Combination of pirfenidone and simvastatin demonstrated a synergistic therapeutic effect in reducing inflammation, fibrosis, and oxidative stress in an L-arginine-induced chronic pancreatitis mouse model, suggesting promise for chronic pancreatitis management.

In this study, a total of 100 patients with AIS were included for the current analysis (n = 50 for combination therapy of evolocumab and atorvastatin, PI group, n = 50 for atorvastatin monotherapy, AT group). http://www.chictr.org.cn; Identifier: ChicTR2200059445. Date of registration: 29 April 2022.

Collectively, these findings suggest that atorvastatin may disrupt the 'CSDH cycle' by modulating critical inflammatory, angiogenic and fibrinolytic mechanisms, providing a scientific rationale for its therapeutic application in CSDH management. Further in vivo studies are warranted to validate these preliminary observations and to explore clinical translation to the clinic.

P1, N=60, Not yet recruiting, International Vaccine Institute

P3, N=400, Recruiting, Central South University | N=200 --> 400

P2, N=60, Recruiting, Dow University of Health Sciences

P3, N=1652, Recruiting, Aarhus University Hospital | Not yet recruiting --> Recruiting

Leveraging the observed sensitivity of muscle cells to atorvastatin in clinical settings and utilizing untargeted metabolomic analysis of atorvastatin-treated RD rhabdomyosarcoma cells, we identified reduced levels of aminoadipic acid, an intermediate in lysine catabolism...However, we demonstrated that it is catabolically cleaved to p-nitroanilide, with this molecule driving the cytotoxic activity observed in our experiments. Although lysine metabolism was not fully suppressed by lysine-p-nitroanilide, these findings provide valuable insights for developing novel therapies for rhabdomyosarcoma.

Fusion cells accumulated abundant intracellular lipid droplets and were highly sensitive to simvastatin treatment in vitro and in vivo. Together, this study uncovered that CBX3-SNX10-ANO6 signaling facilitates generation of an aggressive tumor-LAM fusion cell subpopulation that promotes metastasis, revealing an alternative metastatic mechanism and exposing putative therapeutic vulnerabilities. Single-cell transcriptomic profiling combined with functional and clinical validation identifies fusion of tumor cells and lipid-associated macrophages mediated by the CBX3-SNX10-ANO6 axis as a potentially targetable mechanism driving cancer metastasis.

Moreover, we identified simvastatin as a potent inhibitor of CDT1, effectively inhibiting CDT1-mediated centrosome amplification and PGCC formation. In summary, our findings reveal a critical role for CDT1 in driving centrosome amplification and PGCC formation through activation of the PLK4/SASS6 axis, which subsequently contributes to therapeutic resistance and malignant progression.

P4, N=400, Not yet recruiting, Shiraz University of Medical Sciences