Search Results (2,052)

Experimental acute lung injury (ALI) models are widely used to investigate pulmonary inflammation and evaluate therapeutic strategies for acute respiratory distress syndrome (ARDS). Kaempferia marginata is a traditional medicinal plant used to treat fever and has been reported to possess anti-inflammatory properties in lipopolysaccharide (LPS)-activated macrophages. 6β-Acetoxysandaracopimaradien-1α,9α-diol (ASPD), a major isopimarane-type diterpenoid isolated from this plant, has not previously been investigated for its effects on ALI. This study employed an integrated network pharmacology, molecular docking, and experimental validation strategy to investigate the protective effects and potential mechanisms of ASPD against LPS-induced ALI. Network pharmacology analysis identified several inflammation-related hub targets associated with Src, MAPK, and PI3K/Akt signalling. In LPS-stimulated MLE-12 cells, ASPD reduced inflammatory cytokine production and inhibited the phosphorylation of JNK1/2, ERK1/2, p38 MAPK, Akt, and GSK-3β. In mice with LPS-induced ALI, ASPD alleviated histopathological lung injury, pulmonary oedema, and inflammatory cell infiltration while reducing IL-6, TNF-α, and myeloperoxidase activity without apparent toxicity. Immunohistochemical analysis demonstrated reduced Src and ERK1/2 expression in lung tissue. Molecular docking analysis predicted favourable binding affinities between ASPD and selected Src- and MAPK-related signalling proteins. These findings suggest that ASPD attenuates LPS-induced ALI and is associated with alterations in Src-, MAPK-, and Akt/GSK-3β-related signalling. Full article

Background/Objectives: Systemic sclerosis (SSc) is a heterogeneous systemic autoimmune rheumatic disease characterized by immune dysregulation, vasculopathy, and fibrosis involving the skin and internal organs. Interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and cardiac involvement remain major causes of morbidity and mortality, yet prediction of disease progression and therapeutic responsiveness remains difficult. Methods: This narrative review summarizes studies of circulating blood biomarkers in SSc, with emphasis on literature published since 2020 and on Japanese multicenter longitudinal cohort studies. Disease-specific autoantibodies were intentionally excluded from the main scope, and the review focuses on soluble biomarkers measurable in peripheral blood that reflect inflammation, endothelial injury, and fibrotic remodeling. Results: Multiple cytokines, chemokines, adhesion molecules, endothelial markers, extracellular vesicle-associated molecules, and extracellular matrix (ECM)-related molecules have been associated with disease activity, organ involvement, prognosis, and therapeutic response in SSc. Clinically established biomarkers such as KL-6 and surfactant protein-D (SP-D) for SSc-associated interstitial lung disease (ILD), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for pulmonary arterial hypertension (PAH), are already used as adjunctive tools in routine clinical assessment, whereas many other candidate biomarkers, including interleukin (IL)-6, CCL2, CXCL8, CXCL4, intercellular adhesion molecule-1 (ICAM-1), CCL18, periostin, endostatin, endothelin-1, extracellular vesicle signatures, and ECM turnover markers remain at varying stages of clinical validation. In particular, Japanese multicenter longitudinal studies have demonstrated the prognostic significance of circulating chemokines and adhesion molecules in early SSc and, more recently, identified biomarker-based clusters associated with distinct pulmonary trajectories. Recent multidimensional proteomic and transcriptomic approaches further support biologically based patient stratification in SSc. Conclusions: Blood biomarkers may contribute to risk stratification, prediction of organ progression, and future precision medicine in SSc. Integrated biomarker signatures may better capture the biological heterogeneity of SSc than single biomarkers alone. However, most candidate biomarkers still require external validation, assay standardization, and demonstration of incremental value over conventional clinical variables before routine clinical implementation. Full article

Air pollutants can cause respiratory diseases, highlighting the need for effective preventive and therapeutic strategies. We investigated the protective effects of heat-killed Lacticaseibacillus paracasei ATG-E1 against particulate matter plus diesel exhaust particle (PM₁₀D)-induced airway inflammation. BALB/c mice were intranasally injected with PM₁₀D and treated with heat-killed L. paracasei ATG-E1 via oral gavage for 5 days. In the bronchoalveolar lavage fluid (BALF) and lungs, inflammatory mediators, immune cell subtypes, and histological changes were analyzed, while gut microbiota composition was analyzed in the cecum. Heat-killed L. paracasei ATG-E1 suppressed the infiltration of immune cells, including neutrophils, T cells, and B cells. Furthermore, it decreased various inflammatory mediators, such as C-X-C Motif chemokine ligand (CXCL)-1, macrophage inflammatory protein (MIP)-2, interleukin (IL)-1α, and tumor necrosis factor (TNF)-α, in the BALF and lung tissue, as well as serum symmetric dimethylarginine (SDMA) levels in the PM₁₀D-induced airway inflammation model. Heat-killed L. paracasei ATG-E1 also exhibited a protective effect against lung damage induced by PM₁₀D. Furthermore, heat-killed L. paracasei ATG-E1 treatment shifted the gut microbiota composition, increasing several bacterial genera. The data demonstrate that heat-killed L. paracasei ATG-E1 acts as a protective agent against air pollutant-induced lung injury, suggesting its potential as a candidate adjunctive strategy for prevention. Full article

Background: Kai-Bi-Bu-Fei Decoction (KBD) is derived from the canonical Traditional Chinese Medicine formulas Xuan-Bai-Cheng-Qi and Ma-Xing-Shi-Gan. It has been employed for decades in the treatment of severe pneumonia with significant clinical efficacy. This study aimed to evaluate the protective effects of KBD against influenza virus-induced severe pneumonia in a murine model and to elucidate the underlying molecular mechanisms. Methods: The chemical profile of KBD was characterized using UPLC-Q-TOF-MS. A severe pneumonia model was established in C57BL/6J mice via intranasal infection with influenza A/Puerto Rico/8/34 (H1N1, PR8). Multiple parameters, including 14-day survival rate, body weight, lung index, histopathological changes, viral load, and pulmonary cytokine/chemokine levels, were assessed. Furthermore, multi-omics analyses were integrated to characterize the gut microbiota and metabolic profiles. Fecal microbiota transplantation (FMT) was subsequently performed to validate the functional role of the gut microbiota and its metabolites. Results: KBD treatment significantly improved the survival rate by 40%, reduced the lung index by 27.85%, and alleviated lung injury. It also markedly lowered the viral load by 80.88%, suppressed pro-inflammatory cytokine levels, and restored intestinal barrier integrity. Mechanistically, KBD restored gut microbiota diversity by increasing the abundance of Firmicutes and Bacteroidetes, enriching beneficial genera such as Bifidobacterium and Faecalibaculum, and reducing Verrucomicrobiota. Integrated transcriptomic and metabolomic analyses revealed that KBD enhanced short-chain fatty acid (SCFA) metabolism and up-regulated pyruvate metabolism. Finally, FMT confirmed that the therapeutic benefits of KBD were transferable via the microbiota to microbiota-depleted mice. Conclusions: KBD exerts robust protection against severe influenza pneumonia, a process primarily mediated by the gut microbiota–SCFA axis. The enhancement of mitochondrial energy metabolism also appears to play a critical role in its therapeutic mechanism. Full article

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted in response to food intake that acts biologically by binding to GLP-1 receptors. The primary function of GLP-1 is to stimulate insulin secretion and inhibit glucagon secretion, which helps limit after-meal spikes in blood glucose. GLP-1 reduces intestinal contractility, slows down gastrointestinal motility and emptying, and also acts directly on the hypothalamus, thereby regulating appetite and food intake. Due to its metabolic effects, GLP-1 forms the basis of medications currently used to treat type 2 diabetes (T2DM) and obesity. However, it has also been observed that the use of GLP-1 agonists in the treatment of obesity or diabetes has a beneficial effect on comorbid respiratory conditions. This narrative review analyzes the scientific literature and describes the most recent information on the impact of GLP-1 receptor agonist (GLP-1 RA) therapies on the most common respiratory disorders—both the beneficial and undesirable effects. We discuss evidence that acute lung injury, COVID-19, pulmonary fibrosis, asthma, chronic obstructive pulmonary disease (COPD), and obstructive sleep apnea can benefit from therapies with various GLP-1 RAs. They can complement existing lung-targeted treatments, but as research progresses, they are likely to play an ever more important role in the treatment of respiratory diseases. Full article

Congestion is a major driver of symptoms, hospitalization, and adverse outcomes in heart failure (HF), yet its clinical assessment remains challenging. Traditional approaches based on physical examination, biomarkers, and isolated imaging surrogates often fail to capture the complexity of systemic venous congestion and its impact on organ function. In HF, congestion should be interpreted as a multifactorial process resulting from the interaction between intravascular volume burden, venous compliance, cardiac filling pressures, neurohormonal activation, blood volume redistribution, and organ-specific susceptibility. In this context, point-of-care ultrasound has emerged as a promising adjunctive tool for bedside congestion assessment. The Venous Excess Ultrasound (VExUS) score integrates inferior vena cava assessment with Doppler analysis of hepatic, portal, and intrarenal veins, allowing for the evaluation of venous pressure transmission and organ-level congestion. Observational studies suggest that VExUS and related venous Doppler abnormalities correlate with invasive hemodynamic parameters and are associated with acute kidney injury, diuretic response, heart failure hospitalization, and mortality. Serial changes in venous congestion may provide additional information regarding treatment response and clinical trajectory. However, the available evidence remains heterogeneous across acute HF, ambulatory HF, cardiorenal syndrome, and critical care populations, and randomized trials evaluating VExUS-guided management are lacking. Therefore, VExUS should be interpreted as a complementary tool within a multimodal assessment that includes echocardiography, lung ultrasound, biomarkers, renal function, urine output, physical examination, and response to therapy. By integrating fluid burden with venous pressure transmission and organ perfusion, multimodal ultrasound may support more individualized congestion assessment and risk stratification in HF. Full article

Background/Objectives: Acute lung injury (ALI) currently lacks safe and effective therapeutic strategies with low toxicity. Lonicerae japonicae flos, a traditional herb and functional food, contains polyphenols as its principal active components. This study investigated whether Lonicerae japonicae flos polyphenols (LJP) could exert protective effects against lipopolysaccharide (LPS)-induced ALI in mice. Methods: Eighty-four male C57BL/6J mice were randomly divided into seven groups and treated daily for 7 days with LJP (200, 100, or 50 mg/kg), liproxstatin-1 (10 mg/kg), dexamethasone (5 mg/kg), or saline (control and model groups). Subsequently, another thirty-six mice were used for the fecal microbiota transplantation (FMT) experiment. All groups except the control group received intratracheal instillation of LPS (5 mg/kg) to induce ALI. Results: LJP treatment significantly ameliorated lung histopathological damage and gut microbiota dysbiosis. Lung proteomics analysis revealed the enrichment of the NF-κB and ferroptosis pathways. Mechanistically, LJP downregulated pro-inflammatory factors (IL-6, TNF-α, and IL-1β) by suppressing activation of the TLR4/MyD88/NF-κB pathway. Meanwhile, LJP upregulated SOD and GSH levels, thereby suppressing the accumulation of ROS, GSSG, Fe²⁺, and MDA, which were closely related to the activation of the Nrf2/HO-1 and Sirt3/Nrf2/GPX4 pathways. Furthermore, LJP modulated the gut microbiota and promoted short-chain fatty acid (SCFA) production by elevating the relative abundance of Akkermansia muciniphila and Faecalibaculum. Intriguingly, FMT results confirmed that the LJP-derived gut microbiota markedly alleviated lung tissue injury and intestinal barrier damage in ALI mice. Conclusions: This study demonstrated that LJP could reshape the gut microbiota to enhance the production of SCFAs and inhibit inflammation-related ferroptosis in ALI mice. Full article

Ventilation is an essential function of life, and one of the first to be replicated by artificial means. Annually, it is estimated that 15 to 20 million patients worldwide are intubated and receive invasive mechanical ventilation (MV). However, MV is a non-physiologic intervention and frequent complications are associated with its use, including extravascular lung liquid, impaired cardiac performance, and alveolar rupture. Research shows that injurious MV can cause or aggravate lung damage and initiate an intense inflammatory response, contributing to multiple organ dysfunction and poor outcomes due to ventilator-induced lung liquid and intense alveolar rupture. In this brief commentary, we postulate that this resulting injury is better characterized with the term “ventilator-induced lung liquid and alveolar rupture”. We will summarize key points for clinical implications, existing challenges, and future perspectives for the management of patients with severe acute hypoxemic respiratory failure. Full article

The plastic pieces of synthetic polymers, which were previously regarded as primary pollutants of the environment, are increasingly being discovered as internal pollutants of the human body. This review provides a comprehensive overview of the available evidence on human exposure, tissue distribution, and associated biological effects of micro- and nanoplastics. Ingesting contaminated food and water is the major exposure pathway, with inhalation and dermal contact being secondary routes. Various organ systems have been identified as containing polymer particles through the use of advanced analytical methods, including blood, liver, lungs, placenta, breast milk, and brain tissue. Experimental animal studies suggest associations with tissue injury, metabolic illness, and neurotoxicity. Polyethylene, polypropylene, polystyrene, and polyethylene terephthalate are the most frequently found polymers in human samples. New clinical findings indicate potential health implications, though current human evidence remains largely associative rather than causal: a cardiovascular study observed more than a two-fold rise in mortality among patients with polymer-containing arterial plaques, and recent evidence demonstrates over-accumulation of polymers in brain tissue, raising questions about neuroinflammatory processes. Detection technologies have advanced substantially, with deep learning-based polymer classification achieving 95–99% accuracy and ultrasensitive electrochemical and surface plasmon resonance biosensors reaching detection limits approaching 10⁻¹¹ M. Despite these advances, critical issues remain, including lack of standardized analytical procedures, absence of chronic exposure models for humans, and insufficient longitudinal epidemiological data. To address these gaps, physiologically relevant experimental systems including organoids and organ-on-chip platforms will be required, in addition to well-designed prospective cohort studies. Full article

Objectives: Inflammatory bowel disease (IBD) is associated with extraintestinal comorbidities, and lung diseases are widespread manifestations. Respiratory bacterial insult is a common illness that results in acute lung injury (ALI) in critical patients. IBD concurrence with respiratory infection may further exacerbate lung injury. Tryptophan (Try), an essential amino acid, is processed by gut microbiota and produces aryl hydrocarbon receptor (AhR) ligands. These ligands can activate the AhR pathway that exerts anti-inflammatory properties and provides protection against mucosal barrier injury. This study investigated the effects of dietary Try on lipopolysaccharide (LPS)-stimulated ALI in mice with colitis induced by dextran sodium sulfate (DSS). Methods: Mice with colitis were allocated to four groups: (1) ND-Sal: normal diet + DSS + intratracheal saline injection; (2) ND-LPS: normal diet + DSS + intratracheal LPS injection; (3) TD-Sal: Try diet + DSS + intratracheal saline injection; (4) TD-LPS: Try diet + DSS + intratracheal LPS injection. Mice were sacrificed 24 h after the intratracheal injection. Results: Results showed that colitis resulted in a high disease activity index. Following induction of ALI in colitis mice, neutrophil populations and inflammatory cytokine levels in bronchoalveolar lavage fluid increased. Gene expression levels associated with toll-like receptor (TLR)4/nuclear factor (NF)-κB signaling were upregulated, and tight junction proteins decreased in the lungs. Dietary Try supplementation decreased circulating LPS levels, suppressed pulmonary TLR4/NF-κB signaling, upregulated AhR/interleukin-22 expression, attenuated oxidative stress and improved the capillary–epithelial barrier integrity in DSS-treated mice. Conclusions: These findings imply that Try may have potential therapeutic significance in bacterial-induced ALI in a colitis condition. Full article

Acute inflammatory disorders, including acute lung injury, acute pancreatitis, ischaemia–reperfusion injury, and sepsis, are major clinical challenges characterised by rapid progression, a characteristic cytokine storm, and high mortality rates. The receptor for advanced glycation end-products (RAGE) serves as a pivotal multi-ligand pattern recognition receptor that integrates PAMPs and DAMPs. Excessive RAGE engagement triggers detrimental signalling cascades, notably NF-κB and MAPKs, which exacerbate hyperinflammation and lead to progressive organ dysfunction. Consequently, the RAGE axis represents a potent therapeutic target for mitigating hyperinflammation and improving clinical outcomes in acute inflammatory disorders. While initial pharmacological efforts focused on synthetic inhibitors and biologics, there is a shifting focus toward bioactive alternatives with high safety profiles. Here, we present recent molecular insights into RAGE-mediated pathogenesis in acute inflammatory disorders and evaluate current therapeutic strategies. Furthermore, we emphatically summarise the bioactive natural products, including terpenoids, flavonoids, alkaloids, and a xanthone, that prevent and treat acute inflammatory disorders by disrupting RAGE–ligand interactions and suppressing downstream oxidative stress and cytokine release. Integrating these molecular mechanisms with the pharmacological profiling of natural RAGE modulators provides a robust foundation for the development of next-generation therapeutic strategies to improve clinical outcomes in acute inflammatory disorders. Full article

Preterm infants, especially extremely preterm infants under 28 weeks of gestation, face high mortality rates due to respiratory distress resulting from pulmonary immaturity. Conventional mechanical ventilation and extracorporeal membrane oxygenation (ECMO) therapy inevitably cause irreversible lung injury or severe complications, respectively. Here, we developed a microfluidic oxygenator (MO) mimicking the human alveolar-capillary barrier to provide respiratory support for preterm infants. These structures promoted uniform flow distribution, reduced high-shear stress and flow stagnation, and improved gas exchange efficiency. In vitro experiments demonstrated that a single-layer MO raised blood oxygen saturation from 64.7% to 96.5% at 8 mL/min, with a corrected vol% oxygen transfer of 5.24% (52.4 mL O₂/L blood). Hemolysis and coagulation measurements after a 6 h circulation confirmed good hemocompatibility, with most blood damage attributable to the pump. An eight-layer stacked MO was configured with a total priming volume of approximately 5.6 mL and a pressure drop of 25–35 mmHg at 24–40 mL/min, indicating its potential in pumpless extracorporeal circulation for preterm neonates. This MO holds promise for providing minimally invasive and customizable respiratory support in an artificial uterus system. Full article

The number of pulmonary nodules detected is steadily increasing. While some are low or high risk, most are indeterminate. Within the indeterminate group, the vast majority are benign. Statification of indeterminate pulmonary nodules (IPNs) is challenging. Validated risk calculators are not routinely employed in clinical practice because they are cumbersome. Most clinicians rely upon clinical gestalt. This strategy often results in unnecessary biopsies, which are costly, stressful, and have the potential for iatrogenic injury. There are a number of commercially available lung cancer risk biomarkers, which each have their own strengths and weaknesses. Barriers to widespread adoption include lack of guideline support, clinical practice inertia, and limited clinical utility data. Upcoming multicenter trials aim to provide high quality data that could lead to guideline incorporation. Full article

Pulmonary fibrosis, particularly idiopathic pulmonary fibrosis (IPF), is a chronic and progressive interstitial lung disease characterized by alveolar epithelial injury, fibroblast activation, and excessive extracellular matrix deposition, which collectively lead to respiratory failure. Despite the availability of antifibrotic agents, disease-modifying therapies remain limited. Emerging evidence has identified dysregulated sphingolipid metabolism, especially ceramide accumulation, as a key driver of fibrotic pathogenesis. Ceramide is a central bioactive lipid in the sphingolipid pathway that regulates multiple cellular processes, including apoptosis, inflammation, endothelial barrier dysfunction, and fibroblast activation, all of which contribute to pulmonary fibrosis. This review is a narrative review that systematically summarizes the biosynthetic and metabolic pathways of ceramide, with an emphasis on chain length-specific functions and the ceramide to S1P rheostat. We further discuss the mechanistic roles of ceramide in alveolar epithelial cell apoptosis, inflammatory responses, and vascular barrier disruption in fibrotic lung disease. Finally, we highlight emerging therapeutic strategies that target ceramide metabolism, including inhibitors of acid sphingomyelinase (ASMase) and serine palmitoyltransferase (SPT), and propose future directions for clinical translation. Full article

The influenza A virus (IAV) has been responsible for multiple seasonal epidemics and poses a pandemic threat, and the growing number of variant strains constitutes a persistent threat to humanity. This study aimed to identify anti-influenza compounds from a traditional Chinese medicine (TCM) monomer library using a machine learning approach, with calmodulin as a hypothesis-driven target. The antiviral efficacy of the compounds with the highest predicted binding scores from virtual screening was evaluated using integrated computational and experimental approaches. A pre-trained protein language model (ConPLex) was employed for virtual screening. Molecular docking was used to predict binding characteristics, and network pharmacology was applied to generate hypotheses on multi-target mechanisms. The cytotoxicity and anti-H1N1 activity of the selected compounds were assessed in vitro, followed by in vivo evaluation of survival, lung pathology, viral load, and inflammatory mediators in a lethal mouse infection model. Sodium deoxycholate (NaDC) and deoxycholic acid (DCA) were identified as promising lead compounds. Both exhibited dose-dependent inhibition of viral replication in vitro with low cytotoxicity. Treatment with NaDC and DCA significantly improved survival rates and reduced lung pathology in H1N1-infected mice. Treatment was associated with suppression of nuclear factor kappa-B (NF-κB) activation, reduced pro-inflammatory cytokines, and elevated interleukin-10 (IL-10) levels. Molecular docking predictions indicated that NaDC and DCA exhibit moderate binding affinity for calmodulin, with binding energies of −8.38 kcal/mol and −7.61 kcal/mol, respectively. Furthermore, network pharmacology analysis suggested that these compounds may modulate pathways related to viral infection, inflammation, and immune regulation. NaDC and DCA demonstrate anti-influenza activity both in vitro and in vivo, reducing viral replication and alleviating inflammatory lung injury. These findings position NaDC and DCA as promising lead compounds for anti-influenza drug development and provide a foundation for further mechanistic validation. Full article