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The case report aims to reveal de Winter's electrocardiogram (ECG) pattern as an equivalent to anterior ST‐segment elevation myocardial infarction (STEMI). We report a case of a 49‐year‐old man with a history of smoking who presented to the emergency department with a 1 day history of chest pain that was exacerbated 5 h prior to presentation. Detailed clinical investigations and coronary angiographic characteristics were recorded. The first ECG of the patient was consistent with de Winter syndrome. Acute coronary artery angiography showed that the proximal left anterior descending coronary artery was completely occluded after the first diagonal branch artery was given off. A percutaneous coronary intervention was immediately performed. Our case indicates that early identification and diagnosis of such ECGs and timely reperfusion therapy of de Winter syndrome as a STEMI equivalent are required to improve the prognosis of such patients.

Phenotype switch of vascular smooth muscle cells (VSMCs) plays an important role in the development of atherosclerosis (AS). Endothelial cells can regulate VSMC phenotypic switch by secreting exosomes, crucial mediators of intracellular communication. This study aimed to determine whether exosomal LINC01005 from oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs) plays a role in regulating VSMC phenotypic switch and to validate the underlying molecular mechanism. Exosomes were extracted from ox-LDL-treated HUVECs (ox-LDL-Exo) and then administered into VSMCs. VSMC phenotypic switch was assessed by determining VSMC phenotypic markers using western blot. VSMC cell proliferation and migration were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and wound healing assay, respectively. The interaction between miR-128-3p and LINC01005 or Krüppel-like factor 4 (KLF4) was analyzed by luciferase reporter assay. ox-LDL-Exo contained high expression of LINC01005. Inhibition of LINC01005 expression in ox-LDL-Exo abrogated the ox-LDL-Exo-induced VSMC phenotypic switch, proliferation, and migration. Furthermore, LINC01005 acted as a sponge of miR-128-3p to upregulate KLF4 expression. Moreover, miR-128-3p overexpression and KLF4 silencing in VSMCs attenuated the ox-LDL-Exo-induced VSMC phenotypic switch, proliferation, and migration. Collectively, exosomal LINC01005 from ox-LDL-treated HUVECs promotes VSMC phenotype switch, proliferation, and migration by regulating the miR-128-3p/KLF4 axis.

Inflammation plays an important role in aortic dissection (AD). Macrophages are critically involved in the inflammation after aortic injury. Neuraminidases (NEUs) are a family of enzymes that catalyze the cleavage of terminal sialic acids from glycoproteins or glycolipids, which is emerging as a regulator of macrophage-associated immune responses. However, the role of neuraminidase 1 (NEU1) in pathological vascular remodeling of AD remains largely unknown. This study sought to characterize the role and identify the potential mechanism of NEU1 in pathological aortic degeneration. After β-aminopropionitrile monofumarate (BAPN) administration, NEU1 elevated significantly in the lesion zone of the aorta. Global or macrophage-specific NEU1 knockout (NEU1 CKO) mice had no baseline aortic defects but manifested improved aorta function, and decreased mortality due to aortic rupture. Improved outcomes in NEU1 CKO mice subjected to BAPN treatment were associated with the ameliorated vascular inflammation, lowered apoptosis, decreased reactive oxygen species production, mitigated extracellular matrix degradation, and improved M2 macrophage polarization. Furthermore, macrophages sorted from the aorta of NEU1 CKO mice displayed a significant increase of M2 macrophage markers and a marked decrease of M1 macrophage markers compared with the controls. To summarize, the present study demonstrated that macrophage-derived NEU1 is critical for vascular homeostasis. NEU1 exacerbates BAPN-induced pathological vascular remodeling. NEU1 may therefore represent a potential therapeutic target for the treatment of AD.

Background: Excessive salt intake is considered as an important risk factor for cognitive impairment, which might be the consequence of imbalanced intestinal homeostasis. Objective: To investigate the effects of dietary salt on the gut microbiota and cognitive performance and the underlying mechanisms. Methods: Adult female C57BL/6 mice were maintained on either normal chow (control group, CON) or sodium-rich chow containing 8% NaCl (high-salt diet, HSD) for 8 weeks. Spatial learning and memory ability, short-chain fatty acids (SCFAs) concentrations, gut bacterial flora composition, blood-brain barrier permeability, and proinflammatory cytokine levels and apoptosis in the brain were evaluated. Results: The mice fed a HSD for 8 weeks displayed impaired learning and memory abilities. HSD significantly reduced the proportions of Bacteroidetes (S24-7 and Alloprevotella) and Proteobacteria and increased that of Firmicutes (Lachnospiraceae and Ruminococcaceae). SCFA concentrations decreased in the absolute concentrations of acetate, propionate, and butyrate in the fecal samples from the HSD-fed mice. The HSD induced both BBB dysfunction and microglial activation in the mouse brain, and increased the IL-1β, IL-6, and TNF-α expression levels in the cortex. More importantly, the degree of apoptosis was higher in the cortex and hippocampus region of mice fed the HSD, and this effect was accompanied by significantly higher expression of cleaved caspase-3, caspase-3, and caspase-1. Conclusion: The HSD directly causes cognitive dysfunction in mice by eliciting an inflammatory environment and triggering apoptosis in the brain, and these effects are accompanied by gut dysbiosis, particularly reduced SCFA production.

CD4+ T cells are the central element of the adaptive immune responses and protect the body from a variety of pathogens. Starting from naive cells, CD4+ T cells can differentiate into various effector cell subsets with specialized functions including T helper (Th) 1, Th2, Th17, regulatory T (Treg) and T follicular helper (Tfh) cells. Among them, Tregs and Th17 cells show a strong plasticity allowing the functional adaptation to various physiological and pathological environments during immune responses. Although they are derived from the same precursor cells and their differentiation pathways are interrelated, the terminally differentiated cells have totally opposite functions. Studies have shown that Tregs and Th17 cells have rather complex interplays in viral infection: Th17 cells may contribute to immune activation and disease progression while Tregs may inhibit this process and play a key role in the maintenance of immune homoeostasis, possibly at the cost of compromised viral control. In this review, we take respiratory syncytial virus (RSV), hepatitis B virus (HBV)/hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections as examples to discuss these interplays and their impacts on disease progression in viral infection.

Given the growing evidence of a link between gut microbiota (GM) dysbiosis and multiple sclerosis (MS), fecal microbiota transplantation (FMT), aimed at rebuilding GM, has been proposed as a new therapeutic approach to MS treatment. To evaluate the viability of FMT for MS treatment and its impact on MS pathology, we tested FMT in mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We provide evidence that FMT can rectify altered GM to some extent with a therapeutic effect on EAE. We also found that FMT led to reduced activation of microglia and astrocytes and conferred protection on the blood-brain barrier (BBB), myelin, and axons in EAE. Taken together, our data suggest that FMT, as a GM-based therapy, has the potential to be an effective treatment for MS.

Cardiotoxicity limits the clinical applications of doxorubicin (Dox), which mechanism might be excess generation of intracellular ROS. Quercetin (Que) is a flavonoid that possesses anti-oxidative activities, exerts myocardial protection. We hypothesized that the cardioprotection against Dox injury of Que involved 14-3-3γ, and mitochondria. To investigate the hypothesis, we treated primary cardiomyocytes with Dox and determined the effects of Que pretreatment with or without 14-3-3γ knockdown. We analyzed various cellular and molecular indexes. Our data showed that Que attenuated Dox-induced toxicity in cardiomyocytes by upregulating 14-3-3γ expression. Que pretreatment increased cell viability, SOD, catalase, and GPx activities, GSH levels, MMP and the GSH/GSSG ratio; decreased LDH and caspase-3 activities, MDA and ROS levels, mPTP opening and the percentage of apoptotic cells. However, Que's cardioprotection were attenuated by knocking down 14-3-3γ expression using pAD/14-3-3γ-shRNA. In conclusion, Que protects cardiomyocytes against Dox injury by suppressing oxidative stress and improving mitochondrial function via 14-3-3γ.

Acute myocardial infarction (AMI) is caused by sustained ischemia and is often the manifestation of atherosclerosis-related cardiovascular disease. Circular RNAs (circRNAs) are known to be associated with cardiovascular disease and are enriched in exosomes. However, the expression profile and

Understanding the mechanisms of early cardiac fate determination may lead to better approaches in promoting heart regeneration. We used a mesoderm posterior 1 (Mesp1)-Cre/Rosa26-EYFP reporter system to identify microRNAs (miRNAs) enriched in early cardiac progenitor cells. Most of these miRNA genes bear MESP1-binding sites and active histone signatures. In a calcium transient-based screening assay, we identified miRNAs that may promote the cardiomyocyte program. An X-chromosome miRNA cluster, miR-322/-503, is the most enriched in the Mesp1 lineage and is the most potent in the screening assay. It is specifically expressed in the looping heart. Ectopic miR-322/-503 mimicking the endogenous temporal patterns specifically drives a cardiomyocyte program while inhibiting neural lineages, likely by targeting the RNA-binding protein CUG-binding protein Elav-like family member 1 (Celf1). Thus, early miRNAs in lineage-committed cells may play powerful roles in cell-fate determination by cross-suppressing other lineages. miRNAs identified in this study, especially miR-322/-503, are potent regulators of early cardiac fate.

Myotonic dystrophy 1 (DM1) is a common form of muscular dystrophy. Although several animal models have been established for DM1, myoblast cell models are still important because they offer an efficient cellular alternative for studying cellular and molecular events. Though C2C12 myoblast cells have been widely used to study myogenesis, resistance to gene transfection, or viral transduction, hinders research in C2C12 cells. Here, we describe an optimized protocol that includes daily maintenance, transfection and transduction procedures to introduce genes into C2C12 myoblasts and the induction of myocyte differentiation. Collectively, these procedures enable best transfection/transduction efficiencies, as well as consistent differentiation outcomes. The protocol described in establishing DM1 myoblast cell models would benefit the study of myotonic dystrophy, as well as other muscular diseases.

Summary YAP, a key effector of Hippo pathway, is activated by its translocation from cytoplasm to nucleus to regulate gene expression and promote tumorigenesis. Although the mechanism by which YAP is suppressed in cytoplasm has been well-studied, how the activated YAP is sequestered in the nucleus remains unknown. Here, we demonstrate that YAP is a nucleocytoplasmic shuttling protein and its nuclear export is controlled by SET1A-mediated mono-methylation of YAP at K342, which disrupts the binding of YAP to CRM1. YAP mimetic methylation knockin mice are more susceptible to colorectal tumorigenesis. Clinically, YAP K342 methylation is reversely correlated with cancer survival. Collectively, our study identifies SET1A-mediated mono-methylation at K342 as an essential regulatory mechanism for regulating YAP activity and tumorigenesis.

Objective To investigate the factors that can accurately predict the prognosis for patients with FIGO stage-IB cervical squamous cell carcinoma treated with radical surgery.

Myotonic dystrophy is a neuromuscular disease of RNA toxicity. The disease gene DMPK harbors expanded CTG trinucleotide repeats on its 3′-UTR. The transcripts of this mutant DMPK led to misregulation of RNA-binding proteins including MBNL1 and Celf1. In myoblasts, CUG-expansion impaired terminal differentiation. In this study, we formally tested how the abundance of Celf1 regulates normal myocyte differentiation, and how Celf1 expression level mediates CUG-expansion RNA toxicity-triggered impairment of myocyte differentiation. As the results, overexpression of Celf1 largely recapitulated the defects of myocytes with CUG-expansion, by increasing myocyte cycling. Knockdown of endogenous Celf1 level led to precocious myotube formation, supporting a negative connection between Celf1 abundance and myocyte terminal differentiation. Finally, knockdown of Celf1 in myocyte with CUG-expansion led to partial rescue, by promoting cell cycle exit. Our results suggest that Celf1 plays a distinctive and negative role in terminal myocyte differentiation, which partially contribute to DM1 RNA toxicity. Targeting Celf1 may be a valid strategy in correcting DM1 muscle phenotypes, especially for congenital cases.