Untargeted metabolomics revealed the mechanism of aucubin on glucocorticoid-induced osteoporosis in mice through modulating arachidonic acid metabolism.

Glucocorticoid-induced osteoporosis (GIOP) represents the most prevalent form of secondary osteoporosis. Aucubin (AU), a principal active component found in traditional herbal medicines such as Eucommia ulmoides, has been demonstrated to enhance osteoblast differentiation. Nonetheless, the precise therapeutic effects of AU on GIOP and the complex underlying regulatory mechanisms warrant further investigation. We first established a GIOP model in female mice and then assessed the therapeutic effects of AU using micro-CT analysis, biomechanical testing, measurements of serum calcium (Ca) and phosphorus (P) levels, and histological analyses using Hematoxylin and Eosin (HE) and Masson staining. Subsequently, non-targeted metabolomics was employed in order to study the effects of AU on serum metabolites in GIOP mice. The levels of the factors related to these metabolites were quantified using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot analyses. Finally, the effects of AU on osteoblastic and osteoclastic differentiation were examined. We found that AU significantly ameliorated bone microarchitecture and strength in GIOP mice. It mitigated pathological damages such as impairment of trabecular bone structure and reduction in collagen fibers, while concurrently elevating serum levels of Ca and P. Non-targeted metabolomics revealed that Arachidonic acid (AA) metabolism serves as a common pathway between the control and GIOP groups, as well as between the high-dose AU (AUH) and GIOP groups. AU notably upregulates prostaglandin-endoperoxide synthase 2 (PTGS2) and microsomal prostaglandin-E synthase 1 (PTGES) expression and downregulates prostaglandin-H2 D-isomerase (PTGDS) expression. Furthermore, AU treatment increased the expression of runt-related transcription factor 2 (Runx2) and transcription factor Sp7 (Osterix), enhanced serum alkaline phosphatase (ALP) activity, and reduced osteoclast expression. These results indicate that AU is a potential drug for treating GIOP, and its mechanism is related to regulating AA metabolism and promoting osteoblast differentiation. However, the key targets of AU in treating GIOP still need further exploration.

Identification and characterization of extrachromosomal circular DNA in alcohol induced osteonecrosis of femoral head.

Alcohol-induced osteonecrosis of the femoral head (AIONFH) is a complicated refractory bone disease seen in the clinic. The pathogenesis of AIONFH is still controversial. Extrachromosomal circular DNA (eccDNA) elements have been indicated ubiquitously exist in eukaryotic genomes. However, the characteristics and biological functions of eccDNAs remain unclear in AIONFH. In this study, eccDNAs from AIONFH samples (n = 7) and fracture of femoral neck samples as a control (n = 7) were purified by removing linear DNA and rolling circle amplification. High-throughput sequencing and bioinformatics analysis were performed to study the characterization and biofunction of eccDNAs. We identified more than 600,000 unique eccDNAs. The number of detected eccDNAs in AIONFH was less than that in the control, and eccDNA formation may be related to transcription or other characteristics of coding genes. The eccDNA lengths are mainly distributed between 0.1 kb and 1 kb, with a major peak in 0.358 kb. The bioinformatic analysis showed that 25 significant genes were detected, including MAP3K1, ADCY1, CACNA1S, and MACF1, which contributed to regulating bone formation. GO and KEGG analyses suggested that the related genes derived from exons mainly affected metabolic processes and signal transduction, and bone metabolism-related pathways, such as the MAPK pathway and TGF-ß pathway, were enriched. EccDNAs in AIONFH are common and may play an important role in pathogenesis by regulating bone metabolism.

Effect and safety of intravenous versus oral acetaminophen after unicompartmental knee replacement: A protocol of randomized controlled study.

BACKGROUND: Due to the soft tissue injury and large amount of bone destruction involved, undesirable postoperative pain remains a challenge for both patients and surgeons after unicompartmental knee replacement (UKR). However, there are no studies comparing the effectiveness of oral and intravenous acetaminophen as part of a standard multimodal perioperative pain regimen after UKR. Thus, this prospective randomized study was conducted to compare pain control outcomes with postoperative oral versus intravenous acetaminophen use in adults undergoing UKR. METHODS: The institutional review board of the Traditional Chinese Medicine- western Medicine Hospital of Cangzhou approved the study protocol. This blinded and randomized study was carried out in accordance with the principles of the Helsinki Declaration. We included patients who were scheduled for UKR with an American Society of Anesthesiologists status of I to III, who were mentally competent, and who were able to give consent for enrolment in the study. Patients were randomly assigned on a 1:1 basis to receive either intravenous acetaminophen or oral acetaminophen. We ensured that the patients, care providers, and outcome assessors were blinded to the group assignment during the study period. Primary outcomes were postoperative pain at rest and during motion (knee flexion of 45°) measured using a visual analog scale score. Secondary outcomes included morphine consumption at 24, 48, and 72 hours after surgery, length of hospital stay, range of motion, daily ambulation distance, and adverse events occurrence. All statistical analyses were performed using SPSS 25.0. Differences associated with a P value of <.05 were considered statistically significant. RESULTS: It was hypothesized that patients receiving intravenous acetaminophen would exhibit similar postoperative outcomes compared with patients receiving oral acetaminophen. TRIAL REGISTRATION: This study was registered in Research Registry (researchregistry5825).