition kinetics. Compound 5 had a Ki of 29 nM for human FucT-VI, and is 269 and 11 times more selective than for Helicobacter pylori FucT (Ki = 7.8 □ M) and for human FucT-V (Ki = 0.31 □ M).
Wei-Yi Lei,Shu-Wei Liang,Taher Omari,Wei-Chuan Chang,Ming-Wun Wong,Jui-Sheng Hung,Chih-Hsun Yi,Tso-Tsai Liu,Lin Lin,C Prakash Gyawali,Chien-Lin Chen 대한소화기 기능성질환∙운동학회 2022 Journal of Neurogastroenterology and Motility (JNM Vol.28 No.4
Background/Aims Straight leg raise (SLR) can be utilized to evaluate the integrity of the esophagogastric junction during high-resolution manometry (HRM). We aim to assess the value of transient hiatal separation during SLR in symptomatic reflux patients. Methods Consecutive reflux patients undergoing esophageal HRM and pH monitoring were included. Transient hiatal separation was defined by a ≥ 1 cm separation between the lower esophageal sphincter and crural diaphragm during SLR. We compared esophageal motor patterns and reflux monitoring parameters between patients with normal, transiently abnormal and consistently abnormal esophagogastric junction morphology during SLR. Results Of 85 (56.3% female, mean age: 46.7 ± 12.3 years) completed SLR, esophagogastric junction morphology was normal in 31 (36.5%), transient hiatal separation in 19 (22.3%), and consistently hiatal hernia in 35 (41.2%). The values of total acid exposure time (P = 0.016), longest acid reflux episodes (P = 0.024), and DeMeester scores (P = 0.016) were higher in hiatal hernia compared to patients with non-transient hiatal separation, but there were no differences between those with and without transient hiatal separation. Within ineffective esophageal motility, the presence of transient hiatal separation during SLR significantly associated with a higher total acid exposure time (P = 0.014), higher DeMeester scores (P = 0.019), higher total acid reflux events (P = 0.037), and higher longest acid reflux episodes (P = 0.006). Conclusion Our work suggests that SLR may have value as a provocative test during HRM, and future outcome studies are warranted to elucidate the clinical relevance of motor abnormalities depicted from SLR.
( Ching-ling Lin ),( Ming-lin Tsai ),( Yu-hsin Chen ),( Wei-ni Liu ),( Chun-yu Lin ),( Kai-wen Hsu ),( Chien-yu Huang ),( Yu-jia Chang ),( Po-li Wei ),( Shu-huey Chen ),( Li-chi Huang ),( Chia-hwa Lee 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.5
Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.
( Chien Hui Wu ),( Wei Chen Chien ),( Han Kai Chou ),( Jung Woo Yang ),( Hong Ting Victor Lin ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.9
One-step sulfuric acid saccharification of the red alga Pterocladiella capillacea was optimized, and various detoxification methods (neutralization, overliming, and electrodialysis) of the acid hydrolysate were evaluated for fermentation with the thermotolerant yeast Kluyveromyces marxianus. A proximate composition analysis indicated that P. capillacea was rich in carbohydrates. A significant galactose recovery of 81.1 ± 5% was also achieved under the conditions of a 12% (w/v) biomass load, 5% (v/v) sulfuric acid, 121°C, and hydrolysis for 30 min. Among the various detoxification methods, electrodialysis was identified as the most suitable for fermentable sugar recovery and organic acid removal (100% reduction of formic and levulinic acids), even though it failed to reduce the amount of the inhibitor 5-HMF. As a result, K. marxianus fermentation with the electrodialyzed acid hydrolysate of P. capillacea resulted in the best ethanol levels and fermentation efficiency.
( Wei-yi Lei ),( Taher Omari ),( Tso-tsai Liu ),( Ming-wun Wong ),( Jui-sheng Hung ),( Chih-hsun Yi ),( Shu-wei Liang ),( Charles Cock ),( Chien-lin Chen ) 대한소화기기능성질환·운동학회 2022 Journal of Neurogastroenterology and Motility (JNM Vol.28 No.1
Background/Aims Intrabolus pressures are important for esophageal bolus transport and may detect obstructed bolus flow. This study measured the effect esophageal outflow obstruction experimentally induce by a leg-lift protocol. Methods Twenty-five gastroesophageal reflux disease patients referred for esophageal manometry and a normal motility diagnosis were included. Supine liquid swallows were tested. Leg-lift protocol generated esophageal outflow obstruction by increasing abdominal pressure. Esophageal pressure topography and intrabolus pressure metrics were calculated. These included, (1) mid-domain bolus distension pressure during esophageal emptying (DPE, mmHg) and (2) ramp pressure (mmHg/sec), generated by compression of the bolus between the peristaltic contraction and esophagogastric junction (EGJ). Results EGJ relaxation pressure was increased by leg-lift from 13 (11-17) to 19 (14-30) mmHg (P < 0.005) and distal contractile integral also increased from 1077 (883-1349) to 1620 (1268-2072) mmHgㆍcmㆍsec (P < 0.001) as a physiological response to obstruction. All bolus pressures were increased by leg lift; DPE increased from 17 (15-20) to 27 (19-32) mmHg (P < 0.001), and ramp pressure increased from 3 (1-4) to 5 (2-9) mmHg/sec (P < 0.05). Conclusion Measuring pressures within the intrabolus domain can quantify changes related to obstruction to outflow and may serve as adjunct measures for confirming a diagnosis EGJ outflow obstruction. (J Neurogastroenterol Motil 2022;28:62-68)
Sequencial Enzymatic Synthesis of Sugar nucleotides and Poly-LacNAc
Wei-Ting Chien,Ching-Ching Yu,Chun-Cheng Lin 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1
Poly-N-acetyllactosamine (poly-LacNAc, (3Gal1-4GlcNAc1-)n) is a linear carbohydrate polymer composed by repeatingN-acetylglucosamine (GlcNAc) and galactose (Gal) residues. These polysaccharides are found either on N- / O-linked glycoproteins or glycolipids and involve in diverse cellular functions such as differentiation, apoptosis, and metastasis. Poly-LacNAc can be further modified by various glycosyltransferases to create branched structures and display terminal epitopes. Sialylated and fucosylated derivatives of poly-LacNAc have been characterized as specific ligands for different lectins such as selectins and galectins as well as being tumor-associated antigens.It is demanded to have various lengths of oligo-LacNAc for studying LacNAc associated biology. However, the traditional organic synthesis requires tedious multiple protection and de-protection steps which are heavily relied on labor-intensive and time-consuming synthetic routes. To efficiently and quickly produce oligo-LacNAc, we expressed the recombinant bacterial enzymes, □ - 1,3-N-acetyl-glucosaminyltransferase of Helicobacter pylori (HpGnT) and □ -1,4-galactosyltransferase of Neisseria meningitides (NmGalT), from E. coli. Defined lengths of oligo-LacNAcs were synthesized by using the expressed enzymes in the presence of sugar donors, uridine 5’-diphosphate galactose (UDP- Gal) and uridine 5’-diphosphate N-acetylglucosamine (UDP-GlcNAc). To reduce the cost of NDP-sugars used in the oligo-LacNAc synthesis, we set up an enzymatic system for one-pot synthesis of NDP- sugars by using a wild-type bacterial thymidylyltransferase (RmlA). In this study, we applied RmlA to synthesize both UDP-Gal and UDP-GlcNAc. In combination with the use of corresponding kinases, UDP- GlcNAc and UDP-Gal were obtained from cheap starting materials, GlcNAc and Gal. Take the advantage of the great thermal stability of RmlA, the sugar nucleotides were prepared with quantitative yield at 55 oC within two hours. By the alternative addition of HpGnT and NmGalT, different lengths of oligo-LacNAc were synthesized. Compare to previous report, we successfully achieve the synthesis of oligo-LacNAc with a more economical way.
( Chien Hui Wu ),( Wei Chen Chien ),( Kai Chou Han ),( Jung Woo Yang ),( Hong Ting Victor Lin ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.9
Screening of a gene library from Paenibacillus sp. PBS-2 generated in Escherichia coli led to the identification of a clone with lipolytic activity. Sequence analysis showed an open reading frame encoding a polypeptide of 378 amino acid residues with a predicted molecular mass of 42 kDa. The esterase displayed 69% and 42% identity with the putative β-lactamases from Paenibacillus sp. JDR-2 and Clostridium sp. BNL1100, respectively. The esterase contained a Serx- x-Lys motif that is conserved among all β-lactamases found to date. The protein PBS-2 was produced in both soluble and insoluble forms when E. coli cells harboring the gene were cultured at 18°C. The enzyme is a serine protein and was active against p-nitrophenyl esters of C2, C4, C8, and C10. The optimum pH and temperature for enzyme activity were pH 9.0 and 30°C, respectively. Relative activity of 55% remained at up to 5°C with an activation energy of 5.84 kcal/mol, which indicates that the enzyme is cold-adapted. Enzyme activity was inhibited by Cd2+, Cu2+, and Hg2+ ions. As expected for a serine esterase, activity was inhibited by phenylmethylsulfonyl fluoride. The enzyme was remarkably active and stable in the presence of commercial detergents and organic solvents. This cold-adapted esterase has potential as a biocatalyst and detergent additive for use at low temperatures.