Dauricine attenuates ovariectomized-induced bone loss and RANKL-induced osteoclastogenesis via inhibiting ROS-mediated NF-κB and NFATc1 activity.

BACKGROUND: Osteoclast plays an important role in maintaining the balance between bone anabolism and bone catabolism. The abnormality of osteoclast is closely related to osteolytic bone diseases such as osteoporosis, rheumatoid arthritis and tumor bone metastasis. PURPOSE: We aim to search for natural compound that may suppress osteoclast formation and function. STUDY DESIGN: In this study, we assessed the impact of Dauricine (Dau) on the formation and function of osteoclasts in vitro, as well as its potential in preventing bone loss in an ovariectomy mouse model in vivo. METHODS: Multiple in vitro experiments were carried out, including osteoclastogenesis, podosomal belt formation, bone resorption assay, RNA-sequencing, real-time quantitative PCR, ROS level detection, surface plasmon resonance assay, luciferase assay and western blot. To verify the effect in vivo, an ovariectomized mouse model (OVX model) was constructed, and bone parameters were measured using micro-CT and histology. Furthermore, metabolomics analysis was performed on blood serum samples from the OVX model. RESULTS: In vitro experiments demonstrated that Dau inhibits RANKL-induced osteoclastogenesis, podosomal belt formation, and bone resorption function. RNA-sequencing results revealed that Dau significantly suppresses genes related to osteoclast. Functional enrichment analysis indicated that Dau's inhibition of osteoclasts may be associated with NF-κB signaling pathway and reactive oxygen metabolism pathway. Molecular docking, surface plasmon resonance assay and western blot analysis further confirmed that Dau inhibits RANKL-induced osteoclastogenesis by modulating the ROS/NF-κB/NFATc1 pathway. Moreover, administration of Dau to OVX-induced mice validated its efficacy in treating bone loss disease. CONCLUSION: Dau prevents OVX-induced bone loss by inhibiting osteoclast activity and bone resorption, potentially offering a new approach for preventing and treating metabolic bone diseases such as osteoporosis. This study provides innovative insights into the inhibitory effects of Dau in an in vivo OVX model and elucidates the underlying mechanism.

Cichoric acid targets RANKL to inhibit osteoclastogenesis and prevent ovariectomy-induced bone loss.

BACKGROUND AND AIM: Osteoporosis, a systemic metabolic bone disease, is characterized by the decline of bone mass and quality due to excessive osteoclast activity. Currently, drug-targeting osteoclasts show promising therapy for osteoporosis. In this study, we investigated the effect of cichoric acid (CA) on receptor activator of nuclear kappa-B ligand (RANKL)-induced osteoclastogenesis and the bone loss induced by ovariectomy in mice. EXPERIMENTAL PROCEDURE: Molecular docking technologies were employed to examine the interaction between CA and RANKL. CCK8 assay was used to evaluate the cell viability under CA treatment. TRAcP staining, podosome belt staining, and bone resorption assays were used to test the effect of CA on osteoclastogenesis and osteoclast function. Further, an OVX-induced osteoporosis mice model was employed to identify the effect of CA on bone loss using micro-CT scanning and histological examination. To investigate underlying mechanisms, network pharmacology was applied to predict the downstream signaling pathways, which were verified by Western blot and immunofluorescence staining. KEY RESULTS: The molecular docking analysis revealed that CA exhibited a specific binding affinity to RANKL, engaging multiple binding sites. CA inhibited RANKL-induced osteoclastogenesis and bone resorption without cytotoxic effects. Mechanistically, CA suppressed RANKL-induced intracellular reactive oxygen species, nuclear factor-kappa B, and mitogen-activated protein kinase pathways, followed by abrogated nuclear factor activated T-cells 1 activity. Consistent with this finding, CA attenuated post-ovariectomy-induced osteoporosis by ameliorating osteoclastogenesis. CONCLUSIONS AND IMPLICATIONS: CA inhibited osteoclast activity and bone loss by targeting RANKL. CA might represent a promising candidate for treating osteoclast-related diseases, such as osteoporosis.

Selective Anchoring by Surface Sulfur Species Coupled with Rapid Interface Electron Transfer for Ultrahigh Capacity Extraction of Uranium from Seawater.

Improving the adsorption selectivity, enhancing the extraction capacity, and ensuring the structural stability of the adsorbent are the key to realize the high efficiency recovery of uranium. In this work, we utilized the strong Lewis acid-base interaction between S2- and U(VI)O22+ coupling rapid electron transfer at the MnS/U(VI)O22+ solid-liquid interface to achieve excellent selectivity, high adsorption capacity, and rapid extraction of uranium. The as-synthesized MnS adsorbent exhibited an ultrahigh uranium extraction capacity (2457.05 mg g-1) and a rapid rate constant (K = 9.11 × 10-4 g h-1 mg-1) in seawater with 100.7 ppm of UO2(NO3)2 electrolyte. The kinetic simulation reveals that this adsorption process is a chemical adsorption process and conforms to a pseudo-second-order kinetic model, indicating electron transfer at the MnS/U(VI)O22+ solid-liquid interface. The relevant (quasi) in situ spectroscopic characterization and theoretical calculation results further revealed that the outstanding uranium extraction property of MnS could be attributed to the highly selective UO22+ adsorption of MnS with lower adsorption energy as a result of the strong interaction between S2- and UO22+ and the rapid mass transfer and interface electron transfer from S2- and low-valent Mn(II) to U(VI)O22+.

Traditional Chinese medicine improves myasthenia gravis by regulating the symbiotic homeostasis of the intestinal microbiota and host.

Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies that is dependent on T-cell immunity and complement participation and mainly involves neuromuscular junctions. In this study, 30 patients with myasthenia gravis were selected and divided into pretreatment (Case group) and posttreatment (Treatment group) and 30 healthy volunteers (CON group) were included. Among them, the treatment group was treated with Modified Buzhong Yiqi Decoction (MBZYQD), and the levels of antibodies such as AChR, Musk and Titin in blood and intestinal microbiota were compared before treatment (Case group), after treatment (Treatment group) and in healthy volunteers (CON group). The results showed that after treatment with MBZYQD, the antibody levels of AChR, MuSK, and Titin and the inflammatory factor level of IL-6, IL-1ß, and IL-22 in MG patients decreased significantly and nearly returned to a healthy level. In addition, after treatment with MBZYQD, the diversity, structure and function of intestinal microorganisms in MG patients also recovered to a healthy level. At the phylum level, the relative abundance of Proteobacteria in the Case group increased significantly, accompanied by a significant decrease in the relative abundance of Bacteroides compared with that in the CON group, the relative abundance of Proteobacteria and Bacteroides in the Treatment group was similar to that in the CON group. At the genus level, the relative abundance of Shigella in the Case group was significantly increased, accompanied by a significant decrease in the relative abundance of Prevotella, and the relative abundance of Shigella and Prevotella in Treatment group was similar to that in the CON group. Moreover, the fluorobenzoate degradation pathway (KO00364) was significantly increased in the Case group, while this pathway was significantly decreased in the Treatment group. In conclusion, MBZYQD can improve the immune function of the host by regulating the diversity, structure and function of the intestinal microbiota to treat myasthenia gravis.

Structure-activity relationship study between baicalein and wogonin by spectrometry, molecular docking and microcalorimetry.

Flavones (e.g. baicalein and wogonin) extensively used worldwide in food preparation and traditional medicine. In this study, a systematically comparative study of their structure-activity relationships (SAR) on their interaction with BSA, antioxidant activity and antibacterial activity has been carried out by spectrometry, molecular docking and microcalorimetry. Our results show that the skeleton structure of flavones, the number of hydroxyl groups, the type of functional group, conjugated system and the steric hindrance may be responsible for their different biological activity. These findings not only would lay a scientific foundation for discovering and designing flavones-based food and drug, may also help us to understanding the structure-activity relationship between flavones at the molecular level.

[Value of early application of different doses of amino acids in parenteral nutrition among preterm infants].

OBJECTIVE: To study the short-term response and tolerance of different doses of amino acids in parenteral nutrition among preterm infants. METHODS: This study included 86 preterm infants who had a birth weight between 1 000 to 2 000 g and were admitted to the hospital within 24 hours of birth between March 2013 and June 2014. According to the early application of different doses of amino acids, they were randomized into low-dose group (n=29, 1.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.5 g/kg per day), medium-dose group (n=28, 2.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.7 g/kg per day), and high-dose group (n=29, 3.0 g/kg per day with an increase of 0.5-1.0 g/kg daily and a maximum of 4.0 g/kg per day). Other routine parenteral nutrition and enteral nutrition support were also applied. RESULTS: The maximum weight loss was lower and the growth rate of head circumference was greater in the high-dose group than in the low-dose group (P<0.05). The infants in the medium- and high-dose groups had faster recovery of birth weight, earlier attainment of 100 kcal/(kg·d) of enteral nutrition, shorter duration of hospital stay, and less hospital cost than those in the low-dose group (P<0.05). Blood urea nitrogen (BUN) levels in the high-dose group increased compared with the other two groups 7 days after birth (P<0.05). The levels of creatinine, pH, bicarbonate, bilirubin, and transaminase and the incidence of complications showed no significant differences between groups (P>0.05). CONCLUSIONS: Parenteral administration of high-dose amino acids in preterm infants within 24 hours after birth can improve the short-term nutritional status of preterm infants, but there is a transient increase in BUN level.