Association between sex hormone binding globulin and metabolic syndrome in US adults: insights from National Health and Nutrition Examination Survey (NHANES) 2013-2016.

BACKGROUND: Metabolic syndrome (MetS) presents a notable public health challenge on a global scale, exerting a considerable impact on individuals' health and quality of life. There is mounting evidence indicating a robust association between MetS and levels of sex hormones. Therefore, the study aims to explore the relationship between sex hormone binding-globulin (SHBG) and MetS, and to provide evidence that could inform the development of effective prevention strategies for MetS. METHODS: Data for this cross-sectional investigation were collected during the 2013-2016 cycle of the National Health and Nutrition Examination Survey (NHANES), from which 5,499 adults were sampled. The criteria established by the Adult Treatment Program III of the National Cholesterol Education Program were utilized to define MetS. SHBG levels were measured using a standardized technique. Multivariate-adjusted logistic regression, multivariate restricted cubic spline, and threshold effect analyses were utilized to investigate the association between SHBG levels and MetS. Moreover, the stratified analyses and interaction tests of covariables were presented in a forest plot. Finally, sensitivity analysis was utilized to ensure the robustness of the results. RESULTS: Overall, 1822 participants had MetS. After adjusting for possible confounders, SHBG levels were associated with MetS (Odds ratio [OR], 0.984; 95% confidence interval [CI], 0.981-0.986; P < 0.01). The multivariate restricted cubic spline analysis demonstrated a non-linear association between SHBG and MetS (P < 0.001). With two piecewise regression models, the adjusted OR of developing MetS was 0.964 (95% CI, 0.959-0.969; P < 0.001) among people with SHBG < 76.653 nmol/L, but there was no correlation between SHBG and MetS in participants with SHBG ≥ 76.653 nmol/L. The stability of the association between SHBG levels and MetS was confirmed using subgroup analysis and sensitivity analyses. CONCLUSIONS: Our results suggest that reduced SHBG levels are associated with an increased prevalence of MetS in adults, particularly when SHBG levels are below 76.653 nmol/L. More investigation is required to understand comprehend the mechanisms underlying these results and to delve into their clinical implications.

Assessment of Corneal Epithelial Changes and Related Factors in Ocular Chronic Graft-Versus-Host Disease (GVHD) by in Vivo Confocal Microscopy.

PURPOSE: To evaluate corneal epithelial changes and related factors in chronic ocular graft-versus-host disease (oGVHD) patients. METHODS: 21 patients (35 eyes) with chronic oGVHD and 8 patients (12 eyes) without oGVHD after bone marrow transplantation were recruited for assessment involving in vivo confocal microscopy (IVCM) analysis, ocular surface parameter determination and tear cytokine level analysis. The IVCM corneal epithelial scoring system was used to evaluate corneal epithelial changes. RESULTS: There was a significant difference in the corneal epithelial score (p = .001) between the two groups. The corneal epithelial scores were significantly correlated with the corneal fluorescein staining scores (CFS, r = 0.463, p < .001), Schirmer's test (r = -0.389, p = .009) and tear cytokine levels of EGF (r = -0.491, p < .001) and APRIL (r = -0.318, p = .030). CONCLUSIONS: The depth of corneal epithelial defects can be estimated by the CFS. Corneal epithelial changes of chronic oGVHD are considered to be associated with lacrimal deficiency and a lack of EGF.

Biomarkers in Ocular Graft-Versus-Host Disease: Implications for the Involvement of B Cells.

Graft-versus-host disease (GVHD) is an immune-mediated inflammatory disease resulting from destruction of host tissue by donor immunoreactive cells and occurs in 30% to 70% of post-hematopoietic stem cell transplantation (HSCT) patients. Ocular involvement occurs in up to 60% to 90% of patients with chronic GVHD. T cells have long been recognized as a key driver of alloreactivity in chronic ocular GVHD (oGVHD). However, the role of B-cells has not been elucidated. To further explore the involvement of B-cells in the immune mechanism of chronic oGVHD and to uncover more sensitive biomarker indicators, we conducted this study on the tear cytokine analysis of chronic oGVHD. The study enrolled 18 patients (27 eyes) diagnosed with chronic oGVHD and 11 patients (22 eyes) diagnosed with dry eye disease (DED) as a control group. The microsphere-based immunoassay was used to determine 29 tear cytokines in both groups. Spearman's test was used to analyze the correlation between cytokine levels and different ophthalmic indexes (National Institutes of Health eye score, fluorescein tear film break-up time, corneal fluorescein staining, and Schirmer's test). Receiver operating characteristic curves were used to assess the predictive potential of the identified cytokines for chronic oGVHD. Twenty tear cytokine levels were elevated in patients with chronic oGVHD compared to those with DED (P < .05). Proliferation-inducing ligand (APRIL) and epidermal growth factor showed lower levels in patients with chronic oGVHD. Ultimately, IL-2, 6, and 8, ICAM-1 (CD54), E-selectin (CD62E), neuropilin-1, and B-cell activation factor (BAFF) levels had a strong correlation with ophthalmic indexes and an area under the curve (AUC) > 0.85. BAFF/APRIL exhibited superior diagnostic capabilities (AUC = 0.995; 95% confidence interval, 0.983-1.000). Our study identified IL-2, 6, 8, ICAM-1, CD62E, E-selectin, neuropilin-1, and BAFF as promising tear biomarkers that can indicate the severity of chronic oGVHD. Notably, APRIL/BAFF shows superior diagnostic capabilities, revealing that B cells may play an important role as immune substrates in chronic oGVHD. © 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

A murine model of large-scale bone regeneration reveals a selective requirement for Sonic Hedgehog.

Building and maintaining skeletal tissue requires the activity of skeletal stem and progenitor cells (SSPCs). Following injury, local pools of these SSPCs become active and coordinate to build new cartilage and bone tissues. While recent studies have identified specific markers for these SSPCs, how they become activated in different injury contexts is not well-understood. Here, using a model of large-scale rib bone regeneration in mice, we demonstrate that the growth factor, Sonic Hedgehog (SHH), is an early and essential driver of large-scale bone healing. Shh expression is broadly upregulated in the first few days following rib bone resection, and conditional knockout of Shh at early but not late post-injury stages severely inhibits cartilage callus formation and later bone regeneration. Whereas Smoothened (Smo), a key transmembrane component of the Hh pathway, is required in Sox9+ lineage cells for rib regeneration, we find that Shh is required in a Prrx1-expressing, Sox9-negative mesenchymal population. Intriguingly, upregulation of Shh expression and requirements for Shh and Smo may be unique to large-scale injuries, as they are dispensable for both complete rib and femur fracture repair. In addition, single-cell RNA sequencing of callus tissue from animals with deficient Hedgehog signaling reveals a depletion of Cxcl12-expressing cells, which may indicate failed recruitment of Cxcl12-expressing SSPCs during the regenerative response. These results reveal a mechanism by which Shh expression in the local injury environment unleashes large-scale regenerative abilities in the murine rib.

On the horizon: Hedgehog signaling to heal broken bones.

Uncovering the molecular pathways that drive skeletal repair has been an ongoing challenge. Initial efforts have relied on in vitro assays to identify the key signaling pathways that drive cartilage and bone differentiation. While these assays can provide some clues, assessing specific pathways in animal models is critical. Furthermore, definitive proof that a pathway is required for skeletal repair is best provided using genetic tests. Stimulating the Hh (Hedgehog) pathway can promote cartilage and bone differentiation in cell culture assays. In addition, the application of HH protein or various pathway agonists in vivo has a positive influence on bone healing. Until recently, however, genetic proof that the Hh pathway is involved in bone repair has been lacking. Here, we consider both in vitro and in vivo studies that examine the role of Hh in repair and discuss some of the challenges inherent in their interpretation. We also identify needed areas of study considering a new appreciation for the role of cartilage during repair, the variety of cell types that may have differing roles in repair, and the recent availability of powerful lineage tracing techniques. We are optimistic that emerging genetic tools will make it possible to precisely define when and in which cells promoting Hh signaling can best promote skeletal repair, and thus, the clinical potential for targeting the Hh pathway can be realized.

Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma.

Asthma is a common allergic disorder involving a complex interplay among multiple genetic and environmental factors. Recent studies identified genetic variants of human GAB1 as a novel asthma susceptibility factor. However, the functions of Gab1 in lung remain largely unexplored. In this study, we first observed an elevation of Gab1 level in peripheral blood mononuclear cells from asthmatic patients during acute exacerbation compared with convalescence. Mice with a selectively disrupted Gab1 in myeloid dendritic cells (mDCs) considerably attenuated allergic inflammation in experimental models of asthma. Further investigations revealed a prominent reduction in CCL19-mediated migration of Gab1-deficient mDCs to draining lymph nodes and subsequent impairment of Th2-driven adaptive activation. Mechanistically, Gab1 is an essential component of the CCL19/CCR7 chemokine axis that regulates mDC migration during asthmatic responses. Together, these findings provide the first evidence for the roles of Gab1 in lung, giving us deeper understanding of asthmatic pathogenesis.

Bis(1,3-diethyl-benzimidazolium) tetra-bromidomercurate(II).

In the title compound, (C(11)H(15)N(2))(2)[HgBr(4)], the tetra-coordinated Hg(II) center of the complex anion adopts a distorted tetra-hedral geometry [Hg-Br = 2.5755 (8)-2.623 (11) Šand Br-Hg-Br = 103.78 (19)-116.4 (3)°]. One of the Br atoms is disordered over two sites [site-occupancy factors = 0.51 (6) and 0.49 (6)]. The N-C-N angles in the cations are 110.7 (6) and 111.4 (7)°. In the crystal packing, a supra-molecular chain is formed via both weak inter-molecular C-H⋯Br hydrogen bonds and π-π aromatic ring stacking inter-actions [centroid-centroid separation = 3.803 (1) Å].