2,143 research outputs found
Reactive oxygen species responsive dextran-thioketal conjugate nanocarriers for the delivery of hydrophilic payloads
No full textDextran-thioketal conjugate (DTKC) nanocarrier responsive to endogenous as well as exogenous stimuli is developed for delivering hydrophilic payloads. First, water-soluble reactive oxygen species (ROS)-responsive DTKCs are synthesized and responsiveness to various ROS stimuli is studied. Next, different DTKC nanocarriers (NCs) loaded with the respective hydrophilic molecules - fluorescent dye (rhodamine B, RhoB), photosensitizer, PS (rose bengal, RB), and chemotherapeutic drug (doxorubicin hydrochloride, Dox) - are synthesized using inverse miniemulsion interfacial polymerization. All NCs exhibit nanocapsule morphology, and cargo dependent hydrodynamic diameters (166-194 nm) in water, an encapsulation efficiency between 79 and 91 %, and a drug loading content of about 11 %. RhoB-NCs and Dox-NCs exhibit time-dependent release upon exposure to different H2O2 concentrations and an enhanced release in conditioned medium collected from oral squamous cell carcinoma (OSCC) cells. Further, as a proof-of-concept, light-responsive payload release from PS loaded NCs via a cascade reaction is confirmed. The in vitro studies show that RhoB-NCs and RB-NCs are biocompatible while the Dox-NCs exhibit cytotoxic effects. Such dextran-based ROS-responsive NCs sensitive to endogenous (ROS rich environment) as well as exogenous (light in combination with a PS) stimuli are highly interesting to realize combination therapies, for instance combining a chemotherapeutic drug and a photosensitizer for application in photochemotherapy.The authors thank Prof. Karen Smeets (Biodiversity and Toxicology Group, Centre for Environmental Sciences, UHasselt) for providing access to the LSM900 confocal microscope, Birte Luyck for acquiring TEM images, and Dr. Annelies Sels for supporting elemental analysis. Sourav Nayak is funded by the BOF Special Research Fund of Hasselt University (BOF21OWB04). Esther Wolfs and Anitha Ethirajan received funding from the Hasselt University large BOF project program (BOF21GP08). Esther Wolfs is funded by the Research Foundation Flanders (FWO G040220N and G0A7N24FWO), and Tom Cardeynaels is an FWO postdoctoral fellow (1284623N). The FWO and Hasselt University are acknowledged for the NMR support of this research (AUHL/15/2-GOH3816N)
Adult Neurogenesis in the Subventricular Zone and Its Regulation After Ischemic Stroke: Implications for Therapeutic Approaches
No full textAdult neurogenesis in the subventricular zone is a topic of intense research, since it has vast implications for the fundamental understanding of the neurobiology of the brain and its potential to being harnessed for therapy in various neurological disorders. Investigation of adult neurogenesis has been complicated by the difficulties with characterization of neural stem cells in vivo. However, recent single-cell transcriptomic studies provide more detailed information on marker expression in neural stem cells and their neuronal lineage, which hopefully will result in a more unified discussion. Regulation of the multiple biological steps in adult neurogenesis comprises intrinsic mechanisms as well as extrinsic factors which together orchestrate the process. In this review, we describe the regulating factors and their cellular sources in the physiological condition and provide an overview of the regulating factors mediating stroke-induced stimulation of neurogenesis in the subventricular zone. While there is ongoing debate about the longevity of active post-natal neurogenesis in humans, the subventricular zone has the capacity to upregulate neurogenesis in response to ischemic stroke. Though, the stroke-induced neurogenesis in humans does not seem to translate into adequate functional recovery, which opens discussion about potential treatment strategies to harness this neuroregenerative response. Various therapeutic approaches are explored in preclinical and clinical studies to target endogenous neurogenesis of which some are discussed in this review.sponsorship: This study was funded by grants of "Fonds voor Wetenschappelijk Onderzoek" (FWO) Vlaanderen and Research Funds of Hasselt University. Yorg Dillen is a predoctoral researcher of the "Fonds Wetenschappelijk Onderzoek" (FWO) Vlaanderen. Pascal Gervois, Esther Wolfs, Yorg Dillen and Annelies Bronckaers are funded by FWO grants 12U7718N, G0A7514N, 1134717N, FWO1522518. Hannelore Kemps is funded by the Special Research Fund (BOF) of Hasselt University" (Grant number 18NI06BOF). (Fonds voor Wetenschappelijk Onderzoek (FWO) Vlaanderen, FWO|12U7718N, FWO|G0A7514N, FWO|1134717N, FWO|FWO1522518, Special Research Fund (BOF) of Hasselt University|18NI06BOF, Hasselt University)status: Publishe
Author Interview with Novelist Esther Laforce
No full textNovelist\u27s Corner:
Author Interview with novelist Esther Laforce, author of: In the Early Days of the Anthropocene (Aux premiers temps de l’Anthropocène). Ottawa, CA: Leméac Editeur, 201
The Esther Forbes Papers
No full textThe Esther Forbes Papers contain original manuscripts written by Forbes during her childhood and college years. They also contain manuscripts for The Running of the Tide, Rainbow on the Road, and Paradise. With the papers are housed bibliographic material about Esther Forbes collected by Jack Bales and published as: Esther Forbes: A Bio-Bibliography of the Author of Johnny Tremain, by The Scarecrow Press, Inc., Lanham, Md., 1998, Scarecrow Author Bibliographic Series, No. 98
By the Skin of Your Teeth: A Subcutaneous Mouse Model to Study Pulp Regeneration
No full textExiting developments in tissue engineering and new insights in stem cell biology have led to new possible strategies for the regeneration of damaged tissues in the oral cavity. The regeneration of the pulp–dentin complex regeneration in particular, has drawn the attention of many researchers because of the high clinical needs. While it is still important to perform in vitro research using a wide variety of cells, scaffolds and growth factors, it is also critical to have a reliable animal model for preclinical trials. In this chapter, we describe a mouse model in which a scaffold resembling a tooth containing dental pulp cells is implanted subcutaneously. We also describe which histological stainings could be used to examine blood vessel formation and the regeneration of the pulp–dentin complex
Proteostasis plays an important role in demyelinating Charcot Marie Tooth disease
No full textType 1 Charcot-Marie-Tooth disease (CMT1) is the most common demyelinating peripheral neuropathy. Patients suffer from progressive muscle weakness and sensory problems. The underlying disease mechanisms of CMT1 are still unclear and no therapy is currently available, hence patients completely rely on supportive care. Balancing protein levels is a complex multistep process fundamental to maintain cells in their healthy state and a disrupted proteostasis is a hallmark of several neurodegenerative diseases. When protein misfolding occurs, protein quality control systems are activated such as chaperones, the lysosomal-autophagy system and proteasomal degradation to ensure proper degradation. However, in pathological circumstances, these mechanisms are overloaded and thereby become inefficient to clear the load of misfolded proteins. Recent evidence strongly indicates that a disbalance in proteostasis plays an important role in several forms of CMT1. In this review, we present an overview of the protein quality control systems, their role in CMT1, and potential treatment strategies to restore proteostasis.KL is PhD fellow funded by “Fonds Wetenschappelijk Onderzoek” (FWO: “Research Foundation Flanders”; 11A4120N & 11A4122N) and by the “Special Research Fund” (BOF) of Hasselt University (R-10491). TVG is a Junior postdoc fellow funded by “Fonds Wetenschappelijk Onderzoek” (FWO: “Research Foundation Flanders”; 12Z2620N)
The Effect of Leukocyte- and Platelet-Rich Fibrin on Central and Peripheral Nervous System Neurons-Implications for Biomaterial Applicability
No full textLeukocyte- and Platelet-Rich Fibrin (L-PRF) is a second-generation platelet concentrate that is prepared directly from the patient's own blood. It is widely used in the field of regenerative medicine, and to better understand its clinical applicability we aimed to further explore the biological properties and effects of L-PRF on cells from the central and peripheral nervous system. To this end, L-PRF was prepared from healthy human donors, and confocal, transmission, and scanning electron microscopy as well as secretome analysis were performed on these clots. In addition, functional assays were completed to determine the effect of L-PRF on neural stem cells (NSCs), primary cortical neurons (pCNs), and peripheral dorsal root ganglion (DRG) neurons. We observed that L-PRF consists of a dense but porous fibrin network, containing leukocytes and aggregates of activated platelets that are distributed throughout the clot. Antibody array and ELISA confirmed that it is a reservoir for a plethora of growth factors. Key molecules that are known to have an effect on neuronal cell functions such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) were slowly released over time from the clots. Next, we found that the L-PRF secretome had no significant effect on the proliferative and metabolic activity of NSCs, but it did act as a chemoattractant and improved the migration of these CNS-derived stem cells. More importantly, L-PRF growth factors had a detrimental effect on the survival of pCNs, and consequently, also interfered with their neurite outgrowth. In contrast, we found a positive effect on peripheral DRG neurons, and L-PRF growth factors improved their survival and significantly stimulated the outgrowth and branching of their neurites. Taken together, our study demonstrates the positive effects of the L-PRF secretome on peripheral neurons and supports its use in regenerative medicine but care should be taken when using it for CNS applications
Swedish Landmarks in the Delaware Valley
No full textThis is an English-language edition of Dr. Esther Chilstrom Meixner's book, "Svenska spar vid Delaware." It was published in 1960, and printed by The Chancellor Press, Inc., Bridgeport, CT. The cover shows the Kalmar Nyckel Monument in Fort Christina State Park, Wilmington, Delaware
Walter Benjamin's legacy - Esther Leslie and Stuart Jeffries
No full textTo celebrate Verso’s new edition of The Storyteller by Walter Benjamin, Esther Leslie (writer and translator of many books including The Storyteller, and Professor of Political Aesthetics at Birkbeck, London) and Stuart Jeffries (journalist and author of many books including Grand Hotel Abyss) discuss the life and legacy of Walter Benjamin. From his relationship with his peers, the other members of the Frankfurt School, and his cultural heritage, to his use of, and feelings about, technological advancements, to his approach to storytelling, writing and language more broadly, join Esther and Stuart for this fascinating and wide-ranging discussion of one of Western Marxism's most important philosophers
Pyridoxamine Attenuates Doxorubicin-Induced Cardiomyopathy without Affecting Its Antitumor Effect on Rat Mammary Tumor Cells
No full textDoxorubicin (DOX) is commonly used in cancer treatment but associated with cardiotoxicity. Pyridoxamine (PM), a vitamin B6 derivative, could be a cardioprotectant. This study investigated the effect of PM on DOX cardiotoxicity and DOX antitumor effectiveness. Sprague Dawley rats were treated intravenously with DOX (2 mg/kg/week) or saline over eight weeks. Two other groups received PM via oral intake (1 g/L in water bottles) next to DOX or saline. Echocardiography was performed after eight weeks. PM treatment significantly attenuated the DOX-induced reduction in left ventricular ejection fraction (72 ± 2% vs. 58 ± 3% in DOX; p < 0.001) and increase in left ventricular end-systolic volume (0.24 ± 0.02 µL/cm2 vs. 0.38 ± 0.03 µL/cm2 in DOX; p < 0.0001). Additionally, LA7 tumor cells were exposed to DOX, PM, or DOX and PM for 24 h, 48 h, and 72 h. Cell viability, proliferation, cytotoxicity, and apoptosis were assessed. DOX significantly reduced LA7 cell viability and proliferation (p < 0.0001) and increased cytotoxicity (p < 0.05) and cleaved caspase-3 (p < 0.001). Concomitant PM treatment did not alter the DOX effect on LA7 cells. In conclusion, PM attenuated DOX-induced cardiomyopathy in vivo without affecting the antitumor effect of DOX in vitro, highlighting PM as a promising cardioprotectant for DOX-induced cardiotoxicity.ThisresearchwasfundedbytheFlemishFundforScientificResearch(FWOVlaanderen, Brussels,Belgium)withgrantnumbers1196221NandG040220FWO,UHasseltSpecialResearchFund (BOF19KP07)andLimburgCancerFoundation.
WethankEvelyneVankerckhove,NuranCaz, andJolienVanDenBoschfortheir technicalassistancewiththeIncuCyteS3Live-CellAnalysisSystem.TheauthorsalsothankPetra Bexforhertechnicalsupportwithcellculturing
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