Immunomorphogenesis in Degenerative Disc Disease: The Role of Proinflammatory Cytokines and Angiogenesis Factors.

Back pain (BP) due to degenerative disc disease (DDD) is a severe, often disabling condition. The aim of this study was to determine the association between the expression level of proinflammatory cytokines (IL-1β, IL-6, and IL-17), angiogenesis markers (VEGF-A and CD31) in intervertebral disc (IVD) tissue and IVD degeneration in young people with discogenic BP. In patients who underwent discectomy for a disc herniation, a clinical examination, magnetic resonance imaging of the lumbar spine, histological and immunohistochemical analyses of these factors in IVD were performed in comparison with the parameters of healthy group samples (controls).

Adenylyl cyclase isoform 1 contributes to sinoatrial node automaticity via functional microdomains.

Sinoatrial node (SAN) cells are the heart's primary pacemaker. Their activity is tightly regulated by β-adrenergic receptor (β-AR) signaling. Adenylyl cyclase (AC) is a key enzyme in the β-AR pathway that catalyzes the production of cAMP.

Protocol to record and quantify the intracellular pH in contracting cardiomyocytes.

Intracellular pH (pH) plays critical roles in the regulation of cardiac function. Methods and techniques for cardiac pH measurement have continued to evolve since early 1960s. Fluorescent microscopy is the most recently developed technique with several advantages over other techniques including higher spatial and temporal resolutions, and feasibility for contracting cell measurement.

Beat-to-beat dynamic regulation of intracellular pH in cardiomyocytes.

The mammalian heart beats incessantly with rhythmic mechanical activities generating acids that need to be buffered to maintain a stable intracellular pH (pH) for normal cardiac function. Even though spatial pH non-uniformity in cardiomyocytes has been documented, it remains unknown how pH is regulated to match the dynamic cardiac contractions. Here, we demonstrated beat-to-beat intracellular acidification, termed pH transients, in synchrony with cardiomyocyte contractions.

Protocol to assess two distinct components of the nonlinear capacitance in mouse cardiomyocytes.

Prestin (Slc26a5) is a motor protein previously considered to be expressed exclusively in outer hair cells (OHCs) of the inner ear. However, we recently identified the functional expression of prestin in the heart. Nonlinear capacitance (NLC) measurement in OHCs is used to evaluate the signature function of prestin, which exhibits membrane potential-dependent conformational changes.

Disruption of protein quality control of the human ether-à-go-go related gene K channel results in profound long QT syndrome.

Background: Long QT syndrome (LQTS) is a hereditary disease that predisposes patients to life-threatening cardiac arrhythmias and sudden cardiac death. Our previous study of the human ether-à-go-go related gene (hERG)-encoded K channel (K11.1) supports an association between hERG and RING finger protein 207 (RNF207) variants in aggravating the onset and severity of LQTS, specifically T613M hERG (hERG) and RNF207 frameshift (RNF207) mutations.

Chronic Diclofenac Exposure Increases Mitochondrial Oxidative Stress, Inflammatory Mediators, and Cardiac Dysfunction.

Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among one of the most commonly prescribed medications for pain and inflammation. Diclofenac (DIC) is a commonly prescribed NSAID that is known to increase the risk of cardiovascular diseases. However, the mechanisms underlying its cardiotoxic effects remain largely unknown.

Selectin-targeting glycosaminoglycan-peptide conjugate limits neutrophil-mediated cardiac reperfusion injury.

Aims: One of the hallmarks of myocardial infarction (MI) is excessive inflammation. During an inflammatory insult, damaged endothelial cells shed their glycocalyx, a carbohydrate-rich layer on the cell surface which provides a regulatory interface to immune cell adhesion. Selectin-mediated neutrophilia occurs as a result of endothelial injury and inflammation.

Suppression of inflammation and fibrosis using soluble epoxide hydrolase inhibitors enhances cardiac stem cell-based therapy.

Stem cell replacement offers a great potential for cardiac regenerative therapy. However, one of the critical barriers to stem cell therapy is a significant loss of transplanted stem cells from ischemia and inflammation in the host environment. Here, we tested the hypothesis that inhibition of the soluble epoxide hydrolase (sEH) enzyme using sEH inhibitors (sEHIs) to decrease inflammation and fibrosis in the host myocardium may increase the survival of the transplanted human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CMs) in a murine postmyocardial infarction model.

Cooperativity of K7.4 channels confers ultrafast electromechanical sensitivity and emergent properties in cochlear outer hair cells.

The mammalian cochlea relies on active electromotility of outer hair cells (OHCs) to resolve sound frequencies. OHCs use ionic channels and somatic electromotility to achieve the process. It is unclear, though, how the kinetics of voltage-gated ionic channels operate to overcome extrinsic viscous drag on OHCs at high frequency.

Action Potential Shortening and Impairment of Cardiac Function by Ablation of .

Background: Intracellular pH (pH) is critical to cardiac excitation and contraction; uncompensated changes in pH impair cardiac function and trigger arrhythmia. Several ion transporters participate in cardiac pH regulation. Our previous studies identified several isoforms of a solute carrier Slc26a6 to be highly expressed in cardiomyocytes.

Electrotaxis of cardiac progenitor cells, cardiac fibroblasts, and induced pluripotent stem cell-derived cardiac progenitor cells requires serum and is directed via PI3'K pathways.

Background: The limited regenerative capacity of cardiac tissue has long been an obstacle to treating damaged myocardium. Cell-based therapy offers an enormous potential to the current treatment paradigms. However, the efficacy of regenerative therapies remains limited by inefficient delivery and engraftment.

A Singular Role of I Promoting the Development of Cardiac Automaticity during Cardiomyocyte Differentiation by I -Induced Activation of Pacemaker Current.

The inward rectifier potassium current (I) is generally thought to suppress cardiac automaticity by hyperpolarizing membrane potential (MP). We recently observed that I could promote the spontaneously-firing automaticity induced by upregulation of pacemaker funny current (I) in adult ventricular cardiomyocytes (CMs). However, the intriguing ability of I to activate I and thereby promote automaticity has not been explored.

Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation.

Background: Atrial fibrillation represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme catalyzes the hydrolysis of anti-inflammatory epoxy fatty acids, including epoxyeicosatrienoic acids from arachidonic acid to the corresponding proinflammatory diols.

Feedback mechanisms for cardiac-specific microRNAs and cAMP signaling in electrical remodeling.

Background: Loss of transient outward K(+) current (Ito) is well documented in cardiac hypertrophy and failure both in animal models and in humans. Electrical remodeling contributes to prolonged action potential duration and increased incidence of arrhythmias. Furthermore, there is a growing body of evidence linking microRNA (miR) dysregulation to the progression of both conditions.

Regulation of gene transcription by voltage-gated L-type calcium channel, Cav1.3.

Cav1.3 L-type Ca(2+) channel is known to be highly expressed in neurons and neuroendocrine cells. However, we have previously demonstrated that the Cav1.

Critical roles of a small conductance Ca²⁺-activated K⁺ channel (SK3) in the repolarization process of atrial myocytes.

Aims: Small conductance Ca(2+)-activated K(+) channels (K(Ca)2 or SK channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca(2+) (Ca(i)²⁺) with membrane potentials. We have recently reported the functional expression of SK channels in human and mouse cardiac myocytes. Additionally, we have found that the channel is highly expressed in atria compared with the ventricular myocytes.

Adenylyl cyclase subtype-specific compartmentalization: differential regulation of L-type Ca2+ current in ventricular myocytes.

Rationale: Adenylyl cyclase (AC) represents one of the principal molecules in the β-adrenergic receptor signaling pathway, responsible for the conversion of ATP to the second messenger, cAMP. AC types 5 (ACV) and 6 (ACVI) are the 2 main isoforms in the heart. Although highly homologous in sequence, these 2 proteins play different roles during the development of heart failure.

Triclosan impairs excitation-contraction coupling and Ca2+ dynamics in striated muscle.

Triclosan (TCS), a high-production-volume chemical used as a bactericide in personal care products, is a priority pollutant of growing concern to human and environmental health. TCS is capable of altering the activity of type 1 ryanodine receptor (RyR1), but its potential to influence physiological excitation-contraction coupling (ECC) and muscle function has not been investigated. Here, we report that TCS impairs ECC of both cardiac and skeletal muscle in vitro and in vivo.

MicroRNA profiling predicts a variance in the proliferative potential of cardiac progenitor cells derived from neonatal and adult murine hearts.

Cardiac progenitor cells (CPCs) are multipotent cells that may offer tremendous potentials for the regeneration of injured myocardium. To expand the limited number of CPCs for effective clinical regeneration of myocardium, it is important to understand their proliferative potentials. Single-cell based assays were utilized to purify c-kit(pos) CPCs from human and mouse hearts.

Phorbol ester and endothelin-1 alter functional expression of Na+/Ca2+ exchange, K+, and Ca2+ currents in cultured neonatal rat myocytes.

Endothelin-1 (ET-1) and activation of protein kinase C (PKC) have been implicated in alterations of myocyte function in cardiac hypertrophy and heart failure. Changes in cellular Ca2+ handling and electrophysiological properties also occur in these states and may contribute to mechanical dysfunction and arrhythmias. While ET-1 or PKC stimulation induces cellular hypertrophy in cultured neonatal rat ventricular myocytes (NRVMs), a system widely used in studies of hypertrophic signaling, there is little data about electrophysiological changes.

Expression and roles of Cav1.3 (α1D) L-type Ca²+ channel in atrioventricular node automaticity.

Atrioventricular node (AV node) is the hub where electrical input from the atria is propagated and conveyed to the ventricles. Despite its strategic position and role in governing impulse conduction between atria and ventricles, there is paucity of data regarding the contribution of specific ion channels to the function of the AV node. Here, we examined the roles of Ca(v)1.

Disruption of adenylyl cyclase type V does not rescue the phenotype of cardiac-specific overexpression of Galphaq protein-induced cardiomyopathy.

Adenylyl cyclase (AC) is the principal effector molecule in the β-adrenergic receptor pathway. AC(V) and AC(VI) are the two predominant isoforms in mammalian cardiac myocytes. The disparate roles among AC isoforms in cardiac hypertrophy and progression to heart failure have been under intense investigation.