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https://www.readbyqxmd.com/read/29669940/generation-and-testing-of-clinical-grade-exosomes-for-pancreatic-cancer
#1
Mayela Mendt, Sushrut Kamerkar, Hikaru Sugimoto, Kathleen M McAndrews, Chia-Chin Wu, Mihai Gagea, Sujuan Yang, Elena V Rodriges Blanko, Qian Peng, Xiaoyan Ma, Joseph R Marszalek, Anirban Maitra, Cassian Yee, Katayoun Rezvani, Elizabeth Shpall, Valerie S LeBleu, Raghu Kalluri
Exosomes are extracellular vesicles produced by all cells with a remarkable ability to efficiently transfer genetic material, including exogenously loaded siRNA, to cancer cells. Here, we report on a bioreactor-based, large-scale production of clinical-grade exosomes employing good manufacturing practice (GMP) standards. A standard operating procedure was established to generate engineered exosomes with the ability to target oncogenic Kras (iExosomes). The clinical-grade GMP iExosomes were tested in multiple in vitro and in vivo studies to confirm suppression of oncogenic Kras and an increase in the survival of several mouse models with pancreatic cancer...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29664738/pharmacological-induction-of-hypoxia-inducible-transcription-factor-arnt-attenuates-chronic-kidney-failure
#2
Björn Tampe, Désirée Tampe, Gunsmaa Nyamsuren, Friederike Klöpper, Gregor Rapp, Anne Kauffels, Thomas Lorf, Elisabeth M Zeisberg, Gerhard A Müller, Raghu Kalluri, Samy Hakroush, Michael Zeisberg
Progression of chronic kidney disease associated with progressive fibrosis and impaired tubular epithelial regeneration is still an unmet biomedical challenge, because once chronic lesions have manifested, no effective therapies are available as of yet for clinical use. Prompted by various studies across multiple organs demonstrating that preconditioning regimens to induce endogenous regenerative mechanisms protect various organs from later incurring acute injuries, we here aimed to gain insights into the molecular mechanisms underlying successful protection and to explore whether such pathways could be utilized to inhibit progression of chronic organ injury...
April 17, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29621269/artificial-neural-network-model-for-predicting-the-bioavailability-of-tacrolimus-in-patients-with-renal-transplantation
#3
Kalluri Thishya, Kiran Kumar Vattam, Shaik Mohammad Naushad, Shree Bhushan Raju, Vijay Kumar Kutala
The objective of the current study was to explore the role of ABCB1 and CYP3A5 genetic polymorphisms in predicting the bioavailability of tacrolimus and the risk for post-transplant diabetes. Artificial neural network (ANN) and logistic regression (LR) models were used to predict the bioavailability of tacrolimus and risk for post-transplant diabetes, respectively. The five-fold cross-validation of ANN model showed good correlation with the experimental data of bioavailability (r2 = 0.93-0.96). Younger age, male gender, optimal body mass index were shown to exhibit lower bioavailability of tacrolimus...
2018: PloS One
https://www.readbyqxmd.com/read/29604038/holographic-waveguide-heads-up-display-for-longitudinal-image-magnification-and-pupil-expansion
#4
Colton M Bigler, Pierre-Alexandre Blanche, Kalluri Sarma
The field of view of traditional heads-up display systems is limited by the size of the projection optics. Our research is focused on overcoming this limitation by coupling image-bearing light into a waveguide using holographic elements, propagating the light through that waveguide, and extracting the light several times with additional holographic optical elements. With this configuration, we demonstrated both longitudinal magnification and pupil expansion of the heads-up display. We created a ray-trace model of the optical system to optimize the component parameters and implemented the solution in a prototype that demonstrates the merit of our approach...
March 20, 2018: Applied Optics
https://www.readbyqxmd.com/read/29580275/the-emerging-roles-of-exosomes-in-the-modulation-of-immune-responses-in-cancer
#5
Paul Kurywchak, Jena Tavormina, Raghu Kalluri
Exosomes are promising tools for improving cancer care, but conversely may also contribute to tumor progression. Here, we highlight recently discovered roles of exosomes in modulating immune responses in cancer, with emphasis on exosomal surface proteins and on RNA and DNA content. We also discuss how exosomes could be exploited as biomarkers and delivery vehicles in cancer therapy.
March 26, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29573973/fatty-acid-oxidation-regulates-the-activation-of-endothelial-to-mesenchymal-transition
#6
Sara Lovisa, Raghu Kalluri
The molecular mechanisms underpinning the process of endothelial-to-mesenchymal transition (EndMT) are mostly unknown. Recently Xiong and colleagues explored for the first time the metabolic changes associated with the activation of the mesenchymal program in endothelial cells, and found that reprogramming of fatty acid oxidation pivotally regulates EndMT.
March 21, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29473503/genetic-variants-identified-from-gwas-for-predisposition-to-type-2-diabetes-predict-sulfonylurea-drug-response
#7
N M Phani, M Vohra, P Adhikari, S K Nagri, U Shashikiran, S C D'Souza, P R R Kalluri, K Satyamoorthy, P S Rai
BACKGROUND: Several SNPs were identified through GWAS for their association with type 2 diabetes which has implications to pancreatic β-cell physiology. OBJECTIVE: We aimed to study the role of risk alleles of TCF7L2, KCNJ11, CDKN2A, CDKAL1, IGF2BP2, SLC30A8 and KCNQ1 along with pharmacokinetic variants in response to sulfonylureas. METHOD: We performed a prospective study on 209 newly diagnosed subjects; treatment naive T2D subjects were recruited...
2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/29467822/tension-wood-structure-and-morphology-conducive-for-better-enzymatic-digestion
#8
Daisuke Sawada, Udaya C Kalluri, Hugh O'Neill, Volker Urban, Paul Langan, Brian Davison, Sai Venkatesh Pingali
Background: Tension wood is a type of reaction wood in response to bending or leaning stem as a corrective growth process. Tension wood is formed by both natural and man-made processes. Most attractively, tension wood contains higher glucan content and undergoes higher enzymatic conversion to fermentable sugars. Here, we have employed structural techniques, small-angle neutron scattering (SANS) and wide-angle X-ray diffraction (WAXD) to elucidate structural and morphological aspects of tension wood conducive to higher sugar yields...
2018: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29370845/quality-improvement-initiatives-for-hospitalised-small-and-sick-newborns-in-low-and-middle-income-countries-a-systematic-review
#9
REVIEW
Nabila Zaka, Emma C Alexander, Logan Manikam, Irena C F Norman, Melika Akhbari, Sarah Moxon, Pavani Kalluri Ram, Georgina Murphy, Mike English, Susan Niermeyer, Luwei Pearson
BACKGROUND: An estimated 2.6 million newborns died in 2016; over 98.5% of deaths occurred in low- and middle-income countries (LMICs). Neonates born preterm and small for gestational age are particularly at risk given the high incidence of infectious complications, cardiopulmonary, and neurodevelopmental disorders in this group. Quality improvement (QI) initiatives can reduce the burden of mortality and morbidity for hospitalised newborns in these settings. We undertook a systematic review to synthesise evidence from LMICs on QI approaches used, outcome measures employed to estimate effects, and the nature of implementation challenges...
January 25, 2018: Implementation Science: IS
https://www.readbyqxmd.com/read/29326430/emt-in-cancer
#10
REVIEW
Thomas Brabletz, Raghu Kalluri, M Angela Nieto, Robert A Weinberg
Similar to embryonic development, changes in cell phenotypes defined as an epithelial to mesenchymal transition (EMT) have been shown to play a role in the tumorigenic process. Although the first description of EMT in cancer was in cell cultures, evidence for its role in vivo is now widely reported but also actively debated. Moreover, current research has exemplified just how complex this phenomenon is in cancer, leaving many exciting, open questions for researchers to answer in the future. With these points in mind, we asked four scientists for their opinions on the role of EMT in cancer and the challenges faced by scientists working in this fast-moving field...
February 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29303514/depletion-of-s100a4-stromal-cells-does-not-prevent-hcc-development-but-reduces-the-stem-cell-like-phenotype-of-the-tumors
#11
Jingjing Jiao, Álvaro González, Heather L Stevenson, Mihai Gagea, Hikaru Sugimoto, Raghu Kalluri, Laura Beretta
There is a pressing need for the development of novel approaches to treat and prevent hepatocellular carcinoma (HCC). The S100 calcium-binding protein S100A4 is associated with poor prognosis and metastasis in several human cancers. In addition, a role for S100A4 in modulating cancer-initiating cells stemness properties was recently proposed in head and neck and gastric cancers. Whether S100A4+ stromal cells contribute to tumor onset remains, however, an unanswered question. To address that question, we generated a new mouse model allowing for the depletion of S100A4+ cells in a mouse model of HCC with stemness properties, by crossing mice with hepatic deletion of phosphatase and tensin homolog (PTEN) with mice expressing viral thymidine kinase under the control of S100A4 promoter...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29213313/agronomic-performance-of-populus-deltoides-trees-engineered-for-biofuel-production
#12
David Macaya-Sanz, Jin-Gui Chen, Udaya C Kalluri, Wellington Muchero, Timothy J Tschaplinski, Lee E Gunter, Sandra J Simon, Ajaya K Biswal, Anthony C Bryan, Raja Payyavula, Meng Xie, Yongil Yang, Jin Zhang, Debra Mohnen, Gerald A Tuskan, Stephen P DiFazio
Background: One of the major barriers to the development of lignocellulosic feedstocks is the recalcitrance of plant cell walls to deconstruction and saccharification. Recalcitrance can be reduced by targeting genes involved in cell wall biosynthesis, but this can have unintended consequences that compromise the agronomic performance of the trees under field conditions. Here we report the results of a field trial of fourteen distinct transgenic Populus deltoides lines that had previously demonstrated reduced recalcitrance without yield penalties under greenhouse conditions...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29176801/increasing-vaccine-production-using-pulsed-ultrasound-waves
#13
Jida Xing, Shrishti Singh, Yupeng Zhao, Yan Duan, Huining Guo, Chenxia Hu, Allan Ma, Rajan George, James Z Xing, Ankarao Kalluri, Isaac Macwan, Prabir Patra, Jie Chen
Vaccination is a safe and effective approach to prevent deadly diseases. To increase vaccine production, we propose that a mechanical stimulation can enhance protein production. In order to prove this hypothesis, Sf9 insect cells were used to evaluate the increase in the expression of a fusion protein from hepatitis B virus (HBV S1/S2). We discovered that the ultrasound stimulation at a frequency of 1.5 MHz, intensity of 60 mW/cm2, for a duration of 10 minutes per day increased HBV S1/S2 by 27%. We further derived a model for transport through a cell membrane under the effect of ultrasound waves, tested the key assumptions of the model through a molecular dynamics simulation package, NAMD (Nanoscale Molecular Dynamics program) and utilized CHARMM force field in a steered molecular dynamics environment...
2017: PloS One
https://www.readbyqxmd.com/read/29111753/biogenic-nanostructured-porous-silicon-as-a-carrier-for-stabilization-and-delivery-of-natural-therapeutic-species
#14
Nguyen T Le, Jhansi R Kalluri, Armando Loni, Leigh T Canham, Jeffery L Coffer
Nanostructured mesoporous silicon (pSi) derived from the silicon-accumulator plant Tabasheer (Bambuseae) is demonstrated to serve as a potential carrier matrix for carrying and stabilizing naturally active, but otherwise metastable, therapeutic agents. Particularly, in this study, garlic oil containing phytochemicals (namely, allicin) that are capable of inhibiting Staphylococcus aureus (S. aureus) bacterial growth were incorporated into Tabasheer-derived porous silicon. Thermogravimetric analysis (TGA) indicated that relatively high amounts of the extract (53...
December 4, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29101086/beyond-idiopathic-pulmonary-fibrosis-diagnosis-multidisciplinary-care-with-an-early-integrated-palliative-approach-is-associated-with-a-decrease-in-acute-care-utilization-and-hospital-deaths
#15
Meena Kalluri, Francisca Claveria, Emily Ainsley, Maged Haggag, Susan Armijo-Olivo, Janice Richman-Eisenstat
CONTEXT: Idiopathic pulmonary fibrosis (IPF) is a progressive, incurable interstitial lung disease with heavy symptom burden and poor quality of life. The last year of life is characterized by increased acute care utilization and hospital deaths. Clinical guidelines recommend early integration of palliative care but are rarely implemented. In 2012, we reorganized our clinic into a multidisciplinary team comprising two pulmonologists (expertise in interstitial lung disease and palliative respiratory care, respectively), nurse, respiratory therapist, physiotherapist, and a dietitian...
February 2018: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/29092591/continued-search-for-better-prediction-of-aided-speech-understanding-in-multi-talker-environments
#16
Jing Xia, Sridhar Kalluri, Christophe Micheyl, Ervin Hafter
To better understand issues of hearing-aid benefit during natural listening, this study examined the added demand placed by the goal of understanding speech over the more typically studied goal of simply recognizing speech sounds. The study compared hearing-aid benefit in two conditions, and examined factors that might account for the observed benefits. In the phonetic condition, listeners needed only identify the correct sound to make a correct response. In the semantic condition, listeners had to understand what they had heard to respond correctly, because the answer did not include any keywords from the spoken speech...
October 2017: Journal of the Acoustical Society of America
https://www.readbyqxmd.com/read/29090640/listening-into-2030-workshop-an-experiment-in-envisioning-the-future-of-hearing-and-communication-science
#17
Simon Carlile, Gregory Ciccarelli, Jane Cockburn, Anna C Diedesch, Megan K Finnegan, Ervin Hafter, Simon Henin, Sridhar Kalluri, Alexander J E Kell, Erol J Ozmeral, Casey L Roark, Jessica E Sagers
Here we report the methods and output of a workshop examining possible futures of speech and hearing science out to 2030. Using a design thinking approach, a range of human-centered problems in communication were identified that could provide the motivation for a wide range of research. Nine main research programs were distilled and are summarized: (a) measuring brain and other physiological parameters, (b) auditory and multimodal displays of information, (c) auditory scene analysis, (d) enabling and understanding shared auditory virtual spaces, (e) holistic approaches to health management and hearing impairment, (f) universal access to evolving and individualized technologies, (g) biological intervention for hearing dysfunction, (h) understanding the psychosocial interactions with technology and other humans as mediated by technology, and (i) the impact of changing models of security and privacy...
January 2017: Trends in Hearing
https://www.readbyqxmd.com/read/29071224/process-physicochemical-characterization-and-in-vitro-assessment-of-albendazole-microcrystals
#18
Vandana Kr, Prasanna Raju Yalavarthi, Harini Chowdary Vadlamudi, Jagadesh Kumar Yadav Kalluri, Arun Rasheed
Purpose: Albendazole is a poorly soluble drug which limits its oral bioavailability. The study was focussed to enhance the solubility by in-situ micronization. Methods: Albendazole microcrystals were prepared by solvent change method using gum karaya and hupu gum as stabilizing agents and the effect of each stabilizer on the prepared microcrystals were studied. FT-IR, DSC, XRD and SEM analysis were performed as a part of characterization studies. The formulations were evaluated for micromeritics, solubility and drug release...
September 2017: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29066027/interferon-beta-specific-t-cells-are-associated-with-the-development-of-neutralizing-antibodies-in-interferon-beta-treated-multiple-sclerosis-patients
#19
Sudhakar Reddy Kalluri, Verena Grummel, Zsuzsanna Hracsko, Viola Pongratz, Verena Pernpeintner, Christiane Gasperi, Dorothea Buck, Bernhard Hemmer
Beta-interferons are still among the most commonly used drugs to treat Multiple Sclerosis (MS). The use of beta-interferons is limited by the development of anti-drug antibodies (ADA), which may abrogate the treatment effect of the drug. Although the antibody response has been well studied, little is known about the T cell response to interferon-beta (IFN-β). We investigated T cell responses in four treatment naïve MS patients and twenty-three patients treated with IFN-β who had or had not developed ADA to IFN-β...
October 20, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28936513/solar-cells-with-pbs-quantum-dot-sensitized-tio-2-multiwalled-carbon-nanotube-composites-sulfide-titania-gel-and-tin-sulfide-coated-c-fabric
#20
Ramesh K Kokal, Melepurath Deepa, Ankarao Kalluri, Shrishti Singh, Isaac Macwan, Prabir K Patra, Jeff Gilarde
Novel approaches to boost quantum dot solar cell (QDSC) efficiencies are in demand. Herein, three strategies are used: (i) a hydrothermally synthesized TiO2 -multiwalled carbon nanotube (MWCNT) composite instead of conventional TiO2 , (ii) a counter electrode (CE) that has not been applied to QDSCs until now, namely, tin sulfide (SnS) nanoparticles (NPs) coated over a conductive carbon (C)-fabric, and (iii) a quasi-solid-state gel electrolyte composed of S2- , an inert polymer and TiO2 nanoparticles as opposed to a polysulfide solution based hole transport layer...
October 4, 2017: Physical Chemistry Chemical Physics: PCCP
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