24 research outputs found

    Cubic membranes: a legend beyond the Flatland* of cell membrane organization

    Get PDF
    Cubic membranes represent highly curved, three-dimensional nanoperiodic structures that correspond to mathematically well defined triply periodic minimal surfaces. Although they have been observed in numerous cell types and under different conditions, particularly in stressed, diseased, or virally infected cells, knowledge about the formation and function of nonlamellar, cubic structures in biological systems is scarce, and research so far is restricted to the descriptive level. We show that the “organized smooth endoplasmic reticulum” (OSER; Snapp, E.L., R.S. Hegde, M. Francolini, F. Lombardo, S. Colombo, E. Pedrazzini, N. Borgese, and J. Lippincott-Schwartz. 2003. J. Cell Biol. 163:257–269), which is formed in response to elevated levels of specific membrane-resident proteins, is actually the two-dimensional representation of two subtypes of cubic membrane morphology. Controlled OSER induction may thus provide, for the first time, a valuable tool to study cubic membrane formation and function at the molecular level

    Letter to Editor Interpretation of clopidogrel resistance

    Get PDF

    Sponge cities and sustainable drainage systems: sharing best practice in China and the UK

    Get PDF
    Flooding from rivers, surface water and the sea is a major hazard in many cities of the world and is expected to increase in the future due to climate change. With funding from the UK-China Urban Flooding Research Impact Programme, part of the UK-China Newton Fund, researchers and practitioners from both countries are collaborating on a project which focuses on surface water flooding and aims to enhance technical co-operation and knowledge-sharing in urban flood risk management. A comparison of current approaches to urban flood risk management in China and the UK is presented, and a case study of the benefits of Sponge City construction in the city of Wuhan, China is used by way of demonstration. Interventions to increase infiltration rates and on-site storage prove most effective for the 1-year return period, but have a more limited effect as flood event rarity increases. The paper discusses how similar results have been found in the UK for case studies of Sustainable Drainage Systems (SuDS), either installed in new urban developments or retrofitted in older ones. These studies also recognise the multiple benefits brought by the installation of green infrastructure, particularly in terms of community engagement and well-being

    Self-Assembled Nanoscale Materials for Neuronal Regeneration: A Focus on BDNF Protein and Nucleic Acid Biotherapeutic Delivery

    No full text
    Enabling challenging applications of nanomedicine and precision medicine in the treatment of neurodegenerative disorders requires deeper investigations of nanocarrier-mediated biomolecular delivery for neuronal targeting and recovery. The successful use of macromolecular biotherapeutics (recombinant growth factors, antibodies, enzymes, synthetic peptides, cell-penetrating peptide–drug conjugates, and RNAi sequences) in clinical developments for neuronal regeneration should benefit from the recent strategies for enhancement of their bioavailability. We highlight the advances in the development of nanoscale materials for drug delivery in neurodegenerative disorders. The emphasis is placed on nanoformulations for the delivery of brain-derived neurotrophic factor (BDNF) using different types of lipidic nanocarriers (liposomes, liquid crystalline or solid lipid nanoparticles) and polymer-based scaffolds, nanofibers and hydrogels. Self-assembled soft-matter nanoscale materials show favorable neuroprotective characteristics, safety, and efficacy profiles in drug delivery to the central and peripheral nervous systems. The advances summarized here indicate that neuroprotective biomolecule-loaded nanoparticles and injectable hydrogels can improve neuronal survival and reduce tissue injury. Certain recently reported neuronal dysfunctions in long-COVID-19 survivors represent early manifestations of neurodegenerative pathologies. Therefore, BDNF delivery systems may also help in prospective studies on recovery from long-term COVID-19 neurological complications and be considered as promising systems for personalized treatment of neuronal dysfunctions and prevention or retarding of neurodegenerative disorders

    Chronic inflammation, neuroglial dysfunction, and plasmalogen deficiency as a new pathobiological hypothesis addressing the overlap between post-COVID-19 symptoms and myalgic encephalomyelitis/chronic fatigue syndrome

    No full text
    After five waves of coronavirus disease 2019 (COVID-19) outbreaks, it has been recognized that a significant portion of the affected individuals developed long-term debilitating symptoms marked by chronic fatigue, cognitive difficulties (“brain fog”), post-exertional malaise, and autonomic dysfunction. The onset, progression, and clinical presentation of this condition, generically named post-COVID-19 syndrome, overlap significantly with another enigmatic condition, referred to as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Several pathobiological mechanisms have been proposed for ME/CFS, including redox imbalance, systemic and central nervous system inflammation, and mitochondrial dysfunction. Chronic inflammation and glial pathological reactivity are common hallmarks of several neurodegenerative and neuropsychiatric disorders and have been consistently associated with reduced central and peripheral levels of plasmalogens, one of the major phospholipid components of cell membranes with several homeostatic functions. Of great interest, recent evidence revealed a significant reduction of plasmalogen contents, biosynthesis, and metabolism in ME/CFS and acute COVID-19, with a strong association to symptom severity and other relevant clinical outcomes. These bioactive lipids have increasingly attracted attention due to their reduced levels representing a common pathophysiological manifestation between several disorders associated with aging and chronic inflammation. However, alterations in plasmalogen levels or their lipidic metabolism have not yet been examined in individuals suffering from post-COVID-19 symptoms. Here, we proposed a pathobiological model for post-COVID-19 and ME/CFS based on their common inflammation and dysfunctional glial reactivity, and highlighted the emerging implications of plasmalogen deficiency in the underlying mechanisms. Along with the promising outcomes of plasmalogen replacement therapy (PRT) for various neurodegenerative/neuropsychiatric disorders, we sought to propose PRT as a simple, effective, and safe strategy for the potential relief of the debilitating symptoms associated with ME/CFS and post-COVID-19 syndrome

    Liquid crystalline lipid nanoparticles for combined delivery of curcumin, fish oil and BDNF: In vitro neuroprotective potential in a cellular model of tunicamycin-induced endoplasmic reticulum stress

    No full text
    International audienceWe develop multidrug-loaded cubosome and spongosome lipid nanoparticles for targeting of endoplasmic reticulum stress as a potential emerging therapeutic strategy against neuronal degeneration. The multicompartment organization of the liquid crystalline nanoparticles (LCNPs), fabricated by self-assembly, was characterized by cryogenic transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS). Monooleinbased cubosome and spongosome LCNPs co-encapsulated the natural plant-derived antioxidant curcumin, fish oil rich in ω-3 polyunsaturated fatty acids (PUFA), and the neurotrophin brain-derived neurotrophic factor (BDNF), which is of vital need for neurogenesis. The neuroprotective properties of the nanoparticles were in vitro investigated in a cellular model of tunicamycin-induced endoplasmic reticulum (ER) stress using differentiated human neuroblastoma SH-SY5Y cells deprieved from serum. The intracellular accumulation of aggregates of misfolded proteins, typical for the ER stress process, was analyzed by fluorescence microscopy co-localization imaging and ER staining. The performed cellular bioassays established that the BDNF-loaded LCNPs enhanced the neuronal cell survival. The diminution of the tunicamycin-induced ER stress upon internalization of neuroprotective nanoparticles was quantified via the changes in the Thioflavin T fluorescence, which is a sensitive marker of protein aggregation. LCNPs with multi-drug loading appear to be promising candidates to face the challenges in neuroprotective nanomedicine development by exploiting ER-stress targeting mechanisms
    corecore