Hypoxia plays a critical role in regulating vascular function, with endothelial mechanosensitive proteins, such as the piezo-type mechanosensitive ion channel component 1 (Piezo1), emerging as key players in maintaining vascular homeostasis. Piezo1 is essential for nitric oxide-mediated vasodilation and vascular tone regulation. However, the impact of hypoxia on endothelial Piezo1 expression and function remains poorly understood. The present study investigated the regulation of Piezo1 and mechanosensitive-related genes (MRGs) during hypoxic development and their role in fetal growth restriction (FGR). Using publicly available datasets, we identified distinct transcriptional profiles in placental endothelial cells from human FGR pregnancies and human umbilical vein endothelial cells (HUVEC) exposed to hypoxia. Functional enrichment analysis revealed significant changes in pathways related to PI3K-Akt, MAPK, and VEGF signaling and responses to mechanical stimuli. Hypoxia-related transcription factors, particularly HIF-1α and HIF-1β, were enriched in the promoter regions of differentially expressed MRGs, including Piezo1, suggesting a conserved regulatory mechanism. In vitro experiments confirmed hypoxia-induced down-regulation of Piezo1 in HUVEC, while ex vivo studies using a chicken embryo model demonstrated impaired Piezo1-mediated vasodilation following hypoxic development. Combined, these findings highlight the critical role of hypoxia in modulating endothelial Piezo1 expression and function, providing mechanistic insights into vascular dysfunction associated with FGR. The present study provides evidence for the potential to target Piezo1 and HIF-1α signaling as therapeutic strategies to improve vascular outcomes in offspring of pregnancies complicated by hypoxia and FGR.

Increasing evidence indicates a potential role of white matter (WM) damage in the onset and progression of Alzheimer disease (AD). However, the biological processes underlying in vivo WM imaging biomarkers remain unclear. We sought to determine the molecular signatures associated with WM integrity in cognitively normal individuals with and without amyloid pathology. We selected older individuals without dementia (Clinical Dementia Rating <1) from the Alzheimer Centrum Amsterdam when they had diffusion tensor imaging (DTI) and CSF proteomic (untargeted tandem mass-mass spec) data available. Fractional anisotropy (FA) and mean diffusivity (MD) values were computed for the total WM and for 12 tracts of interest. We tested associations between protein levels (predictors) and both global and regional FA and MD values (outcomes) with linear models. Models further included an interaction between protein levels and amyloid status to evaluate specificity to disease. Gene-set and cell-type enrichment analyses were performed on proteins showing significant associations to characterize the underlying biological and cellular processes. A total of 96 participants were included in this study (mean age 67.82 ± 6.93 years; 45% male participants). A total of 234 protein levels (17.1%) were significantly associated with global DTI measures. Of these, 29.9% was unique for FA, and 29.9% for MD, while levels of the remaining proteins were associated with both measures (WM-generic proteins). WM-generic proteins were mostly enriched for pathways related to lipid metabolism and in endothelial cells, whereas proteins specific to FA were mostly related to blood coagulation and enriched in astrocytes and those specific to MD were mainly associated with processes related to actin filaments and enriched in oligodendrocytes. When looking at the interaction with amyloid status, both global FA and MD alterations in A+ participants were associated with biological processes of axonogenesis and synaptic plasticity. Regional analysis revealed distinct proteomic profiles associated with variations in regional FA and MD, with processes linked to synaptic plasticity specifically related to integrity of limbic fibers. Loss of WM integrity in the very early stages of AD seems to be related to alterations in biological processes associated with neuronal plasticity and oligodendrocyte integrity. Our findings provide new insights into the distinct biological mechanisms regulating WM integrity and its relationship with AD pathology.

Metabolic crosstalk between cancer and stromal cells: Implications for precision oncology.

Exosomal miR-10b derived from protocatechuic acid-treated efferocytic macrophages inhibits endothelial inflammation by targeting MAP3K7/β-TrCP/NF-κB signaling pathway.

A tumor-derived mitochondrial tsRNA drives vascular invasion of lung adenocarcinoma by promoting ribosomal assembly in endothelial cells.

Impinging flow regulates endothelial cell injury via HMGB1-mediated ferroptosis to promote intracranial aneurysm formation and progression.

3D mechanical stimulation modulates endothelial exosomes to promote fibroblast activation.

Hydroalcoholic gel of Angelica sinensis polysaccharides promotes wound healing by suppressing ferroptosis through PI3K/AKT/Nrf2 signaling pathway.

5-Aza-CdR increases expression of the tight junction protein ZO-1 via upregulation of miR-126 through promoter hypomethylation in HMEC-1 cells.

"In situ endothelial modulation and transduction" strategy driven by biomimetic H2S delivery system for targeted repair of vascular injury.

SIRT5 promotes vascular regeneration in peripheral muscle ischemia by regulating malonylation and glycolysis.

Small nucleolar RNA host gene 3 regulates sepsis-induced acute lung injury and inflammation by targeting microRNA-186-5p.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are among the most effective treatments for type 2 diabetes mellitus (T2DM). GLP-1 RAs stimulate pancreatic receptors, improving glycemia by boosting insulin secretion while decreasing glucagon secretion. GLP-1 receptors are present in pancreatic tissue. They are also found in extra-pancreatic tissue and have been shown to reduce body weight while also protecting the heart and endothelial cells. The most prevalent types of GLP-1 RAs can be injected twice daily (exenatide), once daily (lixisenatide and liraglutide), or once weekly (albiglutide, dulaglutide, exenatide once, semaglutide, tirzepatide). GLP-1 receptor agonists also reduce gastric emptying, preventing substantial post-meal glycaemic increases. Many publications have been written regarding GLP-1 RAs, covering various features of this family. However, the purpose of this study is to investigate the pharmacological design models and pharmacokinetic characteristics of the most regularly used members of this class, as well as to highlight contemporary developments in GLP-1 RAs. It also describes the physicochemical features, techniques of manufacture, the effects of molecular structure, and structural modifications on pharmacological activity. The literature review was completed using a structured approach to identify and integrate relevant literature. It involved a broad search of reputable medical databases using inclusion and exclusion criteria. They are classified as short-acting or long-acting based on the length of their action. Short-acting GLP-1 RAs and long-acting GLP-1 RAs have differing efficacy profiles. Furthermore, the methods of administration, mode of action, and side effects of these medications are relevant to their pharmacological design and pharmacokinetic properties. The treatment of type 2 diabetes and obesity has evolved with the advent of GLP-1 RAs. These drugs have a multifaceted approach, emphasizing glycemic regulation, weight loss, and reduction of cardiovascular risk. Their unique mode of action, strong safety profile, and ability to be individualized according to each patient's needs make them a valuable therapeutic option in the management of metabolic disorders. Their pharmacological activities are also influenced by their different structural and pharmacokinetic properties. GLP-1 RAs have a complex strategy due to their pharmacological nature. The variations in their design have led to various members with varying pharmacodynamic and pharmacokinetic features.

Ethyl ferulate suppresses choroidal neovascularization by accelerating Keap1 degradation through the inhibition of PSMD14-mediated deubiquitination.

Targeting macrophage-mediated clearance of apoptotic cells overcomes anti-VEGF resistance in choroidal neovascularization.

Impact of anticoagulants and centrifugal forces on plasma neutrophil extracellular traps assay outcomes.

Gut microbiota-derived isoxanthohumol metabolite, 8-prenylnaringenin, mitigates endothelial dysfunction in Angiotensin II-induced hypertension through G protein-coupled estrogen receptor-mediated eNOS activation.

Metabolic dysregulation in cerebral small vessel disease: pathogenesis and therapeutic targets.

Core regulatory mechanisms of macrophage dynamic polarization and multicellular interaction networks in driving venous thromboembolism.

Transglutaminase 2 modulates inflammatory angiogenesis via vascular endothelial growth factor receptor 2 pathway in inflammatory bowel disease.