RGD_PLGA Nanoparticles with Docetaxel: A Route for Improving Drug Efficiency and Reducing Toxicity in Breast Cancer Treatment

Breast cancer is the leading cause of cancer-related death in women. Although many therapeutic approaches are available, systemic chemotherapy remains the primary choice, especially for triple-negative and advanced breast cancers. Unfortunately, systemic chemotherapy causes serious side effects and requires high doses to achieve an effective concentration in the tumor. Thus, the use of nanosystems for drug delivery may overcome these limitations. Herein, we formulated Poly (lactic-co-glycolic acid) nanoparticles (PLGA-NPs) containing Docetaxel, a fluorescent probe, and a magnetic resonance imaging (MRI) probe. The cyclic RGD tripeptide was linked to the PLGA surface to actively target αvβ3 integrins, which are overexpressed in breast cancer. PLGA-NPs were characterized using dynamic light scattering, fast field-cycling 1H-relaxometry, and 1H-nuclear magnetic resonance. Their therapeutic effects were assessed both in vitro in triple-negative and HER2+ breast cancer cells, and in vivo in murine models. In vivo MRI and inductively coupled plasma mass spectrometry of excised tumors revealed a stronger accumulation of PLGA-NPs in the RGD_PLGA group. Targeted PLGAs have improved therapeutic efficacy and strongly reduced cardiac side effects compared to free Docetaxel. In conclusion, RGD-PLGA is a promising system for breast cancer treatment, with positive outcome in terms of therapeutic efficiency and reduction in side effects

Combined influence of bud load and bud position along the cane on vegetative and reproductive parameters of grape cv. Grillo

Cultivar Grillo vines are characterized by problems with flower biology (the fertility of basal buds) and fructification (millerandage). In this study, to manage the variability in bunch weight with winter pruning and to program others canopy management practices (i.e. early defoliation), three different treatments of bud load were set up by leaving the cane with 3, 6 or 10 buds. The effects of bud load and cane length were studies regarding bud fertility, shoot leaf area, and the number of flowers and berries, as well as the relationship between leaf area and percentage of fruit set, leaf area/flower and percentage of fruit set, and the number of hens and chicks berries. Shoots in the distal position had higher values of fertility and inflorescences with a greater number of flowers, while no ‘apical’ effect of the buds emerged. A good relationship was found between fruit set and the number of flowers, leaf area at flowering and yield, and square centimeters/flower and percentage of fruit set. Cane length was found to be a valid tool for managing bunch weight variability; the value of the leaf area/flower can be used to program early defoliation practice carried out to manage berry set

Brown Tumour in a Patient with Secondary Hyperparathyroidism Resistant to Medical Therapy: Case Report on Successful Treatment after Subtotal Parathyroidectomy

Brown tumour represents a serious complication of hyperparathyroidism. Differential diagnosis, based on histological examination, is only presumptive and clinical, radiological and laboratory data are necessary for definitive diagnosis. Here we describe a case of a brown tumour localised in the maxilla due to secondary hyperparathyroidism in a young women with chronic renal failure. Hemodialysis and pharmacological treatment were unsuccessful in controlling secondary hyperparathyroidism making it necessary to proceed with a subtotal parathyroidectomy. The proper timing of the parathyroidectomy and its favourable effect on regression of the brown tumor made it possible to avoid a potentially disfiguring surgical removal of the brown tumor

Analisi multitemporale delle relazioni tra parametri produttivi e indice di vegetazione in viticoltura

L’efficacia degli interventi agronomici dipendono dalla capacità di programmazione in termini di tempo e intensità di intervento. Questultimi aspetti possono essere calibrati tramite una corretta conoscenza delle caratteristiche produttive e qualitative dei parametric di campo e della loro variabilità nel tempo e nello spazio. La viticoltura di precisione fornisce un supporto valido alla definizione della variabilità di campo e temporale dei parametric vegetative e produttivi. Questo lavoro sintetizza due anni di viticoltura di precisione in Sicilia, nelle campagne agronomiche consotte nel 2012 e 2013 in due aziende vitivinicole “Tenute Rapitalà” e “Donnafugata”. L’indice di vegetazione normalizzato, ottenuto da immagini in multispettrale (Rapideye) acquisite nelle fasi di allegagione, pre-invaiatura e maturazione, è stato relazionato con alcuni parametri produttivi alla raccolta (zuccheri e antociani totali) nella cultivar Nero d’Avola allevata a controspalliera. Il lavoro ha lo scopo di evidenziare la forza del legame esistente nei modelli lineari di relazione tra l’indice di vegetazione ed i parametric produttivi e mettere in evidenza: 1) l’epoca migliore per acquisire le immagini da correlare con i parametri produttivi alla raccolta; 2) se le relazioni sono significative tra gli anni oppure necessitano di ricalibrazione; 3) la trasferibilità delle relazioni nello spazio. I risultati confermano le tre ipotesi indagate per il parametro “zuccheri” alla raccolta ma non tutte per “antociani totali”. Questi risultati evidenziano comunque un possible utilizzo predittivo dei modelli di relazione rilevati da satellite e la possibilità di trasferirli nello spazio, quest’ultimo aspetto necessità però di verifiche svolte in pieno campo

The Role of the Toll-like Receptor 2 and the cGAS-STING Pathways in Breast Cancer: Friends or Foes?

: Breast cancer stands as a primary malignancy among women, ranking second in global cancer-related deaths. Despite treatment advancements, many patients progress to metastatic stages, posing a significant therapeutic challenge. Current therapies primarily target cancer cells, overlooking their intricate interactions with the tumor microenvironment (TME) that fuel progression and treatment resistance. Dysregulated innate immunity in breast cancer triggers chronic inflammation, fostering cancer development and therapy resistance. Innate immune pattern recognition receptors (PRRs) have emerged as crucial regulators of the immune response as well as of several immune-mediated or cancer cell-intrinsic mechanisms that either inhibit or promote tumor progression. In particular, several studies showed that the Toll-like receptor 2 (TLR2) and the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathways play a central role in breast cancer progression. In this review, we present a comprehensive overview of the role of TLR2 and STING in breast cancer, and we explore the potential to target these PRRs for drug development. This information will significantly impact the scientific discussion on the use of PRR agonists or inhibitors in cancer therapy, opening up new and promising avenues for breast cancer treatment

Quality of Grapes Grown Inside Paper Bags in Mediterranean Area

The aim of this study was to evaluate the influence of paper bagging of grape bunches on the morphological, mechanical, and chemical characteristics of berries of three table grapes varieties as an environmentally‐friendly technique for protecting clusters from biotic and abiotic agents. Clusters of Italia, Autumn Royal, and Regal Seedless grape cultivars were bagged and compared to a not‐bagged control. Air temperature inside and outside the bags was monitored. Bunch weight and length, number of berries per bunch, berry longitudinal and transversal diameter, berry mass, number of seeds per berry (normal in size and aborted), soluble solid content, titratable acidity, and skin color by CIEL*a*b* parameters were determined on four points of each berry. Berries were evaluated using texture analysis, and the main texture profile analysis parameters were compared. The air temperatures around not‐bagged clusters were slightly higher than inside the bags. In all the cultivars under evaluation, bagged bunches were heavier compared with not‐bagged ones. In Autumn Royal and Regal Seedless, these differences were mainly owing to the higher number of berries and higher berry weight of the bagged bunches. Regarding mechanical properties, in seedless varieties, the bagging treatment increased berry hardness (related to the berry firmness) and decreased berry cohesiveness and resilience, whereas an opposite behavior was found in cv. Italia. Berry skin break force was lower in the bagging treatment in all the analyzed varieties, indicating a softer and easier‐to‐chew berry skin. The findings demonstrate that the bagging technique affected the three variety parameters to different extents. The main differences were found in the seedless varieties in terms of berry size and bunch characteristics. For all varieties, bagged bunches achieved the quality level required by the market, confirming the suitability of this technique. However, the bag industry is proposing many different bag types (differing in material, shape, color, and closing system); therefore, further studies are needed to obtain more complete and exhaustive technical information

MORPHOLOGICAL ANALYSIS OF ANCIENT GRAPE SEEDS FROM A SINK IN THE MIDDLE-AGE TOWN OF PALERMO

The archaeological excavations in Piazza della Vittoria, in the Roman-Middle Age town of Palermo (Sicily) put in light a sink 3.20 m deep and 1 square m. large, partially filled by thin organic sediments. Grape seeds (grape-stones), fish scales and few vertebrate bones have been found in specific strata sealed under a stratum chronologically attributed to Islamic Middle-Age period (a post-quem limit). The finding of well preserved grape seeds is peculiar and their study opens the opportunity to improve the actual knowledge about evolution, cultivation, use and trade of Vitis L. in the Mediterranean area. This preliminary work focuses on morphologic and morphometric analysis of the ancient grape seeds with two aims: i) systematically describe the remains collection and, ii) define seeds typology and a consequent morphotaxonomic attribution. Over 200 seeds have been carefully dry cleaned (soft brush), photographed and analyzed for total breadth (B), total length (L) and length of stalk (LS) parameters, the most efficient for typological attribution (1, 2); Stummer index has been also calculated (1). Apical notch length (AN) has been for the first time evaluated. Measurements on digital images have been performed using ImageJ 1.31 platform; morphological parameters have been assembled in a dedicated database. Descriptive analysis and linear correlations have been performed using SYSTAT 10. Analysis of variance (ANOVA) and Tukey’s HSD (5% level of significance, α = 0.05) have been applied. All the parameters approximate a normal distribution. Major variation has been observed in LS (c.v. = 35.6%) and AN (c.v. = 35.6%), while B and L showed a c.v. of 9.5% and 12.6% respectively. All the analyzed parameters behave as independent variables with the exception of a significant correlation between Stummer index and L (R2 = 0.45; y = 8.17-0.047x with y = L and x = Stummer index). This correlation reveals that Stummer index depends more from the L and not from the B parameter. On the base of LS measures three subgroups have been arbitrarily created in relationship with the LS: LS1 0.90 mm (35 seeds). Analyzing together the LS groups toward AN, we have found a proportional and significant correlation (p = 0.05) between the extremes LS1 and LS3. In the entire collection, Stummer index varies from 55.76 to 100.86; in the LS groups, the range is 68.38-97.87 in LS1, 61.02-100.86 in LS2 and 55.76-81.70 in LS3. A small group (17) of seeds has been excluded for the impossibility to measure the stalk. The analyzed ancient grape seeds show a wide range of variability for all the considered parameters, revealing a polymorphic collection. In general, the seeds have a rounded heart-like shape, with a noticeable pointy stalk and a very invaginated apical notch. This typical shape is more marked in LS3 group. On the base of LS measures, LS1 is ascribable to wild grapevines, while LS2 and LS3 seem to be ascribable neither to wild nor to cultivated autochthonous Vitis. Furthermore, these seeds differ from those already described in other archaeological horizons in Italy (3) and in France (2). The Stummer index varies highly, exceeding the known range of wild Vitis vinifera (4), although values close to 100 have been already found in wild grapevines in Spain (5) and values above 80 have been also described in Extra-European Vitis species (6). A deep evaluation of the sample, including isotopic analysis and aDNA studies, is in progress. 1) T. T. Korenčič, J. Jakše, Z. Korošec-Koruza (2008) Veget. Hist. Archaeobot., 17(Suppl. 1), S93-S102 2) L. Bouby, I. Figueiral, A. Bouchette, N. Rovina, S. Ivorra, T. Lacombe, T. Pastor, S. Picq, P. Marinval, J. F. Terral (2013) PLoS ONE, 8(5), e63195 3) C. Milanesi, F. Antonucci, P. Menesatti, C. Costa, C. Faleri, M. Cresti (2011) Interdisciplinaria Archaeologica – Natural Sciences in Archaeology, II(2), 95-100 4) A. Stummer (1911) Mitt. Anthropol. Gesellschaft Wien, 41, 283-296 5) F. M. De Toda, J. C. Sancha (1999) Am. J. Enol. Vitic., 50(4), 443-446 6) D. Rivera, B. Miralles, C. Obón, E. Carreño, J. A. Palazón (2007) Vitis, 46(4), 158-16

Association between Sarcopenia and Reduced Bone Mass: Is Osteosarcopenic Obesity a New Phenotype to Consider in Weight Management Settings?

Sarcopenic obesity (SO) is a frequent phenotype in people with obesity; however, it is unclear whether this links with an impaired bone status. In this study, we aimed to investigate the association between SO and low bone mass, and to assess the prevalence of a new entity that combines excessive fat deposition, reduced muscle mass and strength, and low bone mass defined as osteosarcopenic obesity (OSO). Body composition was completed by a DXA scan in 2604 participants with obesity that were categorized as with or without SO, and with low or normal bone mineral content (BMC). Participants with both SO and low BMC were defined as OSO. Among the entire sample, 901 (34.6%) participants met the criteria for SO. This group showed a reduced mean BMC (2.56 ± 0.46 vs. 2.85 ± 0.57, p < 0.01) and displayed a higher prevalence of individuals with low BMC with respect to those without SO (47.3% vs. 25.9%, p < 0.01). Logistic regression analysis showed that the presence of SO increases the odds of having low BMC by 92% [OR = 1.92; 95% CI: (1.60–2.31), p < 0.05] after adjusting for age, body weight, and body fat percentage. Finally, 426 (16.4%) out of the total sample were affected by OSO. Our findings revealed a strong association between SO and reduced bone mass in adults with obesity, and this introduces a new phenotype that combines body fat, muscle, and bone (i.e., OSO) and appears to affect 16% of this population