Quercetin Modulates Ferroptosis via the SIRT1/Nrf-2/HO-1 Pathway and Attenuates Cartilage Destruction in an Osteoarthritis Rat Model.

Osteoarthritis (OA) is the most common joint disease, causing symptoms such as joint pain, swelling, and deformity, which severely affect patients' quality of life. Despite advances in medical treatment, OA management remains challenging, necessitating the development of safe and effective drugs. Quercetin (QUE), a natural flavonoid widely found in fruits and vegetables, shows promise due to its broad range of pharmacological effects, particularly in various degenerative diseases. However, its role in preventing OA progression and its underlying mechanisms remain unclear. In this study, we demonstrated that QUE has a protective effect against OA development both in vivo and in vitro, and we elucidated the underlying molecular mechanisms. In vitro, QUE inhibited the expression of IL-1ß-induced chondrocyte matrix metalloproteinases (MMP3 and MMP13) and inflammatory mediators such as INOS and COX-2. It also promoted the expression of collagen II, thereby preventing the extracellular matrix (ECM). Mechanistically, QUE exerts its protective effect on chondrocytes by activating the SIRT1/Nrf-2/HO-1 and inhibiting chondrocyte ferroptosis. Similarly, in an OA rat model induced by anterior cruciate ligament transection (ACLT), QUE treatment improved articular cartilage damage, reduced joint pain, and normalized abnormal subchondral bone remodeling. QUE also reduced serum IL-1ß, TNF-α, MMP3, CTX-II, and COMP, thereby slowing the progression of OA. QUE exerts chondroprotective effects by inhibiting chondrocyte oxidative damage and ferroptosis through the SIRT1/Nrf-2/HO-1 pathway, effectively alleviating OA progression in rats.

Bifidobacterium longum GL001 alleviates rat intestinal ischemia-reperfusion injury by modulating gut microbiota composition and intestinal tissue metabolism.

Intestinal ischemia-reperfusion (IIR) injury leads to inflammation and oxidative stress, resulting in intestinal barrier damage. Probiotics, due to their anti-inflammatory and antioxidant properties, are considered for potential intervention to protect the intestinal barrier during IIR injury. Bifidobacterium longum, a recognized probiotic, has targeted effects on IIR injury, but its mechanisms of action are not yet understood. To investigate the mechanism of Bifidobacterium longum intervention in IIR injury, we conducted a study using a rat IIR injury model. The results showed that Bifidobacterium longum could alleviate inflammation and oxidative stress induced by IIR injury by suppressing the NF-κB inflammatory pathway and activating the Keap1/Nrf2 signaling pathway. Bifidobacterium longum GL001 also increased the abundance of the gut microbiota such as Oscillospira, Ouminococcus, Corynebacterium, Lactobacillus, and Akkermansia, while decreasing the abundance of Allobaculum, [Prevotella], Bacteroidaceae, Bacteroides, Shigella, and Helicobacter. In addition, Bifidobacterium longum GL001 reversed the changes in amino acids and bile acids induced by IIR injury and reduced the levels of DL-cysteine, an oxidative stress marker, in intestinal tissue. Spearman correlation analysis showed that L-cystine was positively correlated with Lactobacillus and negatively correlated with Shigella, while DL-proline was positively correlated with Akkermansia. Moreover, bile acids, cholic acid and lithocholic acid, were negatively correlated with Lactobacillus and positively correlated with Shigella. Therefore, Bifidobacterium longum GL001 may alleviate IIR injury by regulating the gut microbiota to modulate intestinal lipid peroxidation and bile acid metabolism.

Lactiplantibacillus plantarum GL001 alleviates jejunal oxidative damage induced by intestinal ischemia-reperfusion injury by influencing jejunal tissue metabolism through the improvement of jejunal microbial composition.

Intestinal ischemia-reperfusion (IIR) injury is associated with inflammation and oxidative stress, yet its precise mechanisms remain not fully understood. IIR injury is closely linked to the gut microbiota and its metabolites. The anti-inflammatory and antioxidant effects of Lactiplantibacillus plantarum are specific to IIR. In our study, we conducted a 30-day pre-treatment of SD rats with both a standard strain of Lactiplantibacillus plantarum and Lactiplantibacillus plantarum GL001. After a 7-day cessation of treatment, we induced an IIR injury model to investigate the mechanisms by which Lactiplantibacillus plantarum alleviates IIR damage. The results demonstrate that Lactiplantibacillus plantarum effectively mitigates the inflammatory and oxidative stress damage induced by IIR. Lactiplantibacillus plantarum GL001 can improve the gut microbiota by reducing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria. In IIR intestinal tissue, the levels of secondary bile acids are elevated. The content of the bacterial metabolite Calcimycin increases. Annotations of metabolic pathways suggest that Lactiplantibacillus plantarum GL001 can alleviate IIR damage by modulating calcium-phosphorus homeostasis through the regulation of parathyroid hormone synthesis, secretion, and action. Microbiota-metabolite correlation analysis reveals a significant negative correlation between calcimycin and Lactonacillus and a significant positive correlation between calcimycin and Shigella. There is also a significant positive correlation between calcimycin and secondary bile acids. Lactiplantibacillus plantarum GL001 can alleviate oxidative damage induced by IIR through improvements in gut microbiota and intestinal tissue metabolism.

Dark-light cycle disrupts bone metabolism and suppresses joint deterioration in osteoarthritic rats.

BACKGROUND: Light alteration affects the internal environment and metabolic homeostasis of the body through circadian rhythm disorders (CRD). CRD is one of the factors that induce and accelerate osteoarthritis (OA). Therefore, the aim of this study was to evaluate the effects of continuous dark-light (DL) cycle on joint inflammation, bone structure, and metabolism in normal and OA Sprague-Dawley (SD) rats. METHODS: Interleukin (IL)-1ß, IL-6, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α were used to evaluate the systemic inflammation in rats. The pathological changes and inflammatory reactions of the cartilage and synovium of the knee joint in rats were evaluated by Safranin O-fast green and immunological staining. Bone turnover was assessed by histomorphometry and µCT scanning, as well as bone metabolism markers and proteins. The expression changes of clock proteins BMAL1, NR1D1, PER3, and CRY1 in representative tissues were detected by western blotting. RESULTS: DL cycle significantly inhibited body weight gain in normal and OA rats. The levels of proinflammatory factors in the peripheral blood circulation and degradation enzymes in the cartilage were significantly decreased in OA+DL rats. DL cycle significantly destroyed the structure of subchondral bone in hindlimbs of OA rats and reduced trabecular bone numbers. The decrease of bone mineral density (BMD), percent bone volume with respect to total bone volume (BV/TV), trabecular number (TB.N), osteoclast number, and mineralization could also be found. The ratio of the receptor activator of nuclear factor-kappa B ligand/osteoprotegerin (RANKL/OPG) in the bone marrow of OA rats was markedly increased under DL, along with the activation of the mononuclear/phagocyte system. The expression of representative clock proteins and genes BMAL1, PER3, and CRY1 were markedly changed in the tissues of OA+DL rats. CONCLUSIONS: These results suggested that DL cycle dampened the arthritis and promoted bone resorption and bone mass loss. DL cycle affects bone turnover by regulating osteoclast production in osteoarthritic rats.

Aircraft Landing Gear Retraction/Extension System Fault Diagnosis with 1-D Dilated Convolutional Neural Network.

The faults of the landing gear retraction/extension(R/E) system can result in the deterioration of an aircraft's maneuvering conditions; how to identify the faults of the landing gear R/E system has become a key issue for ensuring aircraft take-off and landing safety. In this paper, we aim to solve this problem by proposing the 1-D dilated convolutional neural network (1-DDCNN). Aiming at developing the limited feature information extraction and inaccurate diagnosis of the traditional 1-DCNN with a single feature, the 1-DDCNN selects multiple feature parameters to realize feature integration. The performance of the 1-DDCNN in feature extraction is explored. Importantly, using padding dilated convolution to multiply the receptive field of the convolution kernel, the 1-DDCNN can completely retain the feature information in the original signal. Experimental results demonstrated that the proposed method has high accuracy and robustness, which provides a novel idea for feature extraction and fault diagnosis of the landing gear R/E system.