Stroke Prevention in Atrial Fibrillation: Focus on Asian Patients

Yan-Guang Li,이소령,최의근,Gregory Y.H. Lip 대한심장학회 2018 Korean Circulation Journal Vol.48 No.8

Atrial fibrillation (AF) is the most common arrhythmia conferring a fivefold increased risk of stroke. Stroke prevention is the cornerstone of management of patients with AF. Asians have a generally higher incidence of AF-related risks of stroke and bleeding (particularly intracranial bleeding), compared with non-Asians. Despite the well-documented efficacy and relative safety of oral anticoagulation for stroke prevention among Asians, the suboptimal use of oral anticoagulation remains common. The current narrative review aims to provide a summary of the available evidence on stroke prevention among patients with AF focused on the Asia region, regarding stroke and bleeding risk evaluation, the performance of oral anticoagulation, and current use of thromboprophylaxis.

Purification and Biochemical Characterization of a Novel Fibrinolytic Enzyme from Streptomyces sp. P3

( Guang Yan Cheng ),( Li Ying He ),( Zhi Bin Sun ),( Zhong Li Cui ),( Ying Xiang Du ),( Yi Kong ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.9

A novel proteolytic enzyme with fibrinolytic activity, FSP3, was purified from the recently isolated Streptomyces sp. P3, which is a novel bacterial strain isolated from soil. FSP3 was purified to electrophoretic homogeneity by ammonium sulfate precipitation, anion exchange, and gel filtration. FSP3 is considered to be a single peptide chain with a molecular mass of 44 kDa. The maximum activity of the enzyme was observed at 50°C and pH 6.5, and the enzyme was stable between pH 6 and 8 and below 40°C. In a fibrin plate assay, FSP3 showed more potent fibrinolytic activity than urokinase, which is a clinical thrombolytic agent acting as a plasminogen activitor. The activity was strongly inhibited by the serine protease inhibitor PMSF, indicating that it is a serine protease. Additionally, metal ions showed different effects on the activity. It was significantly suppressed by Mg2+ and Ca2+ and completely inhibited by Cu2+, but slightly enhanced by Fe2+. According to LC-MS/MS results, its partial amino acid sequences are significantly dissimilar from those of previously reported fibrinolytic enzymes. The sequence of a DNA fragment encoding FSP3 contained an open reading frame of 1287 base pairs encoding 428 amino acids. FSP3 is a bifunctional enzyme in nature. It hydrolyzes the fibrin directly and activates plasminogen, which may reduce the occurrence of side effects. These results suggest that FSP3 is a novel serine protease with potential applications in thrombolytic therapy.

Analysis of the Baroreceptor and Vestibular Receptor Inputs in the Rostral Ventrolateral Medulla following Hypotension in Conscious Rats

Yan Lan,Huan-Jun Lu,Xian Jiang,Li-Wei Li,Yan-Zhao Yang,Guang-Shi Jin,박주영,김민선,박병림,Yuan-Zhe Jin 대한약리학회 2015 The Korean Journal of Physiology & Pharmacology Vol.19 No.2

Input signals originating from baroreceptors and vestibular receptors are integrated in the rostralventrolateral medulla (RVLM) to maintain blood pressure during postural movement. The contributionof baroreceptors and vestibular receptors in the maintenance of blood pressure following hypotensionwere quantitatively analyzed by measuring phosphorylated extracellular regulated protein kinase(pERK) expression and glutamate release in the RVLM. The expression of pERK and glutamate releasein the RVLM were measured in conscious rats that had undergone bilateral labyrinthectomy (BL)and/or sinoaortic denervation (SAD) following hypotension induced by a sodium nitroprusside (SNP)infusion. The expression of pERK was significantly increased in the RVLM in the control groupfollowing SNP infusion, and expression peaked 10 min after SNP infusion. The number of pERKpositive neurons increased following SNP infusion in BL, SAD, and BL+SAD groups, although theincrease was smaller than seen in the control group. The SAD group showed a relatively higherreduction in pERK expression when compared with the BL group. The level of glutamate release wassignificantly increased in the RVLM in control, BL, SAD groups following SNP infusion, and thispeaked 10 min after SNP infusion. The SAD group showed a relatively higher reduction in glutamaterelease when compared with the BL group. These results suggest that the baroreceptors are morepowerful in pERK expression and glutamate release in the RVLM following hypotension than thevestibular receptors, but the vestibular receptors still have an important role in the RVLM.

Lentinus edodes Suppresses Allergen-Induced Airway Hyperresponsiveness and Inflammation by Downregulating Nuclear Factor-kappa B Activity in a Murine Model of Allergic Asthma

Guang Hai Yan(연광해),Yun Ho Choi(최윤호) 대한체질인류학회 2014 대한체질인류학회지 Vol.27 No.2

표고버섯은 대표적인 식용버섯으로 면역조절작용을 비롯한 항암, 항염증 및 항바이러스 효과를 지닌 것으로 알려져 있다. 그럼에도 불구하고 표고버섯이 천식에 미치는 효능은 거의 알려지지 않았다. 이에 본 연구진은 표고버섯의 에탄올 추출물이 마우스에 유발된 천식에서 나타나는 기도 저항과 폐 조직의 염증 반응에 미치는 영향을 관찰하였다. 표고버섯 추출물을 천식 마우스에게 구강으로 투여할 경우, 기도 저항과 알레르기성 염증반응이 현저하게 감소하는 것을 확인할 수 있었다. 천식 마우스의 폐에서 증가하는 Th2 사이토카인(IL-4, IL-5 및 IL-13)과 eotaxin, adhesion molecules의 발현이 이 추출물에 의해 유의하게 억제되는 것을 관찰할 수 있었다. 추가로 표고버섯의 항천식효과에 대한 기전을 규명하고자 표고버섯 추출물이 천식 마우스의 폐조직에서 발현되는 NF-κB에 미치는 영향을 확인하였다. 상기 결과와 마찬가지로 표고버섯 추출물은 NF-κB의 핵 내 이동을 억제함으로써 이 단백질의 활성을 제어하였다. 이들 결과를 통해 표고버섯 추출물이 천식 마우스에서 NF-κB의 활성을 낮춤으로써 기도 과민 반응 및 염증 반응을 개선하는 것으로 사료된다. 따라서 본 연구결과는 표고버섯이 천식을 예방하거나 완화시키는 약물로 사용될 수 있는 가능성을 제시한다. Medicinal mushrooms have been shown to have profound health promoting benefits. Among them, Lentinus edodes is well-known to have anti-tumor, anti-inflammatory, and immunomodulatory effects. The aim of the present study is to evaluate whether Lentinus edodes ethanol extract (LE) inhibit airway inflammatory response in a murine asthma model induced by exposure to ovalbumin (OVA). The pretreatment of LE substantially attenuated airway hyperresponsiveness and eosinophilic inflammation in OVA-challenged mice. In addition, the increased levels of Th2 cytokines (IL-4, IL-5, and IL-13), eotaxin, and adhesion molecules in bronchoalveolar lavage fluids at 48 h after OVA inhalation was significantly reduced by the administration of LE. Furthermore, LE suppressed OVA-induced activation of nuclear factor-kappa B and p38 mitogen-activated protein kinase in lung tissues. Taken together, it is proposed that LE may serve as an effective therapeutic agent for allergic airway disease.

Phellinus linteus Extract Exerts Anti-asthmatic Effects by Suppressing NF-κB and p38 MAPK Activity in an OVA-induced Mouse Model of Asthma

Guang-Hai Yan,최윤호 대한면역학회 2014 Immune Network Vol.14 No.2

Phellinus linteus has been used as a traditional herbal medicine in Asian countries and is known to have anti-tumor, immunomodulatory, anti-inflammatory, and anti-allergic activities. However, the protective effects of P. linteus against experimental asthma have not been fully investigated. The objective of this study was to determine whether P. linteus ethanol extract (PLE) suppresses inflammatory response in an OVA-induced asthma model. As expected, the oral administration of PLE significantly inhibited eosinophilic airway inflammation and airway hyperresponsiveness in OVA-challenged BALB/c mice. Supporting these data, the augmentation of Th2 cytokines (IL-4, IL-5, and IL-13), eotaxin, and adhesion molecules in lung tissues and bronchoalveolar lavage fluid after OVA inhalation was markedly attenuated by PLE. Furthermore, PLE reduced OVA-induced activation of NF-κB and p38 MAPK in lung tissues. Therefore, our results suggest the potential of P. linteus as a therapeutic agent for asthma.

Additive Role of the Vestibular End Organ and Baroreceptors on the Regulation of Blood Pressure in Rats

Yan Lan,Yan-Zhao Yang,Xian Jiang,Guang-Shi Jin,김민선,박병림,Yuan-Zhe Jin,Li-Wei Li 대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.4

Contribution of the vestibular end organ to regulation of arterial pressure was quantitatively compared with the role of baroreceptors in terms of baroreflex sensitivity and c-Fos protein expression in the rostral ventrolateral medulla (RVLM). Baroreflex sensitivity and c-Fos protein expression in the RVLM were measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or baroreceptor unloading. BL attenuated baroreflex sensitivity during intravenous infusion of sodium nitroprusside (SNP), but did not significantly affect the sensitivity following infusion of phenylephrine (PE). Baroreflex sensitivity became positive following sinoaortic denervation (SAD) during infusion of PE and attenuated sensitivity during infusion of SNP. Baroreflex sensitivity also became positive following double ablation (BL+SAD) during infusion of PE, and attenuated sensitivity during infusion of SNP. c-Fos protein expression increased significantly in the RVLM in the sham group after SNP administration. However, the BL, SAD, and SAD+BL groups showed significant decreases in c-Fos protein expression compared with that in the sham group. The SAD group showed more reduced c-Fos protein expression than that in the BL group, and the SAD+BL group showed less expression than that in the SAD group. These results suggest that the vestibular system cooperates with baroreceptors to maintain arterial pressure during hypotension but that baroreceptors regulate arterial pressure during both hypotension and hypertension. Additionally, afferent signals for maintaining blood pressure from the vestibular end organs and the baroreceptors may be integrated in the RVLM.

Phellinus linteus Extract Exerts Anti-asthmatic Effects by Suppressing NF-${\kappa}B$ and p38 MAPK Activity in an OVA-induced Mouse Model of Asthma

Yan, Guang Hai,Choi, Yun Ho The Korean Association of Immunobiologists 2014 Immune Network Vol.14 No.2

Phellinus linteus has been used as a traditional herbal medicine in Asian countries and is known to have anti-tumor, immunomodulatory, anti-inflammatory, and anti-allergic activities. However, the protective effects of P. linteus against experimental asthma have not been fully investigated. The objective of this study was to determine whether P. linteus ethanol extract (PLE) suppresses inflammatory response in an OVA-induced asthma model. As expected, the oral administration of PLE significantly inhibited eosinophilic airway inflammation and airway hyperresponsiveness in OVA-challenged BALB/c mice. Supporting these data, the augmentation of Th2 cytokines (IL-4, IL-5, and IL-13), eotaxin, and adhesion molecules in lung tissues and bronchoalveolar lavage fluid after OVA inhalation was markedly attenuated by PLE. Furthermore, PLE reduced OVA-induced activation of NF-${\kappa}B$ and p38 MAPK in lung tissues. Therefore, our results suggest the potential of P. linteus as a therapeutic agent for asthma.

Sparassis crispa Attenuates Carbon Tetrachloride-Induced Hepatic Injury in Rats

Guang Hai Yan(연광해),Yun Ho Choi(최윤호) 대한체질인류학회 2014 대한체질인류학회지 Vol.27 No.3

꽃송이버섯은 다양한 약리활성을 지닌 식용버섯으로, 한국을 비롯해서 중국과 일본 등지에서 널리 재배된다. 이 논문은 꽃송이버섯의 추출물이 사염화탄소에 의해 유발된 간 독성을 억제할 수 있다는 가능성을 제시한다. 본 연구진은 0.5 mg/kg의 사염화탄소를 6주령 Sprague Dawley 흰쥐의 복강에 투여함으로써 간 독성 모델을 유도하였다. 그리고 꽃송이버섯이 간 독성에 미치는 효과를 확인하고자 이로부터 에탄올 추출물을 얻은 다음, 간 독성 모델을 유도하기 전에 복강으로 5일 연속 투여하였다. 사염화탄소 투여 후 16시간이 경과했을 때, 흰쥐의 혈장에서 aminotransferase와 TNF-α의 농도 및 지질과산화의 정도가 현저히 증가하는 것을 관찰할 수 있었다. 아울러 간 내 항산화효소들의 활성은 감소하는 것이 확인되었다. 반면, 꽃송이버섯의 에탄올 추출물 100, 200 mg/kg을 상기 모델에 전 처리할 경우, 이러한 일련의 변화들이 용량 의존적으로 유의하게 억제되었다. 게다가 조직학적 소견 또한 꽃송이버섯 추출물이 사염화탄소에 의한 간 손상을 억제한다는 사실을 보여주었다. 더 나아가, 간 손상 모델에서 보이는 nitrite, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2)의 증가와 cytochrome p450 2E1 (CYP2E1)의 감소 양상은 꽃송이버섯의 에탄올 추출물에 의해 현저하게 억제되었다. 이상으로부터 꽃송이버섯은 사염화탄소에 의한 자극으로부터 간을 보호할 것으로 예상되는데, 이러한 효과는 꽃송이버섯이 산화적 스트레스를 줄일 뿐 아니라 iNOS와 COX-2에 의한 염증성 반응을 억제하고 CYP2E1의 기능을 회복시키기 때문으로 여겨진다. Sparassis crispa is an edible mushroom with various medicinal properties. Here we demonstrate the effect of Sparassis crispa on carbon tetrachloride (CCl₄)-induced hepatotoxicity and the underlying mechanism. To evaluate the hepatoprotective effects of Sparassis crispa ethanol extract (SCE), 50 male Sprague-Dawley rats were equally divided into 5 groups. Group I is the normal control rats with an intraperitoneal (i.p.) 0.5% carboxy methyl cellulose (CMC) pretreatment and olive oil treatment. Group II is the model group with an i.p. 0.5% CMC and 0.5 mL/kg CCl₄ treatment. Group III and IV is the CCl₄-administered rats pretreated with an i.p. 100 and 200 mg/kg SCE, respectively. Group V includes the silymarin group with an i.p. 50 mg/kg silymarin and CCl₄ treatment. At 16 h after the CCl₄ treatment, the levels of serum aminotransferases, TNF-α, and lipid peroxidation were substantially increased, whereas the activity of hepatic antioxidative enzymes, such as superoxide dismutase and catalase, was decreased. These changes were attenuated by SCE. The histological studies also showed that SCE inhibited the CCl4-induced liver injury. Furthermore, the contents of hepatic nitrite, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were elevated after CCl₄ treatment, while the cytochrome P450 2E1 (CYP2E1) expression was suppressed. SCE treatment inhibited the formation of liver nitrite, reduced the overexpression of iNOS and COX-2 proteins, but restored the liver CYP2E1 content compared with the CCl₄-treated model group. The present data elucidate that SCE protects the liver against CCl₄-induced acute hepatotoxicity, which might be due to its ability to restore the CYP2E1 function and suppress the inflammatory responses, in combination with its capacity to reduce oxidative stress.

Phellinus linteus Extract Exerts Anti-asthmatic Effects by Suppressing NF-κB and p38 MAPK Activity in an OVA-induced Mouse Model of Asthma

Yan, Guang Hai,Choi, Yun Ho 대한면역학회 2014 Immune Network Vol.14 No.2

Phellinus linteus has been used as a traditional herbal medicine in Asian countries and is known to have anti-tumor, immunomodulatory, anti-inflammatory, and anti-allergic activities. However, the protective effects of P. linteus against experimental asthma have not been fully investigated. The objective of this study was to determine whether P. linteus ethanol extract (PLE) suppresses inflammatory response in an OVA-induced asthma model. As expected, the oral administration of PLE significantly inhibited eosinophilic airway inflammation and airway hyperresponsiveness in OVA-challenged BALB/c mice. Supporting these data, the augmentation of Th2 cytokines (IL-4, IL-5, and IL-13), eotaxin, and adhesion molecules in lung tissues and bronchoalveolar lavage fluid after OVA inhalation was markedly attenuated by PLE. Furthermore, PLE reduced OVA-induced activation of NF-κB and p38 MAPK in lung tissues. Therefore, our results suggest the potential of P. linteus as a therapeutic agent for asthma.

Analysis of the Baroreceptor and Vestibular Receptor Inputs in the Rostral Ventrolateral Medulla following Hypotension in Conscious Rats

Lan, Yan,Lu, Huan-Jun,Jiang, Xian,Li, Li-Wei,Yang, Yan-Zhao,Jin, Guang-Shi,Park, Joo Young,Kim, Min Sun,Park, Byung Rim,Jin, Yuan-Zhe The Korean Society of Pharmacology 2015 The Korean Journal of Physiology & Pharmacology Vol.19 No.2

Input signals originating from baroreceptors and vestibular receptors are integrated in the rostral ventrolateral medulla (RVLM) to maintain blood pressure during postural movement. The contribution of baroreceptors and vestibular receptors in the maintenance of blood pressure following hypotension were quantitatively analyzed by measuring phosphorylated extracellular regulated protein kinase (pERK) expression and glutamate release in the RVLM. The expression of pERK and glutamate release in the RVLM were measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or sinoaortic denervation (SAD) following hypotension induced by a sodium nitroprusside (SNP) infusion. The expression of pERK was significantly increased in the RVLM in the control group following SNP infusion, and expression peaked 10 min after SNP infusion. The number of pERK positive neurons increased following SNP infusion in BL, SAD, and BL+SAD groups, although the increase was smaller than seen in the control group. The SAD group showed a relatively higher reduction in pERK expression when compared with the BL group. The level of glutamate release was significantly increased in the RVLM in control, BL, SAD groups following SNP infusion, and this peaked 10 min after SNP infusion. The SAD group showed a relatively higher reduction in glutamate release when compared with the BL group. These results suggest that the baroreceptors are more powerful in pERK expression and glutamate release in the RVLM following hypotension than the vestibular receptors, but the vestibular receptors still have an important role in the RVLM.