Search Results (395)

Inflammatory lung diseases are characterized by complex immune dysregulation and structural tissue damage, demanding the development of novel therapeutic and diagnostic strategies. Exosomes (Exos) have emerged as promising alternatives to address these challenges by serving as key mediators and effective therapeutic nanocarriers. This review systematically analyzes the multifunctional roles of Exos derived from various sources, including immune cells, mesenchymal stem cells (MSCs), lung structural cells, and non-mammalian sources such as plants and milk, in the context of inflammatory lung diseases. These vesicles modulate critical pathological processes, such as macrophage polarization, oxidative stress, and programmed cell death, by delivering functional cargos, including miRNAs and proteins. Studies demonstrating the antioxidant properties of Exos are classified, and their roles in attenuating oxidative stress-mediated lung injury are discussed. Furthermore, engineering and priming strategies, as well as airway-directed delivery methods such as nebulization, are reported to enhance therapeutic efficacy and targeting. Evidence also indicates that plant-derived Exos could be scalable and safer alternatives to mammalian cell-derived Exos. Collectively, Exos represent a next-generation platform for precision medicine, functioning as potent therapeutic agents and efficient drug-delivery systems for the treatment of complex inflammatory lung diseases. Full article

Background: Cang-ai volatile oil (CAVO) is a traditional Chinese medicine with properties that soothe the liver and alleviate depression. CAVO is widely utilized in the field of antidepressant research and has surfaced as a possible treatment for depression. Depression is a common affective disorder and effective treatment methods are still limited. CAVO is effective in treating depression; however, the exact mechanism is still unclear. This study aimed to explore the likely mechanism by which CAVO reduces symptoms of depression in rats exposed to chronic unpredictable mild stress (CUMS). Methods: We established a CUMS model in Sprague–Dawley rats and administered CAVO via nebulization to evaluate its therapeutic effect. Behavioral and histology tests were conducted to evaluate brain tissue damage. We utilized metabolomics combined with proteomics to analyze the effects of CAVO. We then assessed molecular validation to further clarify the molecular mechanism of its activity. Results: In CUMS model rats, inhaling aerosolized CAVO reduced brain pathology and depression-like behaviors. CAVO changed serum levels of inflammatory cytokines and neurotrophic factors. Biomarkers linked to CAVO’s antidepressant effects were found via metabolomics. Functional analyses highlighted key molecular players such as TrkB, and CREB, and a close association with the antidepressant action of CAVO was confirmed. Conclusions: This study reveals that CAVO reduces depression-like behaviors in CUMS rats by regulating the NT/Trk signaling pathway. These results demonstrate CAVO’s therapeutic potential and lay the groundwork for future studies and the creation of depressive treatments. Full article

Background: The aim of this study was to assess in vitro nebulized drug delivery during invasive and non-invasive ventilation, comparing jet nebulizers (JN) and vibrating mesh nebulizers (VMN) across various pediatric ventilation models. Methods: Drug delivery performance was compared between a continuous output JN (Aquineb) and VMN (Aerogen Solo A-VMN). The non-invasive model simulated a spontaneously breathing 9-month-old child using an anatomically correct upper airway model and breathing simulator. The invasive model used a mechanical ventilator with heated humidifier in a pediatric breathing circuit with an endotracheal tube. Nebulizers were driven with supplemental oxygen at manufacturer-recommended rates and positioned at approved locations. Absolute inhaled dose, delivery rate and residual volume were assessed using face mask, mechanical ventilation, high-flow nasal therapy and blow-by delivery methods. Dose was quantified using spectrophotometric analysis. Results: During spontaneous breathing, A-VMN delivered almost double the dose of the evaluated JN (p < 0.001), with a significantly faster delivery rate (p < 0.001) and lower residual volume (p < 0.0001). During mechanical ventilation, A-VMN demonstrated a greater than 3-fold increase in delivered dose (p < 0.0001) and faster delivery (p < 0.0001), with reduced residual volume (p < 0.001). During high-flow nasal therapy, delivery via nasal cannula was affected by gas flow rate for both devices, with A-VMN consistently delivering greater doses. A-VMN delivered significantly greater salbutamol doses during blow-by delivery. Conclusions: VMN demonstrated significantly superior dose delivery, faster delivery rates and reduced residual volumes compared to the evaluated JN across all tested pediatric respiratory support modalities. These in vitro findings provide important performance data for evidence-based device selection and warrant clinical investigation to determine potential therapeutic benefits in pediatric populations requiring aerosol therapy during respiratory support. Full article

Inhalation injury (II) exacerbates burn mortality via obstructive fibrin casts. We evaluated a protocol combining scheduled flexible bronchoscopy (FOB) with nebulized heparin and N-acetylcysteine (NAC). This single-center, randomized controlled trial enrolled 76 mechanically ventilated adult burn patients with bronchoscopically confirmed II. The intervention (n = 38) comprised a 7-day protocol of scheduled FOB with alternating nebulized heparin (5000 IU) and 20% NAC every 4 h. Controls (n = 38) received standard care with on-demand FOB. Primary outcomes were 28-day mortality and day-7 Lung Injury Score (LIS). Unadjusted 28-day mortality was lower in the intervention group (57.9% vs. 81.6%; p = 0.025), alongside a decreased median day-7 LIS (1.0 vs. 1.38; p = 0.021). Respiratory mechanics improved significantly, demonstrating reduced driving pressure and increased static compliance (p < 0.001). However, in multivariable Cox regression, baseline injury severity independently predicted mortality, while the intervention indicated a non-significant hazard reduction trend (aHR = 0.66, 95% CI: 0.36–1.23). No systemic anticoagulation occurred. In conclusion, scheduled FOB with nebulized heparin and NAC improves respiratory mechanics and attenuates lung injury in II. Although unadjusted mortality decreased, baseline severity remains the primary mortality driver, suggesting this protocol is a physiologically beneficial adjunct requiring further multicenter validation. Trial registration: Thai Clinical Trials Registry, TCTR20260408001 (retrospectively registered). Full article

Background/Objectives: High-altitude pulmonary edema (HAPE) remains a serious condition with limited preventive options. This study evaluated the prophylactic protective effects of nebulized human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUC-MSC-EVs) in a rat model of hypobaric hypoxia-induced lung injury and explored potential mechanistic clues, with a focus on oxidative stress and TEK/Tie2 signaling. Methods: Rats were exposed to hypobaric hypoxia (47 kPa; 9.7% O₂) for 72 h and received prophylactic nebulized hUC-MSC-EVs (300 μg/rat). Lung injury was evaluated by histopathology, wet-to-dry ratio, and bronchoalveolar lavage fluid (BALF) protein concentration. Invasive pulmonary function indices were measured using a forced oscillation system. BALF cytokines (TNF-α, IL-6, and IL-10), reactive oxygen species (ROS), and TEK/Tie2 expression in lung tissue were assessed. In addition, transcriptome sequencing (RNA-seq) was performed to characterize global transcriptional changes. N-acetylcysteine (NAC), a classical antioxidant, was included as an auxiliary mechanistic intervention to assess the association of ROS with TEK/Tie2 changes. Results: Compared with hypoxia controls, prophylactic nebulized hUC-MSC-EVs reduced histopathological injury, pulmonary edema, and barrier leakage, and improved pulmonary function indices. hUC-MSC-EV intervention also attenuated inflammatory responses in BALF, with decreased TNF-α and IL-6 and increased IL-10. Hypobaric hypoxia increased ROS accumulation and decreased TEK/Tie2 expression, whereas nebulized hUC-MSC-EVs reduced ROS and partially preserved TEK/Tie2 expression. NAC pretreatment similarly reduced ROS and was accompanied by Tie2 preservation. Conclusions: Prophylactic nebulized hUC-MSC-EVs mitigated hypobaric hypoxia-induced lung injury, accompanied by reduced oxidative stress, improved vascular barrier integrity, and preservation of TEK/Tie2 expression. These findings support nebulized hUC-MSC-EVs as a potential lung-targeted prophylactic strategy for hypobaric hypoxia-induced lung injury and suggest that ROS imbalance may be associated with Tie2 preservation. Full article

Aerosols are a major transmission route for seasonal influenza infections. Titanium dioxide (TiO₂) photocatalyst has broad-spectrum antiviral activity, including in vitro influenza virus inactivation; however, whether the TiO₂ photocatalyst can effectively inactivate airborne influenza A viruses in vivo under conditions that mimic natural aerosol transmission remains unclear. Here, we evaluated in vivo inactivation of airborne H1N1 seasonal influenza virus by a photocatalyst-equipped air purifier using a mouse model. Influenza virus WSN strain aerosols were sprayed in a 60 L acrylic box with a nebulizer, circulated through a photocatalyst-equipped air purifier, exposed to BALB/c mice for 40 min after circulation, and subsequently collected with an air sampler. Thirty minutes of TiO₂ photocatalyst treatment reduced influenza virus infectivity by 99.97%, and significantly lowered lung viral titer in mice on day 3 post-infection. Over 14 days post-infection, mice showed no >10% weight loss, 100% survival, and disease progression to the PBS (−) aerosol group. This suggests that the photocatalyst-equipped air purifier may reduce H1N1 seasonal influenza onset, preventing viral spread. Full article

This study investigates the formation mechanism of lactic-acid-derived coatings produced by open-air atmospheric-pressure plasma polymerization. A comparison of nebulization and bubbling precursor-delivery methods using FT-IR and XPS showed that the bubbling method facilitated plasma-assisted chemical bonding, including the possible formation of copper(II) lactate-like interfacial species and the retention of carbonyl-containing functional groups. However, the present dataset does not provide direct, discriminating evidence for a specific metal-lactate interfacial species, and alternative interpretations such as adsorption, oxidation, hydroxylation, or generic oxygenated carbon deposition cannot be excluded. Time-dependent analysis revealed a transition from oxygen-rich functional layers at short plasma exposure to carbon-rich overlayers at longer exposure, suggesting a fragmentation-recombination mechanism that is consistent with the formation of a metal-lactate-like interfacial region and a carbon-rich overlayer, while alternative interpretations related to signal attenuation and non-uniform coverage remain possible. Antibacterial testing revealed that the observed bacterial responses were not attributable to an intrinsic antibacterial property of the deposited films, but were instead strongly dependent on the underlying substrate chemistry and exposure time. C1100 retained the inherent antibacterial activity of copper, SUS430 showed no activity due to the absence of film formation, and SPCC exhibited only a transient effect attributed to lactic-acid-induced local acidification. Overall, the study elucidates the plasma-assisted deposition mechanism of lactic-acid-derived coatings under open-air conditions and highlights the critical role of interface chemistry in achieving stable and substrate-independent functional properties. Full article

Ocular diseases pose significant therapeutic challenges due to the eye’s intricate anatomy and efficient physiological clearance mechanisms, which result in the rapid elimination of topically administered drugs and an overall bioavailability of less than 5%. Anterior segment disorders—including keratitis, glaucoma, and dry eye syndrome—account for the majority of ophthalmic conditions and are primarily managed with pharmacological agents. However, due to extremely low drug bioavailability and poor patient compliance, their therapeutic outcomes often result in a decreased disease control rate or require early surgical interventions. Nebulized drug delivery, particularly employing advanced vibrating mesh technology, has emerged as a promising strategy to overcome these limitations. By converting liquid formulations into a uniform aerosol of micron-sized (1–10 μm) droplets, this approach achieves extensive and consistent coverage of the ocular surface, increases the absorption contact area, prolongs drug residence time, and ultimately enhances drug bioavailability. Preliminary clinical evidence indicates that nebulized therapies outperform traditional eye drops by achieving higher drug concentrations in the aqueous humor and demonstrating superior pharmacodynamic profiles and patient tolerability—particularly in conditions such as dry eye syndrome and glaucoma. This review presents a comprehensive overview of the mechanistic principles, technological advancements, and translational applications of nebulization-based ocular drug delivery systems. We place special emphasis on the integration of next-generation platforms that incorporate microelectromechanical systems (MEMS) and intelligent sensing technologies, enabling precision medicine approaches tailored to individual ocular pathophysiological characteristics. By bridging biomedical engineering and clinical ophthalmology, these innovations not only optimize existing therapeutic regimens but also pave the way for non-invasive delivery of complex biologics and gene therapies—potentially reshaping the landscape of anterior segment drug delivery. Full article

The efficient delivery of small interfering RNAs (siRNAs) to immune and respiratory cells represents a key methodological challenge in developing inhaled RNA interference (RNAi) approaches. A central question is whether siRNA functionality is preserved following aerosolization, as the mechanical stress of nebulization may compromise siRNA integrity and silencing activity. Here, we report a proof-of-concept study using THP-1-derived macrophage-like cells as a tractable in vitro model to characterize jet nebulization for siRNA delivery. Three siRNA candidates targeting interleukin-1 beta (IL-1β) were computationally designed and validated for potent silencing activity and low cytotoxicity. Using a commercially available, off-the-shelf jet nebulizer combined with Lipofectamine RNAiMAX, we demonstrate that siRNA-lipoplexes retain their gene-silencing activity after aerosolization, achieving robust IL-1β knockdown. The delivery efficiency was influenced by siRNA-lipoplex complexation, highlighting the importance of formulation parameters. These findings establish a practical and accessible in vitro platform for evaluating nebulized siRNA functionality, providing a foundation for future studies in more complex and physiologically relevant airway models. Full article

Inhaled Treprostinil is the primary treatment of pulmonary hypertension related to interstitial lung disease (PH-ILD). Despite treatment effectiveness in clinical trials, the real-world safety and tolerability of this therapy remains unclear. We conducted a multicenter, retrospective review of adults with PH-ILD who were prescribed inhaled treprostinil. We assessed clinical outcomes, 6 min walk distance (6MWD) and changes in natriuretic peptides (BNP, NT-proBNP), as well as medication tolerance. Eighty-three patients met the inclusion criteria. The 6MWD data was collected but a limited number of patients had results within close proximity to initiation of inhalational treprostinil with only seven patients having assessments within the 3 months prior to initiation as well as 3 months post therapy. Limited 6MWD data is likely due, in part, to coinciding with the COVID pandemic, limiting face-to-face interactions and exercise testing. The majority of our subjects, 63%, had an absolute improvement in their BNP level, over a mean duration of 170 days. However, no significant difference was detected between baseline and follow-up natriuretic peptide levels. Adherence was assessed and the majority (77%) of patients remained on therapy at the time of censoring, with three-quarters (75%) meeting the target dose. Of the 15 patients intolerant to nebulized treprostinil who were transitioned to a dry powder inhaler, the majority (87%) were able to tolerate the other formulation. The medication was well-tolerated with a large percentage of patients remaining on therapy indefinitely and reaching the targeted therapeutic dose. Full article

There are many stories in the Hebrew Bible that depict prominent Jews in the epicentre of a foreign imperia, and biblical scholarship essentially classifies every such narrative as court tales in terms of genre. Notwithstanding nuances and sub-categorisations (e.g., court contest and court conflict, wisdom court legend, success story of the wise courtier), to have one catch-all genre designation is imprudent and amorphous. This paper argues, using Formkritik and Gattungskritik, for three subgenres whereby foreign royal stories may be distinguished. One type of tale involves a foreign king who is either sleepless (Dan 6, Esth 6) or dreams (Gen 41, Dan 2 and 4); in the former, a king intervenes favourably for Jews in distress, while in the latter, the king’s dreams are interpreted by a wise Jewish courtier. Another type of tale is the imperial banquet, where an intoxicated gentile king orders the death of a high official (Dan 5, Esth 1, 5/7); this is wrought by a woman who exploits the king’s wine-induced disposition to effect lethal action with disastrous repercussions for the kingdom. Still another type of tale is the court tale proper; these episodes, however, are restricted to the courtly etiquette and decorum of courtiers who sagaciously advise the king, alongside its tensions with monotheism (Dan 3; Esth 3). As a result of this preliminary investigation, the typical setting of the political centre of the foreign imperium in Hebrew Bible narratives comprises three subgenres: court tales, banquet tales, and bedchamber tales. Since genres are determined by the common story forms, each distinct genre is scientifically determined by corresponding distinct narrative structures, vocabulary, and outcomes. Thus, what is proposed is a more illuminating distinction to the wide array and nebulous conglomeration of biblical stories involving Jews in prominent spaces within the foreign king’s court. Furthermore, the implications of the contended three subgenres involve calcifying religious practices, which become vital expressions of Judaism in the Second Temple period. Full article

This study evaluated the sanitization of fertile eggs using a blend of oregano (Origanum vulgare) and cinnamon (Cinnamomum verum) essential oils as an alternative to paraformaldehyde. The experiment was conducted at the Animal Biochemistry and Metabolism Laboratory of IF Goiano, Rio Verde Campus, using 344 incubatable eggs from ROSS breeder hens. A completely randomized design with four treatments and 86 eggs per tray was applied: no sanitization (control); conventional paraformaldehyde fumigation; sanitization with essential oil blend by spraying (nebulization); and sanitization with the essential oil blend by immersion. Hatchability performance showed 133 chicks hatched in both essential oil treatments (immersion and nebulization), like paraformaldehyde (134 chicks). There was a statistical difference for (p < 0.05) and chick weight at hatch was lower for eggs sanitized by immersion (38.54 g) compared to the control (44.50 g), paraformaldehyde (44.48 g), and nebulization (43.78 g). Fertility rates were 77.51%, 78.29%, 77.32%, and 73.67% for the control, paraformaldehyde, nebulization, and immersion treatments, respectively. Hatchability reached 80.67% for paraformaldehyde and 79.83% for nebulization. Fungal contamination was lowest with paraformaldehyde (9 occurrences), followed by immersion (12), while the control and nebulization showed similar counts (19). Overall, sanitization of fertile eggs with the cinnamon–oregano essential oil blend applied by nebulization demonstrated performance comparable to paraformaldehyde, indicating its potential as a natural sanitizing alternative. Full article

Background: Although surfactant replacement therapy has been a cornerstone of respiratory distress syndrome (RDS) management for decades, traditional delivery via endotracheal intubation and mechanical ventilation is associated with procedure-related complications and increased risk of bronchopulmonary dysplasia (BPD). These concerns have driven the development of less invasive surfactant administration strategies. Objective: This review aims to summarize and evaluate the current literature on less invasive surfactant delivery techniques used in preterm infants with RDS, with a focus on their feasibility, efficacy, and short- and long-term neonatal outcomes. Methods: We reviewed the available literature evaluating less invasive surfactant administration methods, including InSurE, Less Invasive Surfactant Therapy/Minimally Invasive Surfactant Therapy (LISA/MIST), surfactant administration via laryngeal mask airway (SALSA/LMA), pharyngeal administration, and nebulized surfactant. We compared major outcomes, namely the need for mechanical ventilation, incidence of BPD, procedural complications and long-term neurodevelopmental outcomes. Results: Non-invasive surfactant administration techniques have been associated with reduced exposure to mechanical ventilation and lower rates of BPD compared with conventional approaches. Studies on LISA/MIST demonstrate the most consistent evidence in reducing the need for mechanical ventilation and BPD, while other techniques such as LMA-assisted delivery and nebulization show promise but remain limited by device constraints, gestational age applicability, and heterogeneous study designs. Long-term neurodevelopmental outcome data remain sparse across all techniques. Conclusions: Non-invasive surfactant administration represents an important advancement in the management of RDS. While several techniques offer potential advantages over traditional intubation-based delivery, further high-quality studies are required to optimize patient selection, standardize techniques, develop safe and effective delivery devices, and evaluate long-term neurodevelopmental outcomes. Full article

Iodine is essential for thyroid hormone synthesis and is particularly critical during pregnancy, where excess and mainly its deficiencies can impair fetal neurodevelopment and increase maternal complications. Bromine has also gained attention due to its potential to interfere with iodine metabolism and contribute to adverse health effects when present in excess. Monitoring iodine and bromine in biological samples, especially urine and serum, is therefore important for assessing thyroid function and population health. This work presents a simple and robust ICP-MS method for simultaneous determination of bromine and iodine in urine and serum. The procedure uses a 20-fold dilution with 10 mmol L⁻¹ ammonia containing 0.1% (w/w) EDTA-2Na, ensuring solution stability, minimizing sample-to-sample variability, and eliminating the need for matrix-matched calibration. EDTA-2Na effectively prevents precipitation of metal species at high pH, avoiding blockages in the sample introduction system. Method accuracy was confirmed through certified reference materials and spike-recovery experiments, both showing suitable agreement for the two analytes. Precision was consistently strong (RSD < 6%), and low detection limits were achieved (0.78 μg L⁻¹ for Br and 0.24 μg L⁻¹ for I). The use of a high-efficiency nebulizer enabled analysis with only 50 µL of sample, making the method suitable for limited-volume specimens. Overall, this approach provides a sensitive, accurate, and practical solution for large-scale population studies and clinical applications. Full article

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) remains a major challenge in healthcare settings due to its persistence on inanimate surfaces and resistance to conventional cleaning methods. Bacteriophages (phages) represent a promising biocontrol option owing to their high specificity and lytic activity. Methods: This study evaluated the use of a personal hand-held vibrating mesh nebulizer (VMN) as a rapid and localized delivery platform for phage aerosols. Using two lytic phages (ϕ2, Podovirus; ϕ11, Myovirus), we assessed phage stability under different storage conditions, viability during VMN operation, and surface decontamination efficacy under varying spray parameters. Results: In saline, both phages showed optimal long-term stability at 4 °C, whereas storage at −20 °C resulted in a progressive reduction in infectivity exceeding 3 logs over the storage period. VMN aerosolization did not compromise viability. A 3 min spray achieved >99.9% surface reduction: ϕ2 was effective at 1 × 10⁷ PFU/mL, whereas ϕ11 required 1 × 10⁸ PFU/mL. Importantly, residual ϕ2 activity persisted for at least 24 h, preventing detectable recolonization under the assay conditions, while ϕ11 protection was limited to 6 h. Conclusions: These findings establish the hand-held sprayer as a practical, low-cost, and flexible approach to deliver viable phage aerosols, providing an effective complement to large-scale disinfection systems and offering a targeted strategy to enhance infection control in healthcare environments. Full article