ABSTRACT
Background: Thyroid-associated ophthalmopathy (TAO) is an orbital disease closely related to thyroid disease with a long-lasting duration that can be blinding and disabling. Recently, structural and functional neuroimaging studies have been performed in TAO patients, but studies have reported inconsistent results. This quantitative meta-analysis was conducted to identify convergent patterns of abnormal brain function among different studies in TAO. Methods: We searched PubMed, EMBASE, Cochrane, and Web of Science, performed reference tracking, and retrieved 15 eligible studies. Peak coordinates were extracted from these studies and subsequently tested for convergence using activation likelihood estimation (ALE). Results: Compared to healthy subjects, resting-state brain activity in the whole brain of TAO patients was significantly increased in the left superior frontal gyrus (SFG) and decreased in the left cuneus/precuneus. Functional decoding analysis of the BrainMap database revealed that these regions are predominantly associated with cognitive and emotional impairment. In this study, task-related meta-analytic connectivity modeling (MACM) analysis was used to describe the connectivity and function of the two seed regions. Significant coactivation of these regions was found primarily in the bilateral superior parietal lobule, medial frontal gyrus, left fusiform gyrus, left cingulate gyrus, supplementary motor area and thalamus. Conclusion: Our findings underscore the role of the SFG and the cuneus/precuneus in the pathophysiology of TAO, highlighting the crucial impact of working memory deficits.
ABSTRACT
Our previous studies have shown that lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) is expressed in liver sinusoidal endothelial cells, and oxidized low-density lipoprotein induces liver sinusoidal dysfunction and defenestration through the LOX-1/ROS/NF-kB pathway, revealing that LOX-1 can mediate liver sinusoidal barrier function, involved in the regulation of non-alcoholic fatty liver disease. Here, we investigated whether, in the context of bone metabolic diseases, LOX-1 could affect bone quality and type H blood vessels in diabetic mice. We used db/db mice as model and found that LOX-1 knockdown can ameliorate bone quality and type H blood vessel generation in db/db mice. This further verifies our hypothesis that LOX-1 is involved in the regulation of bone quality and type H blood vessel homeostasis, thus inhibiting osteoporosis progression in db/db mice.
Subject(s)
Diabetes Mellitus, Experimental , Animals , Mice , Diabetes Mellitus, Experimental/metabolism , Endothelial Cells/metabolism , Lipoproteins, LDL/metabolism , NF-kappa B/metabolism , Scavenger Receptors, Class E/genetics , Scavenger Receptors, Class E/metabolismABSTRACT
Type 2 diabetes mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) is a common cause of death. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in the regulation of autophagy and associated with a variety of diseases, such as atherosclerosis, diabetes, and NAFLD. This study aimed to investigate the effect of LOX-1 on autophagy induced by high glucose levels in human liver sinusoidal endothelial cells (HLSECs) and whether it regulates autophagy through the adenosine monophosphate-activated protein kinase/hepatocyte nuclear factor 4α (AMPK/HNF4α) pathway. In this study, HLSECs cultured with high glucose medium showed increased expression of LOX-1, whereas autophagy was inhibited. High glucose levels decreased the AMPK phosphorylation, increased the HNF4α phosphorylation, and retained the HNF4α in the cytoplasm. By contrast, silencing of LOX-1 reversed the phenomenon induced by high glucose levels and restored the HNF4a localization. Taken together, our findings reveal a novel mechanism of high glucose-induced autophagy in HLSECs, namely, the LOX-1-mediated AMPK/HNF4α signaling pathway. Therefore, LOX-1 is an important target molecule for the regulation of autophagy in HLSECs.
