MBOAT7 in liver and extrahepatic diseases

MBOAT7 is a protein anchored to endomembranes by several transmembrane domains. It has a catalytic dyad involved in remodelling of phosphatidylinositol with polyunsaturated fatty acids. Genetic variants in the MBOAT7 gene have been associated with the entire spectrum of non-alcoholic fatty liver (NAFLD), recently redefined as metabolic dysfunction-associated fatty liver disease (MAFLD) and, lately, steatotic liver disease (SLD), and to an increasing number of extrahepatic conditions. In this review, we will (a) elucidate the molecular mechanisms by which MBOAT7 loss-of-function predisposes to MAFLD and neurodevelopmental disorders and (b) discuss the growing number of genetic studies linking MBOAT7 to hepatic and extrahepatic diseases. MBOAT7 complete loss of function causes severe changes in brain development resulting in several neurological manifestations. Lower MBOAT7 hepatic expression at both the mRNA and protein levels, due to missense nucleotide polymorphisms (SNPs) in the locus containing the MBOAT7 gene, affects specifically metabolic and viral diseases in the liver from simple steatosis to hepatocellular carcinoma, and potentially COVID-19 disease. This body of evidence shows that phosphatidylinositol remodelling is a key factor for human health

Fermi Surface Topology and Rashba-Edelstein Charge-Spin Conversion in Lead-Halide Perovskites

The conversion of charge current into spin current by the Rashba-Edelstein effect enables the reciprocal control of electron charge and magnetization in magnetoelectric and magneto-optical devices. The fundamentals of this effect are described in 3D lead-halide perovskites: due to spin-momentum locking, a strong charge-spin conversion, widely tunable by the injected charge density, is envisaged. The analysis highlights the close relationship between charge-spin conversion and the topological transition occurring from the low-density, torus-shaped Fermi surface (genus 1) to the high-density, simply connected Fermi surfaces (genus 0). At room temperature, spin-polarizations as large as approximate to 10% are obtained for input charge currents in the approximate to 102 to 106 Acm(-2) range; at low temperature, almost full spin-polarization can be achieved, owed to the large, impurity scattering-limited mobilities. The results qualify lead-halide perovskites as suitable materials for spin-orbitronic applications

Atomistic Simulations of P(NDI2OD-T2) Morphologies: From Single Chain to Condensed Phases

We investigate theoretically the structure, crystallinity, and solubility of a high-mobility n-type semiconducting copolymer, P(NDI2OD-T2), and we propose a set of new force field parameters. The force field is reparametrized against density functional theory (DFT) calculations, with the aim to reproduce the correct torsional angles that govern the polymer chain flexibility and morphology. We simulate P(NDI2OD-T2) oligomers in different environments, namely, in vacuo, in the bulk phase, and in liquid toluene and chloronaphthalene solution. The choice of these solvents is motivated by the fact that they induce different kinds of molecular preaggregates during the casting procedures, resulting in variable device performances. Our results are in good agreement with the available experimental data; the polymer bulk structure, in which the chains are quite planar, is correcly reproduced, yet the isolated chains are flexible enough to fold in vacuo. We also calculate the solubility of P(NDI2OD-T2) in toluene and chloronaphthalene, predicting a much better solubility of the polymer in the latter, also in accordance to experimental observations. Different morphologies and dynamics of the oligomers in the two solvents have been observed. The proposed parameters make it possible to obtain the description of P(NDI2OD-T2) in different environments and can serve as a basis for extensive studies of this polymer semiconductor, such as, for example, the dynamics of aggregation in solvent

3D culture models to study pathophysiology of steatotic liver disease

Steatotic liver disease (SLD) refers to a spectrum of diseases caused by hepatic lipid accumulation. SLD has emerged as the leading cause of chronic liver disease worldwide. Despite this burden and many years, understanding the pathophysiology of this disease is challenging due to the inaccessibility to human liver specimens. Therefore, cell-based in vitro systems are widely used as models to investigate the pathophysiology of SLD. Culturing hepatic cells in monolayers causes the loss of their hepatocyte-specific phenotype and, consequently, tissue-specific function and architecture. Hence, three-dimensional (3D) culture models allow cells to mimic the in vivo microenvironment and spatial organization of the liver unit. The utilization of 3D in vitro models minimizes the drawbacks of two-dimensional (2D) cultures and aligns with the 3Rs principles to alleviate the number of in vivo experiments. This article provides an overview of liver 3D models highlighting advantages and limitations, and culminates by discussing their applications in pharmaceutical and biomedical research

Growing CeO2 Nanoparticles Within the Nano-Porous Architecture of the SiO2 Aerogel

In this study, new CeO2-SiO2 aerogel nanocomposites obtained by controlled growth of CeO2 nanoparticles within the highly porous matrix of a SiO2 aerogel are presented. The nanocomposites have been synthesized via a sol-gel route, employing cerium (III) nitrate as the CeO2 precursor and selected surfactants to control the growth of the CeO2 nanoparticles, which occurs during the supercritical drying of the aerogels. Samples with different loading of the CeO2 dispersed phase, ranging from 5 to 15%, were obtained. The nanocomposites showed the morphological features typical of the SiO2 aerogels such as open mesoporosity with surface area values up to 430 m2·g−1. TEM and XRD characterizations show that nanocrystals of the dispersed CeO2 nanophase grow within the aerogel already during the supercritical drying process, with particle sizes in the range of 3 to 5 nm. TEM in particular shows that the CeO2 nanoparticles are well-distributed within the aerogel matrix. We also demonstrate the stability of the nanocomposites under high temperature conditions, performing thermal treatments in air at 450 and 900°C. Interestingly, the CeO2 nanoparticles undergo a very limited crystal growth, with sizes up to only 7 nm in the case of the sample subjected to a 900°C treatment

Fundamentals of tin iodide perovskites:A promising route to highly efficient, lead-free solar cells

Hybrid tin-iodide perovskites are investigated as potential lead-free replacement of the lead-iodide perovskites; however, the intrinsic operational limit of these systems has not been described in detail, so far. In this work we combine advanced ab initio calculations with XRD and absorption measurements to lay out the fundamentals of formamidinium (FASnI3) and methylammonium (MASnI3) tin iodide perovskites, in comparison with the lead-halide MAPbI3 prototype. Our theoretical analysis reveals that the tin-based materials display an intrinsic photoconversion efficiency on a par with the lead perovskites, and even superior in the thick-layer limit, where the theoretical PCE reaches 30.5% for lead-halides, and 32.3% for tin-halides under AM1.5G illumination; this is the result of two competing factors: a smaller absorption cross section at the onset for stannates, and their smaller band gap of 1.36 eV, thus very close to the ideal Shockley-Queisser limit. We found the rate of photoluminescence emission extremely sensitive to the absorption spectral weight at the band extrema, resulting in B-factor as different as 7.6 × 10-9 s-1 cm3 for MASnI3 and 0.4 × 10-10 s-1 cm3 for FASnI3. The additional impact of Urbach energy and hole doping, giving rise to large Burstein-Moss effect, is described in detail. This journal i

Ferulic acid-nlc with lavandula essential oil: A possible strategy for wound-healing?

Nowadays, an increasing interest in combinatorial drug delivery systems is emerging, highlighting the possibility of exploiting essential oils (EO) for topical applications. This work aimed at developing nanostructured lipid carriers (NLC) for the combined delivery of ferulic acid and Lavandula EO, whose beneficial effects in wound-healing processes have been widely reported. Homogeneous (polydispersity index, PDI < 0.2) nanoparticles with a small size ([removed]85%) were obtained. The co-presence of ferulic acid and Lavandula EO, as compared to synthetic isopropyl myristate-based NLC, increased nanoparticles’ stability, due to higher ordering chains, as confirmed by morphological and physicochemical studies. An enhanced cytocompatibility was observed when combining ferulic acid and Lavandula EO, as confirmed by in vitro studies on fibroblasts. Furthermore, the combined delivery of ferulic acid and Lavandula EO significantly promoted cell migration with higher effectiveness in respect to the free drug solution and the carrier without the EO. Taken all together, our results suggest a potential combined effect of the antioxidant ferulic acid and Lavandula EO co-delivered in lipid nanoparticles in promoting cell proliferation and migration, representing a promising strategy in the treatment of wounds

Luminescent gold-thallium derivatives with a pyridine-containing 12-membered aza-thioether macrocycle

The coordination modes of the ligand 2, 5, 8-trithia[9](2, 6)pyridinophane (L) to thallium(i), gold(iii) and gold(i) have been studied. Thallium(i) is coordinated by the macrocyclic ligand in [Tl(L)](PF6) (1) through all the sulfur and nitrogen atoms, in a distorted square-pyramidal geometry with the thallium(i) ion in the apical position and with the presence of an inert lone pair. Gold(iii) is bonded by the ligand only through the nitrogen of the pyridine group in [AuCl3(L)] (2), whereas two AuI-C6F5fragments coordinate the sulfur atoms next to the pyridine moiety of the ligand in [{Au(C6F5)}2(µ-L)] (3), which form a linear polymer through intermolecular aurophilic contacts. The heterometallic TlI/AuIcomplex {[Au(C6F5)2Tl]2(L)}n(4) features a polymeric structural nature with a metallic pseudo-rhombic Au2Tl2core, which repeats itself forming a zig-zag polymer. In each Au2Tl2unit only one thallium atom is bonded by the NS3donor set of the macrocyclic ligand and also forms two unsupported Au-Tl bonds with two [Au(C6F5)2]-units in an overall pseudo-octahedral geometry. The other thallium atom similarly bridges the same [Au(C6F5)2]-units and links a neighbouring Au2Tl2moiety, thus exhibiting a distorted trigonal planar geometry being bonded only to three gold atoms with unsupported Au-Tl interactions. This complex displays an interesting thermochromic behaviour showing emissions mainly resulting from MM'CT transitions at room temperature. At 77 K a dual emission appears, probably arising from the two different thallium environments. DFT calculations have been carried out in the attempt to investigate the origin of the emissions of complex4. © The Royal Society of Chemistry 2021

Phytochemical profile of capsicum annuum l. Cv senise, incorporation into liposomes, and evaluation of cellular antioxidant activity

Overproduction of oxidants in the human body is responsible for oxidative stress, which is associated with several diseases. High intake of vegetables and fruits can reduce the risk of chronic diseases, as they are sources of bioactive compounds capable of contrasting the free radical effects involved in cancer, obesity, diabetes, and neurodegenerative and cardiovascular diseases. Capsicum annuum L. cv Senise is a sweet pepper that is grown in the Basilicata region (Italy). It is an important source of polyphenols, carotenoids, and capsinoids and can play a key role in human health. In this study, an ethanol extract was obtained from C. annuum dried peppers and the analysis of the phytochemical composition was performed by LC-ESI/LTQ Orbitrap/MS. The extract was incorporated into liposomes, which showed small size (~80 nm), good homogeneity, negative surface charge, and good stability in storage. The biological activity of the extract was evaluated in the human hepatoma (HepG2) cell line, used as model cells. The extract showed no cytotoxic activity and reduced the intracellular reactive oxygen species (ROS) level in stressed cells. The antioxidant activity was further improved when the extract was loaded into liposomes. Moreover, the extract promoted the expression of endogenous antioxidants, such as catalase, superoxide dismutase, and glutathione peroxidase through the Nrf-2 pathway evaluated by RT-PCR

1H NMR study of the interaction of trans-resveratrol with soybean phosphatidylcholine liposomes

Resveratrol (RSV) is a well-known natural derivative with a wide range of biological and pharmacological activities. Despite of these demonstrated properties, it exhibits low both aqueous solubility and chemical stability and therefore low bioavailability. Consequently, the major concern of the technological research is to exploit delivery systems able to overcome bioavailability problems. In the recent past liposomes have been successfully studied for these purposes. In this paper, 1H-NMR spectroscopy, Nuclear Overhauser Spectroscopy (NOESY) as well as Paramagnetic Relaxation Enhancements (PRE) experiments have been carried out to quantitatively investigate the incorporation of resveratrol, at both the liposome preparation stage and by preformed liposomes, also with the aim to characterize resveratrol- soybean phosphatidylcholine (P90G) lipid bilayer interactions. Overall results of 1H NMR spectroscopy analysis suggest that RSV is located nearby the phosphocholine headgroups and also provide quantitative data on the incorporation of RSV (5% w/w), which corresponds to a 150-fold increase with respect to the solubility of RSV in water. Beside, considering that the same level of RSV incorporation was obtained via spontaneous uptake by preformed P90G liposomes, it can be concluded that RSV easily diffuses through the lipid bilayer