碩士
中國醫藥大學
醫學研究所
96
Neurotransmitters and cytokines can modulate the bile duct proliferation through c-AMP /PKA/ERK pathway. Dopamine may bind with dopamine type two receptor(D2R) to increase PKC-γ ...expression and decrease PKA activity, them, it could inhibit bile duct proliferation.
We used 6-hydroxyldopamine(6-OHDA) as bioaminergic depletor to lower dopamine level and evaluated that whether reduced endogenous dopamine level may influence the bile duct proliferation in rat bile duct ligated animal model. Previously, our laboratory found bile duct proliferation of Wistar-Kyoto rats(WKY) rats was much higher than Spontaneously hypertensive rat(SHR) rats after 3 weeks bile duct ligation (BDL) . Cholangiocyte expressed D2R and its expression was markedly upregulated after BDL. Our goal in this study was to find out that D2R regulate the cholangiocyte proliferation between SHR and WKY rats after BDL.
Our results in immunohistochemistry(IHC), expression of D2R was upregulated after BDL and much higher after BDL + 6-
博士
國立陽明大學
生化暨分子生物研究所
105
Lung cancer is the leading cause of cancer-related deaths worldwide and the prognosis of non-small-cell lung cancer (NSCLC) remains poor. Identification of novel prognostic ...markers and therapeutic targets are urgently needed. Here we identified G-protein-coupled receptor-kinase interacting protein 1 (GIT1) gene from 5,000 High-throughput antibodies library screening using tissue microarray (TMA) after comparing protein expression differences of five major human cancer primary tumors and normal adjacent tissues. The results were further confirmed by online microarray database analysis to show GIT1 as a prognosis predictor in NSCLC. GIT1 is participated in cell movement activation, which is a fundamental process during tissue development and cancer progression. GIT1/(PAK interacting exchange factor, PIX) forming a functional protein complex that contributes to (Ras-related C3 botulinum toxin suxstrate 1, Rac1)/(Cell division cycle 42, Cdc42) activation, resulting in increasing cell mobility. Although the importance of Rac1/Cdc42 activation is well documented in cancer aggressiveness, the clinical importance of GIT1 remains largely unknown. Here, we investigated the clinical significance of GIT1 expression in NSCLC and also verified the importance of GIT1-Rac1/Cdc42 axis in stimulating NSCLC cell mobility. The result indicated higher GIT1 expression patients had significantly poorer prognoses in disease-free survival (DFS) and overall survival (OS) compared with lower GIT1 expression patients. Higher GIT1 expression was an independent prognostic factor by multivariate analysis and associated with migration/invasion of NSCLC cells in transwell assay. In vivo studies indicated that GIT1 promotes metastasis of NSCLC cells. Finally, GIT1 was found to stimulate migration/invasion by altering the activity of Rac1/Cdc42 in NSCLC cells. Together, the GIT1 expression is associated with poor prognosis in patients with NSCLC. GIT1 is critical for the invasiveness of NSCLC cells through stimulating the activity of Rac1/Cdc42.
Herein, we aim to develop a facile method for the fabrication of mechanical metamaterials from templated polymerization of thermosets including phenolic and epoxy resins using self-assembled block ...copolymer, polystyrene–polydimethylsiloxane with tripod network (gyroid), and tetrapod network (diamond) structures, as templates. Nanoindentation studies on the nanonetwork thermosets fabricated reveal enhanced energy dissipation from intrinsic brittle thermosets due to the deliberate structuring; the calculated energy dissipation for gyroid phenolic resins is 0.23 nJ whereas the one with diamond structure gives a value of 0.33 nJ. Consistently, the gyroid-structured epoxy gives a high energy dissipation value of 0.57 nJ, and the one with diamond structure could reach 0.78 nJ. These enhanced properties are attributed to the isotropic periodicity of the nanonetwork texture with plastic deformation, and the higher number of struts in the tetrapod diamond network in contrast to tripod gyroid, as confirmed by the finite element analysis.
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IJS, KILJ, NUK, PNG, UL, UM
Cancer-initiating cells (CICs) are responsible for tumor initiation, progression, and therapeutic resistance; moreover, redox homeostasis is important in regulating cancer stemness. Previously, we ...have identified that cancer cells containing low intracellular reactive oxygen species levels (ROS
cells) display enhanced features of CICs. However, the specific metabolic signatures of CICs remain unclear and are required for further characterization by systemic screenings. Herein, we first showed CICs mainly relying on glycolysis that was important for the maintenance of stemness properties. Next, we revealed that NRF2, a master regulator of antioxidants, was able to maintain low intracellular ROS levels of CICs, even though in the absence of oxidative stress. We further characterized that NRF2 activation was required for the maintenance of CICs properties. Of ROS
cells, NRF2 activation not only directly activates the transcription of genes encoding glycolytic enzymes but also inhibited the conversion of pyruvate to acetyl-CoA by directly activating pyruvate dehydrogenase kinase 1 (PDK1) to lead to inhibition of tricarboxylic acid (TCA) cycle; therefore, to promote Warburg effect. A positive regulatory ROS-independent ER stress pathway (GRP78/p-PERK/NRF2 signaling) was identified to mediate the metabolic shift (Warburg effect) and stemness of CICs. Lastly, co-expression of p-PERK and p-NRF2 was significantly associated with the clinical outcome. Our data show that NRF2 acting as a central node in the maintenance of low ROS levels and stemness associated properties of the CICs, which is significantly associated with the clinical outcome, but independent from ROS stress. Future treatments by inhibiting NRF2 activation may exhibit great potential in targeting CICs.
Copper catalysed oxidative coupling reaction of formamides with β‐keto esters and 2‐carbonyl‐substituted phenols successfully proceeded through direct C–H bond activation of formamides. The ...corresponding carbamates were formed with high stereoselectivity under mild reaction conditions. This protocol was successfully applied to the synthesis of three novel halogenated carbamates and a carbaryl insecticide derivative. Our results suggest the use of 6.0 equiv. TBHP is crucial for this type of reaction.
Synthesis of carbamates was accomplished through the reaction of β‐keto esters or 2‐carbonyl‐substituted phenols with formamides using copper chloride and an oxidant. Sixteen aliphatic as well as fourteen aromatic carbamates were prepared in good to excellent yields. The methodology was applied to the synthesis of halogenated carbamates and a carbaryl insecticide derivative.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Electroencephalogram (EEG) signals, as it can express the human brain’s activities and reflect awareness, have been widely used in many research and medical equipment to build a noninvasive ...monitoring index to the depth of anesthesia (DOA). Bispectral (BIS) index monitor is one of the famous and important indicators for anesthesiologists primarily using EEG signals when assessing the DOA. In this study, an attempt is made to build a new indicator using EEG signals to provide a more valuable reference to the DOA for clinical researchers. The EEG signals are collected from patients under anesthetic surgery which are filtered using multivariate empirical mode decomposition (MEMD) method and analyzed using sample entropy (SampEn) analysis. The calculated signals from SampEn are utilized to train an artificial neural network (ANN) model through using expert assessment of consciousness level (EACL) which is assessed by experienced anesthesiologists as the target to train, validate, and test the ANN. The results that are achieved using the proposed system are compared to BIS index. The proposed system results show that it is not only having similar characteristic to BIS index but also more close to experienced anesthesiologists which illustrates the consciousness level and reflects the DOA successfully.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Summary
Tongue base deformation may play a critical role in the phenomenon of obstructive sleep apnea, but polysomnography provides limited information regarding the effect of tongue motion during ...natural sleep. We reported on preliminary results of combining a novel ultrasound system and polysomnography for simultaneous recordings during natural sleep in volunteers and patients with obstructive sleep apnea. All participants underwent time‐synchronized polysomnography and submental transcutaneous ultrasound examinations. The wearable ultrasound device detected the air–mucosal interface of the tongue surface and automatically determined the maximum tongue base thickness in real time. All participants reported no sensation of heat, no sign of skin allergy, and an average of mild disturbance after the ultrasound recordings. In the individual patient with obstructive sleep apnea, we demonstrated a significant difference (P < 0.001) between the ultrasonic tongue base thickness measured during eupnea and that measured during snoring, hypopnea and apnea. The ultrasonic tongue base thickness increased and remained before the occurrence of obstructive apnea. On average, increased tongue base thicknesses of 2.5 (4.1%), 6.0 (9.8%) and 7.7 mm (12.5%) are associated with snoring, hypopnea and apnea, respectively. Our present data demonstrate that simultaneous examination of ultrasonic tongue base thickness and polysomnography is feasible for prolonged recording during natural sleep. The proposed method also enables the detection of significant differences in ultrasonic tongue base thickness between eupnea and obstructive respiratory events evaluated using polysomnography. This novel technique can be used to generate hypotheses for subsequent investigations of the underlying mechanisms and individualized combined therapy for obstructive sleep apnea. Clinical trial registration: This study has been registered at the Chinese Clinical Trial Registry website with the registration number of ChiCTR‐DDT‐13003313. The date of registration was 13 July 2013.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Dynamic tongue base thickness (TBT) may be an important anatomic factor in airway narrowing in patients with obstructive sleep apnea (OSA). The development of an accurate clinical assessment of the ...retroglossal airway in patients with OSA is still evolving. Submental ultrasound was used to investigate the association between measurements of TBT in response to negative airway pressure and the existence of OSA. Twenty OSA patients and 20 control participants underwent ultrasound measurement of TBT on eupneic breathing and with the Mueller maneuver, as well as clinical and polysomnographic assessments. Logistic regression analyses indicated that after adjustment for confounding factors, independent predictors of OSA included TBT in response to negative airway pressure, as measured by submental ultrasound with the Mueller maneuver (odds ratio: 2.11, 95% confidence interval: 1.15-3.87, p < 0.05), and the difference between TBT with the Muller maneuver and that without the Mueller maneuver (odds ratio: 2.47, 95% confidence interval: 1.09-5.58, p < 0.05). Ultrasound measurement of TBT during the Mueller maneuver provides a quantitative assessment of the retroglossal airway in OSA patients with minimal invasiveness and easy accessibility.
Aim
Senior healthcare is challenging in remote areas, particularly in an economically disadvantaged population. This study examined the benefits of a combined healthcare system (Houston–Apollo model) ...in improvements of physical performance and medical care utilization of local older people.
Methods
People aged ≥65 years who participated in congregate meal services were recruited. Using concepts of telemedicine and community health records, participants received consultation from local general physicians, who provided advice or arranged referrals to the National Taiwan University Hospital Yunlin Branch. Physical parameters including blood pressure, body mass index, grip strength, walking speed, and five times sit‐to‐stand test (FTSST) were transferred to the National Taiwan University Hospital Yunlin Branch and local doctors in a timely manner. Changes in physical parameters and utilization of healthcare facilities were measured at the beginning of recruitment and 1 year later.
Results
In the 470 registered participants, 66% had hypertension, 50% had weakness in grip strength, 58% were slow at FTSST and 78% had disability in 6‐meter walking speed. In total, 97 participants were followed up at 1 year. The systolic and diastolic blood pressure (mmHg) decreased from 137.4 to 133.3 (P = 0.019) and from 76.9 to 74.4 (P = 0.008), respectively. The time of FTSST (s) decreased from 11.3 to 10.4 (P = 0.011). The walking speed (m/s) increased from 0.71 to 0.74 (P = 0.039). Medical and dental outpatient usage increased by 2 and 1.14 times, respectively.
Conclusions
The Houston–Apollo model could provide benefits for the physical status of older adults, promote proactive and preventive healthcare utilization, and contribute to medical equality. Geriatr Gerontol Int 2021; ••: ••–••.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract Induced pluripotent stem cells (iPSCs) with four reprogramming factors (Oct-4/Sox2/Klf-4/c-Myc) have been shown to differentiate into hepatic lineages. However, it was unclear whether ...obviation of the c-Myc oncogene in iPSCs affected hepatic differentiation or inhibited in vivo tumor formation. In this study, we demonstrated that iPSCs without c-Myc had the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) with biological functions. As detected using planar-radionuclide imaging and Hoechst labeling assays, these iPSCs and iPSC-Heps tended to mobilize to the injured liver area in thioacetamide (TAA)-treated mice. Intravenous transplantation of both iPSCs and iPSC-Heps but not mouse embryonic fibroblasts (MEFs) reduced the hepatic necrotic area, improved liver functions, and rescued TAA-treated mice from lethal acute hepatic failure (AHF). In addition, microarray-based bioinformatics and quantitative RT-PCR showed high expression of antioxidant genes in iPSCs and iPSC-Heps compared to MEFs. In vivo and in vitro studies of NAC pretreatment confirmed that iPSCs and iPSC-Heps potentially suppressed ROS production and activated antioxidant enzymes in TAA-injured livers. Six months after transplantation in TAA-treated mice, tumor formation was not seen in non-c-Myc iPSC grafts. Therefore, reprogramming adult somatic cells without c-Myc may prevent oxidative stress-induced damage and provide a safer alternative for hepatic regeneration in AHF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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