Neurogenesis, a process of generation of new neurons, is reported to be reduced in several neurodegenerative disorders including Alzheimer's disease (AD). Induction of neurogenesis by targeting endogenous neural stem cells (NSC) could be a promising therapeutic approach to such diseases by influencing the brain self-regenerative capacity. Curcumin, a neuroprotective agent, has poor brain bioavailability. Herein, we report that curcumin-encapsulated PLGA nanoparticles (Cur-PLGA-NPs) potently induce NSC proliferation and neuronal differentiation in vitro and in the hippocampus and subventricular zone of adult rats, as compared to uncoated bulk curcumin. Cur-PLGA-NPs induce neurogenesis by internalization into the hippocampal NSC. Cur-PLGA-NPs significantly increase expression of genes involved in cell proliferation (reelin, nestin, and Pax6) and neuronal differentiation (neurogenin, neuroD1, neuregulin, neuroligin, and Stat3). Curcumin nanoparticles increase neuronal differentiation by activating the Wnt/β-catenin pathway, involved in regulation of neurogenesis. These nanoparticles caused enhanced nuclear translocation of β-catenin, decreased GSK-3β levels, and increased promoter activity of the TCF/LEF and cyclin-D1. Pharmacological and siRNA-mediated genetic inhibition of the Wnt pathway blocked neurogenesis-stimulating effects of curcumin. These nanoparticles reverse learning and memory impairments in an amyloid beta induced rat model of AD-like phenotypes, by inducing neurogenesis. In silico molecular docking studies suggest that curcumin interacts with Wif-1, Dkk, and GSK-3β. These results suggest that curcumin nanoparticles induce adult neurogenesis through activation of the canonical Wnt/β-catenin pathway and may offer a therapeutic approach to treating neurodegenerative diseases such as AD, by enhancing a brain self-repair mechanism.
Acute inflammation is a protective reaction by the immune system in response to invading pathogens or tissue damage. Ideally, the response should be localized, self-limited, and returning to homeostasis. If not resolved, acute inflammation can result in organ pathologies leading to chronic inflammatory phenotypes. Acute inflammation and inflammation resolution are complex coordinated processes, involving a number of cell types, interacting in space and time. The biomolecular complexity and the fact that several biomedical fields are involved, make a multi- and interdisciplinary approach necessary. The Atlas of Inflammation Resolution (AIR) is a web-based resource capturing an essential part of the state-of-the-art in acute inflammation and inflammation resolution research. The AIR provides an interface for users to search thousands of interactions, arranged in inter-connected multi-layers of process diagrams, covering a wide range of clinically relevant phenotypes. By mapping experimental data onto the AIR, it can be used to elucidate drug action as well as molecular mechanisms underlying different disease phenotypes. For the visualization and exploration of information, the AIR uses the Minerva platform, which is a well-established tool for the presentation of disease maps. The molecular details of the AIR are encoded using international standards. The AIR was created as a freely accessible resource, supporting research and education in the fields of acute inflammation and inflammation resolution. The AIR connects research communities, facilitates clinical decision making, and supports research scientists in the formulation and validation of hypotheses. The AIR is accessible through
https://air.bio.informatik.uni-rostock.de
We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
Nanoparticles (NPs) cause concern for health and safety as their impact on the environment and humans is not known. Relatively few studies have investigated the toxicological and environmental effects of exposure to naturally occurring NPs (NNPs) and man-made or engineered NPs (ENPs) that are known to have a wide variety of effects once taken up into an organism.A review of recent knowledge (between 2000-2010) on NP sources, and their behaviour, exposure and effects on the environment and humans was performed. An integrated approach was used to comprise available scientific information within an interdisciplinary logical framework, to identify knowledge gaps and to describe environment and health linkages for NNPs and ENPs.The causal diagram has been developed as a method to handle the complexity of issues on NP safety, from their exposure to the effects on the environment and health. It gives an overview of available scientific information starting with common sources of NPs and their interactions with various environmental processes that may pose threats to both human health and the environment. Effects of NNPs on dust cloud formation and decrease in sunlight intensity were found to be important environmental changes with direct and indirect implication in various human health problems. NNPs and ENPs exposure and their accumulation in biological matrices such as microbiota, plants and humans may result in various adverse effects. The impact of some NPs on human health by ROS generation was found to be one of the major causes to develop various diseases.A proposed cause-effects diagram for NPs is designed considering both NNPs and ENPs. It represents a valuable information package and user-friendly tool for various stakeholders including students, researchers and policy makers, to better understand and communicate on issues related to NPs.
Stability concerns of organic solar cell devices have led to the development of alternative hole transporting layers such as NiO which lead to superior device life times over conventional Poly(3,4-ethylenedioxythiophene) Polystyrene sulfonate (PEDOT:PSS) buffered solar cells. From the printability of such devices, it is imperative to be able to print NiO layers in the organic solar cell devices with normal architecture which has so far remained unreported. In this manuscript, we report on the successful ink-jet printing of very thin NiO thin films with controlled thickness and morphology and their integration in organic solar cell devices. The parameters that were found to strongly affect the formation of a thin yet continuous NiO film were substrate surface treatment, drop spacing, and substrate temperature during printing. The effect of these parameters was investigated through detailed morphological characterization using optical and atomic force microscopy and the results suggested that one can achieve a transmittance of ~89% for a ~18 nm thin NiO film with uniform structure and morphology, fabricated using a drop spacing of 50 μm and a heat treatment temperature of 400 °C. The devices fabricated with printed NiO hole transporting layers exhibit power conversion efficiencies comparable to the devices with spin coated NiO films.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.