Cerebral pulsatility in relation with various imaging markers of cerebral small vessel disease: a longitudinal community-based study.

Background: Cerebral pulsatility is thought to reflect arterial stiffness and downstream microvascular resistance. Although previous studies indicated cerebral pulsatility might closely relate to development of cerebral small vessel disease (SVD), yet evidence remain controversial and longitudinal data are rare. Objective: We aimed to explore relationships of cerebral pulsatility with severity and progression of various SVD imaging markers among the community-dwelling elderly. Design: A longitudinal cohort study. Methods: As part of the prospective community-based Shanghai Aging Study cohort, dementia- and stroke-free elderly were recruited for baseline assessment of cerebral pulsatility and SVD severity during 2010-2011 and traced for SVD progression during 2016-2017. Cerebral pulsatility was quantified for both anterior and posterior circulation with transcranial Doppler ultrasound. SVD imaging markers were measured with brain magnetic resonance imaging (MRI) including white matter hyperintensities (WMHs), enlarged perivascular spaces (ePVS), lacunes, and microbleeds. The cross-sectional and longitudinal relationships between cerebral pulsatility and SVD were analyzed by univariable and multivariable regression models. Results: Totally, 188 eligible subjects were included at baseline and out of them, 100 (53.19%) returned for a 7-year follow-up. At baseline, increased pulsatility of posterior circulation was independently associated with more periventricular WMH (PWMH) and ePVS in basal ganglia (BG-ePVS) but not with other SVD markers. Longitudinally, higher posterior pulsatility predicted greater PWMH progression in participants with hypertension (ß = 2.694, standard error [SE] = 1.112, p = 0.020), whereas pulsatility of anterior circulation was shown to prevent BG-ePVS progression among followed-up elderly (ß = -6.737, SE = 2.685, p = 0.012). However, no significant relationship was found between cerebral pulsatility and burden of lacunes or cerebral microbleeds. Conclusion: Higher pulsatility of posterior circulation could worsen PWMH progression, especially for participants with hypertension. But for development of ePVS, increased cerebral pulsatility could play a compensatory role among several healthy elderly. The distinct relationships between cerebral pulsatility and various SVD markers emphasized the importance of individualized SVD management.

Proteomic profiles of patients with atrial fibrillation provide candidate biomarkers for diagnosis.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide with an increasing risk of heart failure, stroke, and thromboembolic events. Currently distinct pathophysiological mechanisms during AF development and valuable biomarkers for AF management remain unknown. METHODS: In this study, we collected peripheral plasma samples from 18 non-valvular AF patients and 10 controls. A LC-MS/MS-DIA-based quantitative proteomic analysis, as well as bioinformatic analysis, was performed for discovery of differentially expressed proteins (DEPs) and dysregulated pathways. Next, we utilized enzyme-linked immunosorbent assay (ELISA) to validate selected DEPs and assessed their abilities for discrimination in another group of 20 AF patients and 10 controls. RESULTS: The plasma proteome provided evidence for vital roles of abnormal inflammation, hemostasis, tissue remodeling and metabolism in AF patients. Differences between paroxysmal and persistent AF mainly lie in proteins or pathways related to hemostasis and cardiac remodeling. In addition, we successfully validated up-regulated proteins of platelet factor 4 variant 1 (PF4V1), thrombospondin-1 (THBS1), platelet basic protein (PBP) and fructose-bisphosphate aldolase A (ALDOA) in another group, which could make discrimination between AF patients and controls. CONCLUSIONS: Our pilot proteomic study provided candidate biomarkers of PF4V1, THBS1, PBP and ALODA with the hope of application in AF management. And we showed the differences in pathophysiological mechanisms between paroxysmal and persistent AF. They mainly focused on pathways of hemostasis and cardiac remodeling, which could be a valuable clue for further research on AF progression.

Functional improvement and maturation of human cardiomyocytes derived from human pluripotent stem cells by barbaloin preconditioning.

The development of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is a significant advancement in our ability to obtain cardiomyocytes in vitro for regenerative therapies and drug discovery. However, hPSC-CMs obtained via existing protocols usually exhibit a markedly immature phenotype, compared with adult cardiomyocytes, thereby limiting their application. Here we report that barbaloin preconditioning dramatically improves the morphology, structure-related cardiac gene expression, calcium handling, and electrophysiological properties of hPSC-CMs, which means that barbaloin may have the potential to induce the maturation of hPSC-CMs, providing a novel strategy to generate more adult-like cardiomyocytes and promoting the application of hPSC-CMs in regenerative medicine, drug development, and disease modeling.

Engineering human ventricular heart tissue based on macroporous iron oxide scaffolds.

Myocardial infarction (MI) is a primary cardiovascular disease threatening human health and quality of life worldwide. The development of engineered heart tissues (EHTs) as a transplantable artificial myocardium provides a promising therapy for MI. Since most MIs occur at the ventricle, engineering ventricular-specific myocardium is therefore more desirable for future applications. Here, by combining a new macroporous 3D iron oxide scaffold (IOS) with a fixed ratio of human pluripotent stem cell (hPSC)-derived ventricular-specific cardiomyocytes and human umbilical cord-derived mesenchymal stem cells, we constructed a new type of engineered human ventricular-specific heart tissue (EhVHT). The EhVHT promoted expression of cardiac-specific genes, ion exchange, and exhibited a better Ca2+ handling behaviors and normal electrophysiological activity in vitro. Furthermore, when patched on the infarcted area, the EhVHT effectively promoted repair of heart tissues in vivo and facilitated the restoration of damaged heart function of rats with acute MI. Our results show that it is feasible to generate functional human ventricular heart tissue based on hPSC-derived ventricular myocytes for the treatment of ventricular-specific myocardium damage. STATEMENT OF SIGNIFICANCE: We successfully generated highly purified homogenous human ventricular myocytes and developed a method to generate human ventricular-specific heart tissue (EhVHT) based on three-dimensional iron oxide scaffolds. The EhVHT promoted expression of cardiac-specific genes, ion exchange, and exhibited a better Ca2+ handling behaviors and normal electrophysiological activity in vitro. Patching the EhVHT on the infarct area significantly improved cardiac function in rat acute MI models. This EhVHT has a great potential to meet the specific requirements for ventricular damages in most MI cases and for screening drugs specifically targeting ventricular myocardium.

Autologous reference types can confound the detection of somatic mutation in solid cancers.

Vast number of somatic mutations has been proved to be affected by the factors of sequencing methods, analysis pipelines and validation methods. We here showed the effect of autologous reference types on the detection of cancer-associated somatic mutations with the somatic single nucleotide variations (SNVs) and clinical data of solid tumors from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). The distribution of somatic SNVs was significantly different among groups of autologous references in 6 cancers detected by whole genome sequencing (WGS) and 5 cancers detected by the random sequencing of exonic regions selected from the genome (WXS), especially in protein coding region of 5 cancers with age, gender and TNM adjusted. In addition, only 60.24% (95% CI: 49.65%-70.83%) of the somatic SNVs called from normal blood by WXS were found in those called from normal solid tissue tested by WXS / WGS, while 31.78% (95%CI: 4.14%-59.42%) of the somatic SNVs called from normal tissue adjacent to primary by WXS were found in those from normal blood tested by WXS / WGS. These findings suggested that more representative types of normal tissues should be included in detection of cancer-associated somatic mutations.

The effect of circulating miR-223 on surveillance of different cancers: a meta-analysis.

PURPOSE: Abnormal expression of miR-223 in cancerous tissue has confirmed it as an important player in tumorigenesis of cancers, such as hepatocellular carcinoma, colorectal carcinoma, osteosarcoma, gastric cancer, and chronic lymphocytic leukemia. The present meta-analysis aimed to explore the association between circulating miR-223 and prognosis of cancers. METHODS: The studies were accessed by an electronic search of multiple databases. RevMan5.3 and STATA14.0 were used to estimate the heterogeneity among studies, pooled effects, and publication bias. RESULTS: Ten studies with data of 1,002 patients with cancer were included in this meta-analysis. The risk of metastasis from stages 3 to 4 of TNM did not decrease when high versus low circulating expression of miR-223 were compared (pooled odds ratio =0.50, 95% CI: 0.24-1.03). In case of prognosis, the overall survival time was not significantly longer with high circulating miR-223 expression (pooled hazard ratio [HR] =0.64, 95% CI: 0.38-1.11) in all cancer types. However, the overall survival time of chronic lymphocytic leukemia (pooled HR =0.19, 95% CI: 0.07-0.54) increased in subgroup analysis. Moreover, the treatment-free survival of chronic lymphocytic leukemia was significantly increased with high circulating miR-223 expression (pooled HR =0.38, 95% CI: 0.23-0.64). CONCLUSION: Circulating miR-223 was not an effective biomarker in prognosis surveillance in all cancers but in chronic lymphocytic leukemia.