SIRT1 (Sirtuin 1)

Our study identified SIRT expression in macrophages of the DLBCL environment and specifically the importance of SIRT1 in the DLBCL M1 macrophage immune microenvironment. This opens an avenue for the potential translational exploitation of SIRT1 modulation as therapeutic target in this hematological malignancy.

Network pharmacology also revealed the involvement of SA1-4 and key targets-regulated SIRTs in neurodegeneration, including non-amyloidogenic cascade, tau phosphorylation, calcium homeostasis, insulin-mediated glucose uptake, and neuroinflammation. Therefore, SA1-4 exert promising multi-target therapeutic strategies against oxidative damage, potentially offering alternative anti-Alzheimer candidates for further clinical neurodegenerative and anti-aging therapeutics.

GA co-treatment significantly ameliorated these alterations, reducing inflammatory and apoptotic markers, restoring SIRT-1, and suppressing p53 activation. Collectively, GA exerts hepatoprotective effects through modulation of the TLR-4/NF-κB/IL-6 pathway and restoration of the SIRT-1/p53 regulatory axis, highlighting its immunopharmacological potential in sepsis-induced hepatic dysfunction.

SIGNIFICANCE STATEMENT: This study demonstrates that empagliflozin attenuates doxorubicin (DOX)-induced renal impairment in rats and promotes DOX's cytotoxic effects via its antioxidant and anti-inflammatory potentials. These preclinical findings highlight empagliflozin as a hopeful therapeutic tool to preserve the kidney during DOX treatment.

Distinct integrated sirtuin scores thus capture subtype-specific metabolic/epigenetic states and provide robust RFS stratification across BC subtypes. These findings highlight sirtuins as integrators of longevity pathways and tumor metabolism, suggesting therapeutically exploitable vulnerabilities along NAD⁺-dependent regulatory axes.

FKBPL-based peptide mimetic, AD-01 (1 nM), in high-glucose conditions, upregulated endothelial vcam1 and glut1 mRNA expression, independent of miR-302b-5p. FKBPL plays an important role in glucose metabolism, endothelial function, angiogenesis, cardiac inflammation and function, and could be explored as a therapeutic target of cardiovascular disease both in nondiabetes and diabetes settings using precision medicine approach.

β-Estradiol mitigates oxidative stress, induces apoptosis, and suppresses pro-survival, metastatic, and chemoresistant pathways-contrasting testosterone's minimal effects. These findings align with HCC's male predominance and highlight the hormone-modulated strategies' potential for future therapeutic exploration.

P=N/A, N=45, Not yet recruiting, Hacettepe University

BaSO4NPs provoked severe hepatic impairments by altering biochemical, computational and histological parameters. The concurrent therapy of AYN mitigated the adverse impacts of BaSO4NPs on hepatic tissues through the regulation of key signaling pathways, redox state, inflammatory and apoptotic indices, and histological alterations.

Although dexrazoxane is the only FDA-approved cardioprotective agent, concerns about its long-term safety and potential interference with doxorubicin's antitumor effectiveness have increased the search for safer alternatives. Despite promising preclinical evidence of their antioxidant, anti-inflammatory, and anti-apoptotic properties, the clinical use of phytochemicals is limited by issues such as low bioavailability, poor specificity, dose-dependent toxicity, variable pharmacokinetics, and lack of standardisation. Therefore, innovative approaches-such as ligand-targeted delivery systems, nanotechnology-based formulations, and structural modifications of lead compounds-are essential to enhance their pharmacological properties, safety, and therapeutic effectiveness for effective cardioprotection against doxorubicin-induced toxicity.

Furthermore, curcumin significantly inhibited tumor growth (p=0.039) and exhibited a synergistic antitumor effect with oxaliplatin in vivo. This study comprehensively elucidates the molecular mechanisms by which curcumin exerts its therapeutic effects in CRC via modulation of ferroptosis and Wnt/β-catenin signaling pathway. These findings provide novel mechanistic insights and support the translational potential of curcumin in preclinical and clinical frameworks.

In contrast, other zinc-dependent HDACs, including HDAC8, displayed negligible or very weak activity on full-length CTTN. These findings provide new mechanistic insight into KDAC substrate preferences and highlight the value of biochemical reconstitution for dissecting complex acetylation networks.