Search Results (954)

Bulbine species (Asphodelaceae) are routinely used in many African communities to treat various dermatological disorders, including wounds, due to their relative accessibility, affordability, safety records, and reported efficacies. However, these reported biological activities lack robust empirical evidence and well-validated cellular mechanisms for plausible applications. Hence, this review was aimed at investigating the bioactive compounds of Bulbine species linked to their cellular wound healing attributes, their toxicity, and cytotoxicity. A detailed literature search was conducted using Web of Science, Google scholar, and PubMed, followed by Scopus and VOSviewer (version 1.6.20) bibliographic analyses. Bulbine frutescens (L.) Willd. and Bulbine natalensis Baker safely mediate tissue healing and coagulation cascade as adaptogens and cytotoxic agents. The wound healing activities of the Bulbine species were linked to the synergistic wound healing or tissue repair properties of bioactive compounds (such as saponins, terpenoids, luteolin, and apigenin) via the expression of collagen type-I, alpha-2 (COL1A2) gene, collagen III, increase in the wound tensile strength, and anti-cytokine interleukin-10 (IL-10) mRNA. Bulbine species were also reported to contain specialised biomarker compounds (such as naphthoquinones, bulbine-emodin, and aloe-emodin) which mediate the activation of hydroxyproline, Aryl Hydrocarbon Receptor, transforming growth factor beta—β1 (TGFβ1), and the suppressor of mothers against decapentaplegic proteins (SMAD), which ultimately induce tissue granulation, myofibroblast differentiation, re-epithelialization, higher protein complexes, and scar tissue formations. These findings give credence to the wound healing therapeutic potential of Bulbine species. However, additional clinical studies are necessary to further ascertain the reported efficacies of Bulbine species’ bioactive principles, their overall safety, and the underlying cellular mechanisms involved in the wound healing process and carcinogenesis. Full article

Background/Objectives: Transforming growth factor-beta (TGF-β) is a multifunctional cytokine involved in immune regulation, extracellular matrix turnover, and tissue repair. Its role in periodontitis remains controversial due to conflicting human studies. This systematic review addressed the PICO-based question: in adults with periodontitis (population), how does the expression and regulation of TGF-β isoforms (intervention/exposure) compare with healthy or post-treatment states (comparator) regarding clinical outcomes (outcomes)? Methods: A systematic search of PubMed and Scopus was conducted on 1 July 2025 for human studies published in English between 2010 and 2025. Eligible studies investigated TGF-β expression, function, or genetic regulation in periodontal tissues or biological fluids. Screening and quality appraisal were performed according to PRISMA guidelines, using design-specific risk-of-bias tools. The review protocol was prospectively registered in PROSPERO (CRD420251138456). Results: Fifteen studies met inclusion criteria. TGF-β1 was the most frequently analyzed isoform and was consistently elevated in diseased gingival tissue and gingival crevicular fluid, correlating with probing depth and attachment loss. Several studies reported post-treatment reductions in TGF-β, supporting its value as a dynamic biomarker. Additional findings linked TGF-β signaling to immune modulation, fibrosis, bone turnover, and systemic comorbidities. Evidence for TGF-β2 and TGF-β3 was limited but suggested isoform-specific roles in epithelial–mesenchymal signaling and scar-free repair. Conclusions: Current evidence supports TGF-β, particularly TGF-β1, as a central mediator of periodontal inflammation and repair, with promise as both a biomarker and therapeutic target. Standardized, isoform-specific, and longitudinal studies are needed to clarify its diagnostic and translational utility. Full article

Therapy resistance is a major obstacle to cancer treatment, and transforming growth factor-beta (TGF-β) signaling has emerged as a major instigator across many cancer types and therapeutic regimens. Solid tumors overexpress TGF-β ligands, and canonical and non-canonical TGF-β signaling pathways drive molecular changes in most cell types within the tumor to hijack therapeutic responses. Cancer therapies further stimulate TGF-β release to potentiate this problem. Molecular mechanisms of TGF-β action supporting resistance include upregulation of drug efflux pumps, enhanced DNA Damage Repair, elaboration of stiffened extracellular matrix, and decreased neoantigen presentation. TGF-β also activates pro-survival pathways, such as epidermal growth factor receptor, B-cell lymphoma-2 expression, and AKT-mTOR signaling. TGF-β-induced epithelial-to-mesenchymal transformation leads to tumor heterogeneity and acquisition of stem-like states. In the tumor microenvironment, TGF-β induces extracellular matrix production, contractility, and secretion of immunosuppressive cytokines by cancer-associated fibroblasts that contribute to drug resistance. TGF-β also blunts cytotoxic T and NK cell activities and stimulates recruitment and differentiation of immunosuppressive cells, including T-regulatory cells, M2 macrophages, and myeloid-derived suppressor cells. The importance of TGF-β signaling in development of drug resistance cannot be understated and should be further explored mechanistically to identify novel molecular approaches and combinatorial drug dosing strategies to prevent drug-resistance. Full article

Background: The human gut microbiome—a diverse ecosystem of trillions of microorganisms—plays an essential role in metabolic, immune, and neurological regulation. However, modern lifestyle factors such as antibiotic overuse, cesarean delivery, reduced breastfeeding, processed and high-sodium diets, alcohol intake, smoking, and exposure to environmental toxins (e.g., glyphosate) significantly reduce microbial diversity. Loss of keystone species like Bifidobacterium infantis (B. infantis) and Lactobacillus reuteri (L. reuteri) contributes to gut dysbiosis, which has been implicated in chronic metabolic, autoimmune, cardiovascular, and neurodegenerative conditions. Materials and Methods: This Qualitative Systematic Review (QualSR) synthesized data from over 547 studies involving human participants and standardized microbiome analysis techniques, including 16S rRNA sequencing and metagenomics. Studies were reviewed for microbial composition, immune and metabolic biomarkers, and clinical outcomes related to microbiome restoration strategies. Results: Multiple cohort studies have consistently reported a 40–60% reduction in microbial diversity among Western populations compared to traditional societies, particularly affecting short-chain fatty acid (SCFA)-producing bacteria. Supplementation with B. infantis is associated with a significant reduction in systemic inflammation—including a 50% decrease in C-reactive protein (CRP) and reduced tumor necrosis factor-alpha (TNF-α) levels—alongside increases in regulatory T cells and anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-β1). L. reuteri demonstrates immunomodulatory and neurobehavioral benefits in preclinical models, while both probiotics enhance epithelial barrier integrity in a strain- and context-specific manner. In murine colitis, B. infantis increases ZO-1 expression by ~35%, and L. reuteri improves occludin and claudin-1 localization, suggesting that keystone restoration strengthens barrier function through tight-junction modulation. Conclusions: Together, these findings support keystone species restoration with B. infantis and L. reuteri as a promising adjunctive strategy to reduce systemic inflammation, reinforce gut barrier integrity, and modulate gut–brain axis (GBA) signaling, indicating translational potential in metabolic and neuroimmune disorders. Future research should emphasize personalized microbiome profiling, long-term outcomes, and transgenerational effects of early-life microbial disruption. Full article

DNA methylation holds promise for the early detection of tissue damage, making it crucial for identifying polycyclic aromatic hydrocarbon (PAH)-associated epigenetic biomarkers in childhood asthma. Sulforaphane (SFN), as a potential epigenetic modulator, can alleviate the adverse effects of environmental pollutants. This study quantified serum PAHs in 370 children via gas chromatography–mass spectrometry, assessed the methylation of target genes using bisulfite sequencing PCR (BSP), and performed mediation analysis to estimate the mediating effects of methylation levels between PAHs and childhood asthma. Murine models exposed to PAHs prenatally or postnatally, with offspring challenged with ovalbumin (OVA), were analyzed for lung DNA methylation. In vitro, HBE cells and HBSMCs treated with benzo(a)pyrene (BaP) and/or SFN were tested for inflammatory cytokines, methylation-related enzymes, and matrix metallopeptidase 9 (MMP9) modifications. The results showed total PAHs were associated with childhood asthma, with mediating effects of long interspersed nuclear element-1 (LINE-1) methylation. Prenatal PAH exposure enriched differentially methylated genes in the extracellular matrix (ECM)-receptor interaction pathway, while postnatal exposure enriched those in purine metabolism, and postnatal exposure also elevated Mmp9 expression via hypomethylation. BaP increased the expression of interferon gamma (IFN-γ), interleukin-4 (IL-4), interleukin-17A (IL-17A), transforming growth factor beta 1 (TGF-β), and ten-eleven translocation methylcytosine dioxygenases (TETs), and it upregulated MMP9 via enhancer hypomethylation and H3K27ac enrichment, while SFN reversed these effects by downregulating histone methyltransferase (HMT), leading to reduced H3K4me1 and subsequent H3K27ac depletion, thus suppressing MMP9 transcription. This study demonstrates that DNA methylation mediates PAH–childhood asthma associations, with distinct patterns in different exposure windows; MMP9 could serve as a crucial target for epigenetic modification during lung inflammation induced by PAH exposure, and SFN reverses PAH-induced epigenetic changes, aiding prevention strategies. Full article

Early-onset colorectal cancer (EOCRC; <50 years) incidence is increasing most rapidly among Hispanic/Latino (H/L) populations. While the transforming growth factor–beta (TGF-β) pathway influences colorectal cancer (CRC) progression, its prognostic role in FOLFOX-treated EOCRC, particularly in H/L patients, is unclear. We analyzed 2515 CRC cases (H/L = 266; NHW = 2249) stratified by ancestry, age at onset, and FOLFOX treatment using Fisher’s exact, chi-square, and Kaplan–Meier analyses. We then applied AI-HOPE and AI-HOPE-TGFβ, conversational artificial intelligence (AI) platforms that integrate clinical, genomic, and treatment data, to perform complex, natural language-driven queries requiring multi-parameter integration. TGF-β pathway alterations occurred in 28–39% of H/L and 23–31% of NHW patients, with SMAD4 being the predominant driver. BMPR1A mutations were enriched in FOLFOX-treated EO H/L patients (5.5% vs. 1.1% EO NHW; p = 0.0272), while late-onset NHW non-FOLFOX cases had higher SMAD2/TGFBR2 mutation rates. In FOLFOX-treated EO H/L patients, TGF-β pathway alterations predicted poorer survival (p = 0.029); no survival impact was seen in other groups. SMAD4 mutations were less frequent in EO H/L than in EO NHW receiving FOLFOX (2.74% vs. 13.87%; p = 0.013). TGF-β pathway alterations may serve as ancestry- and treatment-specific biomarkers of poor prognosis in FOLFOX-treated EO H/L CRC. AI-enabled integration accelerated biomarker discovery, supporting precision medicine. Full article

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) encompasses a spectrum of liver conditions and involves gut–liver axis crosstalk. We aimed to evaluate whether oral vancomycin modifies liver injury and the cecal microbiota in a methionine–choline-deficient (MCD) diet model of NASH. Male C57BL/6J mice (n = 28) were block-randomized to four groups (n = 7 each) for 10 weeks: standard diet (STD); MCD diet; STD + vancomycin (VANC); and MCD + VANC (2 mg/mouse ≈ 50 mg/kg, every 72 h). After 10 weeks, liver tissues were analyzed for histological changes, cytokine levels [interleukin-6 (IL-6), interleukin-8 (IL-8), transforming growth factor beta 1 (TGF-β1)], and immunohistochemical markers [ubiquitin and cytokeratin 18 (CK18)]. Cecal microbiota composition was evaluated with 16S ribosomal RNA (rRNA) sequencing. The MCD reproduced key NASH features (macrovesicular steatosis, lobular inflammation). Vancomycin shifted steatosis toward a microvesicular pattern and reduced hepatocyte injury: CK18 and ubiquitin immunoreactivity were decreased in MCD + VANC vs. MCD, and hepatic IL-8 and TGF-β1 levels were lower in MCD + VANC vs. STD. Taxonomically, STD mice had Lactobacillus-rich microbiota. The MCD diet alone reduced alpha diversity (α-diversity), modestly lowered Firmicutes and increased Desulfobacterota/Fusobacteriota. Vancomycin alone caused a much larger collapse in richness, depleting Gram-positive commensals and promoting blooms of Escherichia–Shigella, Klebsiella, Parabacteroides, and Akkermansia. In the MCD + VANC group, vancomycin profoundly remodeled the microbiota, eliminating key commensals (e.g., Lactobacillus) and enriching Desulfobacterota, Fusobacteriota, and Campylobacterota. Oral vancomycin in the MCD model of NASH improved liver injury markers and altered steatosis morphology, but concurrently reprogrammed the gut into a low-diversity, pathobiont-enriched ecosystem with near-loss of Lactobacillus. These findings highlight a therapeutic trade-off—hepatic benefit accompanied by microbiome cost—that should guide microbiota-targeted strategies for NAFLD/NASH. Full article

Background and Objectives: Obstructive sleep apnea (OSA) represents an increasing public health concern, closely linked with cardiovascular, metabolic, and neurocognitive disorders, as well as impaired quality of life. The complex pathophysiology of OSA involves upper airway dysfunction, oxidative stress, and inflammation, with endothelial dysfunction considered central to its associated comorbidities. Despite notable advances in OSA research, the biological mechanisms driving these complications remain insufficiently understood. The present study aimed to examine the associations between redox status, proinflammatory biomarkers, and the gene expression of full-length receptor for advanced glycation end products (flRAGE) and transforming growth factor beta 1 (TGF-β1) in relation to the presence and severity of OSA. Materials and Methods: The study cohort comprised 125 participants with diagnosed OSA and 42 controls without evidence of OSA. General and clinical characteristics were recorded for all participants. Laboratory analyses included the assessment of redox and inflammatory markers in serum and plasma, while flRAGE and TGF-β1 messenger ribonucleic acids (mRNA) were quantified in peripheral blood mononuclear cells. Results: Patients with OSA demonstrated elevated oxidative stress and inflammation, characterized by increased total antioxidant status (TAS) and C-reactive protein CRP levels, together with reduced concentrations of soluble RAGE (sRAGE). The severity of OSA, indicated by the apnea-hypopnea index, increases total oxidative status (TOS) and TGF-β1 mRNA, while sRAGE decreases. The sRAGE–ROS-related factor was negatively associated with OSA, whereas the redox status factor showed a positive association. TOS was independently and positively correlated with OSA severity. Conclusions: Individuals with OSA exhibit a state of enhanced oxidative stress and inflammation. Increasing severity of OSA was associated with rising TOS and TGF-β1 mRNA expression, accompanied by declining sRAGE concentrations. A combined redox–inflammatory biomarker profile was found to be associated with both the presence and severity of OSA. Full article

Rhabdomyolysis is characterized by the breakdown of skeletal muscle tissue, frequently leading to acute kidney injury (AKI). Traditional conservative treatments have shown limited effectiveness in modifying the disease course, thereby necessitating targeted pharmacological approaches. Zileuton (Z), a selective inhibitor of 5-lipoxygenase (5-LOX), has demonstrated efficacy in enhancing renal function recovery in animal models of AKI induced by agents such as cisplatin, aminoglycosides, and polymyxins. The present study aimed to evaluate the therapeutic potential of a single dose of Z in mitigating rhabdomyolysis-induced AKI (RI-AKI) via modulation of myeloid-derived suppressor cells (MDSCs). Male C57BL/6 mice were assigned to four experimental groups: Sham (intraperitoneal administration of 0.9% saline), Z (single intraperitoneal injection of Z at 30 mg/kg body weight), glycerol (Gly; single intramuscular dose of 50% glycerol at 8 mL/kg), and glycerol plus Z (Z + Gly; concurrent administration of glycerol intramuscularly and Z intraperitoneally). Animals were sacrificed 24 h post-glycerol injection for analysis. Zileuton administration significantly improved renal function, as indicated by reductions in blood urea nitrogen (BUN) levels (129.7 ± 17.9 mg/dL in the Gly group versus 101.7 ± 6.8 mg/dL in the Z + Gly group, p < 0.05) and serum creatinine (Cr) levels (2.2 ± 0.3 mg/dL in the Gly group versus 0.9 ± 0.3 mg/dL in the Gly + Z group p < 0.05). Histopathological assessment revealed a marked decrease in tubular injury scores in the Z + Gly group compared to the Gly group. Molecular analyses demonstrated that Z treatment downregulated mRNA expression of macrophage-inducible C-type lectin (mincle) and associated macrophage infiltration-related factors, including Areg-1, Cx3cl1, and Cx3CR1, which were elevated 24 h following glycerol administration. Furthermore, the expression of NLRP-3, significantly upregulated post-glycerol injection, was attenuated by concurrent Z treatment. Markers of mitochondrial biogenesis, such as mitochondrial DNA (mtDNA), transcription factor A mitochondrial (TFAM), and carnitine palmitoyltransferase 1 alpha (CPT1α), were diminished 24 h after glycerol injection; however, their expression was restored upon simultaneous Z administration. Additionally, Z reduced protein levels of BNIP3, a marker of mitochondrial autophagy, while enhancing the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), suggesting that Z ameliorates RI-AKI severity through the regulation of mitochondrial quality control mechanisms. Zileuton also decreased infiltration of CD11b(+) Gr-1(+) MDSCs and downregulated mRNA levels of MDSC-associated markers, including transforming growth factor-beta (TGF-β), arginase-1 (Arg-1), inducible nitric oxide synthase (iNOS), and iron regulatory protein 4 (Irp4), in glycerol-injured kidneys relative to controls. These markers were elevated 24 h post-glycerol injection but were normalized following concurrent Z treatment. Collectively, these findings suggest that Zileuton confers reno-protective effects in a murine model of RI-AKI, potentially through modulation of mitochondrial dynamics and suppression of MDSC-mediated inflammatory pathways. Further research is warranted to elucidate the precise mechanisms by which Z regulates MDSCs and to assess its therapeutic potential in clinical contexts. Full article

In addition to its role in angiotensin II (Ang II) production, chymase exhibits various functions, including activation of latent transforming growth factor beta 1 (TGF-β1) and pro-matrix metalloproteinases (MMPs). However, the extent to which these Ang II-independent functions contribute to pathological conditions remains unclear. In this study, we investigated the Ang II-independent roles of chymase in cardiac remodeling and dysfunction. Eighteen male Syrian hamsters, aged 6 weeks and weighing 90–110 g, were used. Exogenous Ang II was administered to a hamster model that mirrors the human chymase-dependent Ang II production pathway, via subcutaneous osmotic mini pumps (2 mg/kg/day) for 4 weeks. A chymase-specific inhibitor, TY-51469 (10 mg/kg/day), was given daily starting 1 day after commencement of Ang II infusion. Evaluation showed that while systolic blood pressure increased significantly, only diastolic dysfunction developed over time. Ang II treatment led to elevated cardiac expression of chymase, TGF-β1, and MMP-2, and increased the number of chymase-positive mast cells, resulting in notable cardiac hypertrophy and fibrosis. TY-51469 effectively suppressed these molecular changes and improved both cardiac structure and diastolic dysfunction, despite continued Ang II exposure. These results suggest that chymase promotes cardiac remodeling and dysfunction not only through Ang II generation but also by activating profibrotic and matrix-degrading factors, such as TGF-β1 and MMP-2. Full article

Pirfenidone (PFD) is a pyridine-like compound most well-known for its use in idiopathic pulmonary fibrosis (IPF). However, its broad anti-inflammatory and anti-fibrotic actions make PFD a candidate for other scarring diseases. This review examines the use of PFD for dermatologic conditions. The literature supports the potential for PFD to decrease scarring in a variety of skin conditions. Both oral and topical preparations have been shown to be effective at aiding skin healing. Early clinical evidence demonstrates significant improvements in hypertrophic burn scars, reduction in fibrosis in localized scleroderma, and accelerated epithelialization of skin graft donor sites. These clinical outcomes are supported by PFD’s modulation of the transforming growth factor-beta (TGF-β) pathway, which plays a central role in skin fibrosis and scarring. Evidence in this review suggests topical PFD can be used to fill a clinical need for local anti-fibrotic therapies. Full article

Liver sinusoidal endothelial cells (LSECs) are essential for preserving liver homeostasis. Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a category of hepatic disorders characterized by excessive fat accumulation in the liver, known as steatosis. Over time, accumulated hepatic fat can induce inflammation of the liver (hepatitis). MASLD is among the most prevalent types of chronic liver disease. Obesity and Type 2 diabetes mellitus (T2DM) are frequent etiological factors of MASLD. In the absence of therapy, MASLD can lead to more severe hepatic conditions, which can be life-threatening. MASLD is noteworthy due to its potential progression to MASH and further severe liver impairment, including cirrhosis and hepatocellular carcinoma (HCC), a neoplastic progression. This narrative review examines the distinctive functions of LSECs in regulating immunologic responses, collagenization, and drug-sensitive bioreactivity in healthy livers, MASLD, and metabolic dysfunction-associated steatohepatitis (MASH), as well as in a human primary 3D model. We found that LSECs serve as crucial regulators of immunological equilibrium in the liver by inhibiting disproportionate immunologic activation, concurrently filtering tissue antigens, and engaging with immunologic cells, such as Kupffer cells (KCs) and T lymphocytes. In chronic diseases of the liver, LSECs experience cellular dysfunction, resulting in capillarization (focal to diffuse), loss of fenestrations (fenestrae), and the activation of pro-fibrotic signaling pathways, including transforming growth factor-beta (TGF-β). Indeed, TGF-β is crucial in activating hepatic stellate cells (HSCs), a process that facilitates the progression of liver disease toward fibrosis. In addition to examining the dynamic interplay between LSECs, specifically HSCs, and other liver cells throughout the progression of fatty liver–MASH, we suggest that LSECs may become a potential therapeutic target for modifying immune responses and averting fibrosis in hepatic disorders. The limitations of animal models are also highlighted and discussed. Full article

Astrocytic tumors are a heterogeneous group of glial neoplasms characterized by marked differences in biological behavior and patient prognosis. Transforming growth factor-beta (TGF-β) signaling plays a pivotal role in astrocytoma pathogenesis; however, the extent and mechanisms of its epigenetic regulation remain poorly understood. This study aimed to investigate how promoter methylation and microRNA-mediated mechanisms regulate key genes within the TGF-β signaling pathway across various astrocytoma grades. Tumor tissue samples from 65 patients with WHO grade II–IV astrocytomas were analyzed using Affymetrix gene expression and microRNA microarrays. Promoter methylation of TGF-β signaling genes was assessed using methylation-specific polymerase chain reaction (MSP). Gene expression was validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), and protein levels were quantified using enzyme-linked immunosorbent assay (ELISA). MicroRNA targets were predicted using bioinformatic tools, and survival analyses were conducted using Kaplan–Meier and Cox regression models. Six genes—SMAD1, SMAD3, SKIL, BMP2, SMAD4, and MAPK1—showed significant upregulation in high-grade tumors (fold change > 5.0, p < 0.05), supported by RT-qPCR and protein-level data. Promoter hypomethylation and reduced expression of regulatory microRNAs (e.g., hsa-miR-145-5p targeting SMAD3) were more common in higher-grade tumors. Protein–protein interaction analysis indicated strong functional interconnectivity among the overexpressed genes. High protein levels of SMAD1, SMAD3, and SKIL were significantly associated with shorter overall survival (p < 0.001). This multi-level analysis reveals that astrocytic tumor progression involves epigenetic derepression and microRNA-mediated dysregulation of TGF-β signaling. Elevated expression of SMAD1, SMAD3, and SKIL emerged as strong prognostic indicators, underscoring their potential as biomarkers and therapeutic targets in astrocytic tumors. Full article

Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with male predominance. This study investigated the role of microRNA-125b in PSC-related liver fibrosis, focusing on its interaction with transforming growth factor beta (TGF-β), androgen receptors (ARs), and apelin. Elevated serum and hepatic levels of miR-125b were observed in PSC patients, particularly in males and those with advanced fibrosis, and correlated with increased liver injury markers and FibroScan stiffness. miR-125b expression negatively correlated with apelin and TGF-β levels, while it positively correlated with AR expression. In vitro, miR-125b overexpression induced ARs and suppressed p53 and apelin, whereas lipopolysaccharide stimulation reduced miR-125b and enhanced pro-inflammatory genes, including TNF-α and TGF-β. Notably, ursodeoxycholic acid therapy significantly decreased serum miR-125b levels. These findings suggest that miR-125b contributes to inflammation and fibrogenesis in PSC, partly through the modulation of TGF-β, ARs, and apelin signalling. Moreover, the observed sex-based differences in miR-125b expression underscore the influence of androgens in PSC pathogenesis. Full article

Uterine leiomyomas (ULM) and uterine leiomyosarcomas (ULMS) represent smooth muscle tumors with similar initial presentations but drastically different outcomes. This literature review analyzes the similarities and differences in their epigenetic profiles to identify diagnostic biomarkers and potential therapeutic targets that could improve clinical management. Both tumor types exhibit mostly distinct epigenetic signatures while sharing key pathway dysregulations. ULMS demonstrates global DNA hypomethylation, increased histone acetyltransferase activity, elevated Histone Deacetylase (HDAC) class I expression, and characteristic microRNA profiles. ULM displays focal methylation patterns and specific microRNA alterations that promote extracellular matrix accumulation. Despite these differences in epigenetic mechanisms, both tumors converge on dysregulation of signaling pathways including PI3K/AKT/mTOR, Wnt/β-catenin, and Transforming Growth Factor beta (TGF-β) signaling, suggesting common downstream effects from distinct epigenetic origins. Understanding the shared and distinct epigenetic landscape between ULM and ULMS will enhance our insights into tumor pathogenesis and may offer promising biomarkers and therapeutic targets. Full article