Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes.

Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH

Decaffeinated Green Coffee Bean Extract Attenuates Diet-Induced Obesity and Insulin Resistance in Mice

This study investigated whether decaffeinated green coffee bean extract prevents obesity and improves insulin resistance and elucidated its mechanism of action. Male C57BL/6N mice (N=48) were divided into six dietary groups: chow diet, HFD, HFD-supplemented with 0.1%, 0.3%, and 0.9% decaffeinated green coffee bean extract, and 0.15% 5-caffeoylquinic acid. Based on the reduction in HFD-induced body weight gain and increments in plasma lipids, glucose, and insulin levels, the minimum effective dose of green coffee bean extract appears to be 0.3%. Green coffee bean extract resulted in downregulation of genes involved in WNT10b- and galanin-mediated adipogenesis and TLR4-mediated proinflammatory pathway and stimulation of GLUT4 translocation to the plasma membrane in white adipose tissue. Taken together, decaffeinated green coffee bean extract appeared to reverse HFD-induced fat accumulation and insulin resistance by downregulating the genes involved in adipogenesis and inflammation in visceral adipose tissue

마이코플라즈마, 써코바이러스, 돼지 생식기 호흡기 증후군 바이러스의 상호작용 연구

학위논문 (박사)-- 서울대학교 대학원 : 수의과대학 수의학과 수의병인생물학및예방수의학전공, 2016. 2. 채찬희.Porcine Respiratory Disease Complex (PRDC) is the most serious concern for swine producers in Korea and other countries. The most common viral agents involved in PRDC include Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), Classical Swine Fever (CSF), Swine Influenza Virus (SIV), Pseudorabies Virus (PRV), and Porcine Circovirus type 2 (PCV2). Bacterial Pathogens associated with PRDC include Mycoplasma hyopneumoniae, Pasteurella multocida, Bordetella bronchiseptica, and Haemophilus parasuis, Streptococcus suis and the Actinobacillus spp. It is important to know that the interactions between pathogens can be a major factor in determining severity of the disease. The successful control of PRDC is based on the accurate diagnosis of the problem pathogens present on a herd basis. And it has been found that timing of intervention strategies, whether antibiotics or vaccines, is increasingly important on a herd basis. The objective of this thesis is to determine the effects of those pathogens and vaccine efficacy throughout experimental model and challenge test. Part I is with PCV2 and Mycoplasma hyopneumoniae vaccinations on disease severity in an experimental PCV2-M. hyopneumoniae dual challenge model. Vaccine effectiveness was evaluated using microbiological (PCV2 viremia and M. hyopneumoniae nasal shedding), immunological (neutralizing antibodies and IFN-γ-secreting cells), and pathological (gross lung lesions, histopathologic pulmonary and lymphoid lesions, and the presence of PCV2 antigen and M. hyopneumoniae DNA within the lesions) evaluations. Although M. hyopneumoniae potentiates the severity of PCV2-associated lesions and lesion-associated PCV2 antigen level in dually challenged pigs, vaccination against M. hyopneumoniae alone did not reduce PCV2 viremia, PCV2-induced lesions, or PCV2 antigen in dually challenged pigs. In addition, vaccination against PCV2 did not reduce the nasal shedding of M. hyopneumoniae, the M. hyopneumoniae-induced pulmonary lesions or the lesion-associated M. hyopneumoniae DNA in dually challenged pigs. Dual challenge with PCV2 and M. hyopneumoniae did not interfere with the induction of active immunity induced by a previous single vaccination for either PCV2 or M. hyopneumoniae. The results of this study demonstrated that (i) vaccination against M. hyopneumoniae alone did not decrease the potentiation of PCV2-induced lesions by M. hyopneumoniae and (ii) vaccination against PCV2 alone decreased the potentiation of PCV2-induced lesions by M. hyopneumoniae in dually challenged pigs. Part II is to determine the effects of Mycoplasma hyopneumoniae and/or PRRSV vaccination on dually infected pigs. In total, 72 pigs were randomly divided into nine groups (eight pigs per group), as follows: five vaccinated and challenged groups, three non-vaccinated and challenged groups, and a negative control group. Single-dose vaccination against M. hyopneumoniae alone decreased the levels of PRRSV viremia and PRRSV-induced pulmonary lesions, whereas single-dose vaccination against PRRSV alone did not decrease nasal shedding of M. hyopneumoniae and mycoplasma-induced pulmonary lesions in the dually infected pigs. M. hyopneumoniae challenge impaired the protective cell-mediated immunity induced by the PRRSV vaccine, whereas PRRSV challenge did not impair the protective cell-mediated immunity induced by the M. hyopneumoniae vaccine. The present study provides swine practitioners and producers with efficient vaccination regimesvaccination against M. hyopneumoniae is the first step in protecting pigs against co-infection with M. hyopneumoniae and PRRSV.GENERAL INTRODUCTION 1 LITERATURE REVIEW 4 1. Major Causative Agents of Porcine Respiratory Disease Complex 4 1-1. Mycoplasma hyopneumoniae 4 1-2. Porcine circovirus type 2 (PCV2) 5 1-3. Porcine reproductive and respiratory syndrome virus (PRRSV) 7 2. Immune System and major PRDC pathogens 8 2-1. M. hyopneumoniae and immune system 8 2-2. Porcine circovirus and immune system 10 2-3. Porcine reproductive and respiratory syndrome virus and immune system 11 3. Interaction of M hyopneumoniae, PCV2, and PRRSV 12 3-1. Interaction between Mycoplasma hyopneumoniae and PCV2 12 3-2. Interaction between Mycoplasma hyopneumoniae and PRRSV 15 3-3. Immune responses in co-infections 19 4. Vaccine Efficacy 23 4-1. Mycoplasma hyopneumoniae vaccine efficacy 23 4-2. Porcine circovirus type2 Vaccine Efficacy 25 4-3. Porcine reproductive and respiratory syndrome virus Vaccine Efficacy 26 References 29 PART I. Interaction of porcine circovirus type 2 and Mycoplasma hyopneumoniae vaccines on dually infected pigs 37 Abstract 38 1. Introduction 39 2. Materials and Methods 41 3. Results 46 4. Discussion 69 References 72 PART II. Interaction between single-dose Mycoplasma hyopneumoniae and porcine reproductive and respiratory syndrome virus vaccines on dually infected pigs 79 Abstract 80 1. Introduction 81 2. Materials and Methods 82 3. Results 88 4. Discussion 107 References 110 GENERAL CONCLUSION 116 ABSTRACT IN KOREAN 118Docto