Search Results (88)

Objective: Rho-associated protein kinase (ROCK) inhibitors have recently emerged as promising agents for the treatment of corneal endothelial dysfunction. Because corneal transparency critically depends on endothelial cell function, endothelial failure can lead to persistent visual impairment. However, clinical evidence regarding the use of topical ROCK inhibition in various etiologies of endothelial decompensation remains limited. The aim of this study was to evaluate changes in central corneal thickness (CCT), best-corrected visual acuity (BCVA), and treatment-related adverse events in eyes with corneal edema of different etiologies treated with fixed-combination drops of netarsudil 0.02%/latanoprost 0.005%, Roclanda^®. Methods: In this prospective, uncontrolled, exploratory case series, we investigated the effects of topical ROCK inhibition on corneal endothelial cell function in 13 eyes of 11 patients with persistent, nonhealing corneal edema following intraocular procedures. Patients were treated with topical Roclanda^® once daily for three months. Clinical evaluation included BCVA, CCT, and safety assessment. Changes in CCT and BCVA were assessed before therapy, and after 1 and 3 months of treatment. Results: Mean baseline CCT was 782.8 µm and decreased significantly by 71.0 µm at 1 month and by 120.2 µm at 3 months (p = 0.0074 and 0.0012, respectively). Complete resolution of corneal edema was achieved in 38% of eyes. Mean BCVA improved from 0.744 before treatment to 0.518 logMAR at 3 months (p = 0.0026), with 46.2% of eyes gaining two or more Snellen lines. The analysis including only one eye per patient showed similar results, with statistically significant reductions in CCT at both 1 and 3 months and a significant improvement in BCVA at 3 months after the exclusion of the second eye in bilaterally included patients. Treatment was well tolerated; with mild conjunctival hyperemia as the most common adverse effect, while reticular epithelial corneal edema occurred in one eye and resolved after the completion of the treatment. Conclusions: In this prospective, exploratory case series of patients with nonhealing corneal edema, 3 months of a fixed-dose netarsudil 0.02%/latanoprost 0.005% treatment resulted in significant reduction in CCT, as well as clinically important improvement in BCVA. These exploratory findings cannot explain the mechanism of action, but suggest a potential therapeutic role for ROCK inhibitors in eyes with nonhealing corneal edema and possibly residual endothelial reserve. Larger controlled studies are needed to confirm these observations and further define indications for treatment. Full article

Background: Severe lung compromise from COVID-19, ARDS, and recently AH3N2 can progress to life-threatening hypoxia. Past experience led to standardized protocols that assumed similarity to SARS-CoV. Methods: COVID-19 pathophysiology and histopathological lung biopsy photomicrographs are analyzed. Results: Pneumolysis is defined as progressive alveolar–capillary destruction resulting from SARS-CoV-2 attack on pneumocytes. In the final stages preceding pneumolysis, molecular mechanisms in the lungs include apoptosis in alveolar epithelial type I and II cells, compromising alveolar regeneration, and necrosis, resulting in leakage of intracellular contents and amplifying inflammation. Pyroptosis, driven by inflammasome activity, further disrupts alveolar integrity in ARDS. Histopathological findings include Masson bodies, alveolar-coating cells with nuclear atypia, reactive pneumocytes and reparative fibrosis, intra-alveolar hemorrhage, moderate inflammatory infiltrates and abscesses, microthrombi, hyaline membrane remnants, and emphysema. The three theoretical pathophysiological stages of progressive hypoxemia (silent hypoxemia, gasping, and death zone) are shown. Conclusions: Silent hypoxemia rapidly progresses to critical hypoxemia. This progression results from progressive pneumolysis, inflammation, immune overexpression, autoimmunity, and HAPE-type edema, leading to acute pulmonary insufficiency. Long-lasting COVID-19 can result in fibrosis and, as a compensatory mechanism, polierythrocythemia. The proposed treatment (based on tolerance to hypoxia and the hemoglobin factor) includes prompt oxygen administration, control of inflammatory and immune responses, antibiotics, rehydration, erythropoietin and platelet aggregation inhibitors. Full article

Introduction: Uremic toxins have been shown to cause adverse pulmonary effects by inducing endothelial and epithelial dysfunction, disrupting the alveolar-capillary barrier, and increasing inflammation and oxidative stress. This article reviews these effects with a specific focus on chronic kidney disease and the mechanisms by which uremic toxins affect lung tissue. Methods: A narrative review was conducted using keywords related to uremic toxins and lung injury to search the PubMed database. An advanced literature review was conducted in PubMed to identify studies explaining the mechanisms underlying lung pathophysiology in chronic kidney disease (CKD), with particular focus on CKD-induced pulmonary epithelial and endothelial dysfunction. Additionally, to highlight the pathological processes of lung congestion in CKD, studies on CKD-induced dysfunction of the alveolar-capillary barrier were retrieved. Studies published up to November 2025 were evaluated. Results: A total of 148 articles were reviewed in full text. Uremic toxins negatively impact lung tissue structure and function through multiple mechanisms, including oxidative stress, inflammation, and direct effects. Uremic toxins appear to share signaling pathways in endothelial cells, including those linked to Mitogen-activated protein kinases (MAPK), the Aryl Hydrocarbon Receptor (AhR), the receptor for advanced glycation end products (RAGE), and pro-inflammatory transcription factors such as nuclear factor κB (NF-κB). Additionally, oxidative stress acts as a pro-inflammatory signal shared by several uremic toxins. The mechanisms behind the harmful interactions between CKD and lung disease are mostly unknown, although more evidence exists for acute kidney injury (AKI). Conclusions: Chronic kidney disease, which leads to the buildup of uremic toxins, negatively affects the lungs. Overall, the accumulation of uremic toxins in CKD impairs endothelial and epithelial cells and the alveolar capillary barrier. Further research is needed to understand the specific mechanisms underlying these effects and to identify therapeutic options to protect the lungs in these patients. Full article

Background/Objectives: Cigarette smoke (CS) drives pathogenesis across the spectrum of chronic respiratory disorders, exerting its detrimental effects primarily through oxidative stress and programmed cell death. Scutellarein (Scu), a botanical-origin flavonoid enriched in respiratory therapeutics-oriented Chinese medicinal herbs, demonstrates established anti-inflammatory applications. This study systematically evaluated the protective roles of Scu against CS-induced lung injury and explored the underlying mechanisms. Methods: Subacute CS-exposed mice were used to evaluate the therapeutic effects of Scu on lung injury. Immunofluorescence and quantitative PCR were used to examine the expression levels of junctional proteins and proinflammatory mediators. Apoptotic cell death was quantified using Annexin V-FITC/7-AAD staining. Transepithelial electrical resistance and dextran permeability assay were used to access the barrier integrity in alveolar epithelial MLE-12 cells. Western blotting was used to detect the changes in the signal pathway. Results: In CS-exposed mice, Scu administration dose-dependently reduced histopathological scores, pulmonary edema, changes in the alveolar structure, and inflammatory cell infiltration. In MLE-12 cells, Scu significantly suppressed cigarette smoke condensate (CSC)-induced inflammatory mediators, oxidative stress, caspase-3 activation, and apoptosis and preserved CSC-suppressed tight junction protein expression and barrier disruption. Scu also rescued CSC-altered expression levels of Hrk, Ecscr, and Myo5b and mitigated the CSC-suppressed PI3K/AKT/mTOR pathway. Conclusions: Scu alleviates CS-induced subacute lung injury through its antioxidant, anti-apoptotic effects to maintain epithelial barrier integrity likely via the mitigation of the CSC-suppressed PI3K/AKT/mTOR pathway. Full article

Late-onset Fuchs endothelial corneal dystrophy (FECD) is a hereditary, progressive, bilateral and irreversible disorder that is characterized by thickening of Descemet’s membrane, microscopic collagenous protuberances known as guttae, and accelerated loss of corneal endothelial cells. Patients initially complain of blurred vision, and as the disease progresses, painful epithelial edema develops. Untreated cases of FECD often result in blindness, and then, the only treatment is corneal transplantation. DNA polymorphisms in many genes have been implicated, among them TCF4 on chromosome 18q, encoding a transcription factor protein E2-2, which is involved in regulating cellular growth and differentiation in the cornea. In our previous published study, we confirmed the association of an intronic TCF4 SNP (rs613872) with the disease in our population. The purpose of this present study is to further investigate another intronic point of interest in the same gene, the CTG18.1 trinucleotide repeat expansion. DNA was isolated from EDTA blood from a well-ascertained group of 36 Greek patients with FECD (Krachmer scale ≥ 2) and 58 healthy individuals, age- and sex-matched after obtaining their informed consent. STR-PCR and triplet-repeat primed PCR (TP-PCR) were performed, followed by gel electrophoresis and fragment analysis on an ABI SeqStudio genetic analyzer. Our real-time qPCR genotyping method was used for the SNP in the LightCycler (Roche). Statistical analysis of both genetic results was performed with SPSS and SNPStats. Full article

Background: Acute lung injury (ALI) is a life-threatening respiratory condition and one of the leading causes of mortality worldwide, accounting for approximately 20% of global annual deaths. Despite its high prevalence and severity, effective therapeutic options remain limited. Eupatorium lindleyanum DC., a traditional medicinal herb, has demonstrated therapeutic potential against pulmonary diseases, particularly ALI, in both clinical and experimental settings. However, the protective effects and underlying mechanisms of its characteristic sesquiterpene lactone components against ALI remain unclear. Objective: This study aimed to evaluate the protective effects of sesquiterpene lactones from Eupatorium lindleyanum DC. (SLEL) against lipopolysaccharide (LPS)-induced ALI both in vivo and in vitro. Furthermore, it sought to elucidate the underlying mechanisms by integrating network pharmacology, multi-omics approaches (transcriptomics, metabolomics, and 16S rRNA sequencing), and various molecular biology techniques. Results: SLEL significantly attenuated inflammatory injury in alveolar epithelial cells and alleviated pulmonary edema, hemorrhage, and inflammatory infiltration in rats, accompanied by reduced TNF-α, IL-6, and IL-1β levels and improved lung injury indices. Mechanistically, SLEL exerted dual suppression of the PI3K-Akt and MAPK-NF-κB pathways. Network pharmacology, molecular docking, and UPLC-MS analyses identified Eupalinolide A and Eupalinolide K as potential bioactive constituents, which were further validated to inhibit phosphorylation of key signaling proteins, thereby partially accounting for SLEL’s pharmacological effects. Multi-omics integration further revealed that SLEL restored bile acid metabolism, reshaped gut microbial diversity, and reconstructed the microbiota–metabolite–inflammatory cytokine network, thereby maintaining gut–lung axis homeostasis and enhancing anti-inflammatory effects. Conclusions: SLEL alleviates ALI through multi-component synergistic actions that suppress pro-inflammatory signaling and modulate the gut–lung axis. These findings highlight the potential of SLEL as a promising therapeutic candidate for the treatment of ALI. Full article

The mudflat crab (H. tientsinensis) is a dominant species in coastal tidal flat areas, primarily inhabiting the high tide region of the intertidal zone, and possesses significant ecological and economic value. Vibrio species are one of the main bacterial pathogens responsible for diseases in marine organisms, and they are widely distributed in seawater and estuarine environments. However, the immune mechanisms employed by H. tientsinensis in response to Vibrio infections remain unclear. This study aims to investigate the physiological and immune mechanisms by analyzing the structural changes and differential gene expression in the gill and hepatopancreas following Vibrio parahaemolyticus infection. The results indicate that V. parahaemolyticus infection causes cellular damage, with structural alterations observed in the gills (epithelial cell edema in the gill filaments, and aneurysm formation) and the hepatopancreas (changes in lumen size, nuclear condensation, and modifications in connective tissue morphology). Transcriptome analysis revealed 9766 differentially expressed genes (DEGs) in the gills of the experimental group, with 4687 upregulated and 5079 downregulated genes. These DEGs are primarily involved in different ribosomal subunits. In the hepatopancreas, 1594 DEGs were identified, with 834 upregulated and 760 downregulated. These DEGs are predominantly associated with energy-coupled proton transmembrane transport, electron transport-coupled proton transport, and lipid transporter activity. H. tientsinensis gene annotation and KEGG enrichment analysis revealed that chemical carcinogens DNA adducts, amino acid metabolism, and some immune pathways play key roles in the ability of H. tientsinensis to defend against V. parahaemolyticus infection. The findings of this study contribute to a deeper understanding of the immune mechanisms of H. tientsinensis against V. parahaemolyticus infection and provide new insights for aquaculture management. Full article

Background: The incidence of chemical ocular trauma after accidentally instilling the “wrong” eyedrops is still frequent, but cases resulting from stamper ink refills are rare. Case Presentation: A 73-year-old man presented to our emergency department with a history of inadvertently instilling stamper ink refill into both eyes (BEs) instead of artificial tears. Immediate irrigation and evaluation were performed. The initial visual acuity (VA) was 0.4 in the right eye (RE) and 0.8 in the left eye (LE). Slit lamp examination showed edema palpebra with periocular blue staining in BEs, chemotic conjunctiva with a much darker color in the RE than the LE, and epithelial defects with a positive fluorescein test in BEs. A diagnosis of bilateral corneal abrasion and chemotic conjunctiva was established. Ten hours after the emergency visit, RE VA decreased to 0.2, and corneal edema was found during the follow-up examination. Medications including levofloxacin antibiotic, sodium hyaluronate, sodium chloride, combined polymyxin sulfate–neomycin sulfate and dexamethasone eyedrops, mefenamic acid, and ascorbic acid tablets were prescribed. The RE corneal edema still occurred, and the endothelial cell count was 1952 and 987 cells/mm² in the RE and LE at the one-week follow-up. After three weeks, corneal edema had fully resolved, and the VA was 0.4 and 0.8 in the RE and LE, respectively. Conclusions: This case report adds to the spectrum of the continuing problem of chemical ocular trauma after mistakenly instilling the eyedrops. Promoting and changing to different packages for non-ophthalmic products in plastic bottles mimicking eyedroppers is essential to minimize these injuries. Full article

Background and Clinical Significance: The 45,X0/46,XY mosaic karyotype is categorized as a disorder of sex development and can lead to atypical sexual development. Latent mosaicism involving Y chromosomal segments may be much more prevalent than previously assumed, according to a growing number of findings. This primarily depends on how sensitive cytogenetic methods are—such as traditional karyotype screening, FISH methods, or molecular analyses. Case Presentation: We present the case of a 10-week-old infant with hermaphroditic external genitalia. During pregnancy, ultrasonography revealed severe fetal development difficulties, including severe widespread edema. An abnormal 45,X0/46,XY mosaic karyotype was discovered during a genetic amniocentesis conducted during the 16th week of pregnancy. The infant was born in average general condition at 39 + 6 weeks of gestation. Physical examination of the infant revealed features of facial dysmorphia, webbed neck, and hermaphroditic external genitalia. The testicle was palpable on the left side, but the gonad was absent on the right. Laboratory tests revealed a typical hormonal profile of the mini-puberty period in boys. Moreover, a hormone panel and thyroid ultrasound were performed; congenital hypothyroidism was diagnosed. Three separate independent sources of biological material were used in cytogenetic analysis to determine the karyotype: skin fibroblasts (to confirm tissue mosaicism), oral epithelial cells (FISH), and peripheral blood lymphocytes. It showed that a mosaic occurred very early in embryogenesis by confirming the existence of karyotypes 45,X and 46,XY in various tissues (mosaic tissue distribution). Conclusions: Tissue mosaicism should be compared to the analysis of tissues from other embryonic origins, including blood and oral tissue. Support for gender identity and treatment decisions, including the prediction of the future risk of gonadoblastoma, as well as multidisciplinary care, is necessary. Full article

Acute Respiratory Distress Syndrome (ARDS) is a complex and devastating form of respiratory failure, with high mortality rates, for which there is no pharmacological treatment. The acute exudative phase of ARDS is characterized by severe damage to the alveolar–capillary barrier, infiltration of protein-rich fluid into the lungs, neutrophil recruitment, and high levels of inflammatory mediators. Rapid resolution of this reversible acute phase, with efficient restoration of alveolar functional integrity, is essential before the establishment of irreversible fibrosis and respiratory failure. Several lines of in vitro and in vivo evidence support the involvement of potassium (K⁺) channels—particularly KvLQT1, expressed in alveolar cells—in key cellular mechanisms for ARDS resolution, by promoting alveolar fluid clearance and epithelial repair processes. The aim of our study was to investigate whether pharmacological activation of KvLQT1 channels could elicit beneficial effects on ARDS parameters in an animal model of acute lung injury. We used the well-established bleomycin model, which mimics (at day 7) the key features of the exudative phase of ARDS. Our data demonstrate that treatments with the KvLQT1 activator R-L3, delivered to the lungs, failed to improve endothelial permeability and lung edema in bleomycin mice. However, KvLQT1 activation significantly reduced neutrophil recruitment and tended to decrease levels of pro-inflammatory cytokines/chemokines in bronchoalveolar lavages after bleomycin administration. Importantly, R-L3 treatment was associated with significantly lower injury scores, higher levels of alveolar type I (HTI-56, AQP5) and II (pro-SPC) cell markers, and improved alveolar epithelial repair capacity in the presence of bleomycin. Together, these results suggest that the KvLQT1 K⁺ channel may be a potential target for the resolution of the acute phase of ARDS. Full article

Limbal dermoids are congenital, benign, choristomatous growths affecting the corneal-limbal junction. Conventional excision techniques often result in persistent epithelial defects, corneal thinning, and vascularization due to sectoral limbal stem cell deficiency. This study investigated a novel surgical approach for limbal dermoid excision, utilizing Bowman’s membrane lenticule and autologous limbal stem cell transplantation, aimed at improving epithelial healing and visual outcomes. Thirty-four subjects (24 females, 10 males; mean age 8.33 ± 6.47 years) with limbal dermoids underwent the procedure. After dermoid excision, a Bowman’s membrane lenticule was placed over the defect and tucked 1 mm beneath the surrounding tissue. Sectoral limbal reconstruction was then performed using the AutoSLET technique. Pre- and postoperative assessments included visual acuity, corneal thickness, and epithelialization time. Statistical analysis employed paired t-tests. The mean epithelialization time was 3.36 ± 0.74 weeks, indicating rapid healing. Best-corrected visual acuity (BCVA) significantly improved from a preoperative mean of 0.136 ± 0.121 decimal units to a postoperative mean of 0.336 ± 0.214 decimal units (p < 0.001). Corneal thickness also demonstrated a significant increase, rising from a preoperative mean of 294 ± 49.68 microns to a postoperative mean of 484 ± 5.037 microns (p < 0.001). There is a transient edema below the Bowman lenticule observed in many cases, which resolves with deposition of granulation tissue. The findings suggest that the combined use of Bowman’s membrane lenticule and autologous limbal stem cell transplantation offers a promising surgical strategy for limbal dermoid excision. This technique promotes rapid epithelialization and leads to significant improvements in visual acuity and corneal thickness compared to conventional methods. The utilization of Bowman’s membrane as a natural basement membrane and the direct application of limbal stem cells facilitate enhanced epithelial healing and visual rehabilitation. While the study is limited by its small sample size, the results demonstrate the potential of this novel approach in managing limbal dermoids effectively. Full article

Background: Sepsis-induced acute lung injury (ALI) is a serious disease constituting a heavy burden on society due to high mortality and morbidity. Inflammation and oxidative stress constitute key pathological mechanisms in ALI caused by sepsis. LL-37 can improve the survival of septic mice. Nevertheless, its function and underlying mechanism in sepsis-evoked ALI is elusive. Methods: The human A549 alveolar epithelial cell line was treated with LL-37 or ZBP1 recombinant vector under LPS exposure. Then, the effects on cell oxidative stress injury, inflammatory response, and autophagy were analyzed. RNA-seq analysis was performed to detect the differentially expressed genes (DEGs) between the LPS and LPS/LL-37 groups. Furthermore, the effects of LL-37 on cecal ligation and the puncture (CLP)-constructed ALI model were explored. Results: LL-37 attenuated LPS-evoked oxidative injury in human alveolar epithelial cells by increasing cell viability and suppressing ROS, malondialdehyde, and lactate dehydrogenase levels and apoptosis. Moreover, LPS-induced releases of pro-inflammatory IL-18, TNF-α, and IL-1β were suppressed by LL-37. Furthermore, LPS’s impairment of autophagy was reversed by LL-37. RNA-seq analysis substantiated 1350 differentially expressed genes between the LPS and LPS/LL-37 groups. Among them was ZBP1, a significantly down-regulated gene with the largest fold change. Moreover, LL-37 suppressed LPS-increased ZBP1 expression. Importantly, ZBP1 elevation restrained LL-37-induced autophagy in LPS-treated cells and abrogated LL-37-mediated protection against LPS-evoked oxidative injury and inflammation. LL-37 ameliorated abnormal histopathological changes, tissue edema, the lung injury score, oxygenation index (PaO2/FiO2), and glycemia contents in the CLP-constructed ALI model, which were offset through ZBP1 elevation via its activator CBL0137. Additionally, LL-37 suppressed inflammation and oxidative stress in lung tissues, concomitant with autophagy elevation and ZBP1 down-regulation. Conclusions: LL-37 may alleviate the progression of sepsis-evoked ALI by attenuating pulmonary epithelial cell oxidative injury and inflammatory response via ZBP1-mediated autophagy activation, indicating a promising approach for the therapy of ALI patients. Full article

Patients with sepsis often receive mechanical ventilation (MV). Continued use of MV may increase overdistention in the lungs, inflammatory mediator production, and inflammatory cell recruitment, eventually causing ventilator-induced lung injury (VILI). Endoplasmic reticulum (ER) stress caused by MV, oxidative stress, and sepsis results in dissociation of GRP78 from transmembrane proteins (PERK, IRE1α, and ATF6) and generates abundant incorrect protein structures. Phosphoinositide 3-kinase-γ (PI3K-γ) has been demonstrated to modulate ER stress associated with sepsis and acute lung injury (ALI). However, the regulatory mechanisms by which ER stress is involved in VILI remain unclear. In this study, MV was hypothesized to augment lung injury and induce ER stress through the PI3K-γ pathway, regardless of endotoxemia. Wild-type or PI3K-γ-deficient C57BL/6 mice were exposed to 30 mL/kg tidal volume of MV with or without endotoxemia for 5 h. The control group comprised nonventilated mice. MV with endotoxemia increased microvascular permeability, lung edema, interleukin-6 and metalloproteinase-9 production, oxidative loads, ER stress biomarkers (GRP78, IRE-1α, PERK), morphological rearrangement, PI3K-γ expression, and bronchial epithelial apoptosis in rodent lungs. The increase in lung injury was substantially reduced in PI3K-γ-deficient mice and in mice administered 4-phenylbutyric acid. In conclusion, MV-augmented ALI after endotoxemia partially depends on the PI3K-γ pathway. Full article

Mitogen-Activated Protein Kinase Kinase Kinase 1 (MAP3K1) is a key signaling molecule essential for eyelid closure during embryogenesis. In mice, Map3k1 knockout leads to a fully penetrant eye-open at birth (EOB) phenotype due to disrupted MAPK signaling, abnormal epithelial differentiation, and morphogenesis. To further explore the roles of MAP3K1 in ocular development, we generated a Cre-inducible gain-of-function transgenic mouse, designated as Map3k1^TG, and crossed it with Lens epithelial (Le)-Cre mice to drive MAP3K1 overexpression in developing ocular surface epithelium (OSE). Map3k1^TG;Le-Cre embryos exhibited ocular defects including premature eyelid closure, lens degeneration, and corneal edema. While corneal epithelial differentiation remained intact, the lens epithelium degenerated with lens formation compromised. Eyelid epithelium was markedly thickened, containing cells with aberrant keratin (K)14/K10 co-expression. Genetic rescue experiments revealed that Map3k1^TG;Le-Cre restored eyelid closure in Map3k1 knockout mice, whereas MAP3K1 deficiency attenuated the epithelial thickening caused by transgene expression. Mechanistically, MAP3K1 overexpression enhanced c-Jun phosphorylation in vivo and activated JNK-c-Jun, WNT, TGFβ, and Notch signaling and promoted keratinocyte proliferation and migration in vitro. These findings highlight a dose-sensitive role for MAP3K1 in regulating epithelial proliferation, differentiation, and morphogenesis during eyelid development. Full article

Alveolar active sodium transport is essential for clearing edema from airspaces, in a process known as alveolar fluid clearance (AFC). Although it has been reported that atrial natriuretic peptide (ANP) attenuates AFC, little is known about the underlying molecular effects of natriuretic peptides (NPs). Therefore, we examined the contribution of NPs to AFC and their effects as mediators of active sodium transport. By using the isolated liquid-filled lungs model, we investigated the effects of NPs on AFC. The expression of NPs, Na⁺, K⁺-ATPase, and Na⁺ channels was assessed in alveolar epithelial cells. Congestive heart failure (CHF) was induced by using the aortocaval fistula model. ANP and brain NP (BNP) significantly reduced AFC rate from 0.49 ± 0.02 mL/h in sham rats to 0.26 ± 0.013 and 0.19 ± 0.005 in ANP and BNP-treated groups, respectively. These effects were mediated by downregulating the active Na⁺ transport components in the alveolar epithelium while enhancing the ubiquitination and degradation of αENaC in the lungs, as reflected by increased levels of Nedd4-2. In addition, AFC was reduced in compensated CHF rats treated with ANP, while in decompensated CHF, ANP partially restored AFC. In conclusion, NPs regulate AFC in health and CHF. This research could help optimize pharmacological treatments for severe CHF. Full article