AIMS Differentiation of cardiac fibroblasts (Fbs) into myofibroblasts (MyoFbs) is responsible for connective tissue build-up in myocardial remodelling. We examined MyoFb differentiation and reversibility. METHODS AND RESULTS Adult rat cardiac Fbs were cultured on a plastic substratum providing mechanical stress, with conditions to obtain different levels of Fb differentiation. Fb spontaneousl...

Varieties of transforming growth factor-β (TGF-β) antagonists have been developed to intervene with excessive TGF-β signalling activity in cancer. Activin receptor-like kinase5 (ALK5) inhibitors antagonize TGF-β signalling by blocking TGF-β receptor-activated Smad (R-Smad) phosphorylation. Here we report the novel mechanisms how ALK5 inhibitors exert a therapeutic effect on a mouse B16 melanoma...

The epithelial-to-mesenchymal transition (EMT) is a well-known prerequisite for cancer cells to acquire the migratory and invasive capacity, and to subsequently metastasize. Bufalin is one of the major active components of the traditional Chinese medicine Chan Su, and accumulating evidence has shown its anticancer effect in multipe types of cancer. However, the role of bufalin in transforming g...

Hyperglycemia and hypoxia have independent and convergent roles in the development of renal disease. Transforming growth factor-β(1) (TGF-β(1)) is a key cytokine promoting the production of extracellular matrix proteins. The cationic-independent mannose 6-phosphate receptor (CI-M6PR) is a membrane protein that binds M6P-containing proteins. A key role is to activate latent TGF-β(1). PXS25, a no...

BACKGROUND/AIMS TGF-β plays a key role in the progression of various tumors. The main objective of our study was to investigate whether TGF-β is able to regulate N-nitrosodiethylamine (DEN)-induced hepatocellular carcinoma (HCC) progression in a mouse model by inducing Treg cell polarization. METHODS HCC progression, TGF-β and Foxp3 expression levels, serum TGF-β, IL10 and GP73 levels as well...

ABBREVIATIONS ACF aberrant crypt foci APC adenomatous polyposis coli ATM ataxia-telangiectasia mutated BER base excision repair BLM Bloom syndrome gene bp base pair BRCA1 and-2 breast and ovarian cancer genes 1 and 2 CDH1 cadherin 1 CHK2 checkpoint kinase 2 CIMP CpG island methylated phenotype CIN chromosomal instability COX-2 cyclo-oxygenase-2 CRC colorectal cancer CSGE conformation-sensitive ...

AR signaling is essential for the growth and survival of prostate cancer (PCa), including most of the lethal castration-resistant PCa (CRPC). We previously reported that TGF-β signaling in prostate stroma promotes prostate tumor angiogenesis and growth. By using a PCa/stroma co-culture model, here we show that stromal TGF-β signaling induces comprehensive morphology changes of PCa LNCaP cells. ...

Abstract Background and aims Cytotoxic CD8+ T cells mediate myocardial damage in patients with virus induced myocarditis, plaque erosion during acute coronary syndrome, promote adverse post-ischemic cardiac remodeling. There is emerging evidence to support a link between inflammation atrial fibrillation (AF). Protease-activated receptor 1 (PAR1) the thrombin expressed on platelets, but it also ...

Skin cancer treatment is a combination of BRAF and MEK kinase inhibitors administered as tablets, along with immunotherapy (treatment into the vein) group drugs that inhibit activity immune barrier proteins PD-1 PDL1. Here, we propose new approach to therapy for melanoma BRAF/MEK inhibitor anti-PD-1. With help explicit analytical functions, were able model this combined present in mathematical ...

Human embryonic stem cells (hESCs) hold enormous promise for regenerative medicine. Typically, hESC-based applications would require their in vitro differentiation into a desirable homogenous cell population. A major challenge of the current hESC differentiation paradigm is the inability to effectively capture and, in the long-term, stably expand primitive lineage-specific stem/precursor cells ...