Interleukin-4, hemopexin, and lipoprotein-associated phospholipase A2 are significantly increased in patients with unstable carotid plaque

This study aimed to compare the plasma levels of lipoprotein-associated phospholipase A2 (Lp-PLA2), hemopexin (Hpx), and interleukin-4 (IL-4) in patients with carotid artery atherosclerosis based on neurological symptoms and plaque histopathology and to find association between plaque stability and neurological symptoms. This single-center study included patients treated surgically for significant stenosis of the internal carotid artery. Serum levels of biomarkers were determined, and a histopathological analysis of the carotid plaques was performed. Within 70 patients, 40 asymptomatic and 30 symptomatic; 38 patients (54.3%) were diagnosed with unstable carotid plaque and 32 patients (45.7%) had a stable carotid plaque. Significantly higher incidence of unstable carotid plaque was detected in symptomatic patients (p <0.001). Compared to asymptomatic patients, higher expression of Lp-PLA2 (285.30 ± 2.05 μg/l), Hpx (0.38 ± 0.01 ng/l), and IL-4 (65.77 ± 3.78 ng/l) in plasma were detected in symptomatic patients. Subsequently, higher expression of Lp-PLA2 (297.34 ± 2.3 μg/l), Hpx (0.41 ± 0.02 ng/l), and IL-4 (64.74 ± 4.47 ng/l) in plasma was observed in patients with unstable plaques (n=38). Statistically significant (p <0.001) differences in expression of Lp-PLA2, Hpx, and IL-4 between patients with unstable and stable plaques were detected. Moreover, only the differences between symptomatic and asymptomatic patients in the expression of Lp-PLA2 and IL-4 in plasma were statistically significant (p <0.001). This study showed that Lp-PLA2, IL-4, and Hpx levels are significantly increased in patients with an unstable carotid plaque

Frequent loss of heterozygosity in CRISPR-Cas9-edited early human embryos.

CRISPR-Cas9 genome editing is a promising technique for clinical applications, such as the correction of disease-associated alleles in somatic cells. The use of this approach has also been discussed in the context of heritable editing of the human germ line. However, studies assessing gene correction in early human embryos report low efficiency of mutation repair, high rates of mosaicism, and the possibility of unintended editing outcomes that may have pathologic consequences. We developed computational pipelines to assess single-cell genomics and transcriptomics datasets from OCT4 (POU5F1) CRISPR-Cas9-targeted and control human preimplantation embryos. This allowed us to evaluate on-target mutations that would be missed by more conventional genotyping techniques. We observed loss of heterozygosity in edited cells that spanned regions beyond the POU5F1 on-target locus, as well as segmental loss and gain of chromosome 6, on which the POU5F1 gene is located. Unintended genome editing outcomes were present in ∼16% of the human embryo cells analyzed and spanned 4-20 kb. Our observations are consistent with recent findings indicating complexity at on-target sites following CRISPR-Cas9 genome editing. Our work underscores the importance of further basic research to assess the safety of genome editing techniques in human embryos, which will inform debates about the potential clinical use of this technology