Shih-Shen Lin

Publications (10)26.5 Total impact

• Article: Quantitative diagnosis and analysis of mutations affecting drug resistance to rifampicin and isoniazid of clinical Mycobacterium tuberculosis isolates in Taiwan

  Chao-Wen Hsueh, Shih-Shen Lin, Chun-Hsiu Lin, Shang-Tao Chien, Wen-Sheng Liu, Fu-Gong Lin, Hsiu-Ting Tsai, Chien-Fu Huang, Chi-Chiang Yang
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  ABSTRACT: A SYBR Green I-based real-time quantitative PCR assay was utilized using senX3-regX3 and IS6110 as targets to identify Mycobacterium tuberculosis in 135 clinical samples from southern Taiwan. The bacterial loads of true positive samples estimated in this assay ranged from 33 to 7.7 × 105 CFU/ml, whereas false negative samples ranged from 10 to 25CFU/ml. The specificity and sensitivity were 100% and 88.5%, respectively. Moreover, a multiplex allele-specific PCR was applied to detect mutation at three major hot spots (affecting codons 516, 526 and 531) of the rpoB gene affecting resistance to rifampicin, as well as codon 315 of the katG gene (resistance to isoniazid). The mutation rates of rpoB and katG were 69.6% (32/46) and 45.7% (21/46), respectively. The dual-gene mutation (rpoB and katG) rate was 41.3% (19/46). Among the hot spots on the rpoB gene, the mutation rate for rpoB 531(17/46, 37%) was higher than that of rpoB 516 (10/46, 21.7%) and rpoB 526 (8/46, 17.4%). Furthermore, for the four codons assayed (rpoB 516, 526, 531, and katG), 11 mutations were identified as single mutation (23.9%), 18 as double mutations (39.1%), 3 as triple mutations, and none as quadruple mutations. Our results reveal the prevalence of tuberculosis drug-resistant mutations occurring on rpoB and katG genes in southern Taiwan. KeywordsIsoniazid-PCR-Rifampicin-Taiwan-Tuberculosis
  Annals of Microbiology 04/2012; 60(3):391-397. · 0.69 Impact Factor
• Article: Anti-herpes simplex virus effects of berberine from Coptidis rhizoma, a major component of a Chinese herbal medicine, Ching-Wei-San.

  Lengsu William Chin, Yu-Wen Cheng, Shih-Shen Lin, Ya-Yun Lai, Long-Yau Lin, Ming-Yung Chou, Ming-Chih Chou, Chi-Chiang Yang
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  ABSTRACT: Berberine is an alkaloid extracted from Coptidis rhizome. Among the individual herbal components of a Chinese herb medicine, Ching-Wei-San, Coptidis Rhizoma has the most potent antimicrobial activity. By high-pressure liquid chromatography, the quantitative analysis of berberine from 6.25-mg/mL (w/v) Coptidis rhizome extract or 50.00-mg/mL (w/v) Ching-Wei-San was determined to be 0.26 mg/mL. To explore the potential use of Ching-Wei-San against herpes simplex virus (HSV) infection, the cytotoxicity, anti-HSV-1 and anti-HSV-2 activity in Vero cells were assayed. The selectivity index of berberine was about 1.2-1.5 times higher than that of Coptidis rhizome extract and Ching-Wei-San. Moreover, the antiviral activities correspond to the content of berberine in the aqueous solution. Berberine may interfere with the viral replication cycle after virus penetration and no later than the viral DNA synthesis step, and its activities were not affected by the preparation processes. Berberine, the natural plants that contain this component, including Coptidis rhizome, and Ching-Wei-San have all shown anti-HSV effects.
  Archives of Virology 12/2010; 155(12):1933-41. · 2.11 Impact Factor
• Article: Methylantcinate A induces tumor specific growth inhibition in oral cancer cells via Bax-mediated mitochondrial apoptotic pathway.

  Wan-Chi Tsai, Yerra Koteswara Rao, Shih-Shen Lin, Ming-Yung Chou, Yi-Ting Shen, Chih-Hao Wu, Madamanchi Geethangili, Chi-Chiang Yang, Yew-Min Tzeng
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  ABSTRACT: An ergostane type triterpenoid methylantcinate A (MAA) isolated from the fruiting bodies of Antrodia camphorata inhibited the growth of oral cancer cell lines OEC-M1 and OC-2 in a dose-dependent manner, without cytotoxic to normal oral gingival fibroblast cells. The major mechanism of growth inhibition was apoptosis induction, as shown by flow cytometric analysis of annexin V-FITC and propidium iodide staining, caspase-3 activation and DNA fragmentation. The increased expression of pro-apoptotic Bax, poly-(ADP-ribose) polymerase cleavage, and activated caspase-3 and decreased expression of anti-apoptotic Bcl-2 and Bcl-xL were also observed. These results provide the first evidence that the anti-oral cancer effects of MAA may involve a mechanism through the mitochondrial dependent pathway. Thus, results reported here may offer further impulse to the development of MAA analogues as potential chemotherapeutic targets for oral cancer complications.
  Bioorganic & medicinal chemistry letters 10/2010; 20(20):6145-8. · 2.65 Impact Factor
• Article: Apoptotic death mode of mitomycin C-treated HeLa cells and cellular localization of mitomycin C-induced P-glycoprotein.

  Min-Hsiung Cheng, Hao-Tsai Cheng, Shih-Shen Lin, Su-Chung Young, Chien-Jung Pai, Pao-Hsin Liao, Shu-Chen Chen, Ming-Yung Chou, Jaw-Ji Yang, Chi-Chiang Yang
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  ABSTRACT: Mitomycin C (MMC) is an active antineoplastic agent and is suggested to induce apoptosis in a caspase- dependent manner in human gastric, bladder, and breast cancer cells. In this study, the death mode of human cervical cancer cells (HeLa) induced by MMC and the cellular localization of MMC-induced P-glycoprotein (P-gp) were investigated. The results of caspase-3 activity, Annexin V binding, and DNA fragmentation suggested that the degree of caspase-dependent apoptosis induced by MMC was in a dose-, but not time-dependent, manner. Further, in low-dose (0.0299 microM) and long-term (2 months) treatment with MMC, P-gp is itself extruded from the cells and colocalized with nuclear DNA and the overexpression was achieved.
  Drug and Chemical Toxicology 02/2009; 32(2):158-68. · 1.08 Impact Factor
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  Available from: ustc.edu.cn

  Article: The immunopharmaceutical effects and mechanisms of herb medicine.

  Chien-Fu Huang, Shih-Shen Lin, Pao-Hsin Liao, Su-Chung Young, Chi-Chiang Yang
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  ABSTRACT: In recent years, studies on evaluation of the therapeutic and toxic activity of herbal medicinal products became available and popular. The advances in modern biotechnology have led to discovery of many new active constituents. However, it is a constant challenge to establish the pharmacological basis for efficacy and safety of herbal medicinal products. A better understanding of the effects and bioavailability of phytopharmaceuticals can help in discovering suitable and rational therapies. In this review, we present the bioavailability studies in immune system that has been conducted for some of the more important or widely used phytopharmaceuticals. Furthermore, various new drug targets worthy of using for drug development in immunomodulating herbal medicine area and their regulatory mechanisms are also discussed. Adverse effects, drug interactions, and contraindications are also discussed which show that caution should be exercised when combining phytopharmaceuticals with chemically derived pharmaceutical components.
  Cellular & molecular immunology 03/2008; 5(1):23-31. · 2.99 Impact Factor
• Article: Utilizing self-prepared ELISA plates for a cross-population study of different anti-HBe IgG subclass profiles.

  Lina Wang, Tzu-Hsin Tsai, Chien-Fu Huang, Mei-Shang Ho, Ding-Bang Lin, Yung-Chyuan Ho, Shih-Shen Lin, James Cheng-Chung Wei, Ming-Chih Chou, Chi-Chiang Yang
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  ABSTRACT: Fourteen serum samples obtained from hepatitis B virus (HBV) chronic carriers and patients recovered from hepatitis B infection were used with four sodium dodecyl sulfate-treated enzyme-linked immunosorbent assay (ELISA) plates available commercially, and one self-prepared HBcAg analog for evaluation of anti-HBe subclass pattern absorbance. The self-prepared plates had the best performance and were thus used for samples obtained from 104 (60 male and 44 female) HBV chronic carriers and 439 (247 male and 192 female) recovered individuals. Tests for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also carried out in 21 of the subjects (>25 IU/ml). Statistical comparison of these patients with elevated ALT/AST levels with other ALT/AST-normal chronic carriers revealed no significant differences in the anti-HBe OD, although the mean optical density (OD) of patients with elevated ALT/AST levels was higher. The results suggest that the anti-HBe IgG subclass profiles in the chronic carriers did not change with inflammation of the liver, and were independent of sex and age. In contrast to previous anti-HBc findings, the distribution pattern of anti-HBe subclasses in HBV chronic carriers was IgG1 > IgG4 > IgG3 while in the recovered individuals it was IgG1 > IgG3 > IgG4, for both males and females. Subclasses IgG1 and IgG2 were the most and least prevalent isotypes, respectively, in both study groups. The results of the study suggest that induction of IgG1 and/or IgG3 antibodies is important for effective virus neutralization, while IgG2 antibodies are of limited importance. Significantly higher OD values for anti-HBe IgG4 were observed when comparing samples from the chronic carriers and recovered individuals, which may reflect the effects of persistence. Further, in contrast to previous anti-HBs results, the concentrations of total IgG and IgG1 were higher in the samples from chronic carriers relative to those from recovered individuals.
  Journal of Medical Virology 06/2007; 79(5):495-502. · 2.82 Impact Factor
• Article: In vitro anti-microbial and in vivo cytokine modulating effects of different prepared Chinese herbal medicines.

  Shyh-Jye Lin, Chung-Shih Chen, Shih-Shen Lin, Ming-Yung Chou, Hung-Che Shih, I-Pang Lee, Chia-Tze Kao, Chuan-Chen Ho, Fong-Lin Chen, Yung-Chyuan Ho, Kuang-Hui Hsieh, Chi-Ruei Huang, Chi-Chiang Yang
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  ABSTRACT: The toxicity, antimicrobial and cytokine modulating effects of herbal medicines in treating periodontal diseases were evaluated in this study. Using the broth dilution method and disc agar diffusion test, in individual and combined decocted preparations, different concentrations of Ching-Wei-San and its individual herbal components, Coptidis rhizoma, Angelicae sinensis radix, Rehmanniae radixet rhizom, Moutan radicis cortex, and Cimicifuga foetida, were tested for in vitro inhibitory effects on three well-known plaque-causing bacteria, Porphyromonas gingivialis, Streptococcus sanguis, and Streptococcus mutans, and two common pathogens, Staphylococcus aureus and Escherichia coli. The cytokine modulating effects were evaluated in Balb/c mice. The results suggested that one milliliter Ching-Wei-San at the 25,000 mg/mL concentration daily for the mice had significantly high levels in the liver function indexes in the 3-day acute toxicity test and in both the liver and kidney function indexes in the 28-day subacute toxicity test (P<0.01). The 250 mg/mL Ching-Wei-San is comparable to 250 mg/mL of tetracycline, and had similar inhibitory effects on the tested bacteria. Coptidis rhizoma (62.5 mg/mL) was the only individual herbal component to show 100% inhibitory effects. The mean cytokine ratios of IL-2, IL-4, IFN-gamma, and TNF-alpha in Balb/c mice treated with individual herbal components were shown to be different from each other. Ching-Wei-San modulated the immunity of mice, up-regulated IL-2, IL-4 and TNF-alpha, but down-regulated IFN-gamma. The effects of none of the individual herbal components alone can substitute for the cumulative effect of Ching-Wei-San.
  Food and Chemical Toxicology 12/2006; 44(12):2078-85. · 3.00 Impact Factor
• Source

  Available from: ustc.edu.cn

  Article: The immune response induced by hepatitis B virus principal antigens.

  Chien-Fu Huang, Shih-Shen Lin, Yung-Chyuan Ho, Fong-Ling Chen, Chi-Chiang Yang
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  ABSTRACT: Hepatitis B virus (HBV) infection occurs primarily in hepatocytes in the liver with release of infectious virions and non-infectious empty surface antigen particles into the bloodstream. HBV replication is non-cytopathic. Transient infections run a course of several months, and chronic infections are often life-long. Chronic infections can lead to liver failure with cirrhosis and hepatocellular carcinoma. It is generally accepted that neutralizing anti-HBs antibodies plays a key role in recovery from HBV infection by containing the spread of infection in the infected host and facilitating the removal and destruction of viral particles. However, the immune response initiated by the T-cell response to viral antigens is also important for viral clearance and disease pathogenesis in HBV infection. The three structural forms of the viral proteins, the HBsAg, the particulate HBcAg, and the nonparticulate HBeAg, may preferentially elicit different Th cell subsets. The different IgG subclass profiles of anti-HBs, anti-HBc, and anti-HBe in different HBV infection status were revealed. Moreover, the different IgG subclass profiles in chronic carriers did not change with different ALT and AST levels and may reflect the difference between stimulating antigens, immune response, and the stages of viral disease and provide the basis for the use of vaccines and prophylactic treatments for individuals at high risk of human HBV infection. This review elucidates the detailed understanding of the immune responses induced during transient and persistent infection, and the development of immunotherapy and immunodiagnosis in patients with HBV infection, and possible means of reducing the liver damage.
  Cellular & molecular immunology 05/2006; 3(2):97-106. · 2.99 Impact Factor
• Article: Effects of CAPE-like compounds on HIV replication in vitro and modulation of cytokines in vivo.

  Chuan-Chen Ho, Shih-Shen Lin, Ming-Yung Chou, Fang-Lung Chen, Chao-Chin Hu, Chung-Shih Chen, Guan-Yu Lu, Chi-Chiang Yang
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  ABSTRACT: Five CAPE-like compounds, namely caffeic acid phenethyl ester (CAPE), methyl caffeate (MC), ethyl 3-(3,4-dihydroxyphenyl)acrylate (EC), phenethyl dimethyl caffeate (PEDMC) and phenethyl 3-(4-bromophenyl)acrylic (BrCAPE) were tested for their anti-HIV replication in vitro and immune modulation effects in vivo. Short-term cytotoxicity was assessed by Trypan Blue stain and MTT assay. For antiviral assays, M-tropic (strain JRCSF), T-tropic (strain NL-4-3) and dual tropic (strain 89.6) HIV isolates were used in peripheral blood mononuclear cell (PBMC) culture. None of these CAPE-like compounds showed significant cytotoxicity in the treatment of PBMCs. By P24 EIA tests, CAPE, MC and EC significantly inhibited HIV replication in PBMC cells, but PEDMC and BrCAPE showed only slightly inhibitory effects. The in vivo modulatory effects on six cytokines [interleukin (IL)-2, IL-4, IL-6, interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF) and soluble Fas] were analysed. BALB/c mice treated with different doses or not treated with these CAPE-like chemicals showed that cytokines were increased to different extents by the different treatments. However, the concentrations of IL-6 and GM-CSF were not significantly affected by administration of any of these compounds (P > 0.05). The different effects of treatments on anti-HIV replication and cytokine modulation suggested that these compounds affect virological and immunological response via different mechanisms. The virological and immunological mechanisms and response to these treatments need to be elaborated in further studies in order to derive the structural features of more effective compounds. Since neither death nor pathological change in the mice were observed in this study, these CAPE-like compounds are worth studying further as potential chemotherapy agents for anti-HIV infection and cytokine modulation.
  Journal of Antimicrobial Chemotherapy 08/2005; 56(2):372-9. · 5.07 Impact Factor
• Article: Study of the viral infections and cytokines associated with recurrent aphthous ulceration.

  Shih-Shen Lin, Ming-Yung Chou, Chuan-Chen Ho, Chia-Tze Kao, Chung-Hung Tsai, Lina Wang, Chi-Chiang Yang
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  ABSTRACT: Mouth ulcers are one of the most common oral complaints. However, the association between oral ulceration and viruses and cytokines is uncertain. We detected the presence of human papilloma virus (HPV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV)-1, HSV-2 and human herpesvirus (HHV)-8 DNA in oral tissues by polymerase chain reaction (PCR) and Southern hybridization techniques, and quantified the serum levels of cytokines including interleukin (IL)-2, IL-4, granulocyte-macrophage colony-stimulating factor (GM-CSF), soluble Fas (sFas) and the Fas ligand (FasL) by enzyme-linked immunosorbent assay (ELISA) for 67 recurrent aphthous ulcer (RAU) patients and 72 normal individuals. Seven patient specimens were excluded from the study due to the negative PCR results for the beta-globin used as the internal control. Among the 32 (53.3%) virus-positive results from 60 patients' samples, 8 (13.3%) HPV, 4 (6.7%) HSV-1, 11 (18.3%) CMV, 9 (15.0%) EBV, and 16 (26.7%) HHV-8 samples proved to be positive. No HSV-2-positive samples were found. The percentage of single-virus infection (56.3%) was significantly greater than that of double-virus co-infection (31.3%) and the percentage of double-virus co-infection was significantly greater than the percentage of triple-virus co-infection (12.5%) (P < 0.05). In the 72 normal oral-tissue specimens, no viral DNA was detected. The mean serum cytokine level for patients was significantly (P < 0.05) greater than for controls for most of the separate age groups. The mean serum cytokine concentrations for the patient group demonstrated a diffuse pattern covering a wide range of serum concentrations, a very different result from the compact serum concentration pattern and lower mean serum cytokine concentrations revealed by the normal group. Overall association between viruses and recurrent aphthous ulceration is HHV-8 > CMV > EBV > HPV > HSV-1, regarding the frequency of prevalence (P < 0.05).
  Microbes and Infection 05/2005; 7(4):635-44. · 3.10 Impact Factor