1,022 results on '"Yang Chang Wu"'
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2. Glutathione S‐transferase omega class 1 (GSTO1)‐associated large extracellular vesicles are involved in tumor‐associated macrophage‐mediated cisplatin resistance in bladder cancer
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Yi‐Cheng Pan, Pei‐Yi Chu, Ching‐Chan Lin, Ching‐Yun Hsieh, Wei‐Yu Hsu, Lie‐Fen Shyur, Juan‐Cheng Yang, Wei‐Chao Chang, and Yang‐Chang Wu
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bladder cancer ,cisplatin resistance ,extracellular vesicle ,GSTO1 ,tumor‐associated macrophage ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Bladder cancer poses a significant challenge to chemotherapy due to its resistance to cisplatin, especially at advanced stages. Understanding the mechanisms behind cisplatin resistance is crucial for improving cancer therapy. The enzyme glutathione S‐transferase omega class 1 (GSTO1) is known to be involved in cisplatin resistance in colon cancer. This study focused on its role in cisplatin resistance in bladder cancer. Our analysis of protein expression in bladder cancer cells stimulated by secretions from tumor‐associated macrophages (TAMs) showed a significant increase in GSTO1. This prompted further investigation into the role of GSTO1 in bladder cancer. We found a strong correlation between GSTO1 expression and cisplatin resistance. Mechanistically, GSTO1 triggered the release of large extracellular vesicles (EVs) that promoted cisplatin efflux, thereby reducing cisplatin–DNA adduct formation and enhancing cisplatin resistance. Inhibition of EV release effectively counteracted the cisplatin resistance associated with GSTO1. In conclusion, GSTO1‐mediated EV release may contribute to cisplatin resistance caused by TAMs in bladder cancer. Strategies to target GSTO1 could potentially improve the efficacy of cisplatin in treating bladder cancer.
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- 2024
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3. Raf/ERK/Nrf2 signaling pathway and MMP-7 expression involvement in the trigonelline-mediated inhibition of hepatocarcinoma cell migration
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Jung Chun Liao, Kun Tsung Lee, Bang Jau You, Chia Lin Lee, Wen Te Chang, Yang Chang Wu, and Hong-Zin Lee
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trigonelline ,hepatocarcinoma Hep3B cells ,migration ,Pisum sativum ,chemotherapeutic agent ,Raf/ERK/Nrf2 signaling pathway ,MMP-7 ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Background: Trigonelline occurs in many dietary food plants and has been found to have anti-carcinogenic activity. Trigonelline is also found in coffee which is one of the most widely consumed beverages. Many epidemiological studies have reported that coffee consumption has an inverse relationship with the risk of cirrhosis or hepatocellular carcinoma. It would be interesting to investigate whether trigonelline is an ideal chemoprevent agent to prevent cancer progression. Methods: The protein expression was performed by western blotting. The trigonelline content in snow pea (Pisum sativum) was analyzed by high-performance liquid chromatography (HPLC). The migratory activity of human hepatocarcinoma cells (Hep3B) was assessed by using a wound migration assay. The percentage of each phase in the cell cycle was analyzed on a FACScan flow cytometer. Gene expression was detected by real-time reverse transcriptase-polymerase chain reaction techniques. Native gel analysis was performed to analyze the activity of superoxide dismutase (SOD), catalase and glutathione peroxidase. Results: According to the data of HPLC analysis, P. sativum, which is a popular vegetable, has relatively high content of trigonelline. Our findings suggest that trigonelline is an efficient compound for inhibiting Hep3B cell migration. Trigonelline inhibited the migration of hepatoma cells at concentrations of 75–100 µM without affecting proliferation. Raf/ERK/Nrf2 protein levels and further downstream antioxidative enzymes activity, such as SOD, catalase, and glutathione peroxidase, significantly decreased after treatment with 100 µM of trigonelline for 24 h. The migration inhibition of trigonelline is also related to its ability to regulate the matrix metalloproteinases 7 (MMP-7) gene expression. Conclusions: In this study, protein kinase Cα (PKCα) and Raf/ERK/Nrf2 signaling pathway and MMP-7 gene expression were involved in the trigonelline-mediated migration inhibition of Hep3B cells. We also demonstrated that trigonelline inhibits Hep3B cell migration through downregulation of nuclear factor E2-related factor 2–dependent antioxidant enzymes activity. This study analyzed the trigonelline content in a popular vegetable, snow pea, as a representative proof to prove that trigonelline is often found in the daily intake of food. Our finding suggested that trigonelline should be a useful chemopreventive agent derived from the daily intake of food to prevent cancer progression.
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- 2015
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4. Application of response surface methodology and quantitative NMR for the optimum extraction, characterization, and quantitation of Antrodia cinnamomea triterpenoids
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Chi-Ying Li, Yang-Chang Wu, Fang-Rong Chang, Mohamed El-Shazly, Ying-Chi Du, Chi-Yu Lu, Tsai-Hui Duh, and Tung-Ying Wu
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Medicine ,Science - Abstract
Abstract Antrodia cinnamomea (AC) is a treasured Asian medicinal mushroom, which has attracted attention due to recent research on its effectiveness in targeting a variety of serious ailments such as cancer and liver diseases. Among different A. cinnamomea constituents, triterpenoids are regarded as the most therapeutically attractive components because of their anti-inflammatory and cytotoxic activities. In the present study, we proposed a mathematical and statistical extraction protocol to evaluate the concentrations of total ergostane and lanostane triterpenoid derivatives from the ethanolic extract of the wild fruiting bodies of A. cinnamomea (EEAC) by utilizing response surface methodology (RSM) and quantitative NMR (qNMR) approaches. The optimum response surface model showed that the variations of the investigated response variables reached more than 90%, suggesting that the developed model is accurate in explaining response variability. Furthermore, the EEAC major characteristic triterpenoids were quantified through the comparison of the HPLC-tandem MS results with those of the qNMR results. The precision of the used techniques was also evaluated. The experimental design of the EEAC optimum extraction procedure obtained by using RSM and qNMR enabled accurate characterization and quantitation of A. cinnamomea triterpenoids.
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- 2023
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5. Umbelliferone and eriodictyol suppress the cellular entry of SARS-CoV-2
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Fang-Ju Cheng, Chien-Yi Ho, Tzong-Shiun Li, Yeh Chen, Yi-Lun Yeh, Ya-Ling Wei, Thanh Kieu Huynh, Bo-Rong Chen, Hung-Yu Ko, Chen-Si Hsueh, Ming Tan, Yang-Chang Wu, Hui-Chi Huang, Chih-Hsin Tang, Chia-Hung Chen, Chih-Yen Tu, and Wei-Chien Huang
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Artemisia argyi ,Eriodictyol ,Umbelliferone ,TMPRSS2 ,ACE2 ,SARS-CoV-2 variants ,Biotechnology ,TP248.13-248.65 ,Biology (General) ,QH301-705.5 ,Biochemistry ,QD415-436 - Abstract
Abstract Background Artemisia argyi (A. argyi), also called Chinese mugwort, has been widely used to control pandemic diseases for thousands of years since ancient China due to its anti-microbial infection, anti-allergy, and anti-inflammation activities. Therefore, the potential of A. argyi and its constituents in reducing the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was investigated in this study. Results Among the phytochemicals in A. argyi, eriodictyol and umbelliferone were identified to target transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) proteins, the essential factors for the cellular entry of SARS-CoV-2, in both FRET-based enzymatic assays and molecular docking analyses. These two ingredients of A. argyi suppressed the infection of ACE2-expressed HEK-293 T cells with lentiviral-based pseudo-particles (Vpp) expressing wild-type and variants of SARS-CoV-2 spike (S) protein (SARS-CoV-2 S-Vpp) via interrupting the interaction between S protein and cellular receptor ACE2 and reducing the expressions of ACE2 and TMPRSS2. Oral administration with umbelliferone efficiently prevented the SARS-CoV-2 S-Vpp-induced inflammation in the lung tissues of BALB/c mice. Conclusions Eriodictyol and umbelliferone, the phytochemicals of Artemisia argyi, potentially suppress the cellular entry of SARS-CoV-2 by preventing the protein binding activity of the S protein to ACE2.
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- 2023
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6. Effects of Citrus depressa Hayata juice on high-fat diet-induced obesity in HBV transgenic mice
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Pei-Yi Chu, Chang-Lu Hsu, Yen-An Lin, Yi-Cheng Pan, Yun-Hao Dai, Ying-Chun Yu, Juan-Cheng Yang, Wen-Lung Ma, Yi-Jinn Lillian Chen, Chia-Lin Lee, and Yang-Chang Wu
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Citrus depressa hayata ,Juice ,fermentation ,Polyphenol ,Hesperidin ,High-fat diet-induced obesity ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
The present study investigated the potential anti-obesity properties of Citrus depressa Hayata (CDH) juice in HBV transgenic mice, as well as the impact of fermentation on the effectiveness of the juice. The results revealed that fermentation increased the levels of polyphenols and hesperidin in CDH juice. The animal study demonstrated that both juices were effective in mitigating the weight gain induced by a high-fat diet by correcting metabolic parameter imbalances, reducing hepatic lipid accumulation, and reversing hepatic immune suppression. Furthermore, fermented juice exhibited superior efficacy in managing body weight and inhibiting the expansion of white adipose tissue (WAT). Fermented juice significantly enhanced adiponectin production and PPARγ expression in WAT, while also reducing hypertrophy. This study offers valuable insights into the potential role of CDH juices in combating obesity associated with high fat consumption and underscores the promise of CDH juice as a functional beverage.
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- 2024
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7. Linoleate-pazopanib conjugation as active pharmacological ingredient to abolish hepatocellular carcinoma growth
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Ke Wang, Pei-Yin Liao, Wei-Chun Chang, Cian-Ru Yang, Yu-Ting Su, Ping-Ching Wu, Yang-Chang Wu, Yao-Ching Hung, Najim Akhtar, Hsueh-Chou Lai, and Wen-Lung Ma
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hepatocellular carcinoma ,LDC ,linoleate ,pazopanib ,LAPC ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Small molecule compounds targeting multiple kinases involved in neoangiogenesis have shown survival benefits in patients with unresectable hepatocellular carcinoma (HCC). Nonetheless, despite the beneficial effects of multikinase inhibitors (MKIs), a lack of boosting adjuvant limits their objective response rate. Lipid conjugates have been used to improve delivery efficacy or pharmaceutical benefits for decades. However, the feasibility of utilizing lipid-drug conjugates (LDCs) in HCC regimens remains untested. In this study, oral feeding of linoleate-fluorescein isothiocyanate conjugates showed that the compound was well distributed in a spontaneous HCC mouse model. Therefore, a rationale design was developed for chemically synthesizing a linoleate-pazopanib conjugate (LAPC). The LAPC showed a significantly improved cytotoxicity compared to the parental drug pazopanib. Pazopanib’s angiogenic suppressing signals were not observed in LAPC-treated HCC cells, potentially suggesting an altered mechanism of action (MOA). In an efficacy trial comparing placebo, oral pazopanib, and LAPC treatments in the hepatitis B virus transgene-related spontaneous HCC mouse model (HBVtg-HCC), the LAPC treatment demonstrated superior tumor ablating capacity in comparison to both placebo and pazopanib treatments, without any discernible systemic toxicity. The LAPC exposure is associated with an apoptosis marker (Terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]) and an enhanced ferroptosis (glutathione peroxidase 4 [GPX4]) potential in HBVtg-HCC tumors. Therefore, the LAPC showed excellent HCC ablative efficacy with altered MOA. The molecular mechanisms of the LAPC and LDCs for HCC therapeutics are of great academic interest. Further comprehensive preclinical trials (e.g., chemical-manufacture-control, toxicity, distribution, and pharmacokinetics/pharmacodynamics) are expected.
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- 2024
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8. The Efficacy of Lactobacillus delbrueckii ssp. bulgaricus Supplementation in Managing Body Weight and Blood Lipids of People with Overweight: A Randomized Pilot Trial
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Pei-Yi Chu, Ying-Chun Yu, Yi-Cheng Pan, Yun-Hao Dai, Juan-Cheng Yang, Kuo-Chin Huang, and Yang-Chang Wu
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Lactobacillus delbrueckii ssp. bulgaricus ,body weight ,triglyceride ,lipoprotein ,obesity ,Microbiology ,QR1-502 - Abstract
This study aimed to evaluate the efficacy of Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) in improving body weight, obesity-related outcomes, and lipid profiles of overweight people. Thirty-six overweight participants were randomly assigned to either a probiotic or a placebo group. A placebo powder or L. bulgaricus powder (containing 1 × 108 colony-forming unit (CFU) of the probiotic) was administered daily for 12 weeks. Body composition was determined, and blood tests were performed before and after the intervention. L. bulgaricus supplementation under the present condition did not affect the body weight, fat percentage, or body mass index (BMI) of the participants, while it resulted in a notable decrease in blood triglyceride (TG) levels, which corresponded to a lowering of the TG proportion in the composition of large VLDL (L–XXL sized fractions) and HDL (M and L fractions) in the probiotic-treated group. These results suggest that L. bulgaricus supplementation under the current conditions may not be helpful for losing weight, but it has the potential to decrease blood TG levels by modulating TG accumulation in or transport by VLDL/HDL in obese patients. L. bulgaricus supplements may have health-promoting properties in preventing TG-related diseases in overweight people.
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- 2024
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9. The protoplast two-way fusions and fusant characteristics of Antrodia cinnamomea and Cordyceps militaris
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Wei-Kuang Lai, Yang-Chang Wu, Tai-Sheng Yeh, Chun-Ren Hsieh, Yi-Hong Tsai, Chien-Kei Wei, Chi-Ying Li, Ying-Chen Lu, and Fang-Rong Chang
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Medicinal fungi ,Protoplast fusion ,Antrodia cinnamomea ,Cordyceps militaris ,Secondary metabolite ,Nutrition. Foods and food supply ,TX341-641 - Abstract
This study generated two fused protoplasts of Antrodia cinnamomea and Cordyceps militaris in two ways. The protoplasts of A. cinnamomea were inactivated by heat to inactivate biochemical processes and enzymatic activities in the cytoplasm, and the protoplasts of C. militaris were inactivated by UV radiation to invalidate their genome function, then they were fused under optimal conditions to get a fusion rate as (7.42 ± 0.8) × 10-6 fusants/mL; the new fusants were abbreviated as Ac-Cm. On the other hand, when A. cinnamomea and C. militaris were treated with heat and UV oppositely using similar experiments, the fusion rate was (9.70 ± 0.68) × 10-5 fusants/mL, and the new fusants were abbreviated as Cm-Ac. We selected each of two best-growing fused colonies Ac-Cm-1, Ac-Cm-2, Cm-Ac-1, and Cm-Ac-2, together with parental A. cinnamomea and C. militaris, and studied their morphology, growth antagonism tests, and genetic relationships by 18S rRNA sequencing. In comparison with the initial cultures of 4 fusants, the yields of adenosine, biomass, cordycepic acid, cordycepin, total polysaccharide, and total triterpenoids were increased up 1.305−50.1563 times in the optimal medium conditions. For gene stability tests, those of the four fusants and their outputs were stabilized within 10 generations.
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- 2022
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10. Association of combination antiretroviral therapy with risk of neurological diseases in patients with HIV/AIDS in Taiwan: a nested case-control study
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Chen-Hsing Chou, Jian-Shiun Chiou, Mao-Wang Ho, Ni Tien, Te-Mao Li, Mu-Lin Chiu, Fuu-Jen Tsai, Yang-Chang Wu, I-Ching Chou, Hsing-Fang Lu, Ting-Hsu Lin, Chiu-Chu Liao, Shao-Mei Huang, Wen-Miin Liang, and Ying-Ju Lin
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antiretroviral therapy ,neurocognitive impairment ,nested case-control study ,cumulative defined daily dose ,CNS penetration effectiveness score ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Heterogeneous neurocognitive impairment remains an important issue, even in the era of combination antiretroviral therapy (cART), with an incidence ranging from 15% to 65%. Although ART drugs with higher penetration scores to the central nervous system (CNS) show better HIV replication control in the CNS, the association between CNS penetration effectiveness (CPE) scores and neurocognitive impairment remains inconclusive. To explore whether ART exposure is associated with the risk of neurological diseases among patients with HIV/AIDS, this study in Taiwan involved 2,571 patients with neurological diseases and 10,284 matched, randomly selected patients without neurological diseases between 2010 and 2017. A conditional logistic regression model was used in this study. The parameters for ART exposure included ART usage, timing of exposure, cumulative defined daily dose (DDD), adherence, and cumulative CPE score. Incident cases of neurological diseases, including CNS infections, cognitive disorders, vasculopathy, and peripheral neuropathy, were obtained from the National Health Insurance Research Database in Taiwan. Odds ratios (ORs) for the risk of neurological diseases were conducted using a multivariate conditional logistic regression model. Patients with a history of past exposure (OR: 1.68, 95% confidence interval [CI]:1.22–2.32), low cumulative DDDs (< 2,500) (OR: 1.28, 95% CI: 1.15–1.42), low adherence (0 < adherence (ADH) ≤ 0.8) (OR: 1.46, 95% CI: 1.30–1.64), or high cumulative CPE scores (>14) (OR: 1.34, 95% CI: 1.14–1.57) had a high risk of neurological diseases. When stratified by classes of ART drugs, patients with low cumulative DDDs or low adherence had a high risk of neurological diseases, including NRTIs, PIs, NNRTIs, INSTIs, and multi-drug tablets. Subgroup analyses also suggested that patients with low cumulative DDDs or low adherence had a high risk of neurological diseases when they had high cumulative CPE scores. Patients with high cumulative DDDs or medication adherence were protected against neurological diseases only when they had low cumulative CPE scores (≤ 14). Patients may be at risk for neurological diseases when they have low cumulative DDDs, low adherence, or usage with high cumulative CPE scores. Continuous usage and low cumulative CPE scores of ART drugs may benefit neurocognitive health in patients with HIV/AIDS.
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- 2023
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11. Ursolic acid silences CYP19A1/aromatase to suppress gastric cancer growth
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Wen‐Lung Ma, Ning Chang, Yingchun Yu, Yu‐Ting Su, Guan‐Yu Chen, Wei‐Chung Cheng, Yang‐Chang Wu, Ching‐Chia Li, Wei‐Chun Chang, and Juan‐Cheng Yang
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Ar silencer ,CYP19A1/aromatase ,gastric cancer ,Hedyotis diffusa Willd ,ursolic acid ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Introduction Gastric cancer (GCa) is a malignancy with few effective treatments. Ursolic acid (UA), a bioactive triterpenoid enriched in Hedyotis diffusa Willd, known to suppress GCa without identified target. CYP19A1 (cytochrome P450 family 19A1; also known as aromatase, Ar) was correlated to GCa prognosis. Relatedly, Ar silencers, which halt the expression of Ar exhibited anti‐GCa effects in experimental models, are currently being investigated. Method The docking simulation score of UA was compared with Ar inhibitors, e.g., letrozole, exemestane, in Ar protein crystallization. Hedyotis diffusa Willd ethanol extract, UA, or 5‐fluracil were applied onto AGS, SC‐M1, MKN45 GCa cells for cancer inhibition tests. Immunoblot for measuring gene expressions upon drug treatments, or gene knockdown/overexpression. Treatments were also applied in a MKN45 implantation tumor model. A web‐based GCa cohort for Ar expression association with prognosis was performed. Result The ethanol extracts of Hedyotis diffusa Willd, enrich with UA, exhibited cytotoxic activity against GCa cells. Molecular docking simulations with the 3D Ar structure revealed an excellent fitting score for UA. UA increase cytotoxic, and suppressed colony, in addition to its Ar silencing capacity. Moreover, UA synergistically facilitated 5‐FU, (a standard GCa treatment) regimen in vitro. Consistent with those results, adding estradiol did not reverse the cancer‐suppressing effects of UA, which confirmed UA acts as an Ar silencer. Furthermore, UA exhibited tumor‐suppressing index (TSI) score of 90% over a 6‐week treatment term when used for single dosing in xenograft tumor model. In the clinical setting, Ar expression was found to be higher in GCa tumors than normal parental tissue from the TCGA (The Cancer Genome Atlas) cohort, while high Ar expression associated with poor prognosis. Together, the results indicate UA could be used to treat GCa by silencing Ar expression in GCa. Hedyotis diffusa Willd ethanol extract could be an functional food supplements.
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- 2022
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12. Effect of Chinese herbal medicine therapy on risks of all-cause mortality, infections, parasites, and circulatory-related mortality in HIV/AIDS patients with neurological diseases
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Jian-Shiun Chiou, Chen-Hsing Chou, Mao-Wang Ho, Ni Tien, Wen-Miin Liang, Mu-Lin Chiu, Fuu-Jen Tsai, Yang-Chang Wu, I-Ching Chou, Hsing-Fang Lu, Ting-Hsu Lin, Chiu-Chu Liao, Shao-Mei Huang, Te-Mao Li, and Ying-Ju Lin
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HIV/AIDS ,neurological diseases ,mortality ,Chinese herbal medicine ,network analysis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Introduction: Long-term living with human immunodeficiency virus (HIV) and/or antiretroviral therapy (ART) is associated with various adverse effects, including neurocognitive impairment. Heterogeneous neurocognitive impairment remains an important issue, affecting between 15–65% of human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) patients and resulting in work performance, safety, and health-related outcomes that have a heavy economic burden.Methods: We identified 1,209 HIV/AIDS patients with neurological diseases during 2010–2017. The Kaplan–Meier method, log-rank test, and Cox proportional hazards model were used to analyze 308 CHM users and 901 non-CHM users within this population. Major CHM clusters were determined using association rule mining and network analysis.Results and Discussion: Results showed that CHM users had a 70% lower risk of all-cause mortality (adjusted hazard ratio (aHR) = 0.30, 95% confidence interval (CI):0.16–0.58, p < 0.001) (p = 0.0007, log-rank test). Furthermore, CHM users had an 86% lower risk of infections, parasites, and circulatory-related mortality (aHR = 0.14, 95% confidence interval (CI):0.04–0.46, p = 0.001) (p = 0.0010, log-rank test). Association rule mining and network analysis showed that two CHM clusters were important for patients with neurological diseases. In the first CHM cluster, Huang Qin (HQ; root of Scutellaria baicalensis Georgi), Gan Cao (GC; root of Glycyrrhiza uralensis Fisch.), Huang Lian (HL; root of Coptis chinensis Franch.), Jie Geng (JG; root of Platycodon grandiflorus (Jacq.) A.DC.), and Huang Bai (HB; bark of Phellodendron amurense Rupr.) were identified as important CHMs. Among them, the strongest connection strength was identified between the HL and HQ. In the second CHM cluster, Suan-Zao-Ren-Tang (SZRT) and Ye Jiao Teng (YJT; stem of Polygonum multiflorum Thunb.) were identified as important CHMs with the strongest connection strength. CHMs may thus be effective in treating HIV/AIDS patients with neurological diseases, and future clinical trials are essential for the prevention of neurological dysfunction in the population.
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- 2023
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13. Effect of Chinese Herbal Medicine Therapy on Risks of Overall, Diabetes-Related, and Cardiovascular Diseases-Related Mortalities in Taiwanese Patients With Hereditary Hemolytic Anemias
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Mu-Lin Chiu, Jian-Shiun Chiou, Chao-Jung Chen, Wen-Miin Liang, Fuu-Jen Tsai, Yang-Chang Wu, Ting-Hsu Lin, Chiu-Chu Liao, Shao-Mei Huang, Chen-Hsing Chou, Cheng-Wen Lin, Te-Mao Li, Yu-Lung Hsu, and Ying-Ju Lin
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hereditary hemolytic anemias ,overall mortality ,diabetes-related mortality ,cardiovascular diseases-related mortality ,chinese herbal medicine ,network analysis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Hereditary Hemolytic Anemias (HHAs) are a rare but heterogeneous group of erythrocytic diseases, characterized by intrinsic cellular defects due to inherited genetic mutations. We investigated the efficacy of Chinese herbal medicine (CHM) in reducing the overall, diabetes-related, and cardiovascular diseases (CVDs)-related mortalities among patients with HHAs using a nationwide population database. In total, we identified 33,278 patients with HHAs and included 9,222 non-CHM and 9,222 CHM matched pairs after matching. The Cox proportional hazards model was used to compare the risk of mortality between non-CHM and CHM users. The Kaplan-Meier method and log-rank test were used to compare the cumulative incidence mortality between non-CHM and CHM users. The CHM prescription patterns were presented by the association rules and network analyses, respectively. The CHM prescription patterns were presented by the association rules and network analyses, respectively. CHM users showed significant reduced risks for of overall (adjusted hazard ratio [aHR]: 0.67, 95% confidence interval [CI]: 0.61–0.73, p < 0.001), diabetes-related (aHR: 0.57, 95% CI: 0.40–0.82, p < 0.001), and CVDs-related (aHR: 0.59, 95% CI: 0.49–0.72, p < 0.001) mortalities compared with non-CHM users. Two CHM clusters are frequently used to treat Taiwanese patients with HHAs. Cluster 1 is composed of six CHMs: Bei-Mu (BM; Fritillaria cirrhosa D.Don), Gan-Cao (GC; Glycyrrhiza uralensis Fisch.), Hai-Piao-Xiao (HPX; Endoconcha Sepiae), Jie-Geng (JG; Platycodon grandiflorus (Jacq.) A.DC.), Yu-Xing-Cao (YXC; Houttuynia cordata Thunb.), and Xin-Yi-Qing-Fei-Tang (XYQFT). Cluster 2 is composed of two CHMs, Dang-Gui (DG; Angelica sinensis (Oliv.) Diels) and Huang-Qi (HQi; Astragalus membranaceus (Fisch.) Bunge). Further randomized clinical trials are essential to evaluate the safety and effectiveness of above CHM products and to eliminate potential biases in the current retrospective study.
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- 2022
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14. High-Purity Bioactive Ingredient—3S,3′S-Astaxanthin: A New Preparation from Genetically Modified Kluyveromyces marxianus without Column Chromatography and Gel Filtration
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Wei-Cheng Yuan, Tung-Ying Wu, Pei-Yi Chu, Fang-Rong Chang, and Yang-Chang Wu
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enzyme-assisted extraction ,magnesium perchlorate ,ORAC ,salt-assisted liquid-liquid extraction ,yeast ,Therapeutics. Pharmacology ,RM1-950 - Abstract
A highly efficient methodology for bioactive ingredient 3S,3′S-astaxanthin (3S,3′S-AST) preparation from genetically modified yeast (Kluyveromyces marxianus) with a combination of enzyme-assisted extraction and salt-assisted liquid-liquid extraction (SALLE) was achieved. The highest yield of 3S,3′S-AST indicated that FoodPro® CBL for yeast cell walls hydrolysis could significantly enhance extraction and obtain, with the help of SALLE procedure, quantified 3S,3′S-AST over 99% in purity through cation chelation. In the oxygen radical antioxidant capacity (ORAC) assay, the antioxidant capacity of high-purity 3S,3′S-AST products were 18.3 times higher than that of the original raw material extract. This new combination preparation may replace previous methods and has the potential to be scaled up in the manufacture of high-purity 3S,3′S-AST from low-value bioresources of raw materials to high-value products in the food and/or drug industries with lower cost and simple equipment.
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- 2023
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15. Briavioids E–G, Newly Isolated Briarane-Diterpenoids from a Cultured Octocoral Briareum violaceum
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Thanh Hao Huynh, Chia-Jung Liu, Yi-Hung Liu, Su-Ying Chien, Zhi-Hong Wen, Lee-Shing Fang, Jih-Jung Chen, Yang-Chang Wu, Jui-Hsin Su, and Ping-Jyun Sung
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Briareum violaceum ,briarane ,briavioid ,X-ray ,anti-inflammation ,iNOS ,Biology (General) ,QH301-705.5 - Abstract
The chemical screening of a cultured soft coral, Briareum violaceum, led to the isolation of eight natural, briarane-related diterpenoids, including three unreported metabolites, briavioids E–G (1–3), and five known briaranes, briacavatolides B (4) and C (5), briaexcavatin L (6), briaexcavatolide U (7) and briarenol K (8). The structures of briaranes 1–8 were established using spectroscopic methods. The absolute configuration of briavioid A (9), obtained in a previous study, was reported for the first time in this study by a single-crystal X-ray diffraction analysis using a copper radiation source. The anti-inflammatory activity of briaranes 1 and 2 and briaranes 4–8 was evaluated by screening their inhibitory ability against the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells.
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- 2023
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16. The Use of San-Huang-Xie-Xin-Tang Reduces the Mortality Rate among Breast Cancer Patients
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Daniel Winardi, Chieh-Hsin Wu, Jen-Huai Chiang, Yung-Hsiang Chen, Ching-Liang Hsieh, Juan-Cheng Yang, and Yang-Chang Wu
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breast cancer ,mortality ,population ,risk ,San-Huang-Xie-Xin-Tang (SHXXT) ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Globally, breast cancer is the most common cause of cancer deaths. In Taiwan, it is the most prevalent cancer among females. Since San-Huang-Xie-Xin-Tang (SHXXT) exerts not only an anti-inflammatory but an immunomodulatory effect, it may act as a potent anti-tumor agent. Herein, the study aimed to explore the influence of SHXXT and its constituents on the mortality rate among breast cancer patients in Taiwan regarding the component effect and the dose–relationship effect. By using the Taiwan National Health Insurance (NHI) Research Database (NHIRD), the study analyzed 5387 breast cancer patients taking Chinese herbal medicine (CHM) and 5387 breast cancer patients not using CHM. CHM means SHXXT and its constituents in the study. The Kaplan–Meier method was utilized to determine the mortality probabilities among patients. Whether the CHM influences the mortality rate among patients was estimated by Cox proportional hazard regression analysis. The use of CHM could lower the cancer mortality rate by 59% in breast cancer patients. The protective effect was parallel to the cumulative days of CHM use and the annual average CHM dose. In addition, the mortality rate was lower in patients who used SHXXT compared to those who only used one of its constituents. SHXXT and its constituents were all promising therapeutic weapons against breast cancer.
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- 2023
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17. The Amiloride Derivatives Regulate the Alternative Splicing of Apoptotic Gene Transcripts.
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Chien-Chih Lee, Wen-Hsin Chang, Ting-Yuan Liu, Yu-Chia Chen, Guan-Yu Chen, Yang-Chang Wu, and Jan-Gowth Chang
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- 2018
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18. Hericium erinaceus Mycelium Ameliorates In Vivo Progression of Osteoarthritis
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Shang-Yu Yang, Chi-Jung Fang, Yu-Wen Chen, Wan-Ping Chen, Li-Ya Lee, Chin-Chu Chen, Yen-You Lin, Shan-Chi Liu, Chun-Hao Tsai, Wei-Chien Huang, Yang-Chang Wu, and Chih-Hsin Tang
- Subjects
osteoarthritis ,Hericium erinaceus ,mycelium ,anterior cruciate ligament transection ,interleukin 1 beta ,tumor necrosis factor-alpha ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Osteoarthritis (OA) is an age-related disorder that affects the joints and causes functional disability. Hericium erinaceus is a large edible mushroom with several known medicinal functions. However, the therapeutic effects of H. erinaceus in OA are unknown. In this study, data from Sprague-Dawley rats with knee OA induced by anterior cruciate ligament transection (ACLT) indicated that H. erinaceus mycelium improves ACLT-induced weight-bearing asymmetry and minimizes pain. ACLT-induced increases in articular cartilage degradation and bone erosion were significantly reduced by treatment with H. erinaceus mycelium. In addition, H. erinaceus mycelium reduced the synthesis of proinflammatory cytokines interleukin-1β and tumor necrosis factor-α in OA cartilage and synovium. H. erinaceus mycelium shows promise as a functional food in the treatment of OA.
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- 2022
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19. Composition decipherment of Ficus pumila var. awkeotsang and its potential on COVID-19 symptom amelioration and in silico prediction of SARS-CoV-2 interference
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Hao-Chun Hu, Szu-Yin Yu, Xiao-Shan Hung, Chun-Han Su, Yu-Liang Yang, Chien-Kei Wei, Yuan-Bin Cheng, Yang-Chang Wu, Chia-Hung Yen, Tsong-Long Hwang, Shu-Li Chen, István Szatmári, Attila Hunyadi, Yi-Hong Tsai, and Fang-Rong Chang
- Subjects
Pharmacology ,03.01. Általános orvostudomány ,Food Science - Published
- 2022
20. Natural Products from Octocorals of the Genus Verrucella (Milne Edwards & Haime, 1857)
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Ping-Jyun Sung, Chia-Ching Liaw, Yu-Jen Wu, Choo-Aun Neoh, Yu-Chi Tsai, Yi-Hao Lo, Yang-Chang Wu, and Zhi-Hong Wen
- Subjects
Organic Chemistry - Abstract
Abstract: In this review, we summarize the diverse marine natural compounds obtained from the genus Verrucella and their pharmacological effects and present a survey of the natural products taxonomy according to species. Sixty-six natural substances, including fifty-three steroids, six briarane-type diterpenoids, five nitrogenous bases, one amide, and one glycerol derivative, were obtained from Verrucella spp., which were mainly collected from the South China Sea and the Bay of Bengal, India. Steroids were the major constituents found in Verrucella spp. Moreover, anticancer, antimicrobial, and immunomodulatory activities of those steroids and other compounds are also presented. This review reveals the chemical diversity, chemotaxonomy, and multiple pharmacological effects of the Verrucella genus. It will be helpful for further research and exploration of new steroid analogs and other components with prospective biological activities from this marine organism.
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- 2022
21. Steroidal alkaloids from Solanum erianthum and their anti-breast cancer properties
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Chia-Lin Lee, Wei-Yu Hsu, Chao-Jung Chen, and Yang-Chang Wu
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Plant Science ,Agronomy and Crop Science ,Biochemistry ,Biotechnology - Published
- 2022
22. Hesperidin Is a Potential Inhibitor against SARS-CoV-2 Infection
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Fang-Ju Cheng, Thanh-Kieu Huynh, Chia-Shin Yang, Dai-Wei Hu, Yi-Cheng Shen, Chih-Yen Tu, Yang-Chang Wu, Chih-Hsin Tang, Wei-Chien Huang, Yeh Chen, and Chien-Yi Ho
- Subjects
hesperidin ,TMPRSS2 ,ACE2 ,SARS-CoV-2 ,D614G ,501Y.v2 ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Hesperidin (HD) is a common flavanone glycoside isolated from citrus fruits and possesses great potential for cardiovascular protection. Hesperetin (HT) is an aglycone metabolite of HD with high bioavailability. Through the docking simulation, HD and HT have shown their potential to bind to two cellular proteins: transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2), which are required for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results further found that HT and HD suppressed the infection of VeroE6 cells using lentiviral-based pseudo-particles with wild types and variants of SARS-CoV-2 with spike (S) proteins, by blocking the interaction between the S protein and cellular receptor ACE2 and reducing ACE2 and TMPRSS2 expression. In summary, hesperidin is a potential TMPRSS2 inhibitor for the reduction of the SARS-CoV-2 infection.
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- 2021
- Full Text
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23. Supplementary Figures 1 - 8 from Inhibition of ATR-Dependent Signaling by Protoapigenone and Its Derivative Sensitizes Cancer Cells to Interstrand Cross-link–Generating Agents In Vitro and In Vivo
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Yang-Chang Wu, Attila Hunyadi, Da-Wei Chuang, Fang-Rong Chang, Wen-Lien Lin, Kevin Yen-Ting Liu, Chao-Neng Tseng, Chin-Chung Wu, Wen-Cheng Chou, Alan Yueh-Luen Lee, and Hui-Chun Wang
- Abstract
PDF file, 984KB.
- Published
- 2023
24. Supplementary Methods from Inhibition of ATR-Dependent Signaling by Protoapigenone and Its Derivative Sensitizes Cancer Cells to Interstrand Cross-link–Generating Agents In Vitro and In Vivo
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Yang-Chang Wu, Attila Hunyadi, Da-Wei Chuang, Fang-Rong Chang, Wen-Lien Lin, Kevin Yen-Ting Liu, Chao-Neng Tseng, Chin-Chung Wu, Wen-Cheng Chou, Alan Yueh-Luen Lee, and Hui-Chun Wang
- Abstract
PDF file, 75KB.
- Published
- 2023
25. Chemo‐ and Regioselective Construction of Functionalized Isocoumarin, Flavone, and Isoquinolinedione via a One‐pot Reaction of o ‐Quinol Acetate and Soft Nucleophiles
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Yeong‐Jiunn Jang, Guan‐Yu Chen, Yun‐Lian Jhan, Pei‐Ting Lo, Wei‐Yu Hsu, Ke Wang, Ya‐Ting Hsu, Chia‐Lin Lee, Yu‐Liang Yang, and Yang‐Chang Wu
- Subjects
General Chemistry - Published
- 2023
26. Regiodivergent Synthesis of Methylene and Methyl Ring-Fused Isoquinolinones: Base-Promoted Isomerization of N-Allyl Amides
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Li-Yuan Chen, Rong-Shiow Tang, Yang-Chang Wu, Chin-Hung Lai, and Ta-Hsien Chuang
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Organic Chemistry - Published
- 2022
27. Snail Mucus Enhances Chemosensitivity of Triple-negative Breast Cancer Via Activation of the Fas Pathway
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CHIEN-YI HO, DAI-WEI HU, BO-RONG CHEN, CHUN-CHUN YANG, CHUN-HSU YAO, TIEN NI, WEI-CHUAN HO, YUEH-SHENG CHEN, CHIH-YEN TU, WEI-CHAO CHANG, YANG-CHANG WU, CHIH-HSIN TANG, HUI-CHI HUANG, WEI-CHIEN HUANG, and TZONG-SHIUN LI
- Subjects
Cancer Research ,Oncology ,General Medicine - Published
- 2022
28. Artemisia argyi potentially prevents the infections with SARS-CoV-2 variants
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Fang-Ju Cheng, Thanh Kieu Huynh, Hung-Yu Ko, Chen-Si Hsueh, Yi-Lun Yeh, Yang-Chang Wu, Chih-Hsin Tang, Chia-Hung Chen, Chih-Yen Tu, Wei-Chien Huang, and Chien-Yi Ho
- Abstract
Background Traditional Chinese medicine (TCM) has potential benefits to prevent multi-viral infection including by modulating the immune system or defending oxidative stress. Artemisia argyi (A. argyi) has been widely used for anti-microbial infection, anti-allergy, anti-diabetes, and anti-inflammation in Eastern Asia. However, it remain unclear whether A. argyi has the potential to reduce the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results Through the docking simulation, eriodictyol and umbelliferone, two phytochemicals existed in Artemisia argyi, have showed their potential to bind to cellular proteins transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2), which are required for the cellular entry of SARS-CoV-2. Our results further found that eriodictyol and umbelliferone suppressed the infection of ACE2-expressed HEK-293T cells with lentiviral-based pseudo-particles expressing wild type and variants of SARS-CoV-2 spike (S) protein via interrupting the interaction between S protein and cellular receptor ACE2 and via reducing ACE2 and TMPRSS2 expressions. Conclusions In summary, Artemisia argyi and its ingredients eriodictyol and umbelliferone are potential agents to reduce SARS-CoV-2 infection.
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- 2023
29. Theoretical study of cyano‐promoted intramolecular aza‐Diels–Alder reaction
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Chin‐Hung Lai, Cheng‐En Yang, Yang‐Chang Wu, Youness El Bakri, Eduardo Chamorro, and Ta‐Hsien Chuang
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Organic Chemistry ,Physical and Theoretical Chemistry - Published
- 2022
30. Using NMR, X-ray, and CD analysis in the study on natural products obtained from Vietnamese plant and fungi in terms of pharmaceutical product development
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Dinh Thang Tran, Cong Dung Vo, Ngoc Tuan Nguyen, Manh Dung Doan, Yang-Chang Wu, and Tian-Shung Wu
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absolute configuration ,circular dichroism ,NMR ,X-ray analysis ,Science - Abstract
NMR, X-ray analysis, and CD methods are powerful techniques for the study of absolute configuration of bioactive compounds from natural resources. This study presents the results of a joint-study between Vietnam and Taiwan on the bioactive compounds obtained from Vietnamese plants and fungi. Among the tested compounds, hexatenuin A displayed the most significant inhibition of superoxide anion generation and elastase release. These triterpenoids may be used as potential anti-inflammatory agents.
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- 2017
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31. Estrogenic and anti-neutrophilic inflammatory phenanthrenes from Juncus effusus L
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Yu Ting Kuo, Fang Rong Chang, Yi Hong Tsai, Szu Yin Yu, Tsong-Long Hwang, Chih Chan Lin, Yang Chang Wu, Ferenc Fülöp, Kuei Hung Lai, Yu Ming Hsu, Hao Chun Hu, and Yu Che Chuang
- Subjects
biology ,medicine.drug_class ,Chemistry ,Superoxide ,Organic Chemistry ,Elastase ,Estrogen receptor ,Plant Science ,Traditional Chinese medicine ,Pharmacology ,biology.organism_classification ,Biochemistry ,Anti-inflammatory ,Analytical Chemistry ,chemistry.chemical_compound ,Edema ,Juncus ,medicine ,medicine.symptom ,Phenanthrenes - Abstract
Juncus effusus L. (J. effusus) is a Traditional Chinese Medicine (TCM) that has long been used for dealing with gynaecological disorders, such as relieving insomnia, preventing tinnitus, reducing edema with diuretic effect. In our course of evidence-based medical research focused on this herb, one new phenanthrene, Junfusol B (2), together with seventeen known compounds were isolated and identified. All the structures of these compounds were elucidated by spectroscopic methods. The absolute stereochemistry of compounds 1 and 2 was further determined by comparing their calculated and experimental Electronic Circular Dichroism (ECD) spectra and optical rotation (OR) values. The isolates were evaluated for their estrogenic and anti-inflammatory activities which were considered as relevant etiological factors of insomnia, tinnitus and edema in the ancient TCM theory. The results revealed that most of the obtained phenanthrenes in this work were found exerting agonistic effects on estrogen receptor. This is the first report to declare the exact estrogen-regulating potential among this type of compounds from J. effusus. Moreover, phenanthrenes 3 - 7 exhibited significant inhibitions on superoxide anion generation and elastase release in fMLP/CB-induced human neutrophilic inflammation model. J. effusus may be developed as a complementary agent utilized in menopausal multiple syndromes.
- Published
- 2021
32. Novel Aporphine- and Proaporphine–Clerodane Hybrids Identified from the Barks of Taiwanese Polyalthia longifolia (Sonn.) Thwaites var. pendula with Strong Anti-DENV2 Activity
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I-Wen Lo, Geng-You Liao, Jin-Ching Lee, Chi-I Chang, Yang-Chang Wu, Yen-Yu Chen, Shang-Pin Liu, Huey-Jen Su, Chih-I Liu, Chia-Yi Kuo, Zheng-Yu Lin, Tsung-Lin Li, Yun-Sheng Lin, and Chia-Ching Liaw
- Subjects
Polyalthia longifolia var. pendula ,clerodane ,aporphine ,proaporphine ,anti-DENV2 ,NS2B-NS3 protease ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Hybrid natural products produced via mixed biosynthetic pathways are unique and often surprise one with unexpected medicinal properties in addition to their fascinating structural complexity/diversity. In view of chemical structures, hybridization is a way of diversifying natural products usually through dimerization of two similar or dissimilar subcomponents through a C–C or N–C covalent linkage. Here, we report four structurally attractive diterpene–alkaloid conjugates polyalongarins A–D (1–4), clerodane-containing aporphine and proaporphine alkaloids, the first of its kind from the barks of Taiwanese Polyalthia longifolia (Sonn.) Thwaites var. pendula. In addition to conventional spectroscopic analysis, single crystal X-ray crystallography was employed to determine the chemical structures and stereo-configurations of 1. Compounds 1–4 were subsequently subjected to in vitro antiviral examination against DENV2 by evaluating the expression level of the NS2B protein in DENV2-infected Huh-7 cells. These compounds display encouraging anti-DENV2 activity with superb EC50 (2.8–6.4 μM) and CC50 values (50.4–200 μM). The inhibitory mechanism of 1–4 on NS2B was further explored drawing on in-silico molecular docking analysis. Based on calculated binding affinities and predicted interactions between the functional groups of 1–4 and the allosteric-site residues of the DENV2 NS2B-NS3 protease, our analysis concludes that the clerodane–aporphine/proaporphine-type hybrids are novel and effective DENV NS2B-NS3 protease inhibitors.
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- 2022
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- View/download PDF
33. Chemical Composition and Chronic Toxicity of Disc-Cultured
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Shou-Chou, Liu, Tung-Ying, Wu, Tai-Hao, Hsu, Ming-Nan, Lai, Yang-Chang, Wu, and Lean-Teik, Ng
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- 2022
34. Targeting
- Author
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Wei, Wuli, Shinn-Zong, Lin, Shee-Ping, Chen, Bakhos A, Tannous, Wen-Sheng, Huang, Peng Yeong, Woon, Yang-Chang, Wu, Hsueh-Hui, Yang, Yi-Cheng, Chen, Renata Lopes, Fleming, Jack T, Rogers, Catherine M, Cahill, Tsung-Jung, Ho, Tzyy-Wen, Chiou, and Horng-Jyh, Harn
- Subjects
Mice ,MicroRNAs ,Amyloid beta-Peptides ,Cognition ,Alzheimer Disease ,Presenilin-1 ,Animals ,Biotin ,Plaque, Amyloid ,RNA, Long Noncoding ,Amyloid Precursor Protein Secretases - Published
- 2022
35. Development on potential skin anti-aging agents of Cosmos caudatus Kunth via inhibition of collagenase, MMP-1 and MMP-3 activities
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Yen Chi Loo, Hao-Chun Hu, Szu-Yin Yu, Yi-Hong Tsai, Michal Korinek, Yang-Chang Wu, Fang-Rong Chang, and Ying-Jung Chen
- Subjects
Pharmacology ,Complementary and alternative medicine ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Published
- 2023
36. Drug Screening of Potential Multiple Target Inhibitors for Estrogen Receptor-α-positive Breast Cancer
- Author
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Wei Chien Huang, Yang Chang Wu, Yun-Hao Dai, Guan Yu Chen, Chih-Hsin Tang, and Juan-Cheng Yang
- Subjects
Cancer Research ,Drug Evaluation, Preclinical ,Estrogen receptor ,Breast Neoplasms ,medicine.disease_cause ,Proto-Oncogene Mas ,General Biochemistry, Genetics and Molecular Biology ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Humans ,Protein kinase A ,Protein kinase B ,Early Detection of Cancer ,PI3K/AKT/mTOR pathway ,Pharmacology ,Kinase ,business.industry ,Estrogen Receptor alpha ,Receptors, Estrogen ,030220 oncology & carcinogenesis ,Cancer research ,Female ,KRAS ,business ,Proto-Oncogene Proteins c-akt ,Tyrosine kinase ,Research Article ,Proto-oncogene tyrosine-protein kinase Src - Abstract
Background/aim Estrogen receptor α (ERα) antagonist is the most common treatment for ERα-positive breast cancer. However, compensatory signaling contributes to resistance to ERα antagonists. Thus, to explore the potential agents for targeting compensatory signaling, we screened multiple target inhibitors for breast cancer treatment. Materials and methods We attempted to build a structure-based virtual screening model that can find potential compounds and assay the anticancer ability of these drugs by overall cell survival assay. The downstream compensatory phosphorylated signaling was measured by immunoblotting. Results Hamamelitannin and glucocheirolin were hits for ERα, phosphoinositide 3-kinase (PI3K), and KRAS proto-oncogene, GTPase (KRAS), which were active against estrogen and epidermal growth factor-triggered proliferation. Additionally, we select aminopterin as a hit for ERα, PI3K, KRAS, and SRC proto-oncogene, non-receptor tyrosine kinase (SRC) with inhibitory activities toward AKT serine/threonine kinase 1 (AKT) and mitogen-activated protein kinase kinase (MEK) signaling. Conclusion Our structure-based virtual screening model selected hamamelitannin, glucocheirolin, aminopterin, and pemetrexed as compounds that may act as potential inhibitors for improving endocrine therapies for breast cancer.
- Published
- 2021
37. Antcin K inhibits VCAM-1-dependent monocyte adhesion in human rheumatoid arthritis synovial fibroblasts
- Author
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David Achudhan, Sunny Li-Yun Chang, Shan-Chi Liu, Yen-You Lin, Wei-Chien Huang, Yang-Chang Wu, Chien-Chung Huang, Chun-Hao Tsai, Chih-Yuan Ko, Yueh-Hsiung Kuo, and Chih-Hsin Tang
- Subjects
Nutrition and Dietetics ,Public Health, Environmental and Occupational Health ,Food Science - Abstract
Antcin K, an extract ofRA and healthy synovial tissue samples (Levels of VCAM-1 expression were higher in the GEO database specimens and the study's clinical samples of RA synovial tissue compared with the healthy specimens. Antcin K dose-dependently inhibited VCAM-1 expression and monocyte adhesion in RASFs. Antcin K also significantly inhibited levels of VCAM-1 and monocyte CD11b expression in CIA tissue. These effects appeared to be mediated by MEK1/2-ERK, p38, and AP-1 signaling.Antcin K seems promising for the treatment of RA and deserves further investigations.
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- 2022
38. Novel Aurora A Kinase Inhibitor Fangchinoline Enhances Cisplatin–DNA Adducts and Cisplatin Therapeutic Efficacy in OVCAR-3 Ovarian Cancer Cells-Derived Xenograft Model
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Daniel Winardi, Pei-Yi Chu, Guan-Yu Chen, Ke Wang, Wei-Yu Hsu, Ching-Liang Hsieh, Yung-Hsiang Chen, Yang-Chang Wu, and Juan-Cheng Yang
- Subjects
Models, Molecular ,mice ,Protein Conformation ,QH301-705.5 ,cisplatin ,fangchinoline ,Benzylisoquinolines ,Catalysis ,Inorganic Chemistry ,DNA Adducts ,Cell Line, Tumor ,Animals ,Humans ,Physical and Theoretical Chemistry ,Biology (General) ,Molecular Biology ,QD1-999 ,Spectroscopy ,Aurora Kinase A ,Ovarian Neoplasms ,Organic Chemistry ,Drug Synergism ,General Medicine ,Xenograft Model Antitumor Assays ,Computer Science Applications ,Gene Expression Regulation, Neoplastic ,Molecular Docking Simulation ,inhibitor ,Chemistry ,ovarian cancer ,Drug Resistance, Neoplasm ,Aurora A kinase ,Female - Abstract
Aurora A kinase (Aurora A) is a serine/threonine kinase regulating control of multiple events during cell-cycle progression. Playing roles in promoting proliferation and inhibiting cell death in cancer cells leads Aurora A to become a target for cancer therapy. It is overexpressed and associated with a poor prognosis in ovarian cancer. Improving cisplatin therapy outcomes remains an important issue for advanced-stage ovarian cancer treatment, and Aurora A inhibitors may improve it. In the present study, we identified natural compounds with higher docking scores than the known Aurora A ligand through structure-based virtual screening, including the natural compound fangchinoline, which has been associated with anticancer activities but not yet investigated in ovarian cancer. The binding and inhibition of Aurora A by fangchinoline were verified using cellular thermal shift and enzyme activity assays. Fangchinoline reduced viability and proliferation in ovarian cancer cell lines. Combination fangchinoline and cisplatin treatment enhanced cisplatin–DNA adduct levels, and the combination index revealed synergistic effects on cell viability. An in vivo study showed that fangchinoline significantly enhanced cisplatin therapeutic effects in OVCAR-3 ovarian cancer-bearing mice. Fangchinoline may inhibit tumor growth and enhance cisplatin therapy in ovarian cancer. This study reveals a novel Aurora A inhibitor, fangchinoline, as a potentially viable adjuvant for ovarian cancer therapy.
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- 2022
39. Secondary Metabolites and Bioactivities of Aspergillus ochraceopetaliformis Isolated from Anthurium brownii
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Hao-Chun Hu, Yuan-Bin Cheng, Tsong-Long Hwang, Yi-Hong Tsai, Ferenc Fülöp, Chia-Hung Yen, Shu-Li Chen, Fang Rong Chang, Dai-Yun Yang, Attila Hunyadi, Chi-Ying Li, and Yang Chang Wu
- Subjects
Anthurium ,biology ,Stereochemistry ,Superoxide ,General Chemical Engineering ,Elastase ,Phenylalanine ,General Chemistry ,biology.organism_classification ,Aspergillus ochraceopetaliformis ,chemistry.chemical_compound ,Chemistry ,Biosynthesis ,chemistry ,Penicillic acid ,Two-dimensional nuclear magnetic resonance spectroscopy ,QD1-999 - Abstract
Five new polyketides, asperochrapyran (1) and asperochralactones A-D (2-5), along with 12 known polyketides (6-17), were obtained from the fungal strain Aspergillus ochraceopetaliformis. Structures of all isolates were elucidated by their spectroscopic parameters. The relative configurations of the new compounds were deduced by the data of coupling constants and NOESY spectra. The absolute configurations were determined by the comparison of experimental and calculated ECD spectra. Moreover, the plausible biosynthesis pathway of major isolates was proposed as well. Anti-inflammatory activity of compounds 5 and 7-17 were evaluated with human neutrophils in response to the stimulation of formyl-methionyl-leucyl phenylalanine (fMLP). Asperlactone (9), aspyrone (13), and (-)-(3R)-mellein (14) exerted superoxide anion inhibition at 30 ± 9%, 29 ± 9%, and 26 ± 12%, respectively, at 10 μM. The capacities of asperlactone (9), aspilactonol B (10), penicillic acid (12), and (-)-(3R)-mellein (14) in elastase release inhibition were revealed as 25 ± 4%, 38 ± 8%, 25 ± 5%, and 34 ± 9%, respectively, at 10 μM.
- Published
- 2020
40. Natural products development under epigenetic modulation in fungi
- Author
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Fang Rong Chang, Chi-Ying Li, Attila Hunyadi, Clay C. C. Wang, Yang Chang Wu, and Yu-Ming Chung
- Subjects
0106 biological sciences ,chemistry.chemical_classification ,Plant Science ,Computational biology ,Biology ,01 natural sciences ,DNA methyltransferase ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Clinical therapy ,Enzyme ,chemistry ,Histone deacetylase ,Epigenetics ,Natural Product Research ,Gene ,High potential ,010606 plant biology & botany ,Biotechnology - Abstract
Natural products derived from microorganisms play a key role in the discovery and development of drug candidates. Several drugs have originated from secondary metabolites or their derivatives from microorganisms in clinical therapy, such as penicillin, cyclosporine, and lovastatin. Application of epigenetic methodology on modulation and stimulation of secondary metabolites from fungi provides a practical way to investigate fungal natural products. Addition of enzyme inhibitors such as histone deacetylase (HDAC) or DNA methyltransferase (DNMT) inhibitors to activate silent biosynthetic gene clusters result in the potential for generating a variety of secondary metabolites with novel skeletons and diversity of stereochemistry, as well as unprecedented heterocyclic rings. After triggering the epigenetic modifiers, some species were affected and produced several uncovered secondary metabolites. Although this strategy has been successfully carried out for few reports, the results of this research field have demonstrated high potential for engineering the secondary metabolites from fungi. By utilizing the above strategy, modulation and characterization of the secondary metabolites from fungi make them able to generate several novel or bioactive natural products that will provide sources for discovering new candidates. Furthermore, the epigenetic modulation technique integrated with pharmacological assays for further investigation becomes a promising avenue for improvement of natural products research and development. This review summarizes the progression and development of epigenetic manipulation in fungal natural product research.
- Published
- 2020
41. Anti-inflammatory, Antiplatelet Aggregation, and Antiangiogenesis Polyketides from Epicoccum sorghinum: Toward an Understating of Its Biological Activities and Potential Applications
- Author
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Yang Chang Wu, Yuan-Bin Cheng, Yi Hong Tsai, Judit Hohmann, Ching Chia Chang, Chi Ying Li, Fang Rong Chang, Tsong-Long Hwang, Chin Chung Wu, Zih Jie Yang, Shih-Wei Wang, Mohamed El-Shazly, and Chien Kei Wei
- Subjects
medicine.drug_class ,Chemistry ,General Chemical Engineering ,Ethyl acetate ,Biological activity ,General Chemistry ,Article ,Hemorrhagic disorder ,Anti-inflammatory ,Bioactive compound ,Polyketide ,chemistry.chemical_compound ,Biochemistry ,medicine ,Bioassay ,Cytotoxicity ,QD1-999 - Abstract
The ethyl acetate extract of an endophyte Epicoccum sorghinum exhibited anti-inflammatory activity at a concentration of
- Published
- 2020
42. New trihydroxybriarane diterpenoids from an octocoral Briareum sp
- Author
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You Ying Chen, Yang Chang Wu, Ping-Jyun Sung, Nai Cheng Lin, Zhi-Hong Wen, Yu-Chia Chang, Gene-Hsiang Lee, Bo Rong Peng, and Chiung Chin Hu
- Subjects
Supercritical carbon dioxide ,010405 organic chemistry ,Stereochemistry ,Excavatolide B ,Chemistry ,Absolute configuration ,Plant Science ,01 natural sciences ,Biochemistry ,Terpenoid ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,Agronomy and Crop Science ,Biotechnology - Abstract
Chemical investigation of the extract from the supercritical CO2 extraction of an octocoral identified as Briareum sp., afforded a known briarane-type diterpenoid, excavatolide B (1), and a pair of new briaranes, briaviolides Y (2) and Z (3). The absolute configuration of 1 was determined by a single-crystal diffraction analysis and the structures of briaranes 2 and 3 were elucidated by using spectroscopic methods. Additionally, anti-inflammatory analysis showed that briarane 3 suppressed the iNOS and COX-2 levels, in LPS-stimulated RAW264.7 cells.
- Published
- 2020
43. Soya-cerebroside inhibits VEGF-facilitated angiogenesis in endothelial progenitor cells
- Author
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Hsiang-Ping Lee, Jai Sing Yang, Shih-Wei Wang, Te-Mao Li, Liang-Wei Lin, Chih-Hsin Tang, Fuu Jen Tsai, and Yang Chang Wu
- Subjects
lcsh:Immunologic diseases. Allergy ,Angiogenesis ,VEGF receptors ,Immunology ,soya-cerebroside ,01 natural sciences ,chemistry.chemical_compound ,angiogenesis ,0404 agricultural biotechnology ,Progenitor cell ,lcsh:Agriculture (General) ,vegf ,endothelial progenitor cells ,biology ,Chemistry ,010401 analytical chemistry ,04 agricultural and veterinary sciences ,040401 food science ,lcsh:S1-972 ,Cerebroside ,0104 chemical sciences ,Cell biology ,Vascular endothelial growth factor ,biology.protein ,cardiovascular system ,lcsh:RC581-607 ,Agronomy and Crop Science ,Food Science - Abstract
Vascular endothelial growth factor (VEGF) is well recognized as an essential component of angiogenesis and the increased proliferation and migration of endothelial cells. Bone marrow-derived endothelial progenitor cells (EPCs) are involved in VEGF-induced vessel formation during physiological and pathological states. Soya-cerebroside, an extract from Cordyceps militaris, reduces synovial inflammation and prevents cartilage damage in an osteoarthritis model. However, the role of soya-cerebroside in VEGF-regulated EPC angiogenesis is uncertain. Records from the Oncomine database demonstrate higher levels of VEGF in cancerous tissue compared with normal tissue. This study describes VEGF-induced promotion of EPC-associated angiogenesis in vivo and how the treatment of EPCs with soya-cerebroside inhibited VEGF-facilitated migration and tube formation. The study evidence shows that the c-Src, FAK and Runx2 signalling pathways are involved in the inhibitory effects of soya-cerebroside. This novel agent may therefore be used to inhibit EPC-associated angiogenesis.
- Published
- 2020
44. Soya-cerebroside reduces interleukin production in human rheumatoid arthritis synovial fibroblasts by inhibiting the ERK, NF-κB and AP-1 signalling pathways
- Author
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Yang Chang Wu, Wei Chien Huang, Te-Mao Li, Chih-Hsin Tang, Hsiang-Ping Lee, Chin-Jung Hsu, Shan-Chi Liu, and Bo-Cheng Chen
- Subjects
MAPK/ERK pathway ,rheumatoid arthritis ,lcsh:Immunologic diseases. Allergy ,il-1β ,Immunology ,soya-cerebroside ,01 natural sciences ,Proinflammatory cytokine ,chemistry.chemical_compound ,0404 agricultural biotechnology ,il-8 ,Cordyceps militaris ,il-6 ,medicine ,Synovial fluid ,Interleukin 8 ,lcsh:Agriculture (General) ,Interleukin 6 ,biology ,Chemistry ,010401 analytical chemistry ,food and beverages ,NF-κB ,04 agricultural and veterinary sciences ,medicine.disease ,biology.organism_classification ,040401 food science ,lcsh:S1-972 ,0104 chemical sciences ,biology.protein ,Cancer research ,lcsh:RC581-607 ,Agronomy and Crop Science ,Infiltration (medical) ,Food Science - Abstract
Rheumatoid arthritis (RA) is characterised by the infiltration of a number of proinflammatory cytokines into synovial fluid. Soya-cerebroside, an extract from Cordyceps militaris, inhibits synovial inflammation and reduces cartilage damage in an osteoarthritis model, although the role of soya-cerebroside in inflammatory cytokine expression in RA is uncertain. In this study, Gene Expression Omnibus (GEO) database records revealed higher levels of interleukin (IL)-1β, IL-6 and IL-8 in RA tissue compared with normal tissue. Elevated levels of these inflammatory cytokines were also higher in mice with collagen-induced arthritis (CIA) than in control mice. Soya-cerebroside effectively inhibited IL-1β, IL-6 and IL-8 expression in RA synovial fibroblasts, apparently by inhibiting the ERK, NF-κB and AP-1 signalling pathways. This anti-inflammatory agent shows promise for the treatment of RA.
- Published
- 2020
45. Cordycerebroside A inhibits ICAM-1-dependent M1 monocyte adhesion to osteoarthritis synovial fibroblasts
- Author
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Kun‐Tsan Lee, Chin‐Horng Su, Shan‐Chi Liu, Bo‐Cheng Chen, Jun‐Way Chang, Chun‐Hao Tsai, Wei‐Chien Huang, Chin‐Jung Hsu, Wei‐Cheng Chen, Yang‐Chang Wu, and Chih‐Hsin Tang
- Subjects
Pharmacology ,Osteoarthritis ,Synovial Membrane ,Biophysics ,Animals ,Cell Biology ,Fibroblasts ,Intercellular Adhesion Molecule-1 ,Monocytes ,Food Science ,Rats - Abstract
Osteoarthritis (OA) is represented by the accumulation and adhesion of M1 macrophages into synovium tissues in the joint microenvironment and subsequent inflammatory response. Cordycerebroside A, a cerebroside compound isolated from Cordyceps militaris, exhibits anti-inflammatory activity, but has not yet been examined in M1 macrophages during OA disease. Our results indicate higher expression of M1 macrophage markers in synovium tissue from OA patients compared with normal healthy controls. Records from the Gene Expression Omnibus (GEO) data set and our clinic samples revealed higher levels of ICAM-1 (a critical adhesion molecule during OA disease) and CD86 (a M1 macrophage marker) in OA synovial tissue than in healthy tissue. The same effects were found in rats with OA induced by anterior cruciate ligament transaction (ACLT). We also found that cordycerebroside A inhibited ICAM-1 synthesis and antagonized M1 macrophage adhesion to OA synovial fibroblasts by inhibiting the ERK/AP-1 pathway. Thus, cordycerebroside A displayed novel anti-arthritic effects. PRACTICAL APPLICATIONS: Here we report a higher level of M1 macrophage markers and ICAM-1 in synovium tissue from OA patients compared with normal healthy controls by using GEO data set and our clinic samples. The same effects were revealed in rats with OA induced by ACLT. Cordycerebroside A significantly suppressed ICAM-1 production and diminished M1 macrophage adhesion to OA synovial fibroblasts. Therefore, cordycerebroside A exhibited novel anti-OA functions.
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- 2022
46. Antrodia cinnamomea and its compound dehydroeburicoic acid attenuate nonalcoholic fatty liver disease by upregulating ALDH2 activity
- Author
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Yi-ni Cao, Shan-shan Yue, An-yi Wang, Lu Xu, Yi-tong Hu, Xue Qiao, Tung-Ying Wu, Min Ye, Yang-Chang Wu, and Rong Qi
- Subjects
Pharmacology ,Inflammation ,Aldehyde Dehydrogenase, Mitochondrial ,Fatty Acids ,Diet, High-Fat ,Lipid Metabolism ,Mice, Inbred C57BL ,Lanosterol ,Mice ,Liver ,Non-alcoholic Fatty Liver Disease ,Drug Discovery ,Animals ,Polyporales - Abstract
Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver disease, but currently has no specific medication in clinic. Antrodia cinnamomea (AC) is a medicinal fungus and it has been shown that AC can inhibit high fat diet (HFD)-induced lipid deposition in mouse livers, but the effective monomer in AC and mechanism against NAFLD remain unclear. It has been reported that aldehyde dehydrogenase 2 (ALDH2) activation shows protective effects on NAFLD. Our previous study demonstrates that AC and its monomer dehydroeburicoic acid (DEA) can upregulate the ALDH2 activity on alcoholic fatty liver disease mouse model, but it is not clear whether the anti-NAFLD effects of AC and DEA are mediated by ALDH2.To elucidate the active compound in AC against NAFLD, study whether ALDH2 mediates the anti-NAFLD effects of AC and its effective monomer.WT mice, ALDH2-/- mice and ALDH2-/- mice re-expressed ALDH2 by lentivirus were fed with a methionine-choline deficient (MCD) diet or high fat diet (HFD) to induce NAFLD, and AC at the different doses (200 and/or 500 mg/kg body weight per day) was administrated by gavage at the same time. Primary hepatocytes derived from WT and ALDH2-/-mice were stimulated by oleic acid (OA) to induce lipid deposition, and the cells were treated with AC or DEA in the meantime. Lentivirus-mediated ALDH2-KD or ALDH2-OE were used to knock down or overexpress ALDH2 expression in HepG2 cells, respectively. Finally, the effects of DEA against NAFLD as well as its effects on upregulating liver ALDH2 and removing the harmful aldehyde 4-hydroxynonenal (4-HNE) were studied in the MCD diet-induced NAFLD mouse model.In WT mice fed with a MCD diet or HFD, AC administration reduced hepatic lipid accumulation, upregulated ALDH2 activity in mouse livers, decreased 4-HNE contents both in mouse livers and serum, inhibited lipogenesis, inflammation and oxidative stress and promoted fatty acid β-oxidation. These effects were abolished in ALDH2 KO mice but could be restored by re-expression of ALDH2 by lentivirus. In primary hepatocytes of WT mice, AC and DEA inhibited OA-induced lipid accumulation and triglyceride (TG) synthesis, promoting the β-oxidation of fatty acid in the meantime. However, these effects were lost in primary hepatocytes of ALDH2 KO mice. Moreover, the expression level of ALDH2 significantly affected the inhibitory effects of AC and DEA on OA-induced lipid deposition in HepG2 cells. The effects of AC and DEA on suppressing lipid deposition, inhibiting mitochondrial ROS levels, reducing TG synthesis, and promoting β-oxidation of fatty acid were all enhanced with the overexpression of ALDH2 and reduced with the knockdown of ALDH2 expression. DEA showed dose-dependent effects on inhibiting liver lipid deposition, elevating ALDH2 activity and reducing 4-HNE levels in the livers of MCD diet-induced NAFLD mice.DEA is the effective compound in AC against NAFLD. The related anti-NAFLD mechanisms of AC and DEA were through upregulating ALDH2 expression and activity, thus enhancing the elimination of 4-HNE in the livers, and sequentially alleviating oxidative stress and inflammation, promoting fatty acid β-oxidation and decreasing lipogenesis.
- Published
- 2021
47. Antcin K inhibits VEGF-dependent angiogenesis in human rheumatoid arthritis synovial fibroblasts
- Author
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Yang Chang Wu, Wei Chien Huang, Yen-You Lin, Hsiang-Ping Lee, David Achudhan, Chih-Hsin Tang, Yueh-Hsiung Kuo, Shan-Chi Liu, and Shih-Wei Wang
- Subjects
Pharmacology ,Tube formation ,Vascular Endothelial Growth Factor A ,Angiogenesis ,Cholestenes ,Synovial Membrane ,Biophysics ,Arthritis ,Cell Biology ,Fibroblasts ,medicine.disease ,Endothelial progenitor cell ,Proinflammatory cytokine ,Vascular endothelial growth factor ,Arthritis, Rheumatoid ,chemistry.chemical_compound ,Mice ,chemistry ,Cancer research ,medicine ,Synovial fluid ,Animals ,Humans ,Viability assay ,Food Science - Abstract
Antrodia cinnamomea is a well-known medicinal mushroom in Taiwan that exhibits anti-inflammatory biological activities. In rheumatoid arthritis (RA), chronic inflammation and angiogenesis driven by proinflammatory cytokines reflect the severity of the disease. Although biological treatments have improved the outlook for RA, no healing exists. Moreover, the available pharmacotherapies do not work for all patients and drug safety is a major consideration. Investigations into plant-based medicines hope to reveal better, more tolerable agents. We examined whether Antcin K, a phytosterol isolated from A. cinnamomea, has anti-angiogenic activity in RA. The GSE12021 gene dataset from the Gene Expression Omnibus (GEO) database was examined for levels of vascular endothelial growth factor (VEGF) expression in 10 RA and 10 osteoarthritis (OA) synovial tissue samples. In clinical samples, VEGF expression was analyzed by immunohistochemical staining and ELISA in normal and RA synovial tissue, as well as OA and RA synovial fluid. Collagen-induced arthritis (CIA) and control tissue was stained with hematoxylin and eosin (HE) for histological changes; Safranin O/Fast Green staining examined histopathological changes and evidence of bone erosion. Human RA synovial fibroblasts (RASFs) were incubated with Antcin K and cell viability was examined by the MTT assay. VEGF mRNA expression was detected in RASFs using qPCR. Antcin K significantly inhibited VEGF expression and ameliorates endothelial progenitor cell (EPC) migration and tube formation in RASFs by downregulating the phospholipase C-γ/protein kinase C-α pathway. Antcin K also induced anti-angiogenic effects in human RASFs without cytotoxicity. PRACTICAL APPLICATIONS: Analysis of GEO dataset samples and human synovial fluids or synovial tissues revealed higher VEGF levels in rheumatoid arthritis (RA) samples compared with osteoarthritis (OA) and healthy control samples. VEGF levels were also higher in mice with collagen-induced arthritis (CIA) than in healthy controls. Antcin K markedly suppressed VEGF expression in human RA synovial fibroblasts and inhibited the migration and tube formation of epithelial progenitor cells (EPCs) by downregulating the phospholipase C-γ/protein kinase C-α pathway. Further investigations are warranted to examine the effects of Antcin K in other angiogenesis-associated disorders.
- Published
- 2021
48. Snail Mucus Enhances Chemosensitivity of Triple-negative Breast Cancer
- Author
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Chien-Yi, Ho, Dai-Wei, Hu, Bo-Rong, Chen, Chun-Chun, Yang, Chun-Hsu, Yao, Tien, Ni, Wei-Chuan, Ho, Yueh-Sheng, Chen, Chih-Yen, Tu, Wei-Chao, Chang, Yang-Chang, Wu, Chih-Hsin, Tang, Hui-Chi, Huang, Wei-Chien, Huang, and Tzong-Shiun, Li
- Subjects
Cell Survival ,Snails ,Antineoplastic Agents ,Apoptosis ,Drug Synergism ,Triple Negative Breast Neoplasms ,Mucus ,Doxorubicin ,Drug Resistance, Neoplasm ,Cell Line, Tumor ,Animals ,Humans ,fas Receptor ,Cell Proliferation ,Signal Transduction - Abstract
The poor prognosis and chemoresistance of patients with triple-negative breast cancer (TNBC) urge the development of new therapeutic strategies. Snail mucus has shown its ability against inflammation, a process closely related to tumorigenesis, suggesting a potential anti-cancer activity.The effect and mechanisms of snail mucus on cell viability were determined by IncuCyte Live-cell analysis and molecular biological methods. The anti-cancer fractions of snail mucus were isolated and identified by medium pressure liquid chromatography (MPLC) and nuclear magnetic resonance (NMR) spectrometry analysis.Snail mucus significantly decreased the viability of TNBC cells with relatively lower cytotoxicity to normal breast epithelial cells and enhanced their response to chemotherapy through activation of Fas signaling by suppressing nucleolin. Two peptide fractions have been identified as the anti-cancer ingredients of the snail mucus.Snail mucus can induce programmed cell death via the extrinsic apoptotic pathway and has therapeutic potential by achieving a chemo-sensitizing effect in TNBCs.
- Published
- 2021
49. Ursolic acid silences CYP19A1/aromatase to suppress gastric cancer growth
- Author
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Wen‐Lung Ma, Ning Chang, Yingchun Yu, Yu‐Ting Su, Guan‐Yu Chen, Wei‐Chung Cheng, Yang‐Chang Wu, Ching‐Chia Li, Wei‐Chun Chang, and Juan‐Cheng Yang
- Subjects
Cancer Research ,Ethanol ,Plant Extracts ,Antineoplastic Agents ,Triterpenes ,Molecular Docking Simulation ,Aromatase ,Oncology ,Stomach Neoplasms ,Hedyotis ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Fluorouracil - Abstract
Gastric cancer (GCa) is a malignancy with few effective treatments. Ursolic acid (UA), a bioactive triterpenoid enriched in Hedyotis diffusa Willd, known to suppress GCa without identified target. CYP19A1 (cytochrome P450 family 19A1; also known as aromatase, Ar) was correlated to GCa prognosis. Relatedly, Ar silencers, which halt the expression of Ar exhibited anti-GCa effects in experimental models, are currently being investigated.The docking simulation score of UA was compared with Ar inhibitors, e.g., letrozole, exemestane, in Ar protein crystallization. Hedyotis diffusa Willd ethanol extract, UA, or 5-fluracil were applied onto AGS, SC-M1, MKN45 GCa cells for cancer inhibition tests. Immunoblot for measuring gene expressions upon drug treatments, or gene knockdown/overexpression. Treatments were also applied in a MKN45 implantation tumor model. A web-based GCa cohort for Ar expression association with prognosis was performed.The ethanol extracts of Hedyotis diffusa Willd, enrich with UA, exhibited cytotoxic activity against GCa cells. Molecular docking simulations with the 3D Ar structure revealed an excellent fitting score for UA. UA increase cytotoxic, and suppressed colony, in addition to its Ar silencing capacity. Moreover, UA synergistically facilitated 5-FU, (a standard GCa treatment) regimen in vitro. Consistent with those results, adding estradiol did not reverse the cancer-suppressing effects of UA, which confirmed UA acts as an Ar silencer. Furthermore, UA exhibited tumor-suppressing index (TSI) score of 90% over a 6-week treatment term when used for single dosing in xenograft tumor model. In the clinical setting, Ar expression was found to be higher in GCa tumors than normal parental tissue from the TCGA (The Cancer Genome Atlas) cohort, while high Ar expression associated with poor prognosis. Together, the results indicate UA could be used to treat GCa by silencing Ar expression in GCa. Hedyotis diffusa Willd ethanol extract could be an functional food supplements.
- Published
- 2021
50. Cordycerebroside A suppresses VCAM-dependent monocyte adhesion in osteoarthritis synovial fibroblasts by inhibiting MEK/ERK/AP-1 signaling
- Author
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Chin-Jung Hsu, Hsien-Te Chen, Yang Chang Wu, Yu-Han Wang, Wei Chien Huang, Bo-Cheng Chen, Hsiang-Ping Lee, Te-Mao Li, Shan-Chi Liu, and Chih-Hsin Tang
- Subjects
MAPK/ERK pathway ,VCAM-1 ,Nutrition and Dietetics ,biology ,Monocyte adhesion ,Cell adhesion molecule ,Chemistry ,Nutrition. Foods and food supply ,Monocyte ,Medicine (miscellaneous) ,Motility ,Adhesion ,Osteoarthritis ,medicine.disease ,Nitric oxide synthase ,Cordycerebroside A ,medicine.anatomical_structure ,Integrin alpha M ,biology.protein ,medicine ,Cancer research ,TX341-641 ,Food Science - Abstract
Osteoarthritis (OA) is characterized by the infiltration and adhesion of monocyte into the joint synovium. Vascular cell adhesion molecule 1 (VCAM-1) is a critical cell adhesion molecule that controls monocyte motility during OA progression. Cordycerebroside A, a cerebroside compound isolated from Cordyceps militaris, inhibits the production of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in synovial macrophages, but has not yet been investigated in OA. Gene Expression Omnibus (GEO) dataset analysis revealed higher levels of VCAM-1 and CD11b (a monocyte marker) in OA synovial tissue compared with normal healthy tissue. The same results were observed in anterior cruciate ligament transaction (ACLT)-induced OA in rats compared with normal healthy controls. Cordycerebroside A markedly suppressed VCAM-1 expression and monocyte adhesion in human OA synovial fibroblasts. The MEK, ERK and AP-1 signaling cascades regulated cordycerebroside A-induced inhibition of VCAM-1 production. Thus, cordycerebroside A is a promising agent for the treatment of OA.
- Published
- 2021
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