The association between remnant cholesterol and bone mineral density in US adults: the National Health and Nutrition Examination Survey (NHANES) 2013-2018.

BACKGROUND: Previous evidence showed a possible link of dyslipidemia with bone health. Nevertheless, the correlation of remnant cholesterol (RC) with bone mineral density (BMD) has yet to be well investigated. This study investigated the association of RC with total spine BMD in general Americans. METHODS: This study explored the relationship of RC with total spine BMD in subjects aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) 2013-2018. After adjusting for covariates, multivariate linear regression and stratified analyses were conducted to determine the correlation of serum RC with total spine BMD in adult Americans. Restricted cubic spline (RCS) was applied to examine the nonlinear association of serum RC with total spine BMD. RESULTS: This study included 3815 individuals ≥ 20 years old, 1905 (49.93%) of whom were men and 1910 (50.07%) of whom were women. After adjusting for all covariates, the results showed a negative relationship of serum RC with total spine BMD (ß= -0.024, 95% CI: -0.039, -0.010). The interaction tests of age, sex, race, and BMI showed no statistically significant effects on the association. The RCS also indicated a negative linear correlation of serum RC with total spine BMD (nonlinear P = 0.068, overall P < 0.001). Moreover, RC had a stronger effect on total spine BMD than total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). CONCLUSIONS: This study found that serum RC was negatively related to total spine BMD in U.S. adults. These findings emphasized the important role of RC in bone health in American adults.

No genetic causal association between circulating alpha-tocopherol levels and osteoarthritis, a two-sample Mendelian randomization analysis.

The causal association between vitamin E status and osteoarthritis (OA) remains controversial in previous epidemiological studies. We employed a Mendelian randomization (MR) analysis to explore the causal relationship between circulating alpha-tocopherol levels (main forms of vitamin E in our body) and OA. The instrumental variables (IVs) of circulating alpha-tocopherol levels were obtained from a Genome-wide association study (GWAS) dataset of 7781 individuals of European descent. The outcome of OA was derived from the UK biobank. Two-sample MR analysis was used to estimate the causal relationship between circulating alpha-tocopherol levels and OA. The inverse-variance weighted (IVW) method was the primary analysis in this analysis. We used the MR-Egger method to determine horizontal pleiotropic in this work. The heterogeneity effect of instrumental IVs was detected by MR-Egger and IVW analyses. Sensitivity analysis was performed by removing single nucleotide polymorphism (SNP) one by one. Three SNPs (rs964184, rs2108622, and rs11057830) (P < 5E-8) strongly associated with circulating alpha-tocopherol levels were used in this analysis. The IVW-random effect indicated no causal relationship between circulating alpha-tocopherol levels and clinically diagnosed OA (OR = 0.880, 95% CI 0.626, 1.236, P = 0.461). Similarly, IVW analysis showed no causal association between circulating alpha-tocopherol levels and self-reported OA (OR = 0.980, 95% CI 0.954, 1.006, P = 0.139). Other methods of MR analyses and sensitivity analyses revealed consistent findings. MR-Egger and IVW methods indicated no significant heterogeneity between IVs. The MR-Egger intercept showed no horizontal pleiotropic. The results of this linear Mendelian randomization study indicate no causal association between genetically predicted alpha-tocopherol levels and the progression of OA. Alpha-tocopherol may not provide beneficial and more favorable outcomes for the progression of OA. Further MR analysis based on updated GWASs with more IVs is required to verify the results of our study.

Chaperone-Mediated Autophagy in Brain Injury: A Double-Edged Sword with Therapeutic Potentials.

Autophagy is an intracellular recycling process that maintains cellular homeostasis by degrading excess or defective macromolecules and organelles. Chaperone-mediated autophagy (CMA) is a highly selective form of autophagy in which a substrate containing a KFERQ-like motif is recognized by a chaperone protein, delivered to the lysosomal membrane, and then translocated to the lysosome for degradation with the assistance of lysosomal membrane protein 2A. Normal CMA activity is involved in the regulation of cellular proteostasis, metabolism, differentiation, and survival. CMA dysfunction disturbs cellular homeostasis and directly participates in the pathogenesis of human diseases. Previous investigations on CMA in the central nervous system have primarily focus on neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Recently, mounting evidence suggested that brain injuries involve a wider range of types and severities, making the involvement of CMA in the bidirectional processes of damage and repair even more crucial. In this review, we summarize the basic processes of CMA and its associated regulatory mechanisms and highlight the critical role of CMA in brain injury such as cerebral ischemia, traumatic brain injury, and other specific brain injuries. We also discuss the potential of CMA as a therapeutic target to treat brain injury and provide valuable insights into clinical strategies.

N-acetylserotonin alleviates retinal ischemia-reperfusion injury via HMGB1/RAGE/NF-κB pathway in rats.

AIM: To observe the effects of N-acetylserotonin (NAS) administration on retinal ischemia-reperfusion (RIR) injury in rats and explore the underlying mechanisms involving the high mobility group box 1 (HMGB1)/receptor for advanced glycation end-products (RAGE)/nuclear factor-kappa B (NF-κB) signaling pathway. METHODS: A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye. Eighty male Sprague Dawley were randomly divided into five groups: sham group (n=8), RIR group (n=28), RIR+NAS group (n=28), RIR+FPS-ZM1 group (n=8) and RIR+NAS+ FPS-ZM1 group (n=8). The therapeutic effects of NAS were examined by hematoxylin-eosin (H&E) staining, and retinal ganglion cells (RGCs) counting. The expression of interleukin 1 beta (IL-1ß), HMGB1, RAGE, and nod-like receptor 3 (NLRP3) proteins and the phosphorylation of nuclear factor-kappa B (p-NF-κB) were analyzed by immunohistochemistry staining and Western blot analysis. The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats. With NAS therapy, the HMGB1 and RAGE expression decreased significantly, and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression. Additionally, NAS exhibited an anti-inflammatory effect by reducing IL-1ß expression. The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression, so as to the IL-1ß expression and retinal edema, accompanied by an increase of RGCs in RIR rats. CONCLUSION: NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway, which may be a useful therapeutic target for retinal disease.

Associations Between Serum Selenium and Bone Mineral Density in 8-19-year-old children and adolescents: NHANES 2013-2018.

The peak bone mass (PBM) in puberty has been proven to be a critical determinant of osteoporosis and brittle fractures in the elderly. Selenium is an essential trace element that could influence bone metabolism in our bodies. However, no study has investigated the impact of selenium status on bone mineral density (BMD) among children and adolescents. This was a cross-section study from National Health and Nutrition Examination Survey (NHANES) in the USA involving participants aged 8-19 years. We conducted multiple linear regression models to assess the relationship between selenium status and BMD among children and adolescents, and then stratified analyses were performed according to genders and races. Smooth curve fits and two-piecewise linear regression models were conducted to explore their nonlinear relationship. A total of 4570 participants (2338 boys and 2232 girls) were included in the present study, with a mean age of 13.57 ± 3.41 years. In the multivariable adjustment model, serum selenium was positively associated with lumbar spine BMD (ß = 0.021 95% CI: 0.008, 0.034, P = 0.001). The dose-response analyses indicated a non-linear inverted U-shaped relationship between serum selenium and lumbar spine BMD. Lower and higher selenium concentrations were related to decreased BMD, and the inflection point of serum selenium was 2.60 umol/L. The inverted U-shaped association was also observed in females (inflection point: 2.49 umol/L), males (inflection point: 2.65 umol/L), Non-Hispanic White (inflection point: 2.50 umol/L), Non-Hispanic Black (inflection point: 2.50 umol/L), and other races (Including multi-racial) (inflection point: 2.81 umol/L). Our study first shows a non-linear inversed U-shaped association between selenium status and BMD among children and adolescents. The proper selenium status will benefit bone health in children and adolescents. More research is still required to verify our findings and their potential mechanisms.

Hypoxia ischemia results in blood brain barrier damage via AKT/GSK-3ß/CREB pathway in neonatal rats.

Previous studies have showed that the permeability of blood brain barrier (BBB) increased after hypoxia ischemia (HI). The current research uncovered the mechanism of altered BBB permeability after hypoxic-ischemic brain damage (HIBD) through AKT/GSK-3ß/CREB signaling pathway in neonatal rats. Firstly, Magnetic resonance imaging (MRI) combined with hematoxylin-eosin (H&E) staining was used to assess brain injury. Initial findings showed abnormal signals in T2-weighted imaging (T2WI) and diffusion weighted imaging (DWI). Changes also happened in the morphology of nerve cells. Subsequently, we found that BBB damage is manifested as leakage of immunoglobulin G (IgG) and destruction of BBB-related proteins and ultrastructure. Meanwhile, the levels of matrix metalloproteinase-9 (MMP-9) significantly increased at 24 h after HIBD compared to a series of time points. Additionally, immunohistochemical (IHC) staining combined with Western blot (WB) was used to verify the function of the AKT/GSK-3ß/CREB signaling pathway in BBB damage after HI in neonatal rats. Results showed that less Claudin-5, ZO-1, p-AKT, p-GSK-3ß and p-CREB, along with more MMP-9 protein expression were visible on the damaged side of the cerebral cortex in the HIBD group in contrast to the sham and HIBD + SC79 groups. Together, our findings demonstrated that HI in neonatal rats might upregulate the levels of MMP-9 protein and downregulate the levels of Claudin-5 and ZO-1 by inhibiting the AKT/GSK-3ß/CREB pathway, thus disrupting the BBB, which in turn aggravates brain damage after HI in neonatal rats.

Multi-parametric MRI assessment of melatonin regulating the polarization of microglia in rats after cerebral ischemia/reperfusion injury.

OBJECTIVES: Multi-parametric magnetic resonance imaging (MRI) can provide comprehensive and valuable information for precise diagnosis and treatment evaluation of a number of diseases. In this study, the neuroprotective effects of melatonin (Mel) on a rat model of cerebral ischemia/reperfusion injury (CIRI) were assessed by multi-parametric MRI combined with histopathological techniques for longitudinal monitoring of the lesion microenvironment. METHODS: Sixty Sprague Dawley (SD) rats were randomly divided into three groups: the Sham, CIRI and CIRI + Mel groups. At multiple time points after ischemia, MRI scanning was performed on a 7.0 Tesla MRI scanner. Multi-parametric MRI includes T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), and chemical exchange saturation transfer (CEST)-MRI. CEST effects were calculated by the Lorentzian difference method, 3.5 ppm indicates amide protons of mobile proteins/peptide (Amide-CEST) and 2.0 ppm indicates amine protons (Guan-CEST). Multiple histopathological techniques were used to examine the histopathological changes and explore the therapeutic effects of Mel. RESULTS: T2WI and DWI-MRI could localize the infarct foci and areas in CIRI rats, which was further validated by staining, 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) staining. After Mel treatment, T2WI and DWI-MRI showed smaller infarct volume, and neurons displayed improved morphology with less apoptosis rates. Notably, Amide-CEST and Guan-CEST signal decreased as early as 2 h after CIRI (all P <0.001), reflecting the change of pH after ischemia. After Mel treatment, both Amide-CEST and Guan-CEST signal increased in ischemic cortex and striatum compared with control group (all P < 0.001). The immunofluorescence staining and western blotting analysis suggested the expression of M2 microglia increased after Mel treatment; While，after Mel treatment the inflammatory factor interleukin-1ß (IL-1ß) decreased compared with control CIRI rats. CONCLUSIONS: Multi-parametric MRI was shown to be an effective method to monitor the brain damage in a rat model of CIRI and assess the therapeutic effects of Mel treatment. Amide-CEST and Guan-CEST were especially sensitive to the changes in brain microenvironment during the early stage after CIRI. Furthermore, the neuroprotective effect of Mel treatment is associated with its promotion of the microglia polarized to M2 type in CIRI rats.

Causal association of NAFLD with osteoporosis, fracture and falling risk: a bidirectional Mendelian randomization study.

Introduction: The causal association between non-alcoholic fatty liver disease (NAFLD) and osteoporosis remains controversial in previous epidemiological studies. We employed a bidirectional two-sample Mendelian analysis to explore the causal relationship between NAFLD and osteoporosis. Method: The NAFLD instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Two-sample Mendelian randomization (MR) analyses were used to estimate the causal effect of NAFLD on osteoporosis, fracture, and fall. Reverse Mendelian randomization analysis was conducted to estimate the causal effect of osteoporosis on NAFLD. The inverse-variance weighted (IVW) method was the primary analysis in this analysis. We used the MR-Egger method to determine horizontal pleiotropic. The heterogeneity effect of IVs was detected by MR-Egger and IVW analyses. Results: Five SNPs (rs2980854, rs429358, rs1040196, rs738409, and rs5764430) were chosen as IVs for NAFLD. In forward MR analysis, the IVW-random effect indicated the causal effect of NAFLD on osteoporosis (OR= 1.0021, 95% CI: 1.0006-1.0037, P= 0.007) but not on fracture (OR= 1.0016, 95% CI: 0.998-1.0053, P= 0.389) and fall (OR= 0.9912, 95% CI: 0.9412-1.0440, P= 0.740). Furthermore, the reverse Mendelian randomization did not support a causal effect of osteoporosis on NAFLD (OR= 1.0002, 95% CI: 0.9997-1.0007, P= 0.231). No horizontal pleiotropic was detected in all MR analyses. Conclusions: The results of this study indicate a causal association between NAFLD and osteoporosis. NAFLD patients have a higher risk of osteoporosis but not fracture and falling risk. In addition, our results do not support a causal effect of osteoporosis on NAFLD.

[Protective effect of melatonin against oxygen-induced retinopathy: a study based on the HMGB1/NF-κB/NLRP3 axis]. / 基于HMGB1/NF-κB/NLRP3è½´æŽ¢è®¨è¤ªé»‘ç´ å¯¹æ°§è¯±å¯¼è§†ç½‘è†œç— å˜çš„ä¿æŠ¤ä½œç”¨.

OBJECTIVES: To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis. METHODS: Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase. RESULTS: The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05). CONCLUSIONS: Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.

Association between caffeine consumption and bone mineral density in children and adolescent: Observational and Mendelian randomization study.

BACKGROUND: Coffee is the most commonly consumed beverage among children and adolescences. Caffeine was demonstrated to be associated with bone metabolism. However, the relationship between caffeine intake and BMD in children and adolescents remains unclear. This study aimed to identified relationship between caffeine consumption and bone mineral density (BMD) in children and adolescents. METHODS: Based on National Health and Nutrition Examination Survey (NHANES), we conducted an epidemiological cross-section study to measure the relationship between caffeine consumption and BMD in children and adolescents by multivariate linear regression models. Then, five methods of Mendelian randomization (MR) analyses were performed to estimate their causal relationship between coffee and caffeine intake and BMD in children and adolescents. MR-Egger and inverse-variance weighted (IVW) were used to evaluate the heterogeneity effect of instrumental variables (IVs). RESULTS: In epidemiological studies, individuals with the highest quartile of caffeine intake do not have a significant change in femur neck BMD (ß = 0.0016, 95% CI: -0.0096, 0.0129, P = 0.7747), total femur BMD (ß = 0.0019, P = 0.7552), and total spine BMD (ß = 0.0081, P = 0.1945) compared with the lowest quartile. In MR analysis, the IVW-random effect indicates no causal relationship between coffee consumption and TB- BMD (ß = 0.0034, P = 0.0910). Other methods of MR analyses and sensitivity analysis reveals consistent findings. Similarly, the fixed-effects IVW method shows no causal association between caffeine intake and TB-BMD in children and adolescents (ß = 0.0202, P = 0.7828). CONCLUSIONS: Our study does not support a causal relationship between caffeine consumption and BMD in children and adolescents. However, more studies are needed to verify our findings, such as its underlying molecular mechanisms and the long-term impact of early caffeine exposure at a younger age.

Overall survival comparison between pediatric and adult Ewing sarcoma of bone and adult nomogram construction: a large population-based analysis.

Background: Ewing sarcoma (ES) is a common primary bone tumor in children. Our study aimed to compare overall survival (OS) between pediatric and adult bone ES patients, identify independent prognostic factors and develop a nomogram for predicting OS in adult patients with ES of bone. Methods: We retrospectively analyzed data for the 2004-2015 period from the Surveillance, Epidemiology, and End Results (SEER) database. To guarantee well-balanced characteristics between the comparison groups, propensity score matching (PSM) was used. Kaplan-Meier (KM) curves were used to compare OS between pediatric and adult patients with ES of bone. Univariate and multivariate Cox regression analyses were used to screen independent prognostic factors for ES of bone, and a prognostic nomogram was constructed by using the factors identified. The prediction accuracy and clinical benefit were evaluated using receiver operating characteristic (ROC) curves, areas under the curves (AUCs), calibration curves, and decision curve analysis (DCA). Results: Our results showed that adult ES patients had lower OS than younger ES patients. Age, surgery, chemotherapy, and TNM stage were independent risk factors for bone ES in adults and were used to develop a nomogram. AUCs for 3-, 5-, and 10-year OS were 76.4 (67.5, 85.3), 77.3 (68.6, 85.9) and 76.6 (68.6, 84.5), respectively. Calibration curves and DCA results indicated excellent performance for our nomogram. Conclusion: We found that ES pediatric patients have better OS than adult ES patients, and we constructed a practical nomogram to predict the 3-, 5- and 10-year OS of adult patients with ES of bone based on independent prognostic factors (age, surgery, chemotherapy, T stage, N stage and M stage).

Associations between vitamin E status and bone mineral density in children and adolescents aged 8-19 years: Evidence based on NHANES 2005-2006, 2017-2018.

INTRODUCTION: Bone mineral density (BMD) in adolescence is a crucial determinant in osteoporosis and fragility fractures in older age. Vitamin E is the most abundant lipid-soluble antioxidant present in the blood. However, the association of vitamin E status with BMD in children and adolescents remains unclear. METHODS: We first measured the association of vitamin E status (serum α- and γ tocopherol) with BMD in children and adolescents with the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression models were performed to evaluate their relationship after adjusting for a large range of covariates. Stratified analyses and interaction tests were used to explore their effects on different genders, ages, and races/ethnicities. RESULTS: 13,606 children and adolescents from NHANES (2005-2006, 2017-2018) were included in our analysis. Compared with the lowest α-tocopherol quartile, individuals in the highest α-tocopherol quartile are likelier to be Non-Hispanic White and have a higher value of poverty income ratio (PIR). They have a lower value of serum phosphorus and lumbar spine BMD. Every 1umol/L increase in serum α- and γ- tocopherol, the lumbar spine BMD decreased by -0.0016 and -0.0068 g/cm2. Compared with the lowest quartile serum α- and γ- tocopherol concentration, individuals in the highest quartile have a -0.0223 and -0.0329 g/cm2 lower mean BMD, respectively. Interaction effects suggest that the negative effect is more prominent among female youth, individuals aged 8-13 years, non-Hispanic whites, Mexican Americans, and non-Hispanic blacks. CONCLUSIONS: Our study indicates serum α- and γ-tocopherol are negatively correlated with lumbar BMD. Age, gender, and race may have a modifying effect on this relationship. Our study has an important clinical implication. A higher vitamin E status for children and adolescents could not improve BMD, even decrease BMD. More prospective research with stronger evidence is needed to verify our findings and their underlying mechanisms.

Magnetic Resonance Imaging Combined with Histological Techniques for Dynamic Assessment of Cytotoxic Edema after Cerebral Ischemia-Reperfusion Injury.

BACKGROUND: Reperfusion therapy after ischemic cerebral stroke may cause cerebral ischemia-reperfusion injury (CIRI), and cerebral edema is an important factor that may aggravate CIRI. Our study aimed to dynamically monitor the development of early cytotoxic edema after CIRI by magnetic resonance imaging (MRI) and to validate it using multiple histological imaging methods. METHODS: Male Sprague Dawley rats were divided into sham and CIRI groups. T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI)-MRI scans were performed in the sham and CIRI groups after reperfusion. Relative apparent diffusion coefficient (rADC) values were calculated and the midline shift (MLS) was measured. A series of histological detection techniques were performed to observe changes in the cerebral cortex and striatum of CIRI rats. Correlation analysis of rADC values with aquaporin-4 (AQP4) and sodium-potassium-chloride cotransport protein 1 (Na+-K+-2Cl-- cotransporter 1; NKCC1) was performed. RESULTS: rADC values began to increase and reached a relatively low value in the cerebral cortex and striatum at 24 h after reperfusion, and the MLS reached relatively high values at 24 h after reperfusion (all p < 0.05). Hematoxylin-eosin (HE) staining showed that the nerve cells in the cortex and striatum of the sham group were regular in morphology and neatly arranged, and in the CIRI-24 h group were irregular, disorganized, and loosely structured. Using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, the number of TUNEL+ cells in the ischemic cortex and striatum in CIRI-24 h group was shown to increase significantly compared with the sham group (p < 0.05). Transmission electron microscopy showed that the perivascular astrocytic foot processes were swollen in the cortex and striatum of the CIRI-24 h group. Pearson correlation analysis demonstrated that rADC values were negatively correlated with the number of anti-glial fibrillary acidic protein (GFAP)+AQP4+ and GFAP+NKCC1+ cells of the CIRI rats. CONCLUSIONS: MRI combined with histological techniques can dynamically assess cytotoxic edema after CIRI, in a manner that is clear and intuitive for scientific researchers and clinicians, and provides a scientific basis for the application of MRI techniques for monitoring the dynamic progress of CIRI.

Prevalence, trend, and predictor analyses of vitamin D deficiency in the US population, 2001-2018.

Background: The National Health and Nutrition Examination Surveys (NHANES) collect and release data to the public every 2 years. The latest NHANES study on the vitamin D status of Americans was based on data from 2001 to 2014, and the latest data (2015-2016 and 2017-2018) have not been studied yet. Thus, we extracted all the available data from NHANES (2001-2018), aiming to analyze the prevalence and trends of vitamin D deficiency (VDD) in the US population to bridge the research gap. Methods: According to previous studies and nutritional guidelines for vitamin D, severe VDD was defined as serum 25(OH)D levels of <25 nmol/L, moderate deficiency as 25-50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75 nmol/L. We comprehensively estimated the prevalence of serum 25(OH)D levels of <25, 25-50, 50-75, and >75 nmol/L in Americans and described trends in vitamin D status from 2001 to 2018. Weighted multivariate linear regression models were used to explore the predictors of VDD. All analyses and the data were adjusted for the complex sampling design of NHANES using Mobile Examination Center (MEC) weights. Results: Based on the most recent data of 71,685 participants, our study showed that the weighted prevalence of severe and moderate VDD was 2.6% and 22.0%, and the prevalence of vitamin D insufficiency (VDI) and sufficiency was 40.9% and 34.5%. The prevalence of severe and moderate VDD was higher in women, non-Hispanic black Americans, people aged 20-29 years, and during the season of winter. From 2001 to 2018, we found a slight linear decrease in the prevalence of moderate VDD (coefficient = -0.847; P = 0.009) and VDI (coefficient = -0.810; P = 0.014). We also found a slight linear increase in vitamin D sufficient (coefficient = 1.693; P = 0.004). However, no trend change was observed in severe VDD (coefficient = -0.037; P = 0.698). Age, sex, ethnicity, season, sun-protective behaviors, lower BMI, lower socioeconomic status (SES), drinking, and lower milk consumption were predictors of severe VDD. Conclusion: Vitamin D deficiency is still prevalent in the United States, especially in non-Hispanic black Americans, women, individuals aged 20-29, and during winter. Therefore, individuals, healthcare providers, and policymakers should take public health measures to develop and implement prevention strategies to deal with VDD.

Socioeconomic status influences on bone mineral density in American men: findings from NHANES 2011-2020.

The association between socioeconomic status (SES) and bone mineral density (BMD) in men remains controversial. We showed that SES was positively associated with BMD in American men. Confounding factors like race/ethnicity and age could affect the association. INTRODUCTION: Based on the data from the National Health and Nutrition Examination Survey (NHANES), 2011-2020, this article aims to investigate the association of SES (poverty income ratio (PIR) and education level) with the BMD in American men. METHODS: We evaluated the association of SES with BMD in 4446 men aged ≥ 20 years (mean age, 41.0 ± 13.4 years) from the NHANES 2011-2020. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine. We used multivariate linear regression models to examine the relationship between SES and total spine BMD, adjusted for a large range of confounding factors. RESULTS: Compared with other PIR quarters, individuals in the highest quarter of PIR were more likely to be older and white and had fewer smoking or drinking behaviors. After adjusting for race/ethnicity, age, drinking and smoking behavior, body mass index (BMI), total protein, serum calcium, serum uric acid, cholesterol, serum phosphorus, and blood urea nitrogen, PIR was positively correlated with total spine BMD (ß = 0.004 95% CI: 0.001-0.007, P = 0.006). Individuals with the highest degree (college degree or above) had a 0.057 g/cm2 greater BMD than that of the lowest degree (less than 9th grade) (ß = 0.057 95% CI: 0.037-0.077, P < 0.001). CONCLUSIONS: Our study indicates that SES was positively associated with the lumbar BMD among American men. Clinicians, healthcare providers, and policymakers should consider the unequal SES of men when implementing osteoporosis prevention and treatment strategies.

Blood Lead Level Is Negatively Associated With Bone Mineral Density in U.S. Children and Adolescents Aged 8-19 Years.

Context: The relationship of lead (Pb) exposure with bone health in children and adolescents remains controversial. Objection: We aimed to investigate the association of blood lead levels (BLL) with bone mineral density (BMD) in American children and adolescents using data from the National Health and Nutrition Examination Survey (NHANES), 2005-2010. Methods: We analyzed 5,583 subjects aged 8-19 years (mean age, 13.49 ± 3.35 years) from the NHANES 2005-2010. BLL was tested using inductively coupled plasma mass spectrometry. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, total femur, and femur neck. Multivariate linear regression models were used to explore the association between BLL and BMD, adjusting for age, gender, race/ethnicity, poverty income ratio (PIR), body mass index (BMI), serum calcium, and serum phosphorus. Results: BLL was negatively correlated with BMD at different sites of interest in children and adolescents. For every 1mg/dl increase in BLL, the BMD of the total spine, total hip, and femoral neck decreased by 0.011 g/cm2, 0.008 g/cm2, and 0.006 g/cm2. In addition, Pb affected the lumbar spine more than the femur. The effect estimates were stronger in girls than boys at the lumbar spine (P for interaction= 0.006). This negative association remained significant in American children and adolescents after excluding individuals with BLL more than 3.5 ug/dl. Conclusion: Our study indicates that BLL is negatively correlated with BMD at different sites of interest in children and adolescents aged 8-19 years, even in the reference range. More research is needed to elucidate the relationships between Pb and bone health in children and adolescents, including specific mechanisms and confounding factors like race/ethnicity, gender, and age.

Inhibition of Cpt1a alleviates oxidative stress-induced chondrocyte senescence via regulating mitochondrial dysfunction and activating mitophagy.

Osteoarthritis (OA) is an age-related chronic degenerative disease, and chondrocyte senescence has been established to play an important role in the pathological process. There is ample evidence to suggest that lipid metabolism plays an important role in the aging process. However, the effect of lipid metabolism on chondrocyte senescence and OA remains unclear. Accordingly, we constructed a TBHP-induced senescent chondrocytes model and a destabilization of the medial meniscus (DMM) mouse model. We found that lipid accumulation and fatty acid oxidation were enhanced in senescent chondrocytes. Interestingly, carnitine palmitoyltransferase 1A (Cpt1a), the rate-limiting enzyme for fatty acid oxidation, was highly expressed in senescent chondrocytes and murine knee cartilage tissue. Suppressing Cpt1a expression using siRNA or Etomoxir, an inhibitor of Cpt1a, could attenuate oxidative stress-induced premature senescence and OA phenotype of primary murine chondrocytes, decrease cellular ROS levels, restore mitochondrial function, and maintain mitochondrial homeostasis via activating mitophagy. In vivo, pharmacological inhibition of Cpt1a by Etomoxir attenuated cartilage destruction, relieved joint space narrowing and osteophyte formation in the DMM mouse model. Overall, these findings suggested that knockdown of Cpt1a alleviated chondrocyte senescence by regulating mitochondrial dysfunction and promoting mitophagy, providing a new therapeutic strategy and target for OA treatment.

Prevalence and treatment rate of osteoporosis in patients undergoing total knee and hip arthroplasty: a systematic review and meta-analysis.

PURPOSE: Due to age and gender, patients awaiting total knee or hip arthroplasty (TKA/THA) are at a higher risk of osteoporosis. In joint arthroplasty, low bone mineral density (BMD) is a risk factor for implant osseointegration, durability, and prosthesis complications. This study aims to investigate the prevalence and treatment rate of osteoporosis in patients undergoing total joint arthroplasty (TJA). METHODS: We applied a comprehensive literature search through PubMed, Cochrane Library, and EMBASE from inception to July 10, 2021, for studies investigating the prevalence and treatment rate of osteoporosis in TJA patients. The aggregated prevalence was calculated with the random-effects model, and the heterogeneity between studies was checked by Cochran's Q test and quantified by the I2 statistic. We performed subgroup analyses and meta-regression analyses to determine the source of heterogeneity. Publication bias was assessed by a funnel plot and verified by Egger's test. Anti-osteoporosis treatment for TJA patients was described qualitatively and quantitatively. RESULTS: Of 4561 citations identified by the search strategy, 11 studies including 3462 patients were eligible for inclusion. The pooled prevalence of osteoporosis and osteopenia in TJA patients was 24.8% (95%CI: 14.1-37.2%) and 38.5% (95%CI: 29.3-48.0%), respectively. The prevalence of osteoporosis/osteopenia in TJA patients was 64.0% (95%CI: 45.8-80.3%). In terms of gender, the pooled prevalence of osteoporosis in males, females, and postmenopausal females were 5.5% (95%CI: 1.5-11.4%), 29.0% (95%CI: 18.3-41.1%), and 38.3% (95%CI: 13.2-67.1%), respectively. The treatment rate of osteoporosis in TJA patients was 32.9% (95%CI: 15.2-53.1%) by a random-effects model. CONCLUSIONS: Osteoporosis is highly prevalent in patients undergoing TJA, especially in postmenopausal females. However, the treatment rate of osteoporosis is low. Considering the possibility of surgical complications, clinicians should strengthen their awareness of pre-operative BMD assessment and manage osteoporosis in high-risk patients.

Inulin ameliorates schizophrenia via modulation of the gut microbiota and anti-inflammation in mice.

The microbiome-gut-brain (MGB) axis, which regulates neurological and cognitive functions, plays an essential role in schizophrenia (SCZ) progression. Dietary inulin could be a novel strategy for the treatment of SCZ due to its modulating effects on the gut microbiota. In this study, the effects of inulin on mice with SCZ were studied. As indicated by the behavioural tests, expression of neurotransmitters, inflammatory indicators, and brain morphology, inulin administration ameliorated aberrant behaviours (locomotor hypoactivity, anxiety disorders and depressive behaviours, and impaired learning and spatial recognition memory) and effectively reduced neuroinflammation and neuronal damage. In addition, inulin improved intestinal integrity and permeability, as indicated by the elevated expression of tight junction proteins (p < 0.05). The results of 16S rRNA sequencing and analysis showed that inulin increased the abundance of Lactobacillus and Bifidobacterium, which were negatively correlated with 5-hydroxytryptamine and inflammatory cytokines and positively correlated with brain-derived neurotrophic factor (BDNF). Inulin caused a reduction in Akkermansia that was positively correlated with inflammatory cytokines and negatively correlated with BDNF. These results suggested that dietary inulin modulated the gut microbiota and exerted anti-inflammatory effects in mice though the MGB axis, which further ameliorated SCZ. Therefore, the results of this study provide a potential explanation for inulin intervention in the treatment of SCZ.