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| 1 | A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein显示文摘最新新兴的中东呼吸症候群 coronavirus (MERS-CoV ) 能在人引起严重、致命的急性呼吸疾病。尽管有全球努力,潜力为一联系在未来流行不能被排除。有效相对的措施的发展是迫切的。MERS-CoV-specific 抗病毒的药或疫苗是还没可得到的。使用 MERS-CoV (MERS-RBD ) 的尖铁受体绑定领域使老鼠免疫,我们识别了二抵销 monoclonal 抗体(mAbs ) 4C2 和 2E6。两 mAbs potently 与高功效在 vitro 绑在 MERS-RBD 和块病毒入口。我们进一步由使在 Fab 碎片和 RBD 之间的建筑群结晶调查了他们中立化的机制,并且解决了 4C2 Fab/MERS-RBD 建筑群的结构。结构证明 4C2 认出部分重叠的 epitope 在 MERS-RBD 的受体绑定脚印,从而由位的阻碍者和接口残余竞争防碍病毒 / 受体相互作用。2E6 也堵住受体绑定,并且为绑定与 4C2 竞争到 MERS-RBD。基于结构,我们进一步由保存仅仅 paratope 残余并且从人的免疫球蛋白与对应物代替留下的氨基酸使 4C2 人性化。人性化的 4C2 (4C2h ) 抗体支撑了类似的抵销的活动和生物化学的特征到父母老鼠抗体。最后,我们证明 4C2h 能显著地在感染 MERS-CoV 的 Ad5-hCD26-transduced 鼠标的肺消除病毒 titers,因此在临床的设置为预防和治疗代表一个有希望的代理人。 | Yan Li YuhuaWan Peipei Liu Jincun Zhao Guangwen Lu Jianxun Qi Qihui Wang Xuancheng LU Ying Wu Weniun Liu Buchang Zhang Kwok-Yung Yuen Stanley Perlman George F Gao Jinghua Yan | 2015 | Cell Research2015，25，11： | 14 |
| 2 | Pretreatment with Danhong injection protects the brain against ischemia-reperfusion injury显示文摘Danhong injection(DHI),a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii,is widely used in China for treating acute ischemic stroke.In the present study,we explored the neuroprotective efficacy of DHI in a rat model of temporary middle cerebral artery occlusion,and evaluated the potential mechanisms underlying its effects.Pretreatment with DHI(0.9 and 1.8 mL/kg)resulted in a significantly smaller infarct volume and better neurological scores than pretreatment with saline.Furthermore,DHI significantly reduced the permeability of the blood-brain barrier,increased occludin protein expression and decreased neutrophil infiltration,as well as profoundly suppressing the upregulation of matrix metallopeptidase-9 expression seen in rats that had received vehicle.Matrix metallopeptidase-2 expression was not affected by ischemia or DHI.Moreover,DHI(1.8 mL/kg)administered 3 hours after the onset of ischemia also improved neurological scores and reduced infarct size.Our results indicate that the neuroprotective efficacy of DHI in a rat model of cerebral ischemia-reperfusion injury is mediated by a protective effect on the blood-brain barrier and the reversal of neutrophil infiltration. | Shaoxia Wang Hong Guo Xumei Wang Lijuan Chai Limin Hu Tao Zhao Buchang Zhao Xiaoxu Tan Feifei Jia | 2014 | Neural Regeneration Research2014，9，15： | 12 |
| 3 | Inactivation of SACE_3446, a TetR family transcriptional regulator, stimulates erythromycin production in Saccharopolyspora erythraea显示文摘Erythromycin A is a widely used antibiotic produced by Saccharopolyspora erythraea;however,its biosynthetic cluster lacks a regulatory gene,limiting the yield enhancement via regulation engineering of S.erythraea.Herein,six TetR family transcriptional regulators(TFRs)belonging to three genomic context types were individually inactivated in S.erythraea A226,and one of them,SACE_3446,was proved to play a negative role in regulating erythromycin biosynthesis.EMSA and qRT-PCR analysis revealed that SACE_3446 covering intact N-terminal DNA binding domain specifically bound to the promoter regions of erythromycin biosynthetic gene eryAI,the resistant gene ermE and the adjacent gene SACE_3447(encoding a longchain fatty-acid CoA ligase),and repressed their transcription.Furthermore,we explored the interaction relationships of SACE_3446 and previously identified TFRs(SACE_3986 and SACE_7301)associated with erythromycin production.Given demonstrated relatively independent regulation mode of SACE_3446 and SACE_3986 in erythromycin biosynthesis,we individually and concomitantly inactivated them in an industrial S.erythraea WB.Compared with WB,the WBΔ3446 and WBΔ3446Δ3986 mutants respectively displayed 36%and 65%yield enhancement of erythromycin A,following significantly elevated transcription of eryAI and ermE.When cultured in a 5 L fermentor,erythromycin A ofWBΔ3446 and WBΔ3446Δ3986 successively reached 4095 mg/L and 4670 mg/L with 23%and 41%production improvement relative to WB.The strategy reported here will be useful to improve antibiotics production in other industrial actinomycete. | Hang Wu Yansheng Wang Li Yuan Yongrong Mao Weiwei Wang Lin Zhu Panpan Wu Chengzhang Fu Rolf Muller David T.Weaver Lixin Zhang Buchang Zhang | 2016 | Synthetic and Systems Biotechnology2016，1，1： | 7 |
| 4 | Danhong Injection Inhibits the Development of Atherosclerosis in Both Apoe?/? and Ldlr?/? Mice显示文摘 | Yuanli Chen Mengyang Liu Tao Zhao Buchang Zhao Lifu Jia Yan Zhu Boli Zhang Xiumei Gao Guangliang Li Xiaoju Li Rong Xiang Jihong Han Yajun Duan | 2014 | Journal of Cardiovascular Pharmacology2014，，5： | 1 |
| 5 | Beauvericin counteracted multi-drug resistant Candida albicans by blocking ABC transporters显示文摘Multi-drug resistance of pathogenic microorganisms is becoming a serious threat,particularly to immunocompromised populations.The high mortality of systematic fungal infections necessitates novel antifungal drugs and therapies.Unfortunately,with traditional drug discovery approaches,only echinocandins was approved by FDA as a new class of antifungals in the past two decades.Drug efflux is one of the major contributors to multi-drug resistance,the modulator of drug efflux pumps is considered as one of the keys to conquer multi-drug resistance.In this study,we combined structure-based virtual screening and whole-cell based mechanism study,identified a natural product,beauvericin(BEA)as a drug efflux pump modulator,which can reverse the multi-drug resistant phenotype of Candida albicans by specifically blocking the ATP-binding cassette(ABC)transporters;meantime,BEA alone has fungicidal activity in vitro by elevating intracellular calcium and reactive oxygen species(ROS).It was further demonstrated by histopathological study that BEA synergizes with a sub-therapeutic dose of ketoconazole(KTC)and could cure the murine model of disseminated candidiasis.Toxicity evaluation of BEA,including acute toxicity test,Ames test,and hERG(human ether-a-go-go-related gene)test promised that BEA can be harnessed for treatment of candidiasis,especially the candidiasis caused by ABC overexpressed multi-drug resistant C.albicans. | Yaojun Tong Mei Liu Yu Zhang Xueting Liu Ren Huang Fuhang Song Huanqin Dai Biao Ren Nuo Sun Gang Pei Jiang Bian Xin-Ming Jia Guanghua Huang Xuyu Zhou Shaojie Li Buchang Zhang Takashi Fukuda Hiroshi Tomoda SatoshiOmura Richard DCannon Richard Calderone Lixin Zhang | 2016 | Synthetic and Systems Biotechnology2016，1，3： | 1 |
| 6 | DanHong Injection inhibits the development of primary abdominal aortic aneurysms in apoE knockout mice显示文摘Clinical observations indicate that DanHong Injection(DHI)can increase blood flow and reduce various syndromes in patients with cardiovascular disease.However,it still needs to define the function of DHI and the involved mechanisms in details,such as the protective effect on the development of primary abdominal aortic aneurysms(AAAs).In this study,we determined whether DHI is able to inhibit AAA in apoE knockout(apoE-/-)mice.Thirty apoE-/-male mice on high-fat diet(0.5%cholesterol,21%fat)were randomly divided into two groups and received i.p.injection of saline(100 lL/day)and DHI(100 lL/day),respectively,for 16 weeks.At the end of experiment,we determined the development of atherosclerosis in en face aorta and aneurysms,pathological morphology of arterial wall,and serum lipid levels.We also determined the expression of monocyte chemoattractant protein-1(MCP-1),MMP-2,and MMP-9mRNA in aortic wall using real-time RT-PCR.Our results indicated that high-fat diet induced the development of AAAs in apoE-/-mice,but the induction was totally blocked by DHI(P\0.01).The result of staining of abdominal aortic cross sections showed that DHI maintained the collagen content in arterial wall,thereby preventing the animals from the development of AAA.Although DHI had little effect on serum total-and LDLcholesterol levels,it reduced the expression of MCP-1,MMP-2,and MMP-9 mRNA in aortic wall(P\0.01).Taken together,our study suggests that DHI can inhibit the high-fat diet-induced AAA formation.The inhibitory effects may be related to the maintenance of the collagen content and inhibition of expression of AAA-related genes.Our study may suggest a new application of DHI in clinics. | Mengyang Liu Yuanli Chen Xiaoxiao Yang Ling Zhang Tao Zhao Buchang Zhao Lifu Jia Yan Zhu Xiumei Gao Boli Zhang Xiaoju Li Rong Xiang Jihong Han Yajun Duan | 2014 | Chinese Science Bulletin2014，59，13： | 0 |
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