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Breast cancer represents the main malignancy in women and autologous fat grafting is a diffuse procedure in the management of post-surgical breast defects causing patients' psychosocial problems, with high costs for the public health. Recently, beneficial effects of fat grafting during post-surgical breast reconstruction have been amplified from the enrichment with human adipose-derived stem cells (ASCs) present in the stromal vascular fraction (SVF) of adult adipose tissue isolated during intraoperatory procedures. The major concern about the ASC enrichment during post-surgery breast reconstruction depends on their potential ability to release growth factors and hormones that can promote proliferation of residual or quiescent cancer cells, with the risk of de novo cancer development or recurrence. The recent description that adult stem cells primed in vitro may be vehicle for anti-cancer drug delivery offers a new vision concerning the role of ASCs in breast reconstruction after cancer surgery. Paclitaxel (PTX) is a chemotherapeutic agent acting as a microtubule-stabilizing drug inhibiting cancer cell mitotic activity. We optimized PTX loading and release in cultured ASCs and then analyzed the effects of PTX-loaded ASCs and their conditioned medium on CG5 breast cancer survival, proliferation and apoptosis in vitro, and inCG5 xenograft in vivo. We documented that ASCs can uptake and release PTX in vitro, with slight cytotoxic effects. Interestingly, PTX-loaded ASCs in co-culture, as well as conditioned medium alone, inhibited CG5 cell proliferation and survival in vitro and xenograft tumor growth in vivo. The antitumor effect of PTX-loaded ASCs may offer a new perspective concerning the use of ASCs during breast reconstruction becoming an additional local preventive chemotherapeutic agent against tumor recurrence. However, further experiments in vitro and in vivo are needed to collect more evidence confirming the efficacy and safety in cancer patients.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer in humans. The focal adhesion tyrosine kinase (FAK) is often over-expressed in human HCC and FAK inhibition may reduce HCC cell invasiveness. However, the anti-oncogenic effect of FAK knockdown in HCC cells remains to be clarified. We found that FAK depletion in HCC cells reduced in vitro and in vivo tumorigenicity, by inducing G2/M arrest and apoptosis, decreasing anchorage-independent growth, and modulating the expression of several cancer-related genes. Among these genes, we showed that FAK silencing decreased transcription and nuclear localization of enhancer of zeste homolog 2 (EZH2) and its tri-methylation activity on lysine 27 of histone H3 (H3K27me3). Accordingly, FAK, EZH2 and H3K27me3 were concomitantly upregulated in human HCCs compared to non-tumor livers. In vitro experiments demonstrated that FAK affected EZH2 expression and function by modulating, at least in part, p53 and E2F2/3 transcriptional activity. Moreover, FAK silencing downregulated both EZH2 binding and histone H3K27me3 levels at the promoter of its target gene NOTCH2. Finally, we found that pharmacological inhibition of FAK activity resembled these effects although milder. In summary, we demonstrate that FAK depletion reduces HCC cell growth by affecting cancer-promoting genes including the pro-oncogene EZH2 . Furthermore, we unveil a novel unprecedented FAK/EZH2 crosstalk in HCC cells, thus identifying a targetable network paving the way for new anticancer therapies.

The pentacyclic acridinium salt RHPS4 (3,11-difluoro-6,8,13-trimethyl-8 H -quino [4,3,2- kl ] acridinium methosulfate, compound 1 ) is one of the most interesting DNA G-quadruplex binding molecules due to its high efficacy in tumor cell growth inhibition both in in vitro models and in vivo against human tumor xenografts in combination with conventional chemotherapeutics. Despite compound 1 having desirable chemical and pharmaceutical properties, its potential as a therapeutic agent is compromised by off-target effects on cardiovascular physiology. In this paper we report a new series of structurally-related compounds which were developed in an attempt to minimize its off-target profile, but maintaining the same favorable chemical and pharmacological features of the lead compound. By performing a comparative analysis it was possible to identify which derivatives had the following properties: (i) to show a reduced capacity in respect to compound 1 to inhibit the hERG tail current tested in a patch clamp assay and/or to interact with the human recombinant β2 receptor; (ii) to maintain both a good G4-binding affinity and cancer cell selectivity; and (iii) to trigger DNA damage with specific telomere uncapping. These studies allowed us to identify a novel G4-stabilizing molecule, compound 8 , being characterized by reduced off-target effects and potent telomere on-target properties compared to the prototypic compound 1 . Moreover, compound 8 shares with compound 1 the same molecular mode of action and an anti-tumour activity specifically restricted to replicating cells, as evident with its particularly efficient activity in combination therapy with a topoisomerase I inhibitor. In conclusion, we have identified a new pentacyclic derivative 8 having suitable properties to be the focus of further investigations as a clinical candidate for cancer therapy.

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.

Background The introduction of single-family rooms (SFRs) in neonatal (NICUs) and paediatric intensive care units (PICUs) enhances family involvement and transforms healthcare professionals’ approach to patient care. This shift promotes family-centred care while requiring adjustments in staff workflows and communication. Given the significant implications of this structural change, this review examines the effects of SFRs on paediatric intensive care patient outcomes, families, healthcare staff, and healthcare organizations. Methods A systematic search was conducted in PubMed, CINAHL, PsycINFO, EMBASE, SCOPUS and Web of Science databases and grey literature. Studies published in English, Italian, and Spanish from 2009 to 2025 were included. The review adhered to the Johanna Briggs Institute methodology and PRISMA reporting guidelines to ensure rigor and transparency. Results A total of 649 records were identified, with 30 studies meeting inclusion criteria. Findings suggest that SFRs in NICUs positively impact neonatal neurodevelopment, parental participation, and staff experiences. Infants in SFRs demonstrated improved neurobehavioral outcomes, better sleep regulation, higher exclusive breastfeeding rates, and shorter hospital stays. Increased parental presence strengthened parent-infant bonding, facilitated earlier milk expression, and reduced maternal stress. However, concerns were raised regarding potential sensory deprivation, which could affect long-term language and motor development. From the healthcare staff perspective, SFRs were associated with increased job satisfaction, improved family-centred care, and reduced noise-related stress. However, some nurses reported greater emotional strain, professional isolation, and communication challenges. Organizationally, SFRs improved workflow efficiency, enhanced infection control adherence, and reduced costs due to shorter hospital stays. Despite these benefits, only one study evaluating in PICUs setting was included, highlighting a significant gap in research. Conclusions SFR NICUs offer substantial benefits in family-centred care, neurodevelopment, and hospital efficiency. Successful implementation requires careful planning to support staff well-being, promote collaboration, and address potential sensory deprivation. Healthcare administrators should ensure adequate training and emotional support of staff, and environmental enrichment strategies. Future research should focus on optimizing NICU designs to balance developmental advantages, parental engagement, staff satisfaction, and operational sustainability while expanding studies on PICU settings. Registration This review is registered in PROSPERO (CRD42024501520).

Nurse professionals often practice rectal stimulation in a hospital setting to help premature or full-term babies evacuate or to avoid abdominal pain caused by gas colic. Paediatricians also recommend this technique to newborn caregivers, who can carry it out independently at home. To the best of our knowledge, there are no established national guidelines on how to implement this technique safely or what the clinical/care indications are for its use. Our purpose is to synthesise the evidence on the nursing practice of rectal stimulation in preterm and full-term newborns. A narrative literature review was conducted. A search was conducted across six databases in February, followed by a manual review of the included studies' bibliographies, and another search in October 2023. The search strategy identified studies published without date limits. The articles were screened according to the inclusion criteria. Sixty-two articles were retrieved. Following the screening process, only two articles were selected for inclusion in the final synthesis. Both studies evaluated the effects of enemas and/or rectal stimulation on feeding tolerance and bowel habits in preterm newborns. Even if both studies included information on when rectal stimulation in preterm newborns is indicated and how it is conducted, they are insufficient to provide a clear statement for nursing practice. Nowadays, nurses perform rectal stimulation and teach it to caregivers of newborns without shared international or national guidelines or procedures focused on patient safety. It is desirable to conduct scientific studies to inform nursing practice and enhance the quality of nursing care delivered. This review also highlights a critical gap in evidence regarding the use of rectal stimulation in full-term newborns and in community settings.

Background/Objectives: Adaptation to extrauterine life is challenging for preterm newborns. Environmental stimuli, such as noise, can lead to adverse health outcomes, causing instability of vital parameters and impairment of neurodevelopment. The American Academy of Pediatrics recommends a maximum environmental noise level of 45 decibels (dB) or less in the NICU. The study’s primary aim was to describe environmental noise in a neonatal intensive care unit and to analyze potential associations between noise and vital parameters of preterm newborns, including heart rate, respiratory rate, and oxygen saturation levels. Methods: A pilot observational feasibility study was conducted in a level III NICU. Sound levels and vital parameters were recorded over four hours for each preterm newborn. Confounding variables were controlled. Data were analyzed using descriptive statistics, Kendall’s τ-b, and logistic regression analysis. Ethical approval and parental consent were obtained. Results: The average environmental noise level was consistently above 45 dB. Six patients were enrolled, and 22 recordings (ranging in length from 1 to 4 h) were performed. Data adjusted for confounding variables show a statistically significant Kendall’s correlation between heart rate and decibels (τ-b = 0.89, p = 0.003, n = 520), suggesting a monotonous crescent tendency between these two variables, although the relationship is not strong. The logistic regression model indicates that the odds ratio (OR) for decibels related to tachycardia is 1.066, meaning that for each 1 dB increase, the probability of tachycardia rises by 6.6% (p < 0.001). Conversely, the OR for respiratory rate is 0.959, suggesting that for each unit increase in respiratory rate, the probability of tachycardia decreases by approximately 4.1% (p < 0.001). Conclusions: The study reveals that the mean environmental noise level in the NICU consistently exceeds the recommended safety level. Decibels are one of the significant variables contributing to the likelihood of tachycardia, and an increase in decibels has a significant effect on this, but it is not the only one. Further analysis of a larger sample is needed.

Background/Objectives: In recent years, some hospitals have shifted from traditional to intensity-of-care-based organizational models, where patients allocation is based on the care they require. In this context, Nursing Patient Classification Systems (NPCSs) can lead to the identification of the appropriate nursing care setting based on patient nursing needs; this also applies to pediatrics. In this scenario, the concept of patient nursing complexity has emerged. This narrative literature review aims to provide an overview on validated NPCSs that assess the nursing complexity of pediatric patients. Methods: PubMed, CINAHL, and the Cochrane Library were searched, and inclusion and exclusion criteria were applied to the retrieved papers. Two authors independently screened n = 498 papers, of which n = 7 were read in full and subsequently excluded. Results: No paper met the inclusion criteria. However, papers read in full were analyzed, and their main characteristics were described. They were excluded because they did not concern validated NPCSs that assess pediatric patients’ nursing complexity or did not assess pediatric patients’ nursing complexity as defined in this literature review. Conclusions: This narrative literature review highlighted a critical gap in the field of validated NPCSs that assess the nursing complexity of pediatric patients. The lack of a shared definition of “nursing complexity of the patient” is the primary barrier identified. This constitutes a crucial take-home message. Therefore, future studies should prioritize in-depth exploration of the differences among all the published definitions and concepts related to “complexity” and harmonizing existing conceptual analysis to guide future research and the development of shared NPCSs.

Introduction: the design of neonatal and paediatric neonatal intensive care significantly impacts the outcomes of the families, workers, and organizations. The aim of this review is to identify the effects of the introduction of the single-family room in neonatal intensive care and paediatric intensive care on the outcomes of paediatric patients, families, staff, and organizations. Materials and Methods: we structured this work as a systematic review, registered on PROSPERO (CRD42024501520). This review has been developed using Joanna Briggs Institute recommendations. The database search will include PubMed, CINAHL, SCOPUS, EMBASE, PsycINFO, Web of Science. Documents published in English, Italian and Spanish from 2009 will be included. Results: the results of this review will provide insights on the effects of the introduction of single-family room assessment. This could help nursing stakeholders to effectively evaluate and eventually plan the transition to single-family room assessment to ensure quality of care, user and staff satisfaction. Discussion: the introduction of single-family room structure plays a pivotal role in family involvement and active participation in their child’s care. Also, this requires modifications in healthcare professionals’ way of approaching and planning patient care. Considering the importance and the substantial changes that single-family room could bring to patients, families, staff and organizational outcomes, this review may provide important insights for the introduction of single-family room on patients, families, staff, and organizations building a rationale on the introduction of this new organizational structure. Introduzione: la progettazione della terapia intensiva neonatale e pediatrica ha un impatto significativo sugli esiti delle famiglie, degli operatori e delle organizzazioni. Lo scopo di questa revisione è identificare gli effetti dell'introduzione delle single family room nelle terapie intensive neonatali e pediatriche sugli esiti dei pazienti pediatrici, delle famiglie, del personale e delle organizzazioni. Materiali e metodi: abbiamo strutturato questo lavoro come una revisione sistematica, registrata su PROSPERO (CRD42024501520). Questa revisione è stata sviluppata utilizzando le raccomandazioni del Joanna Briggs Institute. La ricerca nelle banche dati comprende PubMed, CINAHL, SCOPUS, EMBASE, PsycINFO, Web of Science. Saranno inclusi i documenti pubblicati in inglese, italiano e spagnolo a partire dal 2009. Risultati: i risultati di questa revisione forniranno approfondimenti sugli effetti dell'introduzione delle single family room. Ciò potrebbe aiutare gli operatori del settore infermieristico a valutare efficacemente ed eventualmente a strutturare il passaggio alla single family room per garantire la qualità dell'assistenza, la soddisfazione degli utenti e del personale. Discussione: l'introduzione delle single family room gioca un ruolo fondamentale nel coinvolgimento e nella partecipazione attiva della famiglia nella cura del proprio figlio. Inoltre, ciò richiede modifiche nel modo in cui gli operatori sanitari approcciano e pianificano l'assistenza ai pazienti. Considerando l'importanza e i cambiamenti sostanziali che la single family room potrebbe apportare ai pazienti, alle famiglie, al personale e ai risultati organizzativi, questa revisione può fornire importanti spunti per l'introduzione della single family room e i suoi esiti su pazienti, famiglie, personale e organizzazioni, costruendo un razionale sull'introduzione di questa nuova struttura organizzativa.