Background: Galectin-10 (Gal-10), the main constituent of Charcot–Leyden crystals, is a recognized marker of eosinophilic inflammation, yet its role in nasal mucosal remodeling in Seasonal Allergic Rhinitis (SAR) remains poorly defined. Methods: Gal-10, IL-5, MUC5AC, and IFN-γ were analyzed in Nasal lavage (NL) samples from children with SAR by ELISA. Unsupervised clustering and discriminant analyses were applied. The functional effects of Gal-10 were investigated ex vivo using a 3D epithelial–mesenchymal trophic unit (EMTU) model stimulated with NL containing high, low, or depleted Gal-10 levels. EMT (epithelial–mesenchymal transition) markers (vimentin, E-cadherin, SNAIL1) and MUC5AC secretion were assessed by immunohistochemistry, Western blot, and ELISA. Results: Gal-10 levels in NL positively correlated with IL-5 and MUC5AC and inversely with IFN-γ. Clustering analysis identified distinct SAR endotypes, with Gal-10 showing the highest discriminative power. In the 3D EMTU model, high Gal-10 NL induced increased vimentin and SNAIL1 expression and enhanced MUC5AC secretion, effects attenuated after Gal-10 depletion. Conclusions: Gal-10 is associated with Th2-type inflammation, mucus hypersecretion, and early epithelial–mesenchymal transition in pediatric SAR, supporting its role as a mediator of nasal mucosal remodeling and a potential therapeutic target

OBJECTIVE:Asthma is a heterogeneous disorder in which a subset of patients exhibits a type 2 (Th2- or T2-high) endotype driven by eosinophilic, IL-4/IL-13-mediated inflammation. Traditional animal and 2D cell-based models incompletely reproduce human airway immune responses, particularly the Th2 phenotype. To address this gap, we developed a three-dimensional (3D) ex vivo model of human nasal respiratory mucosa incorporating type-2-biased immune stimulation. METHODS:Primary nasal mucosal biopsies were expanded under air-liquid interface (ALI) conditions and either exposed to IL-4/IL-13 or co-cultured with autologous polarized CD4+ Th2 lymphocytes and dendritic cells to generate a Th2-dominated microenvironment. Tissue morphology and barrier function were monitored longitudinally by phase-contrast microscopy and transepithelial electrical resistance (TEER). RESULTS:Induction of a type-2 inflammatory state was confirmed by increased secretion of periostin, STAT-6, IL-4 and IL-13 in apical and basal compartments, together with modest TEER reduction and evidence of epithelial remodeling, whereas IL-8 and chitinase family proteins did not increase, thereby excluding a COPD-like or type-2-low phenotype. CONCLUSIONS:Rather than fully recapitulating clinical asthma, this methodological model reproduces key immunopathologic features of T2-high airway inflammation in a patient-derived 3D context. It provides a stable, human-relevant platform for mechanistic studies and for future preclinical screening of targeted anti-inflammatory therapies.

Proteostasis, defined as the coordinated regulation of protein synthesis, folding, trafficking, and degradation, is essential for maintaining cellular integrity and supporting normal development. During reproduction and early life stages, efficient proteostasis is crucial for gamete quality, successful fertilization, embryonic development, and neurodevelopmental outcomes. Increasing evidence suggests that impaired proteostasis contributes to infertility and may be intertwined with biological vulnerabilities associated with assisted reproductive technologies [ARTs]. This review provides an integrative perspective on the role of disrupted proteostasis in infertility, ART procedures, and neurodevelopmental differences [NDD]. We review epidemiological and molecular findings indicating proteostasis failure in both male and female infertility, with particular emphasis on molecular chaperones. Among these, heat shock protein 60 [Hsp60] is discussed as a central mediator linking mitochondrial function, protein quality control, and reproductive competence. We further highlight that ART procedures coincide with sensitive periods of epigenetic reprogramming and proteostasis regulation during early embryogenesis, indicating that disturbances in proteostasis may affect epigenetic stability and subsequent neurodevelopmental outcomes. In addition, this review emphasizes the importance of proteoforms and proteome complexity as critical determinants of reproductive success and neurodevelopmental robustness in the context of ART. Finally, we discuss the potential of proteomic and chaperone-based biomarkers as emerging tools to optimize ART strategies, improve gamete and embryo selection, and enhance risk assessment and clinical outcomes. The current review underscores proteostasis as a fundamental yet underrecognized mechanism linking reproductive biology, ART outcomes, and long-term neurodevelopment while highlighting future directions for translational investigations.

IntroductionThis study aimed to review the impact of tele-exercise on different adult populations, comparing synchronous and asynchronous interventions and their effects on outcomes such as quality of life, physical fitness, functional capacity, strength, and pain.MethodsRandomised clinical trials and quasi-experimental studies published between 2014 and 2024 were included, totalling 16 studies with 1,416 participants. The interventions varied between synchronous teleexercise (via videoconference) and asynchronous (via apps and recorded videos). The review followed the PRISMA guidelines, ensuring a systematic approach to study selection, data extraction, and bias assessment.ResultsThe results indicate that tele-exercise, especially synchronous, has the potential to primarily improve physical fitness, functional capacity, and pain perception, being effective for the elderly and individuals with specific conditions such as multiple sclerosis and obesity.DiscussionHowever, the methodological heterogeneity of the studies and the lack of consistent data limit the generalisation of the findings, highlighting the need for more high-quality research.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024563241, PROSPERO (CRD42024563241).

Background: This research explored how tele-exercise influenced physical fitness and mental well-being in individuals with and without disabilities and with different training habits. Methods: One hundred and ninety-three participants were categorized into two groups: athletes and non-athletes. Participants were involved in either synchronous or asynchronous tele-exercise programs of two or three sessions of workouts per week, lasting eight weeks. Psychological well-being was evaluated pre- vs. post-intervention by the WHO-Five Well-Being Index (WHO-5), Psychological General Well-Being Index (PGWBI), and Perceived Stress Scale (PSS-10). Fitness assessment tools included the 2-minute step test, curl-up test, forward bending test, and squat test. Body weight was also assessed pre- and post-intervention. Results: The analysis showed a significant increment in all fitness scores (p-value ranged from <0.001 to 0.015) with no change in body weight. Psychological tests indicated an overall increment in the participants’ well-being measured by the WHO-5 and unexpectedly, also in the stress level assessed through PSS-10. Conclusions: Enabled by technology, tele-exercise provides a flexible and convenient complementary approach to conventional workouts, helping individuals maintain an active lifestyle and improve their well-being. Positive effects on the sedentary population’s lifestyles are discussed.

The critical shortage of donor organs remains the foremost challenge in transplantation medicine. Nevertheless, advancements in robotic-assisted surgery (RAS), artificial intelligence (AI)-enhanced donor–recipient matching, and bioengineering—particularly 3D bioprinting—are revolutionizing the field. Today, RAS has evolved from an innovative technique into a reliable clinical tool, with evidence indicating that it enhances surgical precision and results in better patient outcomes. Meanwhile, AI and machine learning are advancing donor–recipient matching and allocation, producing models that offer superior predictive accuracy for graft survival compared to traditional methods. Additionally, bioengineering strategies, especially 3D bioprinting and tissue engineering, are progressing from the creation of acellular scaffolds to the development of vascularized constructs, marking a significant milestone toward functional organ replacement. Despite persistent challenges such as high costs, regulatory obstacles, new structured formation programs, and the necessity for effective vascularization in engineered tissues, the integration of these disciplines is forging a new paradigm in regenerative medicine. The primary objective of this review is to synthesize multidisciplinary innovations by leveraging clinical studies and technological assessments to delineate future directions in regenerative medicine and organ transplantation.

Microplastics (MPs), a class of pollutants, have emerged as a global challenge impacting both ecosystems and human health. Over recent decades, extensive research has been conducted to assess their presence across aquatic, terrestrial, and atmospheric environments. The pervasive accumulation of MPs, resulting from both excessive plastic consumption and inefficient waste management, has established ingestion (via the food chain) and inhalation (via ambient air) as primary routes of human exposure. While numerous studies have investigated the effects of ingested MPs, research on inhaled particles and their respiratory system impacts remains comparatively limited. Owing to their diminutive size, with MPs ranging from 1 μm to 5 mm and Nanoplastics (NPs) being smaller than 1 μm, they can penetrate bronchioles and pulmonary alveoli, eliciting both localized effects (e.g., inflammatory responses, oxidative stress) and systemic consequences. Notably, studies demonstrate that MPs can traverse the Blood-Brain Barrier (BBB), inducing neurotoxic effects. This review provides an overview of MPs' environmental impact and their documented effects on major human organs and tissues, with a focused analysis on the respiratory system. Specifically, we evaluate epidemiological studies and in vitro experimental models employed to elucidate the mechanisms by which MPs may contribute to chronic respiratory disease pathogenesis.

Chronic infection with Helicobacter pylori is the leading environmental cause of gastric carcinogenesis, yet the molecular pathways remain incompletely defined. This review links H. pylori-derived outer membrane vesicles (OMVs) and host epithelial exosomes through their shared cargo of heat shock protein 60 (GroEL/Hsp60). We proposed the concept of the “muco-microbiotic layer” as a fifth, functionally distinct layer of the gastric wall, where bacterial and host extracellular vesicles (EVs) interact within the mucus–microbiota interface. In this compartment, OMVs carrying bacterial GroEL and exosomes containing human Hsp60 engage in bidirectional communication that may promote chronic inflammation and epithelial transformation, with putative participation of molecular mimicry. The high structural homology between microbial and human Hsp60 enables repeated immune exposure to trigger cross-reactive responses—potentially leading to autoimmune-driven tissue damage, immune tolerance, and immune evasion in pre-neoplastic lesions. This vesicular crosstalk aligns with the evolution from non-atrophic gastritis to atrophy, from intestinal metaplasia to dysplasia, and lastly adenocarcinoma. Therapeutically, targeting EV-mediated Hsp60/GroEL signaling might offer promising strategies: EV-based biomarkers for early detection, monoclonal antibodies against extracellular Hsp60/GroEL, modulation of vesicle release, and probiotic-derived nanovesicles to restore mucosal balance. Hence, recognizing the muco-microbiotic layer and its vesicle-mediated signaling provides a new framework for understanding the infection–inflammation–cancer axis and for developing diagnostic and therapeutic approaches in H. pylori-associated gastric cancer.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by obstructed airflow, airway remodeling, and inflammation, with cigarette smoke (CS) exposure being the main risk factor. Although CS extract (CSE) has been shown to activate caspases in various cell types, the role of caspases in human lung fibroblasts (hLFs) in COPD remains poorly understood. Recent studies have linked caspases to extracellular matrix (ECM) remodeling in skin and kidney fibrosis. Caspase activation can be triggered by oxidative stress, with active caspase-3 executing the pore-forming protein gasdermin E (GSDME) in the cleaved N-terminal form GSDME-NT. We investigated whether CSE activates caspases and GSDME in hLFs and their role in ECM remodeling. MRC-5 lung fibroblasts were treated with CSE with or without the antioxidant N-acetyl-cysteine (NAC) and the caspase-8 inhibitor z-IETD-fmk. We measured the effects on caspase-1-8-3/7 activation, GSDME cleavage, ECM remodeling (procollagen Iα1, COLIα1, and fibronectin, FN), and mitochondrial superoxide (mSOX) generation. Key findings were validated in patient-derived hLFs (phLFs). Our results showed that CSE induced caspase-1-8-3/7 activation, mSOX generation, and decreased COLIα1 and FN levels in MRC-5. CSE caused caspase-8-dependent activation of caspase-3, leading to GSDME cleavage. Treatment with NAC inhibited mSOX and caspase activation. Inhibition of caspase-8 and mSOX restored FN and COLIα1 levels. In phLFs, we confirmed caspase-1 and -8 activation, mSOX increase, COLIα1/FN decrease, and the effects of NAC. Our findings highlight the role of the axis caspase-8-3/7-GSDME and mSOX in regulating ECM protein, suggesting that these pathways may contribute to remodeling in COPD.NEW & NOTEWORTHY This research investigates the connection between caspases, gasdermins, and extracellular matrix (ECM) remodeling in the context of cigarette smoke-associated lung diseases. The study found that cigarette smoke extract (CSE) activates caspases and gasdermin E in human lung fibroblasts, leading to decreased ECM protein expression and release. Findings herein reported suggest that targeting the caspase-8-3/7-gasdermin axis and mitochondrial reactive oxygen species may help restore ECM remodeling in chronic lung diseases associated with cigarette smoke exposure.

BACKGROUND:Recent evidence supports the hypothesis that eosinophilic inflammation is a relevant component in the pathogenesis of COPD. OBJECTIVE:The current study aimed to assess the effects of Benralizumab, on ex vivo "COPD smoke-induced" bronchial mucosa equivalents. METHODS:Three-dimensional (3D) composite ex-vivo bronchial mucosa are used to study the mechanisms of repair, regeneration and differentiation within the epithelial-mesenchymal trophic unit (EMTU). After a one month incubation in growth medium and basal membrane extracts, epithelial cells differentiate into ciliated and mucous-producing cells, and mesenchymal cells into fibroblasts. This culture model is induced to express an inflammatory phenotype through exposure to cigarette smoke extracts. Eosinophils (Eos) are placed underneath the connective layers, whereas monocytes are activated and monocyte conditioned medium (MCM) is collected. The inflammatory cells established a cross-talk with resident cells by cytokine productions. The protocol included four experimental conditions: untreated control (K), Eos only (EO), Eos + MCM (EOMO), Eos + MCM + Benralizumab (EMB). RESULTS:Cytokine concentrations at basal and apical side were analyzed. At basal side, IL (interleukin)-5 significantly increased after the addition of eosinophils and monocytes, and decreased after the introduction of Benralizumab to the culture (after 14 days of treatment, K group: 14.6 ± 3.2 pg/mL; EO group: 13.9 ± 4.2 pg/mL; EOMO group: 35.7 ± 5.9 pg/mL; EMB group: 14.04 ± 4 pg/mL, p < 0.005). The reduction persisted for the subsequent 14 days. IL-6 and IL-15 concentration was high in EOMO groups while EMB groups had a reduction in both interleukins concentration. CONCLUSION:The findings described lead to speculate on a potential action of benralizumab on alternative inflammatory targets.

In recent years, the increasing number of long-duration space missions has prompted the scientific community to undertake a more comprehensive examination of the impact of microgravity on the human body during spaceflight. This review aims to assess the current knowledge regarding the consequences of exposure to an extreme environment, like microgravity, on the human body, focusing on the role of heat-shock proteins (HSPs). Previous studies have demonstrated that long-term exposure to microgravity during spaceflight can cause various changes in the human body, such as muscle atrophy, changes in muscle fiber composition, cardiovascular function, bone density, and even immune system functions. It has been postulated that heat-shock proteins (HSPs) may play a role in mitigating the harmful effects of microgravity-induced stress. According to past studies, heat-shock proteins (HSPs) are upregulated under simulated microgravity conditions. This upregulation assists in the maintenance of the proper folding and function of other proteins during stressful conditions, thereby safeguarding the physiological systems of organisms from the detrimental effects of microgravity. HSPs could also be used as biomarkers to assess the level of cellular stress in tissues and cells exposed to microgravity. Therefore, modulation of HSPs by drugs and genetic or environmental techniques could prove to be a potential therapeutic strategy to reduce the negative physiological consequences of long-duration spaceflight in astronauts.

BackgroundThe study investigates the impact of tele-exercise on physical fitness and psychological well-being in healthy individuals. Tele-exercise, facilitated by technology, offers a flexible and accessible alternative to traditional exercise, particularly beneficial during restricted in-person interactions.MethodsIn this study, 52 participants were divided into three groups: athletes, women, and young adults. They took part in an eight-week tele-exercise program, either synchronously or asynchronously. Physical fitness was evaluated using tests such as the 2-Minute Step and Curl Up Test, while psychological well-being was assessed using the Psychological General Well-Being Index (PGWBI) and Perceived Stress Scale (PSS-10).ResultsSignificant improvements in physical fitness and psychological well-being were observed in post-intervention across all groups, regardless of training mode. In the fitness tests, a significant improvement was obtained in the 2-Minute-Step (p = 0.004), in the curls up (p = 0.017), and in squats test (p = 0.004). In the forward bending test, the increment was very close to the significance (p = 0.051). In the psychological well-being tests, both PGWBI and WHO-5 scores increased after the training (p = 0.024 and p = 0.001 respectively) with no significant change in the PSS-10 score. The study found that tele-exercise can effectively introduce physical activity to previously inactive individuals and motivate them to adopt healthier lifestyle behaviors.ConclusionsThe TELEexe4ALL project demonstrates the potential of tele-exercise to improve physical fitness and psychological well-being. The study suggests that tele-exercise is a feasible and well-accepted approach for enhancing overall wellness in healthy populations.

Laryngeal squamous cell carcinoma (LSCC) constitutes a noteworthy subset of head and neck cancers, contributing to about 4.5% of all malignancies. Its clinical behavior and characteristics exhibit variations contingent upon the specific anatomical site affected, with the glottis, supraglottis, and subglottis emerging as the most prevalent locations. Notably, squamous cell carcinoma represents a predominant histological type, accounting for 85% to 95% of all laryngeal cancers. The gender disparity is evident, with a higher incidence among males, exhibiting a ratio of 3.9:1. Moreover, disparities among racial groups are observed, as African American patients tend to manifest the condition at a younger age, coupled with lower overall survival rates compared to their Caucasian, Hispanic, and Asian counterparts. The primary etiological factors implicated in the onset of laryngeal cancer are tobacco and alcohol consumption, with a direct correlation to the intensity and duration of usage. Importantly, the risk diminishes gradually following cessation, necessitating a substantial period of at least 15 years for a return to baseline rates. Given the diverse nature of laryngeal SCC, treatment modalities are tailored based on the specific site and stage of the disease. Therapeutic interventions, such as radiotherapy, transoral laser microsurgery, open horizontal partial laryngectomy, or total laryngectomy, are employed with the overarching goal of preserving organ function. This study delves into the intricate realm of laryngeal SCC, specifically exploring the involvement of heat shock proteins (HSPs) in disease progression. This research meticulously examines the expression levels of Hsp10, Hsp27, Hsp60, and Hsp90 in dysplastic and benign tissue samples extracted from the right vocal cord, utilizing immunohistochemistry analysis. The focal point of the investigation revolves around unraveling the intricate role of these molecular chaperones in tissue differentiation mechanisms and cellular homeostasis, particularly within the inflammatory milieu characteristic of the tumor phenotype. The findings from this study serve as a robust histopathological foundation, paving the way for more in-depth analyses of the underlying mechanisms governing the contribution of the four chaperones to the development of squamous cell carcinoma in the larynx. Additionally, the data gleaned from this research hint at the potential of these four chaperones as valuable biomarkers, not only for diagnostic purposes but also for prognostication and ongoing patient monitoring. As our understanding of the molecular intricacies deepens, the prospect of targeted therapeutic interventions and personalized treatment strategies for laryngeal SCC becomes increasingly promising.

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.

Purpose: This article illustrates the replication of asthma and COPD conditions in a laboratory setting and the potential applications of this methodology. Introduction: Biologic drugs have been shown to enhance the treatment of severe asthma and COPD. Monoclonal antibodies against specific targets have dramatically changed the management of these conditions. Although the inflammatory pathways of asthma and COPD have already been clearly outlined, alternative mechanisms of action remain mostly unexplored. They could provide additional insights into these diseases and their clinical management. Aims: In vivo or in vitro models have thus been developed to test alternative hypotheses. This study describes sophisticated ex vivo models that mimic the response of human respiratory mucosa to disease triggers, aiming to narrow the gap between laboratory studies and clinical practice. Results: These models successfully replicate crucial aspects of these diseases, such as inflammatory cell presence, cytokine production, and changes in tissue structure, offering a dynamic platform for investigating disease processes and evaluating potential treatments, such as monoclonal antibodies. The proposed models have the potential to enhance personalized medicine approaches and patient-specific treatments, helping to advance the understanding and management of respiratory diseases.

The emergence of tele-exercise as a response to the impact of technology on physical activity has opened up new possibilities for promoting physical health. By integrating innovative technologies and open-source platforms, tele-exercise encourages people to stay active. In our latest analysis, we delved into the scientific literature surrounding the use of tele-exercise technologies in training healthy individuals. After conducting an extensive search on the PubMed database using the keywords “tele-exercise” and “physical activity” (from 2020 to 2023), we identified 44 clinical trials that were applicable to tele-exercise, but less than 10% of them were aimed at healthy individuals, precisely 9.09% (four out of forty-four studies analyzed). Our review highlights the potential of tele-exercise to help maintain physical fitness and psychological well-being, especially when traditional fitness facilities are not an option. We also underscore the importance of interoperability, standardization, and the incorporation of biomechanics, exercise physiology, and neuroscience into the development of tele-exercise platforms. Nevertheless, despite these promising benefits, research has shown that there is still a significant gap in the knowledge concerning the definition and evaluation of training parameters for healthy individuals. As a result, we call for further research to establish evidence-based practices for tele-exercise in the healthy population.