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Background Adipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for advanced cell-based therapies. They are routinely obtained enzymatically from fat lipoaspirate (LP) as SVF, and may undergo prolonged ex vivo expansion, with significant senescence and decline in multipotency. Besides, these techniques have complex regulatory issues, thus incurring in the compelling requirements of GMP guidelines. Hence, availability of a minimally manipulated, autologous adipose tissue would have remarkable biomedical and clinical relevance. For this reason, a new device, named Lipogems® (LG), has been developed. This ready-to-use adipose tissue cell derivate has been shown to have in vivo efficacy upon transplantation for ischemic and inflammatory diseases. To broaden our knowledge, we here investigated the angiogenic and anti-inflammatory properties of LG and its derived MSC (LG-MSCs) population. Methods Human LG samples and their LG-MSCs were analyzed by immunohistochemistry for pericyte, endothelial and mesenchymal stromal cell marker expression. Angiogenesis was investigated testing the conditioned media (CM) of LG (LG-CM) and LG-MSCs (LG-MSCs-CM) on cultured endothelial cells (HUVECs), evaluating proliferation, cord formation, and the expression of the adhesion molecules (AM) VCAM-1 and ICAM-1. The macrophage cell line U937 was used to evaluate the anti-inflammatory properties, such as migration, adhesion on HUVECs, and release of RANTES and MCP-1. Results Our results indicate that LG contained a very high number of mesenchymal cells expressing NG2 and CD146 (both pericyte markers) together with an abundant microvascular endothelial cell (mEC) population. Substantially, both LG-CM and LG-MSC-CM increased cord formation, inhibited endothelial ICAM-1 and VCAM-1 expression following TNFα stimulation, and slightly improved HUVEC proliferation. The addition of LG-CM and LG-MSC-CM strongly inhibited U937 migration upon stimulation with the chemokine MCP-1, reduced their adhesion on HUVECs and significantly suppressed the release of RANTES and MCP-1. Conclusions Our data indicate that LG micro-fragmented adipose tissue retains either per se , or in its embedded MSCs content, the capacity to induce vascular stabilization and to inhibit several macrophage functions involved in inflammation.

Background Mesenchymal stromal cells (MSCs) are considered an important therapeutic tool in cancer therapy. They possess intrinsic therapeutic potential and can also be in vitro manipulated and engineered to produce therapeutic molecules that can be delivered to the site of diseases, through their capacity to home pathological tissues. We have recently demonstrated that MSCs, upon in vitro priming with anti-cancer drug, become drug-releasing mesenchymal cells (Dr-MCs) able to strongly inhibit cancer cells growth. Methods Murine mesenchymal stromal cells were loaded with Paclitaxel (Dr-MCsPTX) according to a standardized procedure and their ability to inhibit the growth of a murine B16 melanoma was verified by in vitro assays. The anti-metastatic activity of Dr-MCsPTX was then studied in mice injected i.v. with B16 melanoma cells that produced lung metastatic nodules. Lung nodules were counted under a dissecting stereomicroscope and metastasis investigated by histological analysis. Results We found that three i.v. injections of Dr-MCsPTX on day 5, 10 and 15 after tumor injection almost completely abolished B16 lung metastasis. Dr-MCsPTX arrested into lung by interacting with endothelium and migrate toward cancer nodule through a complex mechanism involving primarily mouse lung stromal cells (mL-StCs) and SDF-1/CXCR4/CXCR7 axis. Conclusions Our results show for the first time that Dr-MCsPTX are very effective to inhibit lung metastasis formation. Actually, a cure for lung metastasis in humans is mostly unlikely and we do not know whether a therapy combining engineered MSCs and Dr-MCs may work synergistically. However, we think that our approach using Dr-MCs loaded with PTX may represent a new valid and additive therapeutic tool to fight lung metastases and, perhaps, primary lung cancers in human.

Glycoconjugates present in the various parts of the digestive apparatus (oesophagus, stomach, intestine) of 27, 34 and 44 days-old Umbrina cirrosa (L.) fries were characterised by means of lectin histochemistry in conjunction with sialidase digestion and KOH treatment. High amounts of carbohydrates were detected especially in goblet cells of the oesophagus. Positivity obtained with the various lectins in oesophagus, stomach and intestine did not change during the development of the fries examined. D-Gal and D-GalNAc appeared to occupy a terminal position in oligosaccharidic chains whereas they are linked to sialic acid residues in adult subjects, which suggests an incomplete chemical structure of the glycoconjugates secreted by the digestive apparatus of fries.

Glycine (Gly), NH2CH2COOH, is the simplest amino acid. Although it has not been directly detected in the interstellar gas-phase medium, it has been identified in comets and meteorites, and its synthesis in these environments has been simulated in terrestrial laboratory experiments. Likewise, condensation of Gly to form peptides in scenarios resembling those present in a primordial Earth has been demonstrated experimentally. Thus, Gly is a paradigmatic system for biomolecular building blocks to investigate how they can be synthesized in astrophysical environments, transported and delivered by fragments of asteroids (meteorites, once they land on Earth) and comets (interplanetary dust particles that land on Earth) to the primitive Earth, and there react to form biopolymers as a step towards the emergence of life. Quantum chemical investigations addressing these Gly-related events have been performed, providing fundamental atomic-scale information and quantitative energetic data. However, they are spread in the literature and difficult to harmonize in a consistent way due to different computational chemistry methodologies and model systems. This review aims to collect the work done so far to characterize, at a quantum mechanical level, the chemical life of Gly, i.e., from its synthesis in the interstellar medium up to its polymerization on Earth.

Purpose The aim of this study is to evaluate the return to sport after surgical treatment of shoulder injuries in professional goalkeepers in relationship with the mechanism of injury and the pattern of related shoulder lesions. Methods Twenty-six shoulders in nineteen elite male professional soccer goalkeepers were retrospectively analyzed considering multiple diseases (instability, rotator cuff, biceps or other tendon injuries). Data was collected for injury modality and context, pathological findings, surgical procedures, time, level of return to sport, and complications. Results The mechanism of injury was “mild trauma without contact” in 46% of the cases and 54% of injuries happened during training. 11 patients (42%) reported multiple pattern lesions and 9 patients (35%) classic anterior instability lesions. The mean time for return to differentiated training and unrestricted sport activity was 14 and 20.2 weeks, respectively. 15 athletes (62.5%) reported 100% return to sport, 4 (16.7%) to 90%, 1 (4.2%) to 85%, 3 (12.5%) to 80% and 1 athlete to 50%, stopping professional activity. 21% of the cases reported the persistence of some shoulder symptoms. 3 cases experienced a new injury. Patients with classic anterior instability had significantly lower age (30.7 vs 19.8 years, P =  0.001), experienced injury in different context and reported symptoms more frequently compared to multiple lesion patients (4/8 vs 0/10, P =  0.011). Conclusion Professional elite goalkeepers which required shoulder surgery for different causes demonstrated high-rate level of return to play despite the persistence of mild symptoms. The high frequency of multiple lesions, patients’ characteristics, injury context and mechanism, increase the concern for injuries in overstressed shoulder for this category of sport. Level of evidence IV.

Aims MicroRNAs are a class of negative regulators of gene expression, which have been shown to be involved in the development of endocrine pancreas and in the regulation of insulin secretion. Since type 2 diabetes (T2D) is characterized by beta cell dysfunction, we aimed at evaluating expression levels of miR-124a and miR-375, both involved in the control of beta cell function, in human pancreatic islets obtained from T2D and from age-matched non-diabetic organ donors. Methods We analyzed miR-124a and miR-375 expression by real-time qRT-PCR in human pancreatic islets and evaluated the potential role of miR-124a by overexpressing or silencing such miRNA in MIN6 pseudoislets. Results We identified a major miR-124a hyperexpression in T2D human pancreatic islets with no differential expression of miR-375. Of note, miR-124a overexpression in MIN6 pseudoislets resulted in an impaired glucose-induced insulin secretion. In addition, miR-124a silencing in MIN6 pseudoislets resulted in increased expression of predicted target genes (Mtpn, Foxa2, Flot2, Akt3, Sirt1 and NeuroD1) involved in beta cell function. For Mtpn and Foxa2, we further demonstrated the actual binding of miR-124a to their 3UTR sequences by luciferase assay. Conclusions We uncovered a major hyperexpression of miR-124a in T2D islets, whose silencing resulted in increased expression of target genes of major importance for beta cell function and whose overexpression impaired glucose-stimulated insulin secretion, leading to the hypothesis that an altered miR-124a expression may contribute to beta cell dysfunction in type 2 diabetes.

Fruit-set, defined as the activation of a developmental program which converts the ovary into a developing fruit, depends on the crosstalk among plant hormones. Here we show that in pollinated ovaries fruit-set is associated with an increase in indole-3-acetic acid (IAA) content and high transcript levels of ToFZY, a gene involved in the tryptophan-dependent auxin biosynthesis pathway. In unpollinated ovaries developed parthenocarpically in response to the synthetic auxin chlorophenoxyacetic acid (4-CPA), ToFZY mRNA levels and IAA content slightly increase. The most likely sequence of events after fertilization involves auxin-mediated activation of gibberellin (GA) synthesis. Fertilization events not only strongly increase SlGA20ox1 and SlGA20ox3 message levels but also increase SlGA2ox2, SlGA2ox4, and SlGA2ox5 mRNA levels, suggesting a concerted regulation to modulate the level of bioactive GAs, GA1 and GA3. 4-chlorophenoxyacetic acid was found to mimic the fertilization events in the stimulation of SlGA20ox1 and SlGA20ox3 mRNA levels, which were also enhanced and increased earlier, but in contrast with pollinated ovaries, SlGA2ox2, SlGA2ox4, and SlGA2ox5 mRNA levels were repressed leading to higher levels of bioactive GAs. We have also analyzed the content of abscisic acid (ABA) and its metabolites dihydrophaseic acid, phaseic acid, and ABA-glucosyl ester and the level of cytokinins (CKs) (free bases and their corresponding ribosides and ribotides) in pollinated and auxin-treated tomato fruits. We show that ABA levels decrease whereas the levels of free CKs increase immediately after pollination or auxin treatment.

Background Increases in migration patterns in the recent years have led to a continuously growing number of unaccompanied foreign minors (UFMs) entering Italy. As part of processing and integration, age assessment is performed by pediatricians upon request of regulatory bodies. Updated guidelines for age estimation procedures were published in 2020 in order to prioritize the well-being of the minors and the accuracy of the assessment. Nonetheless, literature suggests that the recently established multidisciplinary approach has not yet been widely adopted by physicians. Methods A cross-sectional exploratory survey was distributed to pediatricians in Italy in order to gauge their range of experience with UFMs and age assessment protocols. Results In total 344 pediatricians participated in the survey, originating from varied regions in Italy. Out of pediatricians who reported conducting age assessment procedures (38.9%), only a small fraction (14.2%) confirmed being knowledgeable about the methodology. Instead, a significant portion (28.8% and 56.4%) either had partial awareness or lacked knowledge of these procedures. These responses significantly differed when comparing hospital and outpatient pediatricians or according to their geographical area of work ( p <0.05). Conclusion Survey responses suggest that a gap in awareness and experience regarding a multidisciplinary approach to age estimations still exists, likely in part due to a lack of resources, especially at the regional level. In the future, efforts towards the education of professionals and mobilization of resources for investment in the field will be crucial for the improvement of work with UFMs and other migrant populations.