Search Results (29,409)

Background: While live-cell therapies face significant translational hurdles, cell-free secretomes derived from fetal progenitor cells offer a unique, scalable approach natively programmed for scarless tissue repair. Methods: This GLP-compliant study evaluated the therapeutic efficacy spectrum of an off-the-shelf, clinical-grade, intratracheal lyophilized FE002-Lu lung fibroblast conditioned medium (LFCM) across five controlled Wistar rat models of induced lung injury: bleomycin (5 mg/kg), asbestos (100 µg/rat), hyperoxia (100% oxygen exposure), silica (30 mg/rat), and lipopolysaccharide (LPS, 4 mg/kg). Following lung injury induction and symptom onset, symptomatic rats were randomized to receive intratracheal LFCM (low, mid, or high dose) or a vehicle control every 4 days for 28 days. Results: The intervention demonstrated an exceptional safety profile, maintaining 100% survival with no severe procedural toxicity across all cohorts. Across all study arms, LFCM effectively attenuated pulmonary inflammation, reducing pro-inflammatory markers (IL-1β, IL-6, TNF-α, and CINC-1) in bronchoalveolar lavage fluid. Concurrently, high LFCM doses consistently elevated the anti-inflammatory cytokine IL-10. Within the lung tissue, mid- and high doses significantly reduced key pro-fibrotic drivers, including TGF-β1, TIMP-1, WISP-1, and hydroxyproline. Treatments consistently decreased α-SMA expression and pro-fibrotic gene mRNA levels, mitigating pulmonary myofibroblast activation. This correlated with reduced Ashcroft scores and collagen deposition, thereby preserving lung architecture. Notably, the FE002-Lu LFCM treatment exerted a biphasic regulation of extracellular matrix turnover: it elevated Cathepsin-D and MMP-12 in the bleomycin arm to actively clear newly deposited fibrotic debris, while reducing these markers in the hyperoxia and LPS arms to prevent acute collateral degradation of the native lung matrix. In both particulate models (asbestos and silica), the LFCM mid-dose established an optimal therapeutic threshold, avoiding the localized secretome saturation and pro-fibrotic exacerbation occasionally observed at higher doses. Conclusions: Lyophilized FE002-Lu LFCM acts as a potent, pleiotropic biologic that effectively resolves acute pulmonary inflammation and arrests progressive fibrotic remodeling across multiple distinct in vivo models. By overcoming the cold-chain and delivery limitations inherent to pulmonary live-cell therapies, this stable, cell-free secretome represents a highly scalable, “off-the-shelf” candidate poised for non-invasive, aerosolized clinical translation. Full article

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune neurological disorder characterized by pathogenic antibodies against the NMDAR. A systematic protein profiling approach is warranted to identify biomarkers capable of predicting disease status. An Olink proximity extension assay (PEA) profiled 91 inflammation-related proteins from anti-NMDAR encephalitis patients. Disease severity or prognosis were assessed by CASE score or mRS score at 6-month follow-up. Patients were stratified into distinct molecular clusters using unsupervised clustering. Logistic regression models incorporating selected biomarkers were developed to predict disease severity and prognosis, followed by absolute quantification using ELISA. Patients were classified into four consensus clusters. Clusters 1 and 2 corresponded to the mild group, while Cluster 3 represented the severe group, consistent with CASE score above 6. Cluster 4 showed heterogeneous clinical features. Elevated serum levels of IL-10, IL-6, and SIRT2, as well as increased CSF levels of CXCL10, CXCL11, and MMP10, were positively associated with severe disease. Conversely, several proteins including LTA and CCL11, CCL8, TGFB1, CXCL6 were associated with severe disease or unfavorable 6-month outcomes. A logistic regression model combining serum CXCL6 and CCL11 with CSF MMP10 achieved an area under the curve (AUC) of 0.95 for predicting disease severity. Serum CCL11 alone showed predictive value for 6-month prognosis, with an AUC of 0.79. These findings delineate distinct protein signatures associated with clinical heterogeneity of anti-NMDAR encephalitis. Prediction models incorporating multiple biomarkers may provide an approach for disease severity stratification and prognosis forecast. Full article

Acute lung injury (ALI) seriously impairs health and well-being. Although Scutellaria baicalensis Georgi (SBG) extract has been shown to alleviate ALI, the effects of SBG acidic polysaccharides on ALI have not been revealed. In this study, a homogeneous acidic polysaccharide (SBGP1) was purified and characterized, and its impact on ALI was evaluated. Our findings illustrated that the average molecular weight of SBGP1 was 40764.6 Da, and it was mainly composed of GalA (53.14%), Ara (26.99%), Gal (7.75%), Glc (5.95%), and Rha (6.17%). The main chain of SBGP1 consisted of →4)-α-GalpA-6-OMe-(1→ and →4)-α-GalpA-(1→. Furthermore, SBGP1 exhibited a significant alleviating effect on ALI, as evidenced by decreased levels of TNF-α, IL-1β, IL-6, GSSG, and MDA, and increased levels of IL-4, IL-10, GSH, and SOD. Mechanistically, SBGP1’s role in alleviating ALI may be associated with the activation of the Rap1 signaling pathway. SBGP1 improved intestinal homeostasis, manifested as increased abundance of beneficial bacteria (Lactobacillus and norank_f_Muribaculaceae) and decreased abundance of harmful bacteria (Adlercreutzia, Ligilactobacillus, Massiliomicrobiota, and Mucispirillum). Interestingly, SBGP1-derived Lactobacillus johnsonii and propionic acid evidently improved the inflammatory response and oxidative stress in ALI mice. Overall, this study provides novel insights into SBGP1 as a potential therapeutic option for ALI. Full article

Urban particulate matter (UPM) is a major environmental pollutant known to induce systemic inflammation. While its respiratory toxicity is well-documented, the potential vulnerability of the female reproductive system to inhaled UPM remains a critical concern. In this study, we evaluated female reproductive outcomes in a murine model following repeated short-term intratracheal instillation of UPM (40–200 mg/kg) for a month. Our results demonstrate that while UPM exposure induced robust, dose-dependent pulmonary inflammation, characterized by immune cell infiltration (CD45+, F4/80+, and Ly6G+) and upregulation of pro-inflammatory (Il-6, Il-1β, and Tnfα) and fibrotic (Col1a1 and Tgfβ1) markers, no apparent adverse effects were observed in the reproductive endpoints examined. No significant alterations were observed in maternal pregnancy outcomes, including oocyte recovery rates, fertilization competence, gestation duration, litter size, and postnatal development of pups. Furthermore, the mRNA expression of inflammatory markers in the ovaries and uteri was not detectable. Direct in vitro exposure of two-cell embryos to UPM did not interfere with preimplantation embryo development. Although benzanthracene slightly reduced the blastocyst formation rate, UPM and polycyclic aromatic hydrocarbons, major toxic components of UPM, did not severely compromise preimplantation embryo development in vitro. In conclusion, these findings suggest that marked UPM-induced pulmonary inflammation is not accompanied by substantial alterations in the female reproductive outcomes examined under short-term exposure conditions. Full article

Asthma is a chronic inflammatory airway disease strongly influenced by genetic factors. Interleukin-33 (IL-33), a key mediator of type 2 immune responses, has been implicated in airway inflammation and remodeling. However, the effects of IL-33 polymorphisms on asthma susceptibility and severity remain unclear, particularly in East Asian populations. This study investigated five IL-33 polymorphisms (rs1891385, rs16924159, rs12551256, rs1929992, and rs7044343) in relation to asthma risk and severity in Taiwanese individuals. A total of 198 asthmatic patients and 453 age- and sex-matched controls were enrolled. Genotypes were determined using PCR-RFLP. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess associations with asthma susceptibility and severity. Among the five polymorphisms, only rs1929992 was significantly associated with asthma. Compared with the TT genotype, CT and CC carriers had reduced asthma risk (OR = 0.61 and 0.51, respectively). The dominant model (CT+CC) also showed a protective effect (OR = 0.58, 95%CI = 0.40–0.82, p = 0.0032), which was supported by allelic analysis (OR = 0.70, 95%CI = 0.55–0.89, p = 0.0044). Among the five polymorphisms, rs1929992 was associated with asthma susceptibility. Under the dominant model, CT + CC carriers showed lower odds of asthma than TT carriers (OR = 0.58, 95% CI = 0.40–0.82, p = 0.0032), and the association remained significant after correction for multiple testing. Exploratory stratified analyses identified associations in the younger and male subgroups, while exploratory severity analysis suggested lower odds of more severe asthma among variant genotype carriers. These secondary findings should be considered hypothesis-generating because of the reduced subgroup sample sizes. Overall, rs1929992 was associated with asthma susceptibility in this Taiwanese population; however, independent replication and functional studies are required before its biological or clinical relevance can be established. Full article

Background: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss and is strongly driven by oxidative stress and inflammation. This study investigated the protective effects of cynarin against sodium iodate (NaIO₃)-induced retinal pigment epithelium (RPE) injury, focusing on the MAPK and NF-κB signaling pathways. Materials and Methods: Human ARPE-19 cells were exposed to NaIO₃, and cell viability was assessed by the MTT assay. Protein expression of MAPK components (p38, JNK, ERK) and the NF-κB pathway was analyzed by Western blotting, and pro-inflammatory cytokine (IL-1β, IL-6, TNF-α) mRNA expression was measured by RT-qPCR. In vivo, NaIO₃-induced retinal degeneration in C57BL/6 mice was treated with cynarin (3 or 10 mg/kg) for seven days, and retinal changes were evaluated by fundus photography, fluorescein angiography, and OCT. Results: Cynarin preserved ARPE-19 cell viability without cytotoxicity. It significantly attenuated NaIO₃-induced p38 and JNK phosphorylation, IκB degradation, and NF-κB activation while downregulating IL-1β, IL-6, and TNF-α expression. In vivo, cynarin reduced drusen-like lesions, hyperfluorescent abnormalities, and retinal thinning, and dose-dependently suppressed ocular pro-inflammatory cytokines. Conclusions: Cynarin protects against oxidative stress-induced retinal degeneration by suppressing MAPK and NF-κB inflammatory signaling, representing a promising therapeutic candidate for preventing or delaying NaIO₃-induced dry AMD-like retinal injury. Full article

Intensive yak fattening in cold alpine regions requires essential long-term high-concentration feeding, which disrupts rumen microbial homeostasis and causes inefficient digestion of nutrients. Lactobacillus may have probiotic potential for ruminants, yet its regulation of rumen function is poorly understood under high-energy diets. During a 120-day feeding experiment, 120 male Pamir yaks were allocated to four dietary treatments, with LEG and LLG serving as the primary comparison for evaluating 0.02% Lactobacillus supplementation to explore the regulatory effects of Lactobacillus supplementation on the rumen microbiota and host metabolism of yaks during a fattening process based on a concentrate feed diet via phenotypic data (body wight and nutrient digestibility) and multi-omics analyses (rumen microbial sequencing and rumen epithelial transcriptome) in a concentrate-based rearing yak model. The results showed that Lactobacillus intervention reduced OTU (Operational Taxonomic Unit) richness during the early fattening period and subsequently promoted microbial recovery through colonization resistance, which significantly enhanced microbial diversity (p < 0.05), and restructured the microbial community structure toward efficient energy utilization under high-concentrate feeding by reducing Prevotellaceae and Ruminococcaceae abundance, increasing the Bacillota/Bacteroidota ratio (p < 0.05). Concurrently, Lactobacillus enhanced the apparent digestibility of dry matter, crude protein, and fibrous components (p < 0.05). According to the transcriptomic analysis, there was an activation of signaling pathways related to IL-18 and TNF, and up-regulation of immune-and metabolism-related genes, in addition to strengthening the rumen mucosal barrier function. Multi-omics integration supported that dietary supplementation of Lactobacillus can optimize rumen fermentation, enhance nutrient digestion, and strengthen immune defense in Pamir yaks fed high-concentrate in cold seasons. These modifications demonstrate the positive effects of the Lactobacillus supplementation strategy on yak rumen health without interfering with the high-energy intensive rearing pattern. The present research presents a scientific basis for the use of targeted probiotic strategies to improve the rumen health and efficiency of alpine yak production systems. Full article

Background: Epstein–Barr virus (EBV) has long been linked to systemic lupus erythematosus (SLE), mainly through molecular mimicry, altered B-cell biology, defective antiviral immune surveillance and intermittent viral reactivation. However, the detection of EBV DNA in clinical samples does not necessarily indicate transcriptionally active infection or direct viral modulation of host pathways. Methods: Peripheral blood samples from 39 pediatric patients with SLE and 29 healthy controls were analyzed for host immune and apoptotic gene expression, including NFKB1, IL10, TLR3, BCL2, BAX and CASP3. EBV DNA was assessed in both patients and controls. In EBV DNA-positive SLE samples, the expression of EBV transcripts representative of latent, lytic and immunomodulatory programs, including LMP1, EBNA1, BZLF1, and viral IL-10, was also evaluated. Host gene expression was additionally compared between EBV DNA-positive and EBV DNA-negative patients with SLE. Results: EBV DNA was detected in 8 of 39 patients with SLE (20.5%) and in none of the 29 healthy controls (0%; Fisher’s exact test, p = 0.0171). None of the EBV DNA-positive samples showed detectable expression of LMP1, EBNA1, BZLF1 or viral IL-10. Compared with healthy controls, patients with SLE showed increased CASP3 expression that remained significant after FDR correction, whereas the reduction in IL10 expression was nominally significant only in the unadjusted analysis. NFKB1, TLR3, BCL2, and BAX did not differ significantly. In the exploratory comparison between EBV DNA-positive and EBV DNA-negative patients with SLE, no host gene remained significantly associated with EBV DNA status after false discovery rate correction. Conclusions: EBV DNA was detected more frequently in patients with SLE than in healthy controls, but this finding was not accompanied by detectable expression of the selected EBV transcripts under the analytical conditions used or by a consistent host transcriptional signature associated with EBV DNA positivity. These findings emphasize the importance of distinguishing EBV DNA detection from detectable viral transcript expression in SLE. Full article

Ankylosing spondylitis (AS) is a chronic inflammatory disease strongly associated with human leukocyte antigen B27 (HLA-B27). However, the incomplete penetrance of HLA-B27 suggests that additional molecular mechanisms contribute to AS pathogenesis. Circular RNAs (circRNAs) have emerged as important regulators of immune responses, but their roles in AS pathogenesis remain incompletely understood. In this study, circRNA expression profiles were examined by high-throughput RNA sequencing and selected circRNAs were validated by quantitative RT-PCR in T cells from AS patients and healthy controls. Among the validated circRNAs, circRNPS1 was significantly up-regulated in T cells from AS patients. Overexpression of circRNPS1 in activated Jurkat cells increased IL-2, IL-17A, and interferon-γ expression and enhanced JAK2/STAT1 and MEK1/2-ERK signaling. RNA pull-down followed by proteomic analysis identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) that binds to the back-splicing junction region of circRNPS1. CircRNPS1 increased the stability of hnRNPK and VAV1, whereas hnRNPK knockdown attenuated circRNPS1-mediated MEK1/2-ERK activation and inflammatory cytokine expression. Furthermore, an antisense RNA fragment targeting the back-splicing junction region of circRNPS1 suppressed IL-2, IL-17A, and interferon-γ expression in activated circRNPS1-overexpressing Jurkat cells and T cells from AS patients. Disrupting the interaction between circRNPS1 and hnRNPK therefore warrants further investigation as a potential therapeutic strategy for AS. 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

Background: Lycium ruthenicum, commonly known as Black goji berry, is a shrub species native to western China and is rich in bioactive compounds that contribute to its nutritional and health-promoting effects. However, the transcriptional dynamics associated with fruit development and quality formation in black goji berry remain incompletely understood. This study aimed to investigate transcriptional dynamics during fruit development and identify candidate genes associated with sugar accumulation and fruit enlargement. Methods: Fruits were sampled at five developmental stages (S1–S5), and RNA-seq was performed to investigate the alterations in gene expression. Differential expression analysis, temporal expression-pattern analysis, functional enrichment analysis, and weighted gene co-expression network analysis (WGCNA) were performed, followed by the integration of differential expression, temporal expression patterns, co-expression relationships, and functional annotation. Results: Fruit diameter, fresh weight, and total soluble sugar content increased markedly during the later developmental stages. Differential expression analysis revealed extensive transcriptional changes across successive developmental transitions, while temporal expression-pattern analysis identified distinct increasing and decreasing gene clusters. Functional enrichment analysis showed that the DEGs were mainly associated with carbohydrate metabolism, sugar transport, hormone-related processes, photosynthesis, and cell-wall modification. WGCNA identified 13 co-expression modules, among which MEyellow and MEbrown showed strong but opposite associations with developmental stage, total soluble sugar content, fruit diameter, and fruit fresh weight. The integrated analysis highlighted several candidate genes associated with sugar metabolism and transport during late fruit development. Conclusions: These findings provide a transcriptomic perspective on the coordinated changes in sugar accumulation and fruit enlargement during L. ruthenicum fruit development. Full article

The tea tree (Melaleuca alternifolia) essential oil (TTEO) exhibited in vitro antioxidant activities with an inhibition concentration (IC50) of 29.02 ± 0.57 µg/mL. This is due to its content of bioactive compounds; practically α-pinene (1.52%), eucalyptol (9.05%), 2-bornanone (57.94%), 1-dotriacontanol (1.82%), 1-decanol, 2-hexyl- (1.99%), and 1-heptatriacotanol (4.90%). Therefore, this research aimed to determine changes in growth, antioxidant capacity, immune functions, and disease resistance in Nile tilapia (Oreochromis niloticus) when fed on a low-fishmeal (FM) diet enriched with TTEO. Nile tilapia juveniles (14.6–15.9 g) were fed on a low-FM diet containing 0.0 (the control), 0.1, 0.15, 0.2, and 0.25 g TTEO/kg feed up to apparent satiety three times a day for 70 days. Following the feeding trial, fish were intraperitoneally injected with Aeromonas hydrophila, and fish mortality was recorded for an additional 10 days. It is noted that feeding the fish on 0.2 g TTEO/kg feed increased the feed intake as well as the growth indices. Marked declines in FCR values were seen in fish fed on 0.15–0.25 g TTEO/kg feed. However, fish fed on a diet with 0.2 g TTEO/kg feed exhibited highest enhancements in intestinal villi width/length and absorption area compared with other TTEO levels. No statistical (p > 0.05) differences were observed in glucose and cortisol levels among TTEO-fed groups, indicating no stress effects on fish. Conversely, ALT and AST activities in Nile tilapia declined significantly (p < 0.05), especially at 0.20 and 0.25 g TTEO/kg feed, with no difference (p > 0.05) between the two treatments. It is noted that high TTEO levels (0.2–0.25 g/kg feed) increased hepatic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities as well as the mRNA expression of hepatic SOD, CAT, and GPx genes. Compared with other TTEO groups, feeding the fish with 0.2 g TTEO/kg feed showed higher alkaline phosphatase, lysozyme, complement C3, and ACH50 levels, along with marked increases in IL-8 and IL-10 genes expression and declines in the expression TNF-α, IL-1ß, HSP70, Caspase-3, and Caspase-9 genes. After A. hydrophila infection, fish fed on the control diet exhibited the highest mortality (76.7%), whereas fish fed on 0.2 and 0.25 g TTEO/kg feed were more resistant to bacterial infection, with mortality rates of 23.3% and 26.7%, respectively, with no difference (p > 0.05) between them. The results confirmed that dietary TTEO enhanced growth, antioxidant capacity, immunological biomarkers, and disease resistance in Nile tilapia when added to low-FM diets, with an optimum dose of 0.2 g TTEO/kg feed. Full article

This manuscript presents findings from the analysis of three species of Pleurotus mushrooms common in Ile-Ife, Nigeria, detailing evaluations of proximate composition, physicochemical properties, minerals, colour, phenols, and antioxidant capacity. Standard analytical procedures were used to analyse the mushroom flour samples. Moisture content was within the range of 9.56% (P. florida) and 11.01% (P. pulmonarius), indicative of good drying practices. Protein content among the three species was high, with that of P. ostreatus showing the highest value (26.12%), and all had low fat content (3.45–3.70%). The physicochemical analysis showed pH values between 6.12 and 6.31, indicating neutral pH, and perishability was indicated by water activity values of 0.39–0.44. P. florida had significant differences (p < 0.05) in colour analysis, with the highest lightness (L* = 75.45) and colour saturation. P. florida had the highest total phenolic content (58.91 mg GAE/g) and antioxidant activity (ABTS and DPPH: 42.21 and 46.12 µmol TE/g). Of the three species, P. florida had the highest total phenol profile, at 44.10 mg/g. Gallic acid was the predominant phenol with the highest concentration of 12.82 mg/g. The study concluded that all three common mushroom species, P. ostreatus, P. florida, and P. pulmonarius, are rich in nutrients, with P. florida standing out in bioactive compounds. Full article

Hepatocellular carcinoma (HCC) is one of the malignant tumors with high incidence and mortality rates worldwide. Given the poor prognosis of patients with HCC, it is crucial to explore the molecular mechanisms underlying HCC development and to evaluate prognostic markers. Differential expression analysis followed by univariate Cox, LASSO, and multivariate Cox regression identified four genes (EPO, SOCS2, IL18RAP, and KPNA2), and a Cox-based risk score was evaluated in the TCGA-LIHC cohort and externally in GSE14520 using Kaplan–Meier and time-dependent ROC analyses. Bulk, single-cell, and protein resources provided convergent expression context. Survival machine-learning analysis using observed overall-survival time and censoring status identified Cox–Ridge as the best-performing model in TCGA-LIHC, with more modest performance in GSE14520, and immune profiling revealed risk-group-associated differences in estimated immune and stromal components, immune-cell composition, and immune-checkpoint expression. The oncoPredict/GDSC2 screen highlighted five potential drug candidates for experimental prioritization. Because the drug screen is based on computationally predicted sensitivities, these findings should be regarded as hypothesis-generating and require validation in prospective cohorts and experimental systems before clinical translation. 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