Andrea Soluri

Introduction: Berry-derived and berry-based interventions have gained increasing attention for their potential health benefits. Berries are rich in diverse bioactive compounds, including polyphenols and anthocyanins, which are associated with a broad range of biological activities, particularly antioxidant and anti-inflammatory effects. Over the last decade, numerous studies have focused on berries, particularly those from the Ericaceae family (blueberry, cranberry and bilberry), the Solanaceae family (goji berry, Solanum nigrum berries) and the Elaeocarpaceae family (maqui berry). Berries are considered among the best dietary sources of bioactive compounds (BACs). Among chronic gastrointestinal disorders, inflammatory bowel disease (IBD) mainly includes Crohn’s disease (CD) and ulcerative colitis (UC), both chronic inflammatory conditions of the gastrointestinal tract. The multifactorial nature of IBD significantly impairs quality of life and makes disease management particularly challenging, increasing interest in complementary approaches, in addition to pharmacological treatments, such as phytotherapeutic strategies based on plant-derived bioactive compounds and, in particular, berry-derived and berry-based interventions. Methods: A systematic literature search was conducted using PubMed, Web of Science, and Scopus databases. Specific inclusion and exclusion criteria were applied to identify relevant articles published up to July 2026. After the removal of duplicates and a thorough screening of titles, abstracts, and full texts, a total of 19 studies were included, comprising 16 studies conducted on animal models and 3 clinical studies involving patients. The 3 clinical studies corresponded to 5 publications and involved a total of 68 unique participants, as two publications were secondary analyses of the same patient cohorts. These investigations evaluated the possible effects of berry-derived and berry-based interventions in both experimental models and clinical settings. Results: Preclinical studies suggested potential protective effects against intestinal inflammation by reducing pro-inflammatory cytokines, improving epithelial barrier integrity, and restoring gut microbiota composition. The included clinical studies reported improvements in disease activity, fecal calprotectin levels, quality of life, and remission rates in patients with ulcerative colitis. Nevertheless, the available clinical evidence remains limited and heterogeneous, preventing definitive conclusions regarding clinical efficacy. Conclusions: The current clinical data should therefore be considered preliminary. Larger and more rigorous randomized controlled trials are needed to determine whether the biological effects observed in preclinical models translate into clinically relevant benefits in patients with IBD. Overall, preclinical evidence complements clinical findings by providing mechanistic insights that help contextualize and interpret outcomes observed in human studies.

Chemotherapy‐induced peripheral neuropathy (CIPN) is a prevalent and debilitating complication of cancer treatment, characterized by neuropathic pain, sensory disturbances, and functional impairment that can substantially reduce quality of life. Neurotoxicity induced by chemotherapeutic agents affects peripheral nerves, dorsal root ganglia, and supporting structures, contributing to persistent pain and neurological dysfunction. This systematic review evaluated the efficacy and safety of antidepressants, particularly duloxetine and amitriptyline, in the management of CIPN‐related pain. Following PRISMA guidelines and registration in PROSPERO (CRD42024608551), a systematic search of PubMed, Scopus, and Web of Science was conducted for studies published between November 2019 and October 2025. This time frame was selected to capture contemporary evidence and recent developments in multimodal treatment strategies, while acknowledging that foundational studies establishing the efficacy of duloxetine predate this period. Clinical and observational studies involving adult patients with CIPN were included. Of 892 records identified, 11 studies met the eligibility criteria. Duloxetine demonstrated clinically meaningful reductions in neuropathic pain, as assessed by VAS, NRS, and CTCAE measures. Topical amitriptyline also showed promising analgesic effects, although the available evidence remains limited. Combination therapies involving duloxetine and agents such as tapentadol, pregabalin, mirogabalin, or amitriptyline were associated with additional reductions in pain intensity; however, current evidence remains insufficient to establish additive or synergistic effects. Overall, antidepressant therapy was generally well tolerated, with predominantly mild and manageable adverse events. Current evidence supports antidepressants, particularly duloxetine, associated with reductions in pain intensity in heterogeneous studies, whereas evidence for CIPN prevention remains inconclusive. These findings support their continued use in clinical practice and highlight the need for larger, well‐designed randomized controlled trials to optimize treatment strategies and further define the role of combination therapies in CIPN management.

Targeting fibrosis in Duchenne muscular dystrophy (DMD)-associated cardiomyopathy is a critical outstanding clinical issue, as cardiac failure remains a leading cause of death despite advances in supportive care. This study evaluates the therapeutic efficacy of CSPG4-targeted chimeric antigen receptor (CAR) T cells in reducing cardiac fibrosis and improving heart function in a preclinical model of the disease. DMD is a progressive genetic disorder characterized by degeneration of skeletal and cardiac muscle. Cardiomyopathy, driven by fibrosis and chronic inflammation, is a leading contributor to mortality in affected patients. Proteoglycans such as CSPG4, critical regulators of extracellular matrix dynamics, are markedly overexpressed in dystrophic hearts and promote pathological remodeling. Current treatments do not adequately target the fibrotic and inflammatory processes underlying cardiac dysfunction. CSPG4-specific CAR-T cells were engineered and administered to dystrophic mice. Therapeutic efficacy was assessed through histological, molecular, and echocardiographic analyses evaluating cardiac fibrosis, inflammation, innervation, and overall function. Treatment with CSPG4 CAR-T cells preserved myocardial integrity, improved cardiac performance, and reduced both fibrosis and inflammatory markers. The therapy also restored cardiac innervation, indicating a reversal of neural remodeling commonly seen in muscular dystrophy-related cardiomyopathy. CSPG4-targeted CAR-T therapy offers a novel, cell-based strategy to mitigate cardiac remodeling in dystrophic hearts. By addressing core fibrotic and inflammatory drivers of disease, this approach represents a significant advancement in the development of precision immune therapies for muscular dystrophies and cardiovascular conditions.

Duchenne muscular dystrophy (DMD) is caused by the absence of the full form of the dystrophin protein, which is essential for maintaining the structural integrity of muscle cells, including those in the heart and respiratory system. Despite progress in understanding the molecular mechanisms associated with DMD, myocardial insufficiency persists as the primary cause of mortality, and existing therapeutic strategies remain limited. This study investigates the hypothesis that a dysregulation of the biological communication between infiltrating macrophages (MPs) and neurocardiac junctions exists in dystrophic cardiac tissue. In a mouse model of DMD ( mdx ), this phenomenon is influenced by the over‐release of chondroitin sulfate proteoglycan‐4 (CSPG4), a key inhibitor of nerve sprouting and a modulator of the neural function, by MPs infiltrating the cardiac tissue and associated with dilated cardiomyopathy, a hallmark of DMD. Givinostat, the histone deacetylase inhibitor under current development as a clinical treatment for DMD, is effective at both restoring a physiological microenvironment at the neuro‐cardiac junction and cardiac function in mdx mice in addition to a reduction in cardiac fibrosis, MP‐mediated inflammation, and tissue CSPG4 content. This study provides novel insight into the pathophysiology of DMD in the heart, identifying potential new biological targets. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The prognosis for many pediatric brain tumors, including cerebellar medulloblastoma (MB), remains dismal but there is promise in new therapies. We have previously generated a mouse model developing spontaneous MB at high frequency, Ptch1^+/−/Tis21^−/−. In this model, reproducing human tumorigenesis, we identified the decline of the Cxcl3 chemokine in cerebellar granule cell precursors (GCPs) as responsible for a migration defect, which causes GCPs to stay longer in the proliferative area rather than differentiate and migrate internally, making them targets of transforming insults. We demonstrated that 4‐week Cxcl3 infusion in cerebella of 1‐month‐old mice, at the initial stage of MB formation, forces preneoplastic GCPs (pGCPs) to leave lesions and differentiate, with a complete suppression of MB development. In this study, we sought to verify the effect of 4‐week Cxcl3 treatment in 3‐month‐old Ptch1^+/−/Tis21^−/− mice, when MB lesions are at an advanced, irreversible stage. We found that Cxcl3 treatment reduces tumor volumes by sevenfold and stimulates the migration and differentiation of pGCPs from the lesion to the internal cerebellar layers. We also tested whether the pro‐migratory action of Cxcl3 favors metastases formation, by xenografting DAOY human MB cells in the cerebellum of immunosuppressed mice. We showed that DAOY cells express the Cxcl3 receptor, Cxcr2, and that Cxcl3 triggers their migration. However, Cxcl3 did not significantly affect the frequency of metastases or the growth of DAOY‐generated MBs. Finally, we mapped the expression of the Cxcr2 receptor in human MBs, by evaluating a well‐characterized series of 52 human MBs belonging to different MB molecular subgroups. We found that Cxcr2 was variably expressed in all MB subgroups, suggesting that Cxcl3 could be used for therapy of different MBs.

Tumor associated fibroblasts (TAFs) play a key role in tumor growth and metastatization. TAFs overexpress different biomarkers that are usually expressed at low levels in physiological conditions. Among them are the fibroblast growth factor receptors (FGFRs) that bind the fibroblast growth factors (FGFs). In particular, the overexpression of FGFR-2c in tumors has been associated with advanced clinical stages and increased metastatization. Here, we developed a non-invasive tool to evaluate, in vivo, the expression of FGFR-2c in metastatic cancer. This is based on ^99mTc-labelled FGF-2. Methods: ^99mTc-FGF-2 was tested in vitro and in vivo in mice bearing allografts of sarcoma cells. Images of ^99mTc-FGF-2 were acquired using a new portable high-resolution ultra-sensitive gamma camera for small animal imaging. Results: FGF-2 was labeled with high specific activity but low labelling efficiency, thus requiring post-labeling purification by gel-filtration chromatography. In vitro binding to 2C human keratinocytes showed a Kd of 3.36 × 10⁻⁹ M. In mice bearing J774A.1 cell allografts, we observed high and rapid tumor uptake of ^99mTc-FGF-2 with a high Tumor/Blood ratio at 24 h post-injection (26.1 %ID/g and 12.9 %ID) with low kidney activity and moderate liver activity. Conclusions: we labeled FGF-2 with ^99mTc and showed nanomolar Kd in vitro with human keratinocytes expressing FGF-2 receptors. In mice, ^99mTc-FGF-2 rapidly and efficiently accumulated in tumors expressing FGF-2 receptors. This new radiopharmaceutical could be used in humans to image TAFs.

Recently, we described synthetic sulfolipids named Sulfavants as a novel class of molecular adjuvants based on the sulfoquinovosyl-diacylglycerol skeleton. The members of this family, Sulfavant A (1), Sulfavant R (2), and Sulfavant S (3), showed important effects on triggering receptor expressed on myeloid cells 2 (TREM2)-induced differentiation and maturation of human dendritic cells (hDC), through a novel cell mechanism underlying the regulation of the immune response. As these molecules are involved in biological TREM2-mediated processes crucial for cell survival, here, we report the synthesis and application of a fluorescent analogue of Sulfavant A bearing the 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacene moiety (Me₄-BODIPY). The fluorescent derivative, named PB-SULF A (4), preserving the biological activity of Sulfavants, opens the way to chemical biology and cell biology experiments to better understand the interactions with cellular and in vivo organ targets and to improve our comprehension of complex molecular mechanisms underlying the not fully understood ligand-induced TREM2 activity.

The immune system is a fine modulator of the tumor biology supporting or inhibiting its progression, growth, invasion and conveys the pharmacological treatment effect. Tumors, on their side, have developed escaping mechanisms from the immune system action ranging from the direct secretion of biochemical signals to an indirect reaction, in which the cellular actors of the tumor microenvironment (TME) collaborate to mechanically condition the extracellular matrix (ECM) making it inhospitable to immune cells. TME is composed of several cell lines besides cancer cells, including tumor-associated macrophages, cancer-associated fibroblasts, CD4⁺ and CD8⁺ lymphocytes, and innate immunity cells. These populations interface with each other to prepare a conservative response, capable of evading the defense mechanisms implemented by the host’s immune system. The presence or absence, in particular, of cytotoxic CD8⁺ cells in the vicinity of the main tumor mass, is able to predict, respectively, the success or failure of drug therapy. Among various mechanisms of immunescaping, in this study, we characterized the modulation of the phenotypic profile of CD4⁺ and CD8⁺ cells in resting and activated states, in response to the mechanical pressure exerted by a three-dimensional in vitro system, able to recapitulate the rheological and stiffness properties of the tumor ECM.