Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy

Here, a novel strategy of formulating efficient polymeric carriers based on the already described INU-IMI-DETA for gene material whose structural, functional, and biological properties can be modulated and improved was successfully investigated. In particular, two novel derivatives of INU-IMI-DETA graft copolymer were synthesized by chemical functionalisation with epidermal growth factor (EGF) or polyethylenglycol (PEG), named INU-IMI-DETA-EGF and INU-IMI-DETA-PEG, respectively, in order to improve the performance of already described “inulin complex nanoaggregates” (ICONs). The latter were thus prepared by appropriately mixing the two copolymers, by varying each component from 0 to 100 wt% on the total mixture, named EP-ICONs. It was seen that the ability of the INU-IMI-DETA-EGF/INU-IMI-DETA-PEG polymeric mixture to complex siGL3 increases with the increase in the EGF-based component in the EP-ICONs and, for each sample, with the increase in the copolymer:siRNA weight ratio (R). On the other hand, the susceptibility of loaded siRNA towards RNase decreases with the increase in the pegylated component in the polymeric mixture. At all R values, the average size and the zeta potential values are suitable for escaping from the RES system and suitable for prolonged intravenous circulation. By means of biological characterisation, it was shown that MCF-7 cells are able to internalize mainly the siRNA-loaded into EGF-decorated complexes, with a significant difference from ICONs, confirming its targeting function. The targeting effect of EGF on EP-ICONs was further demonstrated by a competitive cell uptake study, i.e., after cell pre-treatment with EGF. Finally, it was shown that the complexes containing both EGF and PEG are capable of promoting the internalisation and therefore the transfection of siSUR, a siRNA acting against surviving mRNA, and to increase the sensitivity to an anticancer agent, such as doxorubicin.     

Vegetable Extracts and Nutrients Useful in the Recovery from Helicobacter pylori Infection: A Systematic Review on Clinical Trials

Helicobacter pylori (H. pylori) infections affect almost half of the world’s population, with gradually increasing incidence in developed countries. Eradication of H. pylori may provide significant benefits to the affected individual by healing a number of gastrointestinal and extra-digestive disorders. But due to increased microbial resistance and lack of patient adherence to the therapy, the eradication rate of H. pylori is below 80% with current pharmacological therapies. The usage of botanicals for their therapeutic purposes and medicinal properties have been increased in last decades. They can be use as alternative H. pylori treatments, especially against drug-resistant strains. Epidemiological studies have revealed that people with lower vegetable and micronutrient intake may be at increased risk of H. pylori infection. We have undertaken a review of clinical trials to evaluate the efficacy of vegetable extracts and micronutrients in patients with H. pylori. Various databases, such as Google Scholar, PubMed, Scopus, Web of Science, and the Cochrane Library, were searched for the articles published in English. A total of 24 clinical studies (15 for vegetable extracts and 9 for micronutrients) were selected to be reviewed and summarized in this article. Vegetable extracts (Broccoli sprouts, curcumin, Burdock complex, and Nigella sativa) and micronutrients (vitamin C and E) were not found to be as effective as single agents in H. pylori eradication, rather their efficacy synergized with conventional pharmacological therapies. Conversely, GutGard was found to be significantly effective as a single agent when compared to placebo control.     

Nanocomposite Polymer Electrolytes of Sodium Alginate and Montmorillonite Clay

Nanocomposite polymer electrolytes (NPEs) were synthesized using sodium alginate (Alg) and either sodium (SCa-3-Na⁺)- or lithium (SCa-3-Li⁺)-modified montmorillonite clays. The samples were characterized by structural, optical, and electrical properties. SCa-3-Na⁺ and SCa-3-Li⁺ clays’ X-ray structural analyses revealed peaks at 2θ = 7.2° and 6.7° that corresponded to the interlamellar distances of 12.3 and 12.8 Å, respectively. Alg-based NPEs X-ray diffractograms showed exfoliated structures for samples with low clay percentages. The increase of clay content promoted the formation of intercalated structures. Electrochemical Impedance Spectroscopy revealed that Alg-based NPEs with 5 wt% of SCa-3-Na⁺ clay presented the highest conductivity of 1.96 × 10⁻² S/cm², and Alg with 10 wt% of SCa-3-Li⁺ showed conductivity of 1.30 × 10⁻² S/cm², both measured at 70 °C. From UV-Vis spectroscopy, it was possible to infer that increasing concentration of clay promoted a decrease of the samples’ transmittance and, consequently, an increase of their reflectance.     

Neuroprotective Effects of Curcumin in Methamphetamine-Induced Toxicity

Curcumin (CUR), a natural polyphenol extracted from rhizome of the Curcuma longa L, has received great attention for its multiple potential health benefits as well as disease prevention. For instance, CUR protects against toxic agents acting on the human body, including the nervous system. In detail, CUR possesses, among others, strong effects as an autophagy activator. The present study indicates that CUR counteracts methamphetamine (METH) toxicity. Such a drug of abuse is toxic by disturbing the autophagy machinery. We profited from an unbiased, low variable cell context by using rat pheochromocytoma PC12 cell line. In such a system, a strong protection was exerted by CUR against METH toxicity. This was associated with increased autophagy flux, merging of autophagosomes with lysosomes and replenishment of autophagy vacuoles with LC3, which instead is moved out from the vacuoles by METH. This is expected to enable the autophagy machinery. In fact, while in METH-treated cells the autophagy substrates α-synuclein accumulates in the cytosol, CUR speeds up α-synuclein clearance. Under the effects of CUR LC3 penetrate in autophagy vacuoles to commit them to cell clearance and promotes the autophagy flux. The present data provide evidence that CUR counteracts the neurotoxic effects induced by METH by promoting autophagy.     

Terroir Effect on the Phenolic Composition and Chromatic Characteristics of Mencía/Jaen Monovarietal Wines: Bierzo D.O. (Spain) and Dão D.O. (Portugal)

‘Mencía’/‘Jaen’ it’s an important red grape variety, exclusive of the Iberian Peninsula, used in wine production namely in Bierzo D.O. and Dão D.O., respectively. This work evaluates the effect of the two different “terroirs” on the phenolic composition and chromatic characteristics of ‘Mencía’/‘Jaen’ monovarietal wines produced at an industrial scale in the same vintage. Using Principal Component Analysis (PCA), Partial Least Squares-Discrimination Analysis (PLS-DA), and Orthogonal PLS-DA (OPLS-DA) it was found that peonidin-3-coumaroylglucoside, petunidin-3-glucoside, malvidin-3-coumaroylglucoside, peonidin-3-glucoside, malvidin-3-acetylglucoside, malvidin-3-glucoside, and ferulic acid were the phenolic compounds with the highest differences between the two regions. PLS regression allowed to correlate the differences in lightness (L*) and redness (a*) of wines from ‘Jaen’ and ‘Mencía’ to differences in colored anthocyanins, polymeric pigments, total pigments, total anthocyanins, cyanidin-3-acetylglucoside, delphinidin-3-acetylglucoside, delphinidin-3-glucoside, peonidin-3-coumaroylglucoside, petunidin-3-glucoside and malvidin-3-glucoside in wines, and the colorless ferulic, caffeic, and coutaric acids, and ethyl caffeate. The wines a* values were more affected by colored anthocyanins, ferulic acid, total anthocyanins, delphinidin-3-acetylglucoside, delphinidin-3-glucoside and petunidin-3-acetylglucoside, and catechin. The positive influence of ferulic acid in the a* values and ferulic, caffeic, coutaric acids, and ethyl caffeate on the L* values can be due to the co-pigmentation phenomena. The higher dryness and lower temperatures during the September nights in this vintage might explain the differences observed in the anthocyanin content and chromatic characteristics of the wines.     

Adventitious isolation of a pseudorotaxane complex of a trans-bis(Hydroxymethylbenzo)-27-crown-9 pyridyl cryptand and a viologen

ABSTRACT

The adventitious isolation and crystal structure of a pseudorotaxane complex of a trans-substituted dibenzo-27-crown-9-based pyridyl cryptand (6) and N,N’-dimethyl-4,4?-bipyridinium bis(hexafluorophosphate) (5) are reported.     

Therapeutic Potential of Highly Selective A3 Adenosine Receptor Ligands in the Central and Peripheral Nervous System

Ligands of the G_i protein-coupled adenosine A₃ receptor (A₃R) are receiving increasing interest as attractive therapeutic tools for the treatment of a number of pathological conditions of the central and peripheral nervous systems (CNS and PNS, respectively). Their safe pharmacological profiles emerging from clinical trials on different pathologies (e.g., rheumatoid arthritis, psoriasis and fatty liver diseases) confer a realistic translational potential to these compounds, thus encouraging the investigation of highly selective agonists and antagonists of A₃R. The present review summarizes information on the effect of latest-generation A₃R ligands, not yet available in commerce, obtained by using different in vitro and in vivo models of various PNS- or CNS-related disorders. This review places particular focus on brain ischemia insults and colitis, where the prototypical A₃R agonist, Cl-IB-MECA, and antagonist, MRS1523, have been used in research studies as reference compounds to explore the effects of latest-generation ligands on this receptor. The advantages and weaknesses of these compounds in terms of therapeutic potential are discussed.     

Synthetic Cathinones: Recent Developments,Enantioselectivity Studies and Enantioseparation Methods

New psychoactive substances represent a public health threat since they are not controlled by international conventions, are easily accessible online and are sold as a legal alternative to illicit drugs. Among them, synthetic cathinones are widely abused due to their stimulant and hallucinogenic effects. To circumvent the law, new derivatives are clandestinely synthesized and, therefore, synthetic cathinones keep emerging on the drug market, with their chemical and toxicological properties still unknown. In this review, a literature assessment about synthetic cathinones is presented focusing on the recent developments, which include more than 50 derivatives since 2014. A summary of their toxicokinetic and toxicodynamic properties are also presented. Furthermore, synthetic cathinones are chiral compounds, meaning that they can exist as two enantiomeric forms which may present different biological and toxicological activities. To analyze the enantiomers, the development of enantiomeric resolution methods for synthetic cathinones is crucial. Many methods have been reported over the years that include mostly chromatographic and electromigration techniques, with liquid chromatography using chiral stationary phases being the technique of choice. This review intended to present an overview of enantioselectivity studies and enantioseparation analysis regarding synthetic cathinones, highlighting the relevance of chirality and current trends.     

Natural Polymers-Based Materials: A Contribution to a Greener Future

Natural polymers have emerged as promising candidates for the sustainable development of materials in areas ranging from food packaging and biomedicine to energy storage and electronics. In tandem, there is a growing interest in the design of advanced materials devised from naturally abundant and renewable feedstocks, in alignment with the principles of Green Chemistry and the 2030 Agenda for Sustainable Development. This review aims to highlight some examples of the research efforts conducted at the Research Team BioPol4fun, Innovation in BioPolymer-based Functional Materials and Bioactive Compounds, from the Portuguese Associate Laboratory CICECO–Aveiro Institute of Materials at the University of Aveiro, regarding the exploitation of natural polymers (and derivatives thereof) for the development of distinct sustainable biobased materials. In particular, focus will be given to the use of polysaccharides (cellulose, chitosan, pullulan, hyaluronic acid, fucoidan, alginate, and agar) and proteins (lysozyme and gelatin) for the assembly of composites, coatings, films, membranes, patches, nanosystems, and microneedles using environmentally friendly strategies, and to address their main domains of application.