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This study aimed to examine the impact of different surface properties of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (P NPs) and PLGA-Poloxamer nanoparticles (PP NPs) on their in vivo biodistribution. For this purpose, NPs were formulated via nanoprecipitation and loaded with diphenylhexatriene (DPH), a fluorescent dye. The obtained NPs underwent comprehensive characterization, encompassing their morphology, technological attributes, DPH release rate, and thermodynamic properties. The produced NPs were then administered to wild-type mice via intraperitoneal injection, and, at scheduled time intervals, the animals were euthanized. Blood samples, as well as the liver, lungs, and kidneys, were extracted for histological examination and biodistribution analysis. The findings of this investigation revealed that the presence of poloxamers led to smaller NP sizes and induced partial crystallinity in the NPs. The biodistribution and histological results from in vivo experiments evidenced that both, P and PP NPs, exhibited comparable concentrations in the bloodstream, while P NPs could not be detected in the other organs examined. Conversely, PP NPs were primarily sequestered by the lungs and, to a lesser extent, by the kidneys. Future research endeavors will focus on investigating the behavior of drug-loaded NPs in pathological animal models.

This study proposed a new workflow for co-registering prostate PET images from a dual-tracer PET/MRI study with histopathological images of resected prostate specimens. The method aims to establish an accurate correspondence between PET/MRI findings and histology, facilitating a deeper understanding of PET tracer distribution and enabling advanced analyses like radiomics. To achieve this, images derived by three patients who underwent both [68Ga]Ga-PSMA and [68Ga]Ga-RM2 PET/MRI before radical prostatectomy were selected. After surgery, in the resected fresh specimens, fiducial markers visible on both histology and MR images were inserted. An ex vivo MRI of the prostate served as an intermediate step for co-registration between histological specimens and in vivo MRI examinations. The co-registration workflow involved five steps, ensuring alignment between histopathological images and PET/MRI data. The target registration error (TRE) was calculated to assess the precision of the co-registration. Furthermore, the DICE score was computed between the dominant intraprostatic tumor lesions delineated by the pathologist and the nuclear medicine physician. The TRE for the co-registration of histopathology and in vivo images was 1.59 mm, while the DICE score related to the site of increased intraprostatic uptake on [68Ga]Ga-PSMA and [68Ga]Ga-RM2 PET images was 0.54 and 0.75, respectively. This work shows an accurate co-registration method for histopathological and in vivo PET/MRI prostate examinations that allows the quantitative assessment of dual-tracer PET/MRI diagnostic accuracy at a millimetric scale. This approach may unveil radiotracer uptake mechanisms and identify new PET/MRI biomarkers, thus establishing the basis for precision medicine and future analyses, such as radiomics.

One of the most relevant aspects in evaluating the impact of natural bioactive compounds on human health is the assessment of their bioavailability. In this regard, abscisic acid (ABA) has attracted particular interest as a plant-derived molecule mainly involved in the regulation of plant physiology. Remarkably, ABA was also found in mammals as an endogenous hormone involved in the upstream control of glucose homeostasis, as evidenced by its increase after glucose load. The present work focused on the development and validation of a method for the determination of ABA in biological samples through liquid–liquid extraction (LLE), followed by liquid mass spectrometry (LC-MS) of the extract. To test method suitability, this optimized and validated method was applied to a pilot study on eight healthy volunteers’ serum levels to evaluate ABA concentration after consumption of a standardized test meal (STM) and the administration of an ABA-rich nutraceutical product. The results obtained could meet the demands of clinical laboratories to determine the response to a glucose-containing meal in terms of ABA concentration. Interestingly, the detection of this endogenous hormone in such a real-world setting could represent a useful tool to investigate the occurrence of impaired ABA release in dysglycemic individuals and to monitor its eventual improvement in response to chronic nutraceutical supplementation.

GeoTh is a new, simple, efficient, flexible, low-cost experimental laboratory apparatus. These features make it an excellent technological tool for measuring the thermal conductivity of granular materials, e.g., soils, sand, silt, clay or artificial composites. In particular, a configuration based on the one-dimensional heat conduction in steady-state regime was designed, built, and assembled to determine the thermal conductivity of the samples. In addition, we developed two user-friendly codes; the first for acquisition of the technical data (time series of air temperature; samples temperatures; and heat power); and the second relative to the elaboration of collected data and the calculation of the physical and thermophysical parameters of each analyzed sample (porosity, bulk density, % of water saturation, thermal conductivity, thermal diffusivity). The developed apparatus allows us to temporarily carry out measurements from one to six samples either in ambient conditions or at constant temperature. The robustness of the system has been tested by analyzing and measuring numerous materials in different conditions. We also performed several tests by varying the water content (between 0% and 100% water saturation) for sandy and silty-sand samples to calibrate and test the robustness of the system as well as for verifying the repeatability of the analytical data. Finally, the obtained thermal conductivity values are compared with other dataset proposed in the literature, showing a good fit.

A method was set up and validated to identify and quantify seven parabens in each of the three skin layers, i.e., Stratum Corneum, Epidermis, and Dermis, because, even if only some analogues are legally allowed in Europe, forbidden parabens are also detected in many personal care products and therefore can be absorbed by the skin. A solid/liquid extraction followed by a gradient elution chromatographic separation method was performed and validated according to European guidelines. Our validated method afforded the detection of all seven parabens with limit of detection values ranging from 0.026 to 0.090 μg mL−1 and recoveries ranging from 61.80 to 105.73 μg mL−1 at high and low concentration values (50.0–5.0 μg mL−1), respectively. The proposed method can help assess paraben’s skin bioaccumulation since people are repeatedly exposed to consumer goods containing parabens in their daily routine, posing a chronic risk to human health.

Parabens (PBs) are used as preservatives to extend the shelf life of various foodstuffs, and pharmaceutical and cosmetic preparations. In this work, the membrane barrier passage potential of a subset of seven parabens, i.e., methyl-, ethyl-, propyl- isopropyl, butyl, isobutyl, and benzyl paraben, along with their parent compound, p-hydroxy benzoic acid, were studied. Thus, the Franz cell diffusion (FDC) method, biomimetic liquid chromatography (BLC), and in silico prediction were performed to evaluate the soundness of both describing their permeation through the skin. While BLC allowed the achievement of a full scale of affinity for membrane phospholipids of the PBs under research, the permeation of parabens through Franz diffusion cells having a carbon chain > ethyl could not be measured in a fully aqueous medium, i.e., permeation enhancer-free conditions. Our results support that BLC and in silico prediction alone can occasionally be misleading in the permeability potential assessment of these preservatives, emphasizing the need for a multi-technique and integrated experimental approach.

The concentration levels of thirteen organic pollutants and selected heavy metals were investigated in 40 plastics bottled and tap water samples. Some of the selected contaminants have an ascertained or suspected endocrine disrupting activity, such as Bisphenol A (BPA) and its analogs, and Bis 2-ethylhexyl phthalate (DEHP), which are used by industries as plasticizers. The most frequently detected pollutants were Bisphenol AF (BPAF) (detection frequency (DF) = 67.5%, mean 387.21 ng L−1), DEHP (DF = 62.5%, mean 46.19 µg L−1) and BPA (DF = 60.0%, mean 458.57 ng L−1), with higher concentration levels found in tap waters. Furthermore, a possible level of exposure to thirteen pollutants via drinking water intake was calculated. Our findings show that, even though the occurrence of contaminants and heavy metals in drinking waters does not pose an immediate, acute health risk for the population, their levels should be constantly monitored and “hard-wired” into everyday practice. Indeed, the health impact to the continuous and simultaneous intake of a huge variety of xenobiotics from various sources by humans is complex and still not fully understood.

The aim of the present study is to investigate the synergic role of 68Ga-PSMA PET/MRI and 68Ga-DOTA-RM2 PET/MRI in prostate cancer (PCa) staging. We present pilot data on twenty-two patients with biopsy-proven PCa that underwent 68Ga-PSMA PET/MRI for staging purposes, with 19/22 also undergoing 68Gaa-DOTA-RM2 PET/MRI. TNM classification based on image findings was performed and quantitative imaging parameters were collected for each scan. Furthermore, twelve patients underwent radical prostatectomy with the availability of histological data that were used as the gold standard to validate intraprostatic findings. A DICE score between regions of interest manually segmented on the primary tumour on 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and on T2 MRI was computed. All imaging modalities detected the primary PCa in 18/19 patients, with 68Ga-DOTA-RM2 PET not detecting any lesion in 1/19 patients. In the remaining patients, 68Ga-PSMA and MRI were concordant. Seven patients presented seminal vesicles involvement on MRI, with two of these being also detected by 68Ga-PSMA, and 68Ga-DOTA-RM2 PET being negative. Regarding extraprostatic disease, 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI resulted positive in seven, four and five patients at lymph-nodal level, respectively, and at a bone level in three, zero and one patients, respectively. These preliminary results suggest the potential complementary role of 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI in PCa characterization during the staging phase.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every continent, registering over 1,250,000 deaths worldwide. The effects of SARS-CoV-2 on host targets remains largely limited, hampering our understanding of Coronavirus Disease 2019 (COVID-19) pathogenesis and the development of therapeutic strategies. The present study used a comprehensive untargeted metabolomic and lipidomic approach to capture the host response to SARS-CoV-2 infection. We found that several circulating lipids acted as potential biomarkers, such as phosphatidylcholine 14:0_22:6 (area under the curve (AUC) = 0.96), phosphatidylcholine 16:1_22:6 (AUC = 0.97), and phosphatidylethanolamine 18:1_20:4 (AUC = 0.94). Furthermore, triglycerides and free fatty acids, especially arachidonic acid (AUC = 0.99) and oleic acid (AUC = 0.98), were well correlated to the severity of the disease. An untargeted analysis of non-critical COVID-19 patients identified a strong alteration of lipids and a perturbation of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, aminoacyl-tRNA degradation, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. The severity of the disease was characterized by the activation of gluconeogenesis and the metabolism of porphyrins, which play a crucial role in the progress of the infection. In addition, our study provided further evidence for considering phospholipase A2 (PLA2) activity as a potential key factor in the pathogenesis of COVID-19 and a possible therapeutic target. To date, the present study provides the largest untargeted metabolomics and lipidomics analysis of plasma from COVID-19 patients and control groups, identifying new mechanisms associated with the host response to COVID-19, potential plasma biomarkers, and therapeutic targets.