Search Results (1,268)

INPP5D, which encodes Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1), has emerged as an Alzheimer’s disease (AD)-associated gene with strong links to microglial biology. As a hematopoietic-enriched lipid phosphatase, SHIP1 converts phosphatidylinositol-3,4,5-trisphosphate to phosphatidylinositol-3,4-bisphosphate, thereby regulating phosphoinositide-dependent receptor signaling, membrane remodeling, phagocytosis, vesicle trafficking, and inflammatory responses. In AD, microglia are chronically exposed to amyloid-β, lipid-rich debris, damaged synapses, complement-tagged structures, and inflammatory mediators. These substrates require coordinated uptake, endolysosomal processing, autophagic adaptation, and controlled inflammatory output. Current data place INPP5D/SHIP1 at a step after receptor engagement, where microglial uptake must be coupled to vesicular routing and lysosomal degradation. When this coupling fails, engulfed amyloid, lipid debris, or synaptic material may accumulate in stressed endolysosomal compartments, promoting defective autophagy, NLRP3 inflammasome activation, and sustained cytokine release. Although current data support a primarily microglial or myeloid-centered role for INPP5D in the brain, altered microglial states may secondarily affect the neurovascular unit through cytokine release, complement activation, oxidative stress, and impaired amyloid or lipid clearance. This review summarizes the molecular function of INPP5D/SHIP1 in AD-related microglial signaling and discusses its implications for phagocytosis, endolysosomal stress, inflammasome activation, therapeutic targeting, and microglia–vascular communication. Full article

This study characterized the genetic basis of reproductive and calving traits in Jersey cattle at different physiological stages and identified potential candidate genes. After quality control, 2716 records were available for heifer reproductive traits, 2707 for multiparous cow reproductive traits, and 5423 calving records for calving ease (CE) and calf birth weight (CBW). CE and CBW were analyzed from the maternal perspective, with records assigned to the corresponding dams. Genetic parameters were estimated using AI-REML in DMU with animal, repeatability, and bivariate models. Genome-wide association analyses were performed using a mixed linear model based on 1,660,477 SNPs from 1578 genotyped Jersey cattle. Heritability estimates for age at first service (AFS) and age at first calving (AFC) were 0.416 and 0.380, respectively, whereas estimates for reproductive traits in multiparous cows were generally low (0.072–0.154). Calving interval (CI) and days open (DO) showed a strong positive genetic correlation (0.781). GWAS identified five significant loci associated with AFC, number of services per conception in heifers, CI, and dam-associated genetic variation in CE. Candidate genes included PIK3C2G, DGKI, ABCC1, CCDC85A, CRMP1, EVC, and EVC2. Exploratory KEGG enrichment suggested potential involvement of phosphatidylinositol signaling, Hedgehog signaling, ABC transporters, and inositol phosphate metabolism. Overall, reproductive traits showed distinct genetic characteristics between heifers and multiparous cows, and AFS and AFC exhibited relatively greater potential for genetic improvement. The identified genomic regions provide preliminary candidates for further validation and potential future application in genomic breeding. Full article

Proteins possessing the Tubby domain (Tubby-like proteins, TLPs) are widespread in plants and represented by protein families. Although the function of TLPs is frequently associated with plant response to stresses, the mechanisms of their action are largely unknown. The recently demonstrated interaction of Tubic (Nicotiana tabacum Tubby-like F-box protein 8) with a cell death protease, phytaspase, prompted us to investigate the possible involvement of Tubic in plant cell death and to perform structural and functional characterization of distinct domains of Tubic. We demonstrated here a requirement for Tubic in the execution of the hypersensitive response of Nicotiana benthamiana plants induced by the INF1 protein of phytophthora. Also in line with the pro-death properties of Tubic was the observation that prolonged overexpression of Tubic compromised plant viability. Notably, inactivating mutations or complete deletion of the F-box domain markedly enhanced the cell death-inducing activity of Tubic. The N domain of Tubic turned out to be necessary for the observed down-regulation of phytaspase activity by Tubic overproduction. Cooperation between the N domain and the Tubby domain was apparently required to achieve maximum (approximately 2-fold) suppressive effect. In turn, for the Tubby domain, an expected capability to bind phospholipids was demonstrated, yet the specificity of this interaction was quite distinct from that reported for plant Tubby domains previously, with phosphatidic acid and phosphatidylinositol monophosphates being by far the strongest interactors. We propose that dissimilarity in phospholipid-binding specificity between the TLP family members may underlie the diversity in their responses to external cues. Full article

Adipose-derived mesenchymal stem cells (ADMSCs) are a crucial source of new adipocytes and play a significant role in regulating adipose tissue physiology. Interestingly, mature adipocytes differentiated from the ADMSCs maintain some characteristic features of their respective depots as well as the metabolic status of the donor patients. The above is true with respect to the cells’ secretory profile and their glycerolipid and sphingolipid composition. In the current paper, we focused our attention on the phospholipid profile of the adipocytes derived from ADMSCs, with a particular emphasis placed on how obesity and metabolic syndrome affect their composition. Surprisingly, the cells displayed a significantly greater (even up to 10-fold) overall phospholipid concentration when compared with the primary human adipocytes described in the literature. The phenomenon may be explained by a geometrical property known as surface-to-volume ratio, which dictates that the total surface area of many small cells (our adipocytes) is greater than the total area of less numerous but more voluminous cells in vivo. Interestingly, also a donor’s metabolic status can influence the characteristics of these fat cells. The study found that subcutaneous adipocytes, when derived from patients with obesity and metabolic syndrome, had an increased concentration of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and sphingomyelin (SM). The above-mentioned changes often reflect the ones found in vivo and may well be the early metabolic disarrangements that occur in the progress of obesity. Full article

Patients with diabetes often develop abnormalities in lipid metabolism that can promote diabetic complications. Lipidomic studies have demonstrated that certain plasma lipid species are associated with the development of cardiovascular diseases. However, the plasma lipids associated with endothelial dysfunction remain unclear. To identify the lipids associated with flow-mediated vasodilation (FMD), an indicator of endothelial function, in patients with diabetes, we performed a cross-sectional analysis as a subanalysis of a previous lipidomic study. In total, 200 patients with type 2 diabetes were included in the analysis. A total of 55.0% were men, and the mean age (±standard deviation) was 61.1 ± 11.3 years. Their HbA1c and FMD values were 9.04 ± 1.79% (75.3 ± 19.5 mmol/mol) and 5.77 ± 2.55%, respectively. Supercritical fluid chromatography/mass spectrometry-based semi-targeted lipidomic analysis identified 349 lipids belonging to 16 lipid classes. We selected 13 distinctive lipids potentially associated with FMD, according to a sparse-group least absolute shrinkage and selection operator regularized regression model. Of these, seven phospholipids, including three phosphatidylethanolamine (PE) plasmalogens and three phosphatidylinositols (PIs), showed a positive association with FMD after adjusting for atherosclerotic risk factors. These findings may contribute to improving the assessment and management of endothelial dysfunction in patients with diabetes. Full article

Ligusticum sinense Oliv. cv. Chaxiong (Chaxiong) has traditionally been used as a medicinal tea for headache relief in southern China, but its bioactive basis and mechanisms remain unclear. This study integrated ultra-performance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS), untargeted metabolomics, network pharmacology, molecular docking, reverse-transcription quantitative PCR (RT-qPCR), and Western blotting in a nitroglycerin-induced migraine-like rat model. Chaxiong extract alleviated migraine-like behavior, reduced calcitonin gene-related peptide (CGRP), nitric oxide (NO), and tumor necrosis factor-α (TNF-α), increased 5-hydroxytryptamine (5-HT), and ameliorated brain histopathological alterations. A total of 48 constituents and 13 differential serum metabolites were annotated or putatively annotated, respectively. Glycerophospholipid metabolism was the principal metabolic pathway affected by treatment, whereas network pharmacology prioritized phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling. Pathway integration identified PIK3CA, PIK3CB, AKT1, AKT2, and INS as candidate bridging targets. Exploratory docking suggested potential interactions between five representative constituents and PIK3CA/AKT1. RT-qPCR showed reduced Pik3ca and Akt1 mRNA expression, while Western blotting showed decreased p-PI3K p85α (Tyr607)/PI3K p85α and p-AKT (Ser473)/AKT1 ratios following treatment. These findings suggest that Chaxiong-associated alleviation of migraine-like responses was accompanied by altered glycerophospholipid metabolism and reduced PI3K/AKT pathway activation. Full article

Background: Diabetes mellitus is characterized by chronic hyperglycemia, which promotes oxidative stress and endothelial dysfunction. MicroRNAs (miRNAs) have emerged as important regulators of diabetic vascular complications. Our previous RNA-sequencing study identified putative novel miR-1133 as an upregulated miRNA in hyperglycemia-induced human umbilical vein endothelial cells (HUVECs). This study aimed to investigate the potential involvement of putative novel miR-1133 in oxidative stress in hyperglycemia-induced HUVECs. Methods: Functional enrichment and protein–protein interaction (PPI) network analyses were performed to identify biologically relevant predicted target genes of putative novel miR-1133. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) was selected for further investigation because it was identified as a hub gene in the PPI network and was involved in the enriched PI3K/Akt signaling pathway. HUVECs were exposed to high glucose (33.3 mM) to establish an in vitro hyperglycemic model, and the effects of transfection with putative novel miR-1133 inhibitor on PIK3CA expression and oxidative stress markers were evaluated. Results: Bioinformatic analyses identified PIK3CA as a hub gene among the predicted targets of putative novel miR-1133 and identified the PI3K/Akt signaling pathway as significantly enriched. Experimentally, hyperglycemia significantly reduced PIK3CA expression, whereas putative novel miR-1133 inhibitor transfection increased PIK3CA expression. Furthermore, putative novel miR-1133 inhibitor transfection was associated with reduced reactive oxygen species and 8-hydroxy-2′-deoxyguanosine levels, together with increased superoxide dismutase 1 (SOD1) mRNA expression and total SOD activity. Conclusions: Transfection with putative novel miR-1133 inhibitor was associated with increased PIK3CA expression and reduced oxidative stress markers in hyperglycemia-induced endothelial cells. Together, bioinformatic and experimental findings support an association between putative novel miR-1133 inhibitor transfection, PIK3CA expression, and oxidative stress under hyperglycemic conditions. Further studies are required to validate the direct interaction between putative novel miR-1133 and PIK3CA and to determine the relevance of these findings in vivo. Full article

Background: Drought is one of the major abiotic stresses that affect and limit cotton growth and production. However, transcriptome differences between drought-tolerant and drought-susceptible cotton lines remain largely unknown. Methods and Results: In this study, two upland cotton cultivars, the drought-tolerant XLZ80 and drought-sensitive XLZ61, were subjected to comparative phenotypic and transcriptomic analyses under drought stress. Phenotypic evaluation showed that XLZ80 exhibited only mild leaf wilting, whereas XLZ61 displayed severe wilting symptoms after drought stress. RNA-seq analysis revealed that differentially expressed genes in XLZ80 were specifically enriched in pathways related to phosphatidylinositol signaling, phenylalanine metabolism, MAPK signaling, and betaine biosynthesis, while DEGs in XLZ61 were primarily involved in basal metabolic processes. A total of 9302 core DEGs were identified across and between the cultivars and were grouped into eight dynamic expression clusters containing 841 transcription factors. Weighted gene co-expression network analysis further identified three key modules associated with drought tolerance. Twelve hub genes, including GH_D02G2153 (MADS-box) and GH_A05G1087 (bZIP), were identified as central regulators. qRT-PCR validation confirmed that these genes exhibited faster and stronger induction in the tolerant cultivar. In summary, this study deepens the transcriptional-level understanding of drought stress responses in cotton and provides valuable gene resources for breeding drought-resistant cultivars. Full article

Background: Acute brain injury (ABI) is a frequent complication of extracorporeal membrane oxygenation (ECMO), but early detection is limited by sedation, imaging constraints, and low sensitivity of conventional neuroimaging. We hypothesized that plasma metabolomics could identify ECMO-mode-specific metabolic shifts and biomarkers preceding ABI. Methods: Untargeted plasma metabolomics was performed in 70 participants across two centers: 30 healthy controls, 17 critically ill controls, and 23 ECMO patients [14 venovenous (VV) and 9 venoarterial (VA)]. Plasma was collected within 24 h and 7 days after cannulation. Fold-change analyses and partial least squares discriminant analysis were used to define metabolic differences and identify metabolites associated with subsequent ABI. Results: ABI occurred in seven ECMO patients, including five venoarterial and two venovenous ECMO patients. ECMO support was associated with broad alterations in circulating lipid metabolism, including changes in sphingomyelins, lysophospholipids, and monoacylglycerols. PLS-DA demonstrated metabolomic separation between ECMO patients and controls. Among ECMO patients, three structurally related glycerophospholipids—GPI (18:0/18:2), GPC (16:0/18:2), and GPE (16:0/18:2)—were significantly decreased before ABI diagnosis. ABI was also associated with broader reductions in phosphatidylethanolamines, phosphatidylinositols, lysophospholipids, and polyunsaturated fatty acids. Conclusions: Early reductions in membrane-associated phospholipids were associated with subsequent ABI during ECMO support, suggesting that alterations in circulating lipid homeostasis may identify neurological vulnerability before clinical or radiographic recognition of injury. Plasma metabolomics may provide a complementary approach for early neurological risk stratification and support future biomarker development. Full article

Soil salinization poses a major environmental threat to global agriculture, affecting approximately 20% of cultivated land and 50% of irrigated land worldwide. Developing salt–alkali tolerant plant varieties represents a sustainable strategy for utilizing these marginal lands. Phosphatidylinositol-specific phospholipase C (PI-PLC) is a key enzyme in the phosphoinositide signaling system and has been implicated in plant stress responses; however, its function under salt–alkali stress remains poorly understood. In this study, the function of AtPLC1 in salt–alkali tolerance was investigated, and only the atplc1 mutant exhibited a pronounced stress-sensitive phenotype, with AtPLC1 being predominantly expressed in roots and leaves, with peak expression at 6 h of treatment. Compared with wild-type, atplc1 mutants displayed significantly reduced seedling survival, retarded root growth, decreased biomass, water content, chlorophyll, and soluble sugar contents, yet accumulated higher levels of Na⁺, malondialdehyde, H₂O₂, and superoxide anions under salt–alkali stress. Notably, atplc1 mutants showed increased stomatal conductance and decreased leaf surface temperature, as detected by thermal imaging, indicating impaired water regulation. Collectively, our findings demonstrate that AtPLC1 positively regulates salt–alkali tolerance and provides a candidate gene for molecular breeding of stress-resistant crops. Full article

Ginkgo biloba extract (GBe) attenuates the transition of cisplatin (CDDP)-induced acute kidney injury to chronic kidney disease (AKI-to-CKD). Purpose: This study aimed to reveal the mechanism by which GBe inhibits CDDP-induced AKI-to-CKD. The potential targets of GBe in alleviating CDDP-induced renal interstitial fibrosis (Cis-RIF) were predicted through network pharmacology. Transcriptomics and metabolomics were used to detect differentially expressed genes (DEGs) and metabolites (DEMs) in renal tissues from Cis-RIF rats. Integrated multi-omics analysis was performed to determine the potential mechanism underlying GBe inhibiting AKI-to-CKD, and experimental verification was conducted in vivo, in vitro, and using siRNA. We identified 100 targets of GBe that could inhibit Cis-RIF using network pharmacology, and these targets were enriched in 194 signaling pathways. Transcriptomics and metabolomics revealed 8907 DEGs (enriched in 51 pathways) and 424 DEMs (enriched in 16 pathways), respectively. Collectively, the phosphatidylinositol signaling pathway was a co-enriched pathway, which may be the key pathway through which GBe inhibits AKI-to-CKD. This was verified experimentally. The related apoptosis and fibrosis indicators, and the key targets of the phosphatidylinositol signaling pathway (PLC, PKC, PIP2, IP3, DAG, Ca²⁺), in rat renal tissues and renal tubular epithelial cells (RTECs) with CDDP-induced AKI-to-CKD were significantly increased. Inhibition of HIF-1α and knockdown of HIF-1α in RTECs reversed the changes the phosphatidylinositol pathway targets. Moreover, both GBe and the HIF-1α inhibitor could inhibit HIF-1α and the phosphatidylinositol pathway targets, as well as the apoptosis and EMT of RTECs. Conclusion: This study reveals for the first time that GBe may inhibit AKI-to-CKD by downregulating apoptosis and EMT in RTECs through the HIF-1α/phosphatidylinositol signaling axis. Full article

Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it has shown potential therapeutic benefits in the management of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ochratoxin A (OTA), a common contaminant found in foods such as cereals, coffee, and raisins, is also present in traditional Chinese medicinal materials, including Astragalus and liquorice. T2DM and NAFLD share intertwined pathophysiological pathways, including insulin resistance, dyslipidaemia, chronic low-grade inflammation and oxidative stress, with insulin resistance serving as the common pathological hub for both conditions. Consequently, they frequently co-occur and exacerbate each other. OTA exerts dual-targeted toxicity to the pancreas and liver, which may synergistically drive the development of the comorbidity of T2DM and NAFLD. These two processes are mutually causal and together constitute the pathological basis of metabolic comorbidity. Methods: Network toxicology employs toxicological data, gene expression, and protein–protein interaction (PPI) networks to predict the targets of toxins, while network pharmacology, based on systems biology principles, reveals how drugs exert regulatory effects through multiple targets and pathways. In this study, we employed an integrated network toxicology and network pharmacology approach to jointly decipher the potential mechanisms by which CA intervenes in OTA-induced comorbid T2DM-NAFLD. First, a network toxicology approach was employed to preliminarily screen for core toxicological targets responsible for OTA’s pathogenicity. Subsequently, network pharmacology was used to identify potential targets of CA-mediated intervention in the disease. Finally, the common overlap among the CA intervention targets, OTA toxicity targets, and disease targets was defined as the final set of potential targets for CA-mediated intervention in OTA-induced T2DM-NAFLD comorbidity. A PPI network was constructed using the STRING database, and topological analysis was performed with Cytoscape. Core targets were selected using the median values of six parameters—betweenness centrality, closeness centrality, degree centrality, eigenvector centrality, LAC (local average connectivity) score, and network centrality—as cut-off thresholds, and the top 10 key genes were further identified using the cytoHubba plugin. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database, and the results were visualized on the CNSknowall platform. Lastly, molecular docking of the core targets was performed using the CB-DOCK2 platform to validate binding affinity. Results: Based on an integrated analysis of network toxicology, network pharmacology, and molecular docking, 10 key targets were systematically identified. These may serve as potential mediators of cinnamaldehyde in the treatment of OTA-induced T2DM-NAFLD comorbidity. Among these, six targets—albumin (ALB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-6 (IL-6), tumor necrosis factor (TNF), actin beta (ACTB), and estrogen receptor 1 (ESR1)—possess crystal structures amenable to molecular docking. KEGG enrichment analysis revealed that CA and OTA jointly participate in key pathological processes such as the cancer pathway, the lipid and atherosclerosis pathway, the advanced glycation end-products–receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway, the TNF signaling pathway, and the interleukin-17 (IL-17) signaling pathway. OTA exacerbates inflammatory responses, impairs insulin signaling, promotes hepatic steatosis, and disrupts systemic metabolic homeostasis, ultimately contributing to T2DM-NAFLD comorbidity. Conversely, cinnamaldehyde counteracts these pathological processes through multiple mechanisms, including antioxidant and anti-inflammatory effects as well as regulation of glucose and lipid metabolism, thereby restoring metabolic homeostasis. Conclusions: This study has preliminarily identified the toxicological targets of OTA and the potential intervention targets of CA, offering new avenues for preventing and intervening in OTA-induced metabolic toxicity. Furthermore, it provides a theoretical basis for CA as a potential multi-target therapeutic agent and presents novel insights worthy of further investigation into the prevention of T2DM-NAFLD comorbidity. Full article

The lipid and fatty acid composition of the little Baikal oilfish (Comephorus dybowskii Korotneff, 1905) was studied to identify the features of its biochemical adaptation to the environmental conditions of Lake Baikal. Multivariate analysis of lipid classes and FA profiles revealed reproducible clustering patterns in both muscle tissue and whole-body samples, indicating the presence of distinct physiological states differing in membrane organization and lipid metabolism. Lipid-class variability was primarily associated with sphingomyelin, cholesterol esters, phosphatidylinositol, and lysophosphatidylcholine, suggesting the coordinated regulation of membrane structure. The fatty-acid profiles were mainly presented by variations in saturated, monounsaturated, and long-chain polyunsaturated fatty acids, with muscle tissues characterized by a relatively longer carbon chain (ACL = 19 vs. 18 I whole body) and unsaturation (UI = 1.98–2.76 vs. 1.64–2.53 in whole body). At the same time, comparative analysis demonstrated low correspondence between lipid and FA profiles, indicating partially independent adaptive mechanisms. The experimental transfer of fish from their natural habitat to controlled conditions resulted in the significant remodeling of both lipid and FA compositions, including increases in acylglycerols, membrane phospholipids, and monounsaturated fatty acids, together with a decline in long-chain n-3 polyunsaturated fatty acids. The results suggest that lipid classes and fatty acids represent complementary but functionally distinct levels of biochemical adaptation contributing to the maintenance of membrane organization and metabolic homeostasis in C. dybowskii, revealing a previously undescribed multi-level organization of lipid-related adaptive responses in this endemic deep-water fish. Full article

Background: Phosphatidylinositol 3-kinase (PI3K) is a promising anticancer drug target, and selective PI3Kα inhibition may provide both efficacy and an improved safety profile. This study aimed to design new potentially selective PI3Kα inhibitors using computer-aided drug design (CADD). Methods: Benzoxazepine and thiazole derivatives were investigated using molecular dynamics, ensemble docking, and Three-Dimensional Quantitative Structure–Activity Relationship (3D-QSAR) analyses. Scaffold hopping, substituent replacement, structure-based virtual screening, and density functional theory (DFT) calculations were then applied to guide the design and characterization of new derivatives. Results: The study identified new chemotypes capable of interacting with PI3Kα Val851 (αVal851) in the hinge region, including chromeno[3,4-d]imidazole, 2H-benzo[b]oxazine, and quinoline derivatives. Additional substructures directed toward hydrophobic region II and the αGln859 interaction environment supported predicted selectivity over PI3Kβ, PI3Kγ, and PI3Kδ. Conclusions: The results establish a comprehensive CADD framework for the rational design of selective PI3Kα inhibitors and provide new compounds with improved predicted selectivity profiles for further development. Full article

Chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, cystic fibrosis, and chronic bronchitis, are characterized by persistent airway inflammation and mucus hypersecretion, leading to airway remodeling and progressive pulmonary dysfunction. Although current therapies improve disease control, they often fail to adequately target the complex molecular mechanisms underlying chronic airway diseases and may cause adverse effects during long-term use. Natural products have therefore emerged as promising multitarget therapeutic agents because they simultaneously regulate oxidative stress, inflammatory signaling, epithelial dysfunction, and mucus production. Recent evidence demonstrates that marine-derived bioactive compounds and plant-derived phytochemicals modulate key signaling pathways, including nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), Janus kinase/signal transducer and activator of transcription (JAK/STAT), the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, and nuclear factor erythroid 2-related factor 2 (Nrf2), thereby suppressing airway inflammation, oxidative stress, goblet cell differentiation, and MUC5AC overexpression. Advances in nanoformulation, pulmonary drug delivery, multi-omics, artificial intelligence-assisted drug discovery, and network pharmacology are expected to accelerate clinical translation. Collectively, natural products represent promising candidates for the development of evidence-based functional foods, nutraceuticals, and novel therapeutic strategies for chronic respiratory diseases. Full article