Background/Aims: Stem cell-derived exosomes (EXs) offer protective effects on various cells via their carried microRNAs (miRs). Meanwhile, miR-210 has been shown to reduce mitochondrial reactive oxygen species (ROS) overproduction. In this study, we determined the potential effects of endothelial progenitor cell-derived EXs (EPC-EXs) on hypoxia/ reoxygenation (H/R) injured endothelial cells (ECs) and investigated whether these effects could be boosted by miR-210 loading. Methods: Human EPCs were used to generate EPCEXs, or transfected with scrambler control or miR-210 mimics to generate EPC-EXs sc and EPCEXs miR-210 . H/R-injured human ECs were used as a model for functional analysis of EXs on apoptosis, viability, ROS production and angiogenic ability (migration and tube formation) by flow cytometry, MTT, dihydroethidium and angiogenesis assay kits, respectively. For mechanism analysis, the mitochondrion morphology, membrane potential (MMP), ATP level and the expression of fission/fusion proteins (dynamin-related protein 1: drp1 and mitofusin-2: mfn2) were assessed by using JC-1 staining, ELISA and western blot, respectively. Results: 1) Transfection of miR-210 mimics into EPCs induced increase of miR-210 in EPC-EXs
A highly selective and sensitive bioluminescent sensor (DME) for human carboxylesterase 1 (hCE1) has been developed and well characterized. DME could be used for real-time monitoring of hCE1 activities in complex biological samples and for bio-imaging of endogenous hCE1 in living cells.
Suxiao Jiuxin pill (SJP) is a traditional Chinese medicine for the treatment of acute coronary syndrome in China, which contains two principal components, tetramethylpyrazine (TMP) and borneol (BOR). Thus far, however, the molecular mechanisms underlying the beneficial effects of SJP on the cardiac microenvironment are unknown. Cardiac mesenchymal stem cells (C-MSCs) communicate with cardiomyocytes (CMs) through the release of microvesicles (exosomes) to restore cardiac homeostasis and elicit repair, in part through epigenetic regulatory mechanisms. In this study, we examined whether SJP treatment altered C-MSC-derived exosomes (SJP-Exos) to cause epigenetic chromatic remodeling in recipient CMs. C-MSC isolated from mouse hearts were pretreated with SJP (SJP-Exos), TMP (TMP-Exos) or BOR (BOR-Exos). Then, HL-1 cells, a mouse cardiomyocyte line, were treated with exosomes from control C-MSCs (Ctrl-Exos), SJP-Exos, TMP-Exos or BOR-Exos. Treatment with SJP-Exos significantly increased the protein levels of histone 3 lysine 27 trimethylation (H3K27me3), a key epigenetic chromatin marker for cardiac transcriptional suppression, in the HL-1 cells. To further explore the mechanisms of SJP-Exo-mediated H3K27me3 upregulation, we assessed the mRNA expression levels of key histone methylases (EZH1, EZH2 and EED) and demethylases (JMJD3 and UTX) in the exosome-treated HL-1 cells. Treatment with SJP-Exo selectively suppressed UTX expression in the recipient HL-1 cells. Furthermore, PCNA, an endogenous marker of cell replication, was significantly higher in SJP-Exo-treated HL-1 cells than in Ctrl-Exo-treated HL-1 cells. These results show that SJP-Exos increase cardiomyocyte proliferation and demonstrate that SJP can modulate C-MSC-derived exosomes to cause epigenetic chromatin remodeling in recipient cardiomyocytes; consequently, SJP-Exos might be used to promote cardiomyocyte proliferation.
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor originally isolated and characterized as the dioxin or xenobiotic receptor. With the discovery of endogenous ligands and studies of AhR knockout mice, AhR has been found to serve an important role in several biological processes, including immune responses and developmental and pathological regulation. In particular, it has been considered as a new major player in cardiovascular diseases. Recent studies have revealed that the development of atherosclerosis is closely associated with AhR function. However, the roles of the AhR in the pathological development of atherosclerosis and atherosclerosis-associated diseases remain unclear. The current review presents the molecular mechanisms involved in the regulation of AhR expression during inflammation, oxidative stress and lipid deposition. Additionally, the role of the AhR in atherosclerosis and atherosclerosis-associated diseases is reviewed.
Summary
Background
The pathogenesis of gastro‐oesophageal reflux disease (GERD) is complex and multifactorial. The oesophageal hypervigilance and anxiety scale (EHAS) is a novel cognitive‐affective evaluation of visceral sensitivity.
Aims
To investigate the interrelationship between EHAS and reflux symptom severity, psychological stress, acid reflux burden, phenotypes, and oesophageal mucosal integrity in patients with GERD.
Methods
Patients with chronic reflux symptoms and negative endoscopy underwent 24‐hour impedance‐pH monitoring for phenotyping, acid reflux burden, and mucosal integrity with mean nocturnal baseline impedance (MNBI) calculation. Validated scores for patient‐reported outcomes, including EHAS, GERD questionnaire (GERDQ), State‐Trait Anxiety Inventory score, and Taiwanese Depression Questionnaire score, were recorded.
Results
We enrolled 105 patients, aged 21‐64 years (mean, 48.8), of whom 58.1% were female; 27 had non‐erosive reflux disease, 43 had reflux hypersensitivity and 35 had functional heartburn. There were no significant differences in sex, EHAS, GERDQ, questionnaires of depression or anxiety among GERD phenotypes. EHAS was significantly correlated with GERDQ, questionnaires of depression and anxiety (P < 0.05). However, there were no significant correlations between GERDQ and questionnaires of depression or anxiety. Regarding patient‐reported outcomes, GERDQ positively correlated with acid exposure time and negatively correlated with MNBI (P < 0.05).
Conclusions
EHAS associates with reflux symptom severity and psychological stress but not with acid reflux burden or mucosal integrity. Thus, EHAS assessment shows promise in assessment of subjective patient outcome and satisfaction with treatment, a hitherto unmet clinical need.
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