Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 25, Issue 2, 2025

The dysregulation of the innate immune system plays a crucial role in the development of Diabetic Retinopathy (DR). To gain an insight into the underlying mechanism of DR, it is essential to identify specific biomarkers associated with immune cell infiltration.

In this study, we retrieved the GSE94019 and GSE60436 datasets from the Gene Expression Omnibus (GEO) database. By utilizing CIBERSORT, MCPcounter, and xCell algorithms, we conducted a comprehensive analysis of the immune cell infiltration landscape in DR. The limma package was employed to identify Differentially Expressed Necroptosis-related Genes (DENRGs). Subsequently, enrichment analysis was performed to investigate the potential functions of the DENRGs. To identify the core DENRGs, the CytoHubba plug-in in Cytoscape software was utilized. The expression levels of these core DENRGs were verified in an independent dataset.

Our analysis identified 213 DENRGs, and among them, Platelet-derived Growth Factor subunit A (PDGFA) was identified as a core DENRG. Notably, the expression of PDGFA was found to be upregulated in DR, and this finding was further validated in the GSE102485 dataset. Additionally, the results of GSVA and GSEA revealed that in the high PDGFA group, there was activation of pathways related to inflammation and the immune system. Moreover, analysis of immune infiltration demonstrated a significant association between PDGFA gene expression and the infiltration levels of specific immune cells, including basophils, macrophages M1, macrophages, neutrophils, monocytes, NK cells, and B cells.

The involvement of neutrophils in the development and progression of DR is suggested. PDGFA has emerged as a potential marker and is linked to the infiltration of immune cells in DR. These findings shed new light on the underlying mechanisms of DR.

The aim of this study was to reveal the biological functionalities associated with endoplasmic reticulum stress (ERS)-related genes (ERSGs) in the context of diabetic retinopathy (DR).

Differentially expressed genes (DEGs) within the DR group and the Control group were identified and then integrated with ERSGs. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) methodologies were used to investigate potential biological mechanisms. A diagnostic model for ERS and a nomogram were formulated based on biomarkers selected through the Least Absolute Shrinkage and Selection Operator method. The diagnostic efficacy of this model was thoroughly evaluated. ERS-associated subtypes were identified, and the Single-Sample GSEA (ssGSEA) and CIBERSORT algorithms were used to assess immune infiltration.

We identified 10 ERS-related DEGs (ERSRDEGs) within the DR Group. Subsequently, a diagnostic model was constructed based on 5 ERS genes, namely CCND1, IGFBP2, TLR4, TXNIP, and VIM. The validation analysis demonstrated the commendable diagnostic performance of the model. Analysis of the ssGSEA immune characteristics revealed a positive correlation in the DR group between myeloid-derived suppressor cells (MDSC), regulatory T cells (Tregs), and CCND1 TXNIP. Furthermore, a significant negative correlation was observed between central memory CD4 T cells and CCND1. In the context of CIBERSORT, the results indicated a positive correlation between macrophages and IGFBP2, as well as Tregs and IGFBP2 in the DR group. Notably, a conspicuous negative correlation was identified between resting mast cells and IGFBP2.

The present study provides novel diagnostic biomarkers for DR from an ERS perspective.

Hepatocellular carcinoma (HCC) is a globally prevalent malignancy accompanied by high incidence, poor outcomes, and high mortality. Anthocyanins can inhibit tumor proliferation, migration, invasion, and promote apoptosis. Moreover, autophagy-related genes (ARGs) may play vital roles in HCC progression. This study aimed to decipher the mechanisms through which anthocyanins influence HCC via ARGs and to establish a novel prognostic model.

Based on data from public databases, differential analysis and the Venn algorithm were employed to detect intersecting genes among differentially expressed genes (DEGs), anthocyanin-related targets, and ARGs. Consensus clustering was implemented to delineate molecular subtypes of HCC. The prognostic model was developed by Cox regression analyses. CIBIRSORT was engaged to assess the immune cell infiltration. Kaplan-Meier (KM) analysis and receiver operating characteristic (ROC) curve were utilized to evaluate the predictive efficiency of the prognostic signature.

A total of 36 intersecting genes were identified from overlapping 1524 ARGs, 537 anthocyanin-related targets, and 5247 DEGs. Consensus clustering determined three molecular subtypes (cluster 1, cluster 2, and cluster 3). Cluster 1 showed worse outcomes and remarkably higher abundances of plasma cells and T follicular helper cells. Furthermore, four prognostic signatures (KDR (Kinase insert domain receptor), BAK1 (BCL2 antagonist/killer 1), HDAC1 (Histone deacetylase 1), and CDK2 (Cyclin-dependent kinase 2)) were identified and showing substantial predictive efficacy.

This investigation identified three molecular subtypes of HCC patients and proposed a promising prognostic signature comprising KDR, BAK1, HDAC1, and CDK2, which could supply further robust evidence for additional clinical and functional studies.

Small molecule phytocompounds can potentially ameliorate degenerative changes in cerebral tissues. Thus, the current study aimed to evaluate the neuroprotective efficacy of phytocompounds of methanolic shoots extract of Calligonum polygonoides L. (MSECP) in hypercholesterolemia-associated neurodegenerations.

Phytochemical screening of the extract was made by LCMS/MS and validated by a repository of the chemical library. The hypercholesterolemia was induced through the intraperitoneal administration of poloxamer-407 with a high-fat diet. The in silico assessments were accomplished by following the molecular docking, ADME and molecular dynamics. MMPBSA and PCA (Principal Component Analysis) analyzed the molecular dynamics simulations. Consequently, in-vivo studies were examined by lipid metabolism, free radical scavenging capabilities and histopathology of brain tissues (cortex and hippocampus).

22 leading phytocompounds were exhibited in the test extract, as revealed by LC-MS/MS scrutiny. Molecular docking evaluated significant interactions of apigenin triacetate with target proteins (HMGCR (HMG-CoA reductase), (AChE-Acetylcholinesterase) and (BuChE- Butyrylcholinesterase). Molecular dynamics examined the interactions through assessments of the radius of gyration, RSMD, RSMF and SASA at 100 ns, which were further analyzed by MMPBSA (Molecular Mechanics Poisson-Boltzmann) and PCA (Principal Component Analysis). Accordingly, the treatment of test extract caused significant alterations in lipid profile, dyslipidemia indices, antioxidant levels and histopathology of brain tissues.

It can be concluded that apigenin triacetate is a potent phytoconstituent of MSEPC and can interact with HMGCR, AChE, and BuChE, which resulted in improved hypercholesterolemia along with neuroprotective ameliorations in the cortex and hippocampus.

The recognition of epicardial adipose tissue (EAT) as a cardiac risk factor has increased the interest in strategies that target cardiac adipose tissue.

The effect of bariatric and metabolic surgery (BMS)-induced weight loss on EAT volume was evaluated in this study.

Fifteen bariatric patients, with (MS) or without (wMS) Metabolic Syndrome, underwent magnetic resonance imaging (MRI) using an open-bore scanner to assess EAT volume, visceral adipose tissue (VAT) thickness, and other cardiac morpho-functional parameters at baseline and 12 months after BMS. Nine patients underwent laparoscopic sleeve gastrectomy (LSG), and 6 patients underwent Roux-en-Y Gastric Bypass (RYGBP).

EAT volume significantly decreased in all the patients 12 months post-BMS from 91.6 cm³ to 67.1 cm³; p = 0.0002 in diastole and from 89.4 cm³ to 68.2 cm³; p = 0.0002 in systole. No significant difference was found between the LSG and RYGBP group. Moreover, EAT volume was significantly reduced among wMS compared with MS. In particular, EAT volume in diastole was significantly reduced from 80.9 cm³ to 54.4 cm³; p = 0.0156 in wMS and from 98.3 cm³ to 79.5 cm³; p = 0.031 in MS. The reduction was also confirmed in systole from 81.2 cm³ to 54.1 cm³; p = 0.0156 in wMS and from 105.7 cm³ to 75.1 cm³; p = 0.031 in MS. Finally, a positive correlation was found between EAT loss, BMI (r = 0.52; p = 0.0443) and VAT (r = 0.66; p = 0.008) reduction after BMS.

These findings suggest that EAT reduction may be a fundamental element for improving the cardio-metabolic prognosis of bariatric patients. Moreover, this is the first study performed with an open-bore MRI scanner to measure EAT volume.