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https://www.readbyqxmd.com/read/29028353/activated-microglia-targeting-dendrimer-minocycline-conjugate-as-therapeutics-for-neuroinflammation
#1
Rishi Sharma, Soo-Young Kim, Anjali Sharma, Zhi Zhang, Siva Pramodh Kambhampati, Sujatha Kannan, Rangaramanujam M Kannan
Brain related disorders have outmatched cancer and cardiovascular diseases worldwide as the leading cause of morbidity and mortality. The lack of effective therapies and the relatively dry central nervous system (CNS) drug pipeline pose formidable challenge. Superior, targeted delivery of current clinically approved drugs may offer significant potential. Minocycline has shown promise for the treatment of neurological diseases owing to its ability to penetrate the blood brain barrier (BBB), and potency. Despite its potential in the clinic, and in preclinical models, the high doses needed to affect a positive therapeutic response has led to side effects...
October 13, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29026924/gene-regulation-two-component-regulatory-systems-and-adaptive-responses-in-treponema-denticola
#2
Richard T Marconi
The oral microbiome consists of a remarkably diverse group of 500-700 bacterial species. The microbial etiology of periodontal disease is similarly complex. Of the ~400 bacterial species identified in subgingival plaque, at least 50 belong to the genus Treponema. As periodontal disease develops and progresses, T. denticola transitions from a low to high abundance species in the subgingival crevice. Changes in the overall composition of the bacterial population trigger significant changes in the local physical, immunological and physiochemical conditions...
October 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/29026294/comparison-of-the-peripheral-blood-eosinophil-count-using-near-patient-testing-and-standard-automated-laboratory-measurement-in-healthy-asthmatic-and-copd-subjects
#3
Kirsty Hambleton, Clare M Connolly, Catherine Borg, Joanne H Davies, Helen P Jeffers, Richard Ek Russell, Mona Bafadhel
Near-patient testing (NPT) allows clinical decisions to be made in a rapid and convenient manner and is often cost effective. In COPD the peripheral blood eosinophil count has been demonstrated to have utility in providing prognostic information and predicting response to treatment during an acute exacerbation. For this potential to be achieved having a reliable NPT of blood eosinophil count would be extremely useful. Therefore, we investigated the use of the HemoCue(®) WBC Diff System and evaluated its sensitivity and specificity in healthy, asthmatic and COPD subjects...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29025653/stepwise-ph-reduction-responsive-polymeric-conjugates-for-enhanced-drug-delivery-to-tumor
#4
Shudi Yang, Ying Wang, Zhaoxiang Ren, Mengtian Chen, Weiliang Chen, Xuenong Zhang
In this research, a charge-conversional polymer, poly-l-lysine-lipoic acid (PLL-LA), was prepared by dimethylmaleic anhydride (DA) modification and applied as a carrier with enhanced cell internalization and intracellular pH- and reduction-triggered doxorubicin (Dox) release. The surface charge of dimethylmaleic anhydride-poly-l-lysine-lipoic acid micelles (DA-PLL-LA) was negative at physiological pH and reversed to positive at the extracellular and intracellular pH of cancer cells. At tumor extracellular pH of 6...
January 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/29025635/how-ethiopia-achieved-millennium-development-goal-4-through-multisectoral-interventions-a-countdown-to-2015-case-study
#5
Jenny Ruducha, Carlyn Mann, Neha S Singh, Tsegaye D Gemebo, Negussie S Tessema, Angela Baschieri, Ingrid Friberg, Taddese A Zerfu, Mohammed Yassin, Giovanny A Franca, Peter Berman
BACKGROUND: 3 years before the 2015 deadline, Ethiopia achieved Millennium Development Goal 4. The under-5 mortality decreased 69%, from 205 deaths per 1000 livebirths in 1990 to 64 deaths per 1000 livebirths in 2013. To understand the underlying factors that contributed to the success in achieving MDG4, Ethiopia was selected as a Countdown to 2015 case study. METHODS: We used a set of complementary methods to analyse progress in child health in Ethiopia between 1990 and 2014...
November 2017: Lancet Global Health
https://www.readbyqxmd.com/read/29024914/-exploring-the-regulation-of-streptomyces-growth-and-development
#6
REVIEW
Stephanie E Jones, Marie A Elliot
The Streptomyces life cycle encompasses three well-established developmental stages: vegetative hyphae, aerial hyphae and spores. Many regulators governing the transitions between these life cycle stages have been identified, and recent work is shedding light on their specific functions. A new discovery has shown Streptomyces can deviate from this classic life cycle through a process termed 'exploration', where cells rapidly traverse solid surfaces. Exploration does not require any of the traditional developmental regulators, and therefore provides an exciting new context in which to uncover novel developmental pathways...
October 9, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29024514/therapeutic-potential-of-haecs-for-early-achilles-tendon-defect-repair-through-regeneration
#7
Barbara Barboni, Valentina Russo, Valentina Gatta, Nicola Bernabò, Paolo Berardinelli, Annunziata Mauro, Alessandra Martelli, Luca Valbonetti, Aurelio Muttini, Oriana Di Giacinto, Maura Turriani, Antonietta Silini, Giuseppe Calabrese, Michele Abate, Ornella Parolini, Liborio Stuppia, Mauro Mattioli
Cell-based therapy hold great promise for tendon disorders, a widespread debilitating musculoskeletal condition. Even if the cell line remains to be defined, preliminary evidences have proven that amniotic-derived cells possess in vitro and in vivo a great tenogenic potential. The present study investigated the efficacy of transplanted human amniotic epithelial cells (hAECs) by testing their early regenerative properties and mechanisms involved on a validated ovine Achilles tendon partial defect performed on 29 animals...
October 11, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29024335/fifty-shades-of-sumo-its-role-in-immunity-and-at-the-fulcrum-of-growth-defense-balance
#8
Vivek Verma, Fenella Crolley, Ari Sadanandom
The sessile nature of plants requires them to cope with an ever changing environment. Effective adaptive responses require sophisticated cellular mechanisms at post-transcriptional and -translational levels. Post-translational modification by Small Ubiquitin-like Modifier (SUMO) proteins is emerging as a key player in these adaptive responses. SUMO conjugation can rapidly change the overall fate of target proteins by altering their stability or interaction with partner proteins or DNA. SUMOylation entails an enzyme cascade that leads to the activation, conjugation and ligation of SUMO to lysine residues of target proteins...
October 10, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/29024118/rice-sumo-protease-overly-tolerant-to-salt-1-targets-the-transcription-factor-osbzip23-to-promote-drought-tolerance-in-rice
#9
Anjil Kumar Srivastava, Cunjin Zhang, Robert S Caine, Julie Gray, Ari Sadanandom
Conjugation of SUMO (Small Ubiquitin-like Modifier) protein to cellular targets is emerging as a very influential protein modification system. Once covalently bound SUMO conjugation can change the stability or functionality of its cognate target proteins. SUMO protease can rapidly reverse SUMO conjugation making this modification system highly dynamic. A major factor in the variation of SUMO-target function is the balance between the conjugated/de-conjugated forms. The mechanistic role of these regulatory SUMO proteases in mediating stress responses has not been defined in any crops...
October 10, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29024110/therapeutic-gas-responsive-hydrogel
#10
Junghong Park, Swapan Pramanick, Dongsik Park, Jiwon Yeo, Jihyun Lee, Haeshin Lee, Won Jong Kim
Nitric oxide (NO) is a crucial signaling molecule with various functions in physiological systems. Due to its potent biological effect, the preparation of responsive biomaterials upon NO having temporally transient properties is a challenging task. This study represents the first therapeutic-gas (i.e., NO)-responsive hydrogel by incorporating a NO-cleavable crosslinker. The hydrogel is rapidly swollen in response to NO, and not to other gases. Furthermore, the NO-responsive gel is converted to enzyme-responsive gels by cascade reactions from an enzyme to NO production for which the NO precursor is a substrate of the enzyme...
October 11, 2017: Advanced Materials
https://www.readbyqxmd.com/read/29023363/lps-induced-systemic-inflammation-does-not-alter-atherosclerotic-plaque-area-or-inflammation-in-apoe3-leiden-mice-in-the-early-phase-up-to-15-days
#11
Wessel W Fuijkschot, Martine C Morrison, Ilse P A Zethof, Paul A J Krijnen, Robert Kleemann, Hans W M Niessen, Yvo M Smulders
BACKGROUND AND AIMS: Observational studies show a peak incidence in cardiovascular events during and early after clinical conditions associated with substantial systemic inflammation, such as pneumonia. The acuteness of this increased risk suggests rapid plaque destabilization and associated intra-plaque inflammation. We evaluated whether LPS-evoked acute systemic inflammation would induce such detrimental vascular changes in murine aortas with manifest atherosclerotic lesions. METHODS AND RESULTS: ApoE3*Leiden mice were fed a high cholesterol diet for 20 weeks to establish atherosclerosis...
October 11, 2017: Shock
https://www.readbyqxmd.com/read/29023360/honokiol-increases-cd4-t-cell-activation-and-decreases-tnf-but-fails-to-improve-survival-following-sepsis
#12
Nathan J Klingensmith, Ching-Wen Chen, Zhe Liang, Eileen M Burd, Alton B Farris, Jack L Arbiser, Mandy L Ford, Craig M Coopersmith
Honokiol is a biphenolic isolate extracted from the bark of the magnolia tree that has been used in traditional Chinese and Japanese medicine, and has more recently been investigated for its anti-inflammatory and anti-bacterial properties. Honokiol has previously been demonstrated to improve survival in sepsis models that have rapid 100% lethality. The purpose of this study was to determine the impact of Honokiol on the host response in a model of sepsis that more closely approximates human disease. Male and female C57BL/6 mice underwent cecal ligation and puncture (CLP) to induce polymicrobial intraabdominal sepsis...
October 11, 2017: Shock
https://www.readbyqxmd.com/read/29022761/noninvasive-ocular-drug-delivery-system-of-dexamethasone-sodium-phosphate-in-the-treatment-of-experimental-uveitis-rabbit
#13
Kongnara Papangkorn, Eri Prendergast, John W Higuchi, Balbir Brar, William I Higuchi
PURPOSE: To investigate the efficacy and safety of dexamethasone sodium phosphate administered through Visulex system (DSP-Visulex) in treating experimental uveitis. METHODS: Uveitis was induced in rabbits by subcutaneous injections of complete Freund's adjuvant and an intravitreal injection of H37RA antigen. After induction, the animals of the control group received no treatment and the others received various treatment regimens of DSP-Visulex. Each regimen was different in DSP strength (4%, 8%, and 15%), application time, or treatment frequency...
October 12, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29022425/biologics-in-pediatric-psoriasis-efficacy-and-safety
#14
Sunil Dogra, Rahul Mahajan
Introduction Childhood psoriasis is a special situation that is a management challenge for the treating dermatologist. As is the situation with traditional systemic agents, which are commonly used in managing severe psoriasis in children, the biologics are being increasingly used in the recalcitrant disease despite limited data on long term safety. Areas covered - We performed an extensive literature search to collect evidence-based data on the use of biologics in pediatric psoriasis. The relevant literature published from 2000 to September 2017 was obtained from PubMed, using the MeSH words 'biologics', 'biologic response modifiers' or 'treatment of pediatric/childhood psoriasis'...
October 12, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29021746/lever-insertion-as-a-salient-stimulus-promoting-insensitivity-to-outcome-devaluation
#15
Youna Vandaele, Heather J Pribut, Patricia H Janak
Flexible and efficient decision-making in complex environments can be achieved through constant interactions between the goal-directed and habitual systems. While goal-directed behavior is considered dependent upon Response-Outcome (R-O) associations, habits instead rely on Stimulus-Response (S-R) associations. However, the stimuli that support the S-R association underlying habitual responding in typical instrumental procedures are poorly defined. To resolve this issue, we designed a discrete-trials procedure, in which rats must wait for lever insertion and complete a sequence of five lever presses to obtain a reward (20% sucrose or grain-based pellets)...
2017: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/29021127/fall-detection-in-individuals-with-lower-limb-amputations-using-mobile-phones-machine-learning-enhances-robustness-for-real-world-applications
#16
Nicholas Shawen, Luca Lonini, Chaithanya Krishna Mummidisetty, Ilona Shparii, Mark V Albert, Konrad Kording, Arun Jayaraman
BACKGROUND: Automatically detecting falls with mobile phones provides an opportunity for rapid response to injuries and better knowledge of what precipitated the fall and its consequences. This is beneficial for populations that are prone to falling, such as people with lower limb amputations. Prior studies have focused on fall detection in able-bodied individuals using data from a laboratory setting. Such approaches may provide a limited ability to detect falls in amputees and in real-world scenarios...
October 11, 2017: JMIR MHealth and UHealth
https://www.readbyqxmd.com/read/29020775/portable-nitric-oxide-no-generator-based-on-electrochemical-reduction-of-nitrite-for-potential-applications-in-inhaled-no-therapy-and-cardiopulmonary-bypass-surgery
#17
Yu Qin, Joanna Zajda, Elizabeth J Brisbois, Hang Ren, John Toomasian, Terry Major, Alvaro Rojas-Pena, Benjamin Carr, Thomas Johnson, Jonathan Haft, Robert H Bartlett, Andrew Hunt, Nicolai Lehnert, Mark E Meyerhoff
A new portable gas phase nitric oxide (NO) generator is described for potential applications in inhaled NO (INO) therapy and during cardiopulmonary bypass (CPB) surgery. In this system, NO is produced at the surface of a large area mesh working electrode by electrochemical reduction of nitrite ions in the presence of a soluble copper(II)-ligand electron transfer mediator complex. The NO generated is then transported into gas phase by either direct purging with nitrogen or via circulating the electrolyte/nitrite solution through a gas extraction silicone fiber-based membrane-dialyzer assembly...
October 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29020709/absorbaseal%C3%A2-vascular-closure-device-a-novel-device-for-hemostasis-following-interventional-peripheral-vascular-procedures
#18
Emily Benham, Koen Deloose, Joren Callaert, Marc Bosiers, Tiffany Cox, Amy Lincourt, B Todd Heniford
INTRODUCTION: Vascular closure devices (VCDs) are designed to achieve rapid hemostasis during percutaneous coronary and peripheral vascular procedures. Studies demonstrate that VCDs improve time to hemostasis (TTH) and time to ambulation (TTA) in comparison to standard manual compression. The available products, however, typically have 13-17 steps in their application, often require hemostatic collagen or other agents as part of the process, and can result in significant scarring at the puncture site that can impact future access...
October 12, 2017: Surgical Technology International
https://www.readbyqxmd.com/read/29018924/rapid-volumetric-photoacoustic-tomographic-imaging-with-a-fabry-perot-ultrasound-sensor-depicts-peripheral-arteries-and-microvascular-vasomotor-responses-to-thermal-stimuli
#19
Andrew A Plumb, Nam Trung Huynh, Jamie Guggenheim, Edward Zhang, Paul Beard
PURPOSE: To determine if a new photoacoustic imaging (PAI) system successfully depicts (1) peripheral arteries and (2) microvascular circulatory changes in response to thermal stimuli. METHODS: Following ethical permission, 8 consenting subjects underwent PAI of the dorsalis pedis (DP) artery, and 13 completed PAI of the index fingertip. Finger images were obtained after immersion in warm (30-35 °C) or cold (10-15 °C) water to promote vasodilation or vasoconstriction...
October 10, 2017: European Radiology
https://www.readbyqxmd.com/read/29018604/effects-of-invasion-history-on-physiological-responses-to-immune-system-activation-in-invasive-australian-cane-toads
#20
Daniel Selechnik, Andrea J West, Gregory P Brown, Kerry V Fanson, BriAnne Addison, Lee A Rollins, Richard Shine
The cane toad (Rhinella marina) has undergone rapid evolution during its invasion of tropical Australia. Toads from invasion front populations (in Western Australia) have been reported to exhibit a stronger baseline phagocytic immune response than do conspecifics from range core populations (in Queensland). To explore this difference, we injected wild-caught toads from both areas with the experimental antigen lipopolysaccharide (LPS, to mimic bacterial infection) and measured whole-blood phagocytosis. Because the hypothalamic-pituitary-adrenal axis is stimulated by infection (and may influence immune responses), we measured glucocorticoid response through urinary corticosterone levels...
2017: PeerJ
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