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Magnolol induces apoptosis via caspase-independent pathways in non-small cell lung cancer cells
Tsai, Jong-Rung,Chong, Inn-Wen,Chen, Yung-Hsiang,Hwang, Jhi-Jhu,Yin, Wei-Hsian,Chen, Hsiu-Lin,Chou, Shah-Hwa,Chiu, Chien-Chih,Liu, Po-Len 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.4
Magnolol, a hydroxylated biphenyl agent isolated from herbal planet Magnolia officinalis, is a component of traditional Asian herbal teas. It has been reported to have anti-microbial, anti-inflammatory, and anti-cancer activity. Non-small cell lung cancer (NSCLC) cell lines (A549, H441 and H520) and normal human bronchial epithelial cells (HBECs) were used to evaluate the cytotoxic effect of magnolol. We show that magnolol inhibited cellular proliferation, increased DNA fragmentation, and decreased mitochondrial membrane potential in all NSCLC cells, but had no cytotoxic effect on HBECs. Magnolol triggered the release of pro-apoptotic proteins: Bid, Bax and cytochrome c from mitochondria, but did not activate the caspase-3, -8, and -9, suggesting that magnolol induces apoptosis of NSCLC cell lines via a caspase-independent pathway. The caspase-independent pathway is mediated through the activation of nuclear translocation of apoptosis-inducing factor, endonuclease G and cleaved poly(-ADP-ribose) polymerase, which played important roles in mediating cell death. Furthermore, magnolol inhibited PI3K/AKT and ERK1/2 activity, but up-regulated p38 and JNK activity in A549 cell lines. The results of this study provided a basis for understanding and developing magnolol as a novel treatment of NSCLC.
Chen, Po-Chuan,Tsai, Shih-Hung,Chen, Yu-Long,Liao, Wen-I The Korean Neurosurgical Society 2014 Journal of Korean neurosurgical society Vol.55 No.5
Post-traumatic cerebral infarction (PTCI) is a secondary insult which causes global cerebral hypoxia or hypoperfusion after traumatic brain injury, and carries a remarkable high mortality rate. PTCI is usually caused by blunt brain injury with gross hematoma and/or brain herniation. Herein, we present the case of a 91-year-old male who had sustained PTCI following a low-energy penetrating craniocerebral injury due to a nail without evidence of hematoma. The patient survived after a decompressive craniectomy, but permanent neurological damage occurred. This is the first case of profound PTCI following a low-energy penetrating craniocerebral nail injury and reminds clinicians of possibility this rare dreadful complication for care of head-injured patients.
Magnolol induces apoptosis via caspase-independent pathways in non-small cell lung cancer cells
Jong-Rung Tsai,Inn-Wen Chong,Yung-Hsiang Chen,Jhi-Jhu Hwang,Wei-Hsian Yin,Hsiu-Lin Chen,Shah-Hwa Chou,Chien-Chih Chiu,Po-Len Liu 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.4
Magnolol, a hydroxylated biphenyl agent isolatedfrom herbal planet Magnolia officinalis, is a componentof traditional Asian herbal teas. It has been reported tohave anti-microbial, anti-inflammatory, and anti-canceractivity. Non-small cell lung cancer (NSCLC) cell lines(A549, H441 and H520) and normal human bronchialepithelial cells (HBECs) were used to evaluate the cytotoxiceffect of magnolol. We show that magnolol inhibitedcellular proliferation, increased DNA fragmentation, anddecreased mitochondrial membrane potential in all NSCLCcells, but had no cytotoxic effect on HBECs. Magnololtriggered the release of pro-apoptotic proteins: Bid, Bax and cytochrome c from mitochondria, but did not activatethe caspase-3, -8, and -9, suggesting that magnolol inducesapoptosis of NSCLC cell lines via a caspase-independentpathway. The caspase-independent pathway is mediatedthrough the activation of nuclear translocation of apoptosis-inducing factor, endonuclease G and cleaved poly(-ADP-ribose) polymerase, which played important roles inmediating cell death. Furthermore, magnolol inhibitedPI3K/AKT and ERK1/2 activity, but up-regulated p38 andJNK activity in A549 cell lines. The results of this studyprovided a basis for understanding and developing magnololas a novel treatment of NSCLC.
Yuan-Hwa Chou,Po-Chung Chu,Szu-Wei Wu,Jen-Chin Lee,Yi-Hsuan Lee,I-Wen Sun,Chen-Lin Chang,Chien-Liang Huang,I-Chao Liu,Chia-Fen Tsai,Yung-Chieh Yen 대한정신약물학회 2015 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.13 No.2
Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician’s clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms.
How-Ji Chen,Wen-Po Tsai,Chao-Wei Tang,Te-Hung Liu 국제구조공학회 2011 Structural Engineering and Mechanics, An Int'l Jou Vol.39 No.6
We have developed a lightweight aggregate (LWA) concrete made by expanding fine sediments dredged from the Shihmen Reservoir (Taiwan) with high heat. In this study, the performance of the concrete and of prestressed concrete beams made of the sedimentary LWA were tested and compared with those made of normal-weight concrete (NC). The test results show that the lightweight concrete (LWAC) exhibited comparable time-dependent properties (i.e., compressive strength, elastic modulus, drying shrinkage, and creep) as compared with the NC samples. In addition, the LWAC beams exhibited a smaller percentage of prestress loss compared with the NC beams. Moreover, on average, the LWAC beams could resist loading up to 96% of that of the NC beams, and the experimental strengths were greater than the nominal strengths calculated by the ACI Code method. This investigation thus established that sedimentary LWA can be recommended for structural concrete applications.
Chen, How-Ji,Tsai, Wen-Po,Tang, Chao-Wei,Liu, Te-Hung Techno-Press 2011 Structural Engineering and Mechanics, An Int'l Jou Vol.39 No.6
We have developed a lightweight aggregate (LWA) concrete made by expanding fine sediments dredged from the Shihmen Reservoir (Taiwan) with high heat. In this study, the performance of the concrete and of prestressed concrete beams made of the sedimentary LWA were tested and compared with those made of normal-weight concrete (NC). The test results show that the lightweight concrete (LWAC) exhibited comparable time-dependent properties (i.e., compressive strength, elastic modulus, drying shrinkage, and creep) as compared with the NC samples. In addition, the LWAC beams exhibited a smaller percentage of prestress loss compared with the NC beams. Moreover, on average, the LWAC beams could resist loading up to 96% of that of the NC beams, and the experimental strengths were greater than the nominal strengths calculated by the ACI Code method. This investigation thus established that sedimentary LWA can be recommended for structural concrete applications.
( Ching-ling Lin ),( Ming-lin Tsai ),( Yu-hsin Chen ),( Wei-ni Liu ),( Chun-yu Lin ),( Kai-wen Hsu ),( Chien-yu Huang ),( Yu-jia Chang ),( Po-li Wei ),( Shu-huey Chen ),( Li-chi Huang ),( Chia-hwa Lee 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.5
Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.
How-Ji Chen,Te-Hung Liu,Chao-Wei Tang,Wen-Po Tsai 국제구조공학회 2011 Structural Engineering and Mechanics, An Int'l Jou Vol.40 No.6
The objective of this study was to experimentally investigate the bond-related tension stiffening behavior of flexural reinforced concrete (RC) beams made with lightweight aggregate concrete (LWAC) under various high-cycle fatigue loading conditions. Based on strain measurements of tensile steel in the RC beams, fatigue-induced degradation of tension stiffening effects was evaluated and was, compared to reinforced normal weight concrete (NWC) beams with equal concrete compressive strengths (40 MPa). According to applied load-mean steel strain relationships, the mean steel strain that developed under loading cycles was divided into elastic and plastic strain components. The experimental results showed that, in the high-cycle fatigue regime, the tension stiffening behavior of LWAC beams was different from that of NWC beams; LWAC beams had a lesser reduction in tension stiffening due to a better bond between steel and concrete. This was reflected in the stability of the elastic mean steel strains and in the higher degree of local plasticity that developed at the primary flexural cracks.
Chen, How-Ji,Liu, Te-Hung,Tang, Chao-Wei,Tsai, Wen-Po Techno-Press 2011 Structural Engineering and Mechanics, An Int'l Jou Vol.40 No.6
The objective of this study was to experimentally investigate the bond-related tension stiffening behavior of flexural reinforced concrete (RC) beams made with lightweight aggregate concrete (LWAC) under various high-cycle fatigue loading conditions. Based on strain measurements of tensile steel in the RC beams, fatigue-induced degradation of tension stiffening effects was evaluated and was, compared to reinforced normal weight concrete (NWC) beams with equal concrete compressive strengths (40 MPa). According to applied load-mean steel strain relationships, the mean steel strain that developed under loading cycles was divided into elastic and plastic strain components. The experimental results showed that, in the high-cycle fatigue regime, the tension stiffening behavior of LWAC beams was different from that of NWC beams; LWAC beams had a lesser reduction in tension stiffening due to a better bond between steel and concrete. This was reflected in the stability of the elastic mean steel strains and in the higher degree of local plasticity that developed at the primary flexural cracks.