Curcumin offers protective effects on the retinas of diabetic mice, likely through the modulation of the Hippo-YAP signaling pathway and the inhibition of EndMT. These findings provide support for the use of curcumin as a promising adjunctive therapy for diabetic retinopathy.

While next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide and abiraterone, have revolutionized CRPC treatment, resistance to these therapies remains a significant challenge, rendering the disease incurable. Compelling evidence further suggests that combining PLK1 inhibition with paclitaxel could serve as an effective therapeutic strategy to overcome resistance in CRPC by targeting microtubule dynamics. This review examines the mechanistic role and broader implications of PLK1 in CRPC treatment, offering valuable insights into potential combination therapies to improve efficacy and patient outcomes.

In contrast, Mode 3 exhibited comparatively more stable and physically interpretable interaction energy profiles with sustained negative interaction energies and reduced fluctuation amplitudes...Among the evaluated docking modes, Modes one and 3 exhibited the most favorable balance between structural persistence and energetic stability. These findings provide computational support for the potential of the quinazoline-based scaffold C9 as a candidate KRAS-targeting compound and establish a mechanistic framework for future structure-guided optimization and experimental validation in KRAS-driven lung cancer systems.

D-box binding protein (DBP) is a high-amplitude proline- and acidic amino acid-rich basic leucine zipper (PAR bZIP) transcription factor that functions as a key circadian output regulator downstream of the core molecular clock...We also highlight the current limits of human translational evidence and propose that DBP-centered signatures may be useful for interpreting circadian output failure in disease. Overall, DBP provides a mechanistically informative framework for understanding how circadian time is transformed into organ-specific physiological function and pathological vulnerability.

The only CYP17A1 inhibitor available in therapy, abiraterone acetate, faces significant limitations due to its steroidal structure, which causes off-target effects and generates agonistic metabolites that paradoxically stimulate the androgen receptor (AR)...In vitro assay results correlated with a suggested mechanism, showing preferential cytotoxicity toward androgen-dependent LNCaP cells (AR+) while sparing AR-negative lines (DU145, PC3) and healthy human fibroblasts (BJ). Our compounds present a promising starting point for further development of non-steroidal CYP17A1 inhibitors.

Blunted nocturnal melatonin amplitude is linked to tumour-promoting inflammation in oesophageal-cancer survivors, but it is unclear whether restoring endogenous rhythms improves clinical outcomes...Behavioural realignment of endogenous melatonin rhythms was associated with sustained reductions in systemic inflammation and fewer adverse events in oesophageal-cancer survivors. Routine circadian-hygiene counselling combined with simple salivary monitoring may help support long-term oncologic and cardiometabolic health.

Current data support a circadian influence on NK biology, but the direction and magnitude of reported effects vary across species, sampling schedules, circadian phase definitions, tissue compartments, and NK-cell readouts. This heterogeneity underscores the need for longitudinal, high-frequency sampling with complementary continuous monitoring to define phase, amplitude, and stability across physiological and clinical contexts.

The tonic current was only partially reverted by the GluN2B subunit specific NMDA receptor (NMDAR) antagonist ifenprodil, whereas SICs were almost fully eliminated. The amplitude of the current was inversely proportional with the age of the patient and disappeared in elderly over the age of 70...In summary, NMDAR-dependent tonic inward currents are overlapping but partially separable phenomena from SICs. One might hypothesize that the tonic current is only present under excitotoxic conditions and do not determine physiological neuronal excitability in human.

Direct AR antagonism enhances functional PSMA availability and increases short-term uptake of PSMA-targeted radioligands in AR-positive prostate cancer models. These findings provide mechanistic support for AR-mediated modulation of PSMA-targeted radioligand delivery and warrant further translational investigation.

P2, N=202, Not yet recruiting, Mayo Clinic

This newly established model of mechanical stress injury effectively recapitulates the pathophysiology of CST damage following ICH. It also provides a simple and reproducible tool for conducting preclinical studies on mechanical stress-induced WMI in ICH.