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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.
Jia-Ming Chen,Wan-Li Chiang,Bin-Chuan Ji,Ruei-Jhe Jhang,Pei-Hsin Chen,Ya-Lun Li,Che-Ju Chang,Sung-Yen Huang,Tsung-Chieh Lee,Chia-Yun Chen,Ching-Hsiung Lin,Sheng-Hao Lin 한국한의학연구원 2023 Integrative Medicine Research Vol.12 No.4
Background: In intensive care units, mechanical ventilation is an important therapy to help patients with dysp- nea. However, long-term ventilator dependence would consume huge medical resources and increase the risk of morbidity and mortality. The aim of the study was to examine the efficacy of the acupuncture combined with western medical care on ventilator parameters in ventilator-dependent patients. Methods: In this clinical trial, 80 ventilator-dependent patients aged 20 to 80 years old were randomly assigned to acupuncture group and control group in the respiratory care center (RCC) of Changhua Christian Hospital. Besides regular medical care and therapy, participants in the acupuncture group received acupuncture therapy at the same 17 acu-points for 20 minutes once a day, a total of 12 sessions. The ventilator parameters were recorded to evaluate the respiratory efficiency for all participants. The primary outcome was rapid shallow breathing index (RSBI), and secondary outcomes were respiratory rate (RR), tidal volume (TV) and ventilation per minute (MV). Results: Though there was no significant difference in the parameter between the acupuncture group and the control group, we found the trend of decreasing RSBI in the acupuncture group. In subgroup analyses, the mean of RSBI significantly decreased 16.02 (with the SD in 60.84) in acupuncture group, while it increased 17.84 (with the SD in 39.38) in control group (p = 0.036) after 12 sessions. Conclusion: Acupuncture treatment can improve breathing ability of patients with respirator dependence in respiratory care center.
Pao-Huan Chen(Pao-Huan Chen),Chun-Ming Shih(Chun-Ming Shih),Chi-Kang Chang(Chi-Kang Chang),Chia-Pei Lin(Chia-Pei Lin),Yung-Han Chang(Yung-Han Chang),Hsin-Chien Lee(Hsin-Chien Lee),El-Wui Loh(El-Wui Lo 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.2
Objective: Predicting disease relapse and early intervention could reduce symptom severity. We attempted to identify potential indicators that predict the duration to next admission for an acute affective episode in patients with bipolar I disorder. Methods: We mathematically defined the duration to next psychiatric admission and performed single-variate regressions using historical data of 101 patients with bipolar I disorder to screen for potential variables for further multivariate regressions. Results: Age of onset, total psychiatric admissions, length of lithium use, and carbamazepine use during the psychiatric hospitalization contributed to the next psychiatric admission duration positively. The all-in-one found that hyperlipidemia during the psychiatric hospitalization demonstrated a negative contribution to the duration to next psychiatric admission; the last duration to psychiatric admission, lithium and carbamazepine uses during the psychiatric hospitalization, and heart rate on the discharge day positively contributed to the duration to next admission. Conclusion: We identified essential variables that may predict the duration of bipolar I patients’ next psychiatric admission. The correlation of a faster heartbeat and a normal lipid profile in delaying the next onset highlights the importance of managing these parameters when treating bipolar I disorder.
Impact Assessments of High Oil Prices on the Agro-Food System and the Role of Bioenergy Crops
Lee, Duu-Hwa,Lin, Hsin-Chun,Chang, Ching-Cheng,Hsu, Shih-Hsun,Chen, Chi-Chun,Sun, Jenny Chin-Hwa Korean Resource Economics Association 2007 자원·환경경제연구 Vol.16 No.3
In this study, multi-sectoral partial equilibrium and computable general equilibrium models of Taiwan are used to investigate the direct and indirect effects of energy price increases on overall economies and agro-food sector in Taiwan. The results suggest that agricultural prices, production cost would increase between 0.27% to 1.88%, and a reduction in GDP around 0.39% to 0.54 %. The negative impact on livestock sector is slightly higher than that on the crop sector. Negative impacts are also observed in the employment and wages. The rising oil price has the potential to discourage production of energy-intensive activity because of the possibility of substitution and adaptations. The growth rate of real GDP will shrink by 0.64% to 1.06% and CPI will increase by 1.17% to 1,95%. Both the agriculture and non-agricultural sector also respond by raising output prices by 0.80% to 1.33%. The rising international oil price has urged the government to take policy actions like using alternative fuels such as biodiesel, bioethanol, and adopting measures to cut down on energy consumptions mainly in transportation sectors in response to public concern over economic shocks.
THE<i>SPITZER</i>c2d SURVEY OF NEARBY DENSE CORES. VII. CHEMISTRY AND DYNAMICS IN L43
Chen, Jo-Hsin,Evans, Neal J.,Lee, Jeong-Eun,Bourke, Tyler L. IOP Publishing 2009 The Astrophysical journal Vol.705 No.2
<P>We present results from the Spitzer Space Telescope and molecular line observations of nine species toward the dark cloud L43. The Spitzer images and molecular line maps suggest that it has a starless core and a Class I protostar evolving in the same environment. CO depletion is seen in both sources, and DCO+ lines are stronger toward the starless core. With a goal of testing the chemical characteristics from pre- to protostellar stages, we adopt an evolutionary chemical model to calculate the molecular abundances and compare with our observations. Among the different model parameters we tested, the best-fit model suggests a longer total timescale at the pre-protostellar stage, but with faster evolution at the later steps with higher densities.</P>
Hsin-Hsi Tsai,Bo-Ching Lee,Ya-Fang Chen,Jiann-Shing Jeng,Li-Kai Tsai 대한뇌졸중학회 2022 Journal of stroke Vol.24 No.3
Background and Purpose Cerebral venous flow alterations potentially contribute to age-related white matter changes, but their role in small vessel disease has not been investigated. Methods This study included 297 patients with hypertensive intracerebral hemorrhages (ICH) who underwent magnetic resonance imaging. Cerebral venous reflux (CVR) was defined as the presence of abnormal signal intensity in the dural venous sinuses or internal jugular vein on time-of-flight angiography. We investigated the association between CVR, dilated perivascular spaces (PVS), and recurrent stroke risk. Results CVR was observed in 38 (12.8%) patients. Compared to patients without CVR those with CVR were more likely to have high grade (>20 in the number) dilated PVS in the basal ganglia (60.5% vs. 35.1%; adjusted odds ratio [aOR], 2.64; 95% confidence interval [CI], 1.25 to 5.60; P=0.011) and large PVS (>3 mm in diameter) (50.0% vs. 18.5%; aOR, 3.87; 95% CI, 1.85 to 8.09; P<0.001). During a median follow-up of 18 months, patients with CVR had a higher recurrent stroke rate (13.6%/year vs. 6.2%/year; aOR, 2.53; 95% CI, 1.09 to 5.84; P=0.03) than those without CVR. Conclusions CVR may contribute to the formation of enlarged PVS and increase the risk of recurrent stroke in patients with hypertensive ICH.
The assessment of host and bacterial proteins in sputum from active pulmonary tuberculosis
Hsin-Chih Lai,Yu-Tze Horng,Pen-Fang Yeh,Jann-Yuan Wang,Chin-Chung Shu,Chia-Chen Lu,Jang-Jih Lu,Jen-Jyh Lee,Po-Chi Soo 한국미생물학회 2016 The journal of microbiology Vol.54 No.11
Pulmonary tuberculosis (TB) is caused by Mycobacterium tuberculosis. The protein composition of sputum may reflect the immune status of the lung. This study aimed to evaluate the protein profiles in spontaneous sputum samples from patients with active pulmonary TB. Sputum samples were collected from patients with pulmonary TB and healthy controls. Western blotting was used to analyze the amount of interleukin 10 (IL-10), interferon-gamma (IFN-γ), IL-25, IL- 17, perforin-1, urease, albumin, transferrin, lactoferrin, adenosine deaminase (also known as adenosine aminohydrolase, or ADA), ADA-2, granzyme B, granulysin, and caspase- 1 in sputum. Results of detection of IL-10, IFN-γ, perforin- 1, urease, ADA2, and caspase-1, showed relatively high specificity in distinguishing patients with TB from healthy controls, although sensitivities varied from 13.3% to 66.1%. By defining a positive result as the detection of any two proteins in sputum samples, combined use of transferrin and urease as markers increased sensitivity to 73.2% and specificity to 71.1%. Furthermore, we observed that the concentration of transferrin was proportional to the number of acidfast bacilli detected in sputum specimens. Detection of sputum transferrin and urease was highly associated with pulmonary TB infection. In addition, a high concentration of transferrin detected in sputum might correlate with active TB infection. This data on sputum proteins in patients with TB may aid in the development of biomarkers to assess the severity of pulmonary TB.
Monacolin K affects lipid metabolism through SIRT1/AMPK pathway in HepG2 cells
Chia-Hsin Huang,Shin-Mau Shiu,Min-Tze Wu,Wei-Lu Chen,Shyang-Guang Wang,Horng-Mo Lee 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.12
Monacolin K is the secondary metabolite isolatedfrom Monascus spp. It is the natural form of lovastatin,which is clinically used to reduce the synthesis of cholesterolby inhibiting 3-hydroxy-3-methylglutaryl coenzyme Areductase. In the present study, monacolin K increased proteinexpression of SIRT1 and phosphorylation level of AMPactivatedprotein kinase (AMPK) in HepG2 cells. Throughactivation of SIRT1/AMPK pathway, monacolin Kincreased phosphorylation of acetyl CoA carboxylase andcaused nuclear translocation of forkhead box O1. The westernblotting results showed that monacolin K increasedexpression of adipose triglyceride lipase but decreasedabundances of fatty acid synthase (FAS) and sterol regulatory element-binding protein 1 (SREBP1). MonacolinK also decreased the intracellular accumulation of lipids asdemonstrated by Oil Red O staining. In addition, theimmunostaining showed that monacolin K prevented thenuclear translocation of SREBP1, indicating the associationwith down-regulation of FAS. All the demonstrated effectsof monacolin K were counteracted by nicotinamide orcompound C, the inhibitors of SIRT1 orAMPK. In summary,monacolin K reduces the lipid content through SIRT1/AMPK pathway in HepG2 cells, which promotes catabolismand inhibits anabolism of lipid.