Nucleophosmin modulates the alleviation of atopic dermatitis caused by the marine-derived compound dihydroaustrasulfone alcohol

Han-Chun Hung,Chien-Wei Feng,Yen-You Lin,Chun-Hong Chen,Kuan-Hao Tsui,Wu-Fu Chen,Chieh-Yu Pa,Jyh-Horng Sheu,Chun-Sung Sung,Zhi-Hong Wen 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Atopic dermatitis (AD) is a chronic inflammatory skin disease, and its prevalence is increasing. AD usually elicits skin barrier dysfunction, dry skin and itching. As the mechanisms of AD remain unknown, there is an urgent need to find effective therapies. Because of the diversity and complexity of marine environments, the discovery of drugs from marine organisms as novel therapeutic agents for human diseases has seen renewed interest. Dihydroaustrasulfone alcohol (WA-25), the synthetic precursor of austrasulfone, which is a natural product isolated from a Formosan soft coral, has been shown to possess many therapeutic effects in our previous studies. However, the detailed mechanisms and therapeutic effects of WA-25 on AD are incompletely understood. We performed in vitro and in vivo studies to examine the effects of WA-25 on AD. We showed that WA-25 blocks inflammation and oxidative stress. Simultaneously, we also found that WA-25 reduces the AD scores and AD-induced transepidermal water loss (TEWL), scratching behavior, and alloknesis. WA-25 is more effective in cases of AD than are the drugs that are currently used clinically. Importantly, we also found that when nucleophosmin (NPM) was inhibited or when its expression was reduced, the anti-inflammatory and anti-AD effects of WA-25 were blocked. These data suggest that NPM plays dual roles in inflammation and AD. Overall, these results suggest that WA-25 is a potential anti-inflammatory and AD therapeutic agent that is modulated by NPM.

Virtual Screening and Testing of GSK-3 Inhibitors Using Human SH-SY5Y Cells Expressing Tau Folding Reporter and Mouse Hippocampal Primary Culture under Tau Cytotoxicity

Lin Chih-Hsin,Hsieh Yu-Shao,Sun Ying-Chieh,Huang Wun-Han,Chen Shu-Ling,Weng Zheng-Kui,Lin Te-Hsien,Wu Yih-Ru,Chang Kuo-Hsuan,Huang Hei-Jen,Lee Guan-Chiun,Hsieh-Li Hsiu Mei,Lee-Chen Guey-Jen 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.1

Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.

Fabrication of alignment layer free flexible liquid crystal cells using thermal nanoimprint lithography

Tzu-Chieh Lin,Shao-Chi Yu,Pei-Shiang Chen,Kai-Yuan Chi,Han-Chang Pan,Chih-Yu Chao 한국물리학회 2009 Current Applied Physics Vol.9 No.3

In this article, thermal nanoimprint lithography (thermal-NIL) has been utilized to transfer the microgroove pattern onto the plastic substrate. Without coating alignment polymer, the microgrooves on the flexible substrates can align liquid crystals (LCs) directly. The flexible LC cell is shown to maintain comparable electro-optical properties while bending. The plastic film and the alignment layer integrated into an alignment substrate could effectively prevent cracks of the additional polymer alignment layer during the bending process. This method is applicable to the roll-to-roll process to increase the production efficiency. In this article, thermal nanoimprint lithography (thermal-NIL) has been utilized to transfer the microgroove pattern onto the plastic substrate. Without coating alignment polymer, the microgrooves on the flexible substrates can align liquid crystals (LCs) directly. The flexible LC cell is shown to maintain comparable electro-optical properties while bending. The plastic film and the alignment layer integrated into an alignment substrate could effectively prevent cracks of the additional polymer alignment layer during the bending process. This method is applicable to the roll-to-roll process to increase the production efficiency.

Rock wool wastes as a supplementary cementitious material replacement in cement-based composites

Wei-Ting Lin,An Cheng,Ran Huang,Yuan-Chieh Wu,Ta-Yuan Han 사단법인 한국계산역학회 2013 Computers and Concrete, An International Journal Vol.11 No.2

The use of rock wool waste, an industrial by-product, in cement-based composites has positive effects on the environment because it reduces the problems associated rock wool disposal. The experiments in this study tested cement-based composites using various rock wool waste contents (10, 20, 30 and 40% by weight of cement) as a partial replacement for Portland cement in mortars. The pozzolanic strength activity test, flow test, compressive strength test, dry shrinkage test, absorption test, initial surface absorption test and scanning electron microscope observations were conducted to evaluate the properties of cement-based composites. Test results demonstrate that the pozzolanic strength activity index for rock wool waste specimens is 103% after 91 days. The inclusion of rock wool waste in cement-based composites decreases its dry shrinkage and initial surface absorption, and increases its compressive strength. These improved properties are the result of the dense structure achieved by the filling effect and pozzolanic reactions of the rock wool waste. The addition of 30% and 10% rock wool wastes to cement is the optimal amount based on the results of compressive strength and initial surface absorption for a w/cm of 0.35 and 0.55, respectively. Therefore, it is feasible to utilize rock wool waste as a partial replacement of cement in cement-based composites.

Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis

Kuei-Chuan Lee,Pei-Shan Wu,Han-Chieh Lin 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.1

The initial presentation of non-alcoholic steatohepatitis (NASH) is hepatic steatosis. The dysfunction of lipid metabolism within hepatocytes caused by genetic factors, diet, and insulin resistance causes lipid accumulation. Lipotoxicity, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum stress would further contribute to hepatocyte injury and death, leading to inflammation and immune dysfunction in the liver. During the healing process, the accumulation of an excessive amount of fibrosis might occur while healing. During the development of NASH and liver fibrosis, the gut-liver axis, adipose-liver axis, and renin-angiotensin system (RAS) may be dysregulated and impaired. Translocation of bacteria or its end-products entering the liver could activate hepatocytes, Kupffer cells, and hepatic stellate cells, exacerbating hepatic steatosis, inflammation, and fibrosis. Bile acids regulate glucose and lipid metabolism through Farnesoid X receptors in the liver and intestine. Increased adipose tissue-derived non-esterified fatty acids would aggravate hepatic steatosis. Increased leptin also plays a role in hepatic fibrogenesis, and decreased adiponectin may contribute to hepatic insulin resistance. Moreover, dysregulation of peroxisome proliferator-activated receptors in the liver, adipose, and muscle tissues may impair lipid metabolism. In addition, the RAS may contribute to hepatic fatty acid metabolism, inflammation, and fibrosis. The treatment includes lifestyle modification, pharmacological therapy, and non-pharmacological therapy. Currently, weight reduction by lifestyle modification or surgery is the most effective therapy. However, vitamin E, pioglitazone, and obeticholic acid have also been suggested. In this review, we will introduce some new clinical trials and experimental therapies for the treatment of NASH and related fibrosis.

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.