Hybrid Self-Assembling Nanoparticles Encapsulating Zoledronic Acid: A Strategy for Fostering Their Clinical Use

Self-assembling nanoparticles (SANPs) promise an effective delivery of bisphosphonates or microRNAs in the treatment of glioblastoma (GBM) and are obtained through the sequential mixing of four components immediately before use. The self-assembling approach facilitates technology transfer, but the complexity of the SANP preparation protocol raises significant concerns in the clinical setting due to the high risk of human errors during the procedure. In this work, it was hypothesized that the SANP preparation protocol could be simplified by using freeze-dried formulations. An in-depth thermodynamic study was conducted on solutions of different cryoprotectants, namely sucrose, mannitol and trehalose, to test their ability to stabilize the produced SANPs. In addition, the ability of SANPs to deliver drugs after lyophilization was assessed on selected formulations encapsulating zoledronic acid in vitro in the T98G GBM cell line and in vivo in an orthotopic mouse model. Results showed that, after lyophilization optimization, freeze-dried SANPs encapsulating zoledronic acid could retain their delivery ability, showing a significant inhibition of T98G cell growth both in vitro and in vivo. Overall, these results suggest that freeze-drying may help boost the industrial development of SANPs for the delivery of drugs to the brain.     

Reactive mcl‐PHA: A Sustainable Alternative for Innovative Hybrid Materials

The ability to incorporate medium chain length poly(hydroxyalkanoate) (mcl‐PHA) in the styrene miniemulsion polymerization process was investigated. As a result, novel poly(hydroxyalkanoate)‐co‐poly(stryrene) (PHA‐co‐PS) copolymers were synthesized in the form of stable organic–organic hybrid latexes. Evidence of chemical grafting of mcl‐PHA and cross‐linking of the PHA grafts was obtained using NMR, differential scanning calorimetry (DSC), gel extraction, and rheological analysis. A high degree of mcl‐PHA grafting was achieved by maintaining proper miniemulsion polymerization conditions throughout the course of the polymerization. The incorporation of PHA grafts was a function of the level of PHA in the formulations as well as the reaction conditions, as evidenced by solvent extraction and rheological analysis. DSC showed shifts in the T_g of PS towards higher temperatures, indicating chemical interaction of PS‐PHA.

     

A note on using expanded graphite for achieving energy- and time-efficient production of graphene nanoplatelets via liquid phase exfoliation

Although easily scalable, the production of graphene nanoplatelets (GNP) by the means of liquid-phase exfoliation of graphite flakes (GF) remains an energy- and time-intensive process. In this work, we demonstrate that significant time and energy can be saved in GNP production when employing expanded graphite (EG) in a surfactant-assisted liquid phase exfoliation process. Owing to its increased interlayer distance, the exfoliation of EG can be accomplished in a much shorter time (<30 min) compared to GF (approximately 7 h in the present case). Moreover, the energy required for the EG exfoliation is close to 80-fold lower than that for GF exfoliation. Monitoring of the mean lateral dimension, specific surface area, and graphite flake-to-GNP transition during exfoliation was performed experimentally using several analytical techniques. The EG-derived GNPs are produced much faster and require less energy for exfoliation compared to GF, thus making it a more efficient alternative technique.     

Selective Growth of α-Sexithiophene by Using Silicon Oxides Patterns

A process for fabricating ordered organic films on large area is presented. The process allows growing sexithiophene ultra-thin films at precise locations on patterned Si/SiO(x) substrates by driving the orientation of growth. This process combines the parallel local anodic oxidation of Si/SiO(x) substrates with the selective arrangement of molecular ultra-thin film. The former is used to fabricate silicon oxide arrays of parallel lines of 400 nm in width over an area of 1 cm(2). Selective growth arises from the interplay between kinetic growth parameters and preferential interactions with the patterned surface. The result is an ultra-thin film of organic molecules that is conformal to the features of the fabricated motives.     

Interrelations between Rheology and Phase Behaviour in Partially Miscible Blends: The Case of Polydimethylsiloxane/Polyethylmethylsiloxane (PDMS/PEMS)

A rheological study of the phase behaviour and the dynamics in the immiscible region of a model partially miscible Upper Critical Solution Temperature (UCST) blend was carried out by using a series of nearly monodisperse polydimethylsiloxane (PDMS) of varying molecular weights blended with polyethylmethylsiloxane (PEMS). The complete phase diagram was established through steady shear rheology, optical microscopy and light scattering. The UCST, interfacial tension and morphology of these blends are very sensitive to the molecular weight of the constituents. Partial miscibility was observed only when the M_w of PDMS was sufficiently low. The viscoelastic behaviour in the phase separated region can be modeled successfully using the Palierne model.     

Abiotic Stress Response of Near-Isogenic Spring Durum Wheat Lines under Different Sowing Densities

A detailed study was made of changes in the plant development, morphology, physiology and yield biology of near-isogenic lines of spring durum wheat sown in the field with different plant densities in two consecutive years (2013–2014). An analysis was made of the drought tolerance of isogenic lines selected for yield QTLs (QYld.idw-2B and QYld.idw-3B), and the presence of QTL effects was examined in spring sowings. Comparisons were made of the traits of the isogenic pairs QYld.idw-3B++ and QYld.idw-3B−− both within and between the pairs. Changes in the polyamine content, antioxidant enzyme activity, chlorophyll content of the flag leaf and the normalized difference vegetation index (NDVI) of the plot were monitored in response to drought stress, and the relationship between these components and the yield was analyzed. In the case of moderate stress, differences between the NIL++ and NIL−− pairs appeared in the early dough stage, indicating that the QYld.idw-3B++ QTL region was able to maintain photosynthetic activity for a longer period, resulting in greater grain number and grain weight at the end of the growing period. The chlorophyll content of the flag leaf in phenophases Z77 and Z83 was significantly correlated with the grain number and grain weight of the main spike. The grain yield was greatly influenced by the treatment, while the genotype had a significant effect on the thousand-kernel weight and on the grain number and grain weight of the main spike. When the lines were compared in the non-irrigated treatment, significantly more grains and significantly higher grain weight were observed in the main spike in NIL++ lines, confirming the theory that the higher yields of the QYld.idw-3B++ lines when sown in spring and exposed to drought stress could be attributed to the positive effect of the “Kofa” QTL on chromosome 3B.     

S100A4 Is Involved in Stimulatory Effects Elicited by the FGF2/FGFR1 Signaling Pathway in Triple-Negative Breast Cancer (TNBC) Cells

Triple-negative breast cancer (TNBC) is an aggressive breast tumor subtype characterized by poor clinical outcome. In recent years, numerous advancements have been made to better understand the biological landscape of TNBC, though appropriate targets still remain to be determined. In the present study, we have determined that the expression levels of FGF2 and S100A4 are higher in TNBC with respect to non-TNBC patients when analyzing “The Invasive Breast Cancer Cohort of The Cancer Genome Atlas” (TCGA) dataset. In addition, we have found that the gene expression of FGF2 is positively correlated with S100A4 in TNBC samples. Performing quantitative PCR, Western blot, CRISPR/Cas9 genome editing, promoter studies, immunofluorescence analysis, subcellular fractionation studies, and ChIP assays, we have also demonstrated that FGF2 induces in TNBC cells the upregulation and secretion of S100A4 via FGFR1, along with the ERK1/2–AKT–c-Rel transduction signaling. Using conditioned medium from TNBC cells stimulated with FGF2, we have also ascertained that the paracrine activation of the S100A4/RAGE pathway triggers angiogenic effects in vascular endothelial cells (HUVECs) and promotes the migration of cancer-associated fibroblasts (CAFs). Collectively, our data provide novel insights into the action of the FGF2/FGFR1 axis through S100A4 toward stimulatory effects elicited in TNBC cells.     

Contribution of Metabolomics to Multiple Sclerosis Diagnosis,Prognosis and Treatment

Metabolomics-based technologies map in vivo biochemical changes that may be used as early indicators of pathological abnormalities prior to the development of clinical symptoms in neurological conditions. Metabolomics may also reveal biochemical pathways implicated in tissue dysfunction and damage and thus assist in the development of novel targeted therapeutics for neuroinflammation and neurodegeneration. Metabolomics holds promise as a non-invasive, high-throughput and cost-effective tool for early diagnosis, follow-up and monitoring of treatment response in multiple sclerosis (MS), in combination with clinical and imaging measures. In this review, we offer evidence in support of the potential of metabolomics as a biomarker and drug discovery tool in MS. We also use pathway analysis of metabolites that are described as potential biomarkers in the literature of MS biofluids to identify the most promising molecules and upstream regulators, and show novel, still unexplored metabolic pathways, whose investigation may open novel avenues of research.     

The Beneficial Effects of Essential Oils in Anti-Obesity Treatment

Obesity is a complex disease caused by an excessive amount of body fat. Obesity is a medical problem and represents an important risk factor for the development of serious diseases such as insulin resistance, type 2 diabetes, cardiovascular disease, and some types of cancer. Not to be overlooked are the psychological issues that, in obese subjects, turn into very serious pathologies, such as depression, phobias, anxiety, and lack of self-esteem. In addition to modifying one’s lifestyle, the reduction of body mass can be promoted by different natural compounds such as essential oils (EOs). EOs are mixtures of aromatic substances produced by many plants, particularly in medicinal and aromatic ones. They are odorous and volatile and contain a mixture of terpenes, alcohols, aldehydes, ketones, and esters. Thanks to the characteristics of the various chemical components present in them, EOs are used in the food, cosmetic, and pharmaceutical fields. Indeed, it has been shown that EOs possess great antibiotic, anti-inflammatory, and antitumor powers. Emerging results also demonstrate the anti-obesity effects of EOs. We have examined the main data obtained in experimental studies and, in this review, we summarize the effect of EOs in obesity and obesity-related metabolic diseases.