PPAR-γ Activation Alleviates Osteoarthritis through Both the Nrf2/NLRP3 and PGC-1α/Δψ m Pathways by Inhibiting Pyroptosis.

Osteoarthritis (OA) is a common degenerative joint disease with a gradually increasing morbidity in the aging and obese population. Emerging evidence has implicated pyroptosis in the etiology of OA and it may be recognized as a therapeutic target in OA. We have previously reported regarding another disease that peroxisome proliferator-activated receptor gamma (PPAR-γ) activation exerts an anti-inflammatory effect by suppressing the nucleotide-binding and oligomerization domain-like receptor containing protein (NLRP) 3 inflammasome. However, the relationship between PPAR-γ and NLRP3-mediated pyroptosis in OA cartilage and its underlying mechanisms is fully unclear. In this study, we found that the level of NLRP3-mediated pyroptosis in severe lateral femoral condyle cartilage wear in the knee of an OA patient was significantly higher than that in the mild lateral femoral condyle cartilage wear areas. Moreover, in lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced primary chondrocytes and knee OA rat models, we demonstrated that activation of PPAR-γ by pioglitazone (Piog) attenuated LPS/ATP-induced chondrocyte pyroptosis and arthritis. These effects were partially counteracted by either blocking the nuclear factor erythroid-2-related factor (Nrf2)/NLRP3 or PGC1-α/Δψ m signaling pathway. Simultaneous depression of these two signaling pathways can completely abrogate the protective effects of Piog on OA and chondrocytes. Taken together, Piog protects OA cartilage against pyroptosis-induced damage by simultaneously activating both the Nrf2/NLRP3 and PGC-1α/Δψ m pathways, which enhances antioxidative and anti-inflammatory responses as well as mitochondrial biogenesis. Therefore, Piog may be a promising agent for human OA cartilage damage in future clinical treatments.

Effects of biowaste-derived biochar on the dynamic behavior of cadmium fractions in soils.

As a commonly used amendment to soil contaminated by heavy metals, biochar has attracted great attention and has been applied for decades due to the benefits to the soil. However, the effects of biochar on the dynamic behavior of soil properties and metal fractions are still unclear. Here, we used two biochars, derived from biowastes (reed and bamboo willow), to treat two cadmium (Cd)-contaminated soils, S1 (loamy sand) and S2 (sandy loam), and determined the dynamic effects. The incubation experiments were designed to investigate the effects of biochar on the dynamic behavior of soil pH, dissolved organic matter (DOM), bioavailable Cd, and the transformation of Cd fractions for 270 days. The results showed that the soil pH, DOM, and bioavailable Cd initially increased and then decreased with incubation time, and the soil pH and DOM were higher, but bioavailable Cd content was lower than the original value. The transformation of the metal fractions changed dynamically, and the exchangeable fraction of Cd decreased with incubation time. Furthermore, the correlation results showed that the DOM can directly control the redistribution of Cd fractions, while soil pH can control it indirectly by regulating the DOM. This study highlighted that biochar can affect soil pH and DOM, redistribute Cd fractions, decrease bioavailable Cd content, and lower the potential risk of heavy metals. This study suggests ways to immobilize heavy metals in contaminated soils using biochar.

Safinamide prevents lipopolysaccharide (LPS)-induced inflammation in macrophages by suppressing TLR4/NF-κB signaling.

Inflammation is a basal host defense response that eliminates the causes and consequences of infection and tissue injury. Macrophages are the primary immune cells involved in the inflammatory response. When activated by LPS, macrophages release various pro-inflammatory cytokines, chemokines, inflammatory mediators, and MMPs. However, unbridled inflammation causes further damage to tissues. Safinamide is a selective and reversible monoamine oxidase B (MAOB) inhibitor that has been used for the treatment of Parkinson's disease. In this study, we aimed to investigate whether safinamide has effects on LPS-treated macrophages. Our results show that safinamide inhibited the expression of pro-inflammatory cytokines such as IL-1α, TNF-α, and IL-6. Furthermore, safinamide suppressed the production of CXCL1 and CCL2, thereby preventing leukocyte migration. In addition, safinamide reduced iNOS-derived NO, COX-2-derived PGE2, MMP-2, and MMP-9. Importantly, the functions of safinamide mentioned above were found to be dependent on its inhibitory effect on the TLR4/NF-κB signaling pathway. Our data indicates that safinamide may exert a protective effect against inflammatory response.

Lysine crotonylation of DgTIL1 at K72 modulates cold tolerance by enhancing DgnsLTP stability in chrysanthemum.

Lysine crotonylation of proteins is a recently identified post-translational modification (PTM) in plants. However, the function of lysine-crotonylated proteins in response to abiotic stress in plants has not been reported. In this study, we identified a temperature-induced lipocalin-1-like gene (DgTIL1) from chrysanthemum and showed that it was notably induced in response to cold stress. Overexpression of DgTIL1 enhanced cold tolerance in transgenic chrysanthemum. Ubiquitin membrane yeast two-hybrid (MYTH) system and bimolecular fluorescence complementation (BIFC) assays showed that DgTIL1 interacts with a nonspecific lipid transfer protein (DgnsLTP), which can promote peroxidase (POD) gene expression and POD activity to reduce the accumulation of reactive oxygen species (ROS) and improve resistance to cold stress in DgnsLTP transgenic chrysanthemum. In addition, we found that DgTIL1 was lysine crotonylated at K72 in response to low temperature in chrysanthemum. Moreover, lysine crotonylation of DgTIL1 prevented DgnsLTP protein degradation in tobacco and chrysanthemum. Inhibition of DgnsLTP degradation by lysine crotonylation of DgTIL1 further enhanced POD expression and POD activity, reduced the accumulation of ROS under cold stress in DgTIL1 transgenic chrysanthemum, thus promoting the cold resistance of chrysanthemum.