Search Results (776)

Methyl-CpG binding domain protein 3 (MBD3) is a member of the nucleosome remodeling and deacetylase (NuRD) corepressor protein complex, which plays a pivotal role in embryonic development, pluripotent stem cell (PSC) differentiation, and induced pluripotent stem cell (iPSC) reprogramming. However, whether MBD3 is also involved in iPSC differentiation into primordial germ cell-like cells (PGCLCs) is unclear. In this study, bovine iPSCs generated by MBD3 knockdown (MBD3 KD) during reprogramming were subjected to PGCLC differentiation using a monolayer cell culture method. Our results revealed that MBD3 KD enhanced the ability of bovine iPSCs to differentiate into PGCLCs. MBD3-KD bovine iPSC-derived PGCLCs exhibited the characteristics of in vivo primordial germ cells (PGCs) in a migratory state. MBD3 KD increased NODAL signal transduction during the induction of PGCLCs and was associated with increased expression of PRDM1 and SOX15. Moreover, MBD3 KD increased the bivalent modification of transforming growth factor beta (TGF-β)-related genes concomitant with the upregulation of DPPA4 and DNMT3L expression in bovine iPSCs, and this epigenetic change was associated with enhanced NODAL signaling. Our results indicate that MBD3 KD during reprogramming favors the differentiation of bovine iPSCs into PGCLCs, further highlighting the impact of MBD3 on histone modifications during germ cell development. Full article

The aim of this study was to summarize current evidence on dust-related diseases of the bronchopulmonary system, medicinal plants, herbal formulations, and their underlying mechanisms of action. A literature review was conducted based on publications indexed in ScienceDirect, Google Scholar, SciFinder, Scopus, and Medline (PubMed), focusing on the mechanisms underlying dust-related diseases of the bronchopulmonary system, pneumoconiosis, and the potential of phytotherapeutic approaches to modulate these processes. The following keywords were used: bronchopulmonary system, pneumoconiosis, dust-related lung diseases, medicinal plants, herbal preparations, pulmonary rehabilitation, and lymphatic sanitation. The pathogenesis of pneumoconiosis involves the deposition of inhaled dust particles in the lung tissue, followed by chronic inflammation, oxidative stress, and progressive fibrosis. In experimental models, flavonoids, alkaloids, terpenoids, glycosides, tannins, and other phytochemical groups have demonstrated therapeutic potential in bronchopulmonary diseases. Among the compounds investigated, emodin, celastrol, kaempferol, sodium tanshinone IIA sulfonate, astragaloside IV, and dioscin have shown promising effects by modulating key signaling pathways and reducing inflammatory responses. Experimental evidence indicates that these phytochemicals can target major pathways involved in inflammation and fibrogenesis, thereby exerting antioxidant, anti-inflammatory, and antifibrotic effects. The lymphatic system also contributes to the pathogenesis of pneumoconiosis by transporting inhaled dust particles to regional lymph nodes, where their accumulation may promote lymph node sclerosis. Therefore, lymphatic sanitation may represent an important therapeutic mechanism of action of herbal formulations in pneumoconiosis. Our proposed lymphotropic herbal formulation enhances physiological lymphatic drainage and may positively influence the motility and functional activity of the tracheobronchial lymph nodes. The therapeutic potential of medicinal plants and herbal formulations in pneumoconiosis is supported by experimental findings for Tripterygium wilfordii (celastrol, through suppression of the EDNRB/Kng1 – (endothelin receptor type B/kininogen1), Delphinium, Camellia, and Berberis species (kaempferol, through inhibition of TLR4 (Toll-like receptor 4 signaling), Astragalus membranaceus (astragaloside IV, through antifibrotic activity mediated by inhibition of the TGF-β1/Smad3 (transforming growth factor beta1)pathway), and Reynoutria japonica Houtt., Rheum, and Aloe species (emodin, through inhibition of Smad3 (Smad family member 3) and NF-κB (nuclear factor kappa B)phosphorylation and reduction of TGF-β1, α-SMA (alpha-smooth muscle actin), collagen I, TNF-α (tumor necrosis factor alpha), and IL-1β (interleukin-1 beta) levels in lung tissue). For these and several other medicinal plants and their flavonoids, antifibrotic activity has been demonstrated through inhibition of the Akt/NF-κB (protein kinase B/nuclear factor kappa B) signaling pathway. A promising direction for future research is to evaluate the combined use of herbal formulations with established antifibrotic agents to determine whether synergistic therapeutic effects can be achieved. Full article

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease driven by aberrant extracellular matrix deposition, with the activity of transforming growth factor-beta 1 (TGF-β1) orchestrating fibrogenesis. Current therapies are limited by severe adverse effects, highlighting the unmet need for safer treatments. In this study, the therapeutic potential of chlorogenic acid (CGA) in a murine model of pulmonary fibrosis was evaluated. Methods: Pathology was induced on day 0 via subcutaneous osmotic minipumps delivering bleomycin (BLM) for one week, followed by pump removal on day 10. Therapeutic interventions with intragastric CGA (60 mg/kg) were administered daily from days 14 to 20. Lung tissue samples obtained on day 21 were analyzed via histological, immunohistochemical, and RT–PCR methods. Results: Histological analysis via H&E and Masson’s trichrome staining revealed that CGA treatment significantly attenuated alveolar thickening, restored the alveolar space, and reduced the total cell density and Ashcroft fibrosis score. Furthermore, CGA markedly decreased collagen deposition. Quantitative RT–PCR and immunohistochemical assays revealed that CGA effectively decreased the expression of Col1a1, TGF-β1, and the myofibroblast marker alpha-smooth muscle actin (α-SMA). Conclusions: CGA exerts important therapeutic effects by decreasing the expression of TGF-β1 and the activation of myofibroblasts, indicating that this natural polyphenol is a promising candidate for mitigating the progression of pulmonary fibrosis. 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

Introduction: IgA nephropathy (IgAN) is a leading cause of end-stage renal disease. Given the significant adverse effects and inconsistent long-term efficacy of conventional immunosuppressive strategies, there is an unmet need for safer adjunctive therapies. Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed as potential candidates to address this therapeutic gap. Purpose: This narrative review summarizes the proposed mechanisms of action of omega-3 PUFAs in IgAN and critically evaluates the current clinical evidence regarding their therapeutic potential and limitations. Mechanisms: Emerging experimental data suggest that omega-3 PUFAs may modulate inflammatory and fibrotic pathways relevant to kidney injury. Proposed mechanisms include modulation of eicosanoid metabolism, attenuation of NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, and generation of specialized pro-resolving mediators. In experimental studies, omega-3 PUFAs may also suppress nuclear factor kappa B (NF-κB)-driven transcription and attenuate mesangial cell proliferation, IgA immune-complex deposition, and transforming growth factor beta 1 (TGF-β1)/Smad3-mediated fibrotic signaling. Clinical Evidence: Conclusions: Omega-3 PUFAs have biological plausibility as adjunctive therapy in IgAN, but their clinical benefit remains uncertain. Available randomized trials and meta-analyses suggest possible modest effects on proteinuria in some settings, whereas evidence for preservation of kidney function or prevention of kidney failure is inconsistent and of low certainty. Future well-designed trials incorporating guideline-directed background therapy and biomarker-guided patient selection are essential to determine optimal dosing, formulation, biological exposure, and whether any patient subgroups derive clinically meaningful benefit. Full article

Erythropoiesis-targeted doping remains a major challenge for sports medicine because pharmacological and genetic manipulation of erythropoiesis can improve oxygen transport and endurance performance while increasing the risk of serious cardiovascular complications. Erythropoiesis-targeting strategies extend beyond recombinant erythropoietin (EPO) to include hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), modified erythropoietin receptor (EPOR) agonists, transforming growth factor beta (TGF-β) signaling inhibitors, cytoprotective EPO derivatives, and gene- or cell-based approaches, and require complementary detection strategies based on direct analytical methods and the Athlete Biological Passport (ABP). Although they may enhance oxygen delivery and endurance performance, excessive stimulation of erythropoiesis may increase blood viscosity, impair vascular function, and elevate the risk of hypertension, thromboembolic complications, and other cardiovascular (CV) events. Erythropoiesis-targeted doping has evolved beyond recombinant EPO into a diverse group of pharmacological and genetic strategies that require increasingly sophisticated detection approaches. A thorough understanding of their molecular mechanisms and cardiovascular consequences is essential for improving anti-doping surveillance and protecting athlete health. This review summarizes current erythropoiesis-targeting agents, their mechanisms of action, detection strategies, cardiovascular risks, and implications for anti-doping practice. 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

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

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

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection remain a world health problem leading to fibrosis and cirrhosis. Liver damage is primarily mediated by the innate and adaptive immune responses since HBV and HCV are not directly cytotoxic. Kupffer cells and liver-recruited macrophages are heavily implicated in both viral elimination and progression of the disease. HBV and HCV proteins polarize macrophages into either an M1 pro-inflammatory phenotype, promoting hepatocyte damage or into an M2 immunosuppressive phenotype, leading to viral persistence and fibrogenesis via cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β). In this review a brief overview of the heterogeneity of liver macrophages in health and during chronic viral infection is presented. Recognition of viruses by macrophages and the modulation of macrophages by viral proteins in the pathogenesis of liver inflammation and injury are discussed in detail. Most importantly, the mechanisms that HBV and HCV are using to manipulate macrophages and escape elimination are also presented. The role of macrophages in the evolution of acute-on-chronic liver failure is analyzed. Finally, a concise presentation of the emerging, but not yet clinically used, therapeutic strategies targeting macrophages to control chronic HBV infection and restore the dysregulated immune response is discussed. In conclusion, this integrated review of liver macrophage implication summarizes the pathophysiology and pathogenesis of HBV and HCV including acute-on-chronic- liver failure and viral cirrhosis. Full article