Search Results (678)

Background: Senescence, a state of permanent cell cycle arrest, is a complex cellular phenomenon closely affiliated with age-related diseases and pathological fibrosis. Cellular senescence is now recognized as a significant contributor to organ fibrosis, largely driven by transforming growth factor beta (TGF-β) signaling, such as in metabolic dysfunction-associated steatohepatitis (MASH), idiopathic pulmonary fibrosis (IPF), chronic kidney disease (CKD), and myocardial fibrosis, which can lead to heart failure, cystic fibrosis, and fibrosis in pancreatic tumors, to name a few. MASH is a progressive inflammatory and fibrotic liver condition that has reached pandemic proportions, now considered the largest non-viral contributor to the need for liver transplantation. Methods: We previously studied Oxy210, an anti-fibrotic and anti-inflammatory, orally bioavailable, oxysterol-based drug candidate for MASH, using APOE*3-Leiden.CETP mice, a humanized hyperlipidemic mouse model that closely recapitulates the hallmarks of human MASH. In this model, treatment of mice with Oxy210 for 16 weeks caused significant amelioration of the disease, evidenced by reduced hepatic inflammation, lipid deposition, and fibrosis, atherosclerosis and adipose tissue inflammation. Results: Here we demonstrate increased hepatic expression of senescence-associated genes and senescence-associated secretory phenotype (SASP), correlated with the expression of pro-fibrotic and pro-inflammatorygenes in these mice during the development of MASH that are significantly inhibited by Oxy210. Using the HepG2 human hepatocyte cell line, we demonstrate the induced expression of senescent-associated genes and SASP by TGF-β and inhibition by Oxy210. Conclusions: These findings further support the potential therapeutic effects of Oxy210 mediated in part through inhibition of senescence-driven hepatic fibrosis and inflammation in MASH and perhaps in other senescence-associated fibrotic diseases. Full article

Background: Blue light (BL) irradiation has been shown to induce photobiomodulation (PBM) in cells. Here, we investigate its influence on cell types involved in wound healing. Methods: Cellular responses of immortalized human keratinocytes (HaCaTs), normal human dermal fibroblasts (NHDFs), and human umbilical vein endothelial cells (HUVECs) after light treatment at 450 nm were analyzed by kinetic assays on cell viability, proliferation, ATP quantification, migration assay, and apoptosis assay. Gene expression was evaluated by transcriptome analysis. Results: A biphasic effect was observed on HaCaTs, NHDFs, and HUVECs. Low-fluence (4.5 J/cm²) irradiation stimulated cell viability, proliferation, and migration. mRNA sequencing indicated involvement of transforming growth factor beta (TGF-β), ErbB, and vascular endothelial growth factor (VEGF) pathways. High-fluence (18 J/cm²) irradiation inhibited these cellular activities by downregulating DNA replication, the cell cycle, and mismatch repair pathways. Conclusions: HaCaTs, NHDFs, and HUVECs exhibited a dose-dependent pattern after BL irradiation. These findings broaden the view of PBM following BL irradiation of these three cell types, thereby promoting their potential application in wound healing and angiogenesis. Our data on low-fluence BL at 450 nm indicates clinical potential for a novel modality in wound therapy. Full article

Cardiorenal syndrome (CRS) is a multifactorial clinical condition characterized by the bidirectional deterioration of cardiac and renal function, driven by mechanisms such as renin–angiotensin–aldosterone system (RAAS) overactivation, systemic inflammation, oxidative stress, endothelial dysfunction, and fibrosis. The aim of this narrative review is to explore the key molecular pathways involved in CRS and to highlight emerging therapeutic approaches, with a special emphasis on nutritional interventions. We examined recent evidence on the contribution of mitochondrial dysfunction, uremic toxins, and immune activation to CRS progression and assessed the role of dietary and micronutrient factors. Results indicate that a high dietary intake of sodium, phosphorus additives, and processed foods is associated with volume overload, vascular damage, and inflammation, whereas deficiencies in potassium, magnesium, and vitamin D correlate with worse clinical outcomes. Anti-inflammatory and antioxidant bioactives, such as omega-3 PUFAs, curcumin, and anthocyanins from maqui, demonstrate potential to modulate key CRS mechanisms, including the nuclear factor kappa B (NF-κB) pathway and the NLRP3 inflammasome. Gene therapy approaches targeting endothelial nitric oxide synthase (eNOS) and transforming growth factor-beta (TGF-β) signaling are also discussed. An integrative approach combining pharmacological RAAS modulation with personalized medical nutrition therapy and anti-inflammatory nutrients may offer a promising strategy to prevent or delay CRS progression and improve patient outcomes. Full article

This study aimed to investigate the tyrosine kinase inhibitor Nintedanib and its potential role in reversing epithelial–mesenchymal transition (EMT) induced by transforming growth factor beta 2 (TGF-β2) in retinal pigment epithelial (RPE) cells, along with its therapeutic potential using a mouse model of subretinal fibrosis. We hypothesized that the blockade of angiogenesis promoting and fibrosis inducing signaling using the receptor tyrosine kinase inhibitor Nintedanib (OfevTM) can prevent or reverse EMT both in vitro and in our in vivo model of subretinal fibrosis. Primary human retinal pigment epithelial cells (phRPE) and adult retinal pigment epithelial cell line (ARPE-19) cells were treated with TGF-β210 ng/mL for two days followed by four days of Nintedanib (1 µM) incubation. Epithelial and mesenchymal phenotypes were assessed by morphological examination, quantitative real-time polymerase chain reaction(qPCR) (ZO-1, Acta2, FN, and Vim), and immunocytochemistry (ZO-1, vimentin, fibronectin, and αSMA). Metabolites were measured using luciferase-based assays. Extracellular acidification and oxygen consumption rates were measured using the Seahorse XF system. Metabolic-related genes (GLUT1, HK2, PFKFB3, CS, LDHA, LDHB) were evaluated by qPCR. A model of subretinal fibrosis using the two-stage laser-induced method in C57BL/6J mice assessed Nintedanib’s therapeutic potential. Fibro-vascular lesions were examined 10 days later via fluorescence angiography and immunohistochemistry. Both primary and ARPE-19 RPE stimulated with TGF-β2 upregulated expression of fibronectin, αSMA, and vimentin, and downregulation of ZO-1, consistent with morphological changes (i.e., elongation). Glucose consumption, lactate production, and glycolytic reserve were significantly increased in TGF-β2-treated cells, with upregulation of glycolysis-related genes (GLUT1, HK2, PFKFB3, CS). Nintedanib treatment reversed TGF-β2-induced EMT signatures, down-regulated glycolytic-related genes, and normalized glycolysis. Nintedanib intravitreal injection significantly reduced collagen-1+ fibrotic lesion size and Isolectin B4+ neovascularization and reduced vascular leakage in the two-stage laser-induced model of subretinal fibrosis. Nintedanib can induce Mesenchymal-to-Epithelial Transition (MET) in RPE cells and reduce subretinal fibrosis through metabolic reprogramming. Nintedanib can therefore potentially be repurposed to treat retinal fibrosis. Full article

Background and Objective: Intervertebral disc degeneration (IVDD) is a leading cause of lower back pain with limited regenerative treatments. Among emerging regenerative approaches, growth factor-based therapies, such as recombinant human transforming growth factor-beta (Rh-TGF-β), have shown potential for disc regeneration but are hindered by rapid degradation and uncontrolled release by direct administration. Additionally, mechanical stress elevates heat shock protein 90 (HSP-90), impairing cell function and extracellular matrix (ECM) production. This study aimed to investigate a dual self-cross-linked alginate di-aldehyde (ADA) hydrogel system for the sustained delivery of Rh-TGF-β and epigallocatechin gallate (EGCG) to enhance protein stability, regulate release, and promote disc regeneration by targeting both regenerative and stress-response pathways. Methods: ELISA and UV-Vis spectrophotometry assessed Rh-TGF-β and EGCG release profiles. A rat tail IVDD model was established with an Ilizarov-type external fixator for loading, followed by hydrogel treatment with or without bioactive agents. Disc height, tissue structure, and protein expression were evaluated via radiography, histological staining, immunohistochemistry, and Western blotting. Results: The hydrogel demonstrated a biphasic release profile with 100% Rh-TGF-β released over 60 days and complete EGCG release achieved within 15 days. Treated groups showed improved disc height, structural integrity, and proteoglycan retention revealed by histological analysis and elevated HSP-90 expression by immunohistochemistry. In contrast, Western blot analysis confirmed that EGCG effectively downregulated HSP-90 expression, suggesting a reduction in mechanical stress-induced degeneration. Conclusions: ADA hydrogel effectively delivers therapeutic agents, offering a promising strategy for IVDD treatment. Full article

Holothuria scabra has long been acknowledged in traditional medicine for its therapeutic properties. The transforming growth factor-beta (TGF-β) superfamily is crucial in regulating cellular processes, including differentiation, proliferation, and immune responses. This study marks the first exploration of the gene expression localization, sequence conservation, and functional roles of H. scabra TGF-β proteins, specifically activin (HolscActivin), inhibin (HolscInhibin), and the TGF-β receptor (HolscTGFBR), across various organs. In situ hybridization indicated that HolscActivin and HolscInhibin are expressed in the intestine, respiratory tree, ovary, testis, and inner body wall. This suggests their roles in nutrient absorption, gas exchange, reproduction, and extracellular matrix remodeling. Notably, HolscTGFBR demonstrated a similar tissue-specific expression pattern, except for its absence in the respiratory tree. Bioinformatics analysis reveals that HolscTGFBR shares significant sequence similarity with HomsaTGFBR, especially in regions essential for signal transduction and inhibition. Molecular docking results indicate that HolscActivin may promote receptor activation, while HolscInhibin functions as a natural antagonist, reflecting the signaling mechanisms of human TGF-β proteins. Interestingly, cross-species ternary complex docking with human TGF-β receptors further supports these findings, showing that HolscActivin moderately engages the receptors, whereas HolscInhibin exhibits strong binding, suggestive of competitive inhibition. These results indicate that H. scabra TGF-β proteins retain the structural and functional features of vertebrate TGF-β ligands, supporting their potential applications as natural modulators in therapeutic and functional food development. Full article

Introduction: Unilateral cleft lip and palate (CLP) is a severe orofacial birth defect characterized by improper fusion of facial parts and disturbed orofacial functions. The defect manifests as a gap in the orofacial tissues that is accompanied by defective healing patterns and chronic inflammation. The immune system’s defense factors modulate immunity, inflammation, and healing. Angiogenesis factors control blood-vessel formation. Therefore, these factors are vital in the immunological assessment and understanding of CLP morphopathogenesis. The aim of the study is to assess the distribution of vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF- β1), the total macrophage population and the M2 subtype, heat-shock proteins (HSP) 60 and 70, and nuclear factor kappa B (NF-κB) p50 and p65 subtypes in the affected tissue of children with CLP before and during primary dentition. Materials and Methods: Tissue samples were obtained from 15 patients aged from 3 to 8 months during veloplastic surgery. Five controls were used for comparison of data. Immunohistochemistry, light microscopy, semi-quantitative evaluation (from 0 to ++++), and statistics (Mann–Whitney U test and Spearman’s rank correlation) were used to evaluate the data for statistically significant differences and correlations between the groups. Results: Epithelial tissues affected by CLP presented with statistically significant increases in levels of VEGF (p = 0.007), total macrophages (p = 0.007), HSP60 (p = 0.001), NF-κB p65 (p = 0.000), and p50 (p = 0.045), but with a decrease in M2 macrophages (p = 0.025). Blood vessels in CLP-affected tissues showed a statistically significant increase in levels of NF-κB p65 (p = 0.003) and a statistically significant decrease in M2 numbers (p = 0.014). Connective tissue presented with no statistically significant differences. Spearman’s rank correlation revealed multiple statistically significant correlations—26 positive and 5 negative. Conclusions: Statistically significant changes in levels of VEGF and both NF-κB subtypes and numbers of total macrophages and M2 macrophages suggest a possible alteration of variable immune and inflammatory reactions and macrophage functions associated with the initiation and maintenance of the chronic process and the resulting damage. Full article

Background: The mechanisms underlying the metastasis of non-small-cell lung cancer (NSCLC) have long been a focal point of medical research. The anti-tumor effects of chelerythrine (CHE) have been confirmed; however, its ability to inhibit tumor metastasis and the underlying mechanisms remain unknown. The aim of this study was to investigate the inhibitory effects and molecular mechanisms of CHE on transforming growth factor-beta (TGF-β)-induced epithelial–mesenchymal transition (EMT). Methods: Wound healing and Transwell assays were employed to evaluate TGF-β-induced migration in A549 cells and the inhibitory effects of CHE. Ribonucleotide reductase subunit M2 (RRM2) expression levels were detected via Western blot and immunofluorescence staining. Western blot and RT-qPCR were used to examine the expression levels of EMT-related markers. Animal experiments were conducted to analyze the role of RRM2 in the CHE inhibition of TGF-β-induced lung cancer metastasis. Results: This study found that TGF-β treatment enhanced the metastasis of A549 cells, while CHE inhibited the expression of TGF-β-induced EMT-related transcription factors by RRM2, thereby suppressing tumor cell migration (p < 0.05). Furthermore, the oral administration of CHE inhibited the metastasis of A549 cells to the lungs from the tail vein in mice, consistent with in vitro findings. Despite the high doses of CHE used, there was no evidence of toxicity. Conclusions: Our data reveal the mechanism of the anti-metastatic effects of CHE on TGF-β-induced EMT and indicate that CHE can be used as an effective anti-tumor treatment. Full article

Fuchs endothelial corneal dystrophy (FECD) is a progressive corneal disease characterized by corneal endothelial cell (CEC) loss and guttae formation. Elevated levels of Transforming Growth Factor-Beta 1 and 2 (TGF-β1/-β2) have been reported in the aqueous humor (AH) of FECD patients and have been implicated with abnormal extracellular matrix (ECM) production, endothelial-to-mesenchymal transition (EndoMT), the unfolded protein response, and cell death. However, how TGF-β signaling affects cell migration in FECD remains to be elucidated. In this study, we found that TGF-β2 levels were significantly elevated in the AH of FECD patients compared to controls. We performed bulk RNA sequencing on FECD CECs treated with TGF-β1 or TGF-β2 and identified the epithelial-to-mesenchymal (EMT) pathway as one of the top dysregulated pathways. We found that TGF-β1 and TGF-β2 increased EMT markers, filamentous-actin (F-actin) expression and produced more EMT-like phenotype in FECD and control CECs. We also observed that TGF-β1 and TGF-β2 significantly increased FECD CEC migration speed as detected by scratch assay and individual cell tracking and promoted individual cellular migration behavior. This study provides novel insight into FECD pathogenesis and how increased TGF-β signaling promotes EndoMT and alters cellular migration in FECD CECs. Full article

The transforming growth factor beta (TGF-$\mathsf{\beta }$) gene family is widely distributed across the animal kingdom, playing a crucial role in various cellular processes and maintaining overall health and homeostasis. The present study identified 34 TGF-$\mathsf{\beta }$ family genes based on the genome sequence in Tupaia belangeri, which were classified into the TGF-$\mathsf{\beta }$, bone morphogenetic protein (BMP), growth differentiation factor (GDF), glial cell-derived neurotrophic factor (GDNF), and Activin/Inhibin subfamilies. A phylogenetic analysis revealed the evolutionary relationships among members of the TGF-$\mathsf{\beta }$ family in T. belangeri and their homologous genes in Homo sapiens, Mus musculus, and Pan troglodytes, indicating a high degree of conservation throughout evolution. A chromosomal distribution and collinearity analysis demonstrated the localization of these genes within the genome of T. belangeri and their collinearity with genes from other species. A gene structure and motif analysis further illustrated the conservation and diversity among TGF-$\mathsf{\beta }$ family members. A protein interaction network analysis highlighted the central roles of TGFB1, TGFB3, BMP7, and BMP2 in signal transduction. A functional enrichment analysis underscored the significance of the TGF-$\mathsf{\beta }$ signaling pathway in the biological processes of T. belangeri, particularly in cell proliferation, differentiation, and apoptosis. We assessed the impact of cold acclimation treatment on the expression of TGF-$\mathsf{\beta }$ family proteins in the adipose tissue (white adipose tissue [WAT] and brown adipose tissue [BAT]) of T. belangeri using ELISA technology, finding that protein expression levels in the experimental group were significantly higher than those of in the control group. These results suggested that cold acclimation may enhance the adaptability of T. belangeri to cold environments by modulating the expression of TGF-$\mathsf{\beta }$ family genes. This study offers new insights into the role of the TGF-$\mathsf{\beta }$ family in the cold acclimation adaptation of T. belangeri, providing a scientific foundation for future genetic improvements and strategies for cold acclimation. Full article

Fibrosis represents a pivotal pathological process in numerous diseases, characterized by excessive deposition of extracellular matrix (ECM) that disrupts normal tissue architecture and function. In the heart, cardiac fibrosis significantly impairs both structural integrity and functional capacity, contributing to the progression of heart failure. Central to this process are cardiac fibroblasts (CFs), which, upon activation, differentiate into contractile myofibroblasts, driving pathological ECM accumulation. Transforming growth factor-beta (TGFβ) is a well-established regulator of fibroblast activation; however, the precise molecular mechanisms, particularly the involvement of ion channels, remain poorly understood. Emerging evidence highlights the regulatory role of ion channels, including calcium-activated potassium (K_Ca) channels, in fibroblast activation. This study elucidates the role of ion channels and investigates the mechanism by which Yoda1, an agonist of the mechanosensitive ion channel Piezo1, modulates TGFβ-induced fibroblast activation. Using NIH/3T3 fibroblasts, we demonstrated that TGFβ-induced activation is regulated by tetraethylammonium (TEA)-sensitive potassium channels, but not by specific K⁺ channel subtypes such as BK, SK, or IK channels. Intriguingly, Yoda1 was found to inhibit TGFβ-induced fibroblast activation through a Piezo1-independent mechanism. Transcriptomic analysis revealed that Yoda1 modulates fibroblast activation by altering gene expression pathways associated with fibrotic processes. Bromodomain-containing protein 4 (BRD4) was identified as a critical mediator of Yoda1’s effects, as pharmacological inhibition of BRD4 with JQ1 or ZL0454 suppressed TGFβ-induced expression of the fibroblast activation marker Periostin (Postn). Conversely, BRD4 overexpression attenuated the inhibitory effects of Yoda1 in both mouse and rat CFs. These results provide novel insights into the pharmacological modulation of TGFβ-induced cardiac fibroblast activation and highlight promising therapeutic targets for the treatment of fibrosis-related cardiac pathologies. Full article

Objective: This study aimed to evaluate the effects of local use of Brazilian Green Propolis (BGP), either as an ethanolic extract (the most common formulation) or incorporated into lipid-based nanostructures, as an adjuvant therapy for non-surgical periodontal treatment in managing experimental periodontitis (EP) in ovariectomized rats. Methods: Fifty-six female Wistar rats underwent bilateral ovariectomies. After 10 weeks, a cotton ligature was placed around the lower first molar and remained in place for two weeks to induce EP. The ligature was removed, and the rats were randomly assigned in the groups NLT (n = 14), SRP (n = 14), SRP-BGPee (n = 14), and SRP-BGPlns (n = 14). In the NLT group, no local treatment was performed. The SRP group received scaling and root planing (SRP), along with irrigation using a physiological saline solution. The SRP-BGPee group underwent SRP and irrigation with ethanolic extract of BGP. The SRP-BGPlns group underwent SRP and irrigation with BGP-loaded lipid nanostructure (BGPlns). Each group received one SRP session followed by four irrigation sessions with the specified solutions, which were conducted immediately after SRP and subsequently after 2, 4, and 6 days. Euthanasia was performed at 7 and 28 days following the removal of the ligatures. The hemimandibles were processed for the following analyses: microtomographic analysis; histological analysis; histometric analysis of the percentage of bone tissue in the furcation region (PBT); and immunohistochemical analysis for tartrate-resistant acid phosphatase activity (TRAP), transforming growth factor beta 1 (TGFβ1), and osteocalcin (OCN). Results: The SRP-BGPlns group demonstrated superior periodontal tissue repair, reduced alveolar bone loss, fewer TRAP-positive cells (at 7 days), and higher levels of immunolabeling for TGFβ1 (at both 7 and 28 days) and OCN (at 28 days) compared to the other experimental groups. Conclusions: The irrigation with BGP is an effective adjuvant therapy for non-surgical periodontal treatment in managing EP in ovariectomized rats. Its application in lipid-based nanostructures proved to be more effective than the ethanolic extract form. Full article

Mesenchymal stem cells (MSCs) represent a promising cell source for cartilage tissue engineering due to their chondrogenic potential. However, current differentiation protocols result in limited efficiency. This study assessed the combined effects of transforming growth factor-beta 3 (TGF-β3) and fibroblast growth factor-2 (FGF-2) on the morphology, proliferation, chondrogenic differentiation, chondrogenic gene expression, and cytokine profile of ovine bone marrow-derived MSCs (BM-MSCs). BM-MSCs were cultured under four conditions: control (αMEM) or αMEM supplemented with FGF-2, TGF-β3, or TGF-β3 + FGF-2. Morphological and proliferation analyses, Alcian blue staining in 2D and 3D, and real-time PCR for early (Chad, Comp, and Sox 5) and late (Agg, Col IX, Sox 9, and Fmod) chondrogenic markers were performed. Cytokine secretion profiles were analyzed using multiplex assay. TGF-β3 induced morphological changes indicative of early chondrogenesis, while FGF-2 enhanced proliferation. The combination of both cytokines led to a synergistic increase in cell proliferation, early and late chondrogenic gene expression, and glycosaminoglycans (GAG) deposition. Cytokine analysis revealed that TGF-β3 enhanced the immunomodulatory and angiogenic profile of BM-MSCs, whereas co-treatment with FGF-2 yielded a balanced and potentially regenerative secretome. Dual stimulation with TGF-β3 and FGF-2 significantly improves the chondrogenic differentiation of ovine BM-MSCs by enhancing both molecular and functional markers of cartilage formation. Full article

Transforming growth factor-beta (TGF-β) exhibits dual roles in pancreatic ductal adenocarcinoma (PDAC), acting as a tumor suppressor in early stages and a tumor promoter in later disease. Among the three isoforms, TGFB2 is particularly associated with poor prognosis and aggressive phenotypes. This study evaluated the prognostic significance of TGFB2 mRNA and methylation levels in PDAC, with an emphasis on age-dependent effects. Bioinformatic analyses revealed that high TGFB2 expression was significantly associated with reduced overall survival (OS) in patients under 65 (TGFB2 high vs. low median OS: 17.9 vs. 66.9 months) but not in older cohorts. IL6 expression, a downstream target of TGF-β, followed a similar survival profile. Moreover, elevated TGFB2 methylation showed improved survival in younger patients (high methylation vs. low methylation median OS: 66.9 vs. 17.9 months). In addition, our clinical data from a PDAC trial using OT-101, an antisense oligonucleotide targeting TGFB2, further supported these findings—young patients treated with OT-101 showed improved OS compared to untreated controls. Notably, the methylation of TGFB1 also correlated with better OS in young patients. These results demonstrate the importance of TGFB2 as both a prognostic biomarker and therapeutic target in younger PDAC patients and further suggest that epigenetic modulation plays a key role in TGF-β signaling in pancreatic cancer progression. Our study emphasizes the isoform- and age-specific prognostic significance of TGFB2 in PDAC and supports the potential insights provided through methylation and expression profiling for personalized treatment strategies, particularly for younger patients who may benefit most from TGFB2-targeted therapies. Full article

Introduction: Thyroid cancer and obesity are prevalent conditions with significant global health implications. Differentiated thyroid cancer (DTC) is influenced by various molecular pathways, including those involving Transforming Growth Factor-Beta (TGF-β), a cytokine implicated in cell proliferation, differentiation, immune regulation, and fibrosis. Obesity (BMI > 30) has been associated with thyroid dysfunction and an increased incidence of nodular goiter. However, the relationship between TGF-β levels, thyroid malignancies, and metabolic disturbances remains unclear. This study aimed to analyze TGF-β1, -2, and -3 concentrations in blood serum before and after thyroidectomy in patients with DTC and obese individuals with nodular goiter to evaluate their potential role in thyroid pathology and obesity-related metabolic changes. Methods: A prospective study was conducted at a high-volume surgical center where over 700 thyroidectomy procedures are performed annually. Seventy-six consecutive patients (aged 26–79 years) were included: 21 with DTC and 55 with euthyroid nodular goiter. The latter group was subdivided based on BMI into obese (BMI > 30, n = 26) and non-obese (BMI < 30, n = 29) cohorts. Blood samples were collected preoperatively and on the first postoperative day for TGF-β quantification using the Bio-Plex Pro™ Human Cytokine Assay. Statistical analysis was performed using the Student’s t-test. Results: Postoperatively, patients with DTC exhibited significantly higher TGF-β1 (210,000 pg/mL), TGF-β2 (360 pg/mL), and TGF-β3 (170 pg/mL) levels compared to obese patients with nodular goiter (p < 0.05). In the nodular goiter group, BMI did not significantly influence preoperative TGF-β levels (p > 0.05). However, postoperatively, obese patients showed lower TGF-β1 (100,000 pg/mL) and TGF-β2 (30 pg/mL) levels compared to normal-weight individuals (p = 0.03), while no significant difference was observed for TGF-β3 (p > 0.05). Conclusions: The study highlights distinct alterations in TGF-β isoform levels in thyroid cancer and obesity. Elevated postoperative TGF-β levels in DTC patients suggest a role in tumor progression and response to surgical intervention. In contrast, the reduction of TGF-β1 and TGF-β2 levels in obese patients postoperatively may indicate a complex interplay between obesity, surgical stress, and cytokine regulation. These findings underscore the need for further research into the molecular mechanisms governing TGF-β dynamics in thyroid disorders and obesity, with potential implications for therapeutic interventions. Full article