Peripapillary vessel wall changes correlate with disease severity in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)Chi, Chang, Liao
et alJ Neurol Sci (2025) 472, 123467
Abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by NOTCH3 mutations. This study explores retinal vascular changes and their associations with neuroimaging biomarkers in preclinical carriers and symptomatic CADASIL patients METHOD: This prospective case-control study enrolled six preclinical NOTCH3 mutations carriers, 21 symptomatic CADASIL patients and 17 controls. Participants underwent Optical coherence tomography (OCT) and OCT-angiography. Brain magnetic resonance imaging, mini-mental state examination, and trail making test A were conducted in CADASIL patients and carriers. White matter hyperintensity (WMH) severity was scored by modified Scheltens scale.There was a significant difference in the retinal arteriolar wall thickness among CADASIL patients (mean, 15.14 μm), carriers (mean, 14.30 μm), and controls (mean, 13.43 μm) (p = 0.009). OCT revealed significantly thinner peripapillary retinal nerve fiber layer thickness in CADASIL patients compared to the controls (p = 0.003), but there were no differences in the thickness of ganglion cell-inner plexiform layer or macular vessel densities among three groups. Multivariate regression analysis found that increased venular inner and outer diameters correlated with a greater WMH severity (p = 0.026 and 0.018), and an increased risk of lacunae and stroke in CADASIL patients.Symptomatic CADASIL patients have the greatest retinal arteriolar wall thickness, followed by preclinical carriers, and healthy controls. Larger venular inner and outer diameters were correlated with the WMH severity and presence of lacunae in CADASIL patients, which may be utilized to assess the disease severity of CADASIL.Copyright © 2025 Elsevier B.V. All rights reserved.
Research and progress of microRNA-136 in metastatic tumorsWang, Chen, Ni
et alFront Oncol (2025) 15, 1555270
Abstract: MiR-136 is abnormally expressed in many types of metastatic tumors and is closely associated with tumor cell proliferation, apoptosis, invasion, and metastasis, indicating its important role in tumor development and progression. This review summarizes current knowledge regarding miR-136's molecular mechanisms, functional roles, and impact on chemotherapy in different human cancers.A literature search was conducted in PubMed and Web of Science using "miR-136" and "metastatic tumors" as English keywords, and in CNKI and Wanfang databases using the same terms in Chinese. Studies related to miR-136 research in metastatic tumors and high-quality evidence from similar studies were included. Meta-analyses, dissertations, conference papers, low-quality articles, unavailable full-text articles, and republished articles were excluded.This review synthesizes the current understanding of miR-136's role in various cancers, including osteosarcoma, gastric cancer, gallbladder cancer, esophageal cancer, prostate cancer, colorectal cancer, breast cancer, glioma, and thyroid cancer. miR-136 acts as a tumor suppressor by targeting various genes, including MTDH, PTEN, MAP2K4, MUC1, LRH-1, MIEN1, RASAL2, CYR61, and KLF7. It influences multiple signaling pathways, including the ERK/mitogen-activated protein kinase, Wnt/β-catenin, Ha-Ras, PI3K/Akt, Aurora-A kinase, nuclear factor-κB, and JNK pathways. Furthermore, miR-136 is involved in chemoresistance by modulating ROCK1, PPP2R2A, and the miR-136-Notch3 signaling axis.MiR-136 demonstrates promising potential as a novel biomarker and therapeutic target in various human cancers. Further research is needed to fully elucidate its complex roles in cancer development, progression, and drug resistance, particularly regarding its potential in immunotherapy.Copyright © 2025 Wang, Chen, Ni, Wang and Zhou.
Assessing changes on large cerebral arteries in CADASIL: Preliminary insights from a case-control analysisLopez-Navarro, Mayer, Barreto
et alJ Stroke Cerebrovasc Dis (2025) 34 (6), 108294
Abstract: Parent large brain arteries are intimately related to their offspring's small arteries. Whether the CADASIL phenotype is confined to small vessels is unclear, and the involvement of large arteries in CADASIL has not been systematically studied.We conducted a retrospective observational study with patients with CADASIL and randomly selected controls with acute lacunar stroke from the New York-Presbyterian Hospital/Columbia University Irving Medical Center Stroke Registry. We measured the diameters of both groups' basilar artery (BA) and intracranial internal carotid artery (ICA) on T2-weighted images. Z-scores of the arteries were calculated to derive a Brain Arterial Remodeling (BAR) score. We rated cervical ICA tortuosity as 0=no tortuosity, 1 = 45-90° deviation, and 2= >90°. Generalized linear models compared large artery characteristics, adjusting for demographics and clinical variables.We matched 37 patients with CADASIL with 104 controls. Patients with CADASIL were less likely to be Hispanic/Latino (p < 0.001), hypertensive (p < 0.001), or current smokers (p = 0.02) but more likely to have a prior stroke (p < 0.001) than controls. In adjusted models, patients with CADASIL had larger BA diameters than controls (p = 0.002), but there were no differences in the right and left ICA diameters (p = 0.73, p = 0.88). There was a statistical trend for higher cervical ICA tortuosity in patients with CADASIL compared to controls (p = 0.08).Traditionally considered a small-vessel disease, patients with CADASIL have larger BA diameters and possibly higher cervical ICA tortuosity than controls. Whether these changes are part of the NOTCH-3 mutation phenotype or influence the clinical course is uncertain but should be further investigated.Copyright © 2025. Published by Elsevier Inc.
Molecular architecture of human atherosclerosis revealed through integrative human geneticsEl-Sabawi, Betti, Lin
et almedRxiv (2025)
Abstract: Current genetic discovery methods are largely restricted to profiling circulating molecules or genetic architecture, limited in use of tissue-based molecular genetics to identify pathogenic and therapeutic targets. Here, we leverage a multi-level genetic discovery platform integrating population-level proteomics with functional genomic analyses based on human coronary artery tissue to reveal determinants of coronary disease susceptibility. Using aptamer-based proteomics (~7,000 aptamers) across ~3,000 individuals, we first identified the circulating proteome of prevalent and incident coronary artery calcium (CAC), a sensitive marker of subclinical coronary artery disease (CAD), with causal implication in calcified plaque formation or disease phenotypes via parallel genetic approaches (Mendelian randomization, MR) and proteome-wide association (PWAS). Identified proteins specified pathways of extracellular matrix remodeling, immune cell function, lipid metabolism, and inflammation. To resolve findings at a coronary tissue level, we performed the largest to date coronary artery-specific transcriptome-wide association study for CAC (TWAS; based on RNA-seq from 268 human coronary arteries) in >35,000 individuals, demonstrating enrichment of targets from the circulating proteome with supportive evidence by traditional MR approaches (NOTCH3, SPINK2, S100A12, RPP25, OAF, HS6ST3, TNFSF12, GPC6), several implicated in CVD-adjacent biological mechanisms. Phenome-wide association and single cell transcriptomics in human coronary arteries across atherosclerosis implicated targets in tissue-specific disease mechanisms. Finally, using coronary artery-specific functional genomic annotations of chromatin structure, conformation, and accessibility, we identified trans regulation of two of these genes (GPC6, RPP25) by CAC GWAS-significant SNPs, resolving targets for previously orphan genome-wide significant loci. These multi-level findings furnish a resource for pathobiology of CAC, atherosclerosis, and establish an adaptable framework applicable to all organ systems to parse precision targets for prevention, surveillance, and therapy of cardiovascular disease.
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