Ginsenoside compound K reduces the progression of Huntington's disease via the inhibition of oxidative stress and overactivation of the ATM/AMPK pathway

Kuo-Feng Hua,A-Ching Chao,Ting-Yu Lin,Wan-Tze Chen,Yu-Chieh Lee,Wan-Han Hsu,Sheau-Long Lee,Hsin-Min Wang,Ding-I. Yang,Tz-Chuen Ju 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.4

Background: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion oftrinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HDinvolve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinaseataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM isinvolved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays acritical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expandedmutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effectivecomponent of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HDremains unclear and warrants further investigation. Methods: This study used the R6/2 transgenic mouse model of HD and performed behavioral tests,survival rate, histological analyses, and immunoblot assays. Results: The systematic administration of CK into R6/2 mice suppressed the activation of ATM/AMPK andreduced neuronal toxicity and mHTT aggregation. Most importantly, CK increased neuronal density andlifespan and improved motor dysfunction in R6/2 mice. Conversely, CK enhanced the expression of Bcl2protected striatal cells from the toxicity induced by the overactivation of mHtt and AMPK. Conclusions: Thus, the oral administration of CK reduced the disease progression and markedlyenhanced lifespan in the transgenic mouse model (R6/2) of HD.

SURGICAL RESULTS IN ROTATOR CUFF LESIONS WITH ADHESIVE CAPSULITIS

Jih-Yang Ko,Mei-Hui Kuo,Han-Shiang Chen,Ching-Jen Wang 대한견주관절의학회 2002 대한견주관절학회 학술대회논문집 Vol.2002 No.5

Effect of Dietary Inclusion of Dehydrated Food Waste Products on Taiwan Native Chicken (Taishi No. 13)

Chen, Kuo-Lung,Chang, Hwang-Jen,Yang, Ching-Ke,You, Shanq-Huei,Jenq, Horng-Der,Yu, Bi Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.5

The effect of dehydrated food waste product (DFWP) inclusion in diets of Taiwan native chickens on the growth performance, carcass traits, clinical blood chemistry and nutrient digestibility was investigated with 320 male Taishi Native Chickens (Taishi No. 13). They were randomly allocated into four levels of DFWP inclusion (0, 5, 10, or 20%) treatment. Each treatment had 80 chickens with four replicates. At 15 weeks of age, 8 chickens were selected from each group for the nutrient digestibility trial. The results showed that body weight gain during the 0 to 4 week period decreased as the feed intake and feed conversion rate (FCR) increased linearly with increasing level of DFWP inclusion. During the 4 to 8 week period, greater body weight gains were recorded for the birds on the 5% DFWP inclusion level than for the control (p<0.05). During 8 to16 weeks, the feed intake and FCR increased linearly (p<0.05). Interestingly too, results of the carcass analysis showed that DFWP inclusion up to 20% in the diet significantly decreased the relative abdominal fat weight but increased the relative proventriculus and gizzard weights of the birds. However, other carcass parameters, meat quality and sensory scores were not significantly influenced by the dietary DFWP inclusion levels (p>0.05). Higher serum aspartate aminotransferase, ${\gamma}$-glutamyltransferase activity and crude protein digestibility, and lower gross energy digestibility were observed in the 20% DFWP group compared to the control (p<0.05). Dietary DFWP inclusion was inappropriate during the 0 to 4 week period. During 4 to 8 weeks, there was no adverse effect on chicken performance in the 20% group. There was no disadvantage on carcass properties and in the meat panel test. This result would not affect consumer determination.

Evolution of Multi-temporal Landslides at Luhu, Miaoli County, Taiwan

( Che-ming Yang ),( Keng-hao Kang ),( Kuo-wei Li ),( Hui-jung Wang ),( Ching-ping Hsiao ),( Jyh-jong Liao ),( Yii-wen Pan ) 대한지질공학회 2019 대한지질공학회 학술발표회논문집 Vol.2019 No.2

A deep-seated landslide took place in Luhu, Miao-Li, Taiwan during intermittent rainfall in April 2018; initially, there were successive rock falls and gully erosion then leaded to a deep-seated landslide failure eventually. This study aims to understand the failure mechanism and the process of deep-seated failure. The study site is a steep anaclinal slope consisting of the Miocence Shihti Formation with thick sandstone, interbedded of sandstone and shale. We collected multi-temporal ortho-images and digital elevation (surface) models from 1980 to 2019 for geological investigation, geomorphological interpretation and numerical simulation. The images reveal several slope failures at 1998, 2003, 2005, 2009, 2015, 2017 and 2018 with various volume and failure types. The study area contains three sub-regions: the north, the northwest and the southwest slopes. The slope failure occurred repeatedly inside the north and the northwest slopes in the early stage. Gully erosion in the southwest slope progressed to a landslide on April 5, 2018 first and expanded to cover the deep-seated landslide failure in the northwest slope eventually; the slope failure resulted in a natural dam. After the landslide, several open cracks appeared near to the crown. The estimated maximum thickness, area and volume of the deep-seated landslide are ~60 m, 65,000 m2 and ~2 Mm3, respectively. Based on these results, we also performed a series of numerical simulation using the software RAMMS to interpret the run out and the deposition of this landslide case.

Photocatalytic study of Zinc Oxide with bismuth doping prepared by spray pyrolysis

Lin, Tzu-Yang,Hsu, Yu-Ting,Lan, Wen-How,Huang, Chien-Jung,Chen, Lung-Chien,Huang, Yu-Hsuan,Lin, Jia-Ching,Chang, Kuo-Jen,Lin, Wen-Jen,Huang, Kai-Feng Techno-Press 2015 Advances in nano research Vol.3 No.3

The unintentionally doped and bismuth (Bi) doped zinc oxide (ZnO) films were prepared by spray pyrolysis at $450^{\circ}C$ with zinc acetate and bismuth nitrate precursor. The n-type conduction with concentration $6.13{\times}10^{16}cm^{-3}$ can be observed for the unintentionally doped ZnO. With the increasing of bismuth nitrate concentration in precursor, the p-type conduction can be observed. The p-type concentration $4.44{\times}10^{17}cm^{-3}$ can be achieved for the film with the Bi/Zn atomic ratio 5% in the precursor. The photoluminescence spectroscopy with HeCd laser light source was studied for films with different Bi doping. The photocatalytic activity for the unintentionally doped and Bi-doped ZnO films was studied through the photodegradation of Congo red under UV light illumination. The effects of different Bi contents on photocatalytic activity are studied and discussed. Results show that appropriate Bi doping in ZnO can increase photocatalytic activity.

Sofosbuvir/Ledipasvir in the Treatment of Chronic Hepatitis C - A Subgroup Analysis from A Nationwide Real-World HCV Registry Program (TACR) in Taiwan

( Ming-Lung Yu ),( Chi-Yi Chen ),( Kuo-Chih Tseng ),( Ching-Chu Lo ),( Pin-Nan Cheng ),( Cheng-Yuan Peng ),( Ming-Jong Bair ),( Chih-Lang Lin ),( Chi-Ming Tai ),( Chi-Chieh Yang ),( Chih-Wen Lin ),( C 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: TASL HCV Registry (TACR) is a nationwide registry program organized and supervised by Taiwan Association for the Study of the Liver (TASL), which aims to setup the database and biobank of patients with chronic hepatitis C (CHC) in Taiwan. The present study aimed to evaluate the treatment outcome of sofosbuvir (SOF)/ledipasvir (LDV) in Taiwanese CHC patients in TACR. Methods: By May 2020, 19 tertiary hospitals, 23 community hospitals and one primary care clinic join the TACR program. The baseline characteristics, prior liver and non-liver related medical history, DAA regimens, laboratory results, treatment course and outcome were recorded. The primary objective was sustained virological response, defined as undetectable HCV RNA 3 months after end-of-treatment (SVR12). Results: A total of 4742 SOF/LDV+ ribavirin treated CHC patients with available SVR12 data from 39 sites were enrolled in the current analysis. The mean age was 61.3 years, and female accounted for 54.8% of the population. The dominant viral genotypes were GT1b (52.6%) and GT2 (35.6%). 1354 (28.6%) patients had liver cirrhosis, including 156 (3.3%) with liver decompensation, 552 (11.6%) had preexisting hepatocellular carcinoma (HCC) before DAAs treatment and 413 (8.7%) had hepatitis B virus dual infections. The overall SVR12 rate was 98.5%, with 98.5%, 98.2%, 99.7% and 98.6% in treatment- naïve non-cirrhotics, treatment-naïve cirrhotics, treatment- experienced non-cirrhotics and treatment-experienced cirrhotics patients, respectively. While patients were stratified by HCV genotype, the SVR12 was 98.5%, 98.4% and 98.5% among those with GT1, GT2 and GT6 infection, respectively. The strongest factor independent associated with treatment failure was DAA adherence < 60% (odds ratio [OR]/95% confidence intervals [CI]: 125.4/25.7-612.4, P<0.0001), followed by active HCC (OR/CI: 6.20/2.57-14.97, P<0.0001), HIV co-infection (OR/CI: 3.01/1.14-7.92, P=0.026), and male gender (OR/ CI: 1.85/1.09-3.13, P=0.023). The eGFR decreased significantly at the end of treatment (EOT) (89.3 ml/min/1.73㎡ vs. 93.2 ml/min/1.73㎡, P< 0.001) and remained stable 3 months after EOT (89.3 ml/min/1.73㎡). However, the decreased eGFR was observed only in patients whose baseline eGFR > 90 ml/ min/1.73㎡. Instead, patients with chronic kidney diseases whose pretreatment eGFR < 60 ml/min/1.73㎡ had improved eGFR after SOF/LDV. Conclusions: SOF/LDV is highly effective in treating CHC patients in real-world setting of Taiwan. The satisfactory result could be explicitly generalized to patients with different viral genotypes and liver disease severities.

Controlled Release of Clenbuterol from a Hydroxyapatite Carrier for the Treatment of Alzheimer’s Disease

Yi-Wen Lin,Chih-Hsiang Fang,Ya-Jyun Liang,Ching-Yun Yang,Wei-Ting Kuo,Feng-Huei Lin 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background Alzheimer’s disease is a neurodegenerative disorder, and Aβ aggregation is considered to be the central process implicated in its pathogenesis. Current treatments are faced by challenges such as serious side effects and reduced drug bioavailability. In this study, we developed a drug delivery system for intramuscular injection that uses cellular activity to achieve constant and long-term drug release. Methods Synthesized mesoporous hydroxyapatite (SHAP) was prepared via co-precipitation, and hydrophobic surface modification using stearic acid was then used to load clenbuterol by physical absorption, thus creating the drug delivery system. Clenbuterol release was achieved through cellular activity, with macrophage uptake triggering lysosome/endosome disruption, cytoplasmic release, extracellular exocytosis, and subsequent systemic circulation. Results We found that clenbuterol-loaded SHAP enabled sustained release for more than 2 weeks and effectively modulated inflammation, reduced Aβ oligomer-induced toxicity, and prevented Aβ aggregation. Conclusions Our findings suggest that treatment with clenbuterol loaded in this SHAP delivery system could be a promising strategy for treating Alzheimer’s disease.

Sofosbuvir/velpatasvir plus ribavirin for Child-Pugh B and Child-Pugh C hepatitis C virus-related cirrhosis

( Chen-hua Liu ),( Chi-yi Chen ),( Wei-wen Su ),( Chun-jen Liu ),( Ching-chu Lo ),( Ke-jhang Huang ),( Jyh-jou Chen ),( Kuo-chih Tseng ),( Chi-yang Chang ),( Cheng-yuan Peng ),( Yu-lueng Shih ),( Chia 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.4

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR₁₂) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. The safety profiles were reported. Results: The SVR₁₂ rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5-94.2%), 94.1% (95% CI, 87.8-97.3%), and 100% (95% CI, 96.2-100%). Number of patients who failed to achieve SVR₁₂ were attributed to virologic failures. The SVR₁₂ rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR₁₂, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16-14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 ㎡/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 ㎡/month; P<0.001). Conclusions: SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis. (Clin Mol Hepatol 2021;27:575-588)

Tenofovir Alafenamide for Chronic Hepatitis B Patients with Advanced Fibrosis and Partial Virologic Responses to Oral Nucleos(T)Ide Analogues- Interim Report

( Ming-lung Yu ),( Ming-lun Yeh ),( Chi-yi Chen ),( Pin-nan Cheng ),( Ming-jong Bair ),( Jyh-jou Chen ),( Ching-chu Lo ),( Chi-ming Tai ),( Ching-yang Tsai ),( Kuo-chih Tseng ),( Chien-hung Chen ),( C 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Insufficient data regarding the treatment strategy for partial response to nucleot(s)ide analogue (NUC) raised the aim of investigating tenofovir alafenamide (TAF) switching for chronic hepatitis B (CHB) patients with advanced fibrosis and partial response to other NUCs. Methods: CHB patients with advanced fibrosis (stage 3 or 4) and under NUC (except TAF) therapy with detectable hepatitis B virus (HBV) DNA for >52 weeks are enrolled to TAF 25 mg/day for 96 weeks. The objectives are viral suppression, alanine aminotransferase (ALT) normalization and safety. Results: From Feb. 2019, 34 patients, including 21 (61.8%) with entecavir, 10 (29.4%) TDF and 3 (8.8%) lamivudine or adefovir, were enrolled (15 [44.1%] male, median 53 years). The fibroscan demonstrated a mean of 10.5 kPa (7 [20.6%] cirrhotic). Sixteen (47.1%) patients were HBV e antigen positive, seven (20.6%) had YMDD mutation. The median HBV DNA level declined from 68.5 IU/mL at enrollment to 27.0 IU/mL at 4^th week, and undetectable at 12^th, 24^th, 36^th week, respectively, after TAF switching, with undetectable HBV DNA in 14/34 (41.2%), 17/33 (51.5%), 15/25 (60.0%), and 9/15 (60.0%) patients and rate of ALT normalization (≤40 U/L) of 85.3%, 85.3%, 84.8%, 92.0%, and 80.0%, respectively, after TAF switching. (figure 1) Two patients experienced transient virological breakthrough and another one developed at the final time follow up. Serum creatinine and eGFR levels were stable after TAF switching (figure 1). Two patients early terminated including one at 12^th week due to personal reason, and another one accidently died at 20^th week due to acute heart attack. Others suffered only mild degrees of adverse events which were considered unrelated to treatment. Conclusions: The preliminary results demonstrated the TAF switching is effective and safe in viral suppression for CHB patients with advanced fibrosis and partial virologic responses to other NUCs.

Angiogenic Blockade and Radiotherapy in Hepatocellular Carcinoma(초)

( Kwan Hwa Chi ),( Chao Sheng Liao ),( Chih Chia Chang ),( Hui Ling Ko ),( Yuk Wah Tsang ),( Kuo Ching Yang ),( Minesh P. Mehta ) 대한간암연구회 2010 대한간암학회지 Vol.10 No.-