Search Results (1,171)

Background: Respiratory syncytial virus (RSV) is a leading global pathogen of acute lower respiratory tract infection, posing significant risks to infants, the elderly, and immunocompromised patients. Artemisia argyi Levl.et Vant Extract (AALE) and its active components have a variety of pharmacological effects, but their anti-RSV potential remains unclear. The aim of this study is to investigate the anti-RSV activity of AALE and parthenolide and its underlying mechanisms. Methods: Cell counting kit-8 (CCK-8) assay was used to determine the anti-RSV activities of AALE and parthenolide. Time-of-addition assay and phase of action analysis were used to explore the effect of drugs on the viral replication cycle. Quantitative polymerase chain reaction (qRCR), immunofluorescence (IF) and Western blot (WB) were used to investigate the effects of AALE and parthenolide on RSV-F gene and protein and on RIG-I/TLR-3 pathway related molecules in vitro. In vivo antiviral efficacy was verified by hematoxylin–eosin (HE) staining for lung histopathology, quantitative real-time PCR (qPCR) quantification of RSV-F, RIG-I, TLR-3, IRF3, IL-6, and IFN-β gene expression in lung tissues, and enzyme-linked immunosorbent assay (ELISA) for serum IL-6 and IFN-β levels. Results: AALE exhibited the strongest anti-RSV activity among the extracts (SI = 27.6), while parthenolide was the most potent monomeric compound (SI = 8.19). In vitro, both AALE and parthenolide were effective in the co-treatment and post-treatment models, reducing RSV-F gene and F protein levels in infected cells. Furthermore, they alleviated RSV infection by regulating RIG-I and TLR-3 pathway-related genes and proteins. In vivo, AALE and parthenolide suppressed lung index and RSV proliferation, attenuated lung injury, and down-regulated RIG-I, TLR-3, IRF3, IL-6, and IFN-β expression in the lungs of RSV-infected mice. Conclusions: AALE and its component parthenolide can inhibit the invasion and replication of RSV, making it a potential candidate for the treatment of RSV-related diseases. Full article

Breast cancer (BRCA) is the most common cancer worldwide, with an incidence exceeding that of lung cancer. Protein lactylation, a newly identified post-translational modification involving the binding of lactic acid to lysine residues, plays an important role in BRCA. However, its role in BRCA progression remains largely unexplored. This study aims to identify and characterize the lactylation-related genes involved in BRCA biology. Transcriptomic and clinical data of BRCA and normal breast tissues were obtained from TCGA and GEO. Lactylation-related genes were curated from literature and intersected with BRCA datasets to identify candidates. A prognostic risk model was constructed using LASSO and Cox regression. Functional enrichment was performed using KEGG, GSVA, and GSEA. Immune correlations were evaluated by ESTIMATE, CIBERSORT. Single-cell RNA-seq data were integrated to assess gene expression heterogeneity across tumor and immune compartments. In vitro, MDA-MB-231 cells were treated with sodium L-lactate and lactylation-inducing agents, and gene expression was validated by Western blot and RT-qPCR, while EdU and wound healing assays evaluated proliferation and migration. We identified six hub genes associated with the immune microenvironment. Notably, S100A4 is significantly underexpressed, suggesting their potential regulatory roles in BRCA. Further analysis demonstrated that lactylation-related genes are closely linked to immune regulation in BRCA, indicating a possible crosstalk between metabolic modification and tumor immunity. Additionally, we found that lactylation significantly influences gene expression patterns and immune infiltration in BRCA. Importantly, lactic acid ions were shown to upregulate lactylation levels in BRCA cells, underscoring the functional impact of metabolic signals on post-translational modifications in tumorigenesis. Our findings indicate a potential mechanism wherein lactylation affects BRCA progression via lactic acid-driven regulation of the immune microenvironment; they also highlight the possible involvement of S100A4 in this process and offer new insights that could contribute to the diagnosis and treatment of BRCA. Full article

Background/Objective: In lung cancer treatment, increasing the concentration of antitumor drugs at the tumor site, enhancing efficacy, and reducing systemic toxicity are significant challenges. This study aims to develop an intelligent responsive polymer micelle system (GPDD) that achieves efficient accumulation and controlled release of drugs at lung tumor sites through targeted and pH-responsive design. Methods: The GPDD system is formed by the self-assembly of GE11-PEG-hyd-DOX conjugates and co-loads free DOX. This system utilizes the targeting effect of the GE11 peptide with the epidermal growth factor receptor (EGFR) to accumulate at the tumor site, while the hydrazone bond serves as a pH-responsive linker that breaks in the acidic tumor microenvironment, triggering drug release. Experiments employed CCK-8 cytotoxicity assays and tumor-bearing nude mouse models (strain not specified) for in vitro and in vivo evaluations. Results: In vitro experiments showed that GE11-modified GPDD effectively inhibited tumor cell growth. In tumor-bearing nude mouse experiments, GPDD demonstrated more significant tumor suppression effects and lower systemic toxicity compared to free DOX and unmodified PDD. Conclusions: The GPDD nanocarrier integrates targeting and pH responsiveness, improving antitumor efficacy and reducing side effects, with translational potential. The novelty of the study lies in its dual-functional design and co-loading strategy, providing new insights for tumor-targeted delivery systems. Full article

Antioxidant peptides show significant activity and can be developed into functional foods for treating chronic diseases. Cigarette smoke components can cause damage or even apoptosis of lung cells, eventually leading to chronic lung diseases. Therefore, this study aimed to investigate the protective effects and mechanisms of Skipjack tuna peptides against in vitro cigarette smoke extract (CSE)-induced chronic obstructive pulmonary disease (COPD). The results demonstrated that tuna peptides DVGRG (S1), PHPR (S5), GRVPR (S6), and SVTEV (S7) significantly enhanced the activities of SOD, CAT, and GSH-Px by upregulating the mRNA transcription levels of Keap1 and Nrf2, consequently reducing ROS and MDA levels in CSE-induced COPD model of MLE-12 cells. Molecular docking analysis revealed that S1, S6, and S7 competitively inhibited the Keap1-Nrf2 interaction by binding to the Kelch domain of Keap1, whereas S5 operated through a non-competitive mechanism. These peptides also downregulated p65 mRNA expression and upregulated IκBα mRNA expression, leading to a significant reduction in inflammatory cytokines of IL-1β, IL-6, and TNF-α, thereby alleviating inflammatory responses. Furthermore, these peptides significantly inhibited CSE-induced apoptosis by restoring mitochondrial membrane potential and upregulating the Bcl-2/Bax ratio. Additionally, S1, S5, S6, and S7 promoted MLE-12 cell migration in a concentration-dependent manner, suggesting a role in lung epithelial repair and regeneration. In conclusion, tuna peptides S1, S5, S6, and S7 exert antioxidant, anti-inflammatory, anti-apoptotic, and cell migration-promoting effects through the regulation of the Keap1/Nrf2 and NF-κB signaling pathways, as well as Bcl-2/Bax apoptotic balance, providing a promising strategy for mitigating CSE-induced lung injury. Full article

Birds serve as the primary natural reservoirs for avian influenza viruses (AIVs), harboring nearly all known AIV subtypes. The seasonal migratory movements of wild birds play a significant role in the transmission and dissemination of AIVs. Jianhu Lake in Dali, Yunnan Province, serves as a vital congregation point along avian migratory routes, providing an ideal habitat for birds. In this study, a total of 619 avian samples were collected from the Jianhu area, from which four H6N2 subtype AIV strains were successfully isolated. Among these, A/grey heron/Jianhu/JH-89/2024 (hereafter referred to as JH-89) and A/grey heron/Jianhu/JH-91/2024 (JH-91) were isolated from grey herons (Ardea cinerea); A/mareca penelope/Jianhu/JH-2-11/2025 (JH-2-11) from a Eurasian wigeon (Mareca penelope); and A/duck/Jianhu/JH-1-1/2025 (JH-1-1) from a domestic duck (Anas platyrhynchos domesticus). Genomic analyses revealed that these four H6N2 isolates belong to the Eurasian lineage, with all eight gene segments originating from complex reassortment events among diverse Asian isolates. In vitro assays demonstrated that the representative strain JH-2-11 replicated efficiently in various human- and animal-derived cell lines. In vivo infection models revealed that, without prior adaptation, the JH-2-11 strain successfully infected BALB/c mice, resulting in suppressed body weight gain and severe pathological lesions in the respiratory tract (nasal turbinates, trachea, and lungs), without causing mortality or extrapulmonary dissemination. Collectively, although these H6N2 viruses evolve primarily within avian hosts, they exhibit potential for mammalian adaptation and require continuous epidemiological monitoring. Full article

This review summarizes innovative co-formulation strategies for non-marketed dry powder inhalers (DPIs), enabling the simultaneous pulmonary delivery of multiple active pharmaceutical ingredients (APIs). Key approaches include co-amorphous systems (COAMS) and co-crystals, which combine two APIs into a single particle, improving aerodynamic properties, solubility, dissolution, and patient compliance while reducing manufacturing complexity. Core–shell microparticles, produced via spray drying, allow spatial separation and controlled release of APIs, minimizing drug–drug interactions and enabling tailored pharmacokinetics. Co-spray drying of dual APIs can yield particles with superior aerosolization and stability, though examples remain limited. Nanoparticle-based systems offer enhanced lung deposition and cellular uptake but face challenges in device compatibility, scalability, and regulatory approval. Each technology presents unique advantages and limitations regarding manufacturability, dose flexibility, and clinical translation. This review also highlights advances in in vitro toxicity testing, including air–liquid interface cultures, organoids, lung-on-chip models, and precision-cut lung slices, which are increasingly important as alternatives to animal studies. The importance of using an aerosol exposure system for the testing is highlighted. Ultimately, the choice of co-formulation platform should balance scientific innovation with practical considerations of manufacturing and regulatory requirements to maximize therapeutic benefit and commercial viability for future DPI combination products. Full article

Background/Objectives: Influenza A virus (IAV) infection triggers robust inflammation and acute lung injury. Andrographolide, a primary active compound from Andrographis paniculata, can mitigate IAV-induced inflammation; however, its precise mechanisms remain poorly elucidated. This study aimed to define its host-directed protective effects and molecular mechanisms. Methods: We used a lethal IAV (H1N1, PR8) model in BALB/c mice and infected A549 cells. Survival, lung pathology, cytokines, and viral titers were measured. Lung RNA sequencing identified dysregulated signaling pathways. PI3K/AKT and pyroptosis pro-teins were analyzed by Western blot. The PI3K/AKT axis was functionally validated with the AKT inhibitor in vivo and AKT1 siRNA in vitro. Results: Andrographolide improved survival, attenuated body weight loss, and reduced lung pathology and inflammatory cytokine levels in IAV-infected mice, without exhibiting direct antiviral activity. Consistent with the in vivo findings, andrographolide enhanced cell viability and suppressed cytokine secretion in infected cells. RNA sequencing revealed marked upregulation of the PI3K/AKT signaling pathway in the lungs of treated mice, as confirmed by increased PI3K and AKT phosphorylation. Furthermore, andrographolide downregulated the expression of key pyroptosis-executing proteins, including cleaved caspase-3 and the gasdermin E (GSDME) N-terminal fragment. These protective effects were substantially abrogated by an AKT inhibitor and AKT1 siRNA. Conclusions: These findings reveal a novel host-directed mechanism by which andrographolide alleviates IAV-induced immunopathology by activating the PI3K/AKT pathway, thereby suppressing caspase-3/GSDME-dependent pyroptosis. Thus, this axis represents a promising target for controlling excessive inflammation in severe influenza. Full article

Background and Objectives: While nisin exhibits promising antitumor properties, its clinical utility is hindered by pharmacokinetic instability and rapid enzymatic degradation. This systematic review evaluates the critical role of advanced pharmaceutical formulations and targeted nanosystems in overcoming these limitations to enhance nisin’s cytotoxic and pro-apoptotic efficacy in vitro. Methods: Following PRISMA guidelines, a comprehensive search was conducted across six electronic databases (PubMed, ScienceDirect, Scopus, Web of Science, SpringerLink, and DOAJ). In vitro studies comparing free nisin against polymeric, metallic, and cyclodextrin-based nanocarriers across diverse neoplastic lineages were included. Methodological quality was assessed using the SciRAP 2.1 tool, and a within-line comparative analysis was performed for MDA-MB-231 and HT-29 models. Results: Twelve studies met the inclusion criteria. A definitive technological inflection point was identified: nisin-loaded nanosystems reduced effective concentrations by up to 2706-fold relative to the free peptide in MDA-MB-231 cells, and 71-fold in A549 lung cancer cells. Mechanistically, nanosystems facilitated membrane pore formation, mitochondrial-mediated apoptosis via Bax/Bcl-2 modulation, caspase 3/7/9 activation, and p53 reactivation. Three previously underreported mechanistic dimensions were identified: TWIST1 downregulation and FZD7 binding in hepatocellular carcinoma, and downregulation of CEA, CEAM6, MMP2F, and MMP9F in colorectal cancer lines. Conclusions: The therapeutic viability of nisin in oncology is strictly dependent on pharmaceutical engineering. Future research must prioritize in vivo pharmacokinetic validation, experimental confirmation of novel mechanistic targets, and standardized nisin purity reporting to consolidate its clinical translation. Full article

Merkel Cell Polyomavirus is an oncogenic virus associated with Merkel Cell Carcinoma (MCC). However, considering viral detection in respiratory specimens and similarities between MCC and neuroendocrine lung cancer, its plausible role in the respiratory tract is disputed. MCPyV-mediated oncogenesis involves viral antigens interfering with host signaling as a DNA Damage Response (DDR). In the current study, respiratory models, including lung cancer cell lines (A549 and H1299), and non-malignant bronchial systems (HBEC-KT and a 2D ALI model) were used to investigate DDR genes’ expression following MCPyV infection. Once the capability to support viral replication and transcription was assessed using qPCR and RT-qPCR, respectively, the mRNA levels of DDR genes, including ATM, ATR, Chk1, Chk2, H2AX, Rad51, p53 and p21, were examined. Our findings showed MCPyV replication in all cellular systems, as proven by the detection of viral DNA and transcripts. Viral infection induced an overexpression of DDR genes, suggesting a role of the virus in manipulating DDR to favor its replication or contribute to tumor progression. These preliminary results provide in vitro models for studying the interplay between MCPyV and DDR within malignant and non-malignant contexts across the respiratory tract, laying the basis for future research exploring the clinical relevance of DDR activation in virus-driven malignancies. Full article

Background/Objectives: Non-small-cell lung cancer (NSCLC) involves oxidative stress and inflammation, driving chemoresistance. Paclitaxel (PTX), a first-line chemotherapy, is limited by these factors. Danggui Buxue Tang (DBT), a polyphenolic-rich traditional Chinese herbal formula, was investigated for its ability to potentiate PTX efficacy by inducing ferroptosis via the Nrf2/GPX4 axis. Methods: Effects of DBT + PTX on cell viability, lipid peroxidation, iron accumulation, and Nrf2/GPX4/SLC7A11 expression were evaluated in A549/HCC827 cells with/without ferrostatin-1 (Fer-1). Findings were validated in an A549 xenograft model. Results: DBT significantly enhanced PTX’s anti-tumor effects in vitro and in vivo, an effect reversed by Fer-1. Combination therapy increased ROS, MDA, and iron while suppressing GPX4/SLC7A11 and promoting Nrf2 nuclear translocation. DBT + PTX synergistically reduced tumor volume and proliferation markers (Ki67/PCNA). Crucially, DBT attenuated PTX-induced hepatotoxicity and nephrotoxicity. Conclusions: DBT potentiates PTX efficacy in NSCLC by disrupting the Nrf2/GPX4 axis to induce ferroptosis while mitigating chemotherapy-related toxicity, supporting its potential as an adjuvant strategy targeting oxidative stress pathways. Full article

Mitochondrial dysfunction plays a central role in the pathogenesis of bronchopulmonary dysplasia (BPD). Solute carrier family 25 member 28 (SLC25A28) is an iron transporter located in the inner mitochondrial membrane. In this study, we aimed to explore the role and underlying molecular mechanisms of SLC25A28 in BPD. Hyperoxia (85% O₂) was used to establish a neonatal murine model of BPD, and mouse lung epithelial cells (MLE-12 cells) were used in vitro. SLC25A28 expression and activity were downregulated under hyperoxic conditions, both in vivo and in vitro. SLC25A28 overexpression restored hyperoxia-induced mitochondrial oxidative phosphorylation (OXPHOS) dysfunction, and further enhanced the proportion of Ki67-positive cells by 37% (p < 0.05) and increased migration by 33% (p < 0.01) in MLE-12 cells. In contrast, SLC25A28 knockdown exacerbated these impairments in MLE-12 cells, with reduced the proportion of Ki67 positive cells by 71% (p < 0.01) and a 35% reduction in the migration rate. SLC25A28 was also knocked down in vivo, which further aggravated alveolar simplification in BPD mice. Furthermore, the mitochondrial-targeted peptide SS-31 could potentially interact with SLC25A28 and preserve its protein abundance. SS-31 administration mitigated hyperoxia-induced alveolar simplification, with the radical alveolar count (RAC) increasing by 28% (p < 0.05) and the mean linear intercept (MLI) decreasing by 20% (p < 0.001). In summary, this study revealed that SLC25A28 ameliorated hyperoxic lung injury by improving mitochondrial OXPHOS in alveolar epithelial cells, suggesting that it may serve as a potential therapeutic target for BPD. Full article

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

Background: Sepsis-induced acute lung injury (ALI) is a life-threatening condition with limited therapeutic options. Neutrophil extracellular traps (NETs) contribute to its pathogenesis. This study investigated whether polydatin (PD) protects against septic ALI by inhibiting NETs via the Nrf2/HO-1 pathway. Methods: A cecal ligation and puncture (CLP)-induced septic ALI mouse model and an LPS-stimulated neutrophil model were established. Lung injury was assessed by histology, lung wet/dry ratio, BALF protein, and inflammatory cytokines. Endothelial junction proteins and NETs markers were examined by Western blot, immunofluorescence, and SYTOX Green staining. Nrf2/HO-1 pathway activation and ML385 inhibitor experiments were performed for mechanistic validation. Results: PD dose-dependently attenuated lung injury, preserved endothelial junction proteins (ZO-1, VE–cadherin, occludin), and suppressed NETs formation in vivo. In vitro, PD activated Nrf2/HO-1, promoted Nrf2 nuclear translocation, reduced ROS, and inhibited LPS-induced NETs. These effects were abrogated by ML385, confirming pathway specificity. Conclusions: PD mitigates septic ALI by inhibiting NETs formation. In vitro mechanistic studies further suggest that this effect is mediated through activation of the Nrf2/HO-1 antioxidant pathway, positioning PD as a potential therapeutic candidate for sepsis-induced ALI. Full article

Aging is a complex biological process characterized by progressive loss of cellular homeostasis, impaired regenerative capacity, and accumulation of senescent cells that collectively predispose tissues to disease. Traditional two-dimensional culture systems and animal models have provided valuable insights but fail to fully recapitulate the spatial organization, cellular heterogeneity, and microenvironmental cues of aging human tissues. Organoid technology—three-dimensional self-organizing structures derived from adult stem cells or pluripotent stem cells has emerged as a transformative platform to model aging in vitro. These mini-tissues retain the architecture, signaling dynamics, and lineage hierarchy of native organs, making them powerful systems to interrogate age-associated cellular phenotypes, DNA damage responses, and senescence programs. This review discusses how organoid models are advancing our understanding of aging biology across multiple organ systems, from the intestines and liver to the brain and lung. We highlighted key molecular pathways driving cellular senescence within organoids—including p16INK4a/p21CIP1 signaling, SASP activation, mitochondrial dysfunction, and epigenetic drift—and how these can be targeted to restore tissue homeostasis. We further discussed how organoids derived from aged tissues, induced pluripotent stem cells, and engineered oncogene systems reveal new therapeutic opportunities to modulate senescence in age-related disorders, cancer, and regenerative medicine. Finally, we discussed emerging integrative tools such as organoid co-cultures, single-cell omics, and senolytics drug screening that are expanding the potential of organoids as translational platforms for anti-aging and disease intervention. Full article

In emphysema, the alveolar septal structure is progressively destroyed, which is believed to be irreversible. However, as it has recently been linked to vascular endothelial growth factor (VEGF) deficiency, we hypothesized that VEGF stimulation can promote lung cell proliferation/migration to reverse emphysema. Our sulfated caffeic acid dehydropolymer, CDSO3, was thus examined in vitro and in vivo, given its VEGF-stimulating activity via ferrous ion (Fe²⁺) chelation-mediated stabilization of hypoxia-inducible factor-1α (HIF-1α). In lung epithelial/endothelial cells, CDSO3 promoted proliferation and wound closure by 1.6–3.0-fold at 10 μM; however, these effects were negated by excess FeSO₄ or an HIF-1α inhibitor, indicating an Fe²⁺- and HIF-1α-dependent mechanism. In rat models of established emphysema induced by cigarette smoke extract or the VEGF receptor antagonist SU5416, two-week lung administration of CDSO3 at 60 μg/kg from day 21 enabled: 68–79% recovery of exercise endurance and airspace enlargement/destruction; a 1.8-fold increase in proliferating cell nuclear antigen above healthy levels; normalization of cleaved caspase-3; restoration of HIF-1α; and a 1.3-fold increase in VEGF above healthy levels. In contrast, CDSO3 pre-chelated with Fe²⁺ was ineffective. In conclusion, Fe²⁺ chelation-mediated HIF-1α stabilization and VEGF stimulation via local lung delivery of CDSO3 can reverse established emphysema by promoting cell growth and survival. Full article