Factors Influencing the Surface Functionalization of Citrate Stabilized Gold Nanoparticles with Cysteamine, 3-Mercaptopropionic Acid or l -Selenocystine for Sensor Applications

Thiols and selenides bind to the surface of gold nanoparticles (AuNPs) and thus provide suitable platforms for the fabrication of sensors. However, the co-existence of adsorbed citrate on the surface of the nanoparticles can influence their functionalization behavior and potentially their sensing performance measured by the extent of particle aggregation. In this study, the functionalization of purchased (7.3 ± 1.2 nm) and in-house prepared AuNPs (13.8 ± 1.2 nm), under the same experimental conditions with either cysteamine (Cys), 3-mercaptopropionic acid (3-MPA), or l-selenocystine (SeCyst) was investigated. 1H-NMR measurements showed distinct citrate signatures on the in-house synthesized citrate-stabilized AuNPs, while no citrate signals were detected on the purchased AuNPs other than evidence of the presence of α-ketoglutaric acid. Carboxylate-containing species attributed to either citrate or α-ketoglutaric acid were identified in all functionalized AuNPs. ATR-FTIR spectroscopy confirmed the functionalization of AuNPs with Cys and 3-MPA, and energy dispersive X-ray (EDX) spectroscopy measurements suggested the formation of SeCyst functionalized AuNPs. Co-adsorption rather than displacement by the functionalizing agents and carboxylate-containing molecules was indicated, which for Cys and SeCyst functionalized AuNPs was also the aggregation limiting factor. In contrast, the behavior of 3-MPA functionalized AuNPs could be attributed to electrostatic repulsions between the functionalized groups

Solid lipid nanoparticles and nanostructured lipid carriers of dual functionality at emulsion interfaces. Part II:active carrying/delivery functionality

The utilisation of lipid nanostructures that can in tandem act as Pickering emulsion stabilisers and as active carrier/delivery systems, could potentially enable the development of liquid (emulsion-based) formulations with the capacity for multi-active encapsulation and delivery. Part I of this work focused on the first aspect of this two-fold functionality by investigating the capacity of both solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) to act as effective Pickering particles in o/w emulsions. Herein, attention shifts to the secondary functionality, with part II of this study assessing both SLNs and NLCs in terms of their capacity to act as carriers and release regulators for curcumin, a model hydrophobic active. The previously established Pickering functionality and physical properties in terms of particle size, zeta potential and interfacial tension of the lipid particles remained unaffected after encapsulation of curcumin. In emulsions, loss of crystalline (solid lipid) matter and particle interfacial presence were specifically investigated, as these aspects can impact upon the particles’ active carrying and delivery performance. Low solid matter losses were recorded for all emulsions (ranging between 0% and 15%), with increasing liquid lipid fraction in the particles (SLNs to NLCs) resulting in relatively higher depletion of crystallinity. Removal of unadsorbed surfactant (remnant from the particle formation processing step) prior to emulsification led to higher particle interfacial occupancy. Despite said changes, the lipid particles’ curcumin carrying capacity, expressed as encapsulation efficiency and loading capacity, did not differ between an emulsion and dispersion setting. Although the active carrying capacity was retained, it was shown that the presence of the particles at the emulsion interfaces affects the curcumin release rate. Partial migration of curcumin to the oil droplet and creation of an additional release-inducing potential to the particles in close proximity to the droplet interface are proposed to be responsible for the overall faster active expulsion. What is more, the curcumin release profile from either SLNs or NLCs (also) stabilising an emulsion microstructure, was shown to persist after storage; either storage of the particles (up to 4 months) prior to emulsification, or storage of emulsions (up to 3 months) stabilised by ‘freshly’ formed lipid particles. Overall, the present study provides evidence that the two-fold functionality of the lipid particles can be indeed realised, markedly demonstrating that their concurrency does not compromise one another

18 alpha-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures

Aims: Proteasomes are constituents of the cellular proteolytic networks that maintain protein homeostasis through regulated proteolysis of normal and abnormal (in any way) proteins. Genetically mediated proteasome activation in multicellular organisms has been shown to promote longevity and to exert protein antiaggregation activity. In this study, we investigate whether compound-mediated proteasome activation is feasible in a multicellular organism and we dissect the effects of such approach in aging and Alzheimer's disease (AD) progression. Results: Feeding of wild-type Caenorhabditis elegans with 18 alpha-glycyrrhetinic acid (18 alpha-GA; a previously shown proteasome activator in cell culture) results in enhanced levels of proteasome activities that lead to a skinhead-1- and proteasomeactivation-dependent life span extension. The elevated proteasome function confers lower paralysis rates in various AD nematode models accompanied by decreased A beta deposits, thus ultimately decelerating the progression of AD phenotype. More importantly, similar positive results are also delivered when human and murine cells of nervous origin are subjected to 18 alpha-GA treatment. Innovation: This is the first report of the use of 18 alpha-GA, a diet-derived compound as prolongevity and antiaggregation factor in the context of a multicellular organism. Conclusion: Our results suggest that proteasome activation with downstream positive outcomes on aging and AD, an aggregation-related disease, is feasible in a nongenetic manipulation manner in a multicellular organism. Moreover, they unveil the need for identification of antiaging and antiamyloidogenic compounds among the nutrients found in our normal diet.Peer reviewe

Solid lipid nanoparticles and nanostructured lipid carriers of dual functionality at emulsion interfaces. Part I : Pickering stabilisation functionality

Solid lipid nanoparticles and nanostructured lipid carriers are two types of lipid nanoparticulate systems, that have been primarily studied for their capability to function as active carriers, and only more recently utilised in Pickering emulsion stabilisation. Unveiling the factors that impact upon the lipid particle characteristics related to their Pickering functionality could enable the development of a liquid formulation with tailored microstructure and potentially the capacity to display a two-fold performance. In part I, this work investigates how certain formulation characteristics, namely solid-to-liquid lipid mass ratio and presence of unadsorbed surfactant in the aqueous carrier phase, affect the structural properties of the lipid particles, and in turn how these influence their Pickering stabilisation capacity. The effect of the formulation parameters was assessed in terms of the wettability and physicochemical properties of the lipid particles, including particle size, crystallinity and interfacial behaviour. Lipid particles fabricated with higher liquid lipid content (70% w/w) were shown to be more hydrophilic and have lower surfactant decoration at their surface compared to particles containing lower or no liquid lipid in their crystalline matrix. The emulsion stabilisation ability through a Pickering mechanism was confirmed for all types of lipid particles using polarised microscopy. Increasing liquid lipid content and removal of excess surfactant did not compromise the particle stabilisation capacity, though emulsion droplets of larger sizes were initially acquired in the latter case. The particle-stabilised emulsions maintained their physical integrity, with particles retaining close association with the emulsion interface over a storage period of 12 weeks

A Survey of Dentists in the Management of Dentine Hypersensitivity: A Questionnaire-based Study.

OBJECTIVE: Previous studies have indicated that dentists may be uncertain about the etiology, diagnosis, and effective management of dentine sensitivity/dentine hypersensitivity (DH).: The purpose of the present study was to evaluate the knowledge and understanding of Greece-based dental professionals in treating DH.: MATERIALS AND METHODS: A 26-item questionnaire was sent to a representative sample of Greek dentists. RESULTS: Two hundred thirty questionnaires were originally provided to the participants and of the 210 questionnaires that were returned, 191 questionnaires (90 M; 86 F; mean age 36.26 years [standard deviation: 11.34]) were included for analysis, a response rate of 83% was observed. 39.8% of dentists indicated that 1 in 10 of their patients experienced discomfort from DH with 76.4% of dentists indicating that their patients initiated the conversation on DH. In contrast, 44% of the dentists indicated that they initiated the relevant conversation. 34.9% of dentists indicated that the duration of discomfort lasted up to 3 weeks and 76.4% indicated that DH had an impact on their patients' quality of life. Incorrect tooth brushing was considered to be a major etiological factor (68.6%) with "air blast" (37.3%) and "probing" (15%) as the main methods for identification. 83.6% of dentists indicated that they were confident in recommending over-the-counter products for home use. CONCLUSION: The results of this study suggest that in terms of knowledge and understanding of DH, there is still confusion concerning some aspects of the diagnosis and management of the condition

Analysis of data collected in the European Society for Blood and Marrow Transplantation (EBMT) Registry on a cohort of lymphoma patients receiving plerixafor

Plerixafor + granulocyte-colony stimulating factor (G-CSF) is administered to patients with lymphoma who are poor mobilizers of hematopoietic stem cells (HSCs) in Europe. This international, multicenter, non-interventional registry study (NCT01362972) evaluated long-term follow-up of patients with lymphoma who received plerixafor for HSC mobilization versus other mobilization methods. Propensity score matching was conducted to balance baseline characteristics between comparison groups. The following mobilization regimens were compared: G-CSF + plerixafor (G + P) versus G-CSF alone; G + P versus G-CSF + chemotherapy (G + C); and G-CSF + plerixafor + chemotherapy (G + P + C) versus G + C. The primary outcomes were progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR). Overall, 313/3749 (8.3%) eligible patients were mobilized with plerixafor-containing regimens. After propensity score matching, 70 versus 36 patients were matched in the G + P versus G-CSF alone cohort, 124 versus 124 in the G + P versus G + C cohort, and 130 versus 130 in the G + P + C versus G + C cohort. For both PFS and OS, the upper bound of confidence interval for the hazard ratio was >1.3 for all comparisons, implying that non-inferiority was not demonstrated. No major differences in PFS, OS, and CIR were observed between the plerixafor and comparison groups

Genetic prediction of ICU hospitalization and mortality in COVID-19 patients using artificial neural networks

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we identified 5 critical variants associated with severe COVID-19: rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and rs414628 (CFHR1). Using age, gender and presence or absence of each variant, we developed an ANN predicting morbidity and mortality in 89.47% of the examined population. Furthermore, THBD and C3a levels were significantly increased in severe COVID-19 patients and those harbouring relevant variants. Thus, we reveal for the first time an ANN accurately predicting ICU hospitalization and death in COVID-19 patients, based on genetic variants in complement genes, age and gender. Importantly, we confirm that genetic dysregulation is associated with impaired complement phenotype

Minocycline Inhibition of Monocyte Activation Correlates with Neuronal Protection in SIV NeuroAIDS

Background: Minocycline is a tetracycline antibiotic that has been proposed as a potential conjunctive therapy for HIV-1 associated cognitive disorders. Precise mechanism(s) of minocycline’s functions are not well defined. Methods: Fourteen rhesus macaques were SIV infected and neuronal metabolites measured by proton magnetic resonance spectroscopy (1H MRS). Seven received minocycline (4 mg/kg) daily starting at day 28 post-infection (pi). Monocyte expansion and activation were assessed by flow cytometry, cell traffic to lymph nodes, CD16 regulation, viral replication, and cytokine production were studied. Results: Minocycline treatment decreased plasma virus and pro-inflammatory CD14+CD16+ and CD14loCD16+ monocytes, and reduced their expression of CD11b, CD163, CD64, CCR2 and HLA-DR. There was reduced recruitment of monocyte/ macrophages and productively infected cells in axillary lymph nodes. There was an inverse correlation between brain NAA/ Cr (neuronal injury) and circulating CD14+CD16+ and CD14loCD16+ monocytes. Minocycline treatment in vitro reduced SIV replication CD16 expression on activated CD14+CD16+ monocytes, and IL-6 production by monocytes following LPS stimulation. Conclusion: Neuroprotective effects of minocycline are due in part to reduction of activated monocytes, monocyte traffic. Mechanisms for these effects include CD16 regulation, reduced viral replication, and inhibited immune activation. Citation: Campbell JH, Burdo TH, Autissier P, Bombardier JP, Westmoreland SV, et al. (2011) Minocycline Inhibition of Monocyte Activation Correlate

Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases : updated guidelines and recommendations from the EBMT autoimmune diseases working party (ADWP) and the joint accreditation committee of EBMT and ISCT (JACIE)

These updated EBMT guidelines review the clinical evidence, registry activity and mechanisms of action of haematopoietic stem cell transplantation (HSCT) in multiple sclerosis (MS) and other immune-mediated neurological diseases and provide recommendations for patient selection, transplant technique, follow-up and future development. The major focus is on autologous HSCT (aHSCT), used in MS for over two decades and currently the fastest growing indication for this treatment in Europe, with increasing evidence to support its use in highly active relapsing remitting MS failing to respond to disease modifying therapies. aHSCT may have a potential role in the treatment of the progressive forms of MS with a significant inflammatory component and other immune-mediated neurological diseases, including chronic inflammatory demyelinating polyneuropathy, neuromyelitis optica, myasthenia gravis and stiff person syndrome. Allogeneic HSCT should only be considered where potential risks are justified. Compared with other immunomodulatory treatments, HSCT is associated with greater short-term risks and requires close interspeciality collaboration between transplant physicians and neurologists with a special interest in these neurological conditions before, during and after treatment in accredited HSCT centres. Other experimental cell therapies are developmental for these diseases and patients should only be treated on clinical trials