Pterostilbene exert an anti-arthritic effect by attenuating inflammation, oxidative stress, and alteration of gut microbiota.

Pterostilbene is a revesterol analog with a long bioavailability and having potent anti-inflammatory activity in animal studies. In this study, we tried to scrutinize the anti-arthritic effect of pterostilbene against complete Freund's adjuvant (CFA)-induced arthritis model in rats. CFA was used for induction of the RA, and rats were divided into groups depending on different doses of pterostilbene given. Hepatic, antioxidant, rheumatoid factor (RF), myeloperoxidase (MPO), inflammatory cytokines, anti-collagen(C)II-Ig, inflammatory mediators, and gut microbiota were estimated. Pterostilbene significantly (p < .001) decreased the paw swelling, arthritic score, and increased the body weight. Besides altered the antioxidant, inflammatory mediators, anti-collagen (C)II Ig, and inflammatory cytokines. Furthermore, pterostilbene treatment helps to restore the ecosystem of gut microbiota in rats by reducing the relative abundance of Helicobacter, Desulfovibrio, Lachnospiraceae, and Mucispirillium. Based on the findings, we can say that pterostilbene has an anti-arthritic effect via suppressing inflammatory responses and altering intestinal bacteria. PRACTICAL APPLICATIONS: Arthritis is the painful disease and affected most of the people worldwide. In this experimental study, we estimated the anti-arthritic effect of pterostilbene against CFA-induced arthritis in rats. Pterostilbene noticeably suppressed the paw thickness, arthritic score, and organ index. Pterostilbene substantially altered the oxidative stress and inflammatory reaction. Pterostilbene considerably modulated the gut microbiota, suggesting the anti-arthritic effect.

The SIAH2-NRF1 axis spatially regulates tumor microenvironment remodeling for tumor progression.

The interactions between tumor cells with their microenvironments, including hypoxia, acidosis and immune cells, lead to the tumor heterogeneity which promotes tumor progression. Here, we show that SIAH2-NRF1 axis remodels tumor microenvironment through regulating tumor mitochondrial function, tumor-associated macrophages (TAMs) polarization and cell death for tumor maintenance and progression. Mechanistically, low mitochondrial gene expression in breast cancers is associated with a poor clinical outcome. The hypoxia-activated E3 ligase SIAH2 spatially downregulates nuclear-encoded mitochondrial gene expression including pyruvate dehydrogenase beta via degrading NRF1 (Nuclear Respiratory Factor 1) through ubiquitination on lysine 230, resulting in enhanced Warburg effect, metabolic reprogramming and pro-tumor immune response. Dampening NRF1 degradation under hypoxia not only impairs the polarization of TAMs, but also promotes tumor cells to become more susceptible to apoptosis in a FADD-dependent fashion, resulting in secondary necrosis due to the impairment of efferocytosis. These data represent that inhibition of NRF1 degradation is a potential therapeutic strategy against cancer.