Recent advances in smart biotechnology: Hydrogels and nanocarriers for tailored bioactive molecules depot

Over the past ten years, the global biopharmaceutical market has remarkably grown, with ten over the top twenty worldwide high performance medical treatment sales being biologics. Thus, biotech R&D (research and development) sector is becoming a key leading branch, with expanding revenues. Biotechnology offers considerable advantages compared to traditional therapeutic approaches, such as reducing side effects, specific treatments, higher patient compliance and therefore more effective treatments leading to lower healthcare costs. Within this sector, smart nanotechnology and colloidal self-assembling systems represent pivotal tools able to modulate the delivery of therapeutics. A comprehensive understanding of the processes involved in the self assembly of the colloidal structures discussed therein is essential for the development of relevant biomedical applications. In this review we report the most promising and best performing platforms for specific classes of bioactive molecules and related target, spanning from siRNAs, gene/plasmids, proteins/growth factors, small synthetic therapeutics and bioimaging probes.Istituto Italiano di Tecnologia (IIT)COST Action [CA 15107]People Program (Marie Curie Actions) of the European Union's Seventh Framework Program under REA [606713 BIBAFOODS]Portuguese Foundation for Science and Technology (FCT) [PTDC/AGR-TEC/4814/2014, IF/01005/2014]Fundacao para a Ciencia e Tecnologia [SFRH/BPD/99982/2014]Danish National Research Foundation [DNRF 122]Villum Foundation [9301]Italian Ministry of Instruction, University and Research (MIUR), PRIN [20109PLMH2]"Fondazione Beneficentia Stiftung" VaduzFondo di Ateneo FRAFRAinfo:eu-repo/semantics/publishedVersio

The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing

Kinetoplastid parasites—trypanosomes and leishmanias—infect millions of humans and cause economically devastating diseases of livestock, and the few existing drugs have serious deficiencies. Benzoxaborole-based compounds are very promising potential novel anti-trypanosomal therapies, with candidates already in human and animal clinical trials. We investigated the mechanism of action of several benzoxaboroles, including AN7973, an early candidate for veterinary trypanosomosis. In all kinetoplastids, transcription is polycistronic. Individual mRNA 5'-ends are created by trans splicing of a short leader sequence, with coupled polyadenylation of the preceding mRNA. Treatment of Trypanosoma brucei with AN7973 inhibited trans splicing within 1h, as judged by loss of the Y-structure splicing intermediate, reduced levels of mRNA, and accumulation of peri-nuclear granules. Methylation of the spliced leader precursor RNA was not affected, but more prolonged AN7973 treatment caused an increase in S-adenosyl methionine and methylated lysine. Together, the results indicate that mRNA processing is a primary target of AN7973. Polyadenylation is required for kinetoplastid trans splicing, and the EC50 for AN7973 in T. brucei was increased three-fold by over-expression of the T. brucei cleavage and polyadenylation factor CPSF3, identifying CPSF3 as a potential molecular target. Molecular modeling results suggested that inhibition of CPSF3 by AN7973 is feasible. Our results thus chemically validate mRNA processing as a viable drug target in trypanosomes. Several other benzoxaboroles showed metabolomic and splicing effects that were similar to those of AN7973, identifying splicing inhibition as a common mode of action and suggesting that it might be linked to subsequent changes in methylated metabolites. Granule formation, splicing inhibition and resistance after CPSF3 expression did not, however, always correlate and prolonged selection of trypanosomes in AN7973 resulted in only 1.5-fold resistance. It is therefore possible that the modes of action of oxaboroles that target trypanosome mRNA processing might extend beyond CPSF3 inhibition

Mechanism of action of drugs with activity against multicellular parasites

Parasiticides have been the most valuable weapons to combat parasites for almost half a century, constituting more than 50 % of veterinary pharmaceuticals and a good part of the products destined for human health. However, in many parts of the world, parasites develop resistance to these drugs, and it is now a major health problem. One way to avoid this inconvenience is the in-depth knowledge of its mechanisms of action, which will allow a more appropriate use. This work is a review of the different physiological aspects of parasite species and an explanation of the different mechanisms of action of antiparasitic agents. Once these drugs are ingested or absorbed by parasites the agents come into contact with the parasites structures, and according to the drug's properties it will define the antiparasitic activity either by altering tegument, carbohydrates, protein and lipid metabolism, or motility of the multicellular parasites.Facultad de Ciencias VeterinariasConsejo Nacional de Investigaciones Científicas y Técnica

Short-Term Pre-Harvest UV-B Supplement Enhances the Polyphenol Content and Antioxidant Capacity of Ocimum basilicum Leaves during Storage

Ocimum basilicum (basil) leaves are rich in polyphenols, conferring them a high antioxidant activity. The application of UV-B can be used to maintain the post-harvest nutraceutical quality of basil leaves. We aimed to investigate the effects of pre-harvest UV-B application on polyphenolic and pigment contents, antioxidant capacity, and the visual quality of basil stored leaves. We also evaluated the applicability of the non-invasive Dualex® for monitoring the accumulation of leaf epidermal phenolics (Flav Index). After exposing plants to white light (control) and to supplemental UV-B radiation for 4 d, the leaves were harvested and stored for 7d (TS7). The UV-B leaves showed both a higher phenolic content and antioxidant capacity than the controls at TS7. In addition, the correlations between the Flav Index and phenolic content demonstrated that Dualex® can reliably assess the content of epidermal phenolics, thus confirming its promising utilization as a non-destructive method for monitoring the phytochemical quality of O. basilicum leaves. In conclusion, a pre-harvesting UV-B application may be a tool for enhancing the content of polyphenols and the antioxidant potential of basil stored leaves without detrimental effects on their visual quality. These results are important considering the nutraceutical value of this plant and its wide commercial distribution

Could hair-lichens of high-elevation forests help detect the impact of global change in the Alps?

Climate change and the anthropic emission of pollutants are likely to have an accelerated impact in high-elevation mountain areas. This phenomenon could have negative consequences on alpine habitats and for species of conservation in relative proximity to dense human populations. This premise implies that the crucial task is in the early detection of warning signals of ecological changes. In alpine landscapes, high-elevation forests provide a unique environment for taking full advantage of epiphytic lichens as sensitive indicators of climate change and air pollution. This literature reviewis intended to provide a starting point for developing practical biomonitoring tools that elucidate the potential of hair-lichens, associated with high-elevation forests, as ecological indicators of global change in the European Alps. We found support for the practical use of hair-lichens to detect the impact of climate change and nitrogen pollution in high-elevation forest habitats. The use of these organisms as ecological indicators presents an opportunity to expand monitoring activities and develop predictive tools that support decisions on how to mitigate the effects of global change in the Alps

Exopolysaccharides from vaginal lactobacilli modulate microbial biofilms

Background: Exopolysaccharides (EPS) secreted by beneficial lactobacilli exert a plethora of positive activities, but little is known about their effects on biofilms of opportunistic vaginal pathogens and especially on biofilms of lactobacilli themselves. Here, the EPS produced by six vaginal lactobacilli, belonging to Lactobacillus crispatus (BC1, BC4, BC5) and Lactobacillus gasseri (BC9, BC12, BC14) species were isolated from cultural supernatants and lyophilized. Results: Lactobacillus EPS were chemically characterized in terms of monosaccharide composition by liquid chromatography (LC) analysis coupled to UV and mass spectrometry (MS) detection. Moreover, the ability of EPS (0.1, 0.5, 1 mg/mL) to stimulate the biofilm formation of lactobacilli and to inhibit the formation of pathogens’ biofilms was evaluated by crystal violet (CV) staining and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Isolated EPS (yields 133–426 mg/L) were heteropolysaccharides mainly composed of d-mannose (40–52%) and d-glucose (11–30%). For the first time we demonstrated that Lactobacillus EPS were able to stimulate in a dose-dependent manner (p < 0.05) the formation of biofilms of ten strains belonging to L. crispatus, L. gasseri and Limosilactobacillus vaginalis species, in terms of cell viability (84–282% increase at 1 mg/mL) and especially biofilm biomass (40–195% increase at 1 mg/mL), quantified with MTT assay and CV staining, respectively. EPS released from L. crispatus and L. gasseri were found to better stimulate the biofilms of the same producer species rather than that of other species, including producing strains themselves and other strains. Conversely, the biofilm formation of bacterial (Escherichia coli, Staphylococcus spp., Enterococcus spp. and Streptococcus agalactiae) and fungal (Candida spp.) pathogens was inhibited. The anti-biofilm activity was dose-dependent and was more marked for L. gasseri-derived EPS (inhibition up to 86%, 70%, and 58% at 1 mg/mL, 0.5 mg/mL, and 0.1 mg/mL, respectively), whilst L. crispatus-derived EPS resulted overall less efficient (inhibition up to 58% at 1 mg/mL and 40% at 0.5 mg/mL) (p < 0.05). Conclusions: Lactobacilli-derived EPS favour the biofilm formation of lactobacilli preventing, at the same time, that of opportunistic pathogens. These results support the possible employment of EPS as postbiotics in medicine as a therapeutic/preventive strategy to counteract vaginal infections

Effect of the solvent on the conformation of monocrotaline as determined by isotropic and anisotropic NMR parameters.

The conformation in solution of monocrotaline, a pyrrolizidine alkaloid presenting an eleven-membered macrocyclic diester ring, has been investigated using a combination of isotropic and anisotropic NMR parameters measured in four solvents of different polarity (D2 O, DMSO-d6 , CDCl3 , and C6 D6 ). Anisotropic NMR parameters were measured in different alignment media, based on their compatibility with the solvent of interest: cromoglycate liquid crystal solution was used for D2 O, while a PMMA polymer gel was chosen for CDCl3 and C6 D6 , and a poly-HEMA gel for DMSO-d6 . Whereas the pyrrolizidine ring shows an E6 exo-puckered conformation in all of the solvents, the macrocyclic eleven-membered ring adopts different populations of syn-parallel and anti-parallel relative orientation of the carbonyl groups according to the polarity of the solvent

Patterns of traumatic brain injury and six-month neuropsychological outcomes in Uganda

Abstract Background Traumatic brain injuries in Uganda are on the increase, however little is known about the neuropsychological outcomes in survivors. This study characterized patients with traumatic brain injury (TBI) and the associated six-month neuropsychological outcomes in a Ugandan tertiary hospital. Methods Patients admitted at Mulago Hospital with head injury from November 2015 to April 2016 were prospectively enrolled during admission and followed up at six months after discharge to assess cognition, posttraumatic stress symptoms (PTSS), depression symptoms and physical disability. The outcomes were compared to a non-head-injury group recruited from among the caretakers, siblings and neighbours of the patients with age and sex entered as covariates. Results One hundred and seventy-one patients and 145 non-head injury participants were enrolled. The age range for the whole sample was 1 to 69 years with the non-head injury group being older (mean age (SD) 33.34 (13.35) vs 29.34 (14.13) years of age, p = 0.01). Overall, motorcycle crashes (36/171, 38.6%) and being hit by an object (58/171, 33.9%) were the leading causes of TBI. Head injury from falls occurred more frequently in children < 18 years (13.8% vs 2.8%, p = 0.03). In adults 18 years and older, patients had higher rates of neurocognitive impairment (28.4% vs 6.6%, p < 0.0001), PTSS (43.9% vs 7.9%, p < 0.0001), depression symptoms (55.4% vs 10%, p < 0.0001) and physical disability (7.2% vs 0%, p = 0.002). Lower Glasgow Coma Score (GCS) on admission was associated with neurocognitive impairment (11.6 vs 13.1, p = 0.04) and physical disability (10 vs 12.9, p = 0.01) six months later. Conclusion This first such study in the East-African region shows that depth of coma on admission in TBI is associated with neurocognitive impairment and physical disability.https://deepblue.lib.umich.edu/bitstream/2027.42/147735/1/12883_2019_Article_1246.pd

The Singular Evolution of Olea Genome Structure

The current view of plant genome evolution proposes that genome size has mainly been determined by polyploidisation and amplification/loss of transposons, with a minor role played by other repeated sequences, such as tandem repeats. In cultivated olive (Olea europaea subsp. europaea var. europaea), available data suggest a singular model of genome evolution, in which a massive expansion of tandem-repeated sequences accompanied changes in nuclear architecture. This peculiar scenario highlights the importance of focusing on Olea genus evolution, to shed light on mechanisms that led to its present genomic structure. Next-generation sequencing technologies, bioinformatics and in situ hybridisation were applied to study the genomic structure of five related Olea taxa, which originated at different times from their last common ancestor. On average, repetitive DNA in the Olea taxa ranged from ~59% to ~73% of the total genome, showing remarkable differences in terms of composition. Among repeats, we identified 11 major families of tandem repeats, with different abundances in the analysed taxa, five of which were novel discoveries. Interestingly, overall tandem repeat abundance was inversely correlated to that of retrotransposons. This trend might imply a competition in the proliferation of these repeat classes. Indeed, O. paniculata, the species closest to the Olea common ancestor, showed very few tandem-repeated sequences, while it was rich in long terminal repeat retrotransposons, suggesting that the amplification of tandem repeats occurred after its divergence from the Olea ancestor. Furthermore, some tandem repeats were physically localised in closely related O. europaea subspecies (i.e., cultivated olive and O. europaea subsp. cuspidata), which showed a significant difference in tandem repeats abundance. For 4 tandem repeats families, a similar number of hybridisation signals were observed in both subspecies, apparently indicating that, after their dissemination throughout the olive genome, these tandem repeats families differentially amplified maintaining the same positions in each genome. Overall, our research identified the temporal dynamics shaping genome structure during Olea speciation, which represented a singular model of genome evolution in higher plants