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Robert Langer

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https://www.readbyqxmd.com/read/28937662/glucose-responsive-insulin-by-molecular-and-physical-design
#1
Naveed A Bakh, Abel B Cortinas, Michael A Weiss, Robert S Langer, Daniel G Anderson, Zhen Gu, Sanjoy Dutta, Michael S Strano
The concept of a glucose-responsive insulin (GRI) has been a recent objective of diabetes technology. The idea behind the GRI is to create a therapeutic that modulates its potency, concentration or dosing relative to a patient's dynamic glucose concentration, thereby approximating aspects of a normally functioning pancreas. From the perspective of the medicinal chemist, the GRI is also important as a generalized model of a potentially new generation of therapeutics that adjust potency in response to a critical therapeutic marker...
September 22, 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28932622/high-throughput-nuclear-delivery-and-rapid-expression-of-dna-via-mechanical-and-electrical-cell-membrane-disruption
#2
Xiaoyun Ding, Martin Stewart, Armon Sharei, James C Weaver, Robert S Langer, Klavs F Jensen
Nuclear transfection of DNA into mammalian cells is challenging yet critical for many biological and medical studies. Here, by combining cell squeezing and electric-field-driven transport in a device that integrates microfluidic channels with constrictions and microelectrodes, we demonstrate nuclear delivery of plasmid DNA within 1 hour after treatment, the most rapid DNA expression in a high-throughput setting (up to millions of cells per minute per device). Passing cells at high speed through microfluidic constrictions smaller than the cell diameter mechanically disrupts the cell membrane, allowing a subsequent electric field to further disrupt the nuclear envelope and drive DNA molecules into the cytoplasm and nucleus...
2017: Nature biomedical engineering
https://www.readbyqxmd.com/read/28912242/fabrication-of-fillable-microparticles-and-other-complex-3d-microstructures
#3
Kevin J McHugh, Thanh D Nguyen, Allison R Linehan, David Yang, Adam M Behrens, Sviatlana Rose, Zachary L Tochka, Stephany Y Tzeng, James J Norman, Aaron C Anselmo, Xian Xu, Stephanie Tomasic, Matthew A Taylor, Jennifer Lu, Rohiverth Guarecuco, Robert Langer, Ana Jaklenec
Three-dimensional (3D) microstructures created by microfabrication and additive manufacturing have demonstrated value across a number of fields, ranging from biomedicine to microelectronics. However, the techniques used to create these devices each have their own characteristic set of advantages and limitations with regards to resolution, material compatibility, and geometrical constraints that determine the types of microstructures that can be formed. We describe a microfabrication method, termed StampEd Assembly of polymer Layers (SEAL), and create injectable pulsatile drug-delivery microparticles, pH sensors, and 3D microfluidic devices that we could not produce using traditional 3D printing...
September 15, 2017: Science
https://www.readbyqxmd.com/read/28903368/expression-analysis-of-lc3b-and-p62-indicates-intact-activated-autophagy-is-associated-with-an-unfavorable-prognosis-in-colon-cancer
#4
Monique Niklaus, Olivia Adams, Sabina Berezowska, Inti Zlobec, Franziska Graber, Julia Slotta-Huspenina, Ulrich Nitsche, Robert Rosenberg, Mario P Tschan, Rupert Langer
Autophagy is a lysosomal degradation and recycling process implicated in cancer progression and therapy resistance. We assessed the impact of basal autophagy in colon cancer (CC) in vitro and ex vivo. Functional autophagy was demonstrated in CC cell lines (LoVo; HT-29) showing a dose-dependent increase of the autophagy markers LC3B, p62 and autophagic vesciles upon increasing concentrations of the autophagy inhibitor chloroquine, which was demonstrated by immunoblotting, immunofluorescence and electron microscopy...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893673/extracorporeal-membrane-oxygenation-ecmo-as-salvage-treatment-for-pulmonary-echinococcus-granulosus-infection-with-acute-cyst-rupture
#5
Sören L Becker, Sebastian Fähndrich, Franziska C Trudzinski, Barbara Gärtner, Frank Langer, Torben K Becker, Robert Bals, Philipp M Lepper, Christian Lensch
Extracorporeal membrane oxygenation (ECMO) has been successfully used for the treatment of patients with respiratory failure due to severe infections. Though rare, parasites can also cause severe pulmonary disease. Tapeworms of the genus Echinococcus give rise to the development of cystic structures in the liver, lungs and other organs. Acute cyst rupture leads to potentially life-threatening infection, and affected patients may deteriorate rapidly. We describe the case of a young woman from Bulgaria who was admitted to hospital with severe dyspnoea, progressive chest pain and haemoptysis...
September 8, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28875984/multiscale-technologies-for-treatment-of-ischemic-cardiomyopathy
#6
REVIEW
Morteza Mahmoudi, Mikyung Yu, Vahid Serpooshan, Joseph C Wu, Robert Langer, Richard T Lee, Jeffrey M Karp, Omid C Farokhzad
The adult mammalian heart possesses only limited capacity for innate regeneration and the response to severe injury is dominated by the formation of scar tissue. Current therapy to replace damaged cardiac tissue is limited to cardiac transplantation and thus many patients suffer progressive decay in the heart's pumping capacity to the point of heart failure. Nanostructured systems have the potential to revolutionize both preventive and therapeutic approaches for treating cardiovascular disease. Here, we outline recent advancements in nanotechnology that could be exploited to overcome the major obstacles in the prevention of and therapy for heart disease...
September 6, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28874662/cre-lox-assisted-non-invasive-in-vivo-tracking-of-specific-cell-populations-by-positron-emission-tomography
#7
Martin Thunemann, Barbara F Schörg, Susanne Feil, Yun Lin, Jakob Voelkl, Matthias Golla, Angelos Vachaviolos, Ursula Kohlhofer, Leticia Quintanilla-Martinez, Marcus Olbrich, Walter Ehrlichmann, Gerald Reischl, Christoph M Griessinger, Harald F Langer, Meinrad Gawaz, Florian Lang, Michael Schäfers, Manfred Kneilling, Bernd J Pichler, Robert Feil
Many pathophysiological processes are associated with proliferation, migration or death of distinct cell populations. Monitoring specific cell types and their progeny in a non-invasive, longitudinal and quantitative manner is still challenging. Here we show a novel cell-tracking system that combines Cre/lox-assisted cell fate mapping with a thymidine kinase (sr39tk) reporter gene for cell detection by positron emission tomography (PET). We generate Rosa26-mT/sr39tk PET reporter mice and induce sr39tk expression in platelets, T lymphocytes or cardiomyocytes...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28872490/menopausal-hormone-therapy-for-primary-prevention-why-the-uspstf-is-wrong
#8
Robert D Langer, James A Simon, Amos Pines, Rogerio A Lobo, Howard N Hodis, James H Pickar, David F Archer, Philip M Sarrel, Wulf H Utian
No abstract text is available yet for this article.
October 2017: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/28839004/ventilation-and-neurochemical-changes-during-%C3%A2%C2%B5-opioid-receptor-activation-or-blockade-of-excitatory-receptors-in-the-hypoglossal-motor-nucleus-of-goats
#9
Thomas M Langer, Suzanne E Neumueller, Emma Crumley, Nicholas J Burgraff, Sawan Talwar, Matthew Robert Hodges, Lawrence G Pan, Hubert V Forster
Neuromodulator interdependence posits that changes in one or more neuromodulators are compensated by changes in other modulators to maintain stability in the respiratory control network. Herein, we studied compensatory neuromodulation in the hypoglossal motor nucleus (HMN) after chronic implantation of microtubules unilaterally (n=5) or bilaterally (n=5) into the HMN. After recovery, receptor agonists or antagonists in mock cerebrospinal fluid (mCSF) were dialyzed during the awake and NREM sleep state. During day studies, dialysis of the µ-opioid inhibitory receptor agonist DAMGO (100 µM) decreased pulmonary ventilation (V̇I), breathing frequency (f), and genioglossus (GG) muscle activity, but did not alter neuromodulators measured in the effluent mCSF...
August 24, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28834756/regulation-of-peripheral-myelination-through-transcriptional-buffering-of-egr2-by-an-antisense-long-non-coding-rna
#10
Margot Martinez-Moreno, Timothy Mark O'Shea, John P Zepecki, Alexander Olaru, Jennifer K Ness, Robert Langer, Nikos Tapinos
Precise regulation of Egr2 transcription is fundamentally important to the control of peripheral myelination. Here, we describe a long non-coding RNA antisense to the promoter of Egr2 (Egr2-AS-RNA). During peripheral nerve injury, the expression of Egr2-AS-RNA is increased and correlates with decreased Egr2 transcript and protein levels. Ectopic expression of Egr2-AS-RNA in dorsal root ganglion (DRG) cultures inhibits the expression of Egr2 mRNA and induces demyelination. In vivo inhibition of Egr2-AS-RNA using oligonucleotide GapMers released from a biodegradable hydrogel following sciatic nerve injury reverts the EGR2-mediated gene expression profile and significantly delays demyelination...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28828455/drug-delivery-by-supramolecular-design
#11
REVIEW
Matthew J Webber, Robert Langer
The rational design of drug delivery approaches leveraging supramolecular chemistry (i.e., "chemistry beyond the molecule") has garnered significant interest in recent years toward improving therapeutics. By using specific, dynamic, and tunable non-covalent interactions, engineered approaches to drug delivery can be realized. Certain benefits to this approach are molecular-level control of composition, improved routes for incorporating and targeting drugs, and new strategies to create delivery devices that respond to a variety of physiologic indicators...
August 22, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28789964/applications-of-ethylene-vinyl-acetate-copolymers-eva-in-drug-delivery-systems
#12
REVIEW
Christian Schneider, Robert Langer, Donald Loveday, Dirk Hair
The potential for use of polymers in controlled drug delivery systems has been long recognized. Since their appearance in the literature, a wide range of degradable and non-degradable polymers have been demonstrated in drug delivery devices. The significance and features of ethylene-vinyl acetate (EVA) copolymers in initial research and development led to commercial drug delivery systems. This review examines the breadth of EVA use in drug delivery, and will aid the researcher in locating key references and experimental results, as well as understanding the features of EVA as a highly versatile, biocompatible polymer for drug delivery devices...
August 5, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28777138/high-serum-bilirubin-levels-nt-pro-bnp-and-lactate-predict-mortality-in-long-term-severely-ill-respiratory-extracorporeal-membrane-oxygenation-patients
#13
Franziska Kaestner, Daniel Rapp, Franziska C Trudzinski, Nicole Olewczynska, Stefan Wagenpfeil, Frank Langer, Monika Flaig, Heinrike Wilkens, Robert Bals, Matthias Klingele, Christian Lensch, Sebastian Fähndrich, Philipp M Lepper
Mortality in patients treated with extracorporeal membrane oxygenation (ECMO) is high. Therefore, it is crucial to better understand conditions that are associated with mortality in ECMO patients. In this retrospective analysis, we observed 51 patients treated with high-flow ECMO in 2013 and 2014 at our center. We recorded laboratory values and intensive care procedures. The hypothesis of bilirubin being a predictor of mortality during ECMO treatment was initially addressed. Therefore, laboratory values were obtained before initiation and at the time of highest bilirubin throughout the procedure...
August 2, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/28743858/triggerable-tough-hydrogels-for-gastric-resident-dosage-forms
#14
Jinyao Liu, Yan Pang, Shiyi Zhang, Cody Cleveland, Xiaolei Yin, Lucas Booth, Jiaqi Lin, Young-Ah Lucy Lee, Hormoz Mazdiyasni, Sarah Saxton, Ameya R Kirtane, Thomas von Erlach, Jaimie Rogner, Robert Langer, Giovanni Traverso
Systems capable of residing for prolonged periods of time in the gastric cavity have transformed our ability to diagnose and treat patients. Gastric resident systems for drug delivery, ideally need to be: ingestible, be able to change shape or swell to ensure prolonged gastric residence, have the mechanical integrity to withstand the forces associated with gastrointestinal motility, be triggerable to address any side effects, and be drug loadable and release drug over a prolonged period of time. Materials that have been primarily utilized for these applications have been largely restricted to thermoplastics and thermosets...
July 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28696296/multiplexed-rnai-therapy-against-brain-tumor-initiating-cells-via-lipopolymeric-nanoparticle-infusion-delays-glioblastoma-progression
#15
Dou Yu, Omar F Khan, Mario L Suvà, Biqin Dong, Wojciech K Panek, Ting Xiao, Meijing Wu, Yu Han, Atique U Ahmed, Irina V Balyasnikova, Hao F Zhang, Cheng Sun, Robert Langer, Daniel G Anderson, Maciej S Lesniak
Brain tumor-initiating cells (BTICs) have been identified as key contributors to therapy resistance, recurrence, and progression of diffuse gliomas, particularly glioblastoma (GBM). BTICs are elusive therapeutic targets that reside across the blood-brain barrier, underscoring the urgent need to develop novel therapeutic strategies. Additionally, intratumoral heterogeneity and adaptations to therapeutic pressure by BTICs impede the discovery of effective anti-BTIC therapies and limit the efficacy of individual gene targeting...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28691930/ly6clo-monocytes-drive-immunosuppression-and-confer-resistance-to-anti-vegfr2-cancer-therapy
#16
Keehoon Jung, Takahiro Heishi, Omar F Khan, Piotr S Kowalski, Joao Incio, Nuh N Rahbari, Euiheon Chung, Jeffrey W Clark, Christopher G Willett, Andrew D Luster, Seok Hyun Yun, Robert Langer, Daniel G Anderson, Timothy P Padera, Rakesh K Jain, Dai Fukumura
Current anti-VEGF therapies for colorectal cancer (CRC) provide limited survival benefit, as tumors rapidly develop resistance to these agents. Here, we have uncovered an immunosuppressive role for nonclassical Ly6Clo monocytes that mediates resistance to anti-VEGFR2 treatment. We found that the chemokine CX3CL1 was upregulated in both human and murine tumors following VEGF signaling blockade, resulting in recruitment of CX3CR1+Ly6Clo monocytes into the tumor. We also found that treatment with VEGFA reduced expression of CX3CL1 in endothelial cells in vitro...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28681930/synthesis-and-biological-evaluation-of-ionizable-lipid-materials-for-the-in-vivo-delivery-of-messenger-rna-to-b-lymphocytes
#17
Owen S Fenton, Kevin J Kauffman, James C Kaczmarek, Rebecca L McClellan, Siddharth Jhunjhunwala, Mark W Tibbitt, Manhao D Zeng, Eric A Appel, Joseph R Dorkin, Faryal F Mir, Jung H Yang, Matthias A Oberli, Michael W Heartlein, Frank DeRosa, Robert Langer, Daniel G Anderson
B lymphocytes regulate several aspects of immunity including antibody production, cytokine secretion, and T-cell activation; moreover, B cell misregulation is implicated in autoimmune disorders and cancers such as multiple sclerosis and non-Hodgkin's lymphomas. The delivery of messenger RNA (mRNA) into B cells can be used to modulate and study these biological functions by means of inducing functional protein expression in a dose-dependent and time-controlled manner. However, current in vivo mRNA delivery systems fail to transfect B lymphocytes and instead primarily target hepatocytes and dendritic cells...
September 2017: Advanced Materials
https://www.readbyqxmd.com/read/28641400/cytosolic-delivery-of-sirna-by-ultra-high-affinity-dsrna-binding-proteins
#18
Nicole J Yang, Monique J Kauke, Fangdi Sun, Lucy F Yang, Katie F Maass, Michael W Traxlmayr, Yao Yu, Yingda Xu, Robert S Langer, Daniel G Anderson, K Dane Wittrup
Protein-based methods of siRNA delivery are capable of uniquely specific targeting, but are limited by technical challenges such as low potency or poor biophysical properties. Here, we engineered a series of ultra-high affinity siRNA binders based on the viral protein p19 and developed them into siRNA carriers targeted to the epidermal growth factor receptor (EGFR). Combined in trans with a previously described endosome-disrupting agent composed of the pore-forming protein Perfringolysin O (PFO), potent silencing was achieved in vitro with no detectable cytotoxicity...
July 27, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28625520/immunogenicity-of-pulsatile-release-plga-microspheres-for-single-injection-vaccination
#19
Rohiverth Guarecuco, Jennifer Lu, Kevin J McHugh, James J Norman, Lavanya S Thapa, Emily Lydon, Robert Langer, Ana Jaklenec
The World Health Organization's Expanded Programme on Immunization has led to a dramatic rise in worldwide vaccination rates over the past 40years, yet 19.4 million infants remain underimmunized each year. Many of these infants have received at least one vaccine dose but may remain unprotected because they did not receive subsequent booster doses due to logistical challenges. This study aimed to develop injectable controlled release microparticles with kinetics that mimic common vaccine dosing regimens consisting of large antigen doses administered periodically over the course of months in order to eliminate the need for boosters...
June 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28591112/the-promise-of-organ-and-tissue-preservation-to-transform-medicine
#20
REVIEW
Sebastian Giwa, Jedediah K Lewis, Luis Alvarez, Robert Langer, Alvin E Roth, George M Church, James F Markmann, David H Sachs, Anil Chandraker, Jason A Wertheim, Martine Rothblatt, Edward S Boyden, Elling Eidbo, W P Andrew Lee, Bohdan Pomahac, Gerald Brandacher, David M Weinstock, Gloria Elliott, David Nelson, Jason P Acker, Korkut Uygun, Boris Schmalz, Brad P Weegman, Alessandro Tocchio, Greg M Fahy, Kenneth B Storey, Boris Rubinsky, John Bischof, Janet A W Elliott, Teresa K Woodruff, G John Morris, Utkan Demirci, Kelvin G M Brockbank, Erik J Woods, Robert N Ben, John G Baust, Dayong Gao, Barry Fuller, Yoed Rabin, David C Kravitz, Michael J Taylor, Mehmet Toner
The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities...
June 7, 2017: Nature Biotechnology
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