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Tuning magnetic frustration via composition : spin-glass dynamics and phase diagrams of sigma-phase Fe–Cr–Ni alloys
No full textLaser-based photobiomodulation in postoperative tissue healing in oral and maxillofacial surgery : systematic review of RCTs
No full textCasticin inhibits AKR1C3 and enhances abiraterone efficacy in castration-resistant prostate cancer
No full textCastration-resistant prostate cancer (CRPC) continues to represent a critical therapeutic hurdle owing to its resistance to both androgen deprivation and next-generation antiandrogens like abiraterone (ABI). One of the key mechanisms underlying this resistance involves overexpression of aldo-keto reductase 1C3 (AKR1C3), an enzyme contributing to intratumoral androgen biosynthesis. In this study, casticin (CAS), a flavonoid derived from Vitex agnus-castus, was identified as a potent inhibitor of AKR1C3. CAS showed potent inhibitory activity in enzymatic assays ( = 5.99 µM), significantly suppressed AKR1C3-mediated coumberone metabolism in 22Rv1 prostate cancer cells, and showed greater cytotoxicity in AKR1C3-expressing 22Rv1 cells relative to AKR1C3-deficient LNCaP cells. CAS significantly enhanced ABI’s cytotoxic efficacy in 22Rv1 cells, as evidenced by synergistic interactions (CI: 0.31-0.71); however, no such synergy was observed in LNCaP cells or with enzalutamide. CAS enhanced apoptosis in ABI-treated 22Rv1 cells, as well as combination showed only a limited effect against normal epithelial PNT-2 cell line. Docking and molecular dynamics simulations indicated a stable CAS-AKR1C3 interaction, characterized by crucial hydrogen bonding and aromatic stacking within the active site. These results suggest that CAS is a promising chemosensitizer targeting AKR1C3 to overcome ABI resistance in CRPC
Neurological hospitalizations of patients with a history of past or present malignancy - an observational study from a tertiary neurology center
No full textVancomycin-resistant enterococci in healthcare settings : clonal analysis, resistance profiles, and biofilm formation of strains isolated from hospitalized patients
No full textThe application of infrared spectroscopy and DFT calculations to better understand interactions between bosentan hydrate and sildenafil base induced by high energy ball milling
No full textIn this study, infrared spectroscopy investigations in combination with DFT calculations were used to elucidate interactions between bosentan monohydrate (BOS) and sildenafil base (SIL) initiated under high energy ball milling. The research was focused mainly on the vibrational properties of their co-milled binary solid dispersions compared to the physical mixtures and single drugs.
First, the stability and structure of sildenafil isomers were established. Theoretical infrared spectra were also calculated for trimers and tetramers of bosentan monohydrate and they were compared to the experimental data. The results revealed shifts in wavenumbers, primarily related to the presence of hydrogen bonds, water interactions, and molecular rearrangements during the optimization process of DFT procedure.
Second, the infrared spectral analysis was carried out for co-milled binary formulations. The results showed significant changes in their vibrational dynamics related to the amorphization of crystalline drugs. Importantly, it was stated that the amorphous form was stabilized by hydrogen bonds created between BOS and SIL molecules. The classification of the spectra revealed distinct vibrational characteristics typical of binary amorphous solid dispersions. Importantly, the unique spectral classifications differed significantly from those of the corresponding physical mixtures. Finally, it was concluded that the mechanical activation of BOS and SIL base molecules under high energy ball milling resulted in a physical modification of their structure, which could translate into drug dissolution enhancement