Search Results (215)

Pulmonary fibrosis (PF) is a progressive and fatal lung disease characterized by irreversible alveolar destruction and pathological extracellular matrix (ECM) deposition. Currently approved agents (pirfenidone and nintedanib) slow functional decline but do not reverse established fibrosis or restore functional alveoli. Multifunctional bioscaffolds present a promising therapeutic strategy through targeted modulation of critical cellular processes, including proliferation, migration, and differentiation. This review synthesizes recent advances in scaffold-based interventions for PF, with a focus on their dual mechano-epigenetic regulatory functions. We delineate how scaffold properties (elastic modulus, stiffness gradients, dynamic mechanical cues) direct cell fate decisions via mechanotransduction pathways, exemplified by focal adhesion–cytoskeleton coupling. Critically, we highlight how pathological mechanical inputs establish and perpetuate self-reinforcing epigenetic barriers to regeneration through aberrant chromatin states. Furthermore, we examine scaffolds as platforms for precision epigenetic drug delivery, particularly controlled release of inhibitors targeting DNA methyltransferases (DNMTi) and histone deacetylases (HDACi) to disrupt this mechano-reinforced barrier. Evidence from PF murine models and ex vivo lung slice cultures demonstrate scaffold-mediated remodeling of the fibrotic niche, with key studies reporting substantial reductions in collagen deposition and significant increases in alveolar epithelial cell markers following intervention. These quantitative outcomes highlight enhanced alveolar epithelial plasticity and upregulating antifibrotic gene networks. Emerging integration of stimuli-responsive biomaterials, CRISPR/dCas9-based epigenetic editors, and AI-driven design to enhance scaffold functionality is discussed. Collectively, multifunctional bioscaffolds hold significant potential for clinical translation by uniquely co-targeting mechanotransduction and epigenetic reprogramming. Future work will need to resolve persistent challenges, including the erasure of pathological mechanical memory and precise spatiotemporal control of epigenetic modifiers in vivo, to unlock their full therapeutic potential. Full article

The enhancement of drug delivery into the lung surfactant is facilitated by research on the interaction between drugs and the lung surfactant. Drug designers must have a thorough theoretical understanding of a drug before performing clinical tests to reduce the experimental cost. The current study uses a coarse-grained molecular dynamics (MD) approach with the MARTINI force field to parameterize the corticosteroid drug mometasone furoate, which is used to treat lung inflammation. Here, we investigate the accurate parametrization of drug molecules and validate the parameters with the help of umbrella sampling simulations. A collection of thermodynamic parameters was studied during the parametrization procedure. The Gibbs free energy gradient was used to calculate the partition coefficient value of mometasone furoate, which was approximately 10.49 based on our umbrella sampling simulation. The value was then matched with the experimental and predicted the partition coefficient of the drug, showing good agreement. The drug molecule was then delivered into the lung surfactant monolayer membrane at the alveolar air–water interface, resulting a concentration-dependent drop in surface tension while controlling the underlying continual compression–expansion of alveoli that maintains the exhalation–inhalation respiratory cycle. The dynamical properties of the monolayer demonstrate that the drug’s capacity to diffuse into the monolayer is considerably diminished in larger clusters, and this effect is intensified when there are more drug molecules present in the monolayer. The monolayer microstructure analysis shows that the drug concentration controls monolayer morphology. The results of this investigation may be helpful for corticosteroid drug delivery into the lung alveoli, which can be applied to comprehend how the drug interacts with lung surfactant monolayers or bilayers. Full article

We previously carried out an in vivo 2-year study to assess the potential toxicity/carcinogenicity of double-walled carbon nanotubes (DWCNTs) in a rat lung. We found that administration of DWCNTs by intratracheal–intrapulmonary spraying (TIPS) at a dose of 0.5 mg/rat induced the development of lung tumors in 7 of 24 treated rats while 1 of 21 untreated rats and 1 of 25 vehicle treated rats developed lung tumors. In the current study, we administered DWCNTs of different lengths, 1.5 µm, 7 µm, and 15 µm, to rats by TIPS to investigate the possible effect of the length of this thin, flexible CNT on toxicity/carcinogenicity in rat lungs. Rats were administered DWCNTs with lengths of 1.5 µm (D1.5), 7 µm (D7), and 15 µm (D15) by TIPS once every other day over the course of two weeks for a total of eight administrations. The total dose administered was approximately 22 × 10¹² fibers per rat, corresponding to 0.0504 mg for D1.5, 0.232 mg for D7, and 0.504 mg for D15. Another group of rats was administered 0.5 mg MWCNT-7, a known carcinogen. Animals were killed at weeks 6 and 104 (4 and 102 weeks after the final TIPS administration). The mean survival time of the rats in the untreated, vehicle, D1.5, D7, and D15 groups was 99 to 104 weeks. One rat in the D1.5 group and one rat in the D15 group died before week 75. The remaining rats in the untreated, vehicle, D1.5, D7, and D15 groups were included in the final assessment of lung toxicity/carcinogenicity. In contrast, 11 rats in the MWCNT-7 group died before week 75 due to the development of malignant mesothelioma. Due to the much shorter survival time of the rats treated with MWCNT-7, accurate assessment of lung proliferative lesions in this group was not possible. At week 6, an increase in alveolar macrophages and granulation tissue foci in the alveoli was observed in all DWCNT administered groups. The alveolar epithelial cell PCNA index was also significantly increased in the D7 and D15 groups. Increases in alveolar macrophages, granulation tissue foci, and the alveolar epithelial cell PCNA index were observed in all DWCNT-treated groups at the final sacrifice. The incidences of lung tumors were 0/13, 0/12, 4/12, 3/8, and 2/10 in the untreated, vehicle, D1.5, D7, and D15 groups, respectively. In agreement with our previous study, the DWCNTs tested in the present study were carcinogenic in the rat lung. In addition, we present evidence that DWCNT fiber length may possibly have an effect on DWCNT-induced carcinogenicity in rat lungs. Full article

The collection of perivitelline fluid (PVF) from early-stage post-activation zebrafish (Danio rerio) eggs/embryos poses a significant challenge owing to the liability of the egg/embryo to sustain damage and rupture during handling. Rupture of the blastoderm and/or yolk presents a major risk of PVF sample contamination. Previous efforts to extract PVF at such early stages have employed formalin fixation to enhance the structural integrity of the blastoderm and yolk syncytial layer, thereby reducing the likelihood of contamination. While this approach successfully mitigates blastoderm and yolk rupture, formaldehyde fixation may cause issues with downstream proteomic analyses. Recent findings indicate that zebrafish PVF contains a range of maternally inherited proteins involved in innate immune defence. However, current extraction methods compromise the reliability of downstream protein analyses, raising concerns that fixation-induced protein crosslinking may obscure the presence of maternally inherited proteins during the earliest stages of development. The micro-aspiration technique described here allows for the precise extraction of PVF from living, water-activated eggs with minimal disruption to the blastodisc and yolk. This method reduces the risk of contamination from other non-target proteinaceous egg sources and eliminates the need for formalin fixation, thereby improving the integrity of PVF samples and enhancing the reliability of subsequent downstream analyses. Full article

Background: The role of collagen membrane fixation during guided bone regeneration (GBR) remains debatable, particularly in post-extraction sockets with buccal defects and concomitant immediate implant placement. This study evaluated whether or not fixation with titanium pins improved regenerative outcomes. Methods: Six adult Beagle dogs received bilateral extractions of the fourth mandibular premolars. An implant was immediately placed in both the distal alveoli, and standardized buccal bone defects (5 mm height, 3–2 mm width) were prepared. All defects were filled with a slowly resorbing equine xenograft and covered by a resorbable pericardium membrane. At the test sites, the membrane was apically fixed with pins, while no fixation was applied to the control sites. After 3 months of healing, histomorphometric analyses were performed. Results: The vertical bone gain of the buccal crest was 3.2 mm in the test sites (pin group) and 2.9 mm in the control sites (no-pin) (p > 0.754). No significant difference was found in terms of bone-to-implant contact (BIC). However, residual graft particles were located significantly more coronally in the pin group compared to the no-pin group (p = 0.021). Morphometric analyses revealed similar new bone formation within the groups, but with higher amounts of residual xenograft and soft tissue in the pin group. Conclusions: Membrane fixation did not significantly enhance vertical bone gain, and although the slightly higher regeneration in the pin group (3.2 mm vs. 2.9 mm) may hold clinical relevance in esthetically sensitive areas and osseointegration, it appeared to limit apical migration of the grafting material. Full article

Colibacillosis is a poultry disease caused by the pathogenic bacterium Escherichia coli (E. coli). This study is an experimental cross-sectional study using herbal-based test materials from Javanese cardamom and turmeric rhizome as treatments to replace the role of antibiotics that experience drug resistance in several types of bacteria. A total of 32 samples were utilized in this study, separated into two control groups and six treatment groups. The analysis was carried out by an histopathological examination of the lung organs using H&E and ImageJ staining to calculate the area of the slide image. The data results were analyzed statistically with one-way ANOVA method and qualitatively. The outcome of the statistical test showed that the differences were not statistically significant p value = 0.922 [p > 0.05] in all groups, and findings from qualitative histopathology showed morphological differences in the alveoli, parabronchi, and vasculature in the lung organs. Full article

Background and Objectives: Neonatal respiratory distress syndrome (NRDS), resulting from a deficiency of pulmonary surfactant (PS), can cause alveoli to collapse. Glucocorticoids reduce inflammation and are effective in reducing pulmonary swelling. This study aims to assess the effectiveness of the combination of PS and budesonide in the management of NRDS. Materials and Methods: Publications between 21 May and 24 November were screened through PubMed, Cochrane and Embase. Data analysis was performed on RevMan 5.3 software. Subgroup analysis was performed to evaluate the routes of administrations. Results: The use of budesonide along with pulmonary surfactant for treating NRDS revealed the following results: (1) a reduced duration of invasive mechanical ventilation (standardized mean difference (SMD) = −1.06, 95% confidence interval (CI) = −1.55 to −0.56, p < 0.0001); (2) reduced rate of bronchopulmonary dysplasia (BPD) occurrence (relative risk (RR) = 0.72, 95% CI = 0.60 to 0.86, p = 0.0003); (3) reduced duration for hospital admittance (SMD = −0.38, 95% CI = −0.64 to −0.11, p = 0.005). The occurrence of complications, i.e., sepsis, pneumothorax, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), rate of mortality, hyperglycemia and intraventricular hemorrhage (IVH), was not significantly different among the intervention and comparison group except for patent ductus arteriosus (PDA) and pulmonary hemorrhage, with their incidence being higher in the control group (p = 0.002 and p = 0.05, respectively). Conclusions: The combination of pulmonary surfactant and budesonide decreases the occurrence of BPD, duration of mechanical ventilation, length of hospital stay and risk of pulmonary hemorrhage and PDA. It does not increase the risk of complications and death and is clinically safe. Full article

Platelet-rich plasma (PRP) has become an increasingly valuable biologic approach for personalized regenerative medicine because of its potent anti-inflammatory/healing effects. It is thought to be an excellent source of growth factors that can promote tissue healing and lessen fibrosis. Although this treatment has demonstrated effectiveness in numerous disease areas, its impact on pulmonary fibrosis (PF) caused by silver nanoparticles (AgNPs) via its antiapoptotic effects remains to be explored. AgNPs were synthesized biologically by Bacillus megaterium ATCC 55000. AgNP characterization was carried out via UV–Vis spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) imaging to reveal monodispersed spheres with a mean diameter of 45.17 nm. A total of 48 male Wistar rats divided into six groups, with 8 rats per group, were used in the current study on the basis of sample size and power. The groups used were the PRP donor, control, AgNP, AgNP + PRP, AgNP + dexamethasone (Dexa) rat groups, and a recovery group. Body weights, hydroxyproline (HP) levels, and CASP3 and TWIST1 gene expression levels were assessed. H&E and Sirius Red staining were performed. Immunohistochemical studies for inducible nitric oxide synthase (iNOS) and cluster of differentiation 68 (CD68) with histomorphometry were conducted. A significant reduction in body weight (BWt) was noted in the AgNP group compared with the AgNP + PRP group (p < 0.001). HP, CASP3, and TWIST1 expression levels were significantly increased by AgNPs but decreased upon PRP (p < 0.001) treatment. Compared with those in the control group, the adverse effects of AgNPs included PF, lung alveolar collapse, thickening of the interalveolar septa, widespread lymphocytic infiltration, increased alveolar macrophage CD68 expression, and iNOS positivity in the cells lining the alveoli. This work revealed that PRP treatment markedly improved the histopathological and immunohistochemical findings observed in the AgNP group in a manner comparable to that of the Dexa. In conclusion, these results demonstrated the therapeutic potential of PRP in a PF rat model induced via AgNPs. This study revealed that PRP treatment significantly improved the histopathological and immunohistochemical alterations observed in the AgNP-induced group, with effects comparable to those of the Dexa. In conclusion, these findings highlight the therapeutic potential of PRP in a rat model of AgNP-induced PF. Full article

Pneumonia is a severe lower respiratory tract infection. This study demonstrates that phospholipase A2 (PLA2), a potential biomarker for pneumonia, contributes to alveoli damage by hydrolyzing pulmonary surfactant phospholipids. This process impairs gas exchange and generates hemolytic phospholipids that disrupt cellular membranes, exacerbating pulmonary injury. Experimental evidence demonstrates that PLA2 inhibitors significantly alleviate cellular damage in lipopolysaccharide (LPS)-induced pulmonary inflammation. These findings reveal a key mechanistic role of PLA2 in pneumonia pathogenesis and suggest novel therapeutic strategies. The results may provide more effective clinical interventions and guide further research in related fields. Full article

Objectives: This study aimed to determine the factors affecting the diagnostic efficacy of frozen sections for assessing tumor spread through air spaces (STAS) and to provide suggestions for the sampling of these frozen sections. Methods: Cases of invasive adenocarcinoma with a pathological diagnosis of stage IA-IIIB were screened, and frozen and paraffin sections were reviewed. Using paraffin sections as the gold standard, the consistency of frozen pathological diagnosis of STAS was calculated. Factors that may affect STAS diagnosis in frozen sections were screened, and a nomogram was drawn. Results: The sensitivity of frozen sections in STAS diagnosis was 55.4% (108/195), the specificity was 74.5% (254/321), and the kappa value was 0.35. In the subsequent logistic regression, the ratio of the tissue diameters of the frozen and paraffin sections, number of frozen section sheets, clarity of the tumor boundary, and number of alveoli from the peritumoral area to tissue edge were all statistically significantly significant (p < 0.05) factors affecting the frozen STAS diagnostic efficacy. Conclusions: The diagnostic efficacy of frozen sections for STAS is poor. In our study, the tissue diameter ratio of the frozen to paraffin sections, the number of frozen sections, the clarity of the tumor boundary, and the number of alveoli from the peritumoral tissue to the tissue edge were considered independent factors affecting diagnostic consistency. The accuracy of the frozen section analysis in STAS diagnosis can be improved by our reasonable suggestions on frozen sampling, making it a reliable indicator of the surgical method. Full article

Klebsiella pneumoniae is a Gram-negative, encapsulated bacterium recognized by the World Health Organization (WHO) as a critical priority for new therapeutic strategies due to its increasing multidrug resistance (MDR). Antimicrobial photodynamic therapy (aPDT) has emerged as a promising alternative to antibiotics, exhibiting a broad spectrum of action and multiple molecular targets, and has been proposed for the treatment of clinically relevant infections such as pneumonia. However, despite excellent in vitro photodynamic inactivation outcomes, the success of in vivo therapy still faces challenges, particularly due to the presence of lung surfactant (LS) in the alveoli. LS entraps photosensitizers, preventing these molecules from reaching microbial targets. This study investigated the potential of indocyanine green (ICG) in combination with the biocompatible polymer Gantrez™ AN-139 for the photoinactivation of K. pneumoniae. Initial in vitro experiments demonstrated that aPDT with ICG alone is effective against K. pneumoniae in a concentration- and light dose-dependent manner, achieving total eradication at 75 µg/mL of ICG and 150 J/cm² of 808 nm light. When aPDT was performed with similar parameters in the presence of LS, no bacterial killing was observed. However, a significant synergistic effect was observed when ICG (25 µg/mL) was combined with a low concentration of Gantrez™ AN-139 (0.5% m/v) in the presence of dipalmitoylphosphatidylcholine (DPPC), the main component of LS. This formulation resulted in a substantial reduction (3.6 log₁₀) in K. pneumoniae viability. These findings highlight the potential of Gantrez™ AN-139 as an efficient carrier to enhance the efficacy of ICG-mediated aPDT against K. pneumoniae, even in the presence of lung surfactant, a necessary step before the in vivo experiments. Full article

Immune homeostasis refers to the immune system’s ability to maintain a dynamic balance, defend against infections while preventing excessive inflammation, and preserve normal physiological activity. However, its regulatory role in the mammary glands (MGs) of cows with clinical mastitis (CM) remains unclear. This study examined MG tissue samples collected from healthy Holstein cows and those with CM caused by Staphylococcus aureus (n = three per group) to identify candidate biomolecular targets involved in immune homeostasis in dairy cows affected by mastitis through a proteomics-based bioinformatic analysis and analyze their expression and localization in MG tissues. A pathological examination revealed that the MG tissues of the CM group exhibited significant alveoli collapse and inflammatory cell infiltration. The presence of activated phagolysosomes and lysosomes indicated active immune and phagocytic responses. Bioinformatics highlighted coronin1A (CORO1A) as a potential modulator of immune responses through phagosome formation. Dysregulation could impair immune homeostasis, thereby exacerbating mastitis. Immunofluorescence and immunohistochemistry staining showed that CORO1A was localized in monocytes, macrophages, and neutrophils. Molecular mechanism analysis revealed that Toll-like receptor 2 (TLR2) recognizes pathogens and recruits CORO1A to the phagosome formation site, thereby enhancing the phagocytic activity of immune cells. The expression levels of CORO1A and TLR2 mRNA and proteins were positively correlated with the incidence of mastitis. In conclusion, CORO1A upregulation may activate immune and phagocytic responses, disrupting MGs’ immune homeostasis during Staphylococcus aureus-induced mastitis. These findings provide novel insights into mastitis pathogenesis and potential therapeutic targets. Full article

Background: Tooth extractions commonly result in dimensional changes of the alveolar ridge. Platelet-rich fibrin (PRF) has emerged as a promising autologous biomaterial for alveolar preservation. This randomized controlled trial aimed to evaluate, through cone beam computed tomography (CBCT), the effect of PRF in maintaining alveolar dimensions post-extraction. Methods: A single-blind, randomized controlled clinical trial was conducted in 10 systemically healthy patients requiring premolar extractions for orthodontic reasons. A total of 36 alveoli were analyzed: 19 with PRF (experimental group) and 17 without PRF (control group). CBCT scans were performed at baseline, 30 days, and 120 days post-extraction to measure alveolar height, vestibulo-palatal/lingual depth at 1, 3, and 5 mm, and bone tissue density using Hounsfield Units (HU). Results: Baseline cephalocaudal alveolar height was similar in both groups (~10.5 mm, p = 0.399). At 30 days, height preservation was significantly greater in the PRF group (10.61 mm vs. 8.82 mm, p < 0.001). At 120 days, the PRF group maintained greater height (10.30 mm vs. 9.31 mm), although this difference was not statistically significant (p = 0.059). No significant differences were observed in alveolar depth at 1, 3, or 5 mm (p > 0.05). The PRF group showed a trend toward better preservation and higher mean bone density values (190–282 HU), although no formal statistical comparison of HU values was performed. Repeated measures ANOVA revealed a significant interaction effect of time and group on alveolar height (p = 0.010, η² = 0.046) and at 1 mm depth (p = 0.035, η² = 0.020). Conclusions: PRF significantly improved short-term alveolar height preservation. Trends toward better depth preservation and higher bone density values were observed in the PRF group, although these findings were not statistically significant. PRF appears to be a safe biomaterial with potential to support alveolar ridge maintenance post-extraction. Full article

Alveolar macrophages (AMs) are immune cells located in the alveoli—the tiny air sacs in the lungs where gas exchange occurs. Their functions are regulated by various epigenetic mechanisms, which are essential for both healthy lung function and disease development. In the lung’s microenvironment, AMs play critical roles in immune surveillance, pathogen clearance, and tissue repair. This review examines how epigenetic regulation influences AM functions and their involvement in lung diseases. Key mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs, regulate gene expression in response to environmental signals. In healthy lungs, these modifications enable AMs to quickly respond to inhaled threats. However, when these processes malfunction, they could contribute to diseases such as pulmonary fibrosis, COPD, and pulmonary hypertension. By exploring how epigenetic changes affect AM polarization, plasticity, and immune responses, we can gain deeper insights into their role in lung diseases and open new avenues for treating and preventing respiratory conditions. Ultimately, understanding the epigenetic mechanisms within AMs enhances our knowledge of lung immunology and offers potential for innovative interventions to restore lung health and prevent respiratory diseases. Full article

Pathogenic fungi that exhibit the ability to alternate between hyphal and yeast morphology in response to environmental stimuli are considered dimorphic. Under saprobic conditions, some fungi exist as filamentous hyphae, producing conidia. When conidia are inhaled by mammals or traumatically inoculated, body temperature (37 °C) triggers dimorphism into yeast cells. This shift promotes fungal dissemination and immune evasion. Some fungal pathogens undergo dimorphism in the contrary way, forming pseudohyphae and hyphae within the host. While temperature is a major driver of dimorphism, other factors, including CO₂ concentration, pH, nitrogen sources, and quorum-sensing molecules, also contribute to morphological shifts. This morphological transition is associated with increased expression of virulence factors that aid in adhesion, colonization, and immune evasion. Candida albicans is a fungus that is commonly found as a commensal on human mucous membranes but has the potential to be an opportunistic fungal pathogen of immunocompromised patients. C. albicans exhibits a dimorphic change from the yeast form to the hyphal form when it becomes established as a pathogen. In contrast, Histoplasma capsulatum is an environmental dimorphic fungus where human infection begins when conidia or hyphal fragments of the fungus are inhaled into the alveoli, where the dimorphic change to yeast occurs, this being the morphology associated with its pathogenic phase. This review examines the main signaling pathways that have been mostly related to fungal dimorphism, using as a basis the information available in the literature on H. capsulatum and C. albicans because these fungi have been widely studied for the morphological transition from hypha to yeast and from yeast to hypha, respectively. In addition, we have included the reported findings of these signaling pathways associated with the dimorphism of other pathogenic fungi, such as Paracoccidioides brasiliensis, Sporothrix schenckii, Cryptococcus neoformans, and Blastomyces dermatitis. Understanding these pathways is essential for advancing therapeutic approaches against systemic fungal infections. Full article