Purpose: This study aims to compare the surface roughness (SR), contact angle (CA), surface free energy (SFE), and bacterial adhesion of resin-based materials used in additive, subtractive, and conventional manufacturing techniques.
Materials And Methods: This study involved four groups of 23 specimens: Indirect conventional resin composite (ICRC), subtractively manufactured resin composite (SMRC), additively manufactured resin composite (AMRC), and soda-lime-silica glass (SLSG). One specimen per group was analyzed by Energy Dispersive X-ray Spectroscopy (EDS) before polishing.
Continuing advancements in human pluripotent stem cell (hPSC)-derived complex three-dimensional (3D) cardiac tissues require the development of novel technologies or adaptation of existing technologies to understand the physiology of the derived 3D cardiac tissues. In this protocol, we describe the use of multielectrode array (MEA) and sharp electrode electrophysiology techniques to investigate the electrical properties of 3D cardiac organoids. This protocol deciphers the electrical behavior of 3D cardiac organoids at both the single-cell level and tissue level.
View Article and Find Full Text PDFAnnu Rev Pharmacol Toxicol
September 2024
In the high-stakes arena of drug discovery, the journey from bench to bedside is hindered by a daunting 92% failure rate, primarily due to unpredicted toxicities and inadequate therapeutic efficacy in clinical trials. The FDA Modernization Act 2.0 heralds a transformative approach, advocating for the integration of alternative methods to conventional animal testing, including cell-based assays that employ human induced pluripotent stem cell (iPSC)-derived organoids, and organ-on-a-chip technologies, in conjunction with sophisticated artificial intelligence (AI) methodologies.
View Article and Find Full Text PDFCardiovascular diseases persist as a global health challenge that requires methodological innovation for effective drug development. Conventional pipelines relying on animal models suffer from high failure rates due to significant interspecies variation between humans and animal models. In response, the recently enacted Food and Drug Administration Modernization Act 2.
View Article and Find Full Text PDFDilated cardiomyopathy (DCM) is a progressive heart muscle disease that can culminate with heart failure and death. Mutations in several genes can cause DCM, including hyperpolarization-activated cyclic nucleotide-gated channel (HCN4), which has a critical function in the autonomic control of the heart rate. Here, we generated two human induced pluripotent stem cell (iPSC) lines generated from two DCM patients carrying variants in the HCN4 gene (c.
View Article and Find Full Text PDFThe unfolded protein response (UPR) is an elaborate signaling network that evolved to maintain proteostasis in the endoplasmic reticulum (ER) and mitochondria (mt). These organelles are functionally and physically associated, and consequently, their stress responses are often intertwined. It is unclear how these two adaptive stress responses are coordinated during ER stress.
View Article and Find Full Text PDFThe double-stranded RNA-dependent protein kinase activating protein (PACT), an RNA-binding protein that is part of the RNA-induced silencing complex, plays a key role in miR-mediated translational repression. Previous studies showed that PACT regulates the expression of various miRs, selects the miR strand to be loaded onto RNA-induced silencing complex, and determines proper miR length. Apart from PACT's role in mediating the antiviral response in immune cells, what PACT does in other cell types is unknown.
View Article and Find Full Text PDFFragile X Mental Retardation protein (FMRP), widely known for its role in hereditary intellectual disability, is an RNA-binding protein (RBP) that controls translation of select mRNAs. We discovered that endoplasmic reticulum (ER) stress induces phosphorylation of FMRP on a site that is known to enhance translation inhibition of FMRP-bound mRNAs. We show ER stress-induced activation of Inositol requiring enzyme-1 (IRE1), an ER-resident stress-sensing kinase/endoribonuclease, leads to FMRP phosphorylation and to suppression of macrophage cholesterol efflux and apoptotic cell clearance (efferocytosis).
View Article and Find Full Text PDFThe aim of this study was to compare the local and systemic effects of current pulp capping materials containing resin with those of traditional materials in an animal study. A total of 48 rats were used: a control group (n=12) (sub-control and negative control), a resin-containing group (n=18) (Calcimol LC, Theracal LC, Activa-BioActive Base/Liner), and a traditional group (n=18) (Biodentine, ProRoot MTA, Dycal). The materials which had been placed in polyethylene tubes were implanted in subcutaneous pockets.
View Article and Find Full Text PDFBackground And Aims: Methionine adenosyltransferase 1A (MAT1A) is responsible for S-adenosylmethionine (SAMe) biosynthesis in the liver. Mice lacking Mat1a have hepatic SAMe depletion and develop NASH and HCC spontaneously. Several kinases are activated in Mat1a knockout (KO) mice livers.
View Article and Find Full Text PDFThe ER-bound kinase/endoribonuclease (RNase), inositol-requiring enzyme-1 (IRE1), regulates the phylogenetically most conserved arm of the unfolded protein response (UPR). However, the complex biology and pathology regulated by mammalian IRE1 cannot be fully explained by IRE1's one known, specific RNA target, X box-binding protein-1 (XBP1) or the RNA substrates of IRE1-dependent RNA degradation (RIDD) activity. Investigating other specific substrates of IRE1 kinase and RNase activities may illuminate how it performs these diverse functions in mammalian cells.
View Article and Find Full Text PDFObjective: Saturated and trans fat consumption is associated with increased cardiovascular disease (CVD) risk. Current dietary guidelines recommend low fat and significantly reduced trans fat intake. Full fat dairy can worsen dyslipidemia, but recent epidemiological studies show full-fat dairy consumption may reduce diabetes and CVD risk.
View Article and Find Full Text PDFObjective: Trichomonas vaginalis is is a monoxenous parasite which lives in human urogenital systems and causes sex transmitted disease through human sexual contact. Disease frequency has been seen at different rates in different communities or in the same community depending on people's sociocultural status. Previously we made a study for determining prevalence of T.
View Article and Find Full Text PDF