Interference with SPARC inhibits Benzophenone-3 induced ferroptosis in osteoarthritis: Evidence from bioinformatics analyses and biological experimentation.

The aim of this study is to conduct a thorough evaluation of the association between Benzophenone-3 (BP-3) exposure and OA, offering critical insights into the underlying mechanisms involved. The National Health and Nutrition Examination Survey (NHANES) database was utilized to investigate the correlation between BP-3 and osteoarthritis. Proteomic sequencing from clinical sample and the PharmMapper online tool were employed to predict the biological target of BP-3. Cellular molecular assays and transfection studies were performed to verify the prediction from bioinformatics analyses. Through cross-sectional analysis of the NHANES database, we identified BP-3 as a risk factor for OA development. The results of proteomic sequencing showed that Secreted Protein Acidic and Rich in Cysteine (SPARC) was significantly elevated in the area of damage compared to the undamaged area. SPARC was also among the potential biological targets of BP-3 predicted by the online program. Through in vitro cell experiments, we further determined that the toxicological effects of BP-3 may be due to SPARC, which elevates intracellular GPX4 levels, activates the glutathione system, and promotes lipid peroxidation to mitigate ferroptosis. Inhibiting SPARC expression has been shown to reduce inflammation and ferroptosis in OA contexts. This research provides an expansive understanding of BP-3's influence on osteoarthritis development. We have identified SPARC as a potent target for combating chondrocyte ferroptosis in BP-3-associated osteoarthritis.

Assessment of the bidirectional causal association between frailty and depression: A Mendelian randomization study.

BACKGROUND: Observational studies have demonstrated a strong bidirectional association between frailty and depression, but it remains unclear whether this association reflects causality. This study aimed to examine the bidirectional causal relationship between frailty and depression. METHODS: Using genome-wide association study summary data, two-sample Mendelian randomization was performed to test for the potential bidirectional causality between frailty, as defined by both the frailty index and the frailty phenotype, and depression. Several frailty-related traits were additionally investigated, including weaker hand grip strength, slower walking pace and physical inactivity. Findings were replicated using an independent depression data source and verified using multiple sensitivity analyses. RESULTS: Genetically predicted higher frailty index (odds ratio [OR], 1.86; P < 0.001), higher frailty phenotype score (OR, 2.79; P < 0.001), lower grip strength (OR, 1.23; P = 0.003), slower walking pace (OR, 1.55; P = 0.027) and physical inactivity (OR, 1.44; P = 0.003) all were associated with a higher risk of depression. As for the reverse direction, genetic liability to depression showed consistent associations with a higher frailty index (beta, 0.167; P < 0.001) and a higher frailty phenotype score (beta, 0.067; P = 0.001), but not with other frailty-related traits that were investigated. The results were stable across sensitivity analyses and across depression datasets. CONCLUSIONS: Our findings add novel evidence supporting the bidirectional causal association between frailty and depression. Improving balance and muscle strength and increasing physical activity may be beneficial in both depression and frailty.

Systemic evaluation of the relationship between asthma and osteoarthritis: Evidence from a meta-analysis and Mendelian randomization study.

Objective: Osteoarthritis (OA) and asthma are two common chronic diseases with increasing incidence and prevalence, whereas there has been rare evidence to suggest the relationship between OA and asthma. This study aimed to analyze the causal relationship between OA and asthma. Methods: Existing studies of the relationship between asthma and OA published till July 18, 2023, were identified from PubMed and Web of Science databases for meta-analysis. Subsequently, the causal relationship of all and site-specific OA with asthma was explored through a bidirectional two-sample Mendelian randomization (MR) analysis. Results: A total of four eligible studies were included in the meta-analysis. In these studies, 80,550 participants were recruited, of whom 13,781 patients had OA. The asthma group had a significantly higher prevalence of OA than the control group (odds ratio (OR) = 2.08; 95% confidence intervals (CI): 1.42-3.03). However, MR analysis did not support a causal relationship between asthma and all OA and site-specific OA: knee and hip OA (OR = 1.03; 95% CI: 0.98-1.09), knee OA (OR = 1.02; 95% CI:0.96-1.08), and hip OA (OR = 1.04; 95% CI: 0.97-1.12). No causal relationship between OA and asthma was found through reverse MR analysis. Conclusions: This meta-analysis suggests that patients with asthma are likely to have a greater prevalence of OA. However, the result of MR analysis reveals that asthma does not have a causal relationship to all OA or site-specific OA.

Association between urinary phthalate levels and chronic pain in US adults, 1999-2004: A nationally representative survey.

Introduction: Chronic pain is a public health concern throughout the world. Ascertaining and managing its risk factors helps develop well-directed treatment plans and prevention strategies. Phthalates (PAEs) exposure leads to various health problems. The present study aims to explore the potential correlation between urinary PAEs metabolites and chronic pain in adults. Methods: The study population data were extracted from the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2004 in the United States. Seven urinary PAEs metabolites were used to assess long-term PAEs exposure. The assessment of chronic pain was determined by a self-report questionnaire. Weighted analyses were conducted to consider the complex sampling design. Models were adjusted by demographic data and lifestyle factors. Urinary PAEs metabolites were assessed as both continuous and categorical variables. Tertile 1 was considered as the reference. Stratified analyses were performed by gender and pain site. All data analyses were conducted with STATA, version 15.1. P < 0.05 was considered with statistical significance. Results: A total of 4,196 participants were considered in our final analysis. Chronic pain prevalence reached 52.19% (n = 2,138) among the participants, with women accounting for a large proportion (57.75% vs. 42.25%). After multivariable logistic regression analysis, a higher prevalence of chronic pain was observed among participants in the third tertile of mono-(2-ethyl)-hexyl phthalate (MEHP) (OR = 1.23, 95% CI = 1.02-1.48, P = 0.034) and mono-benzyl phthalate (MBzP) (OR = 1.28, 95% CI = 1.04-1.58, P = 0.022) in our adjusted model. The logtransformed concentration of MBzP also showed a significant association with chronic pain prevalence (OR = 1.09, 95% CI = 1.01-1.18, P = 0.036) in the adjusted model. In further analysis, the positive correlations of urinary phthalate metabolites with chronic pain remained robust when stratified by gender and chronic pain site. Conclusions: Our findings presented a positive correlation between urinary PAEs metabolites and chronic pain among adult participants, and more causal research should be conducted to ascertain the interactions between the two and to expound their underlying mechanisms.

Structures and magnetic properties of several phenoxo-O bridged dinuclear lanthanide complexes: Dy derivatives displaying substituent dependent magnetic relaxation behavior.

Nine dinuclear Ln(iii) complexes, [Ln(dbm)2(L)]2 (Ln = Eu (), Tb (), Dy (), Ho (), Er ()) and [Ln(dbm)2(L')]2 (Ln = Tb (), Dy (), Ho (), Er ()) (dbm = 1,3-diphenyl-1,3-propanedione, HL = 2-[[(4-methoxy-phenyl)imino]methyl]-8-hydroxy-quinoline and HL' = 2-[[(4-ethoxyphenyl)imino]methyl]-8-hydroxyquinoline) have been synthesized, and structurally and magnetically characterized. The nine complexes are all phenoxo-O bridged binuclear complexes, in which Ln1 and Ln1a are in an eight-coordinated environment bridged by two phenoxido oxygen atoms of two 8-hydroxyquinoline Schiff base ligands. Although complexes and have very similar structures, magnetic studies reveal that they exhibit different magnetic relaxation behaviors with the effective barriers (ΔE/kB) of 34.5 K for and 67.6 K for . The dissimilar dynamic magnetic behaviors of and mostly result from the different electron-donating effect induced by the two alkoxy (-OCH3 and -OC2H5) of the 8-hydroxyquinoline Schiff base ligands. Meanwhile, for complexes , , and , there are no observed magnetic relaxation behaviors under a zero dc field. In addition, the luminescence properties of , and were studied.