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Neovascular diseases, such as neovascular ophthalmopathy, atherosclerosis, and tumors, are characterized by pathological angiogenesis, leading to the formation of leaky, tortuous, and immature blood vessels, often accompanied by chronic inflammation and tissue damage. Among the multiple drivers of angiogenesis in these conditions, the role of oxidized low-density lipoprotein (oxLDL) has garnered increasing attention. Formed from low-density lipoprotein (LDL) under oxidative stress, oxLDL acts as a cross-organ biomarker that systemically impacts multiple organs via the circulatory system, exerting a pivotal pro-angiogenic effect. This review focuses on elucidating the common molecular mechanisms by which oxLDL and its downstream lipid peroxidation products accumulate in disease-specific microenvironments. This accumulation activates inflammatory and oxidative stress pathways in macrophages and endothelial cells, modulating their functional reprogramming and thereby driving pathological neovascularization. Our aim is to provide an integrated framework for understanding the complex role of oxLDL as a cross-organ biomarker in multisystem neovascular diseases and to offer a theoretical basis for its potential as a therapeutic target.

Purpose: to determine the metabolomics profiles in the plasma samples of primary open-angle glaucoma (POAG) patients. Methods: The plasma samples from 20 POAG patients under intraocular pressure (IOP)-lowering medication treatment and 20 control subjects were subjected to the untargeted metabolomics analysis, among which 10 POAG patients and 10 control subjects were further subjected to the oxylipin-targeted metabolomics analysis by liquid chromatography–mass spectrometry analysis. The prediction accuracy of the differentially abundant metabolites was assessed by the receiver operating characteristic curves. Pathway analysis and correlation analysis on the differentially abundant metabolites and clinical and biochemical parameters were also conducted. Results: Untargeted metabolomics profiling identified 33 differentially abundant metabolites in the POAG patients, in which the metabolism of linoleic acid, α-linolenic acid, phenylalanine, and tricarboxylic acid cycle were enriched. The correlation analysis indicated that the differentially abundant metabolites were associated with central corneal thickness, peripapillary retinal nerve fiber layer thickness, visual field defects, and lymphocytes. The oxylipin-targeted metabolomics analysis identified 15-keto-Prostaglandin F2 alpha, 13,14-Dihydro-15-keto-prostaglandin D2, 11-Dehydro-thromboxane B2, 8,9-Epoxyeicosatrienoic acid, and arachidonic acid to be significantly decreased in the POAG patients and enriched in the arachidonic acid (AA) pathway. Conclusions: This study revealed that the metabolites in the arachidonic acid metabolism pathway are differentially abundant, suggesting high IOP may not be the only detrimental factor for optic nerve cell damage in this group of POAG patients. Lipid metabolism instability-mediated alterations in oxylipins and AA pathways may be important in POAG, suggesting that oxidative stress and immune-related inflammation could be valuable directions for future therapeutic strategies.

This study aimed to establish a model of abnormal lipid metabolism in Apolipoprotein E ( ApoE ) knockout mice by feeding them a high-fat diet (HFD) and to investigate the impact of this abnormal lipid metabolism on retinal blood perfusion, structure, and function, particularly the retinal ganglion cell (RGC). Both HFD and regular diet (RD) feeding were conducted in C57BL/6J mice and ApoE −/− mice. Lipid metabolism was assessed using hematoxylin-eosin (HE) staining, oil red staining, and blood lipid detection. Retinal microcirculation was evaluated through fundus fluorescein angiography. The expression levels of inflammatory cytokines were determined using quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Intraocular pressure, retinal structure, and RGCs were assessed using tonometer, optical coherence tomography, HE staining, and immunofluorescence staining. Retinal function was measured by electroretinogram. Hyperlipidemia was induced in ApoE −/− mice fed HFD. Retinal microcirculation was impaired in mice with abnormal lipid metabolism, while the expression of the inflammatory cytokine Tnf-α was significantly increased in atherosclerotic plaques, serum, and retina. Ultimately, compared with normal mice on a RD, ApoE −/− mice fed HFD exhibited no significant changes in intraocular pressure but demonstrated decreased RGC density and impaired retinal structure and function of the inner and outer layers of the retina. The abnormal lipid metabolism in ApoE −/− mice fed a HFD can exacerbate the disturbance of intraocular microcirculation and RGC loss caused by aging, as well as inflammation of the intraocular microenvironment and damage to retinal function.

Purpose: Investigate the oxylipin profiles in the aqueous humor of primary open-angle glaucoma (POAG) patients. Methods: Aqueous humor samples were collected from 17 POAG patients and 15 cataract subjects and subjected to a liquid chromatography/mass spectrometry (LC-MS) analysis to detect the oxylipins. The prediction potential of the differential abundant oxylipins was assessed by the receiver operating characteristic (ROC) curves. Pathway and correlation analyses on the oxylipins and clinical and biochemical parameters were also conducted. Results: The LC-MS analysis detected a total of 76 oxylipins, of which 29 oxylipins reached the detection limit. The multivariate analysis identified five differential abundant oxylipins, 15-keto-prostaglandin F2 alpha (15-kPGF2α), Leukotriene B4 (LTB4), 12,13-Epoxyoctadecenoic acid (12,13-Epome), 15-Hydroxyeicosatetraenoic acid (15-HETE) and 11-Hydroxyeicosatetraenoic acid (11-HETE). The five oxylipins are enriched in the arachidonic acid metabolism and linoleic acid metabolism pathways. Pearson correlation analysis showed that 11-HETE was positively correlated with intraocular pressure and central corneal thickness and negatively with cup/disk area ratio in the POAG patients. In addition, 15-kPGF2α was moderately and positively correlated with the mean deviation (MD) of visual field defect, and LTB4 was moderately and negatively correlated with macular thickness. Conclusions: This study revealed the oxylipin profile in the aqueous humor of POAG patients. Oxylipins involved in the arachidonic acid metabolism pathway could play a role in POAG, and anti-inflammatory therapies could be potential treatment strategies for POAG.

To investigate the plasma lipoprotein subclasses in patients with primary open-angle glaucoma (POAG), a total of 20 Chinese POAG patients on intraocular pressure (IOP)-lowering treatment and 20 age-matched control subjects were recruited. Based on the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), the study subjects were divided into elevated- and normal-level subgroups. The plasma lipoprotein, lipoprotein subclasses, and oxidized LDL (oxLDL) levels were quantitatively measured. The discrimination potential of the lipoproteins was evaluated using the area under the receiver operating characteristic curve (AUC), and their correlation with clinical parameters was also evaluated. Compared to the control subjects with elevated TC and/or LDL-C levels, the levels of TC, LDL-C, non-high-density lipoprotein cholesterol (non-HDL), LDL subclass LDL3 and small dense LDL (sdLDL), and oxLDL were significantly higher in POAG patients with elevated TC and/or LDL-C levels. No differences in any lipoproteins or the subclasses were found between the POAG patients and control subjects with normal TC and LDL-C levels. Moderate-to-good performance of TC, LDL-C, non-HDL, LDL3, sdLDL, and oxLDL was found in discriminating between the POAG patients and control subjects with elevated TC and/or LDL-C levels (AUC: 0.710–0.950). Significant negative correlations between LDL3 and sdLDL with retinal nerve fiber layer (RNFL) thickness in the superior quadrant and between LDL3 and average RNFL thickness were observed in POAG patients with elevated TC and/or LDL-C levels. This study revealed a significant elevation of plasma lipoproteins, especially the LDL subclasses, in POAG patients with elevated TC and/or LDL-C levels, providing insights on monitoring specific lipoproteins in POAG patients with elevated TC and/or LDL-C.

Glaucoma is a leading cause of irreversible blindness worldwide. One hallmark of glaucoma is the degeneration of retinal ganglion cells (RGCs). In this study, a dual role for growth hormone‐releasing hormone receptor (GHRHR) modulation under glaucoma‐relevant conditions and complementary injury paradigms involving the RGCs is identified. Using acute IOP elevation (retinal ischemia‐reperfusion), chronic ocular hypertension (microbead‐induced), and traumatic axonal injury (optic nerve crush) models, we show that GHRHR deficiency preserves RGC survival and uniquely restores visual functions—contrasting with GHRHR activation, which solely promotes cellular survival. Single‐cell transcriptomic analysis uncovers RGC‐specific alterations in genes associated with ferroptosis, lipid metabolism, oxidative stress, and mitochondrial dynamics. At the mechanistic level, GHRHR deficiency prevents the pathological downregulation of key anti‐ferroptotic mediators GPX4 and FTH1 while suppressing pro‐ferroptotic factors ACSL4 caused by glaucomatous neurodegeneration. This multifaceted regulation attenuated iron accumulation, lipid peroxidation, and reactive oxygen species (ROS) accumulation, effects that are diminished by the ferroptosis inducer RSL3. Notably, in mitochondria damaged primary RGCs, pharmacological GHRHR inhibition replicates these benefits, reducing lipid peroxidation and mitochondrial ROS to bolster RGC survival. Collectively, these findings establish GHRHR inhibition as a potent therapeutic strategy for glaucomatous neurodegeneration, synergistically rescuing both structural and functional integrity of the retina.

Objectives Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are beneficial to human health. However, the n-3 PUFAs contents of the livestock meat that we consume daily are relatively low. Utilization of transgenic technology to increase n-3 PUFAs contents in livestock may solve this problem. Results The omega-3 fatty acid desaturase (FAD3), encoded by fat1 gene derived from Caenorhabditis elegans ( C. elegans) , converts omega-6 polyunsaturated fatty acids (n-6 PUFAs) to n-3 PUFAs. In the study, a plasmid containing the codon-optimized C. elegans fat1 gene ( mfat1 ) was constructed and used to produce transgenic beef cattle by somatic cell nuclear transfer. Fourteen transgenic calves were obtained, and the ratio of n-6 to n-3 PUFAs in the transgenic calves decreased from 5.33: 1 to 0.95: 1 compared with negative controls. Conclusions Our results demonstrated that the codon-optimized C. elegans mfat1 gene can be functionally expressed in the beef cattle and converts n-6 PUFAs to n-3 PUFAs.

CCAAT/enhancer binding protein delta (C/EBPδ), an important transcriptional factor, regulates cell growth, differentiation and adipogenesis in humans and mice. However, we lack of directive information on the effects of C/EBPδ gene in bovine cells. In the present study, we cloned the CDS areas of bovine C/EBPδ gene and predicted its sequence characteristics. Moreover, we constructed the recombinant adenovirus plasmids of bovine C/EBPδ gene and harvested the subsequent adenoviruses to infect bovine primary fibroblasts. Oil Red O staining results showed lipid droplets accumulated gradually in the adenoviruses treated fibroblasts. Time course real-time PCR results indicated that over-expression of exogenous C/EBPδ regulated the mRNA expression levels of some key adipogenic genes, herein, activated the C/EBPα expression, increased lipoprotein lipase and fatty acid binding protein 4 mRNA expression levels, whereas inhibited leptin receptor gene. In conclusion, the present study demonstrates that the elevated C/EBPδ can induce the adipogenesis in the fibroblasts of cattle.

The objective of this research were to detect bovine Dickkopf 2 ( DKK2 ) gene polymorphism and analyze their associations with body measurement traits (BMT) and meat quality traits (MQT) of animals. Blood samples were taken from a total of 541 Qinchuan cattle aged from 18 to 24 months. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was employed to find out DKK2 single-polymorphism nucleotide (SNPs) and to explore their possible association with BMT and MQT. Sequence analysis of DKK2 gene revealed 2 SNPs (C29 T and A169C) in 5′ untranslated region (5′UTR) of exon 1.C29T and A164T SNPs are both synonymous mutation, which showed 2 genotypes namely (CC, CT) and (AA and AC), respectively. Association analysis of polymorphism with body measurement and meat quality traits at the two locus showed that there were significant effects on CT, BL, RL, PBW, BFT, LMA, and IFC. These results suggest that the DKK2 gene might have potential effects on BMT and MQT in Qinchuan cattle population and could be used for marker-assisted selection.