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Pharmaceutical Engineering

Guest Editor-in-Chief
Yang, Baofeng, Harbin Medical University, China
Associate Editors
Chen, Zhinan, Fourth Military Medical University, China
Ganser, Arnold, Hannover Medical School, Germany
Ding, Jian, Shanghai Institute of Materia Medica, CAS, China
Fu, Xiaobing, General Hospital of PLA, China
Hoyer, Daniel, Melbourne Medical School, Australia
Huang, Luqi, National Resources Center for Chinese Materia Medica, CAS, China
Li, Ren-Ke, Toronto Medical Discovery Tower, Canada
Li, Song, Beijing Institute of Pharmacology and Toxicology, China
Nattel, Stanley, University of Montreal, Canada
Vanhoutte, Paul M., Hong Kong University, China
Zhang, Boli, China Academy of Chinese Medical Sciences, China
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Cardiac Remote Conditioning and Clinical Relevance: All Together Now!
Kristin Luther,Yang Song,Yang Wang,Xiaoping Ren,W. Keith Jones
Engineering    2015, 1 (4): 490-499.   DOI: 10.15302/J-ENG-2015117
Abstract   HTML   PDF (750KB)

Acute myocardial infarction (AMI) is the leading cause of death and disability worldwide. Timely reperfusion is the standard of care and results in decreased infarct size, improving patient survival and prognosis. However, 25% of patients proceed to develop heart failure (HF) after myocardial infarction (MI) and 50% of these will die within five years. Since the size of the infarct is the major predictor of the outcome, including the development of HF, therapies to improve myocardial salvage have great potential. Over the past three decades, a number of stimuli have been discovered that activate endogenous cardioprotective pathways. In ischemic preconditioning (IPC) and ischemic postconditioning, ischemia within the heart initiates the protection. Brief reversible episodes of ischemia in vascular beds remote from the heart can also trigger cardioprotection when applied before, during, or immediately after myocardial ischemia—known as remote ischemic pre-, per-, and post-conditioning, respectively. Although the mechanism of remote ischemic preconditioning (RIPC) has not yet been fully elucidated, many mechanistic components are shared with IPC. The discovery of RIPC led to research into the use of remote non-ischemic stimuli including nerve stimulation (spinal and vagal), and electroacupuncture (EA). We discovered and, with others, have elucidated mechanistic aspects of a non-ischemic phenomenon we termed remote preconditioning of trauma (RPCT). RPCT operates via neural stimulation of skin sensory nerves and has similarities and differences to nerve stimulation and EA conducted at acupoints. We show herein that RPCT can be mimicked using electrical stimulation of the abdominal midline (EA-like treatment) and that this modality of activating cardioprotection is powerful as both a preconditioning and a postconditioning stimulus (when applied at reperfusion). Investigations of these cardioprotective phenomena have led to a more integrative understanding of mechanisms related to cardioprotection, and in the last five to ten years, it has become clear that the mechanisms are similar, whether induced by ischemic or non-ischemic stimuli. Taking together much of the data in the literature, we propose that all of these cardioprotective “conditioning” phenomena represent activation from different entry points of a cardiac conditioning network that converges upon specific mediators and effectors of myocardial cell survival, including NF-кB, Stat3/5, protein kinase C, bradykinin, and the mitoKATP channel. Nervous system pathways may represent a novel mechanism for initiating conditioning of the heart and other organs. IPC and RIPC have proven difficult to translate clinically, as they have associated risks and cannot be used in some patients. Because of this, the use of neural and nociceptive stimuli is emerging as a potential non-ischemic and non-traumatic means to initiate cardiac conditioning. Clinical relevance is underscored by the demonstration of postconditioning with one of these modalities, supporting the conclusion that the development of pharmaceuticals and electroceuticals for this purpose is an area ripe for clinical development.

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Conjugation with Acridines Turns Nuclear Localization Sequence into Highly Active Antimicrobial Peptide
Wei Zhang,Xiaoli Yang,Jingjing Song,Xin Zheng,Jianbo Chen,Panpan Ma,Bangzhi Zhang,Rui Wang
Engineering    2015, 1 (4): 500-505.   DOI: 10.15302/J-ENG-2015106
Abstract   HTML   PDF (4096KB)

The emergence of multidrug-resistant bacteria creates an urgent need for alternative antibiotics with new mechanisms of action. In this study, we synthesized a novel type of antimicrobial agent, Acr3-NLS, by conjugating hydrophobic acridines to the N-terminus of a nuclear localization sequence (NLS), a short cationic peptide. To further improve the antimicrobial activity of our agent, dimeric (Acr3-NLS)2 was simultaneously synthesized by joining two monomeric Acr3-NLS together via a disulfide linker. Our results show that Acr3-NLS and especially (Acr3-NLS)2 display significant antimicrobial activity against gram-negative and gram-positive bacteria compared to that of the NLS. Subsequently, the results derived from the study on the mechanism of action demonstrate that Acr3-NLS and (Acr3-NLS)2 can kill bacteria by membrane disruption and DNA binding. The double targets–cell membrane and intracellular DNA–will reduce the risk of bacteria developing resistance to Acr3-NLS and (Acr3-NLS)2. Overall, this study provides a novel strategy to design highly effective antimicrobial agents with a dual mode of action for infection treatment.

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Recent Advances in 19Fluorine Magnetic Resonance Imaging with Perfluorocarbon Emulsions
Anne H. Schmieder,Shelton D. Caruthers,Jochen Keupp,Samuel A. Wickline,Gregory M. Lanza
Engineering    2015, 1 (4): 475-489.   DOI: 10.15302/J-ENG-2015103
Abstract   HTML   PDF (2072KB)

The research roots of 19fluorine (19F) magnetic resonance imaging (MRI) date back over 35 years. Over that time span, 1H imaging flourished and was adopted worldwide with an endless array of applications and imaging approaches, making magnetic resonance an indispensable pillar of biomedical diagnostic imaging. For many years during this timeframe, 19F imaging research continued at a slow pace as the various attributes of the technique were explored. However, over the last decade and particularly the last several years, the pace and clinical relevance of 19F imaging has exploded. In part, this is due to advances in MRI instrumentation, 19F/1H coil designs, and ultrafast pulse sequence development for both preclinical and clinical scanners. These achievements, coupled with interest in the molecular imaging of anatomy and physiology, and combined with a cadre of innovative agents, have brought the concept of 19F into early clinical evaluation. In this review, we attempt to provide a slice of this rich history of research and development, with a particular focus on liquid perfluorocarbon compound-based agents.

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A Personal Desktop Liquid-Metal Printer as a Pervasive Electronics Manufacturing Tool for Society in the Near Future
Jun Yang,Yang Yang,Zhizhu He,Bowei Chen,Jing Liu
Engineering    2015, 1 (4): 506-512.   DOI: 10.15302/J-ENG-2015042
Abstract   HTML   PDF (8660KB)

It has long been a dream in the electronics industry to be able to write out electronics directly, as simply as printing a picture onto paper with an office printer. The first-ever prototype of a liquid-metal printer has been invented and demonstrated by our lab, bringing this goal a key step closer. As part of a continuous endeavor, this work is dedicated to significantly extending such technology to the consumer level by making a very practical desktop liquid-metal printer for society in the near future. Through the industrial design and technical optimization of a series of key technical issues such as working reliability, printing resolution, automatic control, human-machine interface design, software, hardware, and integration between software and hardware, a high-quality personal desktop liquid-metal printer that is ready for mass production in industry was fabricated. Its basic features and important technical mechanisms are explained in this paper, along with demonstrations of several possible consumer end-uses for making functional devices such as light-emitting diode (LED) displays. This liquid-metal printer is an automatic, easy-to-use, and low-cost personal electronics manufacturing tool with many possible applications. This paper discusses important roles that the new machine may play for a group of emerging needs. The prospective future of this cutting-edge technology is outlined, along with a comparative interpretation of several historical printing methods. This desktop liquid-metal printer is expected to become a basic electronics manufacturing tool for a wide variety of emerging practices in the academic realm, in industry, and in education as well as for individual end-users in the near future.

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