Effects of structural changes on antibacterial activity and cytotoxicity due to proline substitutions in chimeric peptide HnMc.

Owing to the rapidly increasing emergence of multidrug-resistant pathogens, antimicrobial peptides (AMPs) are being explored as next-generation antibiotics. However, AMPs present in nature are highly toxic and exhibit low antibacterial activity. Simple modifications, such as amino acid substitution, can enhance antimicrobial activity and cell selectivity.

Modeling Reduced Contractility and Stiffness Using iPSC-Derived Cardiomyocytes Generated From Female Becker Muscular Dystrophy Carrier.

Study investigators encountered a female Becker muscular dystrophy (BMD) carrier with advanced heart failure (HF) and identified a stop-gain variant in procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 () as a potential second-hit variant. Isogenic induced pluripotent stem cells (iPSCs) with dominant expression of WT-, Δ45-48-, or Δ45-48- with corrected variant were established. Microforce testing using 3-dimensional self-organized tissue rings (SOTRs) generated from iPSC-derived cardiomyocytes (iPSC-CMs) demonstrated that correction of the heterozygous variant did not improve the reduced force, but it significantly recovered the reduced stiffness in Δ45-48- SOTRs.

Anti-Biofilm Effects of Rationally Designed Peptides against Planktonic Cells and Pre-Formed Biofilm of .

Biofilms are resistant to antibiotics and are a major source of persistent and recurring infections by clinically important pathogens. Drugs used for biofilm-associated infections are limited because biofilm-embedded or biofilm-matrix bacteria are difficult to kill or eradiate. Therefore, many researchers are developing new and effective antibiofilm agents.

Antifungal and Anti-Inflammatory Activities of PS1-2 Peptide against Fluconazole-Resistant .

Clinically, fungal pneumonia rarely occurs in adults, and invasive fungal infections can cause substantial morbidity, and mortality due to sepsis and septic shock. In the present study, we have designed peptides that exhibit potent antifungal activities against fluconazole-resistant in physiological monovalent, and divalent ionic buffers, with minimal fungicidal concentrations ranging from 16 to 32 µM. None of these tested peptides resulted in the development of drug resistance similar to fluconazole.

Potent Anti-Inflammatory Effects of a Helix-to-Helix Peptide against Endotoxin-Mediated Sepsis.

Although considerable scientific research data is available for sepsis and cytokine storm syndrome, there is a need to develop new treatments or drugs for sepsis management. Antimicrobial peptides (AMPs) possess anti-bacterial and anti-inflammatory activity, neutralizing toxins such as lipopolysaccharides (LPS, endotoxin). Most AMPs have been designed as a substitute for conventional antibiotics, which kill drug-resistant pathogens.

Design of Antimicrobial Peptides with Cell-Selective Activity and Membrane-Acting Mechanism against Drug-Resistant Bacteria.

Antimicrobial peptides (AMPs) can combat drug-resistant bacteria with their unique membrane-disruptive mechanisms. This study aimed to investigate the antibacterial effects of several membrane-acting peptides with amphipathic structures and positional alterations of two tryptophan residues. The synthetic peptides exhibited potent antibacterial activities in a length-dependent manner against various pathogenic drug-resistant and susceptible bacteria.

Candidacidal and Antibiofilm Activity of PS1-3 Peptide against Drug-Resistant on Contact Lenses.

The recent emergence of antibiotic-resistant fungi has accelerated research on novel antifungal agents. In particular, infections are related to biofilm formation on medical devices, such as catheters, stents, and contact lenses, resulting in high morbidity and mortality. In this study, we aimed to elucidate the antifungal and antibiofilm effects of a peptide against drug-resistant .

Human-Induced Pluripotent Stem Cell-Derived Cardiomyocyte Model for Δ160E-Induced Cardiomyopathy.

Background: The Δ160E mutation in , which encodes troponin T, is a rare pathogenic variant identified in patients with hypertrophic cardiomyopathy and is associated with poor prognosis. Thus, a convenient human model recapitulating the pathological phenotype caused by Δ160E is required for therapeutic development.

Methods: We identified a heterozygous in-frame deletion mutation (c.

Antifungal Mechanism of Vip3Aa, a Vegetative Insecticidal Protein, against Pathogenic Fungal Strains.

Discovering new antifungal agents is difficult, since, unlike bacteria, mammalian and fungal cells are both eukaryotes. An efficient strategy is to consider new antimicrobial proteins that have variety of action mechanisms. In this study, a cDNA encoding Vip3Aa protein, a vegetative insecticidal protein, was obtained at the vegetative growth stage; its antifungal activity and mechanism were evaluated using a bacterially expressed recombinant Vip3Aa protein.

Aberrant accumulation of TMEM43 accompanied by perturbed transmural gene expression in arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) caused by TMEM43 p.S358L is a fully penetrant heart disease that results in impaired cardiac function or fatal arrhythmia. However, the molecular mechanism of ACM caused by the TMEM43 variant has not yet been fully elucidated.

High-Throughput Drug Screening System Based on Human Induced Pluripotent Stem Cell-Derived Atrial Myocytes ∼ A Novel Platform to Detect Cardiac Toxicity for Atrial Arrhythmias.

Evaluation of proarrhythmic properties is critical for drug discovery. In particular, QT prolongation in electrocardiograms has been utilized as a surrogate marker in many evaluation systems to assess the risk of torsade de pointes and lethal ventricular arrhythmia. Recently, new evaluation systems based on human iPS cell-derived cardiomyocytes have been established.

Protocol for Morphological and Functional Phenotype Analysis of hiPS-Derived Cardiomyocytes.

Induced pluripotent stem cells (iPSCs) have been utilized to study physiological development and also the pathogenesis of heart diseases. iPS-derived cardiomyocytes and engineered cardiac tissues provide a promising capacity for investigating cardiac development and disease modeling. In addition to protocols for cardiac differentiation and 3D cardiac tissue construction, the establishment of protocols for the comprehensive evaluation of the physiological and/or pathophysiological properties for the iPS-derived cells/tissues are indispensable.

Homogeneous 2D and 3D alignment of cardiomyocyte in dilated cardiomyopathy revealed by intravital heart imaging.

In contrast to hypertrophic cardiomyopathy, there has been reported no specific pattern of cardiomyocyte array in dilated cardiomyopathy (DCM), partially because lack of alignment assessment in a three-dimensional (3D) manner. Here we have established a novel method to evaluate cardiomyocyte alignment in 3D using intravital heart imaging and demonstrated homogeneous alignment in DCM mice. Whilst cardiomyocytes of control mice changed their alignment by every layer in 3D and position twistedly even in a single layer, termed myocyte twist, cardiomyocytes of DCM mice aligned homogeneously both in two-dimensional (2D) and in 3D and lost myocyte twist.

Decreased YAP activity reduces proliferative ability in human induced pluripotent stem cell of duchenne muscular dystrophy derived cardiomyocytes.

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration accompanied by dilated cardiomyopathy. Recently, abnormality of yes-associated protein (YAP) has been reported as the pathogenesis of muscle degeneration of DMD; however YAP activity remains unclear in dystrophic heart of DMD. Herein, we investigated YAP activity using disease-specific induced pluripotent stem cell (iPSC) derived cardiomyocytes (CMs) in DMD.

Sintered Characteristics of 3 Mole% Yttria-Stabilized Zirconia Polycrystals (3Y-TZP) Implants Manufactured by Slip-Casting and Computer Aided Design/Computer Aided Manufacturing (CAD/CAM).

Two types of dense and toughened 3Y-TZP zirconia implants were fabricated by the sintering of green compacts. Then, the sintered properties of the two implants were compared. Slip-cast and post-sintered all-ceramic zirconia implants were fabricated by the heat treatment at 1450 °C for 2 h using optimal slurry conditions (60 wt% solid content, 1 wt% dispersant, and pH 12).

Sol-Gel Coating of Hydroxyapatite on Zirconia Substrate.

The zirconia used in dental implants requires excellent mechanical and chemical properties such as high strength, high biological performance, corrosion resistance, and phase stability. In this study, after we prepared a highly fluidized solution of calcium phosphate, we fabricated a hydroxyapatite (HA) coating layer on a zirconia substrate using the sol-gel method to enhance its biocompatibility and bone-bonding ability. We dipped the zirconia substrate into the calcium phosphate sol to obtain the HA-coated film, which was dried at room temperature.

Slurry Coating of Hydroxyapatite on Zirconia Substrate.

Zirconia dental implants require excellent biocompatibility and high bonding strength. In this study, we attempted to fabricate biocompatible zirconia ceramics through surface modification by hydroxyapatite (HA) slurry coating. A hydroxyapatite slurry for spin coating was prepared using two sizes of hydroxyapatite particles.

Bioactivity Improvement of Zirconia Substrate by Hydroxyapatite Coating Using Room Temperature Spray Processing.

Zirconia ceramics has a bioinert property with low bioactivity. So, it is necessary to improve its low bioactivity by the surface modification using effective coating methods. In this study, we fabricated the hydroxyapatite-coated zirconia substrate by room temperature spray processing to improve the bioactivity of the zirconia implant and investigated its coating effect on the biological performance of zirconia substrate via an test in simulated body fluid (SBF) solution.

Scaffold-Mediated Developmental Effects on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Are Preserved After External Support Removal.

Human induced pluripotent stem (hiPS) cells have been used as a cell source for regenerative therapy and disease modeling. The purity of hiPS-cardiomyocytes (hiPS-CMs) has markedly improved with advancements in cell culture and differentiation protocols. However, the morphological features and molecular properties of the relatively immature cells are still unclear, which has hampered their clinical application.

Bicine promotes rapid formation of β-sheet-rich amyloid-β fibrils.

Fibrillar aggregates of amyloid-β (Aβ) are the main component of plaques lining the cerebrovasculature in cerebral amyloid angiopathy. As the predominant Aβ isoform in vascular deposits, Aβ40 is a valuable target in cerebral amyloid angiopathy research. However, the slow process of Aβ40 aggregation in vitro is a bottleneck in the search for Aβ-targeting molecules.

Thermochemical nonequilibrium flow analysis in low enthalpy shock-tunnel facility.

A thermochemical nonequilibrium analysis was performed under the low enthalpy shock-tunnel flows. A quasi-one-dimensional flow calculation was employed by dividing the flow calculations into two parts, for the shock-tube and the Mach 6 nozzle. To describe the thermochemical nonequilibrium of the low enthalpy shock-tunnel flows, a three-temperature model is proposed.

[Constructing iPS cell-based platforms for disease modeling and drug discovery in cardiovascular fields: Phenotype analysis using self-organization and new imaging techniques].

Disease-specific iPS cells have been considered and used as platforms for disease modeling and drug discovery for intractable diseases. In the field of cardiovascular medicine, iPS cells have been generated from patients with heart diseases including inherited cardiomyopathy. The disease-specific iPS cells showed the certain parts of phenotype of the disease on culture dishes in in vitro systems, but the cells do not necessarily recapitulate patients' clinical properties, particularly those of physiological-/pathophysiological aspects.

All d-Lysine Analogues of the Antimicrobial Peptide HPA3NT3-A2 Increased Serum Stability and without Drug Resistance.

Novel antibiotic drugs are urgently needed because of the increase in drug-resistant bacteria. The use of antimicrobial peptides has been suggested to replace antibiotics as they have strong antimicrobial activity and can be extracted from living organisms such as insects, marine organisms, and mammals. HPA3NT3-A2 ([Ala] HPA3NT3) is an antimicrobial peptide that is an analogue of the HP (2-20) peptide derived from ribosomal protein L1.