Inhibition of the upregulated phosphodiesterase 4D isoforms improves SERCA2a function in diabetic cardiomyopathy.

Background And Purpose: Sarcoplasmic reticulum Ca-ATPase (SERCA2a) is impaired in heart failure. Phosphodiesterases (PDEs) are implicated in the modulation of local cAMP signals and protein kinase A (PKA) activity essential for cardiac function. We characterise PDE isoforms that underlie decreased activities of SERCA2a and reduced cardiac contractile function in diabetic cardiomyopathy.

Upregulation of CD244 promotes CD8 T cell exhaustion in patients with alveolar echinococcosis and a murine model.

Background: In patients with alveolar echinococcosis (AE), CD8 T cells undergo functional exhaustion, which accelerates the malignant progression of AE. However, the role of inhibitory receptor CD244 in mediating CD8 T cell exhaustion remains elusive.

Methods: CD244 expression on exhausted CD8 T cells in the close liver tissue (CLT) of AE patients was analyzed using single-cell RNA sequencing data.

Targeting myeloid-derived suppressor cells promotes antiparasitic T-cell immunity and enhances the efficacy of PD-1 blockade (15 words).

Immune exhaustion corresponds to a loss of effector function of T cells that associates with cancer or chronic infection. Here, our objective was to decipher the mechanisms involved in the immune suppression of myeloid-derived suppressor cells (MDSCs) and to explore the potential to target these cells for immunotherapy to enhance checkpoint blockade efficacy in a chronic parasite infection. We demonstrated that programmed cell-death-1 (PD-1) expression was significantly upregulated and associated with T-cell dysfunction in advanced alveolar echinococcosis (AE) patients and in Echinococcus multilocularis-infected mice.

Immunological Characteristics of Hepatic Dendritic Cells in Patients and Mouse Model with Liver Infection.

The cestode which mainly dwells in the liver, leads to a serious parasitic liver disease called alveolar echinococcosis (AE). Despite the increased attention drawn to the immunosuppressive microenvironment formed by hepatic AE tissue, the immunological characteristics of hepatic dendritic cells (DCs) in the AE liver microenvironment have not been fully elucidated. Here, we profiled the immunophenotypic characteristics of hepatic DC subsets in both clinical AE patients and a mouse model.

Sirt5 improves cardiomyocytes fatty acid metabolism and ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via CPT2 de-succinylation.

Rationale: The disruption of the balance between fatty acid (FA) uptake and oxidation (FAO) leads to cardiac lipotoxicity, serving as the driving force behind diabetic cardiomyopathy (DbCM). Sirtuin 5 (Sirt5), a lysine de-succinylase, could impact diverse metabolic pathways, including FA metabolism. Nevertheless, the precise roles of Sirt5 in cardiac lipotoxicity and DbCM remain unknown.

Coexisting Firing Patterns in an Improved Memristive Hindmarsh-Rose Neuron Model with Multi-Frequency Alternating Current Injection.

With the development of memristor theory, the application of memristor in the field of the nervous system has achieved remarkable results and has bright development prospects. Flux-controlled memristor can be used to describe the magnetic induction effect of the neuron. Based on the Hindmarsh-Rose (HR) neuron model, a new HR neuron model is proposed by introducing a flux-controlled memristor and a multi-frequency excitation with high-low frequency current superimposed.

Left bundle branch pacing on mechanical synchrony and myocardial work in bradycardia patients.

Left bundle branch pacing (LBBP) has emerged as a novel physiological pacing method to produce narrower QRS duration, but whether it could restore mechanical synchrony and improve myocardial work still lacks sufficient evidence. Therefore, the goal of this study was to evaluate mechanical synchrony and myocardial work in LBBP. We collected 20 patients with LBBP due to symptomatic bradycardia and another 29 age-matched patients with right ventricular pacing (RVP).

Targeted Metabolomics Study of Human Plasma Revealed Activation of the Cytochrome P450 Epoxygenase/Epoxide Hydrolase Axis in Patients with IgA Nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis and a leading cause of chronic kidney disease. The pathogenic mechanism of IgAN remains largely unknown and thus a specific therapeutic target is lacking. Here, we reported that the cytochrome P450 (CYP) epoxygenase/epoxide hydrolase (EH) axis was activated in the patients and is likely a therapeutic target for IgAN.

Metabolomics analysis of human plasma reveals decreased production of trimethylamine N-oxide retards the progression of chronic kidney disease.

Background And Purpose: Chronic kidney disease (CKD) is a global public health problem and one of the leading causes of all-cause mortality. However, the pathogenic mechanisms and intervention methods for CKD progression are not fully understood.

Experimental Approach: Plasma from patients with uraemia and from healthy controls (n = 30 per group) was analysed with LC-MS/MS-based non-targeted metabolomics to identify potential markers of uraemia.

LINC01207 promotes prostate cancer progression by sponging miR-1182 to upregulate AKT3.

Prostate cancer (PC) is recognized as a common malignancy in male patients. Long non-coding RNA (lncRNA) has been implicated in the development of PC. Recently, long intergenic non-protein coding RNA 1207 (LINC01207) has been reported to regulate the carcinogenesis of multiple cancer types.

Constructing a passive targeting and long retention therapeutic nanoplatform based on water-soluble, non-toxic and highly-stable core-shell poly(amino acid) nanocomplexes.

Drug delivery nanoplatforms have been applied in bioimaging, medical diagnosis, drug delivery and medical therapy. However, insolubility, toxicity, instability, nonspecific targeting and short retention of many hydrophobic drugs limit their extensive applications. Herein, we have constructed a passive targeting and long retention therapeutic nanoplatform of core-shell gefitinib/poly (ethylene glycol)-polytyrosine nanocomplexes (Gef-PY NCs).

Assessment of atrial septal defect using 2D or real-time 3D transesophageal echocardiography and outcomes following transcatheter closure.

Background: The assessment of interatrial septum (IAS) requires a standardized, systematic approach, including two-dimensional transthoracic echocardiography (2D TTE), 2D transesophageal echocardiography (2D TEE), and three-dimensional (3D) TEE. Although 2D TEE has been widely used for the preoperative assessment of atrial septal defect (ASD), its ability to provide reliable information is often limited due to the structural characteristics of IAS. The introduction of 3D TEE provides a unique "en face" view of IAS, which allows the visualization and accurate measurements of diameters, area, and rims of ASD.

3D transesophageal echocardiography assists in evaluating the morphology, function, and presence of thrombi of left atrial appendage in patients with atrial fibrillation.

Background: Left atrial appendage (LAA) is significantly more likely to form thrombi in patients with atrial fibrillation (AFib). Two-dimensional transesophageal echocardiography (2D TEE) is considered the gold standard for assessing and studying LAA morphology and anatomy. However, 2D TEE can only visualize one plane at any given time.

LncRNA H19 governs mitophagy and restores mitochondrial respiration in the heart through Pink1/Parkin signaling during obesity.

Maintaining proper mitochondrial respiratory function is crucial for alleviating cardiac metabolic disorders during obesity, and mitophagy is critically involved in this process. Long non-coding RNA H19 (H19) is crucial for metabolic regulation, but its roles in cardiac disorders, mitochondrial respiratory function, and mitophagy during obesity are largely unknown. In this study, palmitic acid (PA)-treated H9c2 cell and Lep mice were used to investigate cardiac metabolic disorders in vitro and in vivo, respectively.

The Downregulation of ADAM17 Exerts Protective Effects against Cardiac Fibrosis by Regulating Endoplasmic Reticulum Stress and Mitophagy.

Background: A disintegrin and metalloproteinase 17 (ADAM17) is a transmembrane protein that is widely expressed in various tissues; it mediates the shedding of many membrane-bound molecules, involving cell-cell and cell-matrix interactions. We investigated the role of ADAM17 within mouse cardiac fibroblasts (mCFs) in heart fibrosis.

Methods: mCFs were isolated from the hearts of neonatal mice.

Intermittent concurrent use of clopidogrel and proton pump inhibitors did not increase risk of adverse clinical outcomes in Chinese patients with coronary artery disease.

Background: Proton pump inhibitors (PPIs) are frequently prescribed to patients with coronary heart disease (CHD) under antiplatelet therapy to prevent gastrointestinal (GI) bleeding. However, its clinical impact is still under debate, especially in Asian population. This study was undertaken to explore the effects of concurrent use of clopidogrel and PPIs on the clinical outcomes in Chinese patients with CHD in secondary prevention.

Carvedilol induces biased β1 adrenergic receptor-nitric oxide synthase 3-cyclic guanylyl monophosphate signalling to promote cardiac contractility.

Aims: β-blockers are widely used in therapy for heart failure and hypertension. β-blockers are also known to evoke additional diversified pharmacological and physiological effects in patients. We aim to characterize the underlying molecular signalling and effects on cardiac inotropy induced by β-blockers in animal hearts.

Plasma D-dimer as a predictor of intraluminal thrombus burden and progression of abdominal aortic aneurysm.

Aim: Intraluminal thrombus (ILT) is presented in most abdominal aortic aneurysms (AAAs) and is suggested to promote AAA expansion. D-dimer, a breakdown product in the thrombus remodeling, may have prognostic value for AAA. This study investigated the interrelation between plasma D-dimer level, ILT volume, AAA size and progression.

Phosphodiesterase 5 Associates With β2 Adrenergic Receptor to Modulate Cardiac Function in Type 2 Diabetic Hearts.

Background In murine heart failure models and in humans with diabetic-related heart hypertrophy, inhibition of phosphodiesterase 5 (PDE5) by sildenafil improves cardiac outcomes. However, the mechanism by which sildenafil improves cardiac function is unclear. We have observed a relationship between PDE5 and β2 adrenergic receptor (β2AR), which is characterized here as a novel mechanistic axis by which sildenafil improves symptoms of diabetic cardiomyopathy.

CC chemokine receptor 2 functions in osteoblastic transformation of valvular interstitial cells.

Aims: Calcific aortic valve disease (CAVD) emerges as a challenging clinical issue, which is associated with high cardiovascular mortality. It has been demonstrated that osteoblastic transformation of AVICs is a key mechanism of CAVD and C-C motif chemokine receptors (CCRs) may favor this process. Thus, we aimed to investigate whether CCRs were involved in osteoblastic transformation of AVICs during the development CAVD.

[Analysis of PMM2 gene variant in an infant with congenital disorders of glycosylation type 1a].

Objective: To identify potential mutation of PMM2 gene in an infant with congenital disorders of glycosylation type 1a (CDG-1a).

Methods: Genomic DNA was extracted from peripheral blood sample of the patient. All coding exons (exons 1-8) and splicing sites of the PMM2 gene were amplified with PCR.

Inhibition of soluble epoxide hydrolase attenuates a high-fat diet-mediated renal injury by activating PAX2 and AMPK.

A high-fat diet (HFD) causes obesity-associated morbidities involved in macroautophagy and chaperone-mediated autophagy (CMA). AMPK, the mediator of macroautophage, has been reported to be inactivated in HFD-caused renal injury. However, PAX2, the mediator for CMA, has not been reported in HFD-caused renal injury.