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Environmental enteric dysfunction (EED) is a condition associated with malnutrition that can progress to malabsorption and villous atrophy. Severe EED results in linear growth stunting, slowed neurocognitive development, and unresponsiveness to oral vaccines. Prenatal exposure to malnutrition and breast feeding by malnourished mothers replicates EED. Pups are characterized by deprivation of secretory IgA (SIgA) and altered development of the gut immune system and microbiota. Extracellular ATP (eATP) released by microbiota limits T follicular helper (Tfh) cell activity and SIgA generation in Peyer's patches (PPs). Administration of a live biotherapeutic releasing the ATP-degrading enzyme apyrase to malnourished pups restores SIgA levels and ameliorates stunted growth. SIgA is instrumental in improving the growth and intestinal immune competence of mice while they are continuously fed a malnourished diet. The analysis of microbiota composition suggests that amplification of endogenous SIgA may exert a dominant function in correcting malnourishment dysbiosis and its consequences on host organisms, irrespective of the actual microbial ecology.

There has been continuous and growing interest in edible insects. Worldwide, various levels of insect farming are emerging, ranging from small domestic farms to vertical farms reaching heights of 36 meters, accommodating several million growing insects. The appeal of insects lies in their ecological benefits, as they contribute to the valorization of underutilized organic residues while requiring minimal space and water. The selection of insect species is influenced not only by their biology and behavior but also by local preferences and customs, varying with the scale of production and geographical location. This review article aims to provide an updated overview of the main insect species produced across different continents, their current level of industrialization, and production prospects based on available literature.

Nanotechnology offers advanced biomedical tools for diagnosis and drug delivery, stressing the value of investigating the mechanisms by which nanocarriers interact with the biological environment. Herein, the cellular response to CD44-targeted nanoparticles (NPs) was investigated. CD44, the main hyaluronic acid (HA) receptor, is widely exploited as a target for therapeutic purposes. HA NPs were produced by microfluidic platform starting from HA with different molecular weights (Mw, 280, 540, 820 kDa) by polyelectrolyte complexation with chitosan (CS). Thanks to microfluidic technology, HA/CS NPs with the same physical features were produced, and only the effects of HA Mw on CD44-overexpressing cells (human mesenchymal stem cells, hMSCs) were studied. This work provides evidence of the HA/CS NPs biocompatibility regardless the HA Mw and reveals the effect of low Mw HA in improving the cell proliferation. Special attention was paid to the endocytic mechanisms used by HA/CS NPs to enter hMSCs. The results show the notable role of CD44 and the pronounced effect of HA Mw in the NPs' internalization. HA/CS NPs uptake occurs via different endocytic pathways simultaneously, and most notably, NPs with 280 kDa HA were internalized by clathrin-mediated endocytosis. Instead, NPs with 820 kDa HA revealed a greater contribution of caveolae and cytoskeleton components.

Background: To identify indicators of guideline-concordant care in lung cancer, to implement such indicators with cancer registry data linked to health databases, and to pilot them in a cohort of patients from the cancer registry of the Milan Province. Methods: Thirty-four indicators were selected by revision of main guidelines by cancer epidemiologists, and then evaluated by a multidisciplinary panel of clinicians involved in lung cancer care and working on the pathway of lung cancer diagnosis and treatment in the Lombardy region, Italy. With a modified Delphi method, they assessed for each indicator the content validity as a quality measure of the care pathway, the degree of modifiability from the health professional, and the relevance to the health professional. Feasibility was assessed using the cancer registry and the routine health records of the Lombardy region. Feasible indicators were then calculated in the cohort of lung cancer patients diagnosed in 2007–2012 derived from the cancer registry of the Milan Province. Criterion validity was assessed reviewing clinical records of a random sample of 114 patients (threshold for acceptable discordance ≤20%). Finally, reliability was evaluated at the provider level. Results: Initially, 34 indicators were proposed for evaluation in the first Delphi round. Of the finally 22 selected indicators, 3 were not feasible because the required information was actually not available. The remaining 19 were calculated on the pilot cohort. After assessment of criterion validity (3 eliminated), 16 indicators were retained in the final set and evaluated for reliability. Conclusion: The developed and piloted set of indicators is now available to implement and monitor, over time, quality initiatives for lung cancer care in the studied health system.

Hyaluronic acid-based nanoparticles (HA NPs) can be used to deliver a protein cargo to cells overexpressing HA receptors such as CD44 since they combine the low toxicity of the carrier and the retention of the protein integrity with the receptor-mediated internalization. HA properties play a crucial but sometimes unclear role in managing the formation and stability of the meshwork, cell interactions, and ultimately the protein entrapment efficacy. Nowadays, microfluidic is an innovative technology that allows to overcome limits linked to the NPs production, guaranteeing reproducibility and control of individual batches. Taking advantage of this technique, in this research work, the role of HA weight average molecular weight (Mw) in NPs formation inside a microfluidic device has been specifically faced. Based on the relationship between polymer Mw and solution viscosity, a methodological approach has been proposed to ensure critical quality attributes (size of 200 nm, PDI ≤ 0.3) to NPs made by HA with different Mw (280, 540, 710 and 820 kDa). The feasibility of the protein encapsulation was demonstrated by using Myoglobin, as a model neutral protein, with an encapsulation efficiency always higher than 50%. Lastly, all NPs samples were successfully internalized by CD44-expressing cells.

In these recent years nanotechnology has gained interest as a powerful tool for drug delivery. It allows to overcome important drawbacks such as drug poor physico-chemical proprieties, toxicity and bioavailability challenges thereby ensuring better therapeutic efficacy with low side-effects and, sometimes, it permits to discover new drug applications. This review aims to analyse the impact of nanotechnology in the pharmaceutical development of VERTEPORFIN (VP), a benzoporphyrin derivative, which was conceived as second generation photosensitizer (PS) in photodynamic therapy (PDT), and later became a milestone in ophthalmology for treating age-related macular degeneration (AMD) disease. VP photoinduced and non-photoinduced biological features will be surveyed and nanotechnology implication in improving VP performances outlined. Currently, VP loaded nanostructured delivery systems (VP-nanoSs), administered alone or in combination with other drugs, are widely studied for the treatment of many widespread diseases including several tumoral forms and severe fibrotic conditions.

Contrast Induced Nephropathy is the most severe side-effect arising after non-ionic iodinated contrast agents (CAs) intravenous administration. The use of antioxidants (i.e., N-Acetylcysteine; NAC) is one of the attempted prevention approaches. Herein, we describe the microfluidic-assisted synthesis of iodinated polymeric nanoparticles (NPs) as new multifunctional blood pool CA. The aim of this research is to co-encapsulate Iohexol (IOX; iodinated CA) and NAC (preventive agent) into poly-D,L-lactide-co-glycolide (PLGA) and PEGylated-PLGA (PLGA-PEG) NPs to exploit CA diagnostic proprieties and NAC preventing antioxidant activity. A microfluidic-assisted nanoprecipitation protocol has been set-up for PLGA and PLGA-PEG NPs, evaluating the effect of formulation and microfluidic parameters by analysing the size, PDI and IOX and NAC encapsulation efficiency. The optimized NPs (PLGA-PEG, L:G 50:50, 5% PEG, Mw 90 kDa) formulated with a size of 67 ± 2.8 nm with PDI < 0.2, spherical shape, and an IOX and NAC encapsulation efficiency of 38% and 20%, respectively. The IOX and NAC encapsulation was confirmed by FTIR and DSC. In vitro release study showed an IOX retention into the polymeric matrix and NAC sustained release up to 24–48 h stating microfluidics as powerful tool for the formulation of multifunctional nanoplatforms. Finally, the protective effect of NPs and NAC were preliminary assessed on human kidney cells.

In this study, an innovative microfluidics-based method was developed for one-step synthesis of hyaluronic acid (HA)-based nanoparticles (NPs), by exploiting polyelectrolytic interactions between HA and chitosan (CS), in order to improve reliability, reproducibility and possible scale-up of the NPs preparation. The on-chip synthesis, using a staggered herringbone micromixer, allowed to produce HA/CS NPs with tailored-made size and suitable for both parenteral (117.50 - 4.51 nm) and loco-regional (349.15 - 38.09 nm) administration, mainly composed by HA (more than 85% wt) with high negative surface charge (< -20 mV). HA/CS NPs were successfully loaded with a challenging water-insoluble molecule, Everolimus (EVE), an FDA- and EMA-approved anticancer drug able to lead to cell cycle arrest, reduced angiogenesis and promotion of apoptosis. HA/CS NPs resulted to be massively internalized in CD44+ human mesenchymal stem cells via CD44 receptor-mediated endocytosis. HA/CS NPs selectiveness towards CD44 was highlighted by blocking CD44 receptor by anti-CD44 primary antibody and by comparison to CS-based NPs cellular uptake. Eventually, high effectiveness in inhibiting cell proliferation was demonstrated on-chip synthetized EVE loaded HA/CS NPs by tracking in vitro DNA synthesis.