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

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

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

Monitoring of genetically close Tsaiya duck populations using novel microsatellite markers with high polymorphism

Lai, Fang-Yu,Chang, Yi-Ying,Chen, Yi-Chen,Lin, En-Chung,Liu, Hsiu-Chou,Huang, Jeng-Fang,Ding, Shih-Torng,Wang, Pei-Hwa Asian Australasian Association of Animal Productio 2020 Animal Bioscience Vol.33 No.6

Objective: A set of microsatellite markers with high polymorphism from Tsaiya duck were used for the genetic monitoring and genetic structure analysis of Brown and White Tsaiya duck populations in Taiwan. Methods: The synthetic short tandem repeated probes were used to isolate new microsatellite markers from the genomic DNA of Tsaiya ducks. Eight populations, a total of 566 samples, sourced from Ilan Branch, Livestock Research Institute were genotyped through novel and known markers. The population genetic variables were calculated using optional programs in order to describe and monitor the genetic variability and the genetic structures of these Tsaiya duck populations. Results: In total 24 primer pairs, including 17 novel microsatellite loci from this study and seven previously known loci, were constructed for the detection of genetic variations in duck populations. The average values for the allele number, the effective number of alleles, the observed heterozygosity, the expected heterozygosity, and the polymorphism information content were 11.29, 5.370, 0.591, 0.746, and 0.708, respectively. The results of analysis of molecular variance and principal component analysis indicated a contracting Brown Tsaiya duck cluster and a spreading White Tsaiya duck cluster. The Brown Tsaiya ducks and the White Tsaiya ducks with Pekin ducks were just split to six clusters and three clusters when K was set equal to 6 and 3 in the Bayesian cluster analysis. The individual phylogenetic tree revealed eight taxa, and each individual was assigned to its own population. Conclusion: According to our study, the 24 novel microsatellite markers exhibited a high capacity to analyze relationships of inter- and intra-population in those populations with a relatively limited degree of genetic diversity. We suggest that duck farms in Taiwan could use the new (novel) microsatellite set to monitor the genetic characteristics and structures of their Tsaiya duck populations at various intervals in order to ensure quality breeding and conservation strategies.

Heart Rate Variability Biofeedback Increased Autonomic Activation and Improved Symptoms of Depression and Insomnia among Patients with Major Depression Disorder

I-Mei Lin,Sheng-Yu Fan,Cheng-Fang Yen,Yi-Chun Yeh,Tze‐Chun Tang,Mei-Feng Huang,Tai-Ling Liu,Peng-Wei Wang,Huang-Chi Lin,Hsin-Yi Tsai,Yu-Che Tsai 대한정신약물학회 2019 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.17 No.2

Objective: Autonomic imbalance is considered a psychopathological mechanism underlying major depressive disorder (MDD). Heart rate variability (HRV) is an index for autonomic activation. Poor sleep quality is common among patients with MDD. HRV biofeedback (BF) has been used for regulating autonomic balance among patients with physical illness and mental disorders. The purpose of present study was to examine the effects of HRV-BF on depressive symptoms, sleep quality, pre-sleep arousal, and HRV indices, in patients with MDD and insomnia. Methods: In this case-controlled study, patients with MDD and Pittsburgh Sleep Quality Index (PSQI) score higher than 6 were recruited. The HRV-BF group received weekly 60-minute protocol for 6 weeks, and the control group who have matched the age and sex received medical care only. All participants were assessed on Beck Depression Inventory-II, Back Anxiety Inventory, PSQI, and Pre-Sleep Arousal Scale. Breathing rates and electrocardiography were also performed under resting state at pre-testing, and post-testing conditions and for the HRV-BF group, also at 1-month follow-up. Results: In the HRV-BF group, symptoms of depression and anxiety, sleep quality, and pre-sleep arousal were significantly improved, and increased HRV indices, compared with the control group. Moreover, in the HRV-BF group, significantly improved symptoms of depression and anxiety, decreased breathing rates, and increased HRV indices were detected at post-testing and at 1-month follow-up, compared with pre-testing values. Conclusion: This study confirmed that HRV-BF is a useful psychosocial intervention for improving autonomic balance, baroreflex, and symptoms of depression and insomnia in MDD patients.

Treatment Retention Rates of 3-monthly Paliperidone Palmitate and Risk Factors Associated with Discontinuation: A Population-based Cohort Study

Chien-Heng Lin,Huang-Li Lin,Chih-Lin Chiang,Yi-Wen Chen,Yan-Fang Liu,Yen Kuang Yang,Chao-Hsiun Tang 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.3

Objective: Limited evidence exists regarding real-world 3-monthly paliperidone palmitate (PP3M) treatment retention and associated factors. Methods: We conducted a retrospective, nationwide cohort study using the Taiwan National Health Insurance Research Database between October 2017 and December 2019. Adult patients with schizophrenia initiated on PP3M were enrolled. The primary outcomes were time to PP3M discontinuation, time to psychiatric hospitalization, and the proportions of patients receiving the next PP3M dose within 120 days among first-, second-, and third-dose completers. Key covariates included prior PP1M duration and adequate PP3M initiation. Results: The PP3M treatment retention rates were 79.7%, 66.3%, and 52.5% after 6, 12, and 24 months, respectively, with 86.4%, 90.6%, and 90.0% of respective first-, second-, and third-dose completers receiving the next PP3M dose. Adequate PP3M initiation and prior PP1M treatment duration > 180 days were associated with favorable PP3M treatment retention. In multivariate analyses, PP1M durations of 180−360 days (adjusted relative risk [aRR], 1.76) or < 180 days (aRR, 2.79) were associated with PP3M discontinuation at the second dose. Inadequate PP3M initiation was associated with discontinuation at the third dose (aRR, 2.18). Patients fully adherent to PP3M treatment in the first year had a higher probability of being free from psychiatric hospitalization (86.7% at 2 years), compared with those partially adherent or non-adherent to PP3M in the first year. Conclusion: Prior PP1M duration and adequate PP3M initiation are major factors affecting PP3M treatment retention. Higher PP3M treatment retention is associated with a lower risk of psychiatric hospitalization.

Systemic Inflammatory Biomarkers, Especially Fibrinogen to Albumin Ratio, Predict Prognosis in Patients with Pancreatic Cancer

Lin Fang,Fei-Hu Yan,Chao Liu,Jing Chen,Dan Wang,Chun-Hui Zhang,Chang-Jie Lou,Jie Lian,Yang Yao,Bo-Jun Wang,Rui-Yang Li,Shu-Ling Han,Yi-Bing Bai,Jia-Ni Yang,Zhi-Wei Li,Yan-Qiao Zhang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.1

Purpose Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC. Materials and Methods Three hundred fifty-three patients with resectable PC and 807 patients with locally advan-ced or metastatic PC were recruited in this study. These patients were classified into a training set (n=758) and a validation set (n=402). Kaplan-Meier survival plots and Cox proportional hazards regression models were used to analyze prognosis. Results Overall survival (OS) was significantly better for patients with resectable PC with low preoperative PLR (p=0.048) and MLR (p=0.027). Low FAR, MLR, NLR (p < 0.001), and PLR (p=0.003) were significantly associated with decreased risk of death for locally advanced or metastatic PC patients. FAR (hazard ratio [HR], 1.522; 95% confidential interval [CI], 1.261 to 1.837; p < 0.001) and MLR (HR, 1.248; 95% CI, 1.017 to 1.532; p=0.034) were independent prognostic factors for locally advanced or metastatic PC. Conclusion The prognostic roles of FAR, MLR, NLR, and PLR in resectable PC and locally advanced or metastatic PC were different. FAR showed the most prognostic power in locally advanced or metastatic PC. Low FAR was positively correlated with OS in locally advanced or metastatic PC, which could be used to predict the prognosis.

Immature Fruit Recognition using Exposure Fusion and Machine Learning

( Yi-zhen Lin ),( Shih-fang Chen ) 한국농업기계학회 2018 한국농업기계학회 학술발표논문집 Vol.23 No.1

Labor shortage is one of the most serious issues in agriculture industry. During harvest season, a lack of manpower may delay the best time for harvesting and significantly affects the postharvest processes and its quality, especially for perishable products, e.g. fruit and vegetables. Mechanical harvesting provides a solution to alleviate the situation by integrating mechanism design and machine vision to perform automatic harvesting. Precise identification and localization algorithm for targeted crops are keys in the system. However, uneven field illumination and high color similarity between target and background perturb the object identification in machine vision. In this study, exposure fusion, a newly developed method to capture a scene with higher dynamic range, is applied to overcome the influence of light for target images. Eleven exposure values will be tested to obtain a best fused image for further analysis. Color space transformation and machine-learning approaches, such as support vector machine (SVM) and linear discriminant analysis (LDA) are proposed to segment immature green fruits (e.g. cherry tomatoes and kumquats) from leafy background.

To stay or leave: a multiple-case study of the retention of native English-speaking teachers in Taiwan

Fang, Ting,Wang, Li-Yi,Lin, Tzu-Bin,Huang, Chia-Kai 서울대학교 교육연구소 2022 Asia Pacific Education Review Vol.23 No.2

The spread of English as a global language has contributed to the trend of recruiting native English-speaking teachers (NESTs) through government-funded schemes around the world, particularly in East Asia. In Taiwan, the NEST scheme has been recently expanded because of the national policy for a bilingual Taiwan in 2030. However, the NEST scheme in Taiwan has the strictest selection criteria and the least attractive incentives in the region. As these unfavorable conditions could affect the recruitment and effectiveness of the NEST scheme, this study explored the advantages and challenges perceived by NEST participants through in-depth interviews with 24 NESTs working in Taiwanese public schools to identify the factors that could influence their attrition and retention. It was found that most advantages were associated with the participants’ schools, such as the provision of resources and a sense of achievement, rather than from outside the schools. However, most of the perceived challenges also occurred inside the schools, such as the lack of collaboration with colleagues and class sizes. These findings suggested that the issues and agendas at the participating schools had the greatest influence on NEST decisions to stay or leave Taiwan. The implications for policymakers and school leaders are discussed and relevant suggestions are made.

Gallotannins from Nut Shell Extractives of Camellia oleifera

( Yi-chang He ),( Mei-jie Wu ),( Xiao-lin Lei ),( Jie-fang Yang ),( Wei Gao ),( Young-soo Bae ),( Tae-hee Kim ),( Sun-eun Choi ),( Bao-tong Li ) 한국목재공학회 2021 목재공학 Vol.49 No.3

Camellia nut shell was collected, dried at room temperature and ground to get fine powder. The powder was extracted three times with 95% EtOH, combined, evaporated, and then freeze dried. The crude powder was dissolved in H₂O and then sequentially fractionated with n-hexane, CH₂Cl₂, EtOAc and n-BuOH. A part of EtOAc fraction was chromatographed on a silica gel and on a Sephadex LH-20 columns using MeOH, aqueous MeOH, EtOAc-n-hexane and EtOH-n-hexane to isolate gallotannins. Three gallotannins, 1,2-di-O-galloyl-β-D-glucopyranoside (2), 1,2,6-tri-Ogalloyl- β-D-glucopyranoside (3) and 1,2,3,6-tetra-O-galloyl-β-D-glucopyranoside (4), including gallic acid (1), were isolated and elucidated by NMR and Mass spectroscopies. Although nothing new, these gallotannins were first reported from the nut shell extractives of camellia tree (Camellia oleifera C. Abel). This study was to investigate the chemical constituents, especially hydrolysable tannins, of nut shell extractives of Camellia oleifera and to provide basic information for the future chemical utilization of this species.

Pathophysiological Mechanisms Underlying Unilateral Vocal Fold Paralysis in Female Patients: An Ultrasonographic Study

Yi-An Lu,Tuan-Jen Fang,Yu-Cheng Pei,Yun-Chen Tsai,Wan-Ni Lin 대한이비인후과학회 2023 Clinical and Experimental Otorhinolaryngology Vol.16 No.4

Objectives. Laryngeal ultrasonography (LUS) has been suggested as an alternative diagnostic tool for unilateral vocal foldparalysis (UVFP). The present study applied LUS and quantitative laryngeal electromyography (LEMG) in female UVFPpatients to investigate the pathophysiologic mechanisms of UVFP. Methods. In this cross-sectional study, vocal fold (VF) length parameters included resting and phonating VF length measuredusing B-mode LUS, and color Doppler vibrating length (CDVL) measured using the color Doppler mode. Results. Forty female patients with UVFP were enrolled, among whom 11 and 29 were assigned to the thyroarytenoid (TA)muscle+cricothyroid (CT) muscle group (with CT involvement) and the TA (without CT involvement) group, respec-tively. In the TA group, the turn frequency in thyroarytenoid-lateral cricoarytenoid (TA-LCA) on the paralyzed side,as observed through LEMG, correlated with the VF length during the resting phase (R =0.368, P =0.050) and CDVLvalues (R =0.627, P =0.000) on the paralyzed side. In the TA+CT group, the turn ratio in the CT muscle correlatedwith the normalized phonatory vocal length change (nPLC; R =0.621, P =0.041) on the paralyzed side. Conclusion. CDVL and nPLC are two parameters that can be utilized to predict the turn frequencies of TA-LCA in UVFPcases without CT involvement, and the turn ratio of CT in cases of UVFP with CT involvement, respectively. The find-ings suggest that LUS, as a noninvasive tool, can serve as an alternative method for assessing the severity of laryngealnerve injury and offer valuable insights into the pathophysiology of UVFP.

Angelica dahurica attenuates melanogenesis in B16F0 cells by repressing Wnt/β-catenin signaling

Fang Chien-Liang,Goswami Debakshee,Kuo Chia-Hua,Day Cecilia Hsuan,Lin Mei-Yi,Ho Tsung-Jung,Yang Liang-Yo,Hsieh Dennis Jine-Yuan,Lin Tzu-Kai,Huang Chih-Yang 대한독성 유전단백체 학회 2023 Molecular & cellular toxicology Vol.19 No.1

Background Melanogenesis is a complex process which is tightly regulated by several enzymes. However, abnormal melanogenesis can cause severe dermatological problems. Roots of Angelica dahurica have been used for skin care as a part of traditional Chinese medicine for many generations. However, the role of A. dahurica in melanogenesis remains unclear. Objective Previous in vitro and in vivo studies have demonstrated that NK-1R exerts positive effects in melanogenesis via the Wnt/βcatenin signaling pathway. In this study, we investigated the effects of A. dahurica ethanol extract (ADE) on NK-1R and Wnt/β-catenin signaling, and evaluated the effect of NK-1R on melanogenesis in B16F0 cells. Results Angelica dahurica ethanol extract efficiently downregulated Neurokinin-1 receptor and Wnt/β-catenin signaling by decreasing the expression of β-catenin, MITF, LEF-1, TYR, TRP1, and TRP2 and increasing the expression of GSK3β, which resulted from the weakened expression of the Neurokinin-1 receptor inhibitor [Sar9,Met(O2 )11]-Substance P (SMSP). Furthermore, the intracellular melanin assay and cellular tyrosinase activity confirmed these findings. Conclusion This study suggests that ADE has potential to downregulate Neurokinin-1 receptor in SMSP-induced B16F0 cells, thereby repressing the Wnt/β-catenin signaling and reduces melanin production.