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Liu, Kai-Hsi,Lin, Hung-Yin,Thomas, James L.,Shih, Yuan-Pin,Yang, Zhuan-Yi,Chen, Jen-Tsung,Lee, Mei-Hwa The Korean Society of Ginseng 2022 Journal of Ginseng Research Vol.46 No.5
Background: Panax ginseng (ginseng) is a traditional medicine that is reported to have cardioprotective effects; ginsenosides are the major bioactive compounds in the ginseng root. Methods: Magnetic molecularly imprinted polymer (MMIP) nanoparticles might be useful for both the extraction of the targeted (imprinted) molecules, and for the delivery of those molecules to cells. In this work, plant growth regulators were used to enhance the adventitious rooting of ginseng root callus; imprinted polymeric particles were synthesized for the extraction of ginsenoside Rb<sub>1</sub> from root extracts, and then employed for subsequent particle-mediated delivery to cardiomyocytes to mitigate hypoxia/reoxygenation injury. Results: These synthesized composite nanoparticles were first characterized by their specific surface area, adsorption capacity, and magnetization, and then used for the extraction of ginsenoside Rb<sub>1</sub> from a crude extract of ginseng roots. The ginsenoside-loaded MMIPs were then shown to have protective effects on mitochondrial membrane potential and cellular viability for H9c2 cells treated with CoCl<sub>2</sub> to mimic hypoxia injury. The protective effect of the ginsenosides was assessed by staining with JC-1 dye to monitor the mitochondrial membrane potential. Conclusion: MMIPs can play a dual role in both the extraction and cellular delivery of therapeutic ginsenosides.
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Capsaicin-Sensitive Sensory Nerves Indirectly Modulate Motor Function of the Urinary Bladder
Hsi-Hsien Chang,Shang-Jen Chang,Cheng-Hsing Hsieh,Chun-Kai Hsu,Stephen Shei-Dei Yang 대한배뇨장애요실금학회 2018 International Neurourology Journal Vol.22 No.2
Purpose: The urinary bladder (UB) is innervated by both sensory and autonomic nerves. Recent studies have shown that sensory neuropeptides induced contractions in the detrusor muscle. Therefore, in a mouse model, we investigated the presence of interactions between the submucosal sensory nerves and the autonomic nerves that regulate the motor function of the detrusor muscle. Methods: UB samples from male C57BL/6 mice were isolated, cut into strips, and mounted in an organ bath. Dose-response curves to norepinephrine and phenylephrine were studied in UB strips with and without mucosa, and the effects of preincubation with a receptor antagonist and various drugs on relaxation were also studied using tissue bath myography. Results: Phenylephrine-induced relaxation of the UB strips showed concentration-related effects. This relaxation appeared in both mucosa-intact and mucosa-denuded UB strips, and was significantly inhibited by lidocaine, silodosin, and guanethidine (an adrenergic neuronal blocker). Meanwhile, phenylephrine-induced relaxation was inhibited by pretreatment with propranolol and calcitonin gene-related peptide (CGRP)–depletory capsaicin in UB strips with and without mucosa. Conclusions: The present study suggests that phenylephrine activates the α-1A adrenergic receptor (AR) of the sensory nerve, and then activates capsaicin-sensitive sensory nerves to release an unknown substance that facilitates the release of norepinephrine from adrenergic nerves. Subsequently, norepinephrine stimulates β-ARs in the detrusor muscle in mice, leading to neurogenic relaxation of the UB. Further animal and human studies are required to prove this concept and to validate its clinical usefulness.
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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.
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Ho, Wen-Fu,Tsou, Hsi-Kai,Wu, Shih-Ching,Hsu, Shih-Kuang,Chuang, Shao-Hsuan,Hsu, Hsueh-Chuan Techno-Press 2014 Biomaterials and biomedical engineering Vol.1 No.1
The purpose of this experiment was to evaluate the apatite-formation abilities of low-modulus Ti-7.5Mo substrates treated with NaOH aqueous solutions and subsequent ethyl alcohol aging before soaking them in simulated body fluid. Specimens of Ti-7.5Mo were initially treated with 5 M NaOH at $60^{\circ}C$ for 24 h, resulting in the formation of a porous network structure composed of sodium hydrogen titanate. Afterwards, the specimens were aged in ethyl alcohol at $60^{\circ}C$ for 5 or 10 min, and subsequently immersed in simulated body fluid at $37^{\circ}C$ for 3, 7 and 14 days. Ethyl alcohol aging significantly increased the apatite-forming abilities of Ti-7.5Mo. The amount of apatite deposited on the Ti-7.5Mo after NaOH treatment and subsequent ethyl alcohol aging was much greater, especially after the Ti-7.5Mo specimens were aged for 5 min. Due to its excellent combination of bioactivity, low elastic modulus and low processing costs, the Ti-7.5Mo treated with NaOH aqueous solutions and subsequently aged in ethyl alcohol has promising heavy load-bearing applications.
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Ho, Wen-Fu,Tsou, Hsi-Kai,Wu, Shih-Ching,Hsu, Shih-Kuang,Chuang, Shao-Hsuan,Hsu, Hsueh-Chuan Techno-Press 2014 Biomaterials and Biomechanics in Bioengineering Vol.1 No.1
The purpose of this experiment was to evaluate the apatite-formation abilities of low-modulus Ti-7.5Mo substrates treated with NaOH aqueous solutions and subsequent ethyl alcohol aging before soaking them in simulated body fluid. Specimens of Ti-7.5Mo were initially treated with 5 M NaOH at $60^{\circ}C$ for 24 h, resulting in the formation of a porous network structure composed of sodium hydrogen titanate. Afterwards, the specimens were aged in ethyl alcohol at $60^{\circ}C$ for 5 or 10 min, and subsequently immersed in simulated body fluid at $37^{\circ}C$ for 3, 7 and 14 days. Ethyl alcohol aging significantly increased the apatite-forming abilities of Ti-7.5Mo. The amount of apatite deposited on the Ti-7.5Mo after NaOH treatment and subsequent ethyl alcohol aging was much greater, especially after the Ti-7.5Mo specimens were aged for 5 min. Due to its excellent combination of bioactivity, low elastic modulus and low processing costs, the Ti-7.5Mo treated with NaOH aqueous solutions and subsequently aged in ethyl alcohol has promising heavy load-bearing applications.
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Chia-Eng Wu,Chen-Wei Yu,Kai-Wei Chang,Wen-Hsi Chou,Chen-Yu Lu,Elisa Ghelfi,Fang-Chun Wu,Pey-Shynan Jan,Mei-Chi Huang,Patrick Allard,Shau-Ping Lin,Hong-Nerng Ho,Hsin-Fu Chen 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-
Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules. Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity. The expression levels of global immune-related genes were determined by comparing undifferentiated and differentiated stem cells and three types of human somatic cells: dermal papilla cells, ovarian granulosa cells and foreskin fibroblast cells. We identified the differentially expressed genes CD24, GATA3, PROM1, THBS2, LY96, IFIT3, CXCR4, IL1R1, FGFR3, IDO1 and KDR, which overlapped with selected immune-related gene lists. In further analyses, mammalian target of rapamycin complex (mTOR) signaling was investigated in the differentiated stem cells following treatment with rapamycin and lentiviral transduction with specific short-hairpin RNAs. We found that the inhibition of mTOR signal pathways significantly downregulated the immunogenicity of differentiated stem cells. We also tested the immune responses induced in differentiated stem cells by mixed lymphocyte reactions. We found that CD24- and GATA3-deficient differentiated stem cells including neural lineage cells had limited abilities to activate human lymphocytes. By analyzing the transcriptome signature of immune-related genes, we observed a tendency of the hPSCs to differentiate toward an immune cell phenotype. Taken together, these data identify candidate immune-related genes that might constitute valuable targets for clinical applications.
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Tsai Yu-Chen,Cheng Tai-Shan,Liao Hsiu-Jung,Chuang Ming-Hsi,Chen Hui-Ting,Chen Chun-Hung,Zhang Kai-Ling,Chang Chih-Hung,Lin Po-Cheng,Huang Chi-Ying F. 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.6
BACKGROUND: Extracellular vesicles (EVs) are derived from internal cellular compartments, and have potential as a diagnostic and therapeutic tool in degenerative disease associated with aging. Mesenchymal stem cells (MSCs) have become a promising tool for functional EVs production. This study investigated the efficacy of EVs and its effect on differentiation capacity. METHODS: The characteristics of MSCs were evaluated by flow cytometry and stem cell differentiation analysis, and a production mode of functional EVs was scaled from MSCs. The concentration and size of EVs were quantitated by Nanoparticle Tracking Analysis (NTA). Western blot analysis was used to assess the protein expression of exosomespecific markers. The effects of MSC-derived EVs were assessed by chondrogenic and adipogenic differentiation analyses and histological observation. RESULTS: The range of the particle size of adipose-derived stem cells (ADSCs)- and Wharton’s jelly -MSCs-derived EVs were from 130 to 150 nm as measured by NTA, which showed positive expression of exosomal markers. The chondrogenic induction ability was weakened in the absence of EVs in vitro. Interestingly, after EV administration, type II collagen, a major component in the cartilage extracellular matrix, was upregulated compared to the EV-free condition. Moreover, EVs decreased the lipid accumulation rate during adipogenic induction. CONCLUSION: The results indicated that the production model could facilitate production of effective EVs and further demonstrated the role of MSC-derived EVs in cell differentiation. MSC-derived EVs could be successfully used in cell-free therapy to guide chondrogenic differentiation of ADSC for future clinical applications in cartilage regeneration.
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