Search Results (81)

Peritoneal carcinomatosis (PC) and malignant pleural effusions (MPE) are two common complications of cancers metastatic to the respective body cavities. A PC diagnosis indicates metastasis to the tissue lining the abdominal cavity and is most common in patients with gastrointestinal and gynecological cancers. It is often accompanied by ascites, an accumulation of serous fluid in the abdomen. MPE presents as the accumulation of fluid in the space between the lungs and chest wall. It is a common terminal event in patients diagnosed with breast cancer, lung cancer, lymphoma, and mesothelial cancers, and less commonly, in a wide variety of other epithelial cancers. Due to the aggressive nature of cavitary tumors, the outcome of current treatments for both PC and MPE remains bleak. Although PC and MPE are characteristically affected by different sets of primary tumors (lung/breast/mesothelioma for MPE and gynecologic/gastrointestinal for PC), their environments share common cytokines and cellular components. Owing to the unique cytokine and chemokine content, this environment promotes aggressive tumor behavior and paradoxically both recruits and suppresses central memory and effector memory T cells. The cellular and secretomic complexity of the cavitary tumor environment renders most currently available therapeutics ineffective but also invites approaches that leverage the robust T-cell infiltrate while addressing the causes of local suppression of anti-tumor immunity. Interactions between the heterogeneous components of the tumor environment are an area of active research. We highlight the roles of the immune cell infiltrate, stromal cells, and tumor cells, and the soluble products that they secrete into their environment. A more comprehensive understanding of the cavitary tumor environment can be expected to lead to better immunotherapeutic approaches to these devastating conditions. Full article

Background: Eravacycline exhibits potent activity against multidrug-resistant pathogens and holds promise for the management of hospital-acquired and ventilator-associated pneumonia (HAP/VAP). However, sensitive and robust bioanalytical methods to quantify eravacycline in human pulmonary epithelial lining fluid (ELF) for pharmacokinetic (PK) and pulmonary penetration studies in these infections remain limited. Methodology: A simple, rapid, and sensitive LC-MS/MS method was developed for the quantification of eravacycline in bronchoalveolar lavage fluid (BALF). Using urea as a volume normalizer, ELF concentrations were calculated from the eravacycline concentrations in BALF. This method was applied in a clinical study evaluating the pulmonary penetration after intravenous infusion in patients with HAP and VAP. Results: The developed LC-MS/MS method exhibited good linearity in the range of 1–200 ng/mL for quantifying eravacycline in BALF. In BALF, intra-day precision ranged from 1.4% to 6.0%, and inter-day precision from 1.6% to 9.9%, with accuracy between 98.0% and 102.4%. Matrix effects were within 97.4% to 107.6% for BALF samples from six different individuals, with extraction recoveries ranging from 103.5% to 107.2%. Stability studies demonstrated that eravacycline remained stable under various conditions, including storage at room temperature, freeze–thaw cycles, long-term (–70 °C) storage, and post-treatment handling. The method was successfully applied to clinical samples from four HAP or VAP patients, with measured eravacycline pulmonary penetration ratios of 4.29, 17.40, 5.22 and 4.70, indicating efficient pulmonary distribution. The measured eravacycline concentrations ranged from 0.0243 to 0.0436 μg/mL in BALF. The corresponding urea-corrected ELF concentrations ranged from 0.570 to 1.617 μg/mL. Conclusions: This study described a detailed and validated method for quantifying eravacycline concentrations in ELF from patients, providing a reliable analytical approach for investigating the pulmonary distribution of eravacycline. Full article

Cystic fibrosis is a multisystem disorder caused by mutations in the CFTR gene that lead to impaired ion and fluid transport across secretory epithelia. Although the therapeutic impact of CFTR modulators has been extensively studied in airway epithelia, their efficacy in extra-pulmonary tissues, such as the pancreas, has been less explored. This study evaluated the effects of the CFTR modulators, VX770 (ivacaftor), VX661 (tezacaftor), and VX445 (elexacaftor), administered either individually or in combination, on CFPAC-1 cells, a pancreatic ductal epithelial cell line derived from a cystic fibrosis patient harboring the F508del CFTR mutation. The cells were cultured and differentiated onto porous supports, and a panel of functional parameters was assessed. These included transepithelial electrical conductance, fluid reabsorption, apical surface fluid pH, protein concentration, and microviscosity, the latter analyzed with multiple particle tracking. To simulate a pro-inflammatory micro-environment, the cells were preconditioned with lipopolysaccharide (LPS). Treatment with VX661 and VX445 resulted in significant improvement in epithelial function, with the triple combination producing the most pronounced rescue. Pro-inflammatory stimulation by LPS increased the production of cytokine IL6, IL-8, and IL-1β, as well as the protein content of the apical surface fluid. Despite the LPS pro-inflammatory stimulus, CFTR modulators preserved or slightly enhanced their efficacy in restoring CFTR-mediated ion and fluid transport. However, they did not reduce cytokine expression under pro-inflammatory conditions. Collectively, these findings show that CFTR modulators can restore critical aspects of cystic fibrosis pancreatic epithelial physiology in vitro, even under pro-inflammatory stress, supporting their potential relevance beyond the airway disease. 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

Lacrimal cysts (dacryops), which involve lacrimal tissue, are uncommon in dogs with an obscure/unclear pathogenesis. Compared to the current available literature, this report describes the clinicopathologic and immunohistochemical features of two cases of unusual dacryops in brachycephalic dogs. A three-year-old male Cane Corso was referred with a 1-month history of swelling ventromedial to the left eye associated with blepharospasm and epiphora. Furthermore, a severe lower and upper eyelid entropion and a deep corneal ulcer were present. B-mode ultrasonography and a CT scan revealed a subcutaneous cyst, closely adherent to the maxillary bone. Surgical removal and the correction of entropion were performed. No recurrence and/or complication was detected by seven-year follow-up. Histopathology revealed a cystic structure with single- to double-cell-layered, nonciliated, cuboidal epithelia. Alcian blue stain revealed rare, disseminated goblet cells admixed with epithelial cells. The epithelium was strongly Cytokeratin-positive by immunohistochemistry and appeared lined by several layers of smooth muscle actin (SMA)-positive myoepithelial cells. A 1-year-old male French Bulldog with a 3-month lesion of the third eyelid of the right eye. The lesion (15 mm × 7 mm) beneath the conjunctiva appeared pale-pink, smooth, and multilobulated. Excision was performed by blunt dissection through the conjunctiva on the palpebral surface of the third eyelid. Recovery was uncomplicated, and no recurrence has been noted at three-year follow-up. Cytology of the cystic fluid and histopathology and immunohistochemistry of the cyst wall revealed findings for case 1. To further characterize the SMA-positive spindle cells located directly beneath the cyst-lining epithelium, double-color immunofluorescence for SMA and p63 (a myoepithelial cell marker) was performed on the sample from case 2. The analysis revealed that the SMA-positive cells lacked p63 expression, indicating a non-myoepithelial phenotype. The histological findings in our cases are consistent with previous reports of canine dacryops. The positivity of immunohistochemical staining for SMA in cells directly beneath the epithelium of dacryops in the cases here described in two brachycephalic dogs is consistent with previous reports in dogs and horses but in contrast with a retrospective study about a human dacryops. These results support the conclusion that the pathogenesis of dacryops in dogs should exclude failure of ductular “neuromuscular” contractility. Full article

Background/Objectives: Pancreatic cancer (PC) is among the most aggressive malignancies, often diagnosed at late stages. MicroRNAs (miRNAs) and proteins released from the tumor microenvironment into body fluids represent promising non-invasive biomarkers for early cancer detection. In this study, we took advantage of an innovative ultrasound (US)-based instrument (SonoWell^®, Inno-Sol srl, Rome, Italy) to treat PC cells in order to promote and amplify the release of molecules, with the aim of identifying novel putative diagnostic PC biomarkers. Methods: Three human pancreatic adenocarcinoma cell lines (T3M-4, Panc02.03, and PaCa-44) and a non-cancerous pancreatic epithelial line (HPanEPic) were subjected to US using the SonoWell instrument. MiRNAs released in the supernatants were profiled by TaqMan-based qRT-PCR microfluidic cards, while proteins were analyzed by antibody arrays. Publicly available datasets of circulating miRNAs in PC patients were also reviewed. Results: Expression levels of 22 miRNAs in T3M-4 cells, 11 in Panc02.03, and 22 in PaCa-44, none of which were identified in the non-cancerous cell line profiling, were increased in the supernatant of US-treated as opposed to control cells. Among the statistically significant miRNAs or miRNAs common to at least two tumor cell lines, the expression levels of miR-155-5p, miR-320a, miR-32-5p, and miR-93-5p were also found to be significantly upregulated in sera from PC patients compared to the results for healthy controls. With regard to proteins released after sonication, several molecules were identified as candidate biomarkers in cancer US supernatants (Beta-2 microglobulin, CA125, CA19-9, CEA, CRP, Galectin-3, TIMP-1, uPA, and VEGF-A). Conclusions: We demonstrated that US-mediated sonoporation can promote and amplify the release of small molecules, miRNAs, and proteins into cell culture supernatants for consideration as putative biomarkers, thus encouraging further studies aimed at directly validating their expression levels in sera/plasma from PC patients and at deepening their role in the treatment of PC. Full article

Cancer cell spheroids autonomously form in the ascites fluid and are considered a conduit for epithelial ovarian cancer metastasis within the peritoneal cavity. Spheroids are homotypic, avascular 3D structures that acquire resistance to anoikis to remain viable after cellular detachment. We used in vitro spheroid model systems to interrogate pathways critical for spheroid cell proliferation, distinct from those driving monolayer cancer cell proliferation. Using the 105C and KOC-7c human ovarian clear cell carcinoma (OCCC) cell lines, which have distinct proliferative phenotypes as spheroids but the same prototypical OCCC gene mutation profile of constitutively activated AKT signaling with the loss of ARID1A, we revealed therapeutic targets that efficiently kill cells in spheroids. RNA-seq analyses compared the transcriptome of 3-day monolayer and spheroid cells from these lines and identified the characteristics of dormant spheroid cell survival, which included the G2/M checkpoint, autophagy, and other stress pathways induced in 105C spheroids, in sharp contrast to the proliferating spheroid cells of the KOC-7c cell line. Next, we assessed levels of various G2/M checkpoint regulators and found a consistent reduction in steady-state levels of checkpoint regulators in dormant spheroid cells, but not proliferative spheroids. Our studies showed that proliferative spheroid cells were sensitive to Wee1 inhibition by AZD1775, but the dormant spheroid cells showed a degree of resistance to AZD1775, both in terms of EC50 values and spheroid reattachment abilities. Thus, we identified biomarkers of dormant spheroids, including the G2/M checkpoint regulators Wee1, Cdc25c, and PLK1, and showed that, when compared to proliferating spheroid cells, the transcriptome of dormant OCCC spheroids is a source of therapeutic targets. Full article

Orotic acid (OA) is a natural component of milk and is found in many biological fluids such as human ovarian follicular fluid. However, its effect on ovarian cells is unknown. Some studies suggest that OA may alter lipid metabolism and energy production in cells. In the present study, we determine the effect of OA on mitochondrial function and lipid droplet content in the human granulosa cell line. The effect of OA on in vitro mouse oocyte maturation and mitochondrial activity was also investigated. We found that repeated exposure to OA (0.01–1000 µM) did not alter the viability of human epithelial (HOSEpiC) and granulosa (HGrC1) ovarian cells. HGrC1 cells treated with a high dose of OA (500 µM) showed a more aerobic and energetic phenotype than control cells, whereas this effect was not observed after treatment with lower doses (0.01 and 100 µM) of OA. In addition, OA at a high dose (500 µM) reduced lipid droplet (LD) content without altering glucose (GLUT1, GLUT4) and fatty acid transporter (SLC27A1) gene expression in HGrC1 cells. At the same time, OA at 100 µM did not disrupt mouse in vitro oocyte maturation, whereas OA at 500 µM inhibited this process by arresting oocytes at the germinal vesicle (GV) stage with a reduction in mitochondrial activity. Our results show that OA at high doses can disrupt female reproduction, but normal dietary orotate intake does not have a negative effect on ovarian function. Full article

Background: Achieving pharmacokinetic/pharmacodynamic (PK/PD) targets is critical for improving treatment success, particularly in critically ill patients. This study investigates the role of inflammatory biomarkers and their influence on the PK/PD characteristics of polymyxin B (PMB) in patients with extensively drug-resistant Gram-negative (XDR-GN) bacterial nosocomial pneumonia. Methods: Serial blood and/or bronchoalveolar lavage fluid (BALF) samples were collected at specified time points and analyzed for PMB and/or inflammatory biomarkers, including IL-6 and IL-10. Clinical data were also recorded, and their correlations with PK parameters were further analyzed. Results: Among the 27 enrolled patients, 22 (81.5%) achieved treatment success. The pharmacokinetic parameters of PMB included a maximum plasma concentration (C_max) of 8.3 µg/mL, clearance (CL) of 1.55 L/h, volume of distribution (Vd) of 30.44 L, half-life (t_1/2) of 19.56 h, steady-state area under the plasma concentration–time curve from time 0 to 24 h (AUC_ss,0–24h) of 110.08 h·µg/mL, and a plasma protein-binding ratio of 85.53%. The AUC_ss,0–24h metric was identified as a robust predictor of clinical efficacy, with an optimal cutoff value of 77.27 h·µg/mL. Notably, 48.15% of patients achieved the target AUC_ss,0–24h range of 50–100 h·µg/mL, with 76.95% of these patients attaining treatment success. Another 48.15% of patients exceeded this target, and 92.31% of this subgroup achieved treatment success. PMB demonstrated limited pulmonary penetration, with an epithelial lining fluid (ELF)/plasma ratio of 15.69% [16.86, 18.15]. Furthermore, TNF-α and the IL-6/IL-10 ratio were significantly correlated with PMB PK parameters. Conclusions: Our and others’ studies suggest heterogeneity of PMB PK parameters in critically ill patients. The majority of critically ill patients achieved or surpassed the recommended PK/PD targets and attained treatment success through intravenous administration of PMB at a simplified fixed dose. However, PMB did not achieve satisfactory pulmonary concentrations, suggesting that its efficacy may involve alternative mechanisms. The modulation of inflammatory responses may play a pivotal role in the treatment of severe infections, highlighting the potential for biomarker-guided therapeutic strategies. Full article

Little is known about the complex events driving host–pathogen and pathogen–pathogen interplay in polymicrobial infections. Using an in vitro model of a reconstituted vaginal epithelium (RVE) employing the A-431 cell line supplemented with synthetic vaginal fluid (SVF), we studied the consequences of single versus dual infections with Candida albicans and/or Herpes Simplex Virus-2 (HSV-2). Our data show (a) a relevant, SVF-enhanced expression of the differentiation marker cytokeratin 5/6 in the RVE; (b) the ability of Candida albicans to enhance HSV-2 in the dual infection model, with the virus titer almost doubling in the presence of SVF; (c) RVE damage (>20%), mostly attributable to Candida albicans and related to oxidative stress whether SVF is present; (d) the dysregulation of mucin-1, the production of which is enhanced (from 13 to 21 ng/mL) or impaired (from 21 to 10 ng/mL) in response to either SVF or infection, respectively; and (e) a partial-to-negligible cytokine response from the RVE, depending upon SVF presence. In conclusion, using an in vitro RVE model upgraded through the addition of synthetic vaginal fluid, we provide details on epithelial cell–pathogen–pathogen interaction, contributing to a better comprehension of the pathogenesis of polymicrobial infections at a mucosal level. Full article

Backgrounds: Photodynamic therapy (PDT) is an established treatment modality in central serous chorioretinopathy (CSCR). The goal of our study was to evaluate the morphological and functional effects of PDT in patients with long-lasting CSCR and determine the related predictive factors for improvement. Methods: This retrospective analysis included consecutive patients with chronic CSCR who consented to PDT. The material comprised 98 eyes of 81 patients (67 males and 14 females) with a disease duration longer than 6 months followed for 6 months post treatment. All patients underwent a basic ophthalmological examination including best corrected visual acuity (BCVA) testing and imaging, spectral-domain optical coherence tomography (SD-OCT), and fluorescein angiography. Patients without macular neovascularization (MNV) were subjected to half-dose PDT (3 mg/m²) with standard fluence (50 J/cm²), guided by indocyanine green angiography. Cases complicated by MNV were subjected to full-dose PDT. Results: A morphological response, defined as complete resolution of subretinal fluid, was achieved in 76.29% of cases, and an improvement in BCVA of at least one logMAR line was obtained in 77.53% of cases. The mean BCVA gain was 1.2 logMAR line. All SD-OCT measurements (central retinal thickness, macular volume, mean subfield thickness, subretinal fluid height, and subfoveal choroidal thickness) showed a significant reduction post PDT. A multivariate analysis proved better morphological outcome associations with a younger age and male gender and better visual gains achieved in patients without intraretinal abnormalities. Univariate testing also showed strong relationships between better baseline BCVA and greater functional and morphological improvements, between shorter disease duration and morphological gains, and between the absence of MNV or intraretinal abnormalities and morphological gains. PDT was highly effective in providing a resolution of pigment epithelial detachment (p = 0.0004). The observed effect was significantly dependent upon the lower baseline central retinal thickness (p = 0.0095). Patients with intraretinal abnormalities or MNV showed moderate improvements post PDT. Conclusions: PDT in long-lasting CSCR cases provides good morphological results but generally minor visual gains. Patients’ expectations of significant increases in BCVA after prolonged disease with distinct alterations of the neurosensory retina should be managed. Full article

Objective: The aim was to evaluate the pharmacokinetics and underlying mechanisms of peramivir, a clinically approved antiviral agent for severe influenza, subsequent to airway inhalation in rats, thereby surmounting the constraints associated with the sole currently available intravenous formulation. Methods: Pharmacokinetic and tissue distribution investigations of peramivir were carried out in rats following both intravenous and inhaled administration. In vitro cell models were verified to investigate peramivir’s transmembrane transport and cellular uptake across diverse cell systems. Results: In vivo, peramivir exhibited restricted permeability, predominantly localizing within the alveolar epithelial lining fluid and lung tissue after inhalation, accompanied by minimal systemic dissemination. In vitro, it manifested low permeability across cell models, with no participation of efflux transporters. Despite the low rate of A549 uptake, the underlying uptake transport mechanism was still revealed. Peramivir was verified as an OCTN2 substrate. A robust correlation was observed between the in vitro and in vivo findings. Conclusions: A preclinical pharmacokinetic platform applicable to inhaled medications was established. Inhalation of peramivir augments exposure at the target site while diminishing systemic exposure, presenting potential therapeutic benefits in terms of efficacy and safety and suggesting it as a favorable alternative administration pathway. Full article

Background/Objectives: Cytolytic vaginosis or, classically, Doderlein’s cytolysis is characterized by significant growth of species of the Lactobacillus genus, which leads to high amounts of lactic acid in the vaginal environment. Lactobacillus crispatus has been proposed as a key pathogen in this clinical condition. The symptomatology of cytolytic vaginosis is commonly confused with that of vulvovaginal candidosis, leading to inadequate and ineffective azole therapies. Nevertheless, historically, the use of sodium bicarbonate intimate baths was an effective way to reduce the symptoms of cytolytic vaginosis. Methods: In this study, four HPMC gel prototypes were developed, containing sodium bicarbonate concentrations ranging from 4% to 7% (w/w). These gels were evaluated for their physicochemical properties, antimicrobial activity, interference with lactobacilli adhering to cells, and cellular and tissue biocompatibility. Results: The gels presented pH values of around 9.0, and osmolality between 706 mOsm/kg (F4) and 1065 mOsm/kg (F7). The viscosity upon heating to physiologic temperature and dilution with simulated vaginal fluid was highly affected by the concentration of sodium bicarbonate. Gels with higher sodium bicarbonate concentrations (F6 and F7) were not shown to be stable in these conditions. All formulations exhibited effective antimicrobial activity against seven L. crispatus strains, with MIC values ranging from 6.25% to 25% (v/v) in terms of dilution. Additionally, the 4% (w/w) gel significantly interfered with the adhesion of L. crispatus to epithelial cells in competition and exclusion assays, reducing adhesion by more than 90% in relation to the control. Cytotoxicity tests on the Hec-1A, HeLa, and VK2/E6E7 cell lines indicated that the F4 and F5 gels demonstrated lower cytotoxicity levels compared to those with higher concentrations. Furthermore, ex vivo assays using porcine vaginal tissue confirmed that the 4% gel was non-toxic at a 25% (v/v) dilution. Conclusions: Based on these results, the 4% (w/w) sodium bicarbonate gel (F4) emerges as a promising therapeutic option for cytolytic vaginosis, offering effective bacterial interference, favourable physicochemical properties, and biocompatibility suitable for vaginal application. Full article

Background/Objectives: Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for neovascular age-related macular degeneration (nvAMD). While proactive and adequate treatment generally leads to better visual outcomes, various factors, including the disease type, ocular findings, lifestyle, and systemic status, affect the visual prognosis in clinical settings. This study aimed to identify the factors that affect the visual prognosis in patients with nvAMD treated with anti-VEGF therapy. Methods: We conducted a multicenter retrospective cohort study at eight tertiary referral centers in Japan, where we reviewed the medical records of patients newly diagnosed with nvAMD between January 2014 and December 2019. These patients had started treatment with either ranibizumab (0.5 mg) or aflibercept (2.0 mg) and were followed for at least 1 year. We evaluated the impact of the disease type, systemic factors, and initial fundus findings on the best-corrected visual acuity (BCVA) at 1 year. Results: This study included 182 patients (129 men, 53 women), with a mean age of 75.0 ± 8.6 years. The disease types were categorized as typical AMD (53%), polypoidal choroidal vasculopathy (PCV) (43%), and retinal angiomatous proliferation (RAP) (4%). Univariate analysis identified age, the baseline logarithm of the minimum angle of resolution BCVA, intraretinal fluid (IRF), pigment epithelial detachment (PED), and subretinal hyperreflective material (SHRM). Multivariate analysis identified the following significant risk factors associated with vision worsening: age, smoking history, diabetes, and the presence of IRF and PED. Conclusions: The presence of IRF, PED, and SHRM at the start of treatment and a history of smoking and diabetes may be associated with a poor visual prognosis in patients with nvAMD. Full article

Scutellarein is a key active constituent present in many plants, especially in Scutellaria baicalensis Georgi and Erigeron breviscapus (vant.) Hand-Mazz which possesses both anti-inflammatory and anti-oxidative activities. It also is the metabolite of scutellarin, with the ability to relieve LPS-induced acute lung injury (ALI), strongly suggesting that scutellarein could suppress respiratory inflammation. The present study aimed to investigate the effects of scutellarein on lung inflammation by using LPS-activated BEAS-2B cells (a human bronchial epithelial cell line) and LPS-induced ALI mice. The results showed that scutellarein could reduce intracellular reactive oxygen species (ROS) accumulation through inhibiting the activation of NADPH oxidases, markedly downregulating the transcription and translation of pro-inflammatory cytokines, including interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine ligand (CXCL) 8 in LPS-activated BEAS-2B cells. The mechanism study revealed that it suppressed the phosphorylation and degradation of IκBα, consequently hindering the translocation of p65 from the cytoplasm to the nucleus and its subsequent binding to DNA, thereby decreasing NF-κB-regulated gene transcription. Notably, scutellarein had no impact on the activation of AP-1 signaling. In LPS-induced ALI mice, scutellarein significantly decreased IL-6, CCL2, and tumor necrosis factor-α (TNF-α) levels in the bronchoalveolar lavage fluid, attenuated lung injury, and inhibited neutrophil infiltration. Our findings suggest that scutellarein may be a beneficial agent for the treatment of infectious pneumonia by virtue of its anti-oxidative and anti-inflammatory activities. Full article