Search Results (763)

Objectives: To investigate how the FLASH effect modulates radiation response on multiple developmental endpoints of zebrafish embryos under normoxic and hypoxic conditions, after irradiation with proton beams at a conventional and an ultra-high dose rate (UHDR). Methods: Embryos were obtained from adult zebrafish and irradiated with a 228 MeV proton beam 24 h post-fertilization (hpf) at a dose rate of 0.6 and 317 Gy/s. For the hypoxic group, samples were kept inside a hypoxic chamber prior to irradiation, while standard incubation was adopted for the normoxic group. After irradiation, images of single embryos were acquired, and radiation effects on larval length, yolk absorption, pericardial edema, head size, eye size, and spinal curvature were assessed at specific time points. Results: Data indicate a general trend of significantly reduced toxicity after exposure to a UHDR compared to conventional regimes, which is maintained under both normoxic and hypoxic conditions. Differences are significant for the levels of pericardial edema induced by a UHDR versus conventional irradiation in normoxic conditions, and for eye and head size in hypoxic conditions. The toxicity scoring analysis shows a tendency toward a protective effect of the UHDR, which appears to be associated with a lower percentage of embryos in the high score categories. Conclusions: A radioprotective effect at a UHDR is observed both for normoxic (pericardial edema) and hypoxic (head and eye size) conditions. These results suggest that while the UHDR may preserve a potential to reduce radiation-induced damage, its protective effects are endpoint-dependent; the role of oxygenation might also be dependent on the tissue involved. Full article

Infection control and bleeding management in deep wounds remain urgent and unmet clinical challenges that demand innovative, multifunctional, and sustainable solutions. Unlike previously reported sodium alginate and silk fibroin-based gel formulations, the present work introduces a dual-functional system combining antimicrobial and haemostatic activity in the form of conformable aerogel beads. This dual-functional formulation is designed to absorb exudate, promote clotting, and provide localized antimicrobial action, all essential for accelerating wound repair in high-risk scenarios within a single biocompatible system. Aerogel beads were obtained by supercritical drying of a silk fibroin–sodium alginate blend, resulting in highly porous, spherical structures measuring 3–4 mm in diameter. The formulations demonstrated efficient ciprofloxacin encapsulation (42.75–49.05%) and sustained drug release for up to 12 h. Fluid absorption reached up to four times their weight in simulated wound fluid and was accompanied by significantly enhanced blood clotting, outperforming a commercial haemostatic dressing. These findings highlight the potential of silk-based aerogel beads as a multifunctional wound healing platform that combines localized antimicrobial delivery, efficient fluid and exudate management, biodegradability, and superior haemostatic performance in a single formulation. This work also shows for the first time how the prilling encapsulation technique with supercritical drying is able to successfully produce silk fibroin and sodium alginate composite aerogel beads. Full article

In light of pressing global nutritional needs, the valorization of agri-food waste constitutes a vital strategy for enhancing human health and nutrition, while simultaneously supporting planetary health. This integrated approach is increasingly indispensable within sustainable and equitable food systems. Recently, a sustainability-driven focus has shifted attention toward the valorization of the agri-food by-products as rich sources of bioactive compounds useful in preventing or treating chronic diseases. Agri-food by-products, often regarded as waste, actually hold great potential as they are rich in bioactive components, dietary fiber, and other beneficial nutrients from which innovative food ingredients, functional foods, and even therapeutic products are developed. This review aims to provide a comprehensive analysis of the current advances in recovering and applying such compounds from agri-food waste, with a particular focus on their roles in human health, sustainable packaging, and circular economy strategies. Methods: This review critically synthesizes recent scientific literature on the extraction, characterization, and utilization of bioactive molecules from agri-food by-products. After careful analysis of the PubMed and Scopus databases, only English-language articles from the last 10 years were included in the final narrative review. The analysis also encompasses applications in the nutraceutical, pharmaceutical, and food packaging sectors. Results: Emerging technologies have enabled the efficient and eco-friendly recovery of compounds such as polyphenols, carotenoids, and dietary fibers that demonstrate antioxidant, antimicrobial, and anti-inflammatory properties. These bioactive compounds support the development of functional foods and biodegradable packaging materials. Furthermore, these valorization strategies align with global health trends by promoting dietary supplements that counteract the effects of the Western diet and chronic diseases. Conclusions: Valorization of agri-food by-products offers a promising path toward sustainable development by reducing waste, enhancing public health, and driving innovation. This strategy not only minimizes waste and supports sustainability, but also promotes a more nutritious and resilient food system. Full article

The enzyme γ-glutamyl transpeptidase (GGT), located on the surface of cellular membranes, hydrolyzes extracellular glutathione (GSH) to guarantee the recycling of cysteine and maintain intracellular redox homeostasis. High expression levels of GGT on tumor cells are associated with increased cell proliferation and resistance against chemotherapy. Therefore, GGT inhibitors have potential as adjuvants in treating GGT-positive tumors; however, most have been abandoned during clinical trials due to toxicity. Recent studies indicate marine-derived ovothiols as more potent non-competitive GGT inhibitors, inducing a mixed cell-death phenotype of apoptosis and autophagy in GGT-overexpressing cell lines, such as the chronic B leukemic cell HG-3, while displaying no toxicity towards non-proliferative cells. In this work, we characterize the activity of two synthetic ovothiol analogs, L-5-sulfanylhistidine and iso-ovothiol A, in GGT-positive cells, such as HG-3 and HL-60 cells derived from acute promyelocytic leukemia. The two compounds inhibit the activity of membrane-bound GGT, without altering cell vitality nor inducing cytotoxic autophagy in HG-3 cells. We provide evidence that a portion of L-5-sulfanylhistidine enters HG-3 cells and acts as a redox regulator, contributing to the increase in intracellular GSH. On the other hand, ovothiol A, which is mostly sequestered by external membrane-bound GGT, induces intracellular ROS increase and the consequent autophagic pathways. These findings provide the basis for developing ovothiol derivatives as adjuvants in treating GGT-positive tumors’ chemoresistance. Full article

Background/Objectives: Art therapy is a psychotherapeutic technique that involves the creation of tangible visual arts and represents a coping strategy to support children with cancer. Evaluating the effects of such activities on children with cancer is essential for providing evidence of the value that creativity holds within healthcare systems. A dedicated tool for assessing the creative process is the Arts Observational Scale (ArtsObS), focusing on mood and emotional states as key indicators of psychosocial well-being. This study aims to validate a translated version of the ArtsObS in the Italian language. Methods: The translation process followed recommendations for translation and cultural adaptation. The distribution properties of the scores, internal consistency, sensitivity to change, reliability, and convergent validity were assessed through observations conducted by two different evaluators. Results: The ArtsObS in its Italian adaptation is proven to be an adequate tool for capturing changes following an intervention, with good internal consistency and low sensitivity to differences between operators. The analysis supports the reliability of the ArtsObS across different observers. Conclusions: The Italian ArtsObS is a valid and reliable instrument for evaluating the impact of art therapy on pediatric patients’ mood and emotional states. It provides a standardized tool for clinical and research settings to assess creative interventions in pediatric oncology. Full article

The interleukin-20 (IL-20) cytokine subfamily, a subset of the IL-10 superfamily, includes IL-19, IL-20, IL-22, IL-24, and IL-26. Recently, their involvement in cancer biology has gained attention, particularly due to their impact on the tumor microenvironment (TME). Notably, IL-20 subfamily cytokines can exert both pro-tumorigenic and anti-tumorigenic effects, depending on the context. For example, IL-22 promotes tumor growth by enhancing cancer cell proliferation and protecting against apoptosis, whereas IL-24 demonstrates anti-tumor activity by inducing cancer cell death and inhibiting metastasis. Additionally, these cytokines influence macrophage polarization—an essential factor in the immune landscape of tumors—thereby modulating the inflammatory environment and immune evasion strategies. Understanding the dual role of IL-20 subfamily cytokines within the TME and their interactions with cancer cell hallmarks presents a promising avenue for therapeutic development. Interleukin-20 receptor antagonists are being researched for their role in cancer therapy, since they potentially inhibit tumor growth and progression. This review explores the relationship between IL-20 cytokines and key cancer-related processes, including growth and proliferative advantages, angiogenesis, invasion, metastasis, and TME support. Further research is necessary to unravel the specific mechanisms underlying their contributions to tumor progression and to determine their potential for targeted therapeutic strategies. Full article

A comparative analysis of testicular tumors in dogs and humans highlights notable similarities in cancer behavior, particularly regarding environmental influences. The ubiquitous distribution of endocrine disruptors in industrialized countries and their effects are strongly linked to the development of testicular cancers. This study examined 221 and 174 cases of testicular tumor in dogs and humans, respectively, from the Campania Animal Cancer Registry and the database of the National Cancer Institute “Fondazione G. Pascale-IRCCS”, between 2020 and 2023. These data were integrated with environmental data from the Ministry of Environment and Energy Security website and the Campania Regional Agency for Environmental Protection (ARPAC). The areas with the highest frequency of testicular tumors in both species were the municipalities of Napoli, Salerno, and Caserta, and their corresponding provinces. The same locations experienced severe contamination of soil and water by environmental pollutants, probably correlated to testicular tumors. Although the molecular mechanisms are not yet fully understood, our data suggest a strong link between the frequency of testicular tumors in humans and dogs and high concentrations of environmental pollutants in the reported locations. These findings emphasize the value of dogs as a potential animal model for studying human health and the effect of environmental factors on cancer development. Full article

Background/Objectives: Immune-mediated necrotizing myopathy (IMNM) is a severe inflammatory myopathy marked by proximal muscle weakness, elevated creatine kinase (CK), and the presence of anti-HMGCR antibodies. Statin exposure is a recognized trigger for anti-HMGCR-positive IMNM, which may persist despite statin withdrawal. This pilot case series explores, for the first time, the use of bempedoic acid—a liver-specific lipid-lowering agent with minimal muscle toxicity—as an alternative to statins in these patients. Methods: We report 10 anti-HMGCR-antibody-positive IMNM patients (6 females, 4 males) previously on statins for primary prevention (8 on atorvastatin, 2 on simvastatin) without prior cardiovascular events. Statins were discontinued at myositis onset. All patients received prednisone and immunosuppressants (methotrexate in 7, mycophenolate in 3), plus bempedoic acid. Anti-HMGCR antibodies were measured using a chemiluminescence method. Results: Their mean anti-HMGCR antibody levels decreased significantly from 390.93 ± 275.22 to 220.89 ± 113.37 CU/L (p = 0.027) after 6 months of treatment. Their CK levels dropped from 1278.9 ± 769.39 to 315.1 ± 157.72 IU/L (p = 0.001), and aldolase dropped from 11.63 ± 2.18 to 6.61 ± 1.22 U/L (p = 0.0001). The mean LDL-C value was 96.1 ± 8.16 mg/dL. No disease recurrence was observed. Autoimmune panels were negative for other myositis-associated and/or -specific antibodies. Conclusions: Bempedoic acid appears to be a safe, effective, and cost-efficient lipid-lowering alternative in statin-intolerant IMNM patients. Larger studies are warranted to confirm its efficacy across different subgroups and to optimize dyslipidemia management in this setting. Full article

The scientific community’s interest in natural compounds with antiviral properties has considerably increased after the emergence of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), especially for their potential use in the treatment of the COVID-19 infection. From this perspective, bovine coronavirus (BCoV), member of the genus β-CoV, represents a valuable virus model to study human β-CoVs, bypassing the risks of handling highly pathogenic and contagious viruses. Pimarane diterpenes are a significant group of secondary metabolites produced by phytopathogenic fungi, including several Diplodia species. Among the members of this class of natural products, sphaeropsidin A (SphA) and its analog sphaeropsidin B (SphB) are well known for their bioactivities, such as antimicrobial, insecticidal, herbicidal, and anticancer. In this study, the antiviral effects of SphA and SphB were evaluated for the first time on bovine (MDBK) cells infected with BCoV. Our findings showed that both sphaeropsidins significantly increased cell viability in infected cells. These substances also caused substantial declines in the virus yield and in the levels of the viral spike S protein. Interestingly, during the treatment, a cellular defense mechanism was detected in the downregulation of the aryl hydrocarbon receptor (AhR) signaling, which is affected by BCoV infection. We also observed that the presence of SphA and SphB determined the deacidification of the lysosomal environment in infected cells, which may be related to their antiviral activities. In addition, in silico investigations have been performed to elucidate the molecular mechanism governing the recognition of bovine AhR (bAhR) by Sphs. Molecular docking studies revealed significant insights into the structural determinants driving the bAhR binding by the examined compounds. Hence, in vitro and in silico results demonstrated that SphA and SphB are promising drug candidates for the development of efficient therapies able to fight a β-CoV-like BCoV during infection. Full article

Mesenchymal stem cells have been widely investigated in the field of regenerative medicine and also used as a model to study the differentiation-induction properties of a variety of biomaterials. This study evaluates the osteoinductive potential of novel hydroxyapatite scaffolds functionalized with a phage-displayed peptide (SC1) selected via biopanning for its similarity to bone matrix proteins. The peptide, identified through sequence alignment as a mimotope of osteonectin (SPARC), was used to functionalize scaffolds. Results from SC1 were gathered at different time points (14, 28 and 46 days) and compared with those from nonfunctionalized hydroxyapatite (HA) scaffolds. In vitro experiments, by seeding human adipose-derived stem cells (hASCs), indicated satisfactory biocompatibility for both types of scaffolds. Histochemical observations showed that SC1, better than HA scaffolds, was able to improve hASC osteogenic differentiation, as evaluated through Alizarin Red staining (showing on average a darker staining of 100%). An increase was also observed, especially at early stages (14 days), for osterix (up to 60% increase) and osteonectin immunoexpression (up to 50% increase). In in vivo experiments, cell-free scaffolds of both types were subcutaneously implanted into the backs of mice and analyzed after 2, 4, 8 and 16 weeks. Also, in this case, SC1 more effectively promoted the osteogenic differentiation of infiltrated resident cells. In particular, increased immunoexpression of osterix and osteonectin (+30% and 35%, respectively) was found already at 2 weeks. It can be concluded that SC1 scaffolds may represent a valuable tool to address critical-sized bone defects. Full article

Background: Total neoadjuvant therapy (TNT) has emerged as a promising strategy for locally advanced rectal cancer (LARC). By administering both chemoradiotherapy (CRT) and systemic chemotherapy (CHT) pre-surgery, TNT is associated with improved disease-free survival (DFS), reduced distant metastases, and higher pathological complete response (pCR) rates. Materials and Methods: This study included patients with LARC who received various TNT schedules: induction chemotherapy (iCHT), consolidation chemotherapy (cCHT), or a combination of both (sandwichCHT). We analyzed treatment adherence, toxicity, and pathological response. Local and distant disease recurrence, as well as survival outcomes, were also evaluated. Results: Between May 2021 and January 2025, 70 patients received TNT. Treatment included iCHT (41%), sandwichCHT (49%), and cCHT (10%). Most patients (94%) received long-course radiotherapy (LCRT). Overall, TNT was well tolerated, with grade 2 gastrointestinal toxicity during CRT being the most common frequent adverse event (33%). Disease progression during TNT was noted in five patients (7%); three of these patients were receiving chemotherapy, while two underwent surgical resection of the primary tumor. A watch-and-wait strategy was adopted for five patients (7%) following TNT. Surgical procedures performed included anterior resection (92%), abdominoperineal resection (7%), and local excision (1%). Pathological assessment revealed an overall pCR rate of 30%. With a median follow-up of 17 months, no patients experienced local recurrence. Post-surgery, 10 patients (17%) developed disease progression. The median DFS was 14.7 months. Five patients (7%) died during the follow-up period, with only one death attributed to causes other than disease progression. Conclusions: In this cohort of LARC patients, TNT demonstrated favorable tolerability and encouraging short-term efficacy. Full article

Laurus nobilis L. is a widely cultivated plant, used for ornamental purposes, as a high-value spice crop, and in the flavor and fragrance industry. In natural medicine, it is well-known for its many beneficial properties (due to a broad spectrum of biologically active compounds) and used for the treatment of different disorders. In this study, natural deep eutectic solvents (NaDESs), coupled with microwave activation, were studied and applied for a green extraction of L. nobilis leaves. The main objective was to obtain a sustainable and multifunctional cosmetic and pharmaceutical ingredient (the NaDES-based extract itself), exploiting both the intrinsic cosmetic functionalities of NaDES components and the biological properties of laurel bioactive compounds. The most promising candidate was obtained from a eutectic system containing betaine, glycerol, and lactic acid. The evaluation of this NaDES-based complex reveals a considerable number of phenolic compounds (around 11.57 mg of gallic acid equivalents for a gram of fresh leaves) and a notable antioxidant activity (80.1% with respect to Trolox), with values quite constant over a period of six months. The complex exhibits effective antimicrobial activity against different Gram-positive (S. aureus and S. epidermidis) and Gram-negative (E. coli and P. aeruginosa) bacterial strains, with concentrations ranging from 3.8 to 7.5 mg/mL. Furthermore, the extract presents a pleasant fragrance, attributable to the selective extraction of different volatile aromatic compounds, as confirmed by GC-MS analysis. Full article

Osteoporosis (OP) is a chronic disease characterized by reduced bone mass and altered microarchitecture, leading to bone fragility and fractures. Due to its high morbidity, disability, and healthcare costs, identifying new biomarkers and therapeutic strategies is crucial for improving OP diagnosis and prevention. In this context, this narrative review aims to depict the role of carbohydrate-binding proteins Galectins (Gals) in the combined processes of inflammation and aging contributing to bone fragility by exploring their potential as novel therapeutic targets for OP. Full article

Asymptomatic bacteriuria (ASB) is a very frequent condition in kidney transplant recipients (KTRs). Guidelines advise against screening and treatment of ASB beyond the first month after renal transplantation. Here, we report the case of a 40-year-old female KTR with untreated ASB complicated with allograft pyelonephritis with urosepsis and acute kidney injury. The reported case highlights that ASB remains a grey area in the management of KTRs (after the first month), and there is a need for new ad hoc studies to identify which patients should be screened and eventually treated. Until new findings are available, it is suggested not to treat KTRs with ASB; however, if ASB is detected, stricter monitoring and non-antibiotic prophylaxis are necessary to favor prevention or prompt therapy of severe urinary tract infections. Full article

Background: Exophiala dermatitidis is a dematiaceous, thermotolerant, yeast-like fungus increasingly recognized as an opportunistic pathogen in chronic airway diseases. While commonly associated with cystic fibrosis, its clinical significance in non-cystic fibrosis bronchiectasis (NCFB) remains unclear. Case Presentation: We report the case of a 66-year-old immunocompetent woman with a history of breast cancer in remission and NCFB, who presented with chronic cough and dyspnea. Chest CT revealed bilateral bronchiectasis with new pseudonodular opacities. Bronchoalveolar lavage cultures identified E. dermatitidis, along with Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus. Given clinical stability and the absence of systemic signs, initial therapy included oral voriconazole, levofloxacin, doxycycline, and inhaled amikacin. Despite persistent fungal isolation on repeat bronchoscopy, the patient remained asymptomatic with stable radiologic and functional findings. Antifungal therapy was discontinued, and the patient continued under close monitoring. The patient exhibited clinical and radiological stability despite repeated fungal isolation, reinforcing the hypothesis of persistent colonization rather than active infection. Discussion: This case underscores the diagnostic challenges in distinguishing fungal colonization from true infection in structurally abnormal lungs. In NCFB, disrupted mucociliary clearance and microbial dysbiosis may facilitate fungal persistence, even in the absence of overt immunosuppression. The detection of E. dermatitidis should prompt a comprehensive evaluation, integrating clinical, radiologic, and microbiologic data to guide management. Voriconazole is currently the antifungal agent of choice, though therapeutic thresholds and duration remain undefined. Conclusions: This report highlights the potential role of E. dermatitidis as an under-recognized respiratory pathogen in NCFB and the importance of a multidisciplinary, individualized approach to diagnosis and treatment. This case underscores the need for further research on fungal colonization in NCFB and the development of evidence-based treatment guidelines. Further studies are needed to clarify the pathogenic significance, optimal management, and long-term outcomes of E. dermatitidis in non-CF chronic lung diseases. Full article