Cav3.2 T-Type Ca2+ Channel-Dependent Activation of ERK in Paraventricular Thalamus Modulates Acid-Induced Chronic Muscle Pain.

Chen, Wen-Kwei,Liu, Ingrid Y,Chang, Ya-Ting,Chen, Yong-Cyuan,Chen, Chih-Cheng,Yen, Chen-Tung,Shin, Hee-Sup,Chen, Chien-Chang The Society 2010 The Journal of neuroscience Vol.30 No.31

<P>Treatments for chronic musculoskeletal pain, such as lower back pain, fibromyalgia, and myofascial pain syndrome, remain inadequate because of our poor understanding of the mechanisms that underlie these conditions. Although T-type Ca(2+) channels (T-channels) have been implicated in peripheral and central pain sensory pathways, their role in chronic musculoskeletal pain is still unclear. Here, we show that acid-induced chronic mechanical hyperalgesia develops in Ca(v)3.1-deficient and wild-type but not in Ca(v)3.2-deficient male and female mice. We also show that T-channels are required for the initiation, but not maintenance, of acid-induced chronic muscle pain. Blocking T-channels using ethosuximide prevented chronic mechanical hyperalgesia in wild-type mice when administered intraperitoneally or intracerebroventricularly, but not intramuscularly or intrathecally. Furthermore, we found an acid-induced, Ca(v)3.2 T-channel-dependent activation of ERK (extracellular signal-regulated kinase) in the anterior nucleus of paraventricular thalamus (PVA), and prevention of the ERK activation abolished the chronic mechanical hyperalgesia. Our findings suggest that Ca(v)3.2 T-channel-dependent activation of ERK in PVA is required for the development of acid-induced chronic mechanical hyperalgesia.</P>

Disruption of Striated Preferentially Expressed Gene Locus Leads to Dilated Cardiomyopathy in Mice

Liu, Xiaoli,Ramjiganesh, Tripurasundari,Chen, Yen-Hsu,Chung, Su Wol,Hall, Sean R.,Schissel, Scott L.,Padera Jr, Robert F.,Liao, Ronglih,Ackerman, Kate G.,Kajstura, Jan,Leri, Annarosa,Anversa, Piero,Ye Ovid Technologies Wolters Kluwer -American Heart A 2009 CIRCULATION - Vol.119 No.2

<P>BACKGROUND: The striated preferentially expressed gene (Speg) generates 4 different isoforms through alternative promoter use and tissue-specific splicing. Depending on the cell type, Speg isoforms may serve as markers of striated or smooth muscle differentiation. METHODS AND RESULTS: To elucidate function of Speg gene isoforms, we disrupted the Speg gene locus in mice by replacing common exons 8, 9, and 10 with a lacZ gene. beta-Galactosidase activity was detected in cardiomyocytes of the developing heart starting at day 11.5 days post coitum (dpc). beta-Galactosidase activity in other cell types, including vascular smooth muscle cells, did not begin until 18.5 dpc. In the developing heart, protein expression of only Spegalpha and Spegbeta isoforms was present in cardiomyocytes. Homozygous Speg mutant hearts began to enlarge by 16.5 dpc, and by 18.5 dpc, they demonstrated dilation of right and left atria and ventricles. These cardiac abnormalities in the absence of Speg were associated with a cellular hypertrophic response, myofibril degeneration, and a marked decrease in cardiac function. Moreover, Speg mutant mice exhibited significant neonatal mortality, with increased death occurring by 2 days after birth. CONCLUSIONS: These findings demonstrate that mutation of the Speg locus leads to cardiac dysfunction and a phenotype consistent with a dilated cardiomyopathy.</P>

Implementing Action Mask in Proximal Policy Optimization (PPO) Algorithm

Cheng-Yen Tang,Chien-Hung Liu,Woei-Kae Chen,Shingchern D. You 한국통신학회 2020 ICT Express Vol.6 No.3

The proximal policy optimization (PPO) algorithm is a promising algorithm in reinforcement learning. In this paper, we propose to add an action mask in the PPO algorithm. The mask indicates whether an action is valid or invalid for each state. Simulation results show that, when compared with the original version, the proposed algorithm yields much higher return with a moderate number of training steps. Therefore, it is useful and valuable to incorporate such a mask if applicable.

The Antiproliferation Activity of Ganoderma formosanum Extracts on Prostate Cancer Cells

( Cheng-yen Chiang ),( Kai-di Hsu ),( Yen-yi Lin ),( Chang-wei Hsieh ),( Jui-ming Liu ),( Tze-ying Lu ),( Kuan-chen Cheng ) 한국균학회 2020 Mycobiology Vol.48 No.3

Androgen-independent prostate cancer accounts for mortality in the world. In this study, various extracts of a medical fungus dubbed Ganoderma formosanum were screened for inhibition of DU145 cells, an androgen-independent prostate cancer cell line. Results demonstrated that both hexane (GF-EH) and butanol (GF-EB) fraction of G. formosanum ethanol extract inhibited DU145 cell viability in a dose-dependent manner. GF-EH induced cell-cycle arrest in G1 phase of DU145 cells via downregulation of cyclin E2 protein expression. In addition, GF-EB triggered extrinsic apoptosis of DU145 cells by activating caspase 3 gene expression resulting in programed cell death. Above all, both GF-EH and GF-EB show lower toxicity to normal human fibroblast cell line compared to DU145 cell, implying that they possess specific drug action on cancer cells. This study provides a molecular basis of G. formosanum extract as a potential ingredient for treatment of androgen-independent prostate cancer.

Antioxidative and Hepatoprotective Effects of Magnolol on Acetaminophen-induced Liver Damage in Rats

Yung-Hsiang Chen,Feng-Yen Lin,Po-Len Liu,Yi-Tsau Huang,Jen-Hwey Chiu,Yi-Chun Chang,Kee-Ming Man,Chuang-Ye Hong,Yen-Yi Ho,Ming-Tsung Lai 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.2

Acute liver failure (ALF), an often fatal condition characterized by massive hepatocyte necrosis, is frequently caused by drug poisoning, particularly with acetaminophen (N-acetyl-p-aminophenol/APAP). Hepatocyte necrosis is consecutive to glutathione (GSH) depletion and mitochondrial damage caused by reactive oxygen species (ROS) overproduction. Magnolol, one major phenolic constituent of Magnolia officinalis, have been known to exhibit potent antioxidative activity. In this study, the anti-hepatotoxic activity of magnolol on APAP-induced toxicity in the Sprague-Dawley rat liver was examined. After evaluating the changes of several biochemical parameters in serum, the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were elevated by APAP (500 mg/kg) intraperitoneal administration (8 and 24 h) and reduced by treatment with magnolol (0.5 h after APAP administration; 0.01, 0.1, and 1 μg/kg). Histological changes around the hepatic central vein, lipid peroxidation (thiobarbituric acid-reactive substance/TBARS), and GSH depletion in liver tissue induced by APAP were also recovered by magnolol treatment. The data show that oxidative stress followed by lipid peroxidation may play a very important role in the pathogenesis of APAP-induced hepatic injury; treatment with lipid-soluble antioxidant, magnolol, exerts anti-hepatotoxic activity. Our study points out the potential interest of magnolol in the treatment of toxic ALF.

Saikosaponin a and Saikosaponin d Inhibit Proliferation and Migratory Activity of Rat HSC-T6 Cells

Ming Feng Chen,Chao Cheng Huang,Pei Shan Liu,Chang Han Chen,Li Yen Shiu 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.9

The proliferation and migration of hepatic stellate cells (HSCs) profoundly impact the pathogenesis of liver inflammation and fibrogenesis. As a perennial herb native to China, Bupleurum falcatum is administered for its anti-inflammatory,antipyretic, and antihepatotoxic effects. Saikosaponin a (SSa) and Saikosaponin d (SSd) are the major active components of triterpene saponins in Bupleurum falcatum. This study analyzes how SSa and SSd affect rat HSC-T6 cell line proliferation and migration. Experimental results indicate that, in addition to suppressing HSC-T6 proliferation, wound healing activity and cell migration in a time- and dose-dependent manner, SSa and SSd significantly induce apoptosis. Additionally, SSa and SSd decreased the expressions of extracellular matrix-regulated kinase 1/2 (ERK1/2), platelet-derived growth factor receptor 1 (PDGFR1), and subsequently transforming growth factor-b1 receptor (TGF-b1R), a-smooth muscle actin, TGF-b1 and connective tissue growth factor. They also decreased phosphorylation of p38 (p-p38) and ERK1/2 (p-ERK1/2) of HSC-T6. Furthermore, both SSa and SSd can block PDGF-BB and TGF-b1-induced cell proliferation and migration of HSC-T6. These results suggest that SSa and SSd may inhibit proliferation and activation of HSC-T6, and the modulated mechanisms warrant further study.

Resilient Memory Event-triggered Consensus Control for Multi-agent Systems with Aperiodic DoS Attacks

Murugesan Sathishkumar,Yen-Chen Liu 제어·로봇·시스템학회 2022 International Journal of Control, Automation, and Vol.20 No.6

This work addresses the memory event-triggered consensus control design problems of multi-agent systems (MASs) under actuator failures and aperiodic denial-of-service (DoS) attacks. In order to overcome an unpredictable traffic in the network communication channel, an appropriate memory event-triggered scheme (METS) is proposed. The purpose of this scheme is to utilize certain release packets to create new event compared with the existing event-triggered scheme (ETS). In this fashion, the event generator can achieve accurate decision as well as better performance of the control can be expected. Further, a new switched approach is established to describe the consensus performance of system model with aperiodic DoS attacks. By incorporating the Lyapunov-Krasovskii functional (LKF), adequate constraints of the consensus for MASs are derived. Based on the obtained conditions, the consensus control gain matrices are presented by utilizing the technique of linear matrix inequalities (LMIs). Eventually, simulation results are given to validate the applicability of the proposed theoretical results which is based on the F-18 aircraft model systems.

A Mobile P2P Semantic Information Retrieval System with Effective Updates

( Chuan-ming Liu ),( Cheng-hsien Chen ),( Yen-lin Chen ),( Jeng-haur Wang ) 한국인터넷정보학회 2015 KSII Transactions on Internet and Information Syst Vol.9 No.5

As the technologies advance, mobile peer-to-peer (MP2P) networks or systems become one of the major ways to share resources and information. On such a system, the information retrieval (IR), including the development of scalable infrastructures for indexing, becomes more complicated due to a huge increase on the amount of information and rapid information change. To keep the systems on MP2P networks more reliable and consistent, the index structures need to be updated frequently. For a semantic IR system, the index structure is even more complicated than a classic IR system and generally has higher update cost. The most well-known indexing technique used in semantic IR systems is Latent Semantic Indexing (LSI), of which the index structure is generated by singular value decomposition (SVD). Although LSI performs well, updating the index structure is not easy and time consuming. In an MP2P environment, which is fully distributed and dynamic, the update becomes more challenging. In this work, we consider how to update the sematic index generated by LSI and keep the index consistent in the whole MP2P network. The proposed Concept Space Update (CSU) protocol, based on distributed 2-Phase locking strategy, can effectively achieve the objectives in terms of two measurements: coverage speed and update cost. Using the proposed effective synchronization mechanism with the efficient updates on the SVD, re-computing the whole index on the P2P overlay can be avoided and the consistency can be achieved. Simulated experiments are also performed to validate our analysis on the proposed CSU protocol. The experimental results indicate that CSU is effective on updating the concept space with LSI/SVD index structure in MP2P semantic IR systems.

Intestinal Paragonimiasis with Colonic Ulcer and Hematochezia in An Elderly Taiwanese Woman

Chung-Te Liu,Yen-Cheng Chen,Tso-Hsiao Chen,Ursula Barghouth,Chia-Kwung Fan 대한기생충학열대의학회 2012 The Korean Journal of Parasitology Vol.50 No.4

Central Pontine Myelinolysis in a Normonatremic Patient with Depression

Yu Chia Liu,Yen Kuang Yang,Po See Chen,Wei Hung Chang 대한정신약물학회 2021 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.19 No.3

A 76-year-old male presented with a recurrent depressive episode, an unsteady gait and cognitive impairment. Extensive blood tests, including hemogram, biochemical tests, folic acid, vitamin B12, and thyroid hormone, showed normal results. With the exception of the unsteady gait, neurological examination was negative. Brian magnetic resonance imaging (MRI) showed the typical feature of central pontine myelinolysis (CPM); however, there was no history of alcoholism, liver transplantation, malnutrition or rapid correction of hyponatremia. The patient had taken venlafaxine to treat major depressive disorder for more than 20 years. After discontinuation of venlafaxine, the unsteady gait gradually resolved, and subsequent MRI revealed reduction of the lesions over 6 months. We discuss herein the possible correlation between chronic use of venlafaxine and CPM.