Background
Many studies reported that lifestyle, psychosocial characteristics, and sleep status related to sarcopenia, while few studies provided evidence of causal relationships between them.
Methods
The data used in our study were from UK Biobank, FinnGen Release 8, and large genome-wide association study meta-analyses. Two-sample MR was conducted to identify the causal associations of 21 traits of lifestyle, psychosocial characteristics, and sleep status with six traits of sarcopenia. Benjamini–Hochberg correction was performed to reduce the bias caused by multiple tests. Risk factor analyses were performed to explore the potential mechanism behind the exposures.
Results
MR analyses after adjustment proved the causal roles of coffee intake, education years, smoking, leisure screen time, and moderate-to-vigorous intensity physical activity during leisure time (MVPA) in sarcopenia was proven while providing no significant evidence for causal roles for carbohydrates intake, protein intake, alcohol, and sleep status in sarcopenia.
Conclusions
Our results strongly support that coffee intake, education years, smoking, leisure screen time, and MVPA played significantly causal roles in sarcopenia, which may provide new intervention strategies for preventing the development of sarcopenia.
Fracture is the most common traumatic organ injury, and fracture nonunion is a critical clinical challenge. The research on the mechanisms of skeletal stem cell (SSC) differentiation and fracture healing may help develop new treatment strategies and improve the prognosis of patients at high risk of nonunion. Bioinformatic analysis of scRNA-seq data of mouse SSCs and mouse osteoprogenitors was applied to discover major transcription factors for the regulation of SSC differentiation. FACS was used to isolate SSCs prospectively. The expression of Cebpb, osteogenesis-related genes (Runx2, Sp7, and Bglap2), and markers for Notch, Hedgehog, MAPK, BMP2/SMAD, and WNT/β-catenin signaling pathways (Hes1, Gli1, p-Erk1/2, p-Smad1/5/9, and β-catenin) were detected in SSCs with qPCR or western blot, respectively. Alkaline phosphatase assay and alizarin red S staining were used to illustrate the osteogenic differentiation ability of SSCs in vitro. A WNT inhibitor, IWR-1, was further used to explore the mechanism of WNT signaling in the differentiation of SSCs. Micro-CT, mechanical testing, and immunohistochemistry of osteogenic and chondrogenic proteins (Sp7 and Col2α1) were used to demonstrate the capacity of Cebpb knockdown in promoting fracture healing in a monocortical defect model. We found that Cebpb was the crucial transcription factor regulating SSC differentiation. Inhibiting Cebpb in SSCs enhanced the expression of active β-catenin to promote the expression of WNT target genes, thus facilitating the osteogenic differentiation of SSCs. Bone mass, mechanical properties, and osteogenic protein expression were also increased in the Cebpb inhibition group compared to the group without Cebpb inhibition. Collectively, our results proved that Cebpb knockdown promotes SSC osteogenic differentiation and fracture healing via the WNT/β-catenin signaling pathway.
Background
We aimed to explore the predictive value of retinol binding protein (RBP) for outcomes of hip fractures.
Methods
Patients with hip fractures who underwent hip surgeries between December 2017 and February 2021 and met the inclusion criteria were analyzed. Propensity score matching was used to reduce the bias of co-factors and ROC curves based on matched populations were created to determine the optimal cutoff point of RBP. The outcomes between patients with low levels of RBP and high levels of RBP were compared.
Results
Four hundred eighty patients were enrolled in this study and 69 patients died within one year. After a 1:1 PSM, patients with more than 1-year survival had significantly higher RBP (p = 0.013) than those who died within one year, as well as patients divided by 6-months survival (p = 0.012). Logistics analysis showed that low RBP may be an independent risk factor for 3-month survival, 6-month survival, 1-year survival, and 3-month free walking ability.
Conclusion
RBP may be associated with the survival and 3-month walking abilities of patients with hip fractures.
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