Search Results (255)

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 (transforming growth factor beta 1)/Smad3 (SMAD family member 3) pathway), and Reynoutria japonica Houtt., Rheum, and Aloe species (emodin, through inhibition of Smad3 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

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

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

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

The transforming growth factor-beta (TGF-β) superfamily regulates diverse biological processes, including proliferation, differentiation, apoptosis, tissue remodeling, and reproductive signaling across metazoans. Here, we performed a genome-wide characterization of the TGF-β gene family in donkey (Equus asinus, ASM1607732v2) using comparative genomics and bioinformatics analyses, with horse (Equus caballus, EquCab3.0) as a reference to investigate evolutionary conservation and functional divergence. Genome assemblies and proteomes were retrieved from NCBI, and TGF-β genes were identified using BLASTp and HMMER searches (Pfam PF00019), followed by phylogenetic, conserved motif, synteny, Ka/Ks, mutation prediction, subcellular localization, and tissue-specific expression analyses. We identified 40 TGF-β genes in donkeys, exceeding the numbers reported in several mammals, suggesting possible lineage-specific expansion or differential gene retention within Equidae. Phylogenetic and motif analyses demonstrated strong evolutionary conservation across the two principal clades (TGF-β-like and BMP-like). Four segmental duplications were identified, with Ka/Ks ratios ranging from 0.28 to 0.43, indicating strong purifying selection on duplicated genes. Synteny analysis revealed extensive collinearity with the horse genome, supporting conserved equid genomic architecture. Comparative sequence analysis identified 160 amino acid variants, including 11 predicted deleterious mutations in key genes (GDF6, GDF9, GDF10, BMP15, and RGMA), suggesting potential functional divergence associated with reproductive and developmental pathways. Importantly, transcriptomic validation using publicly available donkey RNA-seq tissue expression data (NCBI BioProject: PRJNA1017964) revealed distinct tissue-specific expression patterns, with reproductive tissues (ovary and uterus) displaying enriched expression of TGF-β/BMP signaling components, particularly TGFBR1, TGFBR2, TGFB1, BMP2, BMP4, and BMP7, while canonical fecundity genes (GDF9 and BMP15) exhibited ovary-associated expression. This receptor-dominant signaling profile may have a coordinated TGF-β regulatory network underlying folliculogenesis, reproductive tissue remodeling, and fertility-related processes in donkeys. Subcellular localization predictions showed that most proteins (22/40) were extracellularly localized, consistent with conserved signaling functions. Together, this study provides the first integrated genomic and tissue-expression atlas of the donkey TGF-β superfamily, offering new insights into equid-specific evolutionary conservation, reproductive signaling, and functional divergence. Full article

Atherosclerosis (AS) is the primary underlying cause of cardiovascular and cerebrovascular diseases. The occurrence and development of AS are closely related to lipid deposition, chronic inflammation, phenotypic modulation of vascular smooth muscle cells (VSMCs), and extracellular matrix (ECM) remodeling. Numerous studies indicate that low-density lipoprotein receptor-associated protein 1 (LRP1), as a multifunctional receptor, contributes to vascular homeostasis in AS and vascular remodeling by regulating lipid handling, inflammatory responses, transforming growth factor beta (TGFβ) signaling, and platelet-derived growth factor receptor beta (PDGFRβ) trafficking. Rather than treating the LRP1-TGFβ-PDGFRβ relationship as a fully established linear pathway, this review distinguishes demonstrated mechanisms from inferred cross-talk and proposes an integrated, cell- and stage-dependent regulatory model. This article systematically elaborates on the structure and function of LRP1; LRP1-mediated regulation of TGFβ and PDGFRβ in AS and vascular remodeling; the possible relationship among LRP1, TGFβ, and PDGFRβ; and cell-specific effects in VSMCs, macrophages, endothelial cells, and pericytes. Meanwhile, this article summarizes potential translational strategies such as lipid-lowering, anti-inflammatory therapy, PDGFRβ inhibitor repositioning, TGFβ pathway modulation, biomarker-based stratification, and LRP1-targeted delivery. A deeper understanding of the cell-specificity and stage-dependence of the LRP1-TGFβ-PDGFRβ signaling network may help elucidate the progression mechanism of AS and provide new ideas for risk stratification and precise intervention. Full article

Sudden cardiac death (SCD) in athletes often represents the first manifestation of an underlying inherited cardiovascular disorder exposed by adrenergic stress, altered calcium cycling, mechanical loading, and metabolic demand during intense exercise. This review focuses on the molecular architecture that links genotype to arrhythmogenic phenotype in athletes, emphasizing sarcomeric force generation and energetic inefficiency in hypertrophic cardiomyopathy, desmosomal failure and Hippo/Wnt/transforming growth factor-beta (TGF-β) signaling in arrhythmogenic cardiomyopathy, and ion-channel and calcium/calmodulin-dependent protein kinase II (CaMKII)calcium handling abnormalities in inherited channelopathies. This review further examines how exercise-induced physiological remodeling intersects with these pathways through insulin-like growth factor-1 (IGF-1)/phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) signaling, mitochondrial biogenesis, oxidative stress, inflammatory signaling, and epigenetic regulation. Attention is given to the molecular basis of genotype-positive/phenotype-negative states, variable penetrance, and exercise-mediated disease expression. Finally, the integration of molecular biology with genomic data, polygenic risk, and emerging digital phenotyping is discussed to refine mechanism-based risk stratification and identify future therapeutic targets for prevention of SCD in athletes. Full article

Circulating sex hormone-binding globulin (SHBG) concentrations are lower in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), reflecting its potential role in metabolic liver dysfunction. Our prior studies demonstrated that SHBG can attenuate MASLD by limiting hepatic lipid deposition, partly through suppression of lipogenic pathways, in both cellular and animal models. In the present work, we have examined whether SHBG could protect against development of liver fibrosis. For this purpose, in vitro and in vivo studies were performed. In vitro, we used co-cultures of human hepatocellular carcinoma cell line (HepG2) and human hepatic stellate cell line (LX-2) cells transfected using an SHBG expression vector vs. vehicle and treated with transforming growth factor beta 1 (TGF-β1). For in vivo studies we used wild-type and human SHBG transgenic mice developing liver fibrosis induced by carbon tetrachloride (CCl₄). Our results clearly showed that SHBG overexpression reduced the TGF-β1-induced expression in collagen in LX-2 cells. Moreover, SHBG overexpression reduced the CCl₄ induced liver fibrosis in both male and female mice. Histological examination revealed that SHBG transgenic mice had reduced NAS score and decreased collagen accumulation, assessed by Sirious Red staining. In addition, human SHBG transgenic mice treated with CCl₄ exhibited lower collagen 1A1 (Col1A1) protein levels when compared with wild-type CCl₄ treated mice. Mechanistically, SHBG attenuated fibrosis primarily through modulation of the TGF-β1/matrix metalloproteinases (MMPs)/tissue inhibitor metalloproteinases 1 (TIMP1) axis, characterized by reduced TGF-β1 levels, increased metalloprotease activity, and decreased TIMP1 levels compared with wild-type CCl₄ treated mice. Notably, female SHBG transgenic mice exhibited greater protection against fibrosis than males, indicating a sex-dependent effect likely mediated by differences in sex steroid signaling. Taken together, we demonstrate for the first time that SHBG protects against liver fibrosis by promoting collagen degradation via the TGF-β1/MMPs/TIMP1 pathway. Further research is needed to elucidate the role of sex steroids in the regulation of MMPs and the observed sexual dimorphism. Full article

Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes involved in extracellular matrix remodelling in oral and dental tissues, including the periodontal ligament, alveolar bone, dentin, dental pulp, and periapical tissues. This narrative review summarises selected evidence on the role of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in orthodontic tooth movement, dental trauma and root resorption, restorative adhesive dentistry, and pulp/periapical disease. Particular attention is given to signalling pathways that regulate MMP/TIMP activity, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), Wnt/β-catenin, and transforming growth factor beta (TGF-β)/Smad-related mechanisms. The review also discusses the biomarker potential and translational status of MMP-targeted strategies. Across clinical contexts, MMP activity contributes to both matrix degradation and tissue repair, and its biological effect depends on local stimuli, TIMP-mediated regulation, pathway crosstalk, and the stage of disease or treatment. Full article

Crohn’s disease (CD) is a chronic immune-mediated inflammatory disorder characterized by transmural inflammation and a progressive course that frequently leads to structural complications such as intestinal fibrosis. Fibrostenosing disease represents a major clinical challenge, affecting up to 50% of patients over time and often requiring surgical intervention. Despite advances in anti-inflammatory therapies, no effective treatments currently exist to prevent or reverse established fibrosis. Intestinal fibrosis arises from a dysregulated tissue remodeling process driven by excessive extracellular matrix deposition and persistent activation of mesenchymal cells, particularly fibroblasts and myofibroblasts. This process is orchestrated through complex interactions between immune and non-immune cells and mediated by key signaling pathways, including transforming growth factor beta (TGF-β1) and the TL1A/DR3 axis. Genetic susceptibility, notably variants in NOD2 and other fibrosis-related genes, contributes not only to disease risk but also to phenotype progression. Epigenetic mechanisms, particularly microRNAs such as the miR-29 and miR-200 families, further modulate fibrogenesis and represent promising non-invasive biomarkers. Additionally, intestinal dysbiosis and specific microbial signatures, including reduced short-chain fatty acid-producing bacteria and the presence of adherent-invasive Escherichia coli, play a critical role in promoting fibrotic pathways. Mesenteric adipose tissue, especially creeping fat, also contributes to fibrosis through immune and metabolic signaling. Emerging biomarkers related to collagen metabolism and advances in molecular profiling are improving early detection strategies. Novel therapeutic approaches targeting fibrogenic pathways, including anti-TL1A agents, show promising preliminary results. A deeper understanding of these mechanisms is essential to develop effective antifibrotic therapies and improve long-term outcomes in CD. Full article

Pyrrolizidine alkaloids (PAs), a category of naturally occurring secondary metabolites, are commonly found in various botanical sources. Accumulating evidence indicates that PAs and their biologically active metabolites can interact with cellular components and trigger a variety of toxic effects in animals and humans. Notably, PAs exhibit significant hepatotoxic potential via nutritional supplements, environmental dissemination, food chain contamination, and broader ecological pollution. In this review, we summarize PA-induced hepatotoxicity in humans and animals and the underlying molecular mechanisms. It involves oxidative stress, mitochondrial dysfunction, apoptosis, ER stress, inflammation, autophagy, and ferroptosis. Several key signaling pathways, such as nuclear factor-erythroid 2 related factor 2 (Nrf2), mitogen-activated protein kinase (MAPK), protein kinase RNA-like endoplasmic reticulum kinase (PERK), toll like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB), transforming growth factor beta (TGF-β), p53, farnesoid X receptor (FXR), and pregnane X receptor (PXR), are also implicated. Furthermore, this review discusses diagnostic approaches, metabolic activation pathways, and detoxification strategies targeting PA-induced liver injury. Collectively, this review provides a comprehensive understanding of the molecular basis of PA hepatotoxicity and underscores the urgent need for improved risk assessment, early diagnosis, and effective detoxification interventions to mitigate PA-related liver diseases in humans and animals. Full article

2,3′,4,4′,5-Pentachlorobiphenyl (PCB118) is a persistent environmental pollutant associated with adverse female reproductive outcomes; however, its effects on uterine function and epigenetic regulation remain incompletely understood. This study investigated whether PCB118 disrupts uterine decidualization and angiogenesis through miRNA-mediated regulatory pathways. Human endometrial stromal cells (HESCs) and human umbilical vein endothelial cells (HUVECs) were exposed to an environmentally relevant, non-cytotoxic concentration of PCB118. Decidualization and angiogenesis were evaluated in vitro, and underlying mechanisms were investigated using molecular and miRNA-based approaches. In vivo validation of miR-542-3p expression was performed in pregnant mice following PCB118 exposure. PCB118 exposure was associated with reduced expression of decidualization markers, including prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP-1), as well as impaired angiogenic capacity in HUVECs. PCB118 treatment was accompanied by increased miR-542-3p expression, which was associated with decreased integrin-linked kinase (ILK) levels and changes in transforming growth factor beta 1 (TGF-β1) and total Smad2 protein abundance. ILK overexpression partially restored decidualization and angiogenesis-related phenotypes, supporting a functional involvement of ILK in these processes. Consistently, elevated miR-542-3p expression was observed in murine endometrial tissues following PCB118 exposure, suggesting physiological relevance in vivo. PCB118 exposure is associated with impaired decidualization and angiogenesis, potentially involving dysregulation of the miR-542-3p/ILK signaling axis, suggesting a potential role for epigenetic modulation in PCB118-associated reproductive dysfunction. Full article

Heterotopic ossification (HO), the pathological formation of mature bone in non-skeletal soft tissues (e.g., muscles, tendons), severely impairs patient mobility and quality of life. Despite decades of research, systematic analysis of signaling networks across HO subtypes (acquired traumatic HO, hereditary Fibrodysplasia Ossificans Progressiva (FOP), Progressive Osseous Heteroplasia (POH)) remains insufficient, and clinical therapies suffer from high recurrence and severe side effects. This review synthesizes recent advances in HO pathogenesis: FOP involves gain-of-function activin A receptor type I (ACVR1) mutations (mostly R206H), disrupting bone morphogenetic protein (BMP)/Activin A signaling; POH arises from paternal guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (GNAS) loss-of-function mutations, derepressing Hedgehog signaling via reduced cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) activity; tHO features trauma-induced inflammation/hypoxia activating BMP/transforming growth factor–beta (TGF-β) pathways. Key signaling crosstalk (e.g., BMP-Yes-associated protein (YAP)-Indian hedgehog (IHH)) is integrated, and novel therapies (ACVR1 inhibitors, Activin A antibodies, retinoic acid receptor gamma (RARγ) agonists, adeno-associated virus (AAV)-mediated ACVR1 silencing) are highlighted, with emphasis on subtype-specific efficacy. A stratified, mechanism-based HO management framework is proposed, aiming to accelerate precision therapy development and advance understanding of aberrant tissue regeneration. Full article