4-Octyl itaconate protects chondrocytes against IL-1β-induced oxidative stress and ferroptosis by inhibiting GPX4 methylation in osteoarthritis.

The role of oxidative stress and ferroptosis in osteoarthritis (OA) pathogenesis is increasingly recognized. Notably, 4-octyl Itaconate (OI) has been documented to counteract oxidative stress and inflammatory responses, highlighting its therapeutic potential in OA. This study explored the effects of OI on GPX4 methylation, oxidative stress, and ferroptosis in chondrocytes affected by OA.

Design and evaluation of new analogs of the sweet protein brazzein.

We have previously modeled the interaction of the sweet protein brazzein with the extracellular domains of the sweet taste receptor. Here, we describe the application of that model to the design of 12 new highly potent analogs of brazzein. Eight of the 12 analogs have higher sweetness potency than wild-type brazzein.

Unusually high frequency MHC class I alleles in Mauritian origin cynomolgus macaques.

Acute shortages of Indian origin Rhesus macaques significantly hinder HIV/AIDS research. Cellular immune responses are particularly difficult to study because only a subset of animals possess MHC class I (MHC I) alleles with defined peptide-binding specificities. To expand the pool of nonhuman primates suitable for studies of cellular immunity, we defined 66 MHC I alleles in Cynomolgus macaques (Macaca fascicularis) of Chinese, Vietnamese, and Mauritian origin.

Probing the sweet determinants of brazzein: wild-type brazzein and a tasteless variant, brazzein-ins(R18a-I18b), exhibit different pH-dependent NMR chemical shifts.

Brazzein is a small, intensely sweet protein. As a probe of the functional properties of its solvent-exposed loop, two residues (Arg-Ile) were inserted between Leu18 and Ala19 of brazzein. Psychophysical testing demonstrated that this mutant is totally tasteless.

Monkey electrophysiological and human psychophysical responses to mutants of the sweet protein brazzein: delineating brazzein sweetness.

Responses to brazzein, 25 brazzein mutants and two forms of monellin were studied in two types of experiments: electrophysiological recordings from chorda tympani S fibers of the rhesus monkey, Macaca mulatta, and psychophysical experiments. We found that different mutations at position 29 (changing Asp29 to Ala, Lys or Asn) made the molecule significantly sweeter than brazzein, while mutations at positions 30 or 33 (Lys30Asp or Arg33Ala) removed all sweetness. The same pattern occurred again at the beta-turn region, where Glu41Lys gave the highest sweetness score among the mutants tested, whereas a mutation two residues distant (Arg43Ala) abolished the sweetness.

Critical regions for the sweetness of brazzein.

Brazzein is a small, heat-stable, intensely sweet protein consisting of 54 amino acid residues. Based on the wild-type brazzein, 25 brazzein mutants have been produced to identify critical regions important for sweetness. To assess their sweetness, psychophysical experiments were carried out with 14 human subjects.

Expression of Anti-PCNA mRNA Ribozyme by T7 Vaccinia Virus System in HeLa Cells.

We have designed and synthesized a hammer-head Rz targeted to human proliferating cell nuclear antigen (PCNA) mRNA at site No.524. Results showed that Rz524 can cleave the transcribed substrate RNA site-specifically in vitro.