Association of exposure to a mixture of phenols, parabens, and phthalates with altered serum thyroid hormone levels and the roles of iodine status and thyroid autoantibody status: A study among American adults.

BACKGROUND: Toxicological and epidemiological studies have shown that environmental endocrine disruptors interfere with hormonal homeostasis. However, there is limited research on the effects of mixed exposure to nonpersistent endocrine disruptors on thyroid hormones and the factors (e.g., presence status of thyroid autoantibodies or nutritional status of organismal iodine) that may influence this association. METHODS: Data were collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2008 and 2011-2012. Relationships between single pollutants and thyroid hormone and thyroid autoantibody levels were assessed using generalized linear (GLM) and restricted cubic spline (RCS) regression models. Weighted quantile sum regression (WQS), group-weighted quantile sum regression (GWQS), quantile-based g-computation (qgcomp), and adaptive elasticity network (AENET) were applied to assess the mixed exposure effect. Next, subgroup analyses were performed on the basis of the urinary iodine concentration or thyroid autoantibody status to assess the modifying role of urinary iodine and thyroid autoantibodies. RESULTS: A total of 2385 study participants were included in this study. Both the single-pollutant model and the multipollutant mixed model revealed that parabens and bis(2-ethylhexyl) phthalate (DEHP) metabolites were significantly and negatively associated with serum thyroxine (T4) levels. However, no associations were found between the target pollutants and thyroid autoantibodies (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)). In addition, this study revealed that urinary iodine or thyroid autoantibody status altered the associations of some of the target pollutants with thyroid hormones. WQS and qgcomp analyses, revealed that the associations of mixed pollutants with hormones differed depending on the urinary iodine or antibody status, especially T4 and thyroid-stimulating hormone (TSH). CONCLUSION: Significant associations were found between phenols, parabens, and phthalates and serum thyroid hormone levels, with parabens and DEHP metabolites playing major roles. Urinary iodine and thyroid autoantibody status act as modifiers between environmental endocrine-disrupting pollutants and thyroid hormones.

Disease-Modifying Effects of Lenvatinib, a Multiple Receptor Tyrosine Kinase Inhibitor, on Posttraumatic Osteoarthritis of the Knee.

Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit model of OA. In the current study, we investigated the effects of lenvatinib, an angiogenesis inhibitor targeting the VEGF and fibroblast growth factor receptors, on synovitis, osteophyte formation, and cartilage degeneration in a rabbit OA model. Posttraumatic OA was induced by anterior cruciate ligament transection (ACLT) on one knee of each rabbit. Rabbits were placed into four groups according to the following lenvatinib doses: untreated control (n = 12), L0.3: 0.3 mg/kg/day (n = 15), L1.0: 1.0 mg/kg/day (n = 14), and L3.0: 3.0 mg/kg/day (n = 13) groups. We evaluated limb pain using the weight distribution ratio measured with an incapacitance tester, macroscopic osteophyte formation, and femoral condyle synovium and cartilage histology. For cartilage evaluation, the following distal sites of the femur were evaluated separately: femoral-tibial (FT), femoral-patellar (FP), and femoral corner (between FP and FT). The weight distribution ratio at 12 weeks after surgery was higher in the L0.3 and L1.0 groups than in the control group. Osteophyte formation and synovitis scores were significantly lower in the L0.3, L1.0, and L3.0 groups than in the control group. The Osteoarthritis Research Society International scores of the FT, corner, and FP sites in the L0.3 group were lower than in the control group. The cartilage thickness ratio at the FT and corner sites was significantly lower in the L0.3 group than in the control group. Krenn's grading system of cartilage synovitis showed that all lenvatinib-administered groups had significantly lower scores than the control group. MMP3 expression level in cartilage tissue was significantly lower in the L3.0 group compared with the other three groups. ADAMTS5 expression was lower in the L3.0 group compared with the control and L0.3 groups. Oral administration of lenvatinib inhibited synovitis, osteophyte formation, and cartilage degeneration and reduced pain in a rabbit ACLT model. Lenvatinib is an oral VEGF inhibitor that is easier to administer than other VEGF inhibitors and may have potential as a treatment of posttraumatic OA.

Effects of Multidomain Interventions on Sarcopenia.

Sarcopenia, a complex muscular condition driven by multi-systemic dysregulation and its interactions with lifestyle, physical attributes, and mental health, lacks effective drug treatments, relying primarily on non-pharmacological interventions. Fragmented approaches may prove suboptimal due to its complexity, underscoring the potential for multidomain interventions-a combination of two or more strategies to improve individual health-as a promising treatment option. This review examines the possible roles of multidomain interventions in sarcopenia, specifically addressing their effects on muscle mass and quality, muscle strength, and physical performance in older adults. While the updated literature highlights the beneficial consequences of multidomain interventions in enhancing physical performance outcomes, gaps persist in understanding their influence on the biological aspects of sarcopenia. Promising initial findings suggest changes in plasma inflammatory markers or muscle turnover networks, but further research is necessary to clarify the disease-modifying effects of multidomain intervention in sarcopenic patients.

Sleep time and quality associated with depression and social anxiety among children and adolescents aged 6-18 years, stratified by body composition.

BACKGROUND: Sleep has been suggested as risk factors for depression and social anxiety in children and adolescents, but little is known about the role of individual body composition on these association. METHOD: We conducted a cross-sectional survey of children and adolescents aged 6-18 years in Beijing, China, in 2020, and assessed body composition by using iDXA dual-energy X-ray bone densitometer. Generalized liner model (GLM) and restricted cubic spline (RCS) were employed to analyze the associations between sleep and depression and social anxiety with different body composition. The attributable fraction (AFs) to assess the benefits of improvements of sleep in reducing depression and social anxiety odds. RESULTS: Depression and social anxiety accounted for 13.1 % and 30.3 % of the study population. Sleep time was significantly associated with depression (HR = 2.35[1.58, 3.50]), and social anxiety (HR = 1.65[1.24, 2.20]); and sleep quality was significantly associated with depression (HR = 7.27[4.87, 10.84]), and social anxiety (HR = 2.54 [1.99, 3.25]) among children and adolescents. The exposure to both insufficient sleep time and poor sleep quality were associated with a higher odd of depression and social anxiety, but lower BF%, higher muscle rate and FFM/FM alleviated the adverse effects of sleep quality on depression and social anxiety. LIMITATIONS: Conclusions about causality remain speculative because of the cross-sectional design. CONCLUSION: Insufficient sleep time, poor sleep quality, high BF%, low muscle rate and FFM/FM can jointly associate with anxiety and depression. This study provides new evidence support for accurate prevention and control of mental diseases in children and adolescents with different body types.

Could greenness modify the effects of physical activity and air pollutants on overweight and obesity among children and adolescents?

Greenness could theoretically increase the impact of physical activity (PA) and reduce the adverse effects of air pollution on overweight/obesity. However, no evidence systematically compares these two pathways, especially in longitudinal studies of children and adolescent's cohort. Greenness, PA, and air pollution were assessed by Normalized Difference Vegetation Index (NDVI), International Physical Activity Short Form, and 7 pollutants (PM1, PM2.5, PM10, SO2, NO2, CO, and O3). Each exposure was divided into low-/high-level groups based on the 50% quantile. Proportional hazards and logistic regression model were used to assess the associations of greenness, PA, pollutants with overweight/obesity. The incidence of overweight/obesity was 1.98% in the national survey, and the cumulative incidence and incidence density were 12.76% and 3.43 per 100 person-year in the dynamic cohort, separately. An increase of 0.1 units in NDVI was associated with a 12% lower risk of overweight/obesity, but no significant link between PA and incidence was observed. The HRs of the high-level of PM1, PM2.5, PM10, SO2, NO2, CO, and O3 on the risk of overweight/obesity were 2.21, 2.63, 1.88, 2.38, 1.33, 2.43, and 1.33 in the low-level of greenness, which was higher than those in the high-level of greenness. The AFs of PM1, PM2.5, PM10, SO2, NO2, CO, and O3 were 25.58%, 44.37%, 22.96%, 29.15%, 11.55%, 29.50%, and 10.92% in the low-level of greenness, which simultaneously was higher than those in the high-level of greenness. Moreover, the risk of overweight/obesity associated with high-level of greenness in the high-level of PM10, SO2, CO were 0.83, 0.81, and 0.83 respectively. Our findings confirmed that greenness has a moderating effect on the effects of air pollutants on childhood overweight/obesity especially in heavy-industry areas where PM10, SO2, and CO are the major pollutants, although it did not influence the association between PA and overweight/obesity risks.

The Role of Lipids in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by a progressive loss of dopaminergic neurons from the nigrostriatal pathway, formation of Lewy bodies, and microgliosis. During the past decades multiple cellular pathways have been associated with PD pathology (i.e., oxidative stress, endosomal-lysosomal dysfunction, endoplasmic reticulum stress, and immune response), yet disease-modifying treatments are not available. We have recently used genetic data from familial and sporadic cases in an unbiased approach to build a molecular landscape for PD, revealing lipids as central players in this disease. Here we extensively review the current knowledge concerning the involvement of various subclasses of fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and lipoproteins in PD pathogenesis. Our review corroborates a central role for most lipid classes, but the available information is fragmented, not always reproducible, and sometimes differs by sex, age or PD etiology of the patients. This hinders drawing firm conclusions about causal or associative effects of dietary lipids or defects in specific steps of lipid metabolism in PD. Future technological advances in lipidomics and additional systematic studies on lipid species from PD patient material may improve this situation and lead to a better appreciation of the significance of lipids for this devastating disease.