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Tracking morphologies at the nanoscale： Self-assembly of an amphiphilic designer peptide into a double helix superstructure

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Nano Research 2015年第6期8卷 1822-1833页

作者： Karin Kornmueller Ilse Letofsky-Papst Kerstin Gradauer Christian Mikl Fernando Cacho-Nerin Mario Leypold Walter Keller Gerd Leitinger Heinz Amenitsch Ruth Prassl Institute of Biophysics Medical University ofGraz BioTechMed-Graz 8010 Graz Austria Institute for electron Microscopy and Nanoanalysis Graz University of Technology and Graz Centre for Electron Microscopy 80 10 Graz A us tria Institute of Inorganic Chemistry Graz University of Technology 8010 Graz Austria Institute of Organic Chemistry Graz University of Technology 8010 Graz Austria Institute for Molecular Biosciences KarI-Franzens-University Graz 8010 Graz Austria Research Unit electron Microscopic Techniques Institute of Cell Biology Histology and Embryology Medical University of Graz 80 10 Graz A us tria Center for medical Research Medical University of Graz 8010 Graz Austria

Hierarchical self-assembly is a fundamental principle in nature, which gives rise to astonishing supramolecular architectures that are an inspiration for the development of innovative materials in nanotechnolog）a Here, we present the unique structure of a cone-shaped amphiphilic designer peptide. While tracking its concentration-dependent morphologies, we observed elongated bilayered single tapes at the beginning of the assembly process, which further developed into novel double-helix-like superstructures at high concentrations. This architecture is characterized by a tight intertwisting of two individual helices, resulting in a periodic pitch size over their total lengths of several hundred nanometers. Solution X-ray scattering data revealed a marked 2-layered internal organization. All these characteristics remained unaltered for the investigated period of almost three months. In their collective morphology, the assemblies are integrated into a network with hydrogel characteristics. Such a peptide-based structure holds promise as a building block for next-generation nanostructured biomaterials.

关键词： double helix amphiphilic designerpeptide self-assembl)~SAXS TEM spectroscopy

Total Glycosides of Ranunculus Japonius Prevent Hypertrophy in Cardiomyocytes via Alleviating Chronic Ca^(2+) Overload

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Chinese medical Sciences Journal 2015年第1期30卷 37-43页

作者： Hong-liang Dai Gui-zhi Jia Song Zhao Department of Community Health Nursing Liaoning Medical University Department of Biochemistry and Molecular biology Liaoning Medical University centre of Scientific Experiment Liaoning Medical University

Objective To evaluate the in vitro anti-hypertrophic effect of total Glycosides of Ranunculus Japonius （TGRJ）. Methods Neonatal rat cardiomyocytes were cultured and hypertrophy was induced by adminis- trating isoproterenol （ISO, 10 gmol/L） or angiotensin Ⅱ （AngⅡ, 1 gmol/L） for 48 hours. In the treatment groups, cells were pretreated with TGRJ （0.3 g/L） for 30 minutes prior to hypertrophic stimuli. The anti-hypertrophic effects of TGRJ were examined by measuring cell size, total protein content, and protein synthesis. Intracellular free Ca2＋ concentration （[Ca2＋]i） was evaluated using fluorescence dye Fura-2/AM. Sacroplasmic/endoplasmic reticulum Ca2＋ ATPase 2a （SERCA2a）, atrial natriuretic peptide （ANP）, B-type natriuretic peptide （BNP）, and beta-myosin heavy chain （β-MHC） protein expression levels were measured by Western blotting. SERCA2a activity was assayed by p-nitrophenal phosphate disodium salt hexahydrate method. Results Increased cell size, total protein content, and protein synthesis following ISO or Ang II stimulation were significantly inhibited by pretreatment with TGRJ （all P〈0.05）. This anti-hypertrophic effect of TGRJ was confirmed by its suppressing effect on elevated expression of the three hypertrophic related genetic markers, ANP, BNP, and ^-MHC. In addition, TGRJ inhibited ISO or Ang Ⅱ induced up-regulation of [Ca2＋] under chronic but not acute conditions. And ISO or Ang Ⅱ induced down-regulation of SERCA2a expression and activity was also effectively rectified byTGRJ pretreatment. Conclusions The results of present study suggested that TGRJ could prevent ISO or Ang Ⅱ induced cardiac hypertrophy through improving chronic [Ca2＋]i disorder, might via normalizing SERCA2a expression and activity.

关键词： total Glycosides of RanunculusJaponius cardiac hypertrophy isoproterenol angiotensin Ⅱ Ca2+ sacroplasmic/endoplasmic reticulum Ca2+ ATPase 2a

A fine-scale assessment of the ecosystem service-disservice dichotomy in the context of urban ecosystems affected by alien plant invasions

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Forest Ecosystems 2019年第4期6卷 323-338页

作者： Luke J.Potgieter Mirijam Gaertner Patrick J.O’Farrell David M.Richardson centre for Invasion biology Department of Botany and ZoologyStellenbosch University

Background: Natural resources within and around urban landscapes are under increasing pressure from ongoing urbanisation, and management efforts aimed at ensuring the sustainable provision of ecosystem services(ES) are an important response. Given the limited resources available for assessing urban ES in many cities, practical approaches for integrating ES in decision-making process are ***: We apply remote sensing techniques(integrating LiDAR data with high-resolution multispectral imagery)and combined these with supplementary spatial data to develop a replicable approach for assessing the role of urban vegetation(including invasive alien plants) in providing ES and ecosystem disservices(EDS). We identify areas denoting potential management trade-offs based on the spatial distribution of ES and EDS using a local-scale case study in the city of Cape Town, South Africa. Situated within a global biodiversity hotspot, Cape Town must contend with widespread invasions of alien plants(especially trees and shrubs) along with complex socio-political challenges. This represents a useful system to examine the challenges in managing ES and EDS in the context of urban plant ***: Areas of high ES provision(for example carbon sequestration, shade and visual amenity) are characterized by the presence of large trees. However, many of these areas also result in numerous EDS due to invasions of alien trees and shrubs – particularly along rivers, in wetlands and along the urban edge where tall alien trees have established and spread into the natural vegetation(for example increased water consumption, increased fire risk and reduced soil quality). This suggests significant trade-offs regarding the management of species and the ES and EDS they ***: The approach applied here can be used to provide recommendations and to guide city planners and managers to fine-tune management interventions at local scales to maximise the provision of ES.

关键词： Biodiversity Biological invasions Ecosystem disservices Ecosystem services Remote sensing Trade-offs Tree invasions Urban plant invasions

Variation and significance of microtubules in rat volume overload cardiac hypertrophy

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Chinese medical Journal 2003年第3期116卷 18-21页

作者：刘华胜马爱群王春梅刘勇田红燕白玲 Department of Cardiology First HospitalXi'an Jiaotong UniversityXi'an 710061China Department of electron microscope Fourth Military Medical University Xi'an 710033 China Department of Cell biology Medical College of Xi'an Jiaotong University Xi'an 710033 China

Objective To investigate the function of microtubules in volume overload cardiac hypertrophy of rat. Methods The structure of microtubules was observed using an immunofluorescent microscope, while the pixel intensity and distribution of microtubule imaging was estimated from laser scanning confocal images of left ventricular cardiocytes immuno-labeled with an antibody to β-tubulin. Results The pixels of the microtubule image taken just after volume overload were not evenly distributed. At 6 hours after overload, the pixel intensity of the microtubule image was decreased to less than 150 (arbitrary units), which was the same as the pixel intensity and distribution of the colchicine depolymerized microtubule image. The changes were partially recovered to 200 (arbitrary units) after 4 more days. The pixel intensity of the control microtubule image was 250 (arbitrary units) and had an even distribution. The structuring of the microtubules was more disordered as volume overload hypertrophy developed. Conclusions There are disorders in the signal transduction pathways governing the hypertrophic response of cardiomyocytes in the hypertrophic myocardium and microtubule is one of the members of the signal transduction pathways governing the hypertrophic response of cardiomyocytes in the hypertrophic myocardium. The disordered microtubule array may be targeted during heart failure treatment.

关键词： cardiac hypertrophy tubulin signal transduction

Dynamical Analysis of Protein Regulatory Network in Budding Yeast Nucleus

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Chinese Physics Letters 2006年第8期23卷 2307-2310页

作者：李方廷贾珣 School of Physics and centre for Theoretical biology Peking University Beijing 100871

Recent progresses in the protein regulatory network of budding yeast Saccharomyces cerevisiae have provided a global picture of its protein network for further dynamical research. We simplify and modularize the protein regulatory networks in yeast nucleus, and study the dynamical properties of the core 37-node network by a Boolean network model, especially the evolution steps and final fixed points. Our simulation results show that the number of fixed points N（k） for a given size of the attraction basin k obeys a power-law distribution N（k） χ k^-2.024. The yeast network is more similar to a scale-free network than a random network in the above dynamical properties.

关键词： CELL-CYCLE TRANSCRIPTIONAL REGULATION GENES

Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents

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Acta Pharmaceutica Sinica B 2019年第2期9卷 335-350页

作者： Jiabing Wang Lili Huang Chanchan Cheng Ge Li Jingwen Xie Mengya Shen Qian Chen Wulan Li Wenfei He Peihong Qiu Jianzhang Wu Chemical biology Research Center School of Pharmaceutical Sciences Wenzhou Medical University Municipal Hospital Affiliated to medical School of Taizhou University Ningbo medical centre Li Huili Hospital College of Information Science and Computer Engineering Wenzhou Medical University

Scavenging reactive oxygen species(ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury(CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active 33 not only conferred cytoprotection of H2 O2-induced oxidative damage in PC12 cells through scavenging free radicals directly and activating NRF2/ARE antioxidant pathway at the same time, but also played an important role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds, 33 exhibited higher cytoprotective and neuroprotective potential in vitro and in vivo. Overall, our findings showed compound 33 couldemerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment.

关键词： Reactive oxygen species Cerebral ischemiareperfusion injury Stroke Dual-antioxidant mechanism Chalcones Antioxidants Oxidative stress NRF2/ARE

Hepatitis C virus genotype 3a infection and hepatocellular carcinoma: Pakistan experience

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World Journal of Gastroenterology 2009年第40期15卷 5080-5085页

作者： Muhammad Idrees Shazia Rafi que Irshad-ur Rehman Haji Akbar Muhammad Zubair Yousaf Sadia Butt Zunaira Awan Sobia Manzoor Madiha Akram Mahwish Aftab Bushra Khubaib Sheikh Riazuddin Division of Molecular Virology & Molecular Diagnostics National Centre of Excellence in Molecular BiologyUniversity of the Punjab Lahore National centre of Excellence in Molecular biology University of the Punjab Lahore

AIM: To assess the association between chronic hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) in Pakistan, and the genotype distribution among these HCC ***: One hundred and sixty-one subjects with HCC were included in this study. Liver biopsy was performed on 145 of the patients; sixteen were excluded because they failed to fulfill the inclusion criteria. Qualitative polymerase chain reaction (PCR) was performed for hepatitis B virus and HCV. Samples positive for HCV RNA were genotyped using genotype-specif ic PCR and conf irmed by HCV 5' noncoding region sequencing analysis. RESULTS: Chronic HCV infection was identified a major risk factor (63.44% of tested HCC patients) forthe development of HCC. The time from HCV infection to appearance of cancer was 10-50 years. In the HCC patient population, broader distributions of genotypes were present with genotype 3a as the predominant genotype. Using the type-specific genotyping method, we found HCV genotype 3a in 40.96%, 3b in 15.66%, 1a in 9.63%, and 1b in 2.40% of HCC tissue samples. About 28% of cases were found with mixed genotypes. Two cases were unable to be genotyped because of low viral load. Sixty-six percent of treated patients with cirrhosis had an end of treatment response, but unfortunately they relapsed quickly when the treatment was discontin-ued, and HCC developed during a median 3.8 years. CONCLUSION: There was a strong association between chronic HCV infection and HCC in Pakistan, and between HCV genotype 3a and HCC.

关键词： Hepatocellular carcinoma Hepatitis C Genotyping Etiology Prevalence

Photocatalytic OH radical formation and quantification over TiO_2 P25:Producing a robust and optimised screening method

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Chinese Chemical Letters 2018年第6期29卷 773-777页

作者： Caitlin Buck Nathan Skillen Jeanette Robertson Peter K.J.Robertson School of Chemistry and Chemical Engineering Queen's University Belfast School of Biological Sciences Queen's University Belfast Medical Biology Centre

The development of photocatalytic technology has grown significantly since its initial report and as such,a number of screening methods have been developed to assess activity. In the field of environmental remediation, a crucial factor is the formation of highly oxidising species such as OH radicals. These radicals are often the primary driving force for the removal and breakdown of organic and inorganic contaminants. The quantification of such compounds is challenging due to the nature of the radical,however indirect methods which deploy a chemical probe to essentially capture the radical have been shown to be effective. As discussed in the work presented here, optimisation of such a method is fundamental to the efficiency of the method. A starting concentration range of coumarin from 50 mmol/L to 1000 mmol/L was used along with a catalyst loading of 0.01 g/L to 1 g/L Ti TiO2 to identify that 250 mmol/L and 0.5 g/L Ti TiO2 were the optimum conditions for production. Under these parameters a maximum production rate of 35.91 mmol/L（Rmax= 0.4 mmol/L OH＊ min-1） was achieved which yielded at photonic efficiency of 4.88 OH＊moles photon-1 under UV irradiation. The data set presented also highlighted the limitations which are associated with the method which included; rapid exhaustion of the probe molecule and process inhibition through UV light saturation. Identifying both the optimum conditions and the potential limitations of the process were concluded to be key for the efficient deployment of the photocatalytic screening method.

关键词： Photocatalytic screening OH radical quantification Coumarin Environmental remediation Method optimisation

Strategy against micrometastasis of epithelial cancer: Detection and elimination

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Chinese Science Bulletin 2002年第17期47卷 1415-1421页

作者： QIN Li XIAO Yi CHEN Yinghua Laboratory of Immunology Research Centre for Medical Science and Department of BiologyTsinghua UniversityProtein Science Laboratory of MOEBeijing 100084China

Tumor metastasis is generally agreed to be the major cause of cancer death. Over the last few years, studies of new diagnosis techniques and tumor immunotherapy have made great progress. Recent clinical studies on the occult metastases of breast, lung and colorectal cancer all suggested that the detection of micrometastases in bone marrow is prognostically important and provides substantial evidence of tumor dissemination. On the other hand, two kinds of the mAb-based immunotherapy have been approved for the treatment against epithelial cancer. Monoclonal antibody (mAb) 17-1A for colorectal carcinomas and mAb herceptin for breast cancer both have produced good curative effects. Potential therapeutics based on some antibodies with prominent antitumor activity also has shown obvious clinical effect. These studies indicate that detection of micrometasta-sis in circulatory system and immunotherapy by eliminating metastatic malignant cells suggested a new strategy against the metastatic cancer.

关键词： tumor micrometastasis detection elimination immu-notherapy mAb.