656 research outputs found

    Propolis induces AQP3 expression: A possible way of action in wound healing

    Get PDF
    Propolis is the generic name of a complex of resinous compound collected by honeybees and it has been utilized for many years in folk medicine. As other products generated by honeybees (such as royal jelly, pollen, honey), propolis has great therapeutic properties, but very little scientific information is available. Therefore, this study was aimed at exploring the potential wound healing properties of propolis. To that end, we utilized an in vitro scratch wound healing model consisting of human immortalized keratinocytes. Our scratch wound data clearly demonstrated that propolis induced a pronounced increase in the wound repair abilities of keratinocytes. A cell migration assay showed that propolis stimulated keratinocytes to close the wound. We revealed the role of H2O2 as the main mediator of propolis regenerative properties. We showed that this extracellularly released H2O2 could pass across the plasma membrane through a specific aquaporin (i.e., AQP3) modulating intracellular responses. The data offer a biological characterization of propolis positive effects suggesting that propolis could also be utilized in wound treatment within clinical settings

    Genomic organization and cytokine-mediated inducibility of the human TRIM-8/Gerp gene.

    Get PDF
    Cytokine signaling is negatively regulated by a set of SH2 domain-containing proteins, the Suppressors of Cytokine Signaling (SOCS) acting as intracellular modulators. Experimental evidence indicates that SOCS gene expression is induced by cytokines and pro-inflammatory stimuli and is highly controlled both at transcription and translation level. Furthermore, SOCS proteins appear rapidly degraded inside the cells, mostly controlling their stability by interacting with specific molecules such as elongin B and C. It has been shown that SOCS-1/JAB, a member of the SOCS family, interacts with TRIM-8/Gerp, a new ring protein specifically binding SOCS-1 recombinant polypeptide in-vitro and in-vivo. Trim-8/Gerp, transcribes a 3.0-kb mRNA, spans 551 AA and is highly conserved during evolution. In addition, it can be induced by IFN-γ in epithelial and lymphoid cells and is expressed mostly ubiquitously in murine and human tissues. Here in this report we present the genomic organization of this new SOCS-1 interactor, and we add new tools for extending investigation of the complex mechanism that undergoes negatively regulation of cytokine signaling

    Vis-NIR luminescent lanthanide-doped core-shell nanoparticles for imaging and photodynamic therapy

    Get PDF
    The preparation of smart Ln:ZrO2@SiO2 nanoplatforms with grafted photosensitizer (Rose Bengal) which couple optical imaging with photo-dynamic therapy (PDT) is presented. A careful control of the lanthanide dopant loading is considered to enhance the photoemission properties of the lanthanide ions (Er, Pr, Yb) inside the ZrO2 crystal structure. The nanosystem with the lowest lanthanide loading maintains the size, phase and morphology of pristine ZrO2 nanoparticles and exhibit the best performances in term of the overall luminescence properties. Upon functionalization with a silica shell to covalently bound Rose Bengal, a theranostic platform is prepared which is very efficient in singlet oxygen generation, as demonstrated by EPR and UV\u2013vis spectroscopy studies. Preliminary cell viability tests show that while both pristine and Ln doped ZrO2 nanoparticles do not exert cytotoxicity, neither upon illumination nor in dark condition, Rose Bengal grafted samples are able to significantly reduce cell viability under light exposure, thus confirming the high potential of these nanoparticles as PDT tools

    Alternating block copolymer-based nanoparticles as tools to modulate the loading of multiple chemotherapeutics and imaging probes

    Get PDF
    Abstract Cancer therapy often relies on the combined action of different molecules to overcome drug resistance and enhance patient outcome. Combined strategies relying on molecules with different pharmacokinetics often fail due to the lack of concomitant tumor accumulation and, thus, to the loss of synergistic effect. Due to their ability to enhance treatment efficiency, improve drug pharmacokinetics, and reduce adverse effects, polymer nanoparticles (PNPs) have been widely investigated as co-delivery vehicles for cancer therapies. However, co-encapsulation of different drugs and probes in PNPs requires a flexible polymer platform and a tailored particle design, in which both the bulk and surface properties of the carriers are carefully controlled. In this work, we propose a core-shell PNP design based on a polyurethane (PUR) core and a phospholipid external surface. The modulation of the hydrophilic/hydrophobic balance of the PUR core enhanced the encapsulation of two chemotherapeutics with dramatically different water solubility (Doxorubicin hydrochloride, DOXO and Docetaxel, DCTXL) and of Iron Oxide Nanoparticles for MRI imaging. The outer shell remained unchanged among the platforms, resulting in un-modified cellular uptake and in vivo biodistribution. We demonstrate that the choice of PUR core allowed a high entrapment efficiency of all drugs, superior or comparable to previously reported results, and that higher core hydrophilicity enhances the loading efficiency of the hydrophilic DOXO and the MRI contrast effect. Moreover, we show that changing the PUR core did not alter the surface properties of the carriers, since all particles showed a similar behavior in terms of cell internalization and in vivo biodistribution. We also show that PUR PNPs have high passive tumor accumulation and that they can efficient co-deliver the two drugs to the tumor, reaching an 11-fold higher DOXO/DCTXL ratio in tumor as compared to free drugs. Statement of Significance Exploiting the synergistic action of multiple chemotherapeutics is a promising strategy to improve the outcome of cancer patients, as different agents can simultaneously engage different features of tumor cells and/or their microenvironment. Unfortunately, the choice is limited to drugs with similar pharmacokinetics that can concomitantly accumulate in tumors. To expand the spectrum of agents that can be delivered in combination, we propose a multi-compartmental core-shell nanoparticles approach, in which the core is made of biomaterials with high affinity for drugs of different physical properties. We successfully co-encapsulated Doxorubicin Hydrochloride, Docetaxel, and contrast agents and achieved a significantly higher concomitant accumulation in tumor versus free drugs, demonstrating that nanoparticles can improve synergistic cancer chemotherapy

    A comprehensive overview on Kratom

    Get PDF
    Kratom (Mitragyna speciosa Korth) is a tropical tree, indigenous to South East Asia. Historically, the plant is locally used as a stimulant, a remedy in traditional medicine and in social context. Imported to Western countries, Kratom is classified as a novel psychoactive substance (NPS). A systematic review of the literature on Mitragyna speciosa and its main constituents was carried by our international multidisciplinary group. Results were qualitatively analysed in three main areas of interest: in-vitro and preclinical data on pharmacology and behavioral effects, laboratoristic techniques for identification/characterization, epidemiological/toxicological reports on humans. At present, there is no systematic data on the prevalence of Kratom use in all the native countries, but it seems to be considerable. In South-East Asia, Kratom, even if banned, might be still considered a better option than other illicit drugs, an alternative opioid treatment, a “natural” remedy with no real social stigma attached to its consumption. In parallel, this ethno-drug seems to be popular in Western countries, largely unregulated, easily available on the Internet. Kratom pharmacology appears to be complex, with many alkaloids involved. The subjective effects in humans are very peculiar and seem to be dose-dependent, ranging from psycho-stimulant to sedative-narcotic. Available data on Kratom suggest caution: this psychoactive plant could exhibit a serious harmful potential. Kratom use seems to be associated with drug dependency, development of withdrawal symptoms, craving, serious adverse effects and life-threatening effects in a multidrug-intoxicating scenario. On the other hand, its anxyiolitic, antidepressant and analgesic properties deserve to be further studied

    Manifesto for a European research network into Problematic Usage of the Internet

    Get PDF
    Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.The Internet is now all-pervasive across much of the globe. While it has positive uses (e.g. prompt access to information, rapid news dissemination), many individuals develop Problematic Use of the Internet (PUI), an umbrella term incorporating a range of repetitive impairing behaviours. The Internet can act as a conduit for, and may contribute to, functionally impairing behaviours including excessive and compulsive video gaming, compulsive sexual behaviour, buying, gambling, streaming or social networks use. There is growing public and National health authority concern about the health and societal costs of PUI across the lifespan. Gaming Disorder is being considered for inclusion as a mental disorder in diagnostic classification systems, and was listed in the ICD-11 version released for consideration by Member States (http://www.who.int/classifications/icd/revision/timeline/en/). More research is needed into disorder definitions, validation of clinical tools, prevalence, clinical parameters, brain-based biology, socio-health-economic impact, and empirically validated intervention and policy approaches. Potential cultural differences in the magnitudes and natures of types and patterns of PUI need to be better understood, to inform optimal health policy and service development. To this end, the EU under Horizon 2020 has launched a new four-year European Cooperation in Science and Technology (COST) Action Programme (CA 16207), bringing together scientists and clinicians from across the fields of impulsive, compulsive, and addictive disorders, to advance networked interdisciplinary research into PUI across Europe and beyond, ultimately seeking to inform regulatory policies and clinical practice. This paper describes nine critical and achievable research priorities identified by the Network, needed in order to advance understanding of PUI, with a view towards identifying vulnerable individuals for early intervention. The network shall enable collaborative research networks, shared multinational databases, multicentre studies and joint publications.Peer reviewe

    Extreme rainfall events in karst environments: the case study of September 2014 in the Gargano area (southern Italy)

    Get PDF
    In the first week of September 2014, the Gargano Promontory (Apulia, SE Italy) was hit by an extreme rainfall event that caused several landslides, floods and sinkholes. As a consequence of the floods, two people lost their lives and severe socio-economic damages were reported. The highest peaks of rainfall were recorded between September 3rd and 6th at the Cagnano Varano and San Marco in Lamis rain gauges with a maximum daily rainfall (over 230 mm) that is about 30% the mean annual rainfall. The Gargano Promontory is characterized by complex orographic conditions, with the highest elevation of about 1000 m a.s.l. The geological setting consists of different types of carbonate deposits affected by intensive development of karst processes. The morphological and climatic settings of the area, associated with frequent extreme rainfall events can cause various types of geohazards (e.g., landslides, floods, sinkholes). A further element enhancing the natural predisposition of the area to the occurrence of landslides, floods and sinkholes is an intense human activity, characterized by an inappropriate land use and management. In order to obtain consistent and reliable data on the effects produced by the storm, a systematic collection of information through field observations, a critical analysis of newspaper articles and web-news, and a co-operation with the Regional Civil Protection and local geologists started immediately after the event. The information collected has been organized in a database including the location, the occurrence time and the type of geohazard documented with photographs. The September 2014 extreme rainfall event in the Gargano Promontory was also analyzed to validate the forecasts issued by the Italian national early-warning system for rainfall-induced landslides (SANF), developed by the Research Institute for Geo-Hydrological Protection (IRPI) for the Italian national Department for Civil Protection (DPC). SANF compares rainfall measurements and forecasts with empirical rainfall thresholds for the prediction of landslide occurrence. SANF forecasts were compared to the documented landslides and discussed
    corecore