The Effect of the Hip Flexion Angle in Osteonecrosis of the Femoral Head Based on China-Japan Friendship Hospital Classification - A Finite Element Study.

OBJECTIVE: The alteration in the mechanical environment of the necrotic area is the primary cause of the collapse observed in osteonecrosis of the femoral head (ONFH). This study aims to evaluate the biomechanical implications of the China-Japan Friendship Hospital (CJFH) classification system and hip flexion angles on the necrotic area in ONFH using finite element analysis (FEA). The goal is to provide valuable guidance for hip preservation treatments and serve as a reference for clinical diagnosis and therapeutic interventions. METHODS: Hip tomography CT scan data from a healthy volunteer was used to create a 3D model of the left hip. The model was preprocessed and imported into Solidworks 2018, based on the CJFH classification. Material parameters and boundary conditions were applied to each fractal model in ANSYS 21.0. Von Mises stresses were calculated, and maximum deformation values were obtained to evaluate the biomechanical effects of the load on the necrotic area and post-necrotic femur, as well as assess each fractal model's collapse risk. RESULTS: (1) At the same hip flexion angle, maximum deformation followed this order: M Type < C Type < L Type. The L3 type necrotic area experienced the most significant deformation at 0, 60, and 110° angles (1.121, 1.7913, and 1.8239 mm respectively). (2) Under the same CJFH classification, maximum deformation values increased with hip flexion angle (0 < 60 < 110°), suggesting a higher risk of collapse at larger angles. (3) Von Mises stress results showed that the maximum stress was not located in the necrotic area but near the inner and outer edge of the femoral neck, indicating decreased stiffness and strength of the subchondral bone after osteonecrosis. CONCLUSION: The study found that femoral head collapse risk was higher when the necrotic area was located in the lateral column under the same stress load and flexion angle. Mechanical properties of the necrotic area changed, resulting in decreased bone strength and stiffness. Large-angle hip flexion is more likely to cause excessive deformation of the necrotic area; thus, ONFH patients should reduce or avoid large-angle hip flexion during weight-bearing training in rehabilitation activities.

Plasma lipids, alcohol intake frequency and risk of Osteoarthritis: a Mendelian randomization study.

BACKGROUD: Plasma lipids and alcohol intake frequency have been reported to be associated with the risk of osteoarthritis (OA). However, it remains inconclusive whether plasma lipids and alcohol intake frequency play a role in the development of OA. METHODS: The study employed a comprehensive genome-wide association database to identify independent genetic loci strongly linked to plasma lipids and alcohol intake frequency, which were used as instrumental variables. The causal association between plasma lipids, alcohol intake frequency, and the risk of OA was then analyzed using two-sample Mendelian randomization methods such as inverse variance weighted (IVW), MR-Egger regression, and weighted median estimator (WME), with odds ratios (ORs) as the evaluation criteria. RESULTS: A total of 392 SNPs were included as instrumental variables in this study, including 32 for total cholesterol (TC), 39 for triglycerides (TG), 170 for high-density lipoproteins (HDL), 60 for low-density lipoproteins (LDL), and 91 for alcohol intake frequency. Using the above two-sample Mendelian Randomization method to derive the causal association between exposure and outcome, with the IVW method as the primary analysis method and other MR analysis methods complementing IVW. The results of this study showed that four exposure factors were causally associated with the risk of OA. TC obtained a statistically significant result for IVW (OR = 1.207, 95% CI: 1.018-1.431, P = 0.031); TG obtained a statistically significant result for Simple mode (OR = 1.855, 95% CI: 1.107-3.109, P = 0.024); LDL obtained three statistically significant results for IVW, WME and Weighted mode (IVW: OR = 1.363, 95% CI: 1.043-1.781, P = 0.023; WME: OR = 1.583, 95% CI: 1.088-2.303, P = 0.016; Weighted mode: OR = 1.521, 95% CI: 1.062-2.178, P = 0.026). Three statistically significant results were obtained for alcohol intake frequency with IVW, WME and Weighted mode (IVW: OR = 1.326, 95% CI: 1.047-1.678, P = 0.019; WME: OR = 1.477, 95% CI: 1.059-2.061, P = 0.022; Weighted mode: OR = 1.641, 95% CI: 1.060-2.541, P = 0.029). TC, TG, LDL, and alcohol intake frequency were all considered as risk factors for OA. The Cochran Q test for the IVW and MR-Egger methods indicated intergenic heterogeneity in the SNPs contained in TG, HDL, LDL, and alcohol intake frequency, and the test for pleiotropy indicated a weak likelihood of pleiotropy in all causal analyses. CONCLUSIONS: The results of two-sample Mendelian randomization analysis showed that TC, TG, LDL, and alcohol intake frequency were risk factors for OA, and the risk of OA increased with their rise.

Pyroptosis -related potential diagnostic biomarkers in steroid-induced osteonecrosis of the femoral head.

PURPOSE: Steroid-induced necrosis of the femoral head (SONFH) is a refractory orthopedic hip disease occurring in young and middle-aged people, with glucocorticoids being the most common cause. Previous experimental studies have shown that cell pyroptosis may be involved in the pathological process of SONFH, but its pathogenesis in SONFH is still unclear. This study aims to screen and validate potential pyroptosis-related genes in SONFH diagnosis by bioinformatics analysis to further elucidate the mechanism of pyroptosis in SONFH. METHODS: There were 33 pyroptosis-related genes obtained from the prior reviews. The mRNA expression was downloaded from GSE123568 dataset in the Gene Expression Omnibus (GEO) database, including 10 non-SONFH (following steroid administration) samples and 30 SONFH samples. The pyroptosis-related differentially expressed genes involved in SONFH were identified with "affy" and "limma" R package by intersecting the GSE123568 dataset with pyroptosis genes. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the pyroptosis-related differentially expressed genes involved in SONFH were conducted by "clusterProfiler" R package and visualized by "GOplot" R package. Then, the correlations between the expression levels of the pyroptosis-related differentially expressed genes involved in SONFH were confirmed with "corrplot" R package. Moreover, the protein-protein interaction (PPI) network was analysed by using GeneMANIA database. Next, The ROC curve of pyroptosis-related differentially expressed genes were analyzed by "pROC" R package. RESULTS: A total of 10 pyroptosis-related differentially expressed genes were identified between the peripheral blood samples of SONFH patients and non-SONFH patients based on the defined criteria, including 20 upregulated genes and 10 downregulated genes. The GO and KEGG pathway enrichment analyses revealed that these 10 pyroptosis-related differentially expressed genes involved in SONFH were particularly enriched in cysteine-type endopeptidase activity involved in apoptotic process, positive regulation of interleukin-1 beta secretion and NOD-like receptor signaling pathway. Correlation analysis revealed significant correlations among the 10 differentially expressed pyroptosis-related genes involved in SONFH. The PPI results demonstrated that the 10 pyroptosis-related differentially expressed genes interacted with each other. Compared to non-SONFH samples, these pyroptosis-related differentially expressed genes had good predictive diagnostic efficacy (AUC = 1.000, CI = 1.000-1.000) in the SONFH samples, and NLRP1 had the highest diagnostic value (AUC: 0.953) in the SONFH samples. CONCLUSIONS: There were 10 potential pyroptosis-related differentially expressed genes involved in SONFH were identified via bioinformatics analysis, which might serve as potential diagnostic biomarkers because they regulated pyroptosis. These results expand the understanding of SONFH associated with pyroptosis and provide new insights to further explore the mechanism of action and diagnosis of pyroptosis associated in SONFH.

Impact of Sulfur Fumigation on the Chemistry of Dioscoreae Rhizoma (Chinese Yam).

Dioscoreae Rhizoma (Chinese yam; derived from the rhizome of Dioscorea opposita Thunb.) (DR), commonly consumed as a food or supplement, is often sulfur-fumigated during post-harvest handling, but it remains largely unknown if and how sulfur fumigation impacts the chemistry of DR. In this study, we report the impact of sulfur fumigation on the chemical profile of DR and then the molecular and cellular mechanisms potentially involved in the chemical variations induced by sulfur fumigation. The results show that sulfur fumigation significantly and specifically changed the small metabolites (molecular weight lower than 1000 Da) and polysaccharides of DR at both qualitative and quantitative levels. Multifaceted molecular and cellular mechanisms involving chemical transformations (e.g., acidic hydrolysis, sulfonation, and esterification) and histological damage were found to be responsible for the chemical variations in sulfur-fumigated DR (S-DR). The research outcomes provide a chemical basis for further comprehensive and in-depth safety and functional evaluations of sulfur-fumigated DR.

Engineered geranyl diphosphate methyltransferase produces 2-methyl-dimethylallyl diphosphate as a noncanonical C6 unit for terpenoid biosynthesis.

Terpenoids constitute the largest class of natural products with complex structures, essential functions, and versatile applications. Creation of new building blocks beyond the conventional five-carbon (C5) units, dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate, expands significantly the chemical space of terpenoids. Structure-guided engineering of an S-adenosylmethionine-dependent geranyl diphosphate (GPP) C2-methyltransferase from Streptomyces coelicolor yielded variants converting DMAPP to a new C6 unit, 2-methyl-DMAPP. Mutation of the Gly residue at the position 202 resulted in a smaller substrate-binding pocket to fit DMAPP instead of its native substrate GPP. Replacement of Phe residue at the position 222 with a Tyr residue contributed to DMAPP binding via hydrogen bond. Furthermore, using Escherichia coli as the chassis, we demonstrated that 2-methyl-DMAPP was accepted as a start unit to generate noncanonical trans- and cis-prenyl diphosphates (C5n+1) and terpenoids. This work provides insights into substrate recognition of prenyl diphosphate methyltransferases, and strategies to diversify terpenoids by expanding the building block portfolio.

[Difference of in vitro osteogenic differentiation and osteoclast capacity between stem cells from human exfoliated deciduous teeth and dental pulp stem cells].

OBJECTIVE: To compare the osteogenic differentiation potential and osteoclast capacity between stem cells from human exfoliated deciduous teeth (SHED) in the physiological root resorption period and dental pulp stem cells (DPSCs). METHODS: SHED and DPSCs were isolated, purified and cultured in vitro. The two stem cells were examined with ALP staining at 14 days and with alizarin red staining at 21 days of osteogenic induction, and the expressions of the genes associated with osteogenesis and osteoclastogenesis were detected using real-time PCR. RESULTS: The isolated SHED and DPSCs both showed an elongate spindle-shaped morphology. After osteogenic induction of the cells, Alizarin red staining visualized a greater number of mineralized nodules in SHED than in DPSCs (P<0.05), and SHED also exhibited a stronger ALP activity than DPSCs (P<0.05). RT-PCR test results showed that the two stem cells expressed RANKL,OCN, ALP, OPG and Runx2 mRNA after osteogenic induction, but the expression levels of Runx2, OCN and ALP were lower in DPSCs than in SHED (P<0.05), and the ratio of RANKL/OPG was significantly higher in SHED (P<0.05). CONCLUSIONS: Compared with DPSCs, SHED has not only the ability of osteogenic differentiation but also an osteoclast capacity, which sheds light on the regulatory role of SHED in physiological root resorption bone remodeling.