Search Results (1,686)

Background: Dangguibuxue decoction (DD), containing Angelica sinensis (Oliv.) Diels (AS) and Astragalus membranaceus (Fisch.) Bge. (AM) (1:5), is a well-known traditional Chinese medicine (TCM) used for strengthening qi and nourishing the blood. DD has shown therapeutic effects in nephropathy patients. However, the underlying mechanisms based on the traditional efficacy are still not fully elucidated. Methods: The chemical constituents in DD were identified using UPLC-MS/MS. Network pharmacology analysis was applied to predict the potential target genes and associated signaling pathways. A renal fibrosis mouse model was induced by the intraperitoneal injection of aristolochic acid I (AA I) at 3.0 mg/kg. Mice were treated with AM, AS, and DD at two dosages by oral gavage for 30 days. Body weights, serum biochemistry, hematology, and histopathology observations were assessed. The key targets predicted were validated using qRT-PCR and Western blotting. The active constituents were screened by molecular docking, and their anti-fibrotic effects were evaluated through in vitro assays. Results: DD effectively improved renal functions and alleviated AA I-induced renal fibrosis. DD alleviated anemia and upregulated the expression of Erythropoietin (EPO). Network pharmacology analysis indicated the involvement of signaling pathways, including the PI3K/Akt, hypoxia-inducible factor-1α (HIF-1α) and transforming growth factor-β (TGF-β) signaling pathways. Experimental validation further demonstrated that DD reduced the protein expression of HIF-1α, collagen I, and TGF-β, and the ratios of phosphorylated Smad2/3 to total Smad2/3. Molecular docking and in vitro assays suggested that rutin may be a potential bioactive compound in DD. Conclusions: This research indicated that DD ameliorated AA I-induced renal fibrosis in mice, which may be associated with the modulation of HIF-1α and TGF-β/Smad signaling pathways. Rutin may be a potential bioactive compound in DD with anti-fibrotic activity, but further studies are still needed to clarify the content of rutin in DD, the amount of its exposure in the body, and its contribution to the effects of DD. Full article

Background/Objectives: Isorhamnetin is a naturally occurring flavonoid with reported antioxidant, anti-inflammatory, and anticancer properties. Although its biological activities have been extensively investigated, its effects on ovarian cell physiology remain insufficiently characterized. This study aimed to evaluate the influence of isorhamnetin on the viability, steroid hormone secretion, apoptosis, and growth factor signalling in human ovarian cell lines representing both non-tumour and tumour phenotypes. Methods: Human granulosa (HGL5), granulosa tumour (COV434), and epithelial ovarian carcinoma (OVCAR-3) cell lines were treated with isorhamnetin at concentrations of 5–80 μg/mL for 24 h. Cell viability was determined using the AlamarBlue^TM assay. The secretion of progesterone, 17β-estradiol, and the presence of transforming growth factor β2 (TGF-β2), transforming growth factor β receptor 2 (TGFBR2), and apoptosis-inducing factor (AIF) was quantified by enzyme-linked immunosorbent assay (ELISA). Results: Isorhamnetin significantly reduced cell viability in a dose-dependent manner, with tumour cell lines exhibiting greater sensitivity than non-tumour granulosa cells. A significant decrease in viability was observed in OVCAR-3 cells from 10 μg/mL onward, whereas COV434 cells showed significant reductions at concentrations of 20 μg/mL and higher. In contrast, HGL5 cell viability was significantly affected only at the highest concentration (80 μg/mL). No significant changes were detected in the secretion of progesterone, 17β-estradiol, TGF-β2, or TGFBR2 in any of the examined cell lines. A significant reduction in AIF production was observed only in HGL5 cells treated with 80 μg/mL isorhamnetin. Conclusions: Isorhamnetin preferentially decreased the viability of ovarian tumour cells while exerting only limited effects on non-tumour granulosa cells, indicating preferential cytotoxic activity toward malignant ovarian cells. The absence of significant changes in steroid hormone production and TGF-β suggests that its antiproliferative effects involve molecular pathways that were not investigated in the present study. These findings support further investigation of isorhamnetin as a potential natural compound for ovarian cancer prevention or adjunctive therapy. Full article

Decorin, a proteoglycan shown to inhibit transforming growth factor β1 (TGF-β1) signaling, has been increasingly considered as a potential anti-fibrotic agent to aid in therapies addressing corneal scarring and blindness. Decorin is also known to interact with a wide range of other growth factors, such as platelet-derived growth factor (PDGF), which has been shown to stimulate corneal cell migration to repopulate the decellularized region of the wounded cornea. In other tissues, decorin has been shown to inhibit PDGF-mediated migration and prolong wound healing. However, our understanding of the effect of decorin on PDGF signaling in the corneal stroma environment is limited. Specifically, thus far, there have been no studies investigating the interaction between decorin and PDGF in the context of the uniquely organized fibrillar collagen extracellular matrix (ECM), which provides topographic cues that guide cell migration during wound healing. The purpose of this study is to use an in vitro model of decorin-coated aligned collagen fibrils analogous to the corneal stroma ECM to investigate this interaction. With this in vitro model, we demonstrate that decorin inhibits the response of PDGF-BB-stimulated keratocytes to a 2-dimensional (2D) aligned collagen fibril ECM, reducing cell alignment, motility, PDGF receptor β (PDGFRβ) phosphorylation, and wound closure. We observed that when presented with a decellularized wound region, cells on the decorin-coated substrates migrated more randomly and were less aligned with the underlying aligned collagen fibrils than cells on uncoated fibrils, resulting in slower wound closure. Furthermore, PDGF-BB-stimulated cells on the decorin coating had increased branching and reduced solidity, representing a shift from the elongated, bipolar morphology typically resulting from PDGF-BB treatment towards the stellate, branched keratocyte phenotype. While decorin seems to be an effective agent against TGF-β1-mediated fibrosis, its interaction with PDGF-BB appears to present other challenges to wound healing that should be considered in the development of therapies for healthy corneal wound healing. Full article

Sickle cell disease (SCD) is a globally distributed hereditary red cell disorder with still high mortality. Growing evidence indicates that sickle cell related cardiovascular disease contributes to the early death of adults with SCD. Here, we show that humanized SCD mice developed an age-dependent cardiomyopathy characterized by (i) increased circulating Th17 lymphocytes, Th17 heart infiltration associated with increased plasma IL-17; (ii) collagen deposition and activation of both platelet derived growth factor-B (PDGF-B) and transforming growth factor-β1 (TGF-β1) canonical pathways; (iii) overactivation of heart NF-κB associated with up-regulation of NLRP3 and of inflammatory vasculopathy markers. We then used colchicine (CLC) that acts as anti-inflammatory drug with immunomodulatory effects. In humanized SCD mice, we demonstrated the protective role of low-dose CLC treatment against chronic inflammation and preserving myocardial performance. Of note, we found CLC also attenuating sickle cell related lung damage, suggesting a multiorgan effect of CLC in SCD mice. Our data generate the rationale to further explore CLC as new therapeutic tool to treat early stages of sickle cell cardiomyopathy. Full article

Background: The role of cerebrospinal fluid (CSF) transforming growth factor β (TGF-β) isoforms in Alzheimer’s disease (AD) remains unclear. We examined associations of CSF TGF-β1, TGF-β2, and TGF-β3 with AD biomarkers, neurodegeneration, cognition, and clinical progression. Methods: In 294 ADNI participants with baseline CSF TGF-β measurements, adjusted regression, and mixed-effect models were used to evaluate associations with CSF biomarkers, neuroimaging, cognitive outcomes, and conversion. False-discovery-rate correction was applied. Results: Higher baseline TGF-β1 was associated with higher CSF total tau (β = 52.68 pg/mL per 1 SD increase; q < 0.001) and p-tau (β = 5.68 pg/mL; q < 0.001). Higher TGF-β2 was associated with faster hippocampal volume loss (β = −45.42 mm³/year; q < 0.001). No isoform was robustly associated with FDG-PET decline, cognitive decline, clinical conversion, or time to conversion. Conclusions: CSF TGF-β1 and TGF-β2 show distinct associations with tau-related pathology and hippocampal neurodegeneration, respectively, but do not appear to be prognostic biomarkers of clinical progression in AD. Full article

Objective: The purpose of this study is to study cytokine indicators for the identification of severe fever with thrombocytopenia syndrome (SFTS) severity. Methods: We searched the literature in PubMed, Embase, and Web of Science published before 7 April 2026. The main results are presented as forest plots. Subgroup analyses, sensitivity analyses, and publication bias were also performed. Results: A total of 22 articles were eventually included in our study. Our findings demonstrate that circulating concentrations of Interleukin-6 (IL-6) (SMD = 2.02, 95% CI: 1.53–2.51, I² = 95.2%), Interleukin-10 (IL-10) (SMD = 1.18, 95% CI: 0.92–1.44, I² = 71.3%), Interleukin-8 (IL-8) (SMD = 0.91, 95% CI: 0.61–1.20, I² = 69%), Tumor necrosis factor-alpha (TNF-α) (SMD = 0.70, 95% CI: 0.43–0.96, I² = 64.6%), Interferon-gamma (IFN-γ) (SMD = 1.32, 95% CI: 0.69–1.95, I² = 89.1%), Interleukin-1 beta (IL-1β) (SMD = 1.78, 95% CI: 0.85–2.71, I² = 94.8%), Monocyte chemoattractant protein-1 (MCP-1) (SMD = 1.15, 95% CI: 0.80–1.50, I² = 46.1%), Interferon-alpha (IFN-α) (SMD = 1.53, 95% CI: 0.38–2.68, I² = 89.6%), Granulocyte Colony-Stimulating Factor (G-CSF) (SMD = 1.79, 95% CI: 0.99–2.59, I² = 68.1%) and Inducible protein 10 (IP-10) (SMD = 1.11, 95% CI: 0.60–1.62, I² = 58.3%) are significantly elevated in patients with severe SFTS compared with those with mild disease, whereas Transforming Growth Factor-beta (TGF-β) (SMD = −0.51, 95% CI: −0.78–−0.24, I² = 6.0%) and RANTES (SMD = −0.10, 95% CI: −0.40–0.20, I² = 0.0%) levels are reduced in the severe group. Conclusions: By analyzing the cytokine indicators of SFTS patients, we have found some indicators that are representative of SFTS severity. Our findings provide a clinically actionable basis for early severity prediction and further useful evidence for clinicians to manage severe patients efficiently. Full article

Background/Objectives: Silicosis is a progressive occupational lung disease characterized by persistent inflammation and irreversible pulmonary fibrosis. Reliable circulating biomarkers for the early detection of fibrotic remodeling and monitoring of disease progression remain limited. Prolidase, a key enzyme involved in collagen turnover and extracellular matrix remodeling, has emerged as a potential biomarker in fibrotic disorders. Therefore, this study aimed to evaluate the potential role of serum prolidase as a biomarker for fibrotic remodeling and treatment monitoring in an experimental rat model of silicosis. Methods: Male Wistar rats were divided into three groups: control, silicosis, and silicosis plus nintedanib. Silicosis was induced by intratracheal crystalline silica instillation. Nintedanib was administered by gastric gavage at 50 mg/kg/day from day 10 to day 30. Lung tissues were evaluated histopathologically using hematoxylin and eosin and Masson’s trichrome staining. Serum prolidase, fibroblast growth factor-2 (FGF-2), platelet-derived growth factor (PDGF), and transforming growth factor-beta (TGF-β) levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: Histopathological injury scores were significantly increased in the silicosis group and were attenuated by nintedanib treatment. Serum prolidase levels were significantly higher in both silica-exposed groups than in controls (p = 0.017), but did not differ significantly between untreated and nintedanib-treated animals. TGF-β, FGF-2, and PDGF levels were also significantly elevated following silica exposure. Serum prolidase showed a strong positive correlation with TGF-β (r = 0.69, p < 0.001). ROC analysis demonstrated good diagnostic performance for prolidase (AUC = 0.877), while the combined Prolidase + TGF-β model further improved discrimination (AUC = 0.969). The internally validated multivariable biomarker panel maintained high diagnostic accuracy after leave-one-out cross-validation (LOOCV) (AUC = 0.892). Conclusions: Serum prolidase may serve as a potential circulating biomarker of silica-associated fibrotic remodeling. Although nintedanib improved histopathological lung injury, persistently elevated prolidase levels suggest ongoing extracellular matrix remodeling rather than short-term treatment response. Further longitudinal experimental and clinical studies are warranted to validate its diagnostic and prognostic utility. Full article

Background/Objectives: Pulmonary fibrosis is a progressive and fatal disease characterized by excessive extracellular matrix deposition and irreversible lung remodeling. Although modified mRNA (modRNA) therapeutics offer a promising strategy for regulating disease-driving pathways, effective pulmonary delivery remains challenging due to the inherent liver tropism of conventional lipid nanoparticles (LNPs). This study aimed to establish an optimized platform for lung-selective modRNA delivery and therapeutic screening for pulmonary fibrosis. Methods: A panel of charge-modified LNP formulations was evaluated in vivo for pulmonary tropism following systemic administration of luciferase (Luc) modRNA. Administration routes, biodistribution in healthy and bleomycin (BLM)-induced fibrotic lungs, and endogenous microRNA (miRNA)-mediated de-targeting strategies were assessed. Candidate antifibrotic modRNAs targeting the transforming growth factor-beta (TGF-β) signaling pathway were subsequently evaluated in normal human lung fibroblasts (NHLFs). Results: Among the formulations tested, 50% DOTAP MC3 LNPs demonstrated the most favorable balance of pulmonary transfection, physicochemical properties, and limited off-target expression. Intravenous (IV) administration achieved robust lung expression with a superior safety profile compared with intratracheal (IT) delivery. Importantly, pulmonary biodistribution was preserved in BLM-induced fibrotic lungs despite extensive tissue remodeling. Incorporation of miR-122 recognition sites further enhanced selectivity, resulting in 94.5% of total transgene expression being localized to the lungs while substantially reducing residual hepatic expression. In vitro screening identified dominant-negative TGF-β receptor II (DNTGFBR2) modRNA as a potent inhibitor of TGF-β-induced fibrotic activation, significantly suppressing α-SMA and CTGF expression. Conclusions: These findings establish a comprehensive platform for pulmonary modRNA therapeutic development by integrating lung-selective LNP engineering, optimal systemic delivery, miRNA-mediated de-targeting, and therapeutic payload screening. This strategy provides a foundation for the development of targeted RNA therapies for pulmonary fibrosis and other organ-specific diseases. Full article

A novel low-molecular-weight water-soluble oligosaccharide fraction (LBPP-1) was prepared from lotus bee pollen via microwave-assisted extraction, followed by Sevag deproteinization and diethylaminoethyl (DEAE)-cellulose-52 chromatography purification. Ion chromatography (IC) indicated a glucose-rich composition (84.6 mol% glucose), with minor amounts of arabinose, glucosamine, and galactose. Fourier transform-infrared spectroscopy (FT-IR), methylation analysis, and ¹H nuclear magnetic resonance (NMR) collectively supported the assignment of LBPP-1 as a glucan-rich, structurally heterogeneous oligosaccharide fraction containing candidate →4)-Glcp-rich domains and minor arabinose/galactose-related linkages. However, the marked difference between the IC composition and the sugar-type distribution estimated from PMAA peak areas limits quantitative interpretation of the residue proportions and branching architecture. Furthermore, in vitro biological assays demonstrated that LBPP-1 significantly attenuated lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophages. It effectively reduced the secretion of nitric oxide (NO) and the levels of inducible nitric oxide synthase (iNOS), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in RAW264.7 macrophages. Reverse transcription–quantitative polymerase chain reaction (RT-qPCR) analysis further revealed that LBPP-1 selectively suppressed the mRNA expression of cyclooxygenase-2 (COX-2), IL-1β, IL-6, iNOS, and transforming growth factor (TGF)-β1. These findings collectively suggest that LBPP-1, as a bioactive carbohydrate fraction derived from lotus bee pollen, holds promise as a natural functional food ingredient for managing inflammation-related conditions. Full article

Background: Gestational iron requirements may lead to maternal iron deficiency, increasing susceptibility in offspring. In mice, maternal iron deficiency induces hair loss in pups, but mechanisms remain poorly characterized. Objective: This study investigates mechanisms underlying maternal iron deficiency-induced abnormal hair growth and the impact of iron supplementation on pups’ hair development. Methods: Pregnant C57BL/6J mice (nine-week-old, second week of gestation) were randomly assigned to a standard AIN-76 diet (control, CTRL) or an iron-deficient AIN diet (ID) until parturition and weaning. Offspring were maintained on the same diet as their mothers. At six weeks, hair loss was examined in one set (CTRL1 and ID), while the remaining were transitioned to an iron-replete AIN-76 diet (CTRL2 and IDN) for two additional weeks. An in vitro study with human follicle dermal papilla cells (HFDPC) via deferoxamine (DFO) treatment was performed. Results: ID offspring exhibited truncal hairlessness, reduced body size, and abnormal follicular morphology compared to CTRL1, while IDN demonstrated hair regrowth comparable to CTRL2. ID skin tissues had reduced Wnt/β-catenin signaling, elevated oxidative stress markers, and activation of caspase-3, nuclear factor kappa B (NF-κB), and transforming growth factor-beta (TGF-β) signaling, all reversed by iron supplementation. DFO-treated HFDPCs demonstrated increased cellular and mitochondrial reactive oxygen species (ROS), diminished Wnt/β-catenin signaling, activation of caspase-3, NF-κB, and TGF-β signaling pathways. N-acetylcysteine pretreatment abrogated DFO-induced alterations in Wnt/β-catenin signaling and apoptosis, suggesting ROS mediates iron deficiency-induced hair loss. Conclusions: Early iron deficiency may have impaired hair growth through increased ROS production, reduced Wnt/β-catenin signaling, and enhanced apoptotic signals, while postnatal iron supplementation could reverse these abnormalities. Full article

Platelet-rich plasma (PRP) is widely utilized for skin rejuvenation and tissue regeneration; however, its biological effects vary according to leukocyte content and molecular composition. We investigated the mechanism by which leukocyte-rich PRP (L-PRP) enhances extracellular matrix (ECM) regeneration in aged skin, focusing on the CCL1-CCR8/pyruvate kinase M2 (PKM2) signaling axis. First, we demonstrated that L-PRP contains significantly higher levels of CCL1 than platelet-poor plasma (PPP). In senescent human dermal fibroblasts, L-PRP increased CCL1-CCR8 interactions in a manner linked to enhanced formation and nuclear translocation of PKM2 dimers. This enhancement was accompanied by Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway activation and the upregulation of STAT3-dependent anti-apoptotic proteins (Bcl-2, Bcl-xL) and proliferative markers (Cyclin D1), resulting in increased fibroblast proliferation. Furthermore, L-PRP increased PKM2 tetramer levels, promoted PKM2-SMAD7 binding, and reduced SMAD7-mediated inhibition of transforming growth factor (TGF)-β signaling, leading to enhanced SMAD2/3 activation. These molecular events augmented the synthesis of collagen types I and III in senescent fibroblasts. In aged mice, intradermal L-PRP injections elicited dose-dependent increases in fibroblast proliferation, collagen fiber deposition, and skin elasticity. Nuclear PKM2 dimer/STAT3 signaling and PKM2 tetramer/TGF-β signaling were both more strongly activated in the L-PRP group. Our findings identify PKM2 as a central metabolic and signaling integrator linking immune-derived chemokines to fibroblast rejuvenation. This study provides mechanistic insights concerning how L-PRP promotes ECM regeneration in aged skin via coordinated regulation of fibroblast survival, proliferation, and collagen synthesis. Full article

Transforming Growth Factor-beta (TGF-β) promotes lens epithelial–mesenchymal transition (EMT) and fibrosis, contributing to anterior subcapsular cataract (ASC) formation. Transgenic mice overexpressing TGF-β1 in the lens have been studied for over three decades, and yet the impact of active TGF-β1-overexpression on the lens epithelial transcriptome is undefined. We have addressed this knowledge gap by examining the gene expression landscape of these unique lens epithelia. High-throughput RNA-sequencing was performed on isolated lens epithelia from three-week-old TGF-β1-overexpression transgenic mice from two independent lines, OVE853 and OVE918, and wild-type mice. Downstream analyses included comparisons with lens datasets (e.g., cataract surgery model) and investigations using various resources/tools (e.g., Gene Ontology, CompBio, and iSyTE). Compared to wild-type murine lens epithelia, 384 differentially expressed genes (DEGs) were commonly identified in the lens of both transgenic lines. Candidates involved in EMT, inflammatory response, extracellular matrix organization, and mechano-sensation were elevated, while those involved in lipid metabolism, Wnt-suppression, Bmp- and Notch-activation were reduced. Comparative analyses with temporal transcriptomes on a mouse cataract surgery model identified overlapping pathological pathways, and some elevated genes, for example, endoplasmic reticulum stress genes, were consistent with human ASC data. This study provides the first comprehensive transcriptomic characterization of two independent TGF-β1 transgenic ASC models and identifies novel candidate downstream genes and pathways associated with TGF-β1 overexpression. All our data is made user-friendly and accessible through iSyTE. Full article

Pancreatic adenocarcinoma upregulated factor (PAUF), a novel secreted protein highly expressed in pancreatic ductal adenocarcinoma, also influences cell invasiveness, motility, and proliferation in several cancer types. Transforming growth factor-beta (TGF-β)-induced PAUF expression enhances cancer cell migration and invasion in pancreatic ductal adenocarcinoma through mitogen-activated protein kinase (MEK)–extracellular signal-regulated kinase (ERK) activation; however, the roles of PAUF in regulating epithelial–mesenchymal transition (EMT) and promoting lung metastasis in hepatocellular carcinoma (HCC) remain unclear. Thus, we investigated the regulatory mechanisms and functional roles of TGF-β-induced PAUF expression in the HCC cell lines HepG2 and Huh-7, which showed high and low expression of intact TGF-β type I and II receptors, respectively. We found that TGF-β-induced PAUF expression is mediated through the activation of the TGF-β type I/II receptor–Smads signaling pathway and that PAUF promotes EMT-associated migration and invasion by stimulating the MEK–ERK signaling cascade. In vivo studies further demonstrated that PAUF plays a critical role in lung metastatic potential, as PAUF knockdown HepG2 cells exhibited markedly reduced pulmonary metastasis, whereas PAUF-overexpressing Huh-7 cells showed substantially enhanced lung metastasis. This study identifies PAUF as a critical promoter of lung metastatic potential in HCC cells and a potential therapeutic target for HCC. Full article

Epithelial–mesenchymal transition (EMT) emerged as a phenotypic change associated with the resistance to epidermal growth factor receptor tyrosine kinase inhibitors, both in vitro and in vivo. The mechanisms underlying this biological process have not yet been fully understood. E-cadherin loss, N-cadherin, and vimentin increase are the main markers characterizing EMT, together with the expression of some transcription factors, such as Snail, Slug, Zeb1, Zeb2, and Twist. In this study, we explore the expression of these markers in lung cancer cell lines bearing wild-type or mutated epidermal growth factor receptor (EGFR), A549 and PC9, respectively. We treated PC9 cells with Gefitinib or Osimetinib, alone or combined with the transforming growth factor beta (TGF-β). We evaluated the expression of E-cadherin, N-cadherin, vimentin, and the transcription factors at 24 and 96 h timepoints, to verify the role of EMT in the early phases of the treatment with tyrosine kinase inhibitors (TKIs). At the 96 h timepoint, we found that in PC9 cells, the treatment with gefitinib or osimertinib, regardless of TGF-β, induces E-cadherin reduction and N-cadherin increase, similar to the effects induced by TGF-β in A549 cells at 24 h. Among the transcription factors, at 96 h, Slug mainly increases when PC9 cells are treated with gefitinib or osimertinib. These results imply that changes in the expression of these epithelial–mesenchymal transition markers may have facilitated the development of drug resistance. Full article

Despite reducing hernia recurrence, synthetic meshes often trigger persistent foreign body responses (FBRs). Mesh-enriched therapies (METs), incorporating autologous cellular components (MSCs, PRP, SVF), can regeneratively reprogram the host-prosthetic interactome. Following PRISMA-ScR guidelines, this scoping review involved a systematic search of PubMed, Embase, and Scopus (2000–2025). We utilized the PCC (Population, Concept, Context) framework to map evidence across systemic inflammation, local FBR, and bio-augmentation strategies. A total of sixty-five studies were synthesized and categorized into three primary thematic pillars. Regarding the Systemic Response (n = 25), the data established a predictable “foreign body signature” characterized by prominent C-reactive protein (CRP) and interleukin-6 (IL-6) spikes within the first 48 h post-implantation. For the Local Foreign Body Reaction (FBR, n = 19), human explant data extending up to 180 months revealed a perpetual, immune-mediated state driven by matrix metalloproteinase-2 (MMP-2) matrix remodeling and the development of “bridging fibrosis.” Finally, concerning Mesh-Enriched Therapy (MET) Integration (n = 21), biological enrichment successfully shifted the M1/M2 macrophage ratio toward a pro-regenerative, CD163+/CD206+ phenotype. While MET consistently enhanced vascular endothelial growth factor (VEGF)-driven angiogenesis and optimized the Collagen I/III ratio, a notable 22.2% discrepancy rate across the literature underscores the critical need for precise transforming growth factor-beta 1 (TGF-β1) dosing and release kinetics to prevent hyper-fibrosis. MET shifts hernia repair from passive mechanical reinforcement to active “biocamouflage” and integration. By modulating the Th1/Th2 rheostat, enriched therapies mitigate chronic inflammation and long-term complications. Standardized clinical trials are essential to optimize the therapeutic window for hybrid integration. Full article