Blocking of Cell Proliferation, Cytokines Production and Genes Expression Following Administration of Cordyceps Sinensis in the Bronchoalveolar Lavage Fluids Cells

Kuo, Yuh-Chi,Wu, Chia-Lin,Tasi, Wei-Jern,Wang, Jir-Yenn,Chang, Shi-Chung,Lin, Ching-Yuang,Shiao, Ming-Shi 경희대학교 동서의학연구소 1999 INTERNATIONAL SYMPOSIUM ON EAST-WEST MEDICINE Vol.1999 No.1

Yuh-Chi Kuo¹,Chia-Lin Wn¹,Wei-jern Tasi¹,Jir-Yenn Wang²,Shi-Chung Chang₃,Ching-Yung Lin⁴,and Ming-Shi Shiao⁴¹National Research Institute of Chinese Medicine, ²Department of Biology,Fu Jen University, ³Department of Chest, ⁴Department of Pediatrics, □De[art,amt of Medical Research and Education. Taipei Veterans General Hospital, Taipei, Taiwan Yuh-Chi Kuo¹,Chia-Lin Wn¹,Wei-jern Tasi¹,Jir-Yenn Wang²,Shi-Chung Chang²,Ching-Yung Lin³,and Ming-Shi Shiao⁴.¹National Research Institute of Chinese Medicine, ²Department of Biology,Fu Jen University, ³Department of Chest, ⁴Department of Pediatrics, □De[art,amt of Medical Research and Education. Taipei Veterans General Hospital, Taipei, Taiwan. Blocking of Cell Proliferation, Cytokines Production and Genes Expression Following Administration of Cordyceps sinensis in the Bronchoalveolar Lavage Fluids Cells. Proceedings of international Symposium on East-West Medicine, Seoul. 44-64, 1999.-Cordyceps sinensis is a major parasitic fungus on larva of Lepidoptera. It is one of the well know fungi used in traditional Chinese medicine for treatment asthma, lung and kideney diseases. Many fungi belonging to the genus Cordyceps have been demonstrated to produce natural products with various biological activities. Reported biological activities of genus cordyceps include:(a)inhibition of DNA and RNA synthesis;(b)enhancement of cell differentiation;(c)restruction of cytoskeleton;(d)inhibition of protein kinase activity;(e)antitumor activity on bladder, colon, lung carcinoma as well as fibroblastoma;(f)inhibition of the infection and revers transciptase activity of human immunodeficiency virus type 1; and(g) inhibition of methylation of nucleic acid. Thus, it is suggested that the extracts of Cordyceps sp. Contain antitumor, antiviral, and many other biological activities. In our previous studies, we proved that C. sinensis contains the antitumor and immunomodulatory agents. In the present studies, effects of C. sinensis on bronchoalveolar lavage fluids(BAL)cells were demonstrated. The crude methanolic extracts of C. sinensis were fractionated into 15 fractions by silica gel column chromatography. Effects of various fraction on BAL cells proliferation and lipopolysaccharide(LPS) stimulated interleukin-1β(IL-8),platelet activating factor(PAF), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α),and interleukin-8(IL-8) production on BAL cells were determined. The result indicated that the CS-19-22 fraction suppressed BAL cells proliferation activated by LPS. The median inhibitory concentration(IC50) was 6㎍/ml. The CS-19-22 fraction also decreased IL-1β,PAF,IL-6, TNF-αand IL-8 production.The results of revers transcription-polymerase chain reaction(RT-PCR) demonstrated that the CS-19-22 fraction did not affect IL-1β,PAF,IL-6, TNF-α,and IL-8 mRNAs expression in BAL cells activated by LPS. By contrast, it inhibited the IL-10 mRNA expression but enhanced IFN-γand IL-12 mRNAs expression in activated BAL cells. Moreover, the CS-19-22 fraction blocked PAF-induced platelet aggregation. It is unlikely that cytotoxicity was involved. Because no cell deths were observable. We hypothesize that inhibitory mechanisms of CS-19-22 on BAL cells proliferation may be related to the impairments of gene expression and production of cytokines in BAL cells. The explanation of C. sinensis antiasthma function may involved the following(1)C.sinenesis contained immunomodulatory agents that stimulated IFN-γand IL-12 expression in TH1cells.(2)Enhanced secretion of IFN-γand IL-12 will inhibit the Tγcells immune responses Ex. Decreasing of IL-6 and IL-10 production.(3) The impairments of cytokines production in TH2 cells suppressed th BAL cells proliferation then more cytokines production Ex.IL-1β,PAF,IL-6,TNF-αand IL-8 in activated BAL cells were decreased. (4)The suppression of TH2cells immune responses will inhibit the growth and differentiation of B cells then IgE production will be decreased. (5)Reduced production of IgE will decreased asthma attack occurring in individuals. However, the results of the present study suggested that C. sinensis may also have acted to treat asthma in part by inhibiting BAL cells proliferation and cytokine gene expression and production. Future, experiments with treatment of animals with asthma with C. sinensis will be necessary to defined whether C. sinensis can reduce asthma injury. Plans are underway for the isolation of pure principal growth inhibitors and their mechanisms of action are subjected for further study.

Fixed-point theory for k-set contraction

Chi-Ming Chen,Tong-Huei Chang,Chi-Lin Yen 대한수학회 2004 대한수학회지 Vol.41 No.2

In this note, we get some generalized KKM theorems for the k-set contraction mapping on the nearly-convex sets.

Molecular Epidemiology of Integron-Associated Antimicrobial Gene Cassettes in the Clinical Isolates of Acinetobacter baumannii from Northern Taiwan

Ming-Feng Lin,Ming- Li Liou,Chi-Chao Tu,Hui-Wen Yeh,Chung-YuLan 대한진단검사의학회 2013 Annals of Laboratory Medicine Vol.33 No.4

Background: The aims of this study were to understand the molecular epidemiology of integron-associated gene cassettes in Acinetobacter baumannii across four hospitals in northern Taiwan and to clarify the relationship between the presence of integrons and antibiotic-resistant phenotypes. Methods: Sixty-five A. baumannii isolates, collected from the patients of four regional hospitals in northern Taiwan in 2009, were tested for the presence of integrons and their associated gene cassettes. The susceptibility difference between integron-positive and integron-negative A. baumannii strains was analyzed. Antibiotic-resistant phenotypes among A. baumannii with different types of gene cassette array combinations were also compared. Results: Around 72% of the A. baumannii isolates carried class 1 integrase genes. Despite this, only three gene cassette arrays were found in the integrons. Integron-positive strains were significantly more resistant to all the tested antibiotics than the integrase-negative strains. All the four types of A. baumannii with different gene cassette array combinations were multidrug-resistant in nature. Gene cassette array aacA4-catB8-aadA1 existed in all the integron-positive A. baumannii isolates. Repetitive-sequence-based PCR (rep-PCR)results revealed the prevalence of one major cluster of imipenem-resistant A. baumannii strains (84%) in the four regional hospitals. Conclusions: The presence of integrons with associated antimicrobial resistance gene cassettes can be used as a representative marker of multidrug resistance in A. baumannii. Some prevalent gene cassette arrays may exist among epidemiologically unrelated A. baumannii strains.

Sofosbuvir/Ledipasvir in the Treatment of Chronic Hepatitis C - A Subgroup Analysis from A Nationwide Real-World HCV Registry Program (TACR) in Taiwan

( Ming-Lung Yu ),( Chi-Yi Chen ),( Kuo-Chih Tseng ),( Ching-Chu Lo ),( Pin-Nan Cheng ),( Cheng-Yuan Peng ),( Ming-Jong Bair ),( Chih-Lang Lin ),( Chi-Ming Tai ),( Chi-Chieh Yang ),( Chih-Wen Lin ),( C 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: TASL HCV Registry (TACR) is a nationwide registry program organized and supervised by Taiwan Association for the Study of the Liver (TASL), which aims to setup the database and biobank of patients with chronic hepatitis C (CHC) in Taiwan. The present study aimed to evaluate the treatment outcome of sofosbuvir (SOF)/ledipasvir (LDV) in Taiwanese CHC patients in TACR. Methods: By May 2020, 19 tertiary hospitals, 23 community hospitals and one primary care clinic join the TACR program. The baseline characteristics, prior liver and non-liver related medical history, DAA regimens, laboratory results, treatment course and outcome were recorded. The primary objective was sustained virological response, defined as undetectable HCV RNA 3 months after end-of-treatment (SVR12). Results: A total of 4742 SOF/LDV+ ribavirin treated CHC patients with available SVR12 data from 39 sites were enrolled in the current analysis. The mean age was 61.3 years, and female accounted for 54.8% of the population. The dominant viral genotypes were GT1b (52.6%) and GT2 (35.6%). 1354 (28.6%) patients had liver cirrhosis, including 156 (3.3%) with liver decompensation, 552 (11.6%) had preexisting hepatocellular carcinoma (HCC) before DAAs treatment and 413 (8.7%) had hepatitis B virus dual infections. The overall SVR12 rate was 98.5%, with 98.5%, 98.2%, 99.7% and 98.6% in treatment- naïve non-cirrhotics, treatment-naïve cirrhotics, treatment- experienced non-cirrhotics and treatment-experienced cirrhotics patients, respectively. While patients were stratified by HCV genotype, the SVR12 was 98.5%, 98.4% and 98.5% among those with GT1, GT2 and GT6 infection, respectively. The strongest factor independent associated with treatment failure was DAA adherence < 60% (odds ratio [OR]/95% confidence intervals [CI]: 125.4/25.7-612.4, P<0.0001), followed by active HCC (OR/CI: 6.20/2.57-14.97, P<0.0001), HIV co-infection (OR/CI: 3.01/1.14-7.92, P=0.026), and male gender (OR/ CI: 1.85/1.09-3.13, P=0.023). The eGFR decreased significantly at the end of treatment (EOT) (89.3 ml/min/1.73㎡ vs. 93.2 ml/min/1.73㎡, P< 0.001) and remained stable 3 months after EOT (89.3 ml/min/1.73㎡). However, the decreased eGFR was observed only in patients whose baseline eGFR > 90 ml/ min/1.73㎡. Instead, patients with chronic kidney diseases whose pretreatment eGFR < 60 ml/min/1.73㎡ had improved eGFR after SOF/LDV. Conclusions: SOF/LDV is highly effective in treating CHC patients in real-world setting of Taiwan. The satisfactory result could be explicitly generalized to patients with different viral genotypes and liver disease severities.

FIXED-POINT THEORY FOR k-SET CONTRACTION

Chen, Chi-Ming,Chang, Tong-Huel,Yen, Chi-Lin Korean Mathematical Society 2004 대한수학회지 Vol.41 No.2

In this note, we get some generalized KKM theorems for the k-set contraction mapping on the nearly-convex sets.

Platelet-Derived Growth Factor Receptor-α Subunit Targeting Suppresses Metastasis in Advanced Thyroid Cancer In Vitro and In Vivo

( 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.

Prediction of the Duration to Next Admission for an Acute Affective Episode in Patients with Bipolar I Disorder

Pao-Huan Chen(Pao-Huan Chen),Chun-Ming Shih(Chun-Ming Shih),Chi-Kang Chang(Chi-Kang Chang),Chia-Pei Lin(Chia-Pei Lin),Yung-Han Chang(Yung-Han Chang),Hsin-Chien Lee(Hsin-Chien Lee),El-Wui Loh(El-Wui Lo 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.2

Objective: Predicting disease relapse and early intervention could reduce symptom severity. We attempted to identify potential indicators that predict the duration to next admission for an acute affective episode in patients with bipolar I disorder. Methods: We mathematically defined the duration to next psychiatric admission and performed single-variate regressions using historical data of 101 patients with bipolar I disorder to screen for potential variables for further multivariate regressions. Results: Age of onset, total psychiatric admissions, length of lithium use, and carbamazepine use during the psychiatric hospitalization contributed to the next psychiatric admission duration positively. The all-in-one found that hyperlipidemia during the psychiatric hospitalization demonstrated a negative contribution to the duration to next psychiatric admission; the last duration to psychiatric admission, lithium and carbamazepine uses during the psychiatric hospitalization, and heart rate on the discharge day positively contributed to the duration to next admission. Conclusion: We identified essential variables that may predict the duration of bipolar I patients’ next psychiatric admission. The correlation of a faster heartbeat and a normal lipid profile in delaying the next onset highlights the importance of managing these parameters when treating bipolar I disorder.

Induction of Indoleamine 2,3-dioxygenase (IDO) Enzymatic Activity Contributes to Interferon-Gamma Induced Apoptosis and Death Receptor 5 Expression in Human Non-small Cell Lung Cancer Cells

Chung, Ting Wen,Tan, Kok-Tong,Chan, Hong-Lin,Lai, Ming-Derg,Yen, Meng-Chi,Li, Yi-Ron,Lin, Sheng Hao,Lin, Chi-Chen Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.18

Interferon-gamma (IFN-${\gamma}$) has been used to treat various malignant tumors. However, the molecular mechanisms underlying the direct anti-proliferative activity of IFN-${\gamma}$ are poorly understood. In the present study, we examined the in vitro antitumor activity of IFN-${\gamma}$ on two human non-small-cell lung carcinoma (NSCLC) cell lines, H322M and H226. Our findings indicated that IFN-${\gamma}$ treatment caused a time-dependent reduction in cell viability and induced apoptosis through a FADD-mediated caspase-8/tBid/mitochondria-dependent pathway in both cell lines. Notably, we also postulated that IFN-${\gamma}$ increased indoleamine 2,3-dioxygenase (IDO) expression and enzymatic activity in H322M and H226 cells. In addition, inhibition of IDO activity by the IDO inhibitor 1-MT or tryptophan significantly reduced IFN-${\gamma}$-induced apoptosis and death receptor 5 (DR5) expression, which suggests that IDO enzymatic activity plays an important role in the anti-NSCLC cancer effect of IFN-${\gamma}$. These results provide new mechanistic insights into interferon-${\gamma}$ antitumor activity and further support IFN-${\gamma}$ as a potential therapeutic adjuvant for the treatment of NCSLC.

Galangin Prevents Acute Hepatorenal Toxicity in Novel Propacetamol-Induced Acetaminophen-Overdosed Mice

Ming-Shiun Tsai,Chia-Chih Chien,Ting-Hui Lin,Chia-Chi Liu,Rosa Huang Liu,Hong-Lin Su,Yung-Tsung Chiu,Sue-Hong Wang 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.11

Acetaminophen (APAP) overdose causes severe liver and kidney damage. APAP-induced liver injury (AILI) represents the most frequent cause of drug-induced liver failure. APAP is relatively insoluble and can only be taken orally; however, its prodrug, propacetamol, is water soluble and usually injected directly. In this study, we examined the timedependent effects of AILI after propacetamol injection in mice. After analyses of alanine aminotransferase and aspartate aminotransferase activities and liver histopathology, we demonstrated that a novel AILI mouse model can be established by single propacetamol injection. Furthermore, we compared the protective and therapeutic effects of galangin with a known liver protective extract, silymarin, and the only clinical agent for treating APAP toxicity, N-acetylcysteine (NAC), at the same dose in the model mice. We observed that galangin and silymarin were more effective than NAC for protecting against AILI. However, only NAC greatly improved both the survival time and rate consequent to a lethal dose of propacetamol. To decipher the hepatic protective mechanism(s) of galangin, galangin pretreatment significantly decreased the hepatic oxidative stress, increased hepatic glutathione level, and decreased hepatic microsomal CYP2E1 levels induced by propacetamol injection. In addition, propacetamol injection also reproduced the probability of APAP-induced kidney injury (AIKI), appearing similar to a clinical APAP overdose. Only galangin pretreatment showed the protective effect of AIKI. Thus, we have established a novel mouse model for AILI and AIKI using a single propacetamol injection. We also demonstrated that galangin provides significant protection against AILI and AIKI in this mouse model.

INVESTIGATING SATISFIED BUT DISLOYAL BUSINESS CUSTOMERS

Ming-Chih Tsai,Rico Merkert,Shiau-Chi Lin,Mei-Ting Tsai 글로벌지식마케팅경영학회 2018 Global Marketing Conference Vol.2018 No.07

Satisfaction paradox indicates customer satisfaction does not necessarily translate into customer repurchase. Competitor’s attractiveness and customer demographics are two main moderators for the paradoxical phenomenon. Competitor’s attractiveness exhibits customer switching effect, whereas customer demographics imply customers moored with their current service provider. Still, the cases were few investigated in B2B settings where customers are in general more complex than consumers as involving more intricate organizational network influences. In a business network, transactions may incur buyer/seller relational activities that mitigate paradoxical behavior. Nonetheless, the variable is yet identified and the interacting effects between the moderating variables are not clarified. Thus, this study aims to develop an operational model to classify satisfied customers into loyal, moored and paradoxical segments using three genres of moderators: competitor’s attractiveness, organizational and transactional variables in a B2B setting. In the model, the theoretical bases of switching behaviors are applied for four statistical analysis executed in a logic sequence, including a factor analysis to consolidate quality measurements, a quadrant analysis to locate the effect of competitor’s attractiveness, a clustering analysis to segment satisfied customers into four segments, and finally, nonparametric tests to validate the organizational and transactional segmentation variables. Empirically, we study Taiwanese manufacturers who engaged in global trade and have had experiences in choosing the global air express services that form an oligopolistic market and a strategic group so competitor’s attractiveness can be better calibrated. A total of 180 valid samples are collected and analyzed. The results contribute to the literatures of B2B service marketing.