In view of pleotropic impact of MAPK, we thought whether MAPK targeting would enhance sensitivity of highly resistant PDAC cells toward gemcitabine...Indeed, in-silico data, corroborating in vitro findings, demonstrated that high expression of p38α (MAPK14) confer poor prognosis and disease-free survival in PDAC patients over p38MAPK low tumor patients. Taken together our data, potentially demonstrated that p38MAPK targeting is potential approach for breaking resistance of PDAC toward chemotherapy and may contribute to controlling PDAC burden effectively.

P1, N=6, Completed, GEn1E Lifesciences | Recruiting --> Completed

These findings identify inflammation-induced pyroptosis as a central driver of the pathological changes in PON-induced cardiotoxicity. Notably, our work highlights BMP-7's capacity to inhibit these disease-related alterations. Collectively, these results expand on the current knowledge of the mechanistic framework of PON-induced cardiotoxicity, while also emphasizing BMP-7 as a promising therapeutic candidate with potential translational relevance.

FGFR2 is lowly expressed in DFU and can exert a protective effect by activating the PI3K/Akt pathway. It is a candidate diagnostic biomarker and potential therapeutic target for DFU.

P2, N=159, Completed, EIP Pharma Inc | Trial primary completion date: Oct 2024 --> May 2025

P2, N=25, Completed, EIP Pharma Inc | Active, not recruiting --> Completed

SLC12A8 promotes immune evasion and metastasis in Luminal B breast cancer by inducing CD8+ T-cell exhaustion via activation of the TLR signaling pathway, suggesting its potential as a prognostic biomarker and therapeutic target.

In vivo, endothelial GPRC5B deficiency significantly accelerated tumor growth and neovascularization, phenotypes that were effectively reversed by the p38 inhibitor SB202190. Clinical specimens corroborated reduced GPRC5B expression and increased microvessel density in MetS-associated PCa. Collectively, our findings establish endothelial GPRC5B downregulation as a key molecular driver promoting pathological angiogenesis via the MKK3/6-DUSP1-p38 axis, suggesting that targeting this signaling cascade offers a promising therapeutic strategy for managing MetS-associated PCa aggression.

The p38 MAPK inhibitor SB202190 reversed ORI-induced effects on cell death, cell migration and invasion, and apoptosis, highlighting the critical role of the p38 MAPK/p53 pathway. ORI effectively suppressed subcutaneous tumour growth in nude mice without notable toxicity while upregulating apoptosis-related proteins Bax and cleaved caspase-3 and downregulating Bcl-2 through activation of the p38 MAPK/p53 pathway.

Pharmacodynamic findings confirm that POLB 001 inhibits LPS-induced local and systemic inflammation in vivo through inhibition of p38 MAPK. https://onderzoekmetmensen.nl/en/trial/51741, identifier NL81214.056.22.

These results suggest that BMP-7 might inhibit PON-induced cardiotoxicity. Furthermore, our findings pave the way for future translational studies with BMP-7, which can demonstrate the therapeutic potential of BMP-7 in a clinical setting.

P1, N=6, Recruiting, GEn1E Lifesciences | Not yet recruiting --> Recruiting