82 results on '"Ching-Chih Lin"'
Search Results
2. Regorafenib for Taiwanese patients with unresectable hepatocellular carcinoma after sorafenib failure: Impact of alpha‐fetoprotein levels
- Author
-
Po‐Yao Hsu, Tzu‐Sheng Cheng, Shih‐Chang Chuang, Wen‐Tsan Chang, Po‐Cheng Liang, Cheng‐Ting Hsu, Yu‐Ju Wei, Tyng‐Yuan Jang, Ming‐Lun Yeh, Ching‐I Huang, Yi‐Hung Lin, Chih‐Wen Wang, Ming‐Yen Hsieh, Nai‐Jen Hou, Meng‐Hsuan Hsieh, Yi‐Shan Tsai, Yu‐Min Ko, Ching‐Chih Lin, Kuan‐Yu Chen, Chia‐Yen Dai, Zu‐Yau Lin, Shinn‐Cherng Chen, Jee‐Fu Huang, Wan‐Long Chuang, Chung‐Feng Huang, and Ming‐Lung Yu
- Subjects
efficacy ,hepatocellular carcinoma ,regorafenib ,sorafenib ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background and Aims Regorafenib has demonstrated its survival benefit for unresectable hepatocellular carcinoma (uHCC) patients in a phase III clinical trial. We aimed to assess the efficacy and tolerability of regorafenib and the predictors of treatment outcomes in Taiwanese patients. Methods We analyzed the survival, best overall response, predictors of treatment outcomes, and safety for uHCC patients who had tumor progression on sorafenib therapy and received regorafenib as salvage therapy between March 2018 and November 2020. Results Eighty‐six patients with uHCC were enrolled (median age, 66.5 years; 76.7% male). The median regorafenib treatment duration was 4.0 months (95% confidence interval [CI], 3.6–4.6). The most frequently reported adverse events were hand‐foot skin reaction (44.2%), diarrhea (36.0%), and fatigue (29.1%). No unpredictable toxicity was observed during treatment. The median overall survival (OS) with regorafenib was 12.4 months (95% CI, 7.8–17.0) and the median progression‐free survival (PFS) was 4.2 months (95% CI, 3.7–4.7). Of 82 patients with regorafenib responses assessable, 4 patients (4.9%) achieved a partial response, and 33 (40.2%) had stable disease, leading to a disease control rate (DCR) of 45.1% (n = 37). Patients possessing baseline AFP 10% reduction at 4 weeks or >20% reduction at 8 weeks after regorafenib administration) exhibited comparable treatment outcomes to those with baseline AFP
- Published
- 2022
- Full Text
- View/download PDF
3. Metabolomic Analysis Demonstrates the Impacts of Polyketide Synthases PKS14 and PKS15 on the Production of Beauvericins, Bassianolide, Enniatin A, and Ferricrocin in Entomopathogen Beauveria bassiana
- Author
-
Wachiraporn Toopaang, Kullyanee Panyawicha, Chettida Srisuksam, Wei-Chen Hsu, Ching-Chih Lin, Morakot Tanticharoen, Yu-Liang Yang, and Alongkorn Amnuaykanjanasin
- Subjects
Beauveria bassiana ,polyketide synthase ,nonribosomal peptides ,GNPS ,molecular networking ,Microbiology ,QR1-502 - Abstract
Beauveria bassiana is a globally distributed entomopathogenic fungus that produces various secondary metabolites to support its pathogenesis in insects. Two polyketide synthase genes, pks14 and pks15, are highly conserved in entomopathogenic fungi and are important for insect virulence. However, understanding of their mechanisms in insect pathogenicity is still limited. Here, we overexpressed these two genes in B. bassiana and compared the metabolite profiles of pks14 and pks15 overexpression strains to those of their respective knockout strains in culture and in vivo using tandem liquid chromatography-mass spectrometry (LC-MS/MS) with Global Natural Products Social Molecular Networking (GNPS). The pks14 and pks15 clusters exhibited crosstalk with biosynthetic clusters encoding insect-virulent metabolites, including beauvericins, bassianolide, enniatin A, and the intracellular siderophore ferricrocin under certain conditions. These secondary metabolites were upregulated in the pks14-overexpressing strain in culture and the pks15-overexpressing strain in vivo. These data suggest that pks14 and pks15, their proteins or their cluster components might be directly or indirectly associated with key pathways in insect pathogenesis of B. bassiana, particularly those related to secondary metabolism. Information about interactions between the polyketide clusters and other biosynthetic clusters improves scientific understanding about crosstalk among biosynthetic pathways and mechanisms of pathogenesis.
- Published
- 2023
- Full Text
- View/download PDF
4. Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognos- tic factor in hepatitis C virus-related hepatocellular carcinoma
- Author
-
Ching-Chih Lin, Ta-Wei Liu, Ming-Lun Yeh, Yi-Shan Tsai, Pei-Chien Tsai, Chung-Feng Huang, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, and Ming-Lung Yu
- Subjects
receptors, somatotropin ,carcinoma, hepatocellular ,hepacivirus ,recurrence ,prognosis ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background/Aims Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC. Methods The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed. Results GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II–IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C. Conclusions Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC.
- Published
- 2021
- Full Text
- View/download PDF
5. Changing epidemiology and viral interplay of hepatitis B, C and D among injecting drug user-dominant prisoners in Taiwan
- Author
-
Ming-Ying Lu, Chun-Ting Chen, Yu-Lueng Shih, Pei-Chien Tsai, Meng-Hsuan Hsieh, Chung-Feng Huang, Ming-Lun Yeh, Ching-I Huang, Shu-Chi Wang, Yi-Shan Tsai, Yu-Min Ko, Ching-Chih Lin, Kuan-Yu Chen, Yu-Ju Wei, Po-Yao Hsu, Cheng-Ting Hsu, Tyng-Yuan Jang, Ta-Wei Liu, Po-Cheng Liang, Ming-Yen Hsieh, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chuang, Ming-Lung Yu, and Wen-Yu Chang
- Subjects
Medicine ,Science - Abstract
Abstract The spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10–0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13–0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04–40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.
- Published
- 2021
- Full Text
- View/download PDF
6. Role of hepatitis D virus infection in development of hepatocellular carcinoma among chronic hepatitis B patients treated with nucleotide/nucleoside analogues
- Author
-
Tyng-Yuan Jang, Yu-Ju Wei, Ta-Wei Liu, Ming-Lun Yeh, Shu-Fen Liu, Cheng-Ting Hsu, Po-Yao Hsu, Yi-Hung Lin, Po-Cheng Liang, Meng-Hsuan Hsieh, Yu-Min Ko, Yi-Shan Tsai, Kuan-Yu Chen, Ching-Chih Lin, Pei-Chien Tsai, Shu-Chi Wang, Ching-I. Huang, Zu-Yau Lin, Shinn-Cherng Chen, Wan-Long Chuang, Jee-Fu Huang, Chia-Yen Dai, Chung-Feng Huang, and Ming-Lung Yu
- Subjects
Medicine ,Science - Abstract
Abstract Hepatitis D virus (HDV) infection increases the risk of hepatocellular carcinoma (HCC) in the natural course of chronic hepatitis B (CHB) patients. Its role in patients treated with nucleotide/nucleoside analogues (NAs) is unclear. We aimed to study the role of hepatitis D in the development of HCC in CHB patients treated with NAs. Altogether, 1349 CHB patients treated with NAs were tested for anti-HDV antibody and RNA. The incidence and risk factors of HCC development were analyzed. Rates of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. The annual incidence of HCC was 1.4 per 100 person-years after a follow-up period of over 5409.5 person-years. The strongest factor association with HCC development was liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI] 9.98/5.11–19.46, P 50 years old (HR/CI 3.64/2.03–6.54, P
- Published
- 2021
- Full Text
- View/download PDF
7. Role of hepatitis D virus in persistent alanine aminotransferase abnormality among chronic hepatitis B patients treated with nucleotide/nucleoside analogues
- Author
-
Tyng-Yuan Jang, Yu-Ju Wei, Ming-Lun Yeh, Shu-Fen Liu, Cheng-Ting Hsu, Po-Yao Hsu, Ta-Wei Liu, Yi-Hung Lin, Po-Cheng Liang, Meng-Hsuan Hsieh, Yu-Min Ko, Yi-Shan Tsai, Kuan-Yu Chen, Ching-Chih Lin, Pei-Chien Tsai, Shu-Chi Wang, Ching-I. Huang, Zu-Yau Lin, Shinn-Cherng Chen, Wan-Long Chuang, Jee-Fu Huang, Chia-Yen Dai, Chung-Feng Huang, and Ming-Lung Yu
- Subjects
ALT normalization ,HDV ,NAs ,HBV ,Medicine (General) ,R5-920 - Abstract
Background: The biochemical response is a crucial indicator of prognosis in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues (NAs). The impact of hepatitis D virus (HDV) infection on alanine aminotransferase normalization is elusive. Methods: The longitudinal study recruited 1185 CHB patients who received NAs. These patients were tested for anti-HDV antibody and HDV RNA at the initiation of anti-hepatitis B virus (HBV) therapy and annually for patients who were HDV-seropositive. ALT levels were examined at the first and second year of anti-HBV therapy. ALT abnormality was defined as ALT levels above 40 IU/mL in both male and female, and the risk factors associated with ALT abnormality were analysed. Results: Rates of seropositivity for anti-HDV and HDV RNA were 2.0% and 0.8% among 1185 NA-treated CHB patients, respectively. The strongest factor associated with ALT abnormality (>40 IU/mL) after first year treatment with NAs was HDV RNA seropositivity at year 1 (odds ratio [OR]/95% confidence interval [CI]: 31.44/3.49–283.56, P = 0.002), followed by liver cirrhosis (2.18/1.51–3.15, P
- Published
- 2021
- Full Text
- View/download PDF
8. Text-Mining and Digital Humanities Analysis of 'Eye-Opening' Consecration Ritual of Contemporary Yanling Daoist Altar of Tainan
- Author
-
Ching-Chih Lin
- Subjects
digital humanities ,text-mining ,information visualization ,gis (geographic information system) ,social network analysis ,Bibliography. Library science. Information resources - Abstract
This article uses Digital Humanities methods and technologies, Text mining and GIS (geographic information system) to explore the ritual texts of the Deity “Eye-Opening” Consecration Ritual of Daoist Wu Zhengxian at the Yanling Daoist Altar in Tainan. The author uses the Python data extraction technology to extract the information of deities, temples, and believers contained in the consecration ritual texts, and then uses GIS time-space analysis and social network analysis to examine the rituals of the Yanling Daoist altar. The article demonstrates the visualization of the spatial distribution of the consecration rituals of the Yanling Daoist Altar. In addition, it also illustrates the network relationship between the deities and the ritual locations, mostly temples. This article aims to show how the use of digital humanities technologies and tools can assist humanities research. The proper use of information technology can quickly and massively process patterned documents (such as Daoist ritual texts), extract key data content, and then use GIS spatial and network analysis to explore the spatial significance and network relationship behind the ritual texts. The author tries to make use of the “distant reading” of digital humanities and proposes new research questions for future studies combined with the “close reading” of traditional research approaches.
- Published
- 2020
- Full Text
- View/download PDF
9. Deep Learning Applied to Defect Detection in Powder Spreading Process of Magnetic Material Additive Manufacturing
- Author
-
Hsin-Yu Chen, Ching-Chih Lin, Ming-Huwi Horng, Lien-Kai Chang, Jian-Han Hsu, Tsung-Wei Chang, Jhih-Chen Hung, Rong-Mao Lee, and Mi-Ching Tsai
- Subjects
convolution neural network ,metal additive manufacturing ,powder-spreading defect ,selective laser melting ,Technology ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Microscopy ,QH201-278.5 ,Descriptive and experimental mechanics ,QC120-168.85 - Abstract
Due to its advantages of high customization and rapid production, metal laser melting manufacturing (MAM) has been widely applied in the medical industry, manufacturing, aerospace and boutique industries in recent years. However, defects during the selective laser melting (SLM) manufacturing process can result from thermal stress or hardware failure during the selective laser melting (SLM) manufacturing process. To improve the product’s quality, the use of defect detection during manufacturing is necessary. This study uses the process images recorded by powder bed fusion equipment to develop a detection method, which is based on the convolutional neural network. This uses three powder-spreading defect types: powder uneven, powder uncovered and recoater scratches. This study uses a two-stage convolutional neural network (CNN) model to finish the detection and segmentation of defects. The first stage uses the EfficientNet B7 to classify the images with/without defects, and then to locate the defects by evaluating three different instance segmentation networks in second stage. Experimental results show that the accuracy and Dice measurement of Mask-R-CNN network with ResNet 152 backbone can reach 0.9272 and 0.9438. The computational time of an image only takes approximately 0.2197 sec. The used CNN model meets the requirements of the early detected defects, regarding the SLM manufacturing process.
- Published
- 2022
- Full Text
- View/download PDF
10. Identification of treatment-experienced hepatitis C patients with poor cost-effectiveness of pegylated interferon plus ribavirin from a real-world cohort
- Author
-
Ta-Wei Liu, Pei-Chien Tsai, Ching-I Huang, Yi-Shan Tsai, Shu-Chi Wang, Yu-Min Ko, Ching-Chih Lin, Kuan-Yu Chen, Po-Cheng Liang, Yi-Hung Lin, Ming-Yen Hsieh, Nai-Jen Hou, Chung-Feng Huang, Ming-Lun Yeh, Zu-Yau Lin, Shinn-Cherng Chen, Chia-Yen Dai, Wan-Long Chuang, Jee-Fu Huang, and Ming-Lung Yu
- Subjects
chronic hepatitis C ,cost-effectiveness analysis ,pegylated interferon ,ribavirin ,treatment-experienced ,Medicine (General) ,R5-920 - Abstract
Pegylated interferon (PegIFN) plus ribavirin (RBV) combination therapy has been the standard of care since 2002. Although a better viral response has been achieved among chronic hepatitis C (CHC) patients in Taiwan, approximately 25% of hepatitis C virus (HCV) genotype 1 (G1) patients and 15% of G2 patients failed to achieve a sustained virological response (SVR) at the first therapy. The actual cost-effectiveness of the retreatment remains elusive. The present study conducted a real-world cost-effectiveness analysis of a large cohort among different pre-specified subgroups of treatment-experienced CHC patients. Methods: A total of 117 patients with CHC who failed to achieve SVR at the first IFN-based therapy and received a second IFN-based therapy were enrolled. The inpatient and outpatient costs were acquired from National Health Insurance Research Database of Taiwan. The related medical care costs per treatment and per SVR were calculated. Results: We demonstrated that the average cost per SVR achieved was $13,722 in treatment-experienced CHC patients. Especially, patients with HCV G1 infection, baseline viral loads > 400,000 IU/mL, advanced hepatic fibrosis, not achieving a rapid viral response at week 4 or complete early viral response at week 12, had poorer cost-effectiveness for PegIFN/RBV retherapy, ranging from around $15,520 to as high as $72,546 per SVR achieved. Conclusion: In the current study, we explored the real-world cost-effectiveness data of PegIFN/RBV for different subgroups of treatment-experienced HCV patients. These findings provide information for policy-makers for making decisions on treatment strategies of costly direct-acting antiviral agents for retreating CHC patients.
- Published
- 2018
- Full Text
- View/download PDF
11. Genetics Variants and Serum Levels of MHC Class I Chain-related A in Predicting Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients Post Antiviral Treatment
- Author
-
Chung-Feng Huang, Cing-Yi Huang, Ming-Lun Yeh, Shu-Chi Wang, Kuan-Yu Chen, Yu-Min Ko, Ching-Chih Lin, Yi-Shan Tsai, Pei-Chien Tsai, Zu-Yau Lin, Shinn-Cherng Chen, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, and Ming-Lung Yu
- Subjects
HCC ,SVR ,SNP ,MICA ,PNPLA3 ,IL-28 ,EGF ,sMICA ,Treatment ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background/aims: The genome-wide association study has shown that MHC class I chain-related A (MICA) genetic variants were associated with hepatitis C virus (HCC) related hepatocellular carcinoma. The impact of the genetic variants and its serum levels on post-treatment cohort is elusive. Methods: MICA rs2596542 genotype and serum MICA (sMICA) levels were evaluated in 705 patients receiving antiviral therapy. Results: Fifty-eight (8·2%) patients developed HCC, with a median follow-up period of 48·2 months (range: 6–129 months). The MICA A allele was associated with a significantly increased risk of HCC development in cirrhotic non-SVR patients but not in patients of non-cirrhotic and/or with SVR. For cirrhotic non-SVR patients, high sMICA levels (HR/CI: 5·93/1·86–26.38·61, P = 0·002) and the MICA rs2596542 A allele (HR/CI: 4·37/1·52–12·07, P = 0·002) were independently associated with HCC development. The risk A allele or GG genotype with sMICA > 175 ng/mL provided the best accuracy (79%) and a negative predictive value of 100% in predicting HCC. Conclusions: Cirrhotic patients who carry MICA risk alleles and those without risk alleles but with high sMICA levels possessed the highest risk of HCC development once they failed antiviral therapy.
- Published
- 2017
- Full Text
- View/download PDF
12. Corrigendum to 'Genetics Variants and Serum Levels of MHC Class I Chain-related A in Predicting Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients Post Antiviral Treatment' [EBioMedicine 15 (2017) 81–89]
- Author
-
Chung-Feng Huang, Ching-I Huang, Ming-Lun Yeh, Shu-Chi Wang, Kuan-Yu Chen, Yu-Min Ko, Ching-Chih Lin, Yi-Shan Tsai, Pei-Chien Tsai, Zu-Yau Lin, Shinn-Cherng Chen, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, and Ming-Lung Yu
- Subjects
Medicine ,Medicine (General) ,R5-920 - Published
- 2017
- Full Text
- View/download PDF
13. GSK3beta-mediated Drp1 phosphorylation induced elongated mitochondrial morphology against oxidative stress.
- Author
-
Chia-Hua Chou, Ching-Chih Lin, Ming-Chang Yang, Chih-Chang Wei, Huei-De Liao, Run-Chin Lin, Wen-Yu Tu, Tsung-Chieh Kao, Ching-Mei Hsu, Jiin-Tsuey Cheng, An-Kuo Chou, Chu-I Lee, Joon-Khim Loh, Shen-Long Howng, and Yi-Ren Hong
- Subjects
Medicine ,Science - Abstract
Multiple phosphorylation sites of Drp1 have been characterized for their functional importance. However, the functional consequence of GSK3beta-mediated phosphorylation of Drp1 remains unclear. In this report, we pinpointed 11 Serine/Threonine sites spanning from residue 634~736 of the GED domain and robustly confirmed Drp1 Ser693 as a novel GSK3beta phosphorylation site. Our results suggest that GSK3beta-mediated phosphorylation at Ser693 does cause a dramatic decrease of GTPase activity; in contrast, GSK3beta-mediated phosphorylation at Ser693 appears not to affect Drp1 inter-/intra-molecular interactions. After identifying Ser693 as a GSK3beta phosphorylation site, we also determined that K679 is crucial for GSK3beta-binding, which strongly suggests that Drp1 is a novel substrate for GSK3beta. Thereafter, we found that overexpressed S693D, but not S693A mutant, caused an elongated mitochondrial morphology which is similar to that of K38A, S637D and K679A mutants. Interestedly, using H89 and LiCl to inhibit PKA and GSK3beta signaling, respectively, it appears that a portion of the elongated mitochondria switched to a fragmented phenotype. In investigating the biofunctionality of phosphorylation sites within the GED domain, cells overexpressing Drp1 S693D and S637D, but not S693A, showed an acquired resistance to H(2)O(2)-induced mitochondrial fragmentation and ensuing apoptosis, which affected cytochrome c, capase-3, -7, and PARP, but not LC3B, Atg-5, Beclin-1 and Bcl2 expressions. These results also showed that the S693D group is more effective in protecting both non-neuronal and neuronal cells from apoptotic death than the S637D group. Altogether, our data suggest that GSK3beta-mediated phosphorylation at Ser693 of Drp1 may be associated with mitochondrial elongation via down-regulating apoptosis, but not autophagy upon H(2)O(2) insult.
- Published
- 2012
- Full Text
- View/download PDF
14. Exploring the relationship between metabolite composition and the cold/hot properties ascribed in traditional Chinese medicine by mass spectral molecular networking–a pilot study
- Author
-
Chun-Han Su, Yu-Chieh Cheng, Kuei-Hung Lai, Yu-Chia Chang, Chi-Hui Sun, Po-Wen Tu, Ching-Chih Lin, Tsong-Long Hwang, and Yu-Liang Yang
- Subjects
Pharmacology ,Food Science - Published
- 2022
15. Outreach onsite treatment with a simplified pangenotypic direct-acting anti-viral regimen for hepatitis C virus micro-elimination in a prison
- Author
-
Chun-Ting Chen, Ming-Ying Lu, Meng-Hsuan Hsieh, Pei-Chien Tsai, Tsai-Yuan Hsieh, Ming-Lun Yeh, Ching-I Huang, Yi-Shan Tsai, Yu-Min Ko, Ching-Chih Lin, Kuan-Yu Chen, Yu-Ju Wei, Po-Yao Hsu, Cheng-Ting Hsu, Tyng-Yuan Jang, Ta-Wei Liu, Po-Cheng Liang, Ming-Yen Hsieh, Zu-Yau Lin, Chung-Feng Huang, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chuang, Yu-Lueng Shih, and Ming-Lung Yu
- Subjects
Universal screen ,Gastroenterology ,virus diseases ,General Medicine ,Hepacivirus ,Hepatitis C, Chronic ,Direct-acting antivirals ,Antiviral Agents ,Hepatitis C ,Prisons ,Prospective Study ,Humans ,Sofosbuvir ,People who inject drugs ,Velpatasvir - Abstract
BACKGROUND Prisoners are at risk of hepatitis C virus (HCV) infection, especially among the people who inject drugs (PWID). We implemented an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic direct-acting antivirals (DAA) regimen, 12 wk of sofosbuvir/velpatasvir, in a PWID-dominant prison in Taiwan. AIM To implement an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic DAA regimen in a PWID-dominant prison in Taiwan. METHODS HCV-viremic patients were recruited for onsite treatment program for HCV micro-elimination with a pangenotypic DAA regimen, 12 wk of sofosbuvir/ velpatasvir, from two cohorts in Penghu Prison, either identified by mass screen or in outpatient clinics, in September 2019. Another group of HCV-viremic patients identified sporadically in outpatient clinics before mass screening were enrolled as a control group. The primary endpoint was sustained virological response (SVR12, defined as undetectable HCV ribonucleic acid (RNA) 12 wk after end-of-treatment). RESULTS A total of 212 HCV-viremic subjects were recruited for HCV micro-elimination campaign; 91 patients treated with sofosbuvir/Ledipasvir or glecaprevir/ pibrentasvir before mass screening were enrolled as a control. The HCV micro-elimination group had significantly lower proportion of diabetes, hypertension, hyperlipidemia, advanced fibrosis and chronic kidney diseases, but higher levels of HCV RNA. The SVR12 rate was comparable between the HCV micro-elimination and control groups, 95.8% (203/212) vs 94.5% (86/91), respectively, in intent-to-treat analysis, and 100% (203/203) vs 98.9% (86/87), respectively, in per-protocol analysis. There was no virological failure, treatment discontinuation, and serious adverse event among sofosbuvir/velpatasvir-treated patients in the HCV micro-elimination group. CONCLUSION Outreach mass screening followed by immediate onsite treatment with a simplified pangenotypic DAA regimen, sofosbuvir/velpatasvir, provides successful strategies toward HCV micro-elimination among prisoners.
- Published
- 2022
16. Dynamics of cytokines predicts risk of hepatocellular carcinoma among chronic hepatitis C patients after viral eradication
- Author
-
Ming-Ying Lu, Ming-Lun Yeh, Ching-I Huang, Shu-Chi Wang, Yi-Shan Tsai, Pei-Chien Tsai, Yu-Min Ko, Ching-Chih Lin, Kuan-Yu Chen, Yu-Ju Wei, Po-Yao Hsu, Cheng-Ting Hsu, Tyng-Yuan Jang, Ta-Wei Liu, Po-Cheng Liang, Ming-Yen Hsieh, Zu-Yau Lin, Shinn-Cherng Chen, Chung-Feng Huang, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chuang, and Ming-Lung Yu
- Subjects
Sustained virologic response ,Carcinoma, Hepatocellular ,Hepatitis C virus ,Hepatocellular carcinoma ,Tumor Necrosis Factor-alpha ,Liver Neoplasms ,Gastroenterology ,General Medicine ,Hepacivirus ,Hepatitis C, Chronic ,Antiviral Agents ,digestive system diseases ,Tumor necrosis factor-α ,Risk Factors ,Retrospective Cohort Study ,Cytokines ,Humans ,Cytokine ,Tumor necrosis factor-like weak inducer of apoptosis - Abstract
BACKGROUND Chronic hepatitis C virus (HCV) infection induces profound alterations in the cytokine and chemokine signatures in peripheral blood. Clearance of HCV by antivirals results in host immune modification, which may interfere with immune-mediated cancer surveillance. Identifying HCV patients who remain at risk of hepatocellular carcinoma (HCC) following HCV eradication remains an unmet need. We hypothesized that antiviral therapy-induced immune reconstruction may be relevant to HCC development. AIM To investigate the impact of differential dynamics of cytokine expression on the development of HCC following successful antiviral therapy. METHODS One hundred treatment-naïve HCV patients with advanced fibrosis (F3/4) treated with direct-acting antivirals (DAAs) or peginterferon/ribavirin who achieved sustained virologic response [SVR, defined as undetectable HCV RNA throughout 12 wk (SVR12) for the DAA group or 24 wk (SVR24) for the interferon group after completion of antiviral therapy] were enrolled since 2003. The primary endpoint was the development of new-onset HCC. Standard HCC surveillance (abdominal ultrasound and α-fetoprotein) was performed every six months during the follow-up. Overall, 64 serum cytokines were detected by the multiplex immunoassay at baseline and 24 wk after end-of-treatment. RESULTS HCC developed in 12 of the 97 patients over 459 person-years after HCV eradication. In univariate analysis, the Fibrosis-4 index (FIB-4), hemoglobin A1c (HbA1c), the dynamics of tumor necrosis factor-α (TNF-α), and TNF-like weak inducer of apoptosis (TWEAK) after antiviral therapy were significant HCC predictors. The multivariate Cox regression model showed that ΔTNF-α (≤ -5.7 pg/mL) was the most important risk factor for HCC (HR = 11.54, 95%CI: 2.27-58.72, P = 0.003 in overall cases; HR = 9.98, 95%CI: 1.88-52.87, P = 0.007 in the interferon group). An HCC predictive model comprising FIB-4, HbA1c, ΔTNF-α, and ΔTWEAK had excellent performance, with 3-, 5-, 10-, and 13-year areas under the curve of 0.882, 0.864, 0.903, and 1.000, respectively. The 5-year accumulative risks of HCC were 0%, 16.9%, and 40.0% in the low-, intermediate-, and high-risk groups, respectively. CONCLUSION Downregulation of serum TNF-α significantly increases the risk of HCC after HCV eradication. A predictive model consisting of cytokine kinetics could ameliorate personalized HCC surveillance strategies for post-SVR HCV patients.
- Published
- 2022
17. Graphitic carbon nitride embedded with single-atom Pt for photo-enhanced electrocatalytic hydrogen evolution reaction
- Author
-
En-Jing Lin, Yu-Bin Huang, Po-Kai Chen, Je-Wei Chang, Shu-Yi Chang, Wei-Ting Ou, Ching-Chih Lin, Yu-Hsien Wu, Jeng-Lung Chen, Chi Wen Pao, Chun-Jen Su, Chia-Hsin Wang, U-Ser Jeng, and Ying-Huang Lai
- Subjects
History ,Polymers and Plastics ,General Physics and Astronomy ,Surfaces and Interfaces ,General Chemistry ,Business and International Management ,Condensed Matter Physics ,Industrial and Manufacturing Engineering ,Surfaces, Coatings and Films - Published
- 2023
18. Predicting magnetic characteristics of additive manufactured soft magnetic composites by machine learning
- Author
-
Ching Chih Lin, Mi-Ching Tsai, Tsung Wei Chang, Kai Wei Liao, and Chung-Wei Cheng
- Subjects
0209 industrial biotechnology ,Materials science ,business.industry ,Mechanical Engineering ,Process (computing) ,Evolutionary algorithm ,02 engineering and technology ,Industrial and Manufacturing Engineering ,Computer Science Applications ,020901 industrial engineering & automation ,Control and Systems Engineering ,Permeability (electromagnetism) ,Magnet ,Selective laser melting ,Process engineering ,business ,Software - Abstract
Selective laser melting (SLM) is one of the widely used metal additive manufacturing techniques. While SLM is able to produce high-quality products, the parameter selection process can be very complicated, especially for magnetic materials in that the iron loss and permeability properties must also be considered, which renders the parameter selecting process more complicated. This research explores the parameter selection process of magnetic material for SLM, which integrates machine and evolutionary algorithms to accurately predict magnetic characteristics, such as iron loss and permeability, and generates suggestions for the process parameters according to practical demands.
- Published
- 2021
19. Changing epidemiology and viral interplay of hepatitis B, C and D among injecting drug user-dominant prisoners in Taiwan
- Author
-
Cheng-Ting Hsu, Ming-Lun Yeh, Chun-Ting Chen, Chung-Feng Huang, Ming-Ying Lu, Yu-Ju Wei, Ming-Yen Hsieh, Yi-Shan Tsai, Yu-Min Ko, Ching-I Huang, Pei-Chien Tsai, Shu-Chi Wang, Chia-Yen Dai, Wen-Yu Chang, Shinn-Cherng Chen, Ming-Lung Yu, Wan-Long Chuang, Ching-Chih Lin, Ta-Wei Liu, Po-Cheng Liang, Yu-Lueng Shih, Zu-Yau Lin, Tyng-Yuan Jang, Meng-Hsuan Hsieh, Kuan-Yu Chen, Po-Yao Hsu, and Jee-Fu Huang
- Subjects
Male ,0301 basic medicine ,Hepatitis B virus ,HBsAg ,Genotype ,Hepatitis C virus ,viruses ,Science ,Taiwan ,Viremia ,Hepacivirus ,medicine.disease_cause ,Microbiology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Seroepidemiologic Studies ,medicine ,Humans ,Substance Abuse, Intravenous ,Multidisciplinary ,Coinfection ,business.industry ,Prisoners ,Gastroenterology ,virus diseases ,Middle Aged ,Viral Load ,Hepatitis B ,medicine.disease ,Hepatitis C ,Virology ,Hepatitis D ,digestive system diseases ,030104 developmental biology ,Medicine ,Female ,030211 gastroenterology & hepatology ,Hepatitis D virus ,Hepatitis Delta Virus ,business ,Viral hepatitis ,Viral load - Abstract
The spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10–0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13–0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04–40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.
- Published
- 2021
20. Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognos- tic factor in hepatitis C virus-related hepatocellular carcinoma
- Author
-
Jee-Fu Huang, Ming-Lun Yeh, Ming-Lung Yu, Chung-Feng Huang, Wan-Long Chuang, Ta-Wei Liu, Yi-Shan Tsai, Ching-Chih Lin, Chia-Yen Dai, and Pei-Chien Tsai
- Subjects
Male ,hepacivirus ,Cirrhosis ,recurrence ,Hepacivirus ,Hepatitis C virus ,Down-Regulation ,Growth hormone receptor ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Carcinoma ,Humans ,lcsh:RC799-869 ,Receptor ,Molecular Biology ,carcinoma, hepatocellular ,Hepatology ,biology ,business.industry ,Liver Neoplasms ,Cancer ,Middle Aged ,medicine.disease ,biology.organism_classification ,Hepatitis C ,digestive system diseases ,receptors, somatotropin ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cancer research ,030211 gastroenterology & hepatology ,Original Article ,Female ,lcsh:Diseases of the digestive system. Gastroenterology ,prognosis ,Neoplasm Recurrence, Local ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC.Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed.Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II–IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C.Conclusions: Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC.
- Published
- 2021
21. Role of hepatitis D virus infection in development of hepatocellular carcinoma among chronic hepatitis B patients treated with nucleotide/nucleoside analogues
- Author
-
Po-Cheng Liang, Chung-Feng Huang, Chia-Yen Dai, Zu-Yau Lin, Yi-Shan Tsai, Pei-Chien Tsai, Ming-Lun Yeh, Ching-I Huang, Shu-Fen Liu, Shinn-Cherng Chen, Wan-Long Chuang, Po-Yao Hsu, Tyng-Yuan Jang, Meng-Hsuan Hsieh, Jee-Fu Huang, Ta-Wei Liu, Yu-Ju Wei, Yi-Hung Lin, Ching-Chih Lin, Yu-Min Ko, Shu-Chi Wang, Cheng-Ting Hsu, Kuan-Yu Chen, and Ming-Lung Yu
- Subjects
Adult ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cirrhosis ,Hepatitis D, Chronic ,Hepatocellular carcinoma ,Science ,Taiwan ,Viremia ,Gastroenterology ,Article ,03 medical and health sciences ,Hepatitis B, Chronic ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Cumulative incidence ,Retrospective Studies ,Sex Characteristics ,Multidisciplinary ,Coinfection ,business.industry ,Incidence ,Incidence (epidemiology) ,Liver Neoplasms ,Hazard ratio ,Age Factors ,Nucleosides ,Middle Aged ,Hepatitis B ,medicine.disease ,Survival Analysis ,Hepatitis D ,030220 oncology & carcinogenesis ,RNA, Viral ,Female ,Pre-Exposure Prophylaxis ,030211 gastroenterology & hepatology ,Hepatitis D virus ,Hepatitis Delta Virus ,business - Abstract
Hepatitis D virus (HDV) infection increases the risk of hepatocellular carcinoma (HCC) in the natural course of chronic hepatitis B (CHB) patients. Its role in patients treated with nucleotide/nucleoside analogues (NAs) is unclear. We aimed to study the role of hepatitis D in the development of HCC in CHB patients treated with NAs. Altogether, 1349 CHB patients treated with NAs were tested for anti-HDV antibody and RNA. The incidence and risk factors of HCC development were analyzed. Rates of anti-HDV and HDV RNA positivity were 2.3% and 1.0%, respectively. The annual incidence of HCC was 1.4 per 100 person-years after a follow-up period of over 5409.5 person-years. The strongest factor association with HCC development was liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI] 9.98/5.11–19.46, P P = 0.02), age > 50 years old (HR/CI 3.64/2.03–6.54, P P: 0.01), and body mass index (BMI, HR/CI 1.11/1.03–1.18, P = 0.004). The 5-year cumulative incidence of HCC was 7.3% for patients with HDV RNA negativity compared to that of 22.2% for patients with HDV RNA positivity (P = 0.01). In the subgroup of cirrhotic patients, the factors associated with HCC development were HDV RNA positivity (HR/CI 4.45/1.04–19.09, P = 0.04) and BMI (HR/CI 1.11/1.03–1.19, P = 0.01). HDV viremia played a crucial role in HCC development in CHB patients who underwent NA therapy.
- Published
- 2021
22. Specific inactivation of an antifungal bacterial siderophore by a fungal plant pathogen
- Author
-
Ching-Chih Lin, Chi-Hui Sun, Sin Yong Hoo, Chi-Ting Hsieh, Bo-Wei Wang, Chih Lin, Yu-Liang Yang, Chia-Chi Peng, and Ying-Ning Ho
- Subjects
Siderophore ,Antifungal Agents ,Iron ,Siderophores ,Biology ,Brief Communication ,medicine.disease_cause ,Microbiology ,03 medical and health sciences ,Metabolomics ,Microbial ecology ,Pseudomonas ,medicine ,Pathogen ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,0303 health sciences ,Phellinus noxius ,030306 microbiology ,Pseudomonas aeruginosa ,Fungi ,biology.organism_classification ,medicine.drug_formulation_ingredient ,Bacteria - Abstract
Bacteria and fungi secrete many natural products that inhibit each other’s growth and development. The dynamic changes in secreted metabolites that occur during interactions between bacteria and fungi are complicated. Pyochelin is a siderophore produced by many Pseudomonas and Burkholderia species that induces systemic resistance in plants and has been identified as an antifungal agent. Through imaging mass spectrometry and metabolomics analysis, we found that Phellinus noxius, a plant pathogen, can modify pyochelin and ent-pyochelin to an esterification product, resulting in reduced iron-chelation and loss of antifungal activity. We also observed that dehydroergosterol peroxide, the fungal metabolite, is only accumulated in the presence of pyochelin produced through bacteria–fungi interactions. For the first time, we show the fungal transformation of pyochelin in the microbial interaction. Our findings highlight the importance of understanding the dynamic changes of metabolites in microbial interactions and their influences on microbial communities.
- Published
- 2021
23. Exosome‐derived differentiation antagonizing non‐protein coding RNA with risk of hepatitis C virus‐related hepatocellular carcinoma recurrence
- Author
-
Wen-Tsan Chang, Ming-Lung Yu, Shu-Chi Wang, Wen-Yu Tu, Ching-Chih Lin, Jee-Fu Huang, Chia-Yang Li, Ming-Lun Yeh, Yao-Li Chen, Chia-Hung Yen, Zu-Yau Lin, Chung-Feng Huang, Wei-Chung Cheng, Chia-Yen Dai, and Wan-Long Chuang
- Subjects
Carcinoma, Hepatocellular ,Hepatitis C virus ,Hepacivirus ,Exosomes ,medicine.disease_cause ,Exosome ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,law ,Humans ,Medicine ,Polymerase chain reaction ,Hepatology ,business.industry ,Liver Neoplasms ,RNA ,Hepatitis C ,medicine.disease ,Microvesicles ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cancer research ,RNA, Long Noncoding ,030211 gastroenterology & hepatology ,Neoplasm Recurrence, Local ,business - Abstract
BACKGROUND & AIMS Differentiation antagonizing non-protein coding RNA is associated with various types of neoplasms. Hepatitis C virus-related hepatocellular carcinoma has a high risk of recurrence. Here we determined the role of differentiation antagonizing non-protein coding RNA in hepatitis C virus-related hepatocarcinogenesis and identified potential therapeutic targets and non-invasive prognostic markers for long-term outcome of hepatitis C virus-related hepatocellular carcinoma after surgical resection. METHODS Differentiation antagonizing non-protein coding RNAs relevant to hepatitis C virus-related hepatocellular carcinoma were identified through comparative RNA-sequencing of tumour and adjacent non-tumour (ANT) tissues in a screening set, and were validated using real-time polymerase chain reaction. Target long non-coding RNAs (lncRNAs) in tissues and serum exosomes were used to predict the recurrence of hepatitis C virus-related hepatocellular carcinoma after curative surgical resection in a large application cohort from 2005 to 2012. RESULTS We confirmed that differentiation antagonizing non-protein coding RNA was upregulated following hepatitis C virus infection and identified as the lncRNA most relevant to hepatitis C virus-related hepatocellular carcinoma in tumour tissues as compared to that in ANT tissues. In 183 hepatitis C virus-related hepatocellular carcinoma patients followed for 10 years after curative HCC resection, the expression level of circulating exosomal differentiation antagonizing non-protein coding RNA was positively associated with HCC recurrence and was the most predictive factor associated with HCC recurrence and mortality (hazard ratio/95% confidence intervals: 7.0/4.3-11.6 and 2.7/1.5-5.1 respectively). CONCLUSIONS Differentiation antagonizing non-protein coding RNA is highly relevant to disease progression of hepatitis C virus-related hepatocellular carcinoma. Our finding indicated that circulating exosomal differentiation antagonizing non-protein coding RNA might serve as a non-invasive prognostic biomarker for hepatitis C virus-related hepatocellular carcinoma.
- Published
- 2021
24. Serial serologic changes of hepatitis D virus in chronic hepatitis B patients receiving nucleos(t)ides analogues therapy
- Author
-
Jee-Fu Huang, Yu-Ju Wei, Chung-Feng Huang, Ming-Lun Yeh, Ching-Chih Lin, Zu-Yau Lin, Po-Cheng Liang, Pei-Chien Tsai, Ming-Lung Yu, Shinn-Cherng Chen, Wan-Long Chuang, Ching-I Huang, Shu-Chi Wang, Yi-Hung Lin, Ta-Wei Liu, Yu-Min Ko, Po-Yao Hsu, Yi-Shan Tsai, Meng-Hsuan Hsieh, Cheng-Ting Hsu, Chia-Yen Dai, Tyng-Yuan Jang, and Kuan-Yu Chen
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,viruses ,Taiwan ,Administration, Oral ,Antibodies, Viral ,Gastroenterology ,Virus ,Serology ,03 medical and health sciences ,Hepatitis B, Chronic ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Serologic Tests ,Hepatology ,Coinfection ,business.industry ,Hazard ratio ,Age Factors ,virus diseases ,Nucleosides ,Odds ratio ,Middle Aged ,biochemical phenomena, metabolism, and nutrition ,Hepatitis B ,medicine.disease ,Hepatitis D ,HBeAg ,030220 oncology & carcinogenesis ,RNA, Viral ,Female ,030211 gastroenterology & hepatology ,Hepatitis D virus ,Hepatitis Delta Virus ,business ,Follow-Up Studies - Abstract
BACKGROUND AND AIM The serial serologic changes of hepatitis D virus (HDV) infection among chronic hepatitis B virus (HBV) infected patients who received oral nucleotide/nucleoside analogues are elusive. METHODS Serum anti-HDV and HDV RNA among chronic hepatitis B (CHB) patients were tested at the time of initiating anti-HBV therapy and subsequently during the follow-up period. RESULTS The seropositive rate of anti-HDV and HDV RNA among 2850 CHB patients, was 2.7% and 0.9%, respectively. Factors associated with anti-HDV seropositivity were platelet counts (odds ratio [OR]/95% confidence intervals [CI]: 0.995/0.992-0.999; P = 0.006), HBV DNA levels (OR/CI: 0.81/0.70-0.94; P = 0.005), and hepatitis B e-antigen (HBeAg) seropositivity (OR/CI: 0.22/0.05-0.95; P = 0.04). The only factor associated with HDV RNA positivity among anti-HDV seropositive patients was age (OR/CI: 0.95/0.90-1.00; P = 0.03). The spontaneous clearance rate of serum anti-HDV antibody was 3.0 per 100 person-years with a median follow-up period of 3.5 years (range 2-12 years), whereas the seroclearance rate of HDV RNA was 4.3 per 100 person-years among anti-HDV seropositive patients after a median follow-up period of 6.0 years (range 2-11 years). A baseline anti-HDV titer
- Published
- 2020
25. Multi-omics approach to identify bacterial polyynes and unveil their antifungal mechanism against Candida albicans
- Author
-
Ching-Chih Lin, Sin Yong Hoo, Chih Lin, Kai-Fa Huang, Ying-Ning Ho, Chi-Hui Sun, Han-Jung Lee, Pi-Yu Chen, Lin-Jie Shu, Bo-Wei Wang, Wei-Chen Hsu, and Yu-Liang Yang
- Subjects
Comparative genomics ,chemistry.chemical_compound ,Metabolomics ,Biosynthesis ,Biochemistry ,biology ,Chemistry ,Acetyltransferase ,Gene cluster ,Antimicrobial ,Candida albicans ,biology.organism_classification ,Gene - Abstract
Bacterial polyynes are highly active natural products with a broad-spectrum of antimicrobial activities. However, their detailed mechanism of action remains unclear. Through integrating comparative genomics, transcriptomics, functional genetics, and metabolomics analysis, we identified a unique polyyne resistance gene, masL (encoding acetyl-CoA acetyltransferase), from the biosynthesis gene cluster (BGC) dominant for the production of antifungal polyynes (massilin A, massilin B, collimonin C, and collimonin D) in Massilia sp. YMA4. Phylogenic and chemotaxonomic analyses characterized the core architecture of bacterial polyyne BGC. The crystallographic analysis of the MasL-collimonin C complex indicated that bacterial polyynes serve as a covalent inhibitor of acetyl-CoA acetyltransferase. Moreover, we confirmed that the bacterial polyynes disrupted cell membrane integrity and inhibited cell viability of Candida albicans by targeting ERG10 (homolog of MasL). Overall, understanding of the antifungal mechanism of bacterial polyynes presented herein will be useful for the development of polyynes for fungal infections.
- Published
- 2021
26. Role of hepatitis D virus in persistent alanine aminotransferase abnormality among chronic hepatitis B patients treated with nucleotide/nucleoside analogues
- Author
-
Shinn-Cherng Chen, Wan-Long Chuang, Yi-Shan Tsai, Shu-Chi Wang, Ta-Wei Liu, Shu-Fen Liu, Yu-Min Ko, Zu-Yau Lin, Kuan-Yu Chen, Chung-Feng Huang, Cheng-Ting Hsu, Yi-Hung Lin, Jee-Fu Huang, Ching-Chih Lin, Tyng-Yuan Jang, Yu-Ju Wei, Meng-Hsuan Hsieh, Ming-Lun Yeh, Po-Cheng Liang, Ching-I Huang, Pei-Chien Tsai, Ming-Lung Yu, Po-Yao Hsu, and Chia-Yen Dai
- Subjects
Male ,medicine.medical_specialty ,Hepatitis B virus ,Cirrhosis ,ALT normalization ,Gastroenterology ,Virus ,03 medical and health sciences ,0302 clinical medicine ,Hepatitis B, Chronic ,NAs ,HDV ,Internal medicine ,Diabetes mellitus ,HBV ,medicine ,Humans ,Longitudinal Studies ,lcsh:R5-920 ,biology ,business.industry ,Nucleotides ,Alanine Transaminase ,Nucleosides ,General Medicine ,Odds ratio ,Hepatitis B ,medicine.disease ,Hepatitis D ,030220 oncology & carcinogenesis ,DNA, Viral ,biology.protein ,030211 gastroenterology & hepatology ,Female ,Hepatitis D virus ,Antibody ,Hepatitis Delta Virus ,lcsh:Medicine (General) ,business ,Body mass index - Abstract
Background: The biochemical response is a crucial indicator of prognosis in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues (NAs). The impact of hepatitis D virus (HDV) infection on alanine aminotransferase normalization is elusive. Methods: The longitudinal study recruited 1185 CHB patients who received NAs. These patients were tested for anti-HDV antibody and HDV RNA at the initiation of anti-hepatitis B virus (HBV) therapy and annually for patients who were HDV-seropositive. ALT levels were examined at the first and second year of anti-HBV therapy. ALT abnormality was defined as ALT levels above 40 IU/mL in both male and female, and the risk factors associated with ALT abnormality were analysed. Results: Rates of seropositivity for anti-HDV and HDV RNA were 2.0% and 0.8% among 1185 NA-treated CHB patients, respectively. The strongest factor associated with ALT abnormality (>40 IU/mL) after first year treatment with NAs was HDV RNA seropositivity at year 1 (odds ratio [OR]/95% confidence interval [CI]: 31.44/3.49–283.56, P = 0.002), followed by liver cirrhosis (2.18/1.51–3.15, P
- Published
- 2020
27. The Dynamics of Cytokine Profiles Predicts Risk of Hepatocellular Carcinoma Among Chronic Hepatitis C Patients with Advanced Fibrosis Following Successful Antiviral Therapy
- Author
-
Ming-Ying Lu, Ming-Lun Yeh, Ching-I Huang, Shu-Chi Wang, Yi-Shan Tsai, Pei-Chien Tsai, Yu-Min Ko, Ching-Chih Lin, Kuan-Yu Chen, Yu-Ju Wei, Po-Yao Hsu, Cheng-Ting Hsu, Tyng-Yuan Jang, Ta-Wei Liu, Po-Cheng Liang, Ming-Yen Hsieh, Zu-Yau Lin, Shinn-Cherng Chen, Chung-Feng Huang, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chuang, and Ming-Lung Yu
- Published
- 2020
28. AIBp regulates mitotic entry and mitotic spindle assembly by controlling activation of both Aurora-A and Plk1
- Author
-
Ming-Chang Yang, Joon-Khim Loh, Chihuei Wang, Shen-Long Howng, Ann-Shung Lieu, Chia-Hua Chou, Chung-Lung Cho, Ching-Chih Lin, An-Kuo Chou, Yi-Ren Hong, Ching-Mei Hsu, and Ming-Chang Hong
- Subjects
Regulator ,Mitosis ,Cell Cycle Proteins ,Spindle Apparatus ,Biology ,Protein Serine-Threonine Kinases ,PLK1 ,Spindle pole body ,Proto-Oncogene Proteins ,Humans ,Molecular Biology ,Microtubule nucleation ,Aurora Kinase A ,Cell Biology ,Cell biology ,DNA-Binding Proteins ,enzymes and coenzymes (carbohydrates) ,HEK293 Cells ,Centrosome ,Phosphorylation ,Carrier Proteins ,Multipolar spindles ,Developmental Biology ,Reports ,HeLa Cells - Abstract
We previously reported that Aurora-A and the hNinein binding protein AIBp facilitate centrosomal structure maintenance and contribute to spindle formation. Here, we report that AIBp also interacts with Plk1, raising the possibility of functional similarity to Bora, which subsequently promotes Aurora-A–mediated Plk1 activation at Thr210 as well as Aurora-A activation at Thr288. In kinase assays, AIBp acts not only as a substrate but also as a positive regulator of both Aurora-A and Plk1. However, AIBp functions as a negative regulator to block phosphorylation of hNinein mediated by Aurora-A and Plk1. These findings suggest a novel AIBp-dependent regulatory machinery that controls mitotic entry. Additionally, knockdown of hNinein caused failure of AIBp to target the centrosome, whereas depletion of AIBp did not affect the localization of hNinein and microtubule nucleation. Notably, knockdown of AIBp in HeLa cells impaired both Aurora-A and Plk1 kinase, resulting in phenotypes with multiple spindle pole formation and chromosome misalignment. Our data show that depletion of AIBp results in the mis-localization of TACC3 and ch-TOG, but not CEP192 and CEP215, suggesting that loss of AIBp dominantly affects the Aurora-A substrate to cause mitotic aberrations. Collectively, our data demonstrate that AIBp contributes to mitotic entry and bipolar spindle assembly and may partially control localization, phosphorylation, and activation of both Aurora-A and Plk1 via hNinein during mitotic progression.
- Published
- 2020
- Full Text
- View/download PDF
29. Identification of treatment-experienced hepatitis C patients with poor cost-effectiveness of pegylated interferon plus ribavirin from a real-world cohort
- Author
-
Zu-Yau Lin, Yi-Shan Tsai, Nai-Jen Hou, Po-Cheng Liang, Pei-Chien Tsai, Ching-I Huang, Yi-Hung Lin, Shinn-Cherng Chen, Wan-Long Chuang, Ming-Yen Hsieh, Ta-Wei Liu, Yu-Min Ko, Chung-Feng Huang, Jee-Fu Huang, Ming-Lun Yeh, Ching-Chih Lin, Chia-Yen Dai, Kuan-Yu Chen, Ming-Lung Yu, and Shu-Chi Wang
- Subjects
Adult ,Male ,medicine.medical_specialty ,Sustained Virologic Response ,Combination therapy ,ribavirin ,Cost effectiveness ,Cost-Benefit Analysis ,Hepatitis C virus ,Taiwan ,treatment-experienced ,Hepacivirus ,medicine.disease_cause ,Antiviral Agents ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pegylated interferon ,Internal medicine ,medicine ,Humans ,chronic hepatitis C ,pegylated interferon ,Aged ,lcsh:R5-920 ,business.industry ,Ribavirin ,cost-effectiveness analysis ,Interferon-alpha ,General Medicine ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,Viral Load ,medicine.disease ,Surgery ,chemistry ,030220 oncology & carcinogenesis ,Cohort ,Drug Therapy, Combination ,Female ,030211 gastroenterology & hepatology ,lcsh:Medicine (General) ,business ,Viral load ,medicine.drug - Abstract
Background/Purpose Pegylated interferon (PegIFN) plus ribavirin (RBV) combination therapy has been the standard of care since 2002. Although a better viral response has been achieved among chronic hepatitis C (CHC) patients in Taiwan, approximately 25% of hepatitis C virus (HCV) genotype 1 (G1) patients and 15% of G2 patients failed to achieve a sustained virological response (SVR) at the first therapy. The actual cost-effectiveness of the retreatment remains elusive. The present study conducted a real-world cost-effectiveness analysis of a large cohort among different pre-specified subgroups of treatment-experienced CHC patients. Methods A total of 117 patients with CHC who failed to achieve SVR at the first IFN-based therapy and received a second IFN-based therapy were enrolled. The inpatient and outpatient costs were acquired from National Health Insurance Research Database of Taiwan. The related medical care costs per treatment and per SVR were calculated. Results We demonstrated that the average cost per SVR achieved was $13,722 in treatment-experienced CHC patients. Especially, patients with HCV G1 infection, baseline viral loads > 400,000 IU/mL, advanced hepatic fibrosis, not achieving a rapid viral response at week 4 or complete early viral response at week 12, had poorer cost-effectiveness for PegIFN/RBV retherapy, ranging from around $15,520 to as high as $72,546 per SVR achieved. Conclusion In the current study, we explored the real-world cost-effectiveness data of PegIFN/RBV for different subgroups of treatment-experienced HCV patients. These findings provide information for policy-makers for making decisions on treatment strategies of costly direct-acting antiviral agents for retreating CHC patients.
- Published
- 2018
30. Transient Responses and Appropriate Fault Protection Solutions of Uni-grounded AC Microgrids
- Author
-
Yih-Der Lee, Yung-Ruei Chang, Keng-Yu Lien, Jheng-Lun Jiang, Duong Minh Bui, and Ching-Chih Lin
- Subjects
Control theory ,Computer science ,020208 electrical & electronic engineering ,010401 analytical chemistry ,0202 electrical engineering, electronic engineering, information engineering ,02 engineering and technology ,Transient (oscillation) ,Fault (power engineering) ,01 natural sciences ,0104 chemical sciences - Published
- 2016
31. Available Fault Protection Methods of Ungrounded AC Microgrids Evaluated by Transient Simulation Results
- Author
-
Keng-Yu Lien, Yih-Der Lee, Yung-Ruei Chang, Duong Minh Bui, Ching-Chih Lin, and Jheng-Lun Jiang
- Subjects
Control theory ,Computer science ,business.industry ,020209 energy ,Embedded system ,0202 electrical engineering, electronic engineering, information engineering ,02 engineering and technology ,Microgrid ,Transient (oscillation) ,Fault (power engineering) ,business - Abstract
This paper evaluates fault protection methods of ungrounded low-voltage (LV) AC microgrids (MGs) based on transient simulation results of a typical ungrounded LVAC microgrid. By considering operation characteristics of ungrounded MGs and a literature review on existing MG fault protection solutions in recent years, possible fault protection methods are proposed for an ungrounded AC MG. Transient simulation results of an ungrounded AC MG are obtained by line-to-line (LL) and line-to-ground (LG) faults, and operation transition tests of the microgrid between autonomous and grid-connected operation modes. Based on the simulation results, advantages and disadvantages of each ungrounded microgrid protection solution are highlighted. In order to get the optimal fault protection, combinations among some or all of possible fault protection solutions of an ungrounded LVAC microgrid are found out. As a result, main contributions of the paper contain: (i) proposing and analysing available fault protection solutions of ungrounded LVAC MGs, (ii) doing the transient simulations of a typical ungrounded microgrid under different disturbance cases, and (iii) suggesting the necessary combinations among proposed fault protection solutions of ungrounded MGs.
- Published
- 2016
32. 3D Printing Optical Engine for Controlling Material Microstructure
- Author
-
Kuang-Po Chang, Fang-Hei Tsau, De-Yau Lin, Chih-Hsien Wu, Ji-Bin Horng, Ching-Chih Lin, Ping-Han Wu, Wei-Chin Huang, Sung-Ho Liu, and Chuan-Sheng Chuang
- Subjects
0209 industrial biotechnology ,Selective laser melting ,Materials science ,business.industry ,Alloy ,Process (computing) ,3D printing ,Mechanical engineering ,02 engineering and technology ,engineering.material ,Physics and Astronomy(all) ,021001 nanoscience & nanotechnology ,Microstructure ,material microstructure ,020901 industrial engineering & automation ,Thermal ,engineering ,Head (vessel) ,0210 nano-technology ,business ,Aerospace ,additive manufacturing - Abstract
Controlling the cooling rate of alloy during melting and resolidification is the most commonly used method for varying the material microstructure and consequently the resuling property. However, the cooling rate of a selective laser melting (SLM) production is restricted by a preset optimal parameter of a good dense product. The head room for locally manipulating material property in a process is marginal. In this study, we invent an Optical Engine for locally controlling material microstructure in a SLM process. It develops an invovative method to control and adjust thermal history of the solidification process to gain desired material microstucture and consequently drastically improving the quality. Process parameters selected locally for specific materials requirement according to designed characteristics by using thermal dynamic principles of solidification process. It utilize a technique of complex laser beam shape of adaptive irradiation profile to permit local control of material characteristics as desired. This technology could be useful for industrial application of medical implant, aerospace and automobile industries.
- Published
- 2016
- Full Text
- View/download PDF
33. Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognostic factor in hepatitis C virus-related hepatocellular carcinoma.
- Author
-
Ching-Chih Lin, Ta-Wei Liu, Ming-Lun Yeh, Yi-Shan Tsai, Pei-Chien Tsai, Chung-Feng Huang, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, and Ming-Lung Yu
- Published
- 2021
- Full Text
- View/download PDF
34. Spatial Humanities: An Integrated Approach to Spatiotemporal Research
- Author
-
Ching-Chih Lin, James X. Morris, and David Blundell
- Subjects
Geographic information system ,Computer science ,business.industry ,media_common.quotation_subject ,Timeline ,Integrated approach ,Interactive graphics ,Chart ,Digital humanities ,Information system ,Function (engineering) ,business ,Humanities ,media_common - Abstract
Spatial humanities are a sub-discipline of digital humanities based on geographic information systems (GIS) and timelines providing an effective integrating and contextualizing function for geo-cultural attributes. As information systems from multiple sources and in multiple formats they create visual indexes for diverse cultural data. Spatiotemporal interfaces provide new methods of integrating primary source materials into web-based interactive and 3D visualizations. We are able to chart the extent of specific traits of cultural information via maps using GIS gazetteer style spreadsheets for collecting and curating datasets.
- Published
- 2018
35. 8. Yiguandao under the Shadow of Nationalism: Traitors, Conspirators, Traditionalists, or Loyalists?
- Author
-
Ching-chih Lin
- Subjects
Political science ,Religious studies ,Shadow (psychology) ,Nationalism - Published
- 2017
36. Yiguandao under the Shadow of Nationalism
- Author
-
Ching-chih Lin
- Published
- 2017
37. 3D printed 'smart screw' with built-in LC sensing circuit for wireless monitoring
- Author
-
Chuan-Sheng Chuang, De-Yau Lin, Wei-Chin Huang, Sung-Ho Liu, Ching-Chih Lin, Sung-Yueh Wu, and An-Li Chen
- Subjects
Materials science ,business.industry ,Electrical engineering ,3D printing ,Resonance ,020206 networking & telecommunications ,02 engineering and technology ,Bending ,LC circuit ,Deformation (meteorology) ,021001 nanoscience & nanotechnology ,law.invention ,law ,Electrical network ,0202 electrical engineering, electronic engineering, information engineering ,Wireless ,RLC circuit ,0210 nano-technology ,business - Abstract
This work presents a novel "smart screw" with built-in electrical circuit for sensing. Comparing to conventional screw for industrial application, the designed smart screw contains an inductor-capacitor resonant circuit, of which the resonance frequency is determined by the gap of the structure inside the smart screw. As the gap is changed due to external force or the deformation of the smart screw, the resonance frequency will shift or vanish and be detected wirelessly by an inductive reader in real-time. As a proof-of-concept, M24 smart screws were fabricated by metallic three-dimensional printing. The LC circuit, formed by selective-laser-melting of titanium together with the screw body, is found to have the initial resonance frequency 162.77 MHz. It showed −2.7% and 10.5% frequency shifts during compression and bending tests, respectively. As the deformation exceeded certain level, the resonance even vanished. Both the shift and vanishment of resonance are sensing indicators. This work enables an innovative scheme for wireless built-in sensing application for high-value mechanical components.
- Published
- 2017
38. PECTIN METHYLESTERASE34 Contributes to Heat Tolerance through Its Role in Promoting Stomatal Movement
- Author
-
Ching-Chih Lin, Chia-Hung Liu, Dan-Li Luo, Hui-Chen Wu, Yin-Da Wang, Tsung-Luo Jinn, and Ya-Chen Huang
- Subjects
0301 basic medicine ,food.ingredient ,animal structures ,Pectin ,Physiology ,Research Articles - Focus Issue ,Arabidopsis ,Plant Science ,macromolecular substances ,complex mixtures ,Cell wall ,03 medical and health sciences ,chemistry.chemical_compound ,food ,Cell Wall ,Gene Expression Regulation, Plant ,Guard cell ,Genetics ,Plant defense against herbivory ,Pectinase ,Gene ,Abscisic acid ,biology ,Arabidopsis Proteins ,digestive, oral, and skin physiology ,Cell Membrane ,food and beverages ,Plant Transpiration ,biology.organism_classification ,Plants, Genetically Modified ,030104 developmental biology ,Biochemistry ,chemistry ,Mutation ,Plant Stomata ,Carboxylic Ester Hydrolases ,Heat-Shock Response ,Abscisic Acid - Abstract
Pectin, a major component of the primary cell wall, is synthesized in the Golgi apparatus and exported to the cell wall in a highly methylesterified form, then is partially demethylesterified by pectin methylesterases (PMEs; EC 3.1.1.11). PME activity on the status of pectin methylesterification profoundly affects the properties of pectin and, thereby, is critical for plant development and the plant defense response, although the roles of PMEs under heat stress (HS) are poorly understood. Functional genome annotation predicts that at least 66 potential PME genes are contained in Arabidopsis (Arabidopsis thaliana). Thermotolerance assays of PME gene T-DNA insertion lines revealed two null mutant alleles of PME34 (At3g49220) that both consistently showed reduced thermotolerance. Nevertheless, their impairment was independently associated with the expression of HS-responsive genes. It was also observed that PME34 transcription was induced by abscisic acid and highly expressed in guard cells. We showed that the PME34 mutation has a defect in the control of stomatal movement and greatly altered PME and polygalacturonase (EC 3.2.1.15) activity, resulting in a heat-sensitive phenotype. PME34 has a role in the regulation of transpiration through the control of the stomatal aperture due to its cell wall-modifying enzyme activity during the HS response. Hence, PME34 is required for regulating guard cell wall flexibility to mediate the heat response in Arabidopsis.
- Published
- 2017
39. The Universe, Life and Everything
- Author
-
Sarah Durston, Ton Baggerman, Chi-shen Chang, Yuan-lin Tsai, Ching-chih Lin, Shu-wei Hsieh, Yen-zen Tsai, and Hsun Chang
- Abstract
Our current understanding of our world is nearly 350 years old. It stems from the ideas of Descartes and Newton and has brought us many great things, including modern science and increases in wealth, health and everyday living standards. Furthermore, it is so ingrained in our daily lives that we have forgotten it is a paradigm, not a fact. There are, however, some problems with it. First, there is no satisfactory explanation for why we have consciousness and experience meaning in our lives. Second, modern-day physics tells us that observations depend on characteristics of the observer at the large, cosmic, and small, subatomic scales. Third, ongoing humanitarian and environmental crises show us that our world is vastly interconnected. Our understanding of reality is expanding to incorporate these issues. In The Universe, Life and Everything . . . Dialogues on our Changing Understanding of Reality, some of the scholars at the forefront of this change, from the fields of physics, psychology, and social sciences, discuss the direction it is taking and its urgency.
- Published
- 2017
40. Diversity of the association of serum levels and genetic variants of MHC class I polypeptide-related chain A with liver fibrosis in chronic hepatitis C
- Author
-
Ching-Chih Lin, Jee-Fu Huang, Kuan-Yu Chen, Ming-Lun Yeh, Ming-Lung Yu, Chung-Feng Huang, Ching-I Huang, Yi-Shan Tsai, Pei-Chien Tsai, Zu-Yau Lin, Shu-Chi Wang, Yu-Min Ko, Chia-Yen Dai, Shinn-Cherng Chen, and Wan-Long Chuang
- Subjects
0301 basic medicine ,Gerontology ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Liver fibrosis ,SNP ,Single-nucleotide polymorphism ,Gastroenterology ,03 medical and health sciences ,Liver disease ,Internal medicine ,Genotype ,Biopsy ,medicine ,Genetic predisposition ,Humans ,liver fibrosis ,sMICA ,medicine.diagnostic_test ,business.industry ,Histocompatibility Antigens Class I ,Genetic Variation ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,stomatognathic diseases ,CHC ,030104 developmental biology ,Oncology ,Hepatocellular carcinoma ,MICA ,Female ,business ,Biomedical sciences ,Research Paper - Abstract
// Chung-Feng Huang 1, 2, 3 , Ching-I Huang 1 , Ming-Lun Yeh 1, 2 , Shu-Chi Wang 1 , Kuan-Yu Chen 1 , Yu-Min Ko 1 , Ching-Chih Lin 1 , Yi-Shan Tsai 1 , Pei-Chien Tsai 1 , Zu-Yau Lin 1, 2 , Shinn-Cherng Chen 1, 2 , Chia-Yen Dai 1, 2, 3, 4 , Jee-Fu Huang 1, 2 , Wan-Long Chuang 1, 2 , Ming-Lung Yu 1, 2, 5, 6 1 Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 2 Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Department of Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 4 Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 6 Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Correspondence to: Ming-Lung Yu, email: fish6069@gmail.com Keywords: MICA, SNP, sMICA, liver fibrosis, CHC Received: October 15, 2016 Accepted: February 22, 2017 Published: March 06, 2017 ABSTRACT Background/Aims: Genetic variants of MHC class I polypeptide-related chain A (MICA) at rs2596542 have been associated with hepatocellular carcinoma. The linkage between serum MICA (sMICA) and liver fibrosis in chronic hepatitis C is elusive. Results: Linear regression analysis revealed that sMICA were independently correlated to α-fetoprotein (β: 0.149; 95% confidence interval [CI]: 0.001, 0.003; P = 0.007)and MICA rs2596542 GG genotype (β: 0.209; 95% CI: 0.153, 0.483; P 50 pg/mL provided a positive predictive value of 72 % in predicting advanced liver fibrosis (F3-4) and of 90% in significant fibrosis (> F2) in MICA rs2596542 A allele carriers. Materials and Methods: Serum level and single nucleotide polymorphism at rs2596542 of MICA were tested for the association with liver fibrosis in 319 biopsy proven chronic hepatitis C patients. Conclusions: Levels of sMICA were highly correlated to liver disease severity in chronic hepatitis C patients who carried the MICA rs738409 A allele. Patients possessing the genetic predisposition had a higher likelihood of progressed liver fibrosis if they expressed higher sMICA levels.
- Published
- 2016
41. Differential expression of centrosome-associated proteins in human brain tumors: A possible role of hNinein isoform 6 in cell differentiation
- Author
-
Ming-Chang Yang, Ann-Shung Lieu, Joon-Khim Loh, Chia-Hua Chou, Ching-Chih Lin, Fang-Yi Lin, Yi-Ren Hong, and Shen-Long Howng
- Subjects
Gene isoform ,Clinical Biochemistry ,Brain tumor ,Biology ,Biochemistry ,Tubulin ,medicine ,Humans ,Protein Isoforms ,RNA, Messenger ,Centrosome ,Brain Neoplasms ,Pituitary tumors ,Brain ,Nuclear Proteins ,Astrocytoma ,Cell Differentiation ,General Medicine ,Cell cycle ,medicine.disease ,Cell biology ,Reverse transcription polymerase chain reaction ,Cytoskeletal Proteins ,Centrin ,Cancer research ,Molecular Medicine ,Microtubule-Associated Proteins - Abstract
Dysregulated centrosomal expression has been observed in high grade gliomas. Thus, this study aimed to examine the expression of Aurora family kinase and various centrosomal proteins, including centrin, γ-tubulin, and hNinein isoforms, in human brain tumors, including 29 meningiomas, 34 astrocytomas, 6 pituitary adenomas, and 6 metastatic tumors. mRNA expression was evaluated using reverse transcription polymerase chain reaction. The role of hNinein isoform 6 expression in cell differentiation was assessed in BrdU-treated IMR-32 cells. Differential expression of centrosomal proteins of brain tumors and cell lines was observed. Specifically, centrin 2 and centrin 3 expression levels were classified as moderate or abundant in >97% of samples in the meningioma group, 63% of astrocytomas, >83% of metastatic and pituitary tumors. Alternatively, hNinein isoform 6 expression was only detected in normal brain and astrocytoma tumors (17/34); however, it was not expressed in meningioma (0/29), metastatic tumors (0/6) (P < 0.001). Of the six neuroblastoma cell lines analyzed only IMR-32 cells expressed hNinein isoform 6. Furthermore, downregulated expression of hNinein isoform 6 and upregulation of γ-tubulin was correlated to astrocytoma tumor grade (P < 0.001). Increased hNinein isoform 6 mRNA expression was observed in response to BrdU treatment, and its expression was greater in teratomas as compared to embryonic stem cells. Further studies are necessary to determine if hNinein isoform 6 functions as a tumor-suppressor gene in brain tumors. Differential centrosomal protein expression may result in altered centrosome function that is observed the in progression of various brain tumors. © 2012 International Union of Biochemistry and Molecular Biology, Inc.
- Published
- 2012
42. Dynamics of PBMC gene expression in hepatitis C virus genotype 1-infected patients during combined peginterferon/ribavirin therapy
- Author
-
Jee-Fu Huang, Meng-Hsuan Hsieh, Ching-Chih Lin, Tusty-Juan Hsieh, Shinn-Cherng Chen, Wan-Long Chuang, Edward Hsi, Po-Cheng Liang, Ming-Ying Lu, Pei-Chien Tsai, Ming-Lung Yu, Zu-Yau Lin, Nai-Jen Hou, Ming-Lun Yeh, Ming-Yen Hsieh, Chia-Yen Dai, Yi-Hung Lin, Ching-I Huang, Chung-Feng Huang, and Yi-Shan Tsai
- Subjects
0301 basic medicine ,Male ,Hepacivirus ,medicine.disease_cause ,Polyethylene Glycols ,Cohort Studies ,chemistry.chemical_compound ,0302 clinical medicine ,Interferon ,Traditional medicine ,sustained virologic response ,virus diseases ,Hepatitis C ,interferon ,Middle Aged ,Gene Expression Regulation, Neoplastic ,Real-time polymerase chain reaction ,Treatment Outcome ,Oncology ,030211 gastroenterology & hepatology ,Drug Therapy, Combination ,Female ,Viral load ,medicine.drug ,Research Paper ,Adult ,Genotype ,Hepatitis C virus ,Antiviral Agents ,Virus ,03 medical and health sciences ,Ribavirin ,medicine ,Humans ,Rapid Virologic Response ,Aged ,business.industry ,Sequence Analysis, RNA ,Gene Expression Profiling ,Interferon-alpha ,Hepatitis C, Chronic ,medicine.disease ,digestive system diseases ,030104 developmental biology ,chemistry ,Gene Expression Regulation ,Immunology ,Leukocytes, Mononuclear ,hepatitis C ,business - Abstract
Hepatitis C virus (HCV) can replicate in peripheral blood mononuclear cells (PBMCs), which can produce interferon to defend against virus infection. We hypothesized that dynamic gene expression in PBMCs might impact the treatment efficacy of peginterferon/ribavirin in HCV patients. PBMCs were collected at baseline, 1st week and 4th week of treatment from 27 chronic HCV-1 patients with 48-week peginterferon/ribavirin therapy (screening dataset n = 7; validation dataset n = 20). A sustained virologic response (SVR) was defined as undetectable HCV RNA throughout the 24 weeks after end-of-treatment. A complete early virologic response (cEVR) was defined as negative HCV RNA at treatment week 12. Forty-three differentially expressed genes identified by Affymetrix microarray were validated by quantitative polymerase chain reaction. Thirteen genes at week 1 and 24 genes at week 4 were upregulated in the SVR group compared with the non-SVR group. We selected 8 target genes (RSAD2, LOC26010, HERC5, HERC6, IFI44, SERPING1, IFITM3, and DDX60) at week 1 as the major components of the predictive model. This predictive model reliably stratified the responders and non-responders at week 1 (AUC = 0.89, p = 0.007 for SVR; AUC = 0.95, p = 0.003 for cEVR), especially among patients carrying the IL28B rs8099917 TT genotype (AUC = 0.89, p = 0.02 for SVR; AUC = 1.0, p = 0.008 for cEVR). The performance of this predictive model was superior to traditional predictors, including the rapid virologic response, viral load and IL28B genotype.
- Published
- 2016
43. GSK3β regulates Bcl2L12 and Bcl2L12A anti-apoptosis signaling in glioblastoma and is inhibited by LiCl
- Author
-
Ching-Mei Hsu, Joon-Khim Loh, Wei-Jay Chen, Shen-Long Howng, Ming-Chang Yang, Chia-Hua Chou, Yi-Ren Hong, For-Wey Lung, Ching-Chih Lin, Chih-Chang Wei, and An-Kuo Chou
- Subjects
Muscle Proteins ,Apoptosis ,tau Proteins ,Biology ,Glycogen Synthase Kinase 3 ,GSK-3 ,Cell Line, Tumor ,Two-Hybrid System Techniques ,medicine ,Humans ,Protein Isoforms ,Staurosporine ,Phosphorylation ,Molecular Biology ,GSK3B ,Glycogen Synthase Kinase 3 beta ,Brain Neoplasms ,Kinase ,HEK 293 cells ,Cell Biology ,Molecular biology ,Protein Structure, Tertiary ,HEK293 Cells ,Proto-Oncogene Proteins c-bcl-2 ,Ectopic expression ,Signal transduction ,Glioblastoma ,Lithium Chloride ,Protein Binding ,Signal Transduction ,Developmental Biology ,medicine.drug - Abstract
BCL2L12 has been reported to be involved in post-mitochondrial apoptotic events in glioblastoma, but the role of BCL2L12A, a splicing variant of BCL2L12, remains unknown. In this study, we showed that BCL2L12 and BCL2L12A were overexpressed in glioblastoma multiforme (GBM). Large-scale yeast two-hybrid screening showed that BCL2L12 was a GSK3b binding partner in a testis cDNA library. Our data demonstrated that GSK3b interacts with BCL2L12 but not BCL2L12A, whose C terminus lacks a binding region. We found that a BCL2L12(153-191) fragment located outside of the C-terminal BH2 motif is responsible for GSK3b binding. In contrast, no interaction was detected between BCL2L12A and GSK3b. In vitro kinase and l-phosphatase assays showed that GSK3b phosphorylates BCL2L12 at S156, while this site is absent on BCL2L12A. Moreover, our data also showed that the BCL2L12(153-191) fragment directly interrupted GSK3bmediated Tau phosphorylation in a dose-dependent manner. Ectopic expression of GFP-fused BCL2L12 or BCL2L12A in U87MG cells leads to repression of apoptotic markers and protects against staurosporine (STS) insults, indicating an antiapoptotic role for both BCL2L12 and BCL2L12A. In contrast, no anti-apoptotic ability was seen in BCL2L12(S156A). When BCL2L12-expressing U87MG cells were co-administrated with STS and LiCl, cells underwent apoptosis. This effect could be reversed by LiCl. In short, we established a model to demonstrate that GSK3b interacts with and phosphorylates BCL2L12 and might also affect BCL2L12A to modulate the apoptosis signaling pathway in glioblastoma. These findings suggest that LiCl may be a prospective therapeutic agent against GBM.
- Published
- 2012
44. Nondestructive web thickness measurement of micro-drills with an integrated laser inspection system
- Author
-
Y.S. Tarng, Wen-Tung Chang, Shui-Fa Chuang, Ching-Chih Lin, and Yen-Chung Chen
- Subjects
Engineering ,Drill ,Nondestructive measurement ,business.industry ,Mechanical Engineering ,General Physics and Astronomy ,Mechanical engineering ,Fixture ,Laser ,law.invention ,Nominal size ,Printed circuit board ,Mechanics of Materials ,law ,Measuring principle ,Electronic engineering ,General Materials Science ,business - Abstract
Nowadays, the electric and semiconductor industries use numerous micro-drills to machine micro-holes in printed circuit boards. The measurement of web thickness of micro-drills, a key parameter of micro-drill geometry influencing drill rigidity and chip-removal ability, is quite important to ensure quality control. Traditionally, inefficiently destructive measuring method is adopted by inspectors. To improve quality and efficiency of the web thickness measuring tasks, a nondestructive measuring method is required. In this paper, based on the laser micro-gauge (LMG) and laser confocal displacement meter (LCDM) techniques, a nondestructive measuring principle of web thickness of micro-drills is introduced. An integrated laser inspection system, mainly consisting of a LMG, a LCDM and a two-axis-driven micro-drill fixture device, was developed. Experiments meant to inspect web thickness of micro-drill samples with a nominal diameter of 0.25 mm were conducted to test the feasibility of the developed laser insp...
- Published
- 2010
45. GSKIP is homologous to the axin GSK3[beta] interaction domain and functions as a negative regulator of GSK3[beta]
- Author
-
He-Yen Chou, Shen-Long Howng, Tai-Shan Cheng, Yun-Ling Hsiao, Ann-Shung Lieu, Joon-Khim Loh, Shiuh-Lin Hwang, Ching-Chih Lin, Ching-Mei Hsu, Chihuei Wang, Chu-I Lee, Pei-Jung Lu, Chen-Kung Chou, Chi-Ying Huang, and Yi-Pen Hong
- Subjects
Phosphorylation -- Analysis ,Glycogen -- Research ,Biological sciences ,Chemistry - Abstract
A study was conducted to identify a naturally occurring GSK3[beta] binding protein, GSK3[beta] interaction protein (GSKIP), whose C-terminal region possesses a 25-amino acid region similar to [GID.sub.381-405] of axin. The results indicate that GSKIP is a good GSK3[beta] substrate, and both the full-length protein and a C-terminal fragment of GSKIP could block phosphorylation of primed and nonprimed substrates in different fashions.
- Published
- 2006
46. 2-(6-Aryl-3(Z)-hexen-1,5-diynyl)anilines as a New Class of Potent Antitubulin Agents
- Author
-
Ying-Ting Lin, Shinne-Ren Lin, Ching-Chih Lin, Chi-Fong Lin, Yu-Hsiang Lo, Hong Yi-Ren, Tsai-Hui Duh, Sheng-Huei Yang, Shyh-Chyun Yang, Long-Sen Chang, and Ming-Jung Wu
- Subjects
Stereochemistry ,Microtubules ,Chemical synthesis ,Structure-Activity Relationship ,chemistry.chemical_compound ,Biopolymers ,Tubulin ,Cell Line, Tumor ,Drug Discovery ,Humans ,Caspase ,Cell Proliferation ,chemistry.chemical_classification ,Aniline Compounds ,biology ,Cell Cycle ,Aromatic amine ,Stereoisomerism ,Tubulin Modulators ,chemistry ,Cell culture ,Apoptosis ,Cancer cell ,biology.protein ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Growth inhibition ,Aliphatic compound - Abstract
Compounds 2a- h and 6 displayed significant GI 50 values of 10(-7)-10(-6) M against various cancer cell lines. Of these compounds, 2-(6-(2-trifluoromethylphenyl))-3(Z)-hexen-1,5-diynyl)aniline (2c) showed the most potent growth inhibition activity. Compound 2c also arrested cancer cells in the G2/M phase and in low concentration reduced a significant percentage of MDA-MB-231/ATCC breast cancer tetraploid cells. In addition to the G2/M block, compound 2c caused microtubule depolymerization and induced apoptosis via activation of the caspase family.
- Published
- 2008
47. Characterization and Functional Aspects of Human Ninein Isoforms that Regulated by Centrosomal Targeting Signals and Evidence for Docking Sites to Direct Gamma-Tubulin
- Author
-
Ching-Chih Lin, Ching-Mei Hsu, Long-Sen Chang, Hung-Ming Yeh, Shen-Long Howng, Yi-Ren Hong, Zhi-Shiang Shen, Li-Kwan Chang, Tai-Shan Cheng, and Che-Hsiang Wu
- Subjects
Gene isoform ,Centriole ,Protein Conformation ,Molecular Sequence Data ,Biology ,Glycogen Synthase Kinase 3 ,Tubulin ,Microtubule ,Humans ,Protein Isoforms ,Tissue Distribution ,Amino Acid Sequence ,Molecular Biology ,Microtubule nucleation ,Centrosome ,Glycogen Synthase Kinase 3 beta ,Sequence Homology, Amino Acid ,Nuclear Proteins ,Cell Biology ,Fusion protein ,Protein Structure, Tertiary ,Cell biology ,Microtubule minus-end ,Cytoskeletal Proteins ,Gene Expression Regulation ,biology.protein ,HeLa Cells ,Protein Binding ,Developmental Biology - Abstract
The functions of centrosomal protein ninein may be involved in microtubule minus end capping, centriole positioning, protein anchoring and microtubule nucleation, but the true physiological function of various human hNinein isoforms remains to be determined. Here we describe the identification of four diverse CCII-termini of human hNinein isoforms, including a novel isoform 6, by differential expression in a tissue-specific manner. These hNinein isoforms exhibit centrosomal (concentrated) and noncentrosomal (aggregated) localization when GFP-tagged fusion proteins are expressed transiently in mammalian cells. In a kinase assay, we show that the CCII region of hNinein provides a differential phosphorylation site by GSK3beta. In addition, our data indicate that either N-terminal or CCIIZ domain disruption may cause hNinein conformational change which recruits gamma-tubulin to centrosomal or noncentrosomal hNinein-containing sites, implying that the gamma-tubulin localization may be hNinein-dependent. Further, our RNA interference experiment against all hNinein isoforms caused a significant decrease in the gamma-tubulin signal in the centrosome. In domain swapping, we clearly show that the CCIIX-CCIIY region provides docking sites for gamma-tubulin. Moreover, our data also show that nucleation of microtubules from the centrosome is significantly affected by the presence of either the full -length hNinein or CCIIX-CCIIY region overexpression. Taken together, these results show that the centrosomal targeting signals of hNinein have a role not only in regulating hNinein conformation, resulting in localization change, but also provide docking sites to recruit gamma-tubulin at centrosomal and noncentrosomal sites.
- Published
- 2006
48. Identification of groups with poor cost-effectiveness of peginterferon plus ribavirin for naïve hepatitis C patients with a real-world cohort and database
- Author
-
Po-Cheng Liang, Shinn-Cherng Chen, Wan-Long Chuang, Yi-Hung Lin, Ta-Wei Liu, Nai-Jen Hou, Ching-Chih Lin, Chia-Yen Dai, Chung-Feng Huang, Ming-Yen Hsieh, Ching-I Huang, Ming-Lung Yu, Yi-Shan Tsai, Pei-Chien Tsai, Zu-Yau Lin, Kuan-Yu Chen, Jee-Fu Huang, Ming-Lun Yeh, and Yu-Min Ko
- Subjects
Male ,Pediatrics ,Databases, Factual ,National Health Programs ,Cost effectiveness ,Cost-Benefit Analysis ,Polyethylene Glycols ,Cohort Studies ,chemistry.chemical_compound ,0302 clinical medicine ,Ambulatory Care ,cost-effectiveness analysis ,virus diseases ,Health Care Costs ,General Medicine ,Hepatitis C ,Middle Aged ,Viral Load ,Recombinant Proteins ,treatment-naïve ,Hospitalization ,Treatment Outcome ,030220 oncology & carcinogenesis ,Cohort ,chronic hepatitis c ,Drug Therapy, Combination ,Female ,030211 gastroenterology & hepatology ,sustained virological response ,Viral load ,Research Article ,Cohort study ,Adult ,medicine.medical_specialty ,ribavirin ,Taiwan ,Antiviral Agents ,03 medical and health sciences ,Pharmacotherapy ,Chronic hepatitis ,medicine ,Humans ,pegylated interferon ,Economic Evaluation Study ,business.industry ,Ribavirin ,Hepatitis C, Chronic ,medicine.disease ,digestive system diseases ,chemistry ,Immunology ,Interferons ,business - Abstract
Background: For decades, peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (CHC) infection. However, the actual cost-effectiveness of this therapy remains unclear. We purposed to explore the real-world cost effectiveness for subgroups of treatment-naïve CHC patients with PegIFN/RBV therapy in a large real-world cohort using a whole population database. Methods: A total of 1809 treatment-naïve chronic hepatitis C virus (HCV) patients (829 HCV genotype 1 [G1] and 980 HCV G2) treated with PegIFN/RBV therapies were linked to the National Health Insurance Research Database, covering the entire population of Taiwan from 1998 to 2013 to collect the total medical-care expenses of outpatient (antiviral agents, nonantiviral agents, laboratory, and consultation costs) and inpatient (medication, logistic, laboratory, and intervention costs) visits. The costs per treatment and the cost per sustained virological response (SVR) achieved were calculated. Results: The average medical-care cost was USD $4823 (±$2984) per treatment and $6105 (±$3778) per SVR achieved. With SVR rates of 68.6% and 87.8%, the cost/SVR was significantly higher in G1 than those in G2 patients, respectively ($8285 vs $4663, P
- Published
- 2017
49. Corrigendum to 'Genetics Variants and Serum Levels of MHC Class I Chain-related A in Predicting Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients Post Antiviral Treatment' [EBioMedicine 15 (2017) 81–89]
- Author
-
Yu-Min Ko, Chung-Feng Huang, Shinn-Cherng Chen, Wan-Long Chuang, Ming-Lun Yeh, Ching-I Huang, Pei-Chien Tsai, Yi-Shan Tsai, Shu-Chi Wang, Kuan-Yu Chen, Jee-Fu Huang, Ming-Lung Yu, Zu-Yau Lin, Ching-Chih Lin, and Chia-Yen Dai
- Subjects
Liver Cirrhosis ,Male ,IL-28B, interleukin-28B ,lcsh:Medicine ,AST, aspartate aminotransferase ,030204 cardiovascular system & hematology ,Cohort Studies ,IL-28 ,0302 clinical medicine ,CHC, chronic hepatitis C ,APRI, the aspartate aminotransferase-to-platelet ratio index ,HCC ,lcsh:R5-920 ,AFP, α-fetoprotein ,Incidence ,Liver Neoplasms ,General Medicine ,Middle Aged ,Prognosis ,HCV, hepatitis C virus ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,MICA, MHC class I chain-related A ,Female ,SNP, single-nucleotide polymorphism ,lcsh:Medicine (General) ,Corrigendum ,Research Paper ,Adult ,PNPLA3, patatin-like phospholipase domain-containing 3 ,SVR ,Carcinoma, Hepatocellular ,Genotype ,SNP ,Biology ,Antiviral Agents ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Chronic hepatitis ,ALT, alanine aminotransferase ,MHC class I ,medicine ,Humans ,Antiviral treatment ,PNPLA3 ,Alleles ,EGF ,Aged ,EGF, epidermal growth factor ,sMICA ,lcsh:R ,Histocompatibility Antigens Class I ,Genetic Variation ,Hepatitis C, Chronic ,medicine.disease ,Virology ,digestive system diseases ,Treatment ,MICA ,Immunology ,biology.protein ,Follow-Up Studies - Abstract
Background/aims The genome-wide association study has shown that MHC class I chain-related A (MICA) genetic variants were associated with hepatitis C virus (HCC) related hepatocellular carcinoma. The impact of the genetic variants and its serum levels on post-treatment cohort is elusive. Methods MICA rs2596542 genotype and serum MICA (sMICA) levels were evaluated in 705 patients receiving antiviral therapy. Results Fifty-eight (8·2%) patients developed HCC, with a median follow-up period of 48·2 months (range: 6–129 months). The MICA A allele was associated with a significantly increased risk of HCC development in cirrhotic non-SVR patients but not in patients of non-cirrhotic and/or with SVR. For cirrhotic non-SVR patients, high sMICA levels (HR/CI: 5·93/1·86–26.38·61, P = 0·002) and the MICA rs2596542 A allele (HR/CI: 4·37/1·52–12·07, P = 0·002) were independently associated with HCC development. The risk A allele or GG genotype with sMICA > 175 ng/mL provided the best accuracy (79%) and a negative predictive value of 100% in predicting HCC. Conclusions Cirrhotic patients who carry MICA risk alleles and those without risk alleles but with high sMICA levels possessed the highest risk of HCC development once they failed antiviral therapy., Highlights • MICA rs2596542 SNP predicts HCC development in LC patients with persistent viremia. • High sMICA levels predicts HCC occurrence in LC patients without SVR • Combining the 2 surrogate markers enhance the predicting power of HCC. The genome-wide association study has shown that MHC class I chain-related A (MICA) genetic variants were associated with hepatitis C virus (HCC) related hepatocellular carcinoma. The impact of the genetic variants and its serum levels on post-treatment cohort is elusive. We demonstrated that cirrhotic patients who carry MICA risk alleles and those without risk alleles but with high sMICA levels possessed the highest risk of HCC development once they failed antiviral therapy. Combining the host genetic variants of MICA gene and serum levels of MICA proteins greatly enhanced the predictive power in the high-risk population, which provides insight for closer follow-up strategies and re-treatment priority in the era of direct antiviral agents.
- Published
- 2017
50. GSK3beta-Mediated Drp1 Phosphorylation Induced Elongated Mitochondrial Morphology against Oxidative Stress
- Author
-
An-Kuo Chou, Chia-Hua Chou, Huei-De Liao, Yi-Ren Hong, Chu-I Lee, Chih-Chang Wei, Ching-Mei Hsu, Ming-Chang Yang, Run-Chin Lin, Ching-Chih Lin, Joon-Khim Loh, Shen-Long Howng, Tsung-Chieh Kao, Jiin-Tsuey Cheng, and Wen-Yu Tu
- Subjects
lcsh:Medicine ,Apoptosis ,Mitochondrion ,Signal transduction ,Biochemistry ,Mitochondrial Dynamics ,GTP Phosphohydrolases ,Serine ,chemistry.chemical_compound ,Glycogen Synthase Kinase 3 ,Phosphoserine ,Molecular cell biology ,GSK-3 ,Threonine ,Phosphorylation ,lcsh:Science ,Energy-Producing Organelles ,Apoptotic Signaling Cascade ,Cellular Stress Responses ,Multidisciplinary ,biology ,Cell Death ,Cytochrome c ,Hydrolysis ,Signaling Cascades ,Cell biology ,Mitochondria ,Protein Transport ,Research Article ,Protein Binding ,Dynamins ,endocrine system ,Signaling in cellular processes ,Molecular Sequence Data ,macromolecular substances ,Bioenergetics ,Models, Biological ,Two-Hybrid System Techniques ,Autophagy ,Humans ,Amino Acid Sequence ,Biology ,GTPase signaling ,Glycogen Synthase Kinase 3 beta ,Lysine ,lcsh:R ,Hydrogen Peroxide ,Molecular biology ,Apoptotic signaling ,Protein Structure, Tertiary ,enzymes and coenzymes (carbohydrates) ,Oxidative Stress ,HEK293 Cells ,chemistry ,biology.protein ,lcsh:Q ,Mutant Proteins ,Antiapoptotic signaling ,HeLa Cells - Abstract
Multiple phosphorylation sites of Drp1 have been characterized for their functional importance. However, the functional consequence of GSK3beta-mediated phosphorylation of Drp1 remains unclear. In this report, we pinpointed 11 Serine/Threonine sites spanning from residue 634~736 of the GED domain and robustly confirmed Drp1 Ser693 as a novel GSK3beta phosphorylation site. Our results suggest that GSK3beta-mediated phosphorylation at Ser693 does cause a dramatic decrease of GTPase activity; in contrast, GSK3beta-mediated phosphorylation at Ser693 appears not to affect Drp1 inter-/intra-molecular interactions. After identifying Ser693 as a GSK3beta phosphorylation site, we also determined that K679 is crucial for GSK3beta-binding, which strongly suggests that Drp1 is a novel substrate for GSK3beta. Thereafter, we found that overexpressed S693D, but not S693A mutant, caused an elongated mitochondrial morphology which is similar to that of K38A, S637D and K679A mutants. Interestedly, using H89 and LiCl to inhibit PKA and GSK3beta signaling, respectively, it appears that a portion of the elongated mitochondria switched to a fragmented phenotype. In investigating the biofunctionality of phosphorylation sites within the GED domain, cells overexpressing Drp1 S693D and S637D, but not S693A, showed an acquired resistance to H(2)O(2)-induced mitochondrial fragmentation and ensuing apoptosis, which affected cytochrome c, capase-3, -7, and PARP, but not LC3B, Atg-5, Beclin-1 and Bcl2 expressions. These results also showed that the S693D group is more effective in protecting both non-neuronal and neuronal cells from apoptotic death than the S637D group. Altogether, our data suggest that GSK3beta-mediated phosphorylation at Ser693 of Drp1 may be associated with mitochondrial elongation via down-regulating apoptosis, but not autophagy upon H(2)O(2) insult.
- Published
- 2012
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.