Explore the vast range of titles available.

Background Pulmonary fibrosis is a progressive interstitial lung disease driven by aberrant alveolar epithelial repair and dysregulated crosstalk with mesenchymal cells, leading to myofibroblast activation and excessive extracellular matrix deposition. Current mouse models for studying its pathogenesis often use invasive methods like intratracheal bleomycin administration, which can cause significant animal distress. This study aims to refine the bleomycin model via intranasal instillation, reducing animal suffering while improving reproducibility and translational value. Methods The MALDI-TOF MS analysis allowed for the identification of the spatial distribution of bleomycin directly on the lung tissue of C57BL/6 J mice after intranasal administration to demonstrate the effectiveness of this route. Different doses (1, 3, 5 mg/kg) of bleomycin were tested in mice. Non-invasive whole-body plethysmography enabled the monitoring of the disease progression and the assessment of pulmonary function in conscious mice. Histopathological analyses were performed to follow fibrosis progression. Results This method resulted in impaired respiratory function, with a similar pattern observed for both 5 and 3 mg/kg doses. Histopathological evaluations revealed rapid acute inflammation followed by chronic fibrosis in both dosage groups, similar to human IPF. Key molecular markers (CD68 and COL 1a1) were upregulated in response to the treatment, with similar expression patterns between the two doses, suggesting an inflammatory response and established fibrosis. 1 mg/kg dosage did not lead to any relevant clinical changes and was therefore excluded from further analyses. Conclusions Intranasal administration proved to be an efficient technique, delivering a uniform bleomycin distribution in the lungs. Bleomycin instillation induced lung injury and fibrosis comparable to those achieved with the conventional intratracheal protocol, both histologically and functionally, while reducing invasiveness and animal distress. The optimal bleomycin dosage was determined to be 3 mg/kg, which induced a similar level of respiratory distress, but with less weight loss and reduced risk of mortality. This approach provides a reproducible model for preclinical studies of pulmonary fibrosis. This strategy ensures consistent and reproducible scientific data, pivotal for bridging the gap between benchside and bedside. Graphical abstract

Introduction The usual interstitial pneumonia (UIP) pattern, hallmark of idiopathic pulmonary fibrosis (IPF), may induce harmful local overdistension during mechanical ventilation given the juxtaposition of different tissue elasticities. Mechanotransduction, linking mechanical stress and strain to molecular pro-fibrotic pathways, likely contributes to fibrosis progression. Understanding the mechanical forces and aeration patterns in the lungs of IPF patients is crucial for unraveling potential mechanisms of disease progression. Quantitative lung computed tomography (CT) can accurately assess the air content of lung regions, thus informing on zonal distension. This study aims to investigate radiological evidence of lung over aeration in spontaneously breathing UIP patients compared to healthy controls during maximal inspiration. Methods Patients with IPF diagnosis referred to the Center for Rare Lung Diseases of the University Hospital of Modena (Italy) in the period 2020–2023 who underwent High Resolution Computed Tomography (HRCT) scans at residual volume (RV) and total lung capacity (TLC) using standardized protocols were retrospectively considered eligible. Patients with no signs of lung disease at HRCT performed with the same image acquisition protocol nor at pulmonary function test (PFTs) served as controls. Lung segmentation and quantitative analysis were performed using 3D Slicer software. Lung volumes were measured, and specific density thresholds defined over aerated and fibrotic regions. Comparison between over aerated lung at RV and TLC in the two groups and according to lung lobes was sought. Further, the correlation between aerated lung and the extent of fibrosis was assessed and compared at RV and TLC. Results IPF patients (N = 20) exhibited higher over aerated lung proportions than controls (N = 15) both at RV and TLC (4.5% vs. 0.7%, p < 0.0001 and 13.8% vs. 7%, p < 0.0001 respectively). Over aeration increased significantly from RV to TLC in both groups, with no intergroup difference (p = 0.67). Sensitivity analysis revealed significant variations in over aerated lung areas among lobes when passing from RV to TLC with no difference within lobes (p = 0.28). Correlation between over aeration and fibrosis extent was moderate at RV (r = 0.62, p < 0.0001) and weak at TLC (r = 0.27, p = 0.01), being the two significantly different at interpolation analysis (p < 0.0001). Conclusions This study provides the first evidence of radiological signs of lung over aeration in patients with UIP-pattern patients when passing from RV to TLC. These findings offer new insights into the complex interplay between mechanical forces, lung structure, and fibrosis and warrant larger and longitudinal investigations.

Idiopathic pulmonary fibrosis (IPF) is a chronic, rare, and fatal disease that is the consequence of aberrant remodeling and defective repair mechanisms within the lung, culminating in the loss of alveolar integrity. Although significant progress has been made in understanding the pathogenesis, it would be crucial to identify biomarkers for diagnosis, prognosis, and prediction of therapy response to improve the management of this challenging and debilitating disease. Omics technologies have profoundly advanced the understanding of disease mechanisms, presenting considerable potential for the identification of clinically relevant biomarkers. To date, specific molecular pathways have been implicated in the onset and progression of idiopathic pulmonary fibrosis, including abnormal wounding, fibroblast proliferation, inflammation, deposition of the extracellular matrix, oxidative stress, endoplasmic reticulum stress, and the coagulation system. This review highlights the role of proteomics in identifying key biomarkers for IPF, focusing on their clinical relevance, including diagnosis, prognosis, disease progression, and the identification of new therapeutic options, in light of the most recent technological advancements in mass spectrometry.

Recent advances in genetics and epigenetics have provided critical insights into the pathogenesis of both idiopathic and non-idiopathic interstitial lung diseases (ILDs). Mutations in telomere-related genes and surfactant proteins have been linked to familial pulmonary fibrosis, while variants in MUC5B and TOLLIP increase the risk of ILD, including idiopathic pulmonary fibrosis and rheumatoid arthritis-associated ILD. Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs such as miR-21 and miR-29, regulate fibrotic pathways, influencing disease onset and progression. Although no standardized genetic panel for ILD exists, understanding the interplay of genetic mutations and epigenetic alterations could aid in the development of personalized therapeutic approaches. This review highlights the genetic and epigenetic factors driving ILD, emphasizing their potential for refining diagnosis and treatment.

Virtual reality (VR) can be a promising tool to simulate reality in various settings but the real impact of this technology on the human mental system is still unclear as to how VR might (if at all) interfere with cognitive functioning. Using a computer, we can concentrate, enter a state of flow, and still maintain control over our surrounding world. Differently, VR is a very immersive experience which could be a challenge for our ability to allocate divided attention to the environment to perform executive functioning tasks. This may also have a different impact on women and men since gender differences in both executive functioning and the immersivity experience have been referred to by the literature. The present study aims to investigate cognitive multitasking performance as a function of (1) virtual reality and computer administration and (2) gender differences. To explore this issue, subjects were asked to perform simultaneous tasks (span forward and backward, logical–arithmetic reasoning, and visuospatial reasoning) in virtual reality via a head-mounted display system (HDMS) and on a personal computer (PC). Our results showed in virtual reality an overall impairment of executive functioning but a better performance of women, compared to men, in visuospatial reasoning. These findings are consistent with previous studies showing a detrimental effect of virtual reality on cognitive functioning.

Background: The molecular pathways involved in the onset and progression of idiopathic pulmonary fibrosis (IPF) still need to be fully clarified as some are shared with lung cancer development. HOXB7, a member of the homeobox (Hox) gene family, has been found involved in various cancers. Methods: Immunohistochemical (IHC) analysis was run on lung tissue samples from surgical lung biopsy (SLB) of 19 patients with IPF, retrospectively selected from the IPF database of the University Hospital of Modena. HOXB7 expression was analyzed and compared with that of five patients with no evidence of pulmonary fibrosis as controls. Results: The semi-quantitative analysis of IHC showed that HOXB7 protein expression was higher in IPF patients compared to controls (difference between means = 6.2 ± 2.37, p = 0.0157). Further, HOXB7 expression was higher in IPF patients with a higher extent of fibrosis (50–75%)—measured with high-resolution computer tomography—compared to those with a lower extent (0–25%) (difference between means = 25.74 ± 6.72, p = 0.004). Conclusions: The expression of HOXB7 is higher in the lung of IPF patients compared to controls, and was represented in different cellular compartments within the lung niche. Further investigations are needed to clarify its role in the pathogenesis and progression of IPF.

Background Although patients with interstitial pneumonia pattern (ILD-UIP) and acute exacerbation (AE) leading to severe acute respiratory failure may require invasive mechanical ventilation (MV), physiological data on lung mechanics during MV are lacking. We aimed at describing the physiological effect of lung-protective ventilation in patients with AE-ILD-UIP compared with primary ARDS. Methods Partitioned lung and chest wall mechanics were assessed in a series of AE-ILD-UIP patients matched 1:1 with primary ARDS as controls (based on BMI and PaO 2 /FiO 2 ratio). Three PEEP levels (zero =  ZEEP , 4–8 cmH 2 O =  PEEP LOW , and titrated to achieve positive end-expiratory transpulmonary pressure P L,EE  =  PEEP TITRATED ) were used for measurements. Results Ten AE-ILD-UIP patients and 10 matched ARDS were included. In AE-ILD-UIP median P L,EE at ZEEP was − 4.3 [− 7.6– − 2.3] cmH 2 O and lung elastance ( E L ) 44 [40–51] cmH 2 O/L. At PEEP LOW , P L,EE remained negative and E L did not change ( p  = 0.995) versus ZEEP. At PEEP TITRATED , P L,EE increased to 0.8 [0.3–1.5] cmH 2 O and E L to 49 [43–59] ( p  = 0.004 and p  < 0.001 compared to ZEEP and PEEP LOW , respectively). Δ P L decreased at PEEP LOW ( p  = 0.018) and increased at PEEP TITRATED ( p  = 0.003). In matched ARDS control PEEP titration to obtain a positive P L,EE did not result in significant changes in E L and Δ P L . Conclusions In mechanically ventilated AE-ILD-UIP patients, differently than in patients with primary ARDS, PEEP titrated to obtain a positive P L,EE significantly worsened lung mechanics.

In recent years, several studies have examined the impact of sleep-disordered breathing (SBD) on the quality of life and prognosis of patients with idiopathic pulmonary fibrosis (IPF). Among these disorders, obstructive sleep apnea (OSA) and nocturnal hypoxemia (NH) are the most prevalent and extensively studied, whereas central sleep apnea (CSA) has only been documented in recent research. The mechanisms underlying the relationship between IPF and SBDs are complex and remain an area of active investigation. Despite growing recognition of SBDs in IPF, no standardized guidelines exist for their management and treatment, particularly in a population characterized by distinct structural pulmonary abnormalities. This review outlines the pathophysiological connections between sleep-breathing disorders (SBDs) and idiopathic pulmonary fibrosis (IPF), as well as current therapeutic options. A comprehensive literature search using PubMed identified relevant studies, confirming the efficacy of CPAP in treating severe OSA and CSA. While high-flow oxygen therapy has not been validated in this patient cohort, it may offer a potential solution for select patients, particularly the elderly and those with low compliance. Conventional oxygen therapy, however, is limited to cases of isolated nocturnal hypoxemia or mild central sleep apnea.

ICOSL/ICOS are costimulatory molecules pertaining to immune checkpoints; their binding transduces signals having anti-tumor activity. Osteopontin (OPN) is here identified as a ligand for ICOSL. OPN binds a different domain from that used by ICOS, and the binding induces a conformational change in OPN, exposing domains that are relevant for its functions. Here we show that in vitro, ICOSL triggering by OPN induces cell migration, while inhibiting anchorage-independent cell growth. The mouse 4T1 breast cancer model confirms these data. In vivo, OPN-triggering of ICOSL increases angiogenesis and tumor metastatization. The findings shed new light on ICOSL function and indicate that another partner beside ICOS may be involved; they also provide a rationale for developing alternative therapeutic approaches targeting this molecular trio. Davide Raineri, Chiara Dianzani et al. show that osteopontin binds ICOSL at a different domain than the one used by ICOS. Activation of ICOSL by osteopontin induces cell migration in vitro and tumor metastatization in a 4T1 breast cancer mouse model; highlighting the functional role of this interaction in cancer progression.

Persistent left ventricular (LV) systolic dysfunction in patients with acute lymphocytic myocarditis (LM) is widely unexplored. To assess the frequency and predictors of persistent LV dysfunction in patients with LM and reduced LVEF at admission. We retrospectively evaluated 89 consecutive patients with histologically-proven acute myocarditis enrolled at three Italian referral hospitals. A subgroup of 48 patients with LM, baseline systolic impairment and an available echocardiographic assessment at 12 months (6-18) from discharge constituted the study population. The primary study end-point was persistent LV dysfunction, defined as LVEF <50% at 1-year, and was observed in 27/48 patients (56.3%). Higher LV end-diastolic diameter at admission (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.04-1.43, p = 0.002), non-fulminant presentation (OR 8.46, 95% CI 1.28-55.75, p = 0.013) and presence of a poor lymphocytic infiltrate (OR 12.40, 95% CI 1.23-124.97, p = 0.010) emerged as independent predictors of persistent LV dysfunction at multivariate analysis (area under the curve 0.91, 95% CI 0.82-0.99). Pre-discharge LVEF was lower in patients with persistent LV dysfunction compared to the others (32%±8 vs. 53%±8, p <0.001), and this single variable showed the best accuracy in predicting the study end-point (area under the curve 0.95, 95% CI 0.89-1.00). More than half of patients presenting with acute LM and LVEF <50% who survive the acute phase show persistent LV dysfunction after 1-year from hospital discharge. Features of subacute inflammatory process and of established myocardial damage at initial hospitalization emerged as predictors of this end-point.