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Objectives: To investigate the use of intravoxel incoherent motion (IVIM) to study microperfusion and microstructural characteristics of lungs, brain, and placenta in normal and small fetuses., Methods: We retrospectively enrolled 30 small fetuses and 82 normal pregnancies who underwent a 1.5-T MRI examination using an IVIM-DWI. Small fetuses were distinguished in small for gestational age (SGA) and "true" fetal growth restriction (FGR). ROIs were placed on the brain parenchyma, lungs, and fetal/maternal placental sides. Differences in perfusion fraction f, diffusion coefficient D, and pseudo-diffusion coefficient D* and their correlation with gestational age (GA) and birth weight (BW) were investigated., Results: LUNG: f showed significantly lower values (p = 2·10 -7 ) in small fetuses (SGA + FGR); f discriminates SGA and FGR from normal (p = 0.001; p = 1·10 -6 ). f increases with GA (p < 0.0001) in the control group; a positive correlation was also obtained in small fetuses, although less significant., Placenta: FGR showed lower f values than normal ones, in both the fetal (p = 1.4·10 -7 ) and maternal side (p = 0.001); f discriminates between SGA and FGR (p = 0.03). In small fetuses (SGA + FGR), f correlates positively with BW., Brain: D values in supratentorial white matter (WM) were significantly higher compared to other regions, in both normal and small fetuses. Small fetuses showed higher D values in occipital WM and pons (p = 0.041; p = 0.027) than in normal. D correlates negatively with GA in the healthy group. No correlation between D and GA was found in SGA + FGR group., Conclusions: In our study, IVIM-MRI allowed us to detect microstructural and microperfusion changes in the placenta, brain, and lung of small fetuses, noninvasively., Competing Interests: Declarations Conflict of interest Autor Robert Grimm is an employee of Siemens Healthcare GmbH. He didn’t receive any financial support for this work that could have influenced its outcome. The remaining authors declare no relationships with any companies whose products or services may be related to the subject matter of the article. Ethical approval The study was conducted in accordance with the Declaration of Helsinki. Informed consent Informed consent was obtained from all subjects involved in the study., (© 2024. Italian Society of Medical Radiology.)

Competing Interests: The authors declare no funding or conflicts of interest.

Human amniotic mesenchymal stromal cells (hAMSCs) have unique immunomodulatory properties making them attractive candidates for regenerative applications in inflammatory diseases. Most of their beneficial properties are mediated through their secretome. The bioactive factors concurring to its therapeutic activity are still unknown. Evidence suggests synergy between the two main components of the secretome, soluble factors and vesicular fractions, pivotal in shifting inflammation and promoting self-healing. Biological variability and the absence of quality control (QC) protocols hinder secretome-based therapy translation to clinical applications. Moreover, vesicular secretome contains a multitude of particles with varying size, cargos and functions whose complexity hinders full characterization and comprehension. This study achieved a significant advancement in secretome characterization by utilizing native, FFF-based separation and characterizing extracellular vesicles derived from hAMSCs. This was accomplished by obtaining dimensionally homogeneous fractions then characterized based on their protein content, potentially enabling the identification of subpopulations with diverse functionalities. This method proved to be successful as an independent technique for secretome profiling, with the potential to contribute to the standardization of a qualitative method. Additionally, it served as a preparative separation tool, streamlining populations before ELISA and LC-MS characterization. This approach facilitated the categorization of distinctive and recurring proteins, along with the identification of clusters associated with vesicle activity and functions. However, the presence of proteins unique to each fraction obtained through the FFF separation tool presents a challenge for further analysis of the protein content within these cargoes., Competing Interests: Funding The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: Ornella Parolini reports financial support was provided by PRIN 2017 program of Italian Ministry of Research and University (MIUR, Grant No. 2017RSAFK7). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate the diagnostic accuracy of the Node-RADS score and the utility of apparent diffusion coefficient (ADC) values in predicting metastatic lymph nodes (LNs) involvement in cervical cancer (CC) patients using magnetic resonance imaging (MRI). The applicability of the Node RADS score across three readers with different years of experience in pelvic imaging was also assessed., Material and Methods: Among 140 patients, 68 underwent staging MRI, neoadjuvant chemotherapy and radical surgery, forming the study cohort. Node-RADS scores of the main pelvic stations were retrospectively determined to assess LN metastatic likelihood and compared with the histological findings. Mean ADC, relative ADC (rADC), and correct ADC (cADC) values of LNs classified as Node-RADS ≥ 3 were measured and compared with histological reports, considered as gold standard., Results: Sensitivity, specificity, positive and negative predictive values (PPVs and NPVs), and accuracy were calculated for different Node-RADS thresholds. Node RADS ≥ 3 showed a sensitivity of 92.8% and specificity of 72.5%. Node RADS ≥ 4 yielded a sensitivity of 71.4% and specificity of 100%, while Node RADS 5 yielded 42.9% and 100%, respectively. The diagnostic performance of mean ADC, cADC and rADC values from 78 LNs with Node-RADS score ≥ 3 was assessed, with ADC demonstrating the highest area under the curve (AUC 0.820), compared to cADC and rADC values., Conclusion: The Node-RADS score provides a standardized LNs assessment, enhancing diagnostic accuracy in CC patients. Its ease of use and high inter-observer concordance support its clinical utility. ADC measurement of LNs shows promise as an additional tool for optimizing patient diagnostic evaluation., (© 2024. The Author(s).)

Mesenchymal stromal/stem cells (MSCs) are a heterogeneous population of multipotent cells that can be obtained from various tissues, such as dental pulp, adipose tissue, bone marrow and placenta. MSCs have gained importance in the field of regenerative medicine because of their promising role in cell therapy and their regulatory abilities in tissue repair and regeneration. However, a better characterization of these cells and their products is necessary to further potentiate their clinical application. In this study, we used unbiased high-resolution mass spectrometry-based proteomic analysis to investigate the impact of distinct priming strategies, such as hypoxia and IFN-γ treatment, on the composition and therapeutic functionality of the secretome produced by MSCs derived from the amniotic membrane of the human placenta (hAMSCs). Our investigation revealed that both types of priming improved the therapeutic efficacy of hAMSCs, and these improvements were related to the secretion of functional factors present in the conditioned medium (CM) and exosomes (EXOs), which play crucial roles in mediating the paracrine effects of MSCs. In particular, hypoxia was able to induce a pro-angiogenic, innate immune response-activating, and tissue-regenerative hAMSC phenotype, as highlighted by the elevated production of regulatory factors such as VEGFA, PDGFRB, ANGPTL4, ENG, GRO-γ, IL8, and GRO-α. IFN-γ priming, instead, led to an immunosuppressive profile in hAMSCs, as indicated by increased levels of TGFB1, ANXA1, THBS1, HOMER2, GRN, TOLLIP and MCP-1. Functional assays validated the increased angiogenic properties of hypoxic hAMSCs and the enhanced immunosuppressive activity of IFN-γ-treated hAMSCs. This study extends beyond the direct priming effects on hAMSCs, demonstrating that hypoxia and IFN-γ can influence the functional characteristics of hAMSC-derived secretomes, which, in turn, orchestrate the production of functional factors by peripheral blood cells. This research provides valuable insights into the optimization of MSC-based therapies by systematically assessing and comparing the priming type-specific functional features of hAMSCs. These findings highlight new strategies for enhancing the therapeutic efficacy of MSCs, particularly in the context of multifactorial diseases, paving the way for the use of hAMSC-derived products in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Calligaris, Zito, Busà, Bulati, Iannolo, Gallo, Carreca, Cuscino, Castelbuono, Carcione, Centi, Amico, Bertani, Chinnici, Conaldi, Scilabra and Miceli.)

Lung cancer represents the leading cause of cancer-related mortality worldwide, with around 1.8 million deaths in 2020. For this reason, there is an enormous interest in finding early diagnostic tools and novel therapeutic approaches, one of which is extracellular vesicles (EVs). EVs are nanoscale membranous particles that can carry proteins, lipids, and nucleic acids (DNA and RNA), mediating various biological processes, especially in cell-cell communication. As such, they represent an interesting biomarker for diagnostic analysis that can be performed easily by liquid biopsy. Moreover, their growing dataset shows promising results as drug delivery cargo. The aim of our work is to summarize the recent advances in and possible implications of EVs for early diagnosis and innovative therapies for lung cancer., Competing Interests: The authors declare no conflicts of interest.