Slow Pathway Modification

BACKGROUND: Catheter-based slow pathway modification (SPM) for atrioventricular nodal reentrant tachycardia (AVNRT) is traditionally performed at empiric sites using anatomical landmarks and test ablation feedback within the triangle of Koch (TK). While studies have described more tailored techniques such as bipolar low voltage bridge (LVB) and wavefront collision identification, few have systematically compared the diagnostic yields of each and none have investigated whether omnipolar mapping technology provides incremental benefit...

Development of non-surgical treatment of human abdominal aortic aneurysm (AAA) has clinical significance. Colchicine emerges as an effective therapeutic regimen in cardiovascular diseases. Yet, whether colchicine slows AAA growth remain controversy. Here, we demonstrated that daily intragastric administration of low-dose colchicine blocked AAA formation, prevented vascular smooth muscle cell (SMC) phenotype switching and apoptosis, and vascular inflammation in both peri-aortic CaPO4 injury and subcutaneous angiotensin-II infusion induced experimental AAA mice models...

The monoamine transporters, including the serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET), are the therapeutic targets for the treatment of many neuropsychiatric disorders. Despite significant progress in characterizing the structures and transport mechanisms of these transporters, the regulation of their transport functions through dimerization or oligomerization remains to be understood. In the present study, we identified a conserved intramolecular ion-pair at the third extracellular loop (EL3) connecting TM5 and TM6 that plays a critical but divergent role in the modulation of dimerization and transport functions among the monoamine transporters...

BACKGROUND: The precise details of atrial activation around the triangle of Koch (ToK) remain unknown. We evaluated the relationship between the atrial-activation pattern around the ToK and success sites for slow-pathway (SP) modification ablation in slow-fast atrioventricular reentrant tachycardia (AVNRT). METHODS: Thirty patients with slow-fast AVNRT who underwent successful ablation were enrolled. Atrial activation around the ToK during sinus rhythm was investigated using ultra-high-density mapping pre-ablation...

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Age-associated osteosarcopenia is an unresolved syndrome characterized by the concomitant loss of bone (osteopenia) and skeletal muscle (sarcopenia) tissues increasing falls, immobility, morbidity, and mortality. Unbalanced resorption of bone in the remodeling process and excessive protein breakdown, especially fast type II myosin heavy chain (MyHC-II) isoform and myofiber metabolic shift, are the leading causes of bone and muscle deterioration in the elderly, respectively. Equisetum arvense (EQ) is a plant traditionally recommended for many pathological conditions due to its anti-inflammatory properties...

A novel delivery system comprising N-succinic anhydride (N-SAA) and D-fructose co-conjugated chitosan (NSCF)-modified polymeric liposomes (NSCF-PLip) were designed to enhance oral delivery of paclitaxel (PTX) by targeting monocarboxylate transporters (MCT) and glucose transporters (GLUT). The synthesized NSCF was characterised by FT-IR and 1 H NMR spectra. The prepared 30.78 % (degree of substitution of N-SAA) NSCF-PTX-PLip were approximately 150 nm in size, with a regular spherical shape, the zeta potential of -25...

BACKGROUND: Cold as a common environmental stress, causes increased heat production, accelerated metabolism and even affects its production performance. How to improve the adaptability of the animal organism to cold has been an urgent problem. As a key hub of lipid metabolism, the liver can regulate lipid metabolism to maintain energy balance, and O-GlcNAcylation is a kind of important PTMs, which participates in a variety of signaling and mechanism regulation, and at the same time, is very sensitive to changes in stress and nutritional levels, and is the body's "stress receptors" and "nutrient receptors"...

Diabetic kidney disease (DKD) is a major cause of chronic kidney disease (CKD), and it heightens the risk of cardiovascular incidents. The pathogenesis of DKD is thought to involve hemodynamic, inflammatory, and metabolic factors that converge on the fibrotic pathway. Genetic predisposition and unhealthy lifestyle practices both play a significant role in the development and progression of DKD. In spite of the recent emergence of angiotensin receptors blockers (ARBs)/angiotensin converting enzyme inhibitor (ACEI), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid receptors antagonists (NS-MRAs), current therapies still fail to effectively arrest the progression of DKD...

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease caused by pulmonary vascular remodeling, with a high incidence and mortality. At present, many clinical drugs for treating PAH mainly exert effects by relaxing the pulmonary artery, with limited therapeutic effects, so the search for viable therapeutic agents continues uninterrupted. In recent years, natural flavonoids have shown promising potential in the treatment of cardiovascular diseases. It is necessary to comprehensively elucidate the potential of natural flavonoids to combat PAH...

Glioblastoma, the most lethal primary brain tumor, harbors glioma stem cells (GSCs) that not only initiate and maintain malignant phenotypes but also enhance therapeutic resistance. Although frequently mutated in glioblastomas, the function and regulation of PTEN in PTEN-intact GSCs are unknown. Here, we found that PTEN directly interacted with MMS19 and competitively disrupted MMS19-based cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) machinery in differentiated glioma cells. PTEN was specifically succinated at cysteine (C) 211 in GSCs compared with matched differentiated glioma cells...

The drug-drug interaction (DDI) between Amiodarone (AMIO) and Sofosbuvir (SOF), a direct-acting Hepatitis-C NS5B Nucleotide Polymerase Inhibitor, has been associated with severe bradyarrhythmia in patients. Recent Cryo-EM data has revealed that this DDI occurs at the α-subunit of L-type Cav channels (LTCC), with AMIO binding at the fenestration site and SOF (or MNI-1: analog of SOF) binding at the central cavity of the conductance pathway. In this study, we investigated the DDI between 21 AMIO analogs, including Dronedarone (DRON), and MNI-1 (or SOF) in hiPSC-CMs (human induced pluripotent stem cell-derived cardiomyocytes) and hCav1...

Low-protein diets (LPDs), usually defined as a daily dietary protein intake of 0.6 to 0.8 g/kg body weight, have been recommended for decades as a safe and effective lifestyle modification to ameliorate inflammatory damage and proteinuria, reduce glomerular hyperfiltration, and improve metabolic acidosis control in patients with chronic kidney disease (CKD). The mechanism for this is largely attributed to altered tubuloglomerular feedback and afferent arteriole contraction leading to decreased glomerular pressure...

A small chemical modification of the nucleobase structure can significantly enhance the photoactivity of DNA, which may incur DNA damage, thus holding promising applications in photochemotherapy treatment of cancers or pathogens. However, single substitution confers only limited phototoxicity to DNA. Herein, we combine femtosecond and nanosecond time-resolved spectroscopy with high-level ab initio calculations to disentangle the excited-state dynamics of 6-methylthioguanine (me6-TG) under variable wavelength UVA excitation (310-330 nm)...

PURPOSE OF REVIEW: Sarcopenia is a wasting disease, mostly age-related in which muscle strength and mass decline, such as physical performance. With aging, both lower dietary protein intake and anabolic resistance lead to sarcopenia. Moreover, aging and sarcopenia display low-grade inflammation, which also worsen muscle condition. In this review, we focused on these two main targets to study dietary strategies. RECENT FINDINGS: The better understanding in mechanisms involved in sarcopenia helps building combined dietary approaches including physical activity that would slow the disease progression...

BACKGROUND: In all organisms, the innate immune system defends against pathogens through basal expression of molecules that provide critical barriers to invasion and inducible expression of effectors that combat infection. The adenosine deaminase that act on RNA (ADAR) family of RNA-binding proteins has been reported to influence innate immunity in metazoans. However, studies on the susceptibility of ADAR mutant animals to infection are largely lacking. RESULTS: Here, by analyzing adr-1 and adr-2 null mutants in well-established slow-killing assays, we find that both Caenorhabditis elegans ADARs are important for organismal survival to gram-negative and gram-positive bacteria, all of which are pathogenic to humans...

BACKGROUND: Redlining has been associated with worse health outcomes and various environmental disparities, separately, but little is known of the interaction between these two factors, if any. We aimed to estimate whether living in a historically-redlined area modifies the effects of exposures to ambient PM2.5 and extreme heat on mortality by non-external causes. METHODS: We merged 8,884,733 adult mortality records from thirteen state departments of public health with scanned and georeferenced Home Owners Loan Corporation (HOLC) maps from the University of Richmond, daily average PM2...

Pentacyclic triterpenoids are a diverse subclass of naturally occurring terpenes with various biological activities and applications. These compounds are broadly distributed in natural plant resources, but their low abundance and the slow growth cycle of plants pose challenges to their extraction and production. The biosynthesis of pentacyclic triterpenoids occurs through two main pathways, the mevalonic acid (MVA) pathway and the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway, which involve several enzymes and modifications...

Lipids are characterized by extremely high structural diversity translated into a wide range of physicochemical properties. As such, lipids are vital for many different functions including organization of cellular and organelle membranes, control of cellular and organismal energy metabolism, as well as mediating multiple signaling pathways. To maintain the lipid chemical diversity and to achieve rapid lipid remodeling required for the responsiveness and adaptability of cellular membranes, living systems make use of a network of chemical modifications of already existing lipids that complement the rather slow biosynthetic pathways...

The Ni-rich Co-poor layered cathode (LiNi x Co y Mn1- x - y O2 , x ≥ 0.9) is a candidate for the next-generation lithium-ion batteries due to its high specific capacity and low cost. However, the inherent structural instability and slow kinetics of Li+ migration hinder their large-scale application. Mo doping is proposed to enhance the crystal structure stability of LiNi0.9 Co0.05 Mn0.05 O2 and to ensure the preservation of the spherical secondary particles after the cycle. The characterization results indicate that Mo doping not only significantly relieves the lattice strain accompanied by H2 → H3 phase transition but also alleviates particle stress accumulation to avoid pulverization...