Search Results (3,347)

Tendinopathy is a prevalent musculoskeletal condition characterised by chronic inflammatory and degenerative changes. Pulsed electromagnetic fields (PEMFs) represent a promising biophysical therapeutic modality, yet their effects across different inflammatory states of tendinopathy remain poorly characterised. To evaluate PEMF biological effects on human tenocytes, three in vitro models differing in IL-1β dose and duration were tested: acute low-dose (0.1 ng/mL, 96 h), acute high-dose (1 ng/mL, 96 h), and prolonged (0.1 ng/mL, 9 days). At the transcriptional level, PEMFs significantly reduced IL-6 and IL-8 mRNA overexpression in the acute low-dose model and CCL2 upregulation in the prolonged model. At the secretome level, PEMFs reduced GM-CSF and IL-8 secretion in the acute high-dose model, and suppressed CCL2 and CCL5 protein secretion in the prolonged model. MMP activity was not modulated by PEMFs in any condition. PEMFs consistently increased tenocyte proliferation across both the acute models. Finally, in wound healing assays, non-inflamed tenocytes exposed to PEMFs showed significantly enhanced wound closure compared to IL-1β-treated cells across all models; in the acute low-dose model, PEMFs also significantly improved wound closure in IL-1β-treated cells at an early timepoint, whereas no such effect was observed in cells exposed to high-dose or prolonged inflammation. PEMFs exert context-dependent effects, promoting healing primarily during acute or mild inflammation. These findings suggest that the inflammatory stage of tenocytes may influence PEMF responsiveness in vitro, highlighting the importance of considering this variable in the design of future clinical studies evaluating PEMF therapy for tendinopathy. Full article

Background and Objectives: Conduction disorders (CDs) and permanent pacemaker implantation (PPI) remain among the most common complications after transcatheter aortic valve implantation (TAVI). Given their potential impact on long-term outcomes, improved preprocedural identification of patients at high risk for new-onset CDs is increasingly important. We investigated whether selected preprocedural inflammatory and fibrotic biomarkers, along with echocardiographic indices of regional myocardial remodeling, were associated with new-onset CDs after TAVI. Materials and Methods: This single-center prospective observational study included 112 patients with severe aortic stenosis undergoing TAVI. Peripheral blood samples were obtained within 24 h before TAVI for measurement of inflammatory and fibrotic biomarkers, including interleukin-6 (IL-6), C-reactive protein (CRP), CRP-to-albumin ratio (CAR), procalcitonin, ferritin, lactate dehydrogenase, and transforming growth factor-β1. The primary outcome was the occurrence of new-onset CDs during the index hospitalization or within three months after TAVI. Results: New-onset CDs occurred in 58 patients (51.8%). IL-6 showed the strongest association with the outcome in univariable analysis (OR per 1-SD increase, 9.55; 95% CI 3.00–30.40; p < 0.001), remained associated after adjustment for selected clinical and procedural predictors in exploratory models (adjusted OR 10.70; 95% CI 2.43–47.07; p = 0.002), and demonstrated the highest, although moderate, discriminatory performance among the evaluated biomarkers (AUC 0.730; 95% CI 0.637–0.823). CRP and CAR were higher in patients with CDs and were significant in univariable analysis, but showed weaker and less consistent adjusted associations. Among echocardiographic markers, AB strain ratio ≥ 2 was the most consistent imaging correlate in exploratory biomarker–echocardiographic models. Conclusions: Elevated preprocedural IL-6 was the biomarker most consistently associated with new-onset CDs after TAVI. These findings suggest that higher preprocedural IL-6 levels may reflect patient-specific susceptibility to new-onset CDs after TAVI and could have potential value as an adjunctive biomarker, alongside echocardiographic assessment, for preprocedural risk evaluation, with further validation required in larger prospective studies. Full article

Regular exercise mediates inter-tissue communication between skeletal muscle and the immune system through skeletal muscle-derived secretory factors, providing an important molecular basis for the beneficial effects of exercise on chronic inflammation, metabolic dysregulation, and impaired tissue repair. As key effector cells of the innate immune system, macrophages do not simply conform to a dichotomous classification of classically activated M1 macrophages and alternatively activated M2 macrophages; rather, their functional states constitute a dynamic spectrum shaped by exercise load, recovery time window, tissue microenvironment, and disease context. This review focuses on recent advances in exercise-induced skeletal muscle secretory factors involved in macrophage functional remodeling. Representative signals, including interleukin-6 (IL-6), irisin, meteorin-like protein (METRNL), fibroblast growth factor 21 (FGF21), oncostatin M (OSM), decorin, myostatin, chemokines, and extracellular vesicles, are systematically summarized in terms of their exercise responsiveness, evidence for skeletal muscle origin, and evidence supporting macrophage regulation. Based on these dimensions, an evidence-strength grading framework is further proposed. Moreover, this review integrates key signaling axes, including glycoprotein 130 (gp130)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT), signal transducer and activator of transcription 6 (STAT6)/peroxisome proliferator-activated receptor gamma (PPARγ), AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/nuclear factor kappa B (NF-κB), transforming growth factor beta (TGF-β)/Smad, and chemokine receptor pathways, to explain how exercise-induced secretory networks participate in the dynamic regulation of the macrophage functional spectrum through immune cell recruitment, inflammatory clearance, immunometabolic reprogramming, matrix remodeling, and repair-niche formation. Current evidence indicates the translational potential of exercise-induced skeletal muscle secretory factors in skeletal muscle repair, metabolic inflammation, aging-related functional decline, and cancer rehabilitation. However, this field still faces several major challenges, including insufficient tracing of skeletal muscle-derived signals, limited direct causal validation, a lack of human tissue-level evidence, and unclear exercise dose–response relationships. Future studies should combine tissue-specific genetic interventions, receptor blockade, single-cell and spatial omics, metabolic flux analysis, and standardized human exercise interventions to further clarify the mechanistic basis and application boundaries of exercise-induced skeletal muscle–macrophage communication, thereby providing a theoretical foundation for precision exercise prescription and chronic inflammation intervention. Full article

Background/Objectives: Older adults residing in long-term care facilities (LTCFs) are at increased risk of poor oral health because of functional dependence and limited access to professional oral healthcare. Although oral healthcare education programs for care workers improve knowledge and performance, evidence of their effects on residents’ biological oral health outcomes remains limited. This study evaluated the effects of a care worker-centered oral healthcare program on oral inflammatory status in LTCF residents using salivary interleukin-1 beta (IL-1β) as an objective biomarker. Methods: A single-group pretest–posttest quasi-experimental study was conducted in two LTCFs in the Republic of Korea. Forty care workers completed a structured oral healthcare education program and provided daily oral healthcare to residents for 4 weeks. Saliva samples were collected before and after the intervention, and salivary IL-1β concentrations were measured using enzyme-linked immunosorbent assay. Changes in IL-1β concentrations were analyzed using the Wilcoxon signed-rank, Mann–Whitney U, and Kruskal–Wallis tests. Results: Thirty-seven residents completed the study. Median salivary IL-1β concentrations significantly decreased from 19.33 pg/mL (interquartile range [IQR], 11.49–34.66) at baseline to 10.78 pg/mL (IQR, 0.65–33.64) after the intervention (Z = −3.764, p = 0.001). Greater reductions were observed among residents with greater functional dependence, whereas limited communication ability or oral care refusal was associated with minimal improvement. Conclusions: A care worker-centered oral healthcare program significantly reduced salivary IL-1β concentrations among older adults residing in LTCFs. Findings support care worker training and highlight the use of salivary IL-1β as an objective biomarker for evaluating oral healthcare interventions. Full article

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine–metabolic disorder frequently associated with insulin resistance (IR) and increased cardiovascular risk. Soluble CD40 ligand (sCD40L) and soluble E-selectin (sE-selectin) are circulating biomarkers reflecting immune activation and endothelial dysfunction, respectively. However, their differential associations with IR in PCOS, particularly in the context of central obesity, remain incompletely understood. This cross-sectional study included 80 women with PCOS stratified according to waist-to-height ratio (WHtR > 0.50 vs. ≤0.50). Clinical, metabolic, hormonal, inflammatory, and endothelial parameters were evaluated. Correlation and multivariable regression analyses were performed to identify independent determinants of circulating sCD40L and sE-selectin. Women with central obesity exhibited significantly higher fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, non-high-density lipoprotein (non-HDL) cholesterol, systolic blood pressure (SBP), and sE-selectin concentrations, together with lower HDL cholesterol. No significant differences were observed in tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), or sCD40L. In adjusted regression models, fasting glucose independently predicted sCD40L (β = −0.27, 95% confidence interval (CI): −0.50 to −0.04, p = 0.020), whereas fasting insulin emerged as the strongest determinant of sE-selectin (β = 0.41, 95% CI: 0.17 to 0.65, p < 0.001). These findings suggest distinct associations of immune and endothelial biomarkers with IR in PCOS. Assessment of sCD40L and sE-selectin may provide complementary information for early cardiometabolic risk stratification in affected women. Full article

This study aimed to investigate the regulatory effects of dietary dandelion supplementation on the ruminal physiological status of lambs fed a high-concentrate diet. Twenty-two 6-month-old female crossbred lambs with an initial body weight of 32.05 ± 0.43 kg were randomly assigned to two groups (n = 11 per group): the HC group (fed a high-concentrate basal diet) and the DD group (basal diet supplemented with 2 g/kg dandelion powder), with a 14-day adaptation and 60-day experimental period. The results showed that compared with the HC group, dandelion supplementation significantly improved lamb growth performance and modulated ruminal fermentation parameters and tissue morphology. For inflammatory indices, the concentration of interleukin-10 (IL-10) was significantly increased, while the concentrations of interleukin-1β (IL-1β), lipopolysaccharide (LPS) and histamine (HIS) were significantly decreased (p < 0.05). Meanwhile, dandelion supplementation upregulated the mRNA expression of ruminal epithelial tight junction proteins and hexokinase II (HK-II), while downregulating the mRNA expression of myeloid differentiation factor 88 (MyD88), voltage-dependent anion channel 1 (VDAC1), inositol 1,4,5-trisphosphate receptor (IP3R), NLR family pyrin domain containing 3 (NLRP3), and caspase-1. Metagenomic analysis revealed that dandelion supplementation did not alter ruminal microbial α-diversity, but slightly modulated community composition and functional profiles. The abundances of dominant phyla Bacteroidota and Bacillota showed only slight fluctuations, while fiber-degrading genera (Xylanibacter, Quinella, Selenomonas) showed a trend toward enrichment, and proteolytic taxa were decreased. CAZyme analysis revealed an upward trend in families CE4, CE8, GH32, and GH13_46 (pectin/starch degradation) and a downward trend in GH73, GH27, and GT14 (oligosaccharide/peptidoglycan/polysaccharide metabolism) in the DD group. KEGG orthology annotation suggested that nominal KO differences were mainly associated with carbohydrate metabolism pathways, including starch and sucrose metabolism and peptidoglycan biosynthesis. None of these features, however, remained significant after FDR correction (raw p < 0.05; all q > 0.05). Collectively, dietary dandelion supplementation was associated with alterations in ruminal physiological status and microbial community in lambs fed a high-concentrate diet, providing foundational data for dandelion application in lamb diets under short-term feeding conditions. Full article

A pro-inflammatory state, characterized by elevated levels of pro-inflammatory cytokines, is frequently reported among individuals presenting with primary first-episode psychosis (FEP), particularly those with environmental risk factors such as maternal infections and early childhood traumatic experiences. These findings suggest that immune system disturbances may play a crucial role in the onset of psychotic disorders. Building on this, cytokines may contribute to the risk of FEP from the stage of neurodevelopment, where they can induce aberrant changes in neuronal growth. During early childhood, these cytokine-mediated processes may disrupt normal neuronal maturation and lead to brain alterations that increase vulnerability to primary psychotic disorders. Furthermore, pro-inflammatory cytokines exhibit strong bidirectional modulatory interactions with dopamine, a key neurotransmitter implicated in the pathogenesis and persistence of psychosis. Notably, these cytokines may also influence the clinical presentation and severity of psychosis. In addition, antipsychotic medications can partially modulate cytokine levels, and this modulation has been correlated with the efficacy of antipsychotics in treating various psychotic symptoms. Frequently reported cytokines in this context include interleukins (IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10), tumour necrosis factor-α (TNF-α), and interferon-gamma (IFN-γ). We conducted a non-systematized literature search on Google Scholar and PubMed for studies looking at cytokines in primary psychotic disorders during FEP. In this narrative review, we provide an overview of the literature on immune dysregulation in FEP, with a particular emphasis on cytokines. Full article

Background: Lipid mediators (LM), comprising 17S-hydroxy-docosahexaenoic acid, resolvin D5, and protectin DX in a ratio of 3:47:50, were naturally generated from docosahexaenoic acid by soybean lipoxygenase and exhibit potent anti-inflammatory activities. However, their therapeutic potential in periodontitis (PD) remains unclear. Therefore, this study investigated the protective effects of LM against PD in vitro and in vivo. Methods: Human gingival fibroblasts (HGFs) were stimulated with Porphyromonas gingivalis lipopolysaccharide (PG-LPS) to evaluate the anti-inflammatory effects of LM. Nitric oxide (NO) production, prostaglandin E2 (PGE2) level, inflammatory cytokines secretion, matrix metalloproteinase 9 (MMP9) expression, and NF-κB/STAT3 signaling pathways were analyzed. In vivo, a ligature-induced rat model of PD was established, and LM were orally administered at doses of 5, 10, and 20 μg/kg once daily. The effects of LM were evaluated by histopathological examination, micro-computed tomography (micro-CT), quantitative real-time PCR (qRT-PCR), and immunohistochemistry (IHC). Results: In PG-LPS-stimulated HGFs, LM significantly reduced NO and PGE2 production by downregulating inducible nitric oxide synthase and cyclooxygenase-2 expression. Moreover, LM decreased the levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-1β, and MMP9, accompanied by suppression of the NF-κB and STAT3 signaling pathways. In the ligature-induced rat model of PD, LM significantly attenuated gingival inflammation and alveolar bone loss. Furthermore, IHC analysis revealed that LM markedly reduced the level of IL-6, TNF-α, MMP9, and phosphorylated STAT3 in gingival tissues. Conclusions: LM exerted protective effects against periodontitis by alleviating inflammatory response and reducing alveolar bone loss, which may be associated with suppression of the NF-κB and STAT3 signaling pathways. Full article

Wle vanillin is widely used as a flavoring agent in food products, its potential as a non-antibiotic feed additive for broilers remains unexplored. This study primarily investigated the effects of dietary supplementation of vanillin on antioxidant activity, anti-inflammatory response, immune function, and gut microbiota composition in broilers. One-day-old male broilers were randomly assigned to five groups: a basal diet group, a positive control group (basal diet + 100 mg/kg chlortetracycline (CTC)), and three vanillin-supplemented groups (0.1%, 0.2%, or 0.4%) for 42 days. Results showed that vanillin improved antioxidant capacity, with elevated serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity and reduced malondialdehyde (MDA) levels. Broilers receiving vanillin supplementation showed lower levels of pro-inflammatory cytokines (interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)) and higher interleukin-10 (IL-10) expression compared with controls. Additionally, serum immunoglobulin A (IgA) and immunoglobulin M (IgM) levels were also greater in the vanillin group. It also enhanced intestinal health by increasing the duodenal villus height-to-crypt depth ratio, improving intestinal morphology, raising the Firmicutes-to-Bacteroidetes ratio, and promoting Lactobacillus proliferation compared with CTC. Notably, growth performance data were exploratory in nature; vanillin was associated with numerical improvements in average daily gain (ADG) and feed conversion (F/G) ratio. These preliminary findings suggest that vanillin requires further investigation as a potential feed additive. Full article

Differentiating active ulcerative colitis (UC) from Crohn’s disease (CD) is one of the unmet needs addressed by biomarkers in inflammatory bowel disease (IBD). The immune landscapes of UC and CD differ, justifying the search for discriminatory markers and novel therapy targets among their mediators. Herein, 27 systemic cytokines were measured using flow cytometry-based methodology in 138 IBD patients, with an additional 21 being determined in 67 of the patients. Their discriminatory power was assessed individually and as exploratory multivariable signatures generated using logistic regression, hierarchical clustering, and principal component analysis. Eotaxin-1, macrophage inflammatory protein (MIP)-1β, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) showed fair discriminatory potential, while multivariable models performed better. Interleukin (IL)-1β, IL-4, and MIP-1α were strongly associated with CD, whereas IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), MIP-1β, and TRAIL were associated with UC. Active UC was characterized by mediators linked to eosinophil-, mastocyte-, and neutrophil-driven inflammation and tissue repair (eotaxin-1, IL-5, growth-regulated oncogene (GRO), MIP-1β, stem cell factor (SCF), GM-CSF, IL-1 receptor antagonist, TRAIL, stem cell growth factor (SCGF)-β, and cutaneous T cell-attracting chemokine (CTACK)), whereas active CD was associated with Th1/Th17 immunity, myeloid activation, fibrosis, angiogenesis, and neuroimmune remodeling (IL-1β, IL-12p70, IL-15, ‘regulated on activation, normal T-cell expressed and secreted’ (RANTES), MIP-1α, stromal cell-derived factor (SDF)-1α, nerve growth factor β (β-NGF), and leukemia inhibitory factor (LIF)). In conclusion, integrated circulating immune signatures identify several understudied cytokines as potential contributors to disease-specific pathways and show potential in distinguishing active UC from CD warranting further mechanistic studies and independent validation in larger cohorts. Full article

Background: Peri-implantitis is a chronic condition that reflects an interaction between local tissue destruction, systemic inflammation and corrosion-related implant alterations. This preliminary prospective exploratory clinical study aimed to characterize the systemic cytokine profile of patients with advanced peri-implantitis requiring explantation and to explore associations between clinical severity, cytokine behavior and scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDX)-defined corrosion-related findings. Methods: Thirteen patients with active advanced peri-implantitis were included. Probing depth and cone-beam computed tomography (CBCT)-based bone loss were assessed at four implant surfaces. Peripheral blood was collected before and 4 weeks after explantation. Serum interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-12p70 (IL-12p70), tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hsCRP), and fibrinogen were analyzed. Explanted implants underwent SEM/EDX assessment and were classified according to the presence or absence of SEM/EDX-defined corrosion-related findings. Results: IL-6 showed the strongest and most consistent associations with clinical and radiographic severity, whereas hsCRP and fibrinogen were not similarly related. Cytokines did not show a uniform post-explantation decrease after explantation. SEM/EDX-defined corrosion-related findings were not associated with higher baseline cytokines, but exploratory subgroup analysis suggested a divergent TNF-α trajectory. Conclusions: These findings suggest that IL-6 may reflect the clinical inflammatory burden of advanced peri-implantitis, while corrosion-related findings may be associated with post-explantation TNF-α behavior. Larger controlled studies are required. Full article

This study investigated the effects of noni fruit flavonoids (NFF) on antioxidant status and anti-inflammatory responses in cashmere goats and explored the underlying mechanisms based on liver transcriptomics and metabolomics. Sixteen male Albas cashmere goats were randomly assigned to two groups: a control (CON) group and a group supplemented with 0.1% NFF. The adaptation and trial periods were 2 and 12 weeks, respectively. The results showed that NFF significantly enhanced antioxidant capacity, with mean increases of 32.9%, 20.7%, and 35.5% for total antioxidant capacity (T-AOC), glutathione peroxidase (GPx), and catalase (CAT) activities, respectively, across serum, liver, spleen, and thymus (p < 0.05). NFF also modulated the inflammatory profile, with a mean increase of 18.0% for interleukin (IL)-10 and mean reductions of 18.6%, 19.4%, and 16.7% for IL-1β, IL-2, and tumor necrosis factor (TNF)-α, respectively, across the serum, liver, and thymus (p < 0.05). Integrative transcriptomic and metabolomic analyses suggested that the AMPK signaling pathway, glutathione metabolism, and TGF-β signaling pathway may be critically involved in mediating these effects. GPX3, GPX8, GCLM, NFKB1, and IL1B were identified as key candidate genes, while adenosine-5′-monophosphate (AMP), cysteinylglycine, and pyroglutamic acid were key differential metabolites. Dietary supplementation with 0.1% NFF enhanced the antioxidant levels and anti-inflammatory response in cashmere goats. Full article

Chronic inflammatory signaling contributes to cartilage degeneration across multiple joint diseases, yet the molecular consequences of sustained cytokine exposure remain incompletely understood. We investigated how prolonged interleukin-1β (IL-1β) stimulation remodels the chondrocyte proteome and whether these changes are associated with senescence-associated traits. Primary human articular chondrocytes were exposed to IL-1β (10 ng/mL) for up to four days. Time-resolved data-independent acquisition (DIA) proteomics was integrated with immunofluorescence, quantitative PCR, multiplex metalloproteinase profiling, BrdU incorporation, growth-curve analysis, and senescence-associated β-galactosidase assays. Sustained IL-1β induced extensive time-dependent proteomic remodeling, with early inflammatory and extracellular matrix responses followed by alterations in cell-cycle regulation and cytoskeletal organization. Prolonged stimulation was associated with persistent downregulation of CDK4, Cyclin D1, DNA replication-associated proteins, and Rho GTPase-associated components, accompanied by actin cytoskeletal remodeling. These molecular changes were associated with impaired proliferation, increased senescence-associated β-galactosidase activity, and transient modulation of p21. Following cytokine withdrawal, BrdU incorporation showed partial recovery. Together, these findings indicate that sustained IL-1β progressively reshapes the chondrocyte cellular state through coordinated remodeling of proliferative, cytoskeletal, and metalloprotease programs while showing some degree of proliferative plasticity under the conditions tested. Full article

Currently, emerging pharmaceutical contaminants (EPCs) pose a significant risk to aquatic biodiversity on both a global and regional scale. Their accumulation in the environment presents several challenges to both human health and ecological integrity. Among EPCs, cyclophosphamide (COP), a widely used alkylating cytotoxic and immunosuppressive drug in human and veterinary oncology, has become one of the most frequently detected environmental contaminants. It has been reported to impair the immune system, induce oxidative stress, and exhibit genotoxic and cytotoxic effects in various fish species. However, limited research has evaluated its toxicity in the Siamese fighting fish (Betta splendens), an endemic significant aquatic species in Thailand. This study evaluated the acute toxicity of COP in Betta splendens by assessing systemic oxidative stress responses, alterations in gene expression, and localized histopathological changes within both hepatic and renal tissues. The 96 h of median lethal concentration (LC₅₀) value for COP in Betta splendens was determined to be 793.4 mg/L. High-concentration exposure (800 mg/L) induced severe systemic oxidative stress, evidenced by a significant reduction in superoxide dismutase (SOD) activity and a marked elevation in malondialdehyde (MDA) levels across both liver and kidney. At the transcriptomic level, acute COP exposure significantly upregulated pro-inflammatory (interleukin-1β, IL-1β and tumor necrosis factor, TNF-α), cellular stress (heat shock protein 70, HSP70), and apoptotic (caspase-3, Casp3) genes. Semi-quantitative histopathological evaluation revealed severe concentration-dependent structural damage. Hepatic lesions peaked at 800 mg/L characterized by diffuse vacuolation, vascular congestion, and extensive necrosis. Similarly, severe renal damage occurred at 800 mg/L, featuring marked vascular congestion, melanomacrophage aggregation, and widespread tubular necrosis. Overall, these findings demonstrate that acute waterborne COP exposure induces severe hepatotoxicity and nephrotoxicity in Betta splendens driven by oxidative stress, pro-inflammatory signaling, and apoptotic pathways. This study provides essential baseline toxicity thresholds and highlights the physiological risks COP spills pose to tropical freshwater labyrinth fish. Full article

Zoonotic bacterial pathogens are transmitted through various routes and are traditionally associated with acute febrile illnesses that may include pulmonary complications. However, in some survivors, the disease extends beyond the acute phase, leading to the remodeling of pulmonary architecture and driving progressive fibrosis. Although no direct cases have been reported, these pathogens may plausibly predispose injured lungs to carcinogenesis, similar to the well-recognized phenomenon of tuberculosis-associated scar cancer. As such long-term sequelae remain largely overlooked in current clinical practice, their potential contribution to fibrotic and malignant lung disease represents a critical and underexplored knowledge gap. This review proposes a unified mechanistic framework linking acute pathogen-mediated alveolar damage to chronic pulmonary fibrosis and subsequent lung carcinogenesis. We delineate four convergent biological pillars driving this continuum: (1) pathogen persistence establishing chronic Interleukin-1β (IL-1β)/Tumor necrosis factor-α (TNF-α)-mediated inflammation; (2) sustained TGF-β signaling and mechanotransduction driving progressive extracellular matrix remodeling; (3) unresolved reactive oxygen species (ROS) generation causing profound oxidative DNA damage; and (4) aberrant epithelial–mesenchymal transition (EMT) that perpetuates fibrosis and generates pre-malignant cell populations. Together, these sequelae alter lung biomechanics, suppress local immune surveillance, and create a mutagenic environment that is highly conducive to malignant transformation. Although direct epidemiological data is still emerging, the significant mechanistic overlap with idiopathic pulmonary fibrosis (IPF) presents a compelling rationale for shared oncogenic risk. We advocate for a paradigm shift in clinical practice, emphasizing the potential value of long-term surveillance for survivors of severe pulmonary infections. By integrating infectious diseases, pulmonology, and oncology, this framework highlights a neglected cause of fibrotic lung disease and establishes a foundation for future translational research. Full article