Nitroaromatic-based triazene prodrugs to target the hypoxic microenvironment in glioblastoma.

Hypoxia is a hallmark of the glioblastoma multiforme microenvironment and represents a promising therapeutic target for cancer treatment. Herein, we report nitroaromatic-based triazene prodrugs designed for selective activation by tumoral endogenous reductases and release of the cytotoxic methyldiazonium ion a self-immolative mechanism. While compounds bearing a 2-nitrofuran bioreductive group were more efficiently activated by nitroreductases, 4-nitrobenzyl prodrugs 1b, 1d and 1e elicited a more pronounced cytotoxic effect against LN-229 and U-87 MG glioblastoma cell lines under hypoxic conditions when compared to temozolomide (TMZ), the golden standard for glioblastoma treatment.

Herbacetin Inhibits Human Fructose 1,6-Bisphosphatase Among a Panel of Chromone Derivatives and Pyrazoles, Demonstrating Positive Effects on Insulin-Resistant HepG2 Cells.

In patients with type 2 diabetes mellitus (DM), excessive gluconeogenesis is considered a major contributor to hyperglycemia. Therefore, targeting fructose 1,6-bisphosphatase (FBPase), a key regulatory enzyme involved in gluconeogenesis, has gained interest as a potential therapeutic target for managing DM. In this study, a library of 42 structurally-related chromone derivatives (including flavonoids, 2-styrylchromones, and 2-(4-arylbuta-1,3-dien-1-yl)chromones, named as 2-styrylchromone-related derivatives), as well as 4- and 5-styrylpyrazoles, were tested against human FBPase using a noncellular microanalysis screening system.

Poly(Ionic) Liquid-Enhanced Ion Dynamics in Cellulose-Derived Gel Polymer Electrolytes.

Gel polymer electrolytes (GPEs) are regarded as a promising alternative to conventional electrolytes, combining the advantages of solid and liquid electrolytes. Leveraging the abundance and eco-friendliness of cellulose-based materials, GPEs were produced using methyl cellulose and incorporating various doping agents, either an ionic liquid (1-Butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide [Pyr14][TFSI]), its polymeric ionic liquid analogue (Poly(diallyldimethylammonium bis(trifluoromethylsulfonyl)imide) [PDADMA][TFSI]), or an anionically charged backbone polymeric ionic liquid (lithium poly[(4-styrenesulfonyl)(trifluoromethyl(S-trifluoromethylsulfonylimino) sulfonyl) imide] LiP[STFSI]). The ion dynamics and molecular interactions within the GPEs were thoroughly analyzed using Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy (ATR-FTIR), Heteronuclear Overhauser Enhancement Spectroscopy (HOESY), and Pulsed-Field Gradient Nuclear Magnetic Resonance Diffusion (PFG-NMR).

Tumor microenvironment of Burkitt lymphoma: different immune signatures with different clinical behavior.

Burkitt lymphoma (BL) is characterized by a tumor microenvironment (TME) in which macrophages represent the main component, determining a distinct histological appearance known as "starry sky" pattern. However, in some instances, BL may exhibit a granulomatous reaction that has been previously linked to favorable prognosis and spontaneous regression. The aim of our study was to deeply characterize the immune landscape of 7 cases of Epstein-Barr virus-positive (EBV+) BL with granulomatous reaction compared with 8 cases of EBV+ BL and 8 EBV-negative (EBV-) BL, both with typical starry sky pattern, by Gene expression profiling performed on the NanoString nCounter platform.

Pyrazoles have a multifaceted anti-inflammatory effect targeting prostaglandin E, cyclooxygenases and leukocytes' oxidative burst.

Elevated levels of prostaglandin E have been implicated in the pathophysiology of various diseases. Anti-inflammatory drugs that act through the inhibition of cyclooxygenase enzymatic activity, thereby leading to the suppression of prostaglandin E, are often associated with several side effects due to their non-specific inhibition of cyclooxygenase enzymes. Consequently, the targeted suppression of prostaglandin E production with innovative molecules and/or mechanisms emerges as a compelling therapeutic strategy for the treatment of inflammatory-related diseases.