SMAD3 (SMAD Family Member 3)

Notably, the AXL inhibitor Bemcentinib effectively suppressed CML-BP progression in both in vivo and in vitro models. Collectively, our findings establish SE-driven SOX4 and SMAD3 as key regulators in CML-BP and identify Bemcentinib as a promising therapeutic strategy.

This study investigates the therapeutic efficacy of sacubitril/valsartan in a bleomycin-induced rat model of pulmonary fibrosis. Additionally, sacubitril/valsartan treatment resulted in a notable reduction in pulmonary levels of transforming growth factor-β (TGF-β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), indicating attenuation of both fibrotic and inflammatory responses. Collectively, these findings suggest that sacubitril/valsartan mitigates pulmonary fibrosis through modulation of the SNHG-16/miR-455 axis and inhibition of the Notch-2/Smad-3/TGF-β signaling cascade, highlighting its potential as a promising therapeutic strategy for the management of pulmonary fibrosis.

Compared to normal tissue an increased expression of NOX4, OGG1, MSH2/MSH6 proteins and phospho-Smad3 was found in RAI Refractory BRAFV600E mutated tumors. Collectively, our findings reveal a mechanistic basis for NOX4's role in thyroid dedifferentiation.

More encouragingly, this optimized AANG can effectively block MMT-derived cancer progression on mouse cancer models with syngeneic lung cancer LLC and human NSCLC xenograft A549 without side-effect in vivo. Thus, AANG may represent the first natural compound formulation for blocking MMT-derived pro-tumoral CAF formation in the clinical NSCLC.

RARγ also acts as a co-factor to Smad3 and reduced or enhanced TGFβ-driven and Smad3-mediated events when liganded and non-liganded, respectively. Collectively the findings support the view that RARγ plays a crucial role in controlling stem and progenitor cell behavior.

Thus, our data support a model in which cyclin D1/D2-CDK4 promotes phosphorylation of Smad3, leading to upregulation of integrin subunits, activation of FAK and Rac1, and consequent lamellipodia formation and cell migration. These findings provide direct evidence that CDK4 regulates actin cytoskeletal reorganization during cell migration and suggest that CDK4/6 inhibitors may dampen cytoskeleton-dependent tumor invasion, in addition to their antiproliferative effects.

Tissue analysis revealed immune activation in the tumor microenvironment, while peripheral blood and spleen showed systemic immune responses following ARA + RT. Our study provides novel insights into how ARAs enhance RT efficacy through immunomodulation involving TGF-β/pSmad3C cascade, offering therapeutic implications in GBM.

Seventy-two rats were divided into six groups: Control, BLM, BHD, prednisone acetate, SN, and PC. BHD, PC, and SN alleviated BLM-induced lung inflammation and collagen deposition, reduced Wnt3a, glycogen synthase kinase 3 beta, β-catenin, and transforming growth factor beta 1 (TGF-β1) mRNA/protein expression, and decreased the p-Smad3/Smad3 ratio. BHD and its fractions alleviate PF through dual inhibition of Wnt/β-catenin and TGF-β1/Smad pathways, with SN demonstrating the highest overall efficacy.

Notably, low-dose 6-mercaptopurine disrupted SAICAR-driven immunosuppression and synergized with anti-PD-1 treatment without inducing systemic immune toxicity. Together, these findings establish SAICAR as an immunometabolic regulator that links purine metabolism to immune evasion and highlight a therapeutically actionable pathway to overcome metabolite-driven resistance to immune checkpoint blockade.

In addition, PAQR3 overexpression reduced TGF-b1, p-Smad3, and p-Smad2 (P < 0.001), while increasing Smad3 and Smad2, indicating suppression of the TGF-b pathway. These findings suggest that PAQR3 inhibits metastasis and induces ferroptosis in HCC through TGF-b pathway regulation.

Targeting surface ENO1 with HuL001, a first-in-class humanized antibody, significantly reduced glycolysis, decreased extracellular lactate accumulation, reprogrammed macrophage polarization and inhibited tumor growth and distant metastasis. Moreover, targeting surface ENO1 significantly increased the therapeutic response to radiotherapy and delayed tumor regrowth by increasing antitumoral M1 macrophages and cytotoxic CD8+ T cells infiltration within TME. These results indicated that targeting surface ENO1 remodeled the tumor microenvironment and provided better therapeutic effects to radiotherapy in poorly immunogenic colorectal cancer (CRC) and triple-negative breast cancer (TNBC).

This study aims to contrast the protective effects of "Canagliflozin; Cana" versus "Sitagliptin; Sita" in countering the chronic Cd-induced cardiac and hepatic damage. Both medications showed comparable cardio-hepatic protective effects. Yet, Cana outperformed Sita as a potentially effective therapy to counteract the negative consequences of chronic Cd-induced cardiac and hepatic pathologies.