Hua Wang's research while affiliated with First Affiliated Hospital of China Medical University and other places

Background Richter’s syndrome (RS) defines the transformation of chronic lymphocytic leukemia into high-grade lymphoma, which usually involves lymph nodes and bone marrow. Extranodal involvement of the heart is an extremely rare condition. Patients with heart involvement tended to have a low response to chemotherapy and relative poor prognosis. The transformation process of RS is often insidious and nonspecific making it challenging to diagnose. Case presentation A 64-year-old woman wih a history of chronic lymphocytic leukemia (CLL) presented with intermittent chest pain and was diagnosed with non-ST-elevation myocardial infarction (NSTEMI). However, the contrast enhanced echocardiography revealed a large irregular mass, measuring about 75.4 mm × 37.5 mm, located on the lateral and posterior wall of the right ventricle. Biopsy of the cardiac mass and the results revealed diffuse large B-cell lymphoma. Conclusions We present a case of a 64-year-old woman with aggressive diffuse large B-cell lymphoma involving the heart. This case could provide some insights in the diagnosis of cardiac lymphoma.

Cerebral dopamine neurotrophic factor (CDNF) is a unique neurotrophic factor (NTF) that has shown significant neuroprotective and neurorestorative functions on midbrain dopaminergic neurons. The secondary structure of human CDNF protein contains eight α-helices. We previously found that two key helices, α1 and α7, regulated the intracellular trafficking and secretion of CDNF protein in different manners. The α1 mutation (M1) induced most CDNF proteins to reside in the endoplasmic reticulum and little be secreted extracellularly, while the α7 mutation (M7) caused the majority of CDNF proteins to be secreted out of the cells and little reside in the cells. However, the regulation of the two mutants on the function of CDNF remains unclear. In this study, we investigated the effects of M1 and M7 on the protective activity of CDNF in PC12 cells, which were treated with 6-hydroxydopamine (6-OHDA) to mimic Parkinson's disease. We found that both M1 and M7 could promote survival and inhibit apoptosis more effectively than Wt in 6-OHDA-lesioned PC12 cells. Therefore, these findings will advance our understanding of the important regulation of subdomains on the function of NTFs.

Background Foam cells play crucial roles in all phases of atherosclerosis. However, until now, the specific mechanisms by which these foam cells contribute to atherosclerosis remain unclear. We aimed to identify novel foam cell biomarkers and interventional targets for atherosclerosis, characterizing their potential mechanisms in the progression of atherosclerosis. Methods Microarray data of atherosclerosis and foam cells were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expression genes (DEGs) were screened using the “LIMMA” package in R software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) annotation were both carried out. Hub genes were found in Cytoscape after a protein-protein interaction (PPI) enrichment analysis was carried out. Validation of important genes in the GSE41571 dataset, cellular assays, and tissue samples. Results A total of 407 DEGs in atherosclerosis and 219 DEGs in foam cells were identified, and the DEGs in atherosclerosis were mainly involved in cell proliferation and differentiation. CSF1R and PLAUR were identified as common hub genes and validated in GSE41571 . In addition, we also found that the expression of CSF1R and PLAUR gradually increased with the accumulation of lipids and disease progression in cell and tissue experiments. Conclusion CSF1R and PLAUR are key hub genes of foam cells and may play an important role in the biological process of atherosclerosis. These results advance our understanding of the mechanism behind atherosclerosis and potential therapeutic targets for future development.

The inflammatory microenvironment of macrophage plays an important role in acute myocardial infarction (AMI), but the regulatory mechanism is unknown. Here, we aimed to investigate the role of Malat1 on inflammation microenvironment of macrophage in AMI. Our study found that Malat1 expression was increased in AMI, which mainly expressed in macrophages. Malat1 inhibition improved collagen deposition and inflammation in infarcted heart. In vitro, Malat1 inhibition evidently reduced macrophage-associated inflammation. The results from ribonucleic acid pull-down (RNA pull-down) and RNA Immunoprecipitation (RIP) assay demonstrated that Malat1 directly binds to EZH2. Malat1 and EZH2 complex could increase histone H3K27me3 expression and further inhibit the production of PPAR-γ. In vivo, inhibition of Malat1 also leaded to the down-regulation of both EZH2 and H3K27me3, as well as up-regulation of PPAR-γ in infarcted heart. Therefore, these findings demonstrate a novel mechanism of Malat1 on inflammation microenvironment of macrophage in AMI, which provide a new target for its treatment.

Background: There are few myocardial damage markers that could be used to diagnose acute myocardial infarction(AMI) or assess its severity, especially glycosylated apolipoprotein J(ApoJ-Glyc) has demonstrated superiority in cardiomyocytes and animal STEMI models in the early stages of myocardial ischemia(MI). We aimed to excavate the potential role of ApoJ-Glyc as a protein marker in the pathogenesis of AMI in humans and its added value in the evolution of the disease. Methods and Results: ELISA was used to determine the serum concentration of ApoJ-Glyc in 163 patients enrolled by the criteria. Statistical analysis could used to discuss the relationship between ApoJ-Glyc and AMI. Compared to control groups, serum ApoJ-Glyc levels decreased by 36% and 37% in early AMI patients and AMI patients, respectively (P<0.0001), showing a higher discriminant value for early diagnosis and diagnosis of AMI [ area under the curve (AUC) :0.871 and 0.886, P< 0.0001]. For the first time, we demonstrated that ApoJ-Glyc was not statistically significant in the comparative difference between NSTEMI and STEMI groups (P> 0.05). Patients with gradually declining ApoJ-Glyc had a higher Grace Risk Scores. Subsequent studies have also demonstrated that more MACCE did occur with a 6-month follow-up(P<0.05). Conclusions: ApoJ-Glyc which serve as an alarm bell for the detection of early ischaemia, may be a new biomarker for AMI. ApoJ-Glyc can assess the severity of myocardial infarction. The continuous decrease of serum ApoJ-Glyc suggests an increase in the risk of post-AMI ischaemia and the onset of unpredictable MACCE.

Background: Richter’s syndrome (RS) defines the transformation of chronic lymphocytic leukemia into high-grade lymphoma, which usually involves nodal and bone marrow. Extranodal involvement of the heart is an extremely rare condition. Patients with heart involvement tended to have a low response to chemotherapy and relative poor prognosis. The transformation process of RS is often insidious and nonspecific making it challenging to diagnose. Case presentation: A 64-year-old woman wih a history of chronic lymphocytic leukemia (CLL) presented with intermittent chest pain and was diagnosed with non-ST-elevation myocardial infarction (NSTEMI). However, the contrast enhanced echocardiography revealed a large irregular mass, measuring about 75.4 mm×37.5 mm, located on the lateral and posterior wall of the right ventricle. Biopsy of the cardiac mass and the results revealed diffuse large B-cell lymphoma. Conclusions: We present a case of a 64-year-old woman with aggressive diffuse large B-cell lymphoma involving the heart. This case could provide some insights in the diagnosis of cardiac lymphoma.

It has been shown that SGLT2 suppresses atherosclerosis (AS). Recent studies indicate that autophagy widely participates in atherogenesis. This study aimed to assess the effect of canagliflozin (CAN) on atherogenesis via autophagy. Macrophages and ApoE − / − mice were used in this study. In macrophages, the results showed that CAN promoted LC3II expression and autophagosome formation. Furthermore, the cholesterol efflux assay demonstrated that CAN enhanced cholesterol efflux from macrophages via autophagy, resulting in lower lipid droplet concentrations in macrophages. The western blot revealed that CAN regulated autophagy via the AMPK/ULK1/Beclin1 signaling pathway. CAN resulted in increased macrophage autophagy in atherosclerotic plaques of ApoE − / − mice, confirming that CAN could inhibit the progression of AS via promoting macrophage autophagy. The current study found that CAN reduced the production of atherosclerotic lesions, which adds to our understanding of how SGLT2 inhibitors function to delay the progression of AS. Graphical abstract

FURIN, a member of the mammalian proprotein convertases (PCs) family, can promote the proteolytic maturation of proproteins. It has been shown that FURIN plays an important role in the progression of atherosclerosis (AS). Current evidence indicates that autophagy widely participates in atherogenesis. This study aimed to explore whether FURIN could affect atherogenesis via autophagy. The effect of FURIN on autophagy was studied using aortic tissues from aortic dissection patients who had BENTALL surgery, as well as macrophages and ApoE−/− mice. In atherosclerotic plaques of aortic tissues from patients, FURIN expression and autophagy were elevated. In macrophages, FURIN‐shRNA and FURIN‐overexpression lentivirus were used to intervene in FURIN expression. The results showed that FURIN overexpression accelerated LC3 formation in macrophages during the autophagosome formation phase. Furthermore, FURIN‐induced autophagy resulted in lower lipid droplet concentrations in macrophages. The western blot revealed that FURIN regulated autophagy via the AMPK/mTOR/ULK1/PI3KIII signaling pathway. In vivo, FURIN overexpression resulted in increased macrophage LC3 formation in ApoE−/− mice atherosclerotic plaques, confirming that FURIN could inhibit the progression of AS by promoting macrophage autophagy. The present study demonstrated that FURIN suppressed the progression of AS by promoting macrophage autophagy via the AMPK/mTOR/ULK1/PI3KIII signaling pathway, which attenuated atherosclerotic lesion formation. Based on this data, current findings add to our understanding of the complexity of AS.

Introduction The pathophysiological mechanisms linking the overweight and prothrombotic state of non-valvular atrial fibrillation (NVAF) are incompletely understood. Our objective was to evaluate the effect of platelet CD36 on the risk of stroke associated with overweight in NVAF patients. Methods A cross-sectional study enrolled 182 subjects with NVAF in two groups: normal weight (18.5 < body mass index(BMI) < 25.0 kg/m ² ) and overweight (BMI ≥ 25.0 kg/m ² ). Clinical data, medical history, vital signs, transthoracic echocardiography parameters, and medication were recorded. Biochemical characteristics including blood glucose and serum lipid were analyzed in the Laboratory. Results The expression of platelet CD36 and integrin α IIb β 3 was detected by flow cytometry. Among the 182 patients with NVAF, 68 (37.36%) were classified as normal weight, 114 (62.64%) as overweight. With an increase in BMI, waist-hip ratio, cholesterol, triglycerides, left atrium diameters, and the ratio of mitral inflow E velocity to myocardial e' velocity in the mitral annulus (E/e') increased significantly ( P < 0.05). The mean fluorescent intensity of platelet CD36 increased significantly in overweight patients ( P < 0.01), in line with platelet activation biomarkers (platelet integrin αIIbβ3). Platelet CD36 was positively correlated with BMI and platelet integrin αIIbβ3, respectively ( P < 0.05). Additionally, platelet CD36 and BMI were independent risk factors for platelet activation in patients with NVAF. Conclusions Platelet CD36 is speculated to mediate the complex crosstalk between overweight and platelet hyperactivity, leading to the prothrombotic state in overweight patients with NVAF. Platelet CD36 could be a potential target for preventing the prothrombotic state in overweight patients with NVAF.

Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, which is associated with cardiac dysfunction. This study aimed to compare the impairment severity of left ventricular strain and intra-ventricular dyssynchrony using echocardiography-derived velocity vector imaging in patients with different types of AF without heart failure.Methods168 non-valvular AF patients with normal left ventricular ejection fraction (98 paroxysmal AF patients and 70 persistent AF patients) and 86 healthy control subjects were included in this study. Regional and global left ventricular longitudinal and circumferential strain were measured. Time to regional peak longitudinal strain was measured and the standard deviation of all 12 segments (SDT-S) was used as a measure of intra-ventricular dyssynchrony.ResultsSignificantly lower GLS (−18.71 ± 3.00% in controls vs. −17.10 ± 3.01% in paroxysmal AF vs. −12.23 ± 3.25% in persistent AF, P < 0.05) and GCS (−28.75 ± 6.34% in controls vs. −24.43 ± 6.86% in paroxysmal AF vs. −18.46 ± 6.42% in persistent AF, P < 0.01) were observed in either persistent AF subjects or paroxysmal AF subjects compared with healthy control subjects (P < 0.05). The impairment was much worse in persistent AF subjects compared with paroxysmal AF subjects (P < 0.001). Intraventricular dyssynchrony was found in both persistent AF patients and paroxysmal AF patients, and it’s worse in persistent AF patients (52 ± 18 ms in controls, 61 ± 17 ms in paroxysmal AF, and 70 ± 28 ms in persistent AF, P < 0.05). Multivariate regression analysis revealed AF types were independent risk factors of GLS, GCS, and intraventricular dyssynchrony.ConclusionAF types were not only associated with impaired longitudinal and circumferential left ventricle mechanics but also intra-ventricular mechanical dyssynchrony. Worse systolic mechanics and intra-ventricular dyssynchrony were found in patients with persistent AF compared with these in patients with paroxysmal AF.