Dextrin-based nanomagnetogel: in vivo biodistribution and stability

The biodistribution profile of a new dextrin nanomagnetogel, which consists on -Fe2O3 superparamagnetic nanoparticles loaded within a polymeric matrix of modified dextrin, was studied in mice. The nanomagnetogel bear a monomodal size distribution profile (average diameter 110 nm) close to neutral surface charge and higher relaxivity (r2 = 215-248 mM-1s-1 and r2/r1 = 13-11) than those of commercial formulations (r2 = 160-177 mM-1s-1 and r2/r1 = 4-7). Also the observed blood half-life - approximately 4 hours - is superior to that of similar commercially available formulations, which remain few minutes in circulation. Pegylation resulted in 1.7 and 1.2-fold lower accumulation in the liver and spleen, respectively, within the first 24 h. Noteworthy, a good correlation was obtained between the amount of polymer (quantified by scintigraphy) in the spleen, 48 h after administration, and the amount of iron physically loaded through hydrophobic interactions (quantified by ICP) indicating the absence of iron leakage from the polymeric matrix. This study provides evidence on the in vivo stability of a self-assembled nanomagnetogel, a much relevant feature which is seldom reported in the literature.The authors thank the Project “strong>BioHealth - Biotechnology and Bioengineering approaches to improve health quality”, Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON.2 O Novo Norte), QREN, FEDER. The authors thank the Magnisense Corporation for providing a MIAplex Reader and CFGCG the EU COST TD1004 Action “Theragnostics Imaging and Therapy”. The authors thank Professor Cidália Botelho for the iron analysis by Atomic Absorbance Spectroscopy at the Oporto University, Chemical Engineering Department. C. Gonçalves, J. P. Silva, J. A. Martins, and M. F. M. Ferreira acknowledge FCT Portugal, for postdoc grants SFRH/BPD/70524/2010 and SFRH/BPD/64958/2009, sabbatical grant SFRH/BSAB/ 1328/2013 and PhD grant SFRH/BD/63994/2009, respectively

The aquaporin-3-inhibiting potential of polyoxotungstates

Polyoxometalates (POMs) are of increasing interest due to their proven anticancer activities. Aquaporins (AQPs) were found to be overexpressed in tumors bringing particular attention to their inhibitors as anticancer drugs. Herein, we report for the first time the ability of polyoxotungstates (POTs), such as of Wells-Dawson P2W18, P2W12, and P2W15, and Preyssler P5W30 structures, to affect aquaporin-3 (AQP3) activity and impair melanoma cell migration. The tested POTs were revealed to inhibit AQP3 function with different effects, with P2W18, P2W12, and P5W30 being the most potent (50% inhibitory concentration (IC50) = 0.8, 2.8, and 3.2 µM), and P2W15 being the weakest (IC50 > 100 µM). The selectivity of P2W18 toward AQP3 was confirmed in yeast cells transformed with human aquaglyceroporins. The effect of P2W12 and P2W18 on melanoma cells that highly express AQP3 revealed an impairment of cell migration between 55% and 65% after 24 h, indicating that the anticancer properties of these compounds may in part be due to the blockage of AQP3-mediated permeability. Altogether, our data revealed that P2W18 strongly affects AQP3 activity and cancer cell growth, unveiling its potential as an anticancer drug against tumors where AQP3 is highly expressed.Fundação para a Ciência e a Tecnologia (FCT) (PTDC/BTM-SAL/28977/2017, PTDC/MED-QUI/31721/2017, UID/DTP/04138/2019, UIDB/04326/2020, SFRH/BD/117586/2016. Austrian Science Fund (FWF) P27534, M2203info:eu-repo/semantics/publishedVersio

Nanostructured hollow tubes based on chitosan and alginate multilayers

The design and production of structures with nanometer-sized polymer fi lms based on layer-by-layer (LbL) are of particular interest for tissue engineering since they allow the precise control of physical and biochemical cues of implantable devices. In this work, a method is developed for the preparation of nanostructured hollow multilayers tubes combining LbL and template leaching. The aim is to produce hollow tubes based on polyelectrolyte multilayer fi lms with tuned physical-chemical properties and study their effects on cell behavior. The final tubular structures are characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), microscopy, swelling, and mechanical tests, including dynamic mechanical analysis (DMA) in physiological simulated conditions. It is found that more robust films could be produced upon chemical cross-linking with genipin. In particular, the mechanical properties confi rms the viscoelastic properties and a storage and young modulus about two times higher. The water uptake decreases from about 390% to 110% after the cross-linking. The biological performance is assessed in terms of cell adhesion, viability, and proliferation. The results obtained with the cross-linked tubes demonstrate that these are more suitable structures for cell adhesion and spreading. The results suggest the potential of these structures to boost the development of innovative tubular structures for tissue engineering approaches.The authors acknowledge the financial support by the Portuguese Foundation for Science and Technology (FCT) through the doctoral and post-doctoral grants with the reference numbers SFRH/BD/81372/2011 (J.M.S.), SFRH/BD/61390/2009 (C.A.C.), SFRH/BD/73119/2010 (I.N.), and SFRH/BPD/489948/2008 (P.S.), respectively, co-financed by the Operational Human Potential Program (POPH) developed under the scope of the National Strategic Reference Framework (QREN) from the European Social Fund (FSE). The authors would also like to acknowledge the project novel smart and biomimetic materials for innovative regenerative medicine approaches (Ref.: RL1 - ABMR - NORTE-01-0124-FEDER-000016) co-financed by North Portugal Regional Operational Programme (ON.2 - O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF)

Valorization of sugarcane by-products through synthesis of biogenic amorphous silica microspheres for sustainable cosmetics

Ashes from sugarcane by-product incineration were used to synthesize silica powders through alkaline hot extraction, followed by ethanol/acid precipitation or the sol–gel method. Both production methods allowed amorphous spherical silica microparticles with sizes ranging from 1–15 μm and 97% purity to be obtained. Water absorption ranged from 135–155 mL/100 g and 150–250 mL/100 g for precipitated silica and silica gel, respectively, while oil absorption ranged from 305 to 390 and from 250 to 350 mL/100 g. The precipitation with ethanol allowed the recovery of 178 g silica/kg ash, with a lab process cost of EUR 28.95/kg, while the sol-gel process showed a yield of 198 g silica/kg ash with a cost of EUR 10.89/kg. The experimental data suggest that ash from sugarcane by-products is a promising source to be converted into a competitive value-added product, minimizing the environmental impact of disposal problems.info:eu-repo/semantics/publishedVersio

Red light represses the photophysiology of the scleractinian coral Stylophora pistillata

Light spectrum plays a key role in the biology of symbiotic corals, with blue light resulting in higher coral growth, zooxanthellae density, chlorophyll a content and photosynthesis rates as compared to red light. However, it is still unclear whether these physiological processes are blue-enhanced or red-repressed. This study investigated the individual and combined effects of blue and red light on the health, zooxanthellae density, photophysiology and colouration of the scleractinian coral Stylophora pistillata over 6 weeks. Coral fragments were exposed to blue, red, and combined 50/50% blue red light, at two irradiance levels (128 and 256 μmol m−2 s−1). Light spectrum affected the health/survival, zooxanthellae density, and NDVI (a proxy for chlorophyll a content) of S. pistillata. Blue light resulted in highest survival rates, whereas red light resulted in low survival at 256 μmol m−2 s−1. Blue light also resulted in higher zooxanthellae densities compared to red light at 256 μmol m−2 s−1, and a higher NDVI compared to red and combined blue red light. Overall, our results suggest that red light negatively affects the health, survival, symbiont density and NDVI of S. pistillata, with a dominance of red over blue light for NDVI

Hydrolysates containing xylooligosaccharides produced by different strategies: structural characterization, antioxidant and prebiotic activities

" Available online 22 May 2022"This study explores the structural characterization, antioxidant and prebiotic activities of hydrolysates containing xylooligosaccharides (XOS) produced by different strategies: direct fermentation of beechwood xylan (FermBX) and enzymatic treatment of beechwood (EnzBX) and rice husk (EnzRH) xylans. EnzBX and EnzRH showed XOS with a backbone of (1 4)-linked-xylopyranosyl residues and branches of arabinose, galactose, and uronic acids. FermBX presented the highest content of total phenolic compounds (14 mg GAE/g) and flavonoids (0.6 mg QE/g), which may contribute to its antioxidant capacity 39.1 mol TE/g (DPPH), 45.7 mol TE/g (ABTS), and 79.9 mol Fe II/g (FRAP). The fermentation of hydrolysates decreased the abundance of microorganisms associated with intestinal diseases from Eubacteriales, Desulfovibrionales and Methanobacteriales orders, while stimulating the growth of organisms belonging to Bacteroides, Megamonas and Limosilactobacillus genera. The production of short-chain fatty acids, ammonia, and CO2 suggested the prebiotic potential. In conclusion, hydrolysates without previous purification and obtained from non-chemical approaches demonstrated promising biological activities for further food applications.This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) – Finance Code 001; by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) – Grant numbers 423285/2018-1 and 304857/2018-1; by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit; by the BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 – Programa Operacional Regional do Norte; by the COMPETE 2020 (POCI-01-0145- FEDER-006684); by the FoSynBio (POCI-01-0145-FEDER-029549); and LAQV/REQUIMTE (UIDB/50006/2020, UIDP/50006/2020) through national founds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement. GG acknowledges the Universidade Federal do Rio Grande for the financial support from Postgraduate Student Mobility Program (PROPESP/FURG). BC, CA, and SPS acknowledge their grants (SFRH/BD/132324/2017, 2020.00293 CEECIND, and SFRH/BD/136471/2018) from FCT. LB also acknowledge FCT for the junior research contract (CEECIND/03280/2020). EC thanks the research contract (CDL-CTTRI-88-ARH/2018 – REF. 049-88-ARH/2018) funded by national funds (OE), through FCT, in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19.info:eu-repo/semantics/publishedVersio

Behavioural stress responses predict environmental perception in European sea bass (Dicentrarchus labrax)

Individual variation in the response to environmental challenges depends partly on innate reaction norms, partly on experience-based cognitive/emotional evaluations that individuals make of the situation. The goal of this study was to investigate whether pre-existing differences in behaviour predict the outcome of such assessment of environmental cues, using a conditioned place preference/avoidance (CPP/CPA) paradigm. A comparative vertebrate model (European sea bass, Dicentrarchus labrax) was used, and ninety juvenile individuals were initially screened for behavioural reactivity using a net restraining test. Thereafter each individual was tested in a choice tank using net chasing as aversive stimulus or exposure to familiar conspecifics as appetitive stimulus in the preferred or non preferred side respectively (called hereafter stimulation side). Locomotor behaviour (i.e. time spent, distance travelled and swimming speed in each tank side) of each individual was recorded and analysed with video software. The results showed that fish which were previously exposed to appetitive stimulus increased significantly the time spent on the stimulation side, while aversive stimulus led to a strong decrease in time spent on the stimulation side. Moreover, this study showed clearly that proactive fish were characterised by a stronger preference for the social stimulus and when placed in a putative aversive environment showed a lower physiological stress responses than reactive fish. In conclusion, this study showed for the first time in sea bass, that the CPP/CPA paradigm can be used to assess the valence (positive vs. negative) that fish attribute to different stimuli and that individual behavioural traits is predictive of how stimuli are perceived and thus of the magnitude of preference or avoidance behaviour.European Commission [265957]; Portuguese Fundacao para a Ciencia e Tecnologia (FCT) [FRH/BPD/72952/2010]; FCT [SFRH/BD/80029/2011

Absorption of bioactive peptides following collagen hydrolysate intake: a randomized, double-blind crossover study in healthy individuals

BackgroundCollagen hydrolysates (CH) in functional foods and supplements are dietary sources of amino acids (AAs) and di-and tripeptides linked to various health benefits. This study aimed to investigate the single-dose bioavailability of skin- and hide-derived CH from fish, porcine and bovine origin with different molecular weights (bovine 2,000 and 5,000 Da).MethodsA randomized, double-blind crossover clinical study was performed with healthy volunteers assessing the plasma concentration of free and peptide-bound hydroxyproline (Hyp) as well as selected peptides reported to be abundantly present in collagen.ResultsThe pharmacokinetic endpoints demonstrated comparable uptake of free Hyp from all CH. A higher amount of total compared to free Hyp indicated the uptake of substantial amounts of Hyp-containing di- or tripeptides.ConclusionIndependently of source and molecular weight, all CH yielded relevant plasma concentrations of the investigated metabolites. Larger studies are needed to estimate an ideal level of selected circulating metabolites needed to trigger distinct physiological reactions in target tissues

Antigenic response to CT-P13 and infliximab originator in inflammatory bowel disease patients shows similar epitope recognition

Funding Information: Declaration of personal interests: JG received consultancy fees and/or research support from Pfizer, Merck, Biogen, Celltrion, and Samsung Bioepis. TD received fees for scientific advice and/or research support from Pfizer/Hospira, Amgen, MSD, Biogen, Roche, and Samsung Bioepis. IR was the lead investigator in a MSD sponsored prospective observational study, consultant/speaker at scientific meetings sponsored by MSD, AbbVie, Falk Ferring, Janssen, and received support to participate in scientific meetings from MSD, AbbVie, Falk, Ferring, Norgine, Hospira, Pharmakern, Janssen. JEF received unrestricted research grants or acted as a speaker for AbbVie, Ache, Amgen, Biogen, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB. PLL has been a speaker and/or advisory board member: Abb-Vie, EGIS, Falk Pharma GmbH, Ferring, Genetech, Jansen, Kyowa Hakko Kirin Pharma, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka Pharma, Pharmacosmos, Pfizer, Roche, Shire and Takeda and has received unrestricted research grant: AbbVie, MSD, and Pfizer. Funding Information: Declaration of personal interests: JG received consultancy fees and/or research support from Pfizer, Merck, Biogen, Celltrion, and Samsung Bioepis. TD received fees for scientific advice and/or research support from Pfizer/Hospira, Amgen, MSD, Biogen, Roche, and Samsung Bioepis. IR was the lead investigator in a MSD sponsored prospective observational study, consultant/speaker at scientific meetings sponsored by MSD, AbbVie, Falk Ferring, Janssen, and received support to participate in scientific meetings from MSD, AbbVie, Falk, Ferring, Norgine, Hospira, Pharmakern, Janssen. JEF received unrestricted research grants or acted as a speaker for AbbVie, Ache, Amgen, Biogen, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB. PLL has been a speaker and/or advisory board member: AbbVie, EGIS, Falk Pharma GmbH, Ferring, Genetech, Jansen, Kyowa Hakko Kirin Pharma, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka Pharma, Pharmacosmos, Pfizer, Roche, Shire and Takeda and has received unrestricted research grant: AbbVie, MSD, and Pfizer. Declaration of funding interests: This work was supported by grants from Fundação para a Ciência e Tecnologia, HIVERA ERA-NET HIVERA/0002/2013 and PTDC/QEQ-MED/4412/2014 to J.G. Funding Information: Declaration of funding interests: This work was supported by grants from Fundac©ão para a Ciência e Tecnologia, HIVERA ERA-NET HIVERA/0002/2013 and PTDC/QEQ-MED/4412/2014 to J.G. Publisher Copyright: © 2018 John Wiley & Sons LtdAim: To test the cross-immunogenicity of anti-CT-P13 IBD patients’ sera to CT-P13/infliximab originator and the comparative antigenicity evoked by CT-P13/infliximab originator sera. Methods: Sera of patients with IBD with measurable anti-CT-P13 antibodies were tested for their cross-reactivity to 5 batches of infliximab originator and CT-P13. Anti-drug antibody positive sera from treated patients were used to compare antigenic epitopes. Results: All 42 anti-CT-P13 and 37 anti-infliximab originator IBD sera were cross-reactive with infliximab originator and CT-P13 respectively. Concentration of anti-drug antibodies against infliximab originator or CT-P13 were strongly correlated both for IgG1 and IgG4 (P < 0.001). Anti-CT-P13 sera of patients with IBD (n = 32) exerted similar functional inhibition on CT-P13 or infliximab originator TNF binding capacity and showed reduced binding to CT-P13 in the presence of five different batches of CT-P13 and infliximab originator. Anti-CT-P13 and anti-infliximab originator IBD sera selectively enriched phage-peptides from the VH (CDR1 and CDR3) and VL domains (CDR2 and CDR3) of infliximab. Sera reactivity detected major infliximab epitopes in these regions of infliximab in 60%-79% of patients, and no significant differences were identified between CT-P13 and infliximab originator immunogenic sera. Minor epitopes were localised in framework regions of infliximab with reduced antibody reactivity shown, in 30%-50% of patients. Monoclonal antibodies derived from naïve individuals and ADA-positive IBD patients treated with CT-P13 provided comparable epitope specificity to five different batches of CT-P13 and infliximab originator. Conclusions: These results strongly support a similar antigenic profile for infliximab originator and CT-P13, and point toward a safe switching between the two drugs in anti-drug antibody negative patients.publishersversionpublishe

Linking Fearfulness and Coping Styles in Fish

Consistent individual differences in cognitive appraisal and emotional reactivity, including fearfulness, are important personality traits in humans, non-human mammals, and birds. Comparative studies on teleost fishes support the existence of coping styles and behavioral syndromes also in poikilothermic animals. The functionalist approach to emotions hold that emotions have evolved to ensure appropriate behavioral responses to dangerous or rewarding stimuli. Little information is however available on how evolutionary widespread these putative links between personality and the expression of emotional or affective states such as fear are. Here we disclose that individual variation in coping style predicts fear responses in Nile tilapia Oreochromis niloticus, using the principle of avoidance learning. Fish previously screened for coping style were given the possibility to escape a signalled aversive stimulus. Fearful individuals showed a range of typically reactive traits such as slow recovery of feed intake in a novel environment, neophobia, and high post-stress cortisol levels. Hence, emotional reactivity and appraisal would appear to be an essential component of animal personality in species distributed throughout the vertebrate subphylum