Search Results (90)

Congenital heart disease (CHD) represents a prevalent group of structural cardiac anomalies often associated with alterations in key transcription factors including NKX2-5, TBX5, and, particularly, GATA4. GATA4 is a zinc finger transcription factor essential for regulating genes involved in cardiogenesis. Here, we report the identification of a novel heterozygous missense variant in GATA4 (NM_002052.5:c.907G>T, p.Gly303Trp) in a family with a history of CHD. The proband, exhibiting ventricular septal defect (VSD) and pulmonary stenosis, was referred for genetic evaluation after recurrent spontaneous abortions occurred in their partner. In addition, the mother of the proband has a history of atrial septal defect (ASD) with pulmonary stenosis, which suggests a familial inheritance pattern. Full article

Background/Objectives: Peristomal skin complications (PSCs) are common among patients with ostomies, significantly impacting quality of life and increasing healthcare utilization. This study aimed to evaluate the effects of the Dermamecum protocol, a risk-stratified educational intervention, on the prevention of PSCs, self-care improvements, health-related quality of life (HRQoL), and patient satisfaction over a 90-day follow-up period. Methods: This prospective cohort study included 305 patients stratified into three risk-based groups (green, yellow, and red paths) according to the Dermamecum protocol. Primary outcomes included PSC rates at 30, 60, and 90 days. Secondary outcomes included self-care scores, HRQoL, and patient satisfaction. Comparative analyses and trend assessments were performed across groups and time points. Temporal trends in PSCs were analyzed using Poisson regression. Results: Early PSC rates were 8.5% at 30 days, with late complications at 7.9% and 6.2% at 60 and 90 days, respectively. No significant differences in PSC rates were observed between paths. Self-care scores improved over time, with stability across groups and domains. HRQoL remained stable, with minor fluctuations in physical and mental components. Patient satisfaction was high across all paths. Poisson regression identified significant temporal trends in PSC rates, with higher risks at 30, 60, and 90 days compared to baseline. Age, BMI, and path assignment (lower risk for the green path) were significant predictors of PSCs. Conclusions: The Dermamecum protocol effectively maintained low PSC rates, supported self-care, and sustained HRQoL and patient satisfaction. These findings highlight the value of risk-stratified, patient-centered interventions in ostomy care. Further studies are needed to validate these results and explore long-term outcomes. Full article

Background/Objectives: Recent studies have highlighted the role of the gut–muscle axis, suggesting that modulation of the gut microbiota may indirectly benefit skeletal muscle. This study aimed to evaluate the effects of Lactobacillus fermentum (L. fermentum) supplementation in a model of muscle atrophy induced by chronic ethanol (EtOH) intake, focusing on inflammatory and antioxidant mechanisms. Methods: Sixty 12-month-old female Balb/c mice were divided randomly into three groups (n = 20/group): (1) Ethanol (EtOH) group, receiving ethanol daily for 8 and 12 weeks to induce systemic oxidative stress and inflammation; (2) Ethanol + Probiotic (EtOH + P) group, receiving both ethanol and L. fermentum supplementation for the same durations; and (3) Control (Ctrl) group, receiving only water. Muscle samples were analyzed for the fiber morphology, inflammatory markers, oxidative stress indicators, and satellite cell (SC) activity. All data were tested for normality using the Shapiro–Wilk test before applying a parametric analysis. A statistical analysis was performed using one-way ANOVA followed by a Bonferroni post-hoc test. The level of significance was set at p < 0.05. Results: EtOH exposure caused significant atrophy in all muscle fiber types (type I, IIa, and IIb), with the most pronounced effects on oxidative fibers. L. fermentum supplementation significantly reversed atrophy in type I and IIa fibers, accompanied by a significant reduction in IL-6, TNF-α, and Hsp60 expression levels, indicating the protective effect of L. fermentum against oxidative stress and inflammation. Moreover, the probiotic treatment increased MyoD expression in SCs, suggesting enhanced regenerative activity, without histological evidence of fibrosis. Conclusions: These findings suggest that L. fermentum supplementation could counteract EtOH-induced skeletal muscle damage by reducing inflammation and oxidative stress and promoting muscle repair, indicating its potential as an adjuvant, in the therapeutic strategy of models of muscle degeneration. Full article

Background: Implant-based breast reconstruction (IBBR) following conservative mastectomy is the most common approach for women undergoing breast cancer surgery. The aim of this study was to compare the oncological outcomes of conservative mastectomy combined with prepectoral IBBR to the subpectoral technique. Methods: The clinical and demographic data of consecutive breast cancer patients who underwent conservative mastectomy with either prepectoral or subpectoral IBBR between January 2018 and December 2023 were retrospectively analyzed. The primary outcome was the impact of conservative mastectomy with prepectoral IBBR on local recurrence-free survival (LRFS). Secondary outcomes included distant disease-free survival (DDFS) and overall survival (OS). Results: A total of 842 women (with a median age of 46 years and a range of 20–79 years) were included in the study. Of these, 648 patients (77.0%) underwent prepectoral IBBR, while 194 (23.0%) received subpectoral IBBR. The median follow-up was 32 months (3–74). Locoregional relapse occurred in 19 patients (2.9%) in the prepectoral group and 14 (7.2%) in the subpectoral group. Distant metastases were observed in 21 (3.2%) patients in the prepectoral group and 11 (5.7%) in the subpectoral group. Deaths were reported in eight patients (1.2%) in the prepectoral group and five (2.6%) in the subpectoral group. There were no statistically significant differences between the two groups in terms of the LRFS, DDFS, and OS (p = 0.676; p = 0.994; p = 0.940, respectively). Conclusions: Our study indicates that conservative mastectomy combined with prepectoral IBBR produces similar results to those of the subpectoral approach, with no significant differences in LRFS, DDFS, and OS. Full article

In recent years, the invasive Atlantic blue crab (Callinectes sapidus) has increased its spread throughout the Mediterranean Sea, threatening native biodiversity and local economies. This study aimed to valorize C. sapidus sampled in Sicily by utilizing its exoskeleton as a source of chitosan, astaxanthin, and bio-phenolic compounds. These biomolecules were evaluated for their reducing, radical scavenging, and antitumor activity. The ferric ion reducing antioxidant power (FRAP) and the free radical scavenging activity against radical 2,2-Diphenyl-1-picrylhydrazyl (DPPH) were significantly higher for chitosan (3.16 ± 0.10 mg AAE/g and 8.1 ± 0.10 µmol TE/g). No significant differences were observed among the tested biomolecules in their activity in scavenging the radical 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Both bio-phenolic compounds and astaxanthin exhibited dose-dependent cytotoxicity on CaCo-2 (IC₅₀ = 12.47 and 18 µg/mL) and HepG2 (IC₅₀ = 10.25 and 1.26 µg/mL) cell lines, while only bio-phenols showed no cytotoxic effect on differentiated CaCo-2 cells up to 20 µg/mL. These findings highlight the value of blue crab by-products in supporting a circular economy, offering a sustainable approach to managing this invasive species while providing bioactive compounds with promising medical and nutraceutical applications. Full article

This study evaluates, for the first time, the reducing capacity, radical scavenger activity, and in vitro antitumor and anti-inflammatory effects of chitosan, astaxanthin, and bio-phenols extracted from the exoskeleton of Sicilian Procambarus clarkii, the most widespread species of invasive crayfish in the Mediterranean region. Among the extracted compounds, astaxanthin exhibited the highest antioxidant activity in all assays. Chitosan and polyphenols demonstrated reducing and radical scavenging activity; chitosan showed significant ferric ion reducing capacity in the FRAP test, while bio-phenolic compounds displayed notable radical scavenging activity in the DPPH and ABTS assays. Both astaxanthin and polyphenols showed dose-dependent cytotoxicity on two different cancer cell lines, with IC50 values of 1.45 µg/mL (phenolic extract) and 4.28 µg/mL (astaxanthin extract) for HepG2 cells and 2.45 µg/mL (phenolic extract) and 4.57 µg/mL (astaxanthin extract) for CaCo-2 cells. The bio-phenolic extract also showed potential anti-inflammatory effects in vitro by inhibiting nitric oxide production in inflamed RAW 264.7 macrophages, reducing the treated/control NO ratio to 77% and 74% at concentrations of 1.25 and 1.5 μg/mL, respectively. These results suggest that P. clarkii exoskeletons could be a valuable source of bioactive molecules for biomedical, pharmaceutical, and nutraceutical application while contributing to the sustainable management of this invasive species. Full article

Protein tyrosine phosphatases (PTPs) are a family of enzymes essential for numerous cellular processes, such as cell growth, inflammation, differentiation, immune-mediated responses and oncogenic transformation. The aim of this review is to review the literature concerning the role of several PTPs—PTPN22, PTPN2, PTPN6, PTPN11, PTPσ, DUSP2, DUSP6 and PTPRK—at the level of the intestinal mucosa in inflammatory bowel disease (IBD), celiac disease (CeD) and type 1 diabetes (T1D) in both in vitro and in vivo models. The results revealed shared features, at the level of the intestinal mucosa, between these diseases characterized by alterations of different biological processes, such as proliferation, autoimmunity, cell death, autophagy and inflammation. PTPs are now actively studied to develop new drugs. Also considering the availability of organoids as models to test new drugs in personalized ways, it is very likely that soon these proteins will be the targets of useful drugs. Full article

This study, employing an interim analysis, investigates the effects of the Dermamecum protocol, a structured educational and tailored approach that stratifies ostomy patients into risk paths (green, yellow, red) based on pre-operative and post-operative characteristics. The green path indicates a low risk of peristomal skin complications (PSCs), focusing on sustaining healthy behaviours and basic stoma care. The yellow path represents a moderate risk, emphasizing the need for patients to self-monitor and recognize early signs of complications. The red path corresponds to high risk, requiring stringent monitoring and immediate access to healthcare support. The study aims to reduce PSCs and improve patient outcomes. Methods include the stratification of 226 patients, with significant differences in gender distribution, BMI categories, and stoma types across the paths. Results show an occurrence rate of PSCs of 5.9% in all risk paths (5.7% green path, 4.7% yellow path, and 7.9% red path, p = 0.685), significantly lower than the median rate of 35% reported in the literature. Multiple correspondence analysis validated the stratification, with distinct clusters for each path. Poisson regression models in the exploratory framework of an interim analysis identified male gender as the only significant predictor of PSCs, indicating the need for gender-specific interventions. The findings suggest that the Dermamecum protocol effectively reduces early PSCs, providing a foundation for further research. Full article

The occurrence of antibiotic-resistant bacteria in foodstuff involves a human health risk. Edible insects are a precious resource; however, their consumption raises food safety issues. In this study, the occurrence of antibiotic resistant bacteria in laboratory-reared fresh mealworm larvae (Tenebrio molitor L.) and frass was assessed. Antibiotics were not used during the rearing. Enterobacteriaceae and enterococci were isolated from 17 larvae and eight frass samples. In total, 62 and 69 isolates presumed to belong to Enterobacteriaceae and Enterococcus spp., respectively, were obtained and tested for antibiotic susceptibility via disk diffusion. Based on the results, isolates were grouped, and representative resistant isolates were identified at species level through 16S rRNA gene sequencing. For enterococci resistance, percentages higher than 15% were observed for vancomycin and quinupristin–dalfopristin, whereas Enterobacteriaceae resistance higher than 25% was found against cefoxitin, ampicillin, and amoxicillin–clavulanic acid. Based on the species identification, the observed resistances seemed to be intrinsic both for enterococci and Enterobacteriaceae, except for some β-lactams resistance in Shigella boydii (cefoxitin and aztreonam). These could be due to transferable genetic elements. This study suggests the need for further investigations to clarify the role of edible insects in the spreading of antibiotic resistance determinants through the food chain. Full article

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by self-immune tolerance breakdown and the production of autoantibodies, causing the deposition of immune complexes and triggering inflammation and immune-mediated damage. SLE pathogenesis involves genetic predisposition and a combination of environmental factors. Clinical manifestations are variable, making an early diagnosis challenging. Heat shock proteins (Hsps), belonging to the chaperone system, interact with the immune system, acting as pro-inflammatory factors, autoantigens, as well as immune tolerance promoters. Increased levels of some Hsps and the production of autoantibodies against them are correlated with SLE onset and progression. The production of these autoantibodies has been attributed to molecular mimicry, occurring upon viral and bacterial infections, since they are evolutionary highly conserved. Gut microbiota dysbiosis has been associated with the occurrence and severity of SLE. Numerous findings suggest that proteins and metabolites of commensal bacteria can mimic autoantigens, inducing autoimmunity, because of molecular mimicry. Here, we propose that shared epitopes between human Hsps and those of gut commensal bacteria cause the production of anti-Hsp autoantibodies that cross-react with human molecules, contributing to SLE pathogenesis. Thus, the involvement of the chaperone system, gut microbiota dysbiosis, and molecular mimicry in SLE ought to be coordinately studied. Full article

Background: Dysbiosis, influenced by poor diet or stress, is associated with various systemic diseases. Probiotic supplements are recognized for stabilizing gut microbiota and alleviating gastrointestinal issues, like irritable bowel syndrome (IBS). This study focused on the tryptophan pathways, which are important for the regulation of serotonin levels, and on host physiology and behavior regulation. Methods: Nanovesicles were isolated from the plasma of subjects with chronic diarrhea, both before and after 60 days of consuming a probiotic mix (Acronelle^®, Bromatech S.r.l., Milan, Italy). These nanovesicles were assessed for the presence of Tryptophan 2,3-dioxygenase 2 (TDO 2). Furthermore, the probiotics mix, in combination with H₂O₂, was used to treat HT29 cells to explore its cytoprotective and anti-stress effect. Results: In vivo, levels of TDO 2 in nanovesicles were enhanced in the blood after probiotic treatment, suggesting a role in the gut–brain axis. In the in vitro model, a typical H₂O₂-induced stress effect occurred, which the probiotics mix was able to recover, showing a cytoprotective effect. The probiotics mix treatment significantly reduced the heat shock protein 60 kDa levels and was able to preserve intestinal integrity and barrier function by restoring the expression and redistribution of tight junction proteins. Moreover, the probiotics mix increased the expression of TDO 2 and serotonin receptors. Conclusions: This study provides evidence for the gut–brain axis mediation by nanovesicles, influencing central nervous system function. Full article

Acoustic radiation forced impulse (ARFI) is an integrated ultrasound method, measuring stiffness by point shear wave elastography. To evaluate the diagnostic performance of the ARFI of the liver and the spleen, combined with spleen dimension and platelet count, in predicting high-risk esophageal varices (HRVs) in cirrhotic patients, a prospective and cross-sectional study was conducted between February 2017 and February 2021. The following ratio scores were calculated based on ARFI measurements: ALSDP (ARFI Liver–Spleen Diameter-to-Platelet Ratio Score), ASSDP (ARFI Spleen–Spleen Diameter-to-Platelet Ratio Score), ASSAP (ARFI Spleen–Spleen Area-to-Platelet Ratio Score), and ALSAP (ARFI Liver–Spleen Area-to-Platelet Ratio Score). In 100 enrolled subjects, spleen ARFI, ASSDP, and ASSAP were significantly associated with HRVs in the prospective short- and long-term follow-ups and in the cross-sectional study (p < 0.05), while ALSDP and ALSAP were associated with HRVs only in the prospective long-term follow-up and cross-sectional study (p< 0.05). ASSAP was the best ARFI ratio score for HRVs at the long-term follow-up [value of area under curve (AUC) = 0.88], although all the ARFI ratio scores performed better than individual liver and spleen ARFI (AUC > 0.7). In our study, ARFI ratio scores can predict, in well-compensated cirrhotic patients, the risk of developing HVRs in short- and long-term periods. Full article

Glioblastoma multiforme (GBM) is a malignancy of bad prognosis, and advances in early detection and treatment are needed. GBM is heterogenous, with varieties differing in malignancy within a tumor of a patient and between patients. Means are needed to distinguish these GMB forms, so that specific strategies can be deployed for patient management. We study the participation of the chaperone system (CS) in carcinogenesis. The CS is dynamic, with its members moving around the body in extracellular vesicles (EVs) and interacting with components of other physiological systems in health and disease, including GBM. Here, we describe the finding of high amounts of Hsp70 (HSPA1A) and the calcitonin receptor protein (CTR) in EVs in patients with GBM. We present a standardized protocol for collecting, purifying, and characterizing EVs carrying Hsp70 and CTR in plasma-derived EVs from patients with GBM. EVs from GBM patients were obtained just before tumor ablative surgery (T0) and 7 days afterwards (T1); Hsp70 was highly elevated at T0 and less so at T1, and CTR was greatly increased at T0 and reduced to below normal values at T1. Our results encourage further research to assess Hsp70 and CTR as biomarkers for differentiating tumor forms and to determine their roles in GBM carcinogenesis. Full article

Liver stiffness measurement (LSM) by Fibroscan is the most used non-invasive method to assess liver fibrosis. Recently, point-shear wave elastography (pSWE) has been introduced as a simple alternative non-invasive test. Therefore, we aimed to compare the results of these two techniques. One hundred and eighty-four consecutive patients attending our outpatient ultrasound clinic were recruited. LSM was performed by both Fibroscan and pSWE. Statistical analysis was conducted by Spearman’s test for correlation and linear regression. Bland–Altman graphs and ROC curves were drawn with area under the curve (AUC). Overall, the correlation of LS between Fibroscan and pSWE was substantial (r = 0.68, p < 0.001). Linear regression showed a coefficient b= 0.94 ± 0.02. The Bland–Altman plot found a bias of −0.10, with only 11 values exceeding the 95% confidence interval. When only considering patients with a LSM of > 10 kPa (n = 31), we found an excellent r = 0.79 (0.60–0.90, p < 0.001). A cutoff of 12.15 kPa for pSWE had sensitivity = 74.2% and specificity = 99.3% to detect relevant fibrosis, with an AUC = 0.98. The highest correlation was observed for hepatitis C (r = 0.91) and alcoholic liver disease (ALD)(r = 0.99). In conclusion, pSWE shows LSM estimation in agreement with Fibroscan in most cases, and the best concordance was observed for hepatitis C and ALD, and for higher ranges of LS. Full article

Probiotics have shown the potential to counteract the loss of muscle mass, reduce physical fatigue, and mitigate inflammatory response following intense exercise, although the mechanisms by which they work are not very clear. The objective of this review is to describe the main harmful effects of alcohol on skeletal muscle and to provide important strategies based on the use of probiotics. The excessive consumption of alcohol is a worldwide problem and has been shown to be crucial in the progression of alcoholic liver disease (ALD), for which, to date, the only therapy available is lifestyle modification, including cessation of drinking. In ALD, alcohol contributes significantly to the loss of skeletal muscle, and also to changes in the intestinal microbiota, which are the basis for a series of problems related to the onset of sarcopenia. Some of the main effects of alcohol on the skeletal muscle are described in this review, with particular emphasis on the “gut-liver-muscle axis”, which seems to be the primary cause of a series of muscle dysfunctions related to the onset of ALD. The modulation of the intestinal microbiota through probiotics utilization has appeared to be crucial in mitigating the muscle damage induced by the high amounts of alcohol consumed. Full article