Rapid Electrical Stimulation Increased Cardiac Apoptosis Through Disturbance of Calcium Homeostasis and Mitochondrial Dysfunction in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Background/Aims: Heart failure induced by tachycardia, the most common arrhythmia, is frequently observed in clinical practice. This study was designed to investigate the underlying mechanisms. Methods: Rapid electrical stimulation (RES) at a frequency of 3 Hz was applied on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for 7 days, with 8 h/day and 24 h/day set to represent short-term and long-term tachycardia, respectively. Age-matched hiPSC-CMs without electrical stimulation or with slow electrical stimulation (1 Hz) were set as no electrical stimulation (NES) control or low-frequency electrical stimulation (LES) control. Following stimulation, JC-1 staining flow cytometry analysis was performed to examine mitochondrial conditions. Apoptosis in hiPSC-CMs was evaluated using Hoechst staining and Annexin V/propidium iodide (AV/PI) staining flow cytometry analysis. Calcium transients and L-type calcium currents were recorded to evaluate calcium homeostasis. Western blotting and qPCR were performed to evaluate the protein and mRNA expression levels of apoptosis-related genes and calcium homeostasis-regulated genes. Results: Compared to the controls, hiPSC-CMs following RES presented mitochondrial dysfunction and an increased apoptotic percentage. Amplitudes of calcium transients and L-type calcium currents were significantly decreased in hiPSC-CMs with RES. Molecular analysis demonstrated upregulated expression of Caspase3 and increased Bax/Bcl-2 ratio. Genes related to calcium re-sequence were downregulated, while phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) was significantly upregulated following RES. There was no significant difference between the NES control and LES control groups in these aspects. Inhibition of CaMKII with 1 µM KN93 partly reversed these adverse effects of RES. Conclusion: RES on hiPSC-CMs disturbed calcium homeostasis, which led to mitochondrial stress, promoted cell apoptosis and caused electrophysiological remodeling in a time-dependent manner. CaMKII played a central role in the damages induced by RES, pharmacological inhibition of CaMKII activity partly reversed the adverse effects of RES on both structural and electrophysiological properties of cells

Synthesis, Structures, and Properties of Two Three-Dimensional Metal–Organic Frameworks, Based on Concurrent Ligand Extension

A tritopic carboxylate ligand, tris­(4′-carboxybiphenyl)­amine (<b>L-H</b>_<b>3</b>), has been synthesized and applied in the construction of microporous metal–organic frameworks (MOFs). Two novel metal–organic frameworks (MOFs), {[Zn₂(<b>L</b>)­(OH)]·2DMF·H₂O}_∞ (<b>1</b>) and {[Cu­(<b>L-H</b>)­(DMA)]·DMA·2H₂O}_∞ (<b>2</b>), have been constructed out of <b>L-H</b>_<b>3</b>, Zn²⁺, and Cu²⁺, respectively. <b>1</b> has a 2-fold interpenetrating three-dimensional framework formed by <b>L</b> connectors and the [Zn₂(CO₂)₃] secondary building units (SBUs). As for <b>1</b>, it is worth pointing out that one μ₂–OH group links two Zn atoms between two neighboring SBUs to produce interesting Zn–O–Zn zigzag chains in the structure. <b>2</b> has a two-dimensional grid sheet formed by <b>L-H</b> connectors and the typical paddle-wheel [Cu₂(CO₂)₄] SBUs. Two-dimensional (2D) sheets nest with each other, which finally forms a three-dimensional (3D) nested framework. Two MOFs are characterized by infrared (IR) spectroscopy, thermogravimetry, single-crystal and elemental analyses, and powder X-ray diffraction methods. Framework <b>1</b>′ exhibits high permanent porosity (Langmuir surface area = 848 m²/g), high thermal stability (up to 450 °C), highly active properties for Friedel–Crafts alkylation reaction, as well as the potential application for the CO₂ gas storage and luminescent material. The catalytic results reveal that <b>2</b>′ is indeed an efficient heterogeneous catalyst for olefin epoxidation reactions

Příloha - nedílná součást účetní závěrky podnikatelských subjektů

Import 20/04/2006Prezenční výpůjčkaVŠB - Technická univerzita Ostrava. Ekonomická fakulta. Katedra (116) marketingu a obchod

Synthesis, Structures, and Properties of Two Three-Dimensional Metal–Organic Frameworks, Based on Concurrent Ligand Extension

A tritopic carboxylate ligand, tris­(4′-carboxybiphenyl)­amine (<b>L-H</b>_<b>3</b>), has been synthesized and applied in the construction of microporous metal–organic frameworks (MOFs). Two novel metal–organic frameworks (MOFs), {[Zn₂(<b>L</b>)­(OH)]·2DMF·H₂O}_∞ (<b>1</b>) and {[Cu­(<b>L-H</b>)­(DMA)]·DMA·2H₂O}_∞ (<b>2</b>), have been constructed out of <b>L-H</b>_<b>3</b>, Zn²⁺, and Cu²⁺, respectively. <b>1</b> has a 2-fold interpenetrating three-dimensional framework formed by <b>L</b> connectors and the [Zn₂(CO₂)₃] secondary building units (SBUs). As for <b>1</b>, it is worth pointing out that one μ₂–OH group links two Zn atoms between two neighboring SBUs to produce interesting Zn–O–Zn zigzag chains in the structure. <b>2</b> has a two-dimensional grid sheet formed by <b>L-H</b> connectors and the typical paddle-wheel [Cu₂(CO₂)₄] SBUs. Two-dimensional (2D) sheets nest with each other, which finally forms a three-dimensional (3D) nested framework. Two MOFs are characterized by infrared (IR) spectroscopy, thermogravimetry, single-crystal and elemental analyses, and powder X-ray diffraction methods. Framework <b>1</b>′ exhibits high permanent porosity (Langmuir surface area = 848 m²/g), high thermal stability (up to 450 °C), highly active properties for Friedel–Crafts alkylation reaction, as well as the potential application for the CO₂ gas storage and luminescent material. The catalytic results reveal that <b>2</b>′ is indeed an efficient heterogeneous catalyst for olefin epoxidation reactions

Synthesis, Structures, and Properties of Two Three-Dimensional Metal–Organic Frameworks, Based on Concurrent Ligand Extension

A tritopic carboxylate ligand, tris­(4′-carboxybiphenyl)­amine (<b>L-H</b>_<b>3</b>), has been synthesized and applied in the construction of microporous metal–organic frameworks (MOFs). Two novel metal–organic frameworks (MOFs), {[Zn₂(<b>L</b>)­(OH)]·2DMF·H₂O}_∞ (<b>1</b>) and {[Cu­(<b>L-H</b>)­(DMA)]·DMA·2H₂O}_∞ (<b>2</b>), have been constructed out of <b>L-H</b>_<b>3</b>, Zn²⁺, and Cu²⁺, respectively. <b>1</b> has a 2-fold interpenetrating three-dimensional framework formed by <b>L</b> connectors and the [Zn₂(CO₂)₃] secondary building units (SBUs). As for <b>1</b>, it is worth pointing out that one μ₂–OH group links two Zn atoms between two neighboring SBUs to produce interesting Zn–O–Zn zigzag chains in the structure. <b>2</b> has a two-dimensional grid sheet formed by <b>L-H</b> connectors and the typical paddle-wheel [Cu₂(CO₂)₄] SBUs. Two-dimensional (2D) sheets nest with each other, which finally forms a three-dimensional (3D) nested framework. Two MOFs are characterized by infrared (IR) spectroscopy, thermogravimetry, single-crystal and elemental analyses, and powder X-ray diffraction methods. Framework <b>1</b>′ exhibits high permanent porosity (Langmuir surface area = 848 m²/g), high thermal stability (up to 450 °C), highly active properties for Friedel–Crafts alkylation reaction, as well as the potential application for the CO₂ gas storage and luminescent material. The catalytic results reveal that <b>2</b>′ is indeed an efficient heterogeneous catalyst for olefin epoxidation reactions

Additional file 1: Table S1. of Structural and electrophysiological dysfunctions due to increased endoplasmic reticulum stress in a long-term pacing model using human induced pluripotent stem cell-derived ventricular cardiomyocytes

List of oligonucleotide sequences used. (DOC 237 kb

Additional file 2: Figure S1. of Structural and electrophysiological dysfunctions due to increased endoplasmic reticulum stress in a long-term pacing model using human induced pluripotent stem cell-derived ventricular cardiomyocytes

The contactless optical mapping displayed action potential prolongation in situ. It was confirmed that the average beating rate increased from 36.1 bpm to 71.0 bpm during stimulation, indicative of the excellent pacing capture efficiency. (DOC 102 kb

Polycationic Open‐Shell Cyclophanes: Synthesis of Electron‐Rich Chiral Macrocycles, and Redox‐Dependent Electronic States

π-Conjugated chiral nanorings with intriguing electronic structures and chiroptical properties have attracted considerable interests in synthetic chemistry and materials science. We present the design principles to access new chiral macrocycles (1 and 2) that are essentially built on the key components of main-group electron-donating carbazolyl moieties or the π-expanded aza[7]helicenes. Both macrocycles show the unique molecular conformations with a (quasi) figure-of-eight topology as a result of the conjugation patterns of 2,2',7,7'-spirobifluorenyl in 1 and triarylamine-coupled aza[7]helicene-based building blocks in 2. This electronic nature of redox-active, carbazole-rich backbones enabled these macrocycles to be readily oxidized chemically and electrochemically, leading to the sequential production of a series of positively charged polycationic open-shell cyclophanes. Their redox-dependent electronic states of the resulting multispin polyradicals have been characterized by VT-ESR, UV-vis-NIR absorption and spectroelectrochemical measurements. The singlet (ΔES-T = -1.29 kcal mol-1) and a nearly degenerate singlet-triplet ground state (ΔES-T(calcd) = -0.15 kcal mol-1 and ΔES-T(exp) = 0.01 kcal mol-1) were proved for diradical dications 12+2• and 22+2•, respectively. Our work provides an experimental proof for the construction of electron-donating new chiral nanorings, and more importantly for highly charged polyradicals with potential applications in chirospintronics and organic conductors