3D-Printed Myocardium-Specific Structure Enhances Maturation and Therapeutic Efficacy of Engineered Heart Tissue in Myocardial Infarction.

Despite advancements in engineered heart tissue (EHT), challenges persist in achieving accurate dimensional accuracy of scaffolds and maturing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), a primary source of functional cardiac cells. Drawing inspiration from cardiac muscle fiber arrangement, a three-dimensional (3D)-printed multi-layered microporous polycaprolactone (PCL) scaffold is created with interlayer angles set at 45° to replicate the precise structure of native cardiac tissue. Compared with the control group and 90° PCL scaffolds, the 45° PCL scaffolds exhibited superior biocompatibility for cell culture and improved hiPSC-CM maturation in calcium handling.

Follistatin From hiPSC-Cardiomyocytes Promotes Myocyte Proliferation in Pigs With Postinfarction LV Remodeling.

Background: When human induced pluripotent stem cells (hiPSCs) that CCND2-OE (overexpressed cyclin-D2) were differentiated into cardiomyocytes (hiPSC-CMs) and administered to the infarcted hearts of immunodeficient mice, the cells proliferated after administration and repopulated >50% of the scar. Here, we knocked out human leukocyte antigen class I and class II expression in hiPSC-CMs (hiPSC-CMs) to reduce the cells' immunogenicity and then assessed the therapeutic efficacy of hiPSC-CMs for the treatment of myocardial infarction.

Methods: hiPSC-CM and wild-type hiPSC-CM (hiPSC-CM) spheroids were differentiated in shaking flasks, purified, characterized, and intramyocardially injected into pigs after ischemia/reperfusion injury; control animals were injected with basal medium.

From Global to Nano: A Geographical Perspective of .

The periodontal disease pathobiont () may exert a range of detrimental effects on periodontal diseases in general and, more specifically, with the initiation and progression of Localized Stage III Grade C periodontitis (molar-incisor pattern). In this review of the biogeography of this pathobiont, the full range of geographical scales for , from global origins and transmission to local geographical regions, to more locally exposed probands and families, to the individual host, down to the oral cavity, and finally, to spatial interactions with other commensals and pathobionts within the plaque biofilms at the micron/nanoscale, are reviewed. Using the newest technologies in genetics, imaging, in vitro cultures, and other research disciplines, investigators may be able to gain new insights to the role of this pathobiont in the unique initial destructive patterns of Localized Stage III Grade C periodontitis.

Regulators of placental antibody transfer through a modeling lens.

Infants are vulnerable to infections owing to a limited ability to mount a humoral immune response and their tolerogenic immune phenotype, which has impeded the success of newborn vaccination. Transplacental transfer of IgG from mother to fetus provides crucial protection in the first weeks of life, and maternal immunization has recently been implemented as a public health strategy to protect newborns against serious infections. Despite their early success, current maternal vaccines do not provide comparable protection across pregnancies with varying gestational lengths and placental and maternal immune features, and they do not account for the dynamic interplay between the maternal immune response and placental transfer.

Doxycycline-Mediated Control of Cyclin D2 Overexpression in Human-Induced Pluripotent Stem Cells.

Previous studies have demonstrated that when the cyclin D2 (CCND2), a cell-cycle regulatory protein, is overexpressed in human-induced pluripotent stem cells (hiPSCs), cardiomyocytes (CMs) differentiated from these CCND2-overexpressing hiPSCs can proliferate after transplantation into infarcted hearts, which significantly improves the cells' potency for myocardial regeneration. However, persistent CM proliferation could lead to tumor growth or the development of arrhythmogenic complications; thus, the goal of the current study was to generate a line of hiPSCs in which CCND2 overexpression could be tightly controlled. First, we transfected hiPSCs with vectors coding for a doxycycline-inducible Tet-On transactivator and dCas9 fused to the VPR activation domain; then, the same hiPSCs were engineered to express guide RNAs targeting the CCND2 promotor.

CRISPR screen of venetoclax response-associated genes identifies transcription factor ZNF740 as a key functional regulator.

BCL-2 inhibitors such as venetoclax offer therapeutic promise in acute myeloid leukemia (AML) and other cancers, but drug resistance poses a significant challenge. It is crucial to understand the mechanisms that regulate venetoclax response. While correlative studies have identified numerous genes linked to venetoclax sensitivity, their direct impact on the drug response remains unclear.

Identification of FDA-approved drugs that induce heart regeneration in mammals.

Targeting Meis1 and Hoxb13 transcriptional activity could be a viable therapeutic strategy for heart regeneration. In this study, we performd an in silico screening to identify FDA-approved drugs that can inhibit Meis1 and Hoxb13 transcriptional activity based on the resolved crystal structure of Meis1 and Hoxb13 bound to DNA. Paromomycin (Paro) and neomycin (Neo) induced proliferation of neonatal rat ventricular myocytes in vitro and displayed dose-dependent inhibition of Meis1 and Hoxb13 transcriptional activity by luciferase assay and disruption of DNA binding by electromobility shift assay.

Epigenetic regulation of noncanonical menin targets modulates menin inhibitor response in acute myeloid leukemia.

Menin inhibitors that disrupt the menin-MLL interaction hold promise for treating specific acute myeloid leukemia (AML) subtypes, including those with KMT2A rearrangements (KMT2A-r), yet resistance remains a challenge. Here, through systematic chromatin-focused CRISPR screens, along with genetic, epigenetic, and pharmacologic studies in a variety of human and mouse KMT2A-r AML models, we uncovered a potential resistance mechanism independent of canonical menin-MLL targets. We show that a group of noncanonical menin targets, which are bivalently cooccupied by active menin and repressive H2AK119ub marks, are typically downregulated after menin inhibition.

Exosomes: Methods for Isolation and Characterization in Biological Samples.

Exosomes are small lipid bilayer-encapsulated nanosized extracellular vesicles of endosomal origin. Exosomes are secreted by almost all cell types and are a crucial player in intercellular communication. Exosomes transmit cellular information from donor to recipient cells in the form of proteins, lipids, and nucleic acids and influence several physiological and pathological responses.

Fibroblast-Specific Depletion of Human Antigen R Alleviates Myocardial Fibrosis Induced by Cardiac Stress.

Cardiac fibrosis can be mitigated by limiting fibroblast-to-myofibroblast differentiation and proliferation. Human antigen R (HuR) modulates messenger RNA stability and expression of multiple genes. However, the direct role of cardiac myofibroblast HuR is unknown.

Rapid, antibiotic incubation-free determination of tuberculosis drug resistance using machine learning and Raman spectroscopy.

Tuberculosis (TB) is the world's deadliest infectious disease, with over 1.5 million deaths and 10 million new cases reported anually. The causative organism (Mtb) can take nearly 40 d to culture, a required step to determine the pathogen's antibiotic susceptibility.

Circadian control of histone turnover during cardiac development and growth.

During postnatal cardiac hypertrophy, cardiomyocytes undergo mitotic exit, relying on DNA replication-independent mechanisms of histone turnover to maintain chromatin organization and gene transcription. In other tissues, circadian oscillations in nucleosome occupancy influence clock-controlled gene expression, suggesting a role for the circadian clock in temporal control of histone turnover and coordinated cardiomyocyte gene expression. We sought to elucidate roles for the master circadian transcription factor, Bmal1, in histone turnover, chromatin organization, and myocyte-specific gene expression and cell growth in the neonatal period.

Posttranscriptional regulation of the T-box gene midline via the 3'UTR in Drosophila is complex and cell- and tissue-dependent.

The T-box (Tbx) proteins have a 180-230 amino acid DNA-binding domain, first reported in the Brachyury (T) protein. They are highly conserved among metazoans. They regulate a multitude of cellular functions in development and disease.

Histone H1.0 couples cellular mechanical behaviors to chromatin structure.

Tuning of genome structure and function is accomplished by chromatin-binding proteins, which determine the transcriptome and phenotype of the cell. Here we investigate how communication between extracellular stress and chromatin structure may regulate cellular mechanical behaviors. We demonstrate that histone H1.

Acoustic Trapping and Manipulation of Hollow Microparticles under Fluid Flow Using a Single-Lens Focused Ultrasound Transducer.

Microparticle manipulation and trapping play pivotal roles in biotechnology. To achieve effective manipulation within fluidic flow conditions and confined spaces, it is necessary to consider the physical properties of microparticles and the types of trapping forces applied. While acoustic waves have shown potential for manipulating microparticles, the existing setups involve complex actuation mechanisms and unstable microbubbles.

Size-Dependent Locomotion Ability of Surface Microrollers on Physiologically Relevant Microtopographical Surfaces.

Controlled microrobotic navigation inside the body possesses significant potential for various biomedical engineering applications. Successful application requires considering imaging, control, and biocompatibility. Interaction with biological environments is also a crucial factor in ensuring safe application, but can also pose counterintuitive hydrodynamic barriers, limiting the use of microrobots.

The mismatch between experimental and computational fluid dynamics analyses for magnetic surface microrollers.

Magnetically actuated Janus surface microrollers are promising microrobotic platform with numerous potential biomedical engineering applications. While the locomotion models based on a "rotating sphere on a nearby wall" can be adapted to surface microrollers, real-world dynamics may differ from the proposed theories/simulations. In this study, we examine the locomotion efficiency of surface microrollers with diameters of 5, 10, 25, and 50 µm and demonstrate that computational fluid dynamics simulations cannot accurately capture locomotion characteristics for different sizes of microrollers.

Rapid, antibiotic incubation-free determination of tuberculosis drug resistance using machine learning and Raman spectroscopy.

Tuberculosis (TB) is the world's deadliest infectious disease, with over 1.5 million deaths annually and 10 million new cases reported each year. The causative organism, (Mtb) can take nearly 40 days to culture, a required step to determine the pathogen's antibiotic susceptibility.

Analysis of cardiac single-cell RNA-sequencing data can be improved by the use of artificial-intelligence-based tools.

Single-cell RNA sequencing (scRNAseq) enables researchers to identify and characterize populations and subpopulations of different cell types in hearts recovering from myocardial infarction (MI) by characterizing the transcriptomes in thousands of individual cells. However, the effectiveness of the currently available tools for processing and interpreting these immense datasets is limited. We incorporated three Artificial Intelligence (AI) techniques into a toolkit for evaluating scRNAseq data: AI Autoencoding separates data from different cell types and subpopulations of cell types (cluster analysis); AI Sparse Modeling identifies genes and signaling mechanisms that are differentially activated between subpopulations (pathway/gene set enrichment analysis), and AI Semisupervised Learning tracks the transformation of cells from one subpopulation into another (trajectory analysis).

Combining Acoustic Bioprinting with AI-Assisted Raman Spectroscopy for High-Throughput Identification of Bacteria in Blood.

Identifying pathogens in complex samples such as blood, urine, and wastewater is critical to detect infection and inform optimal treatment. Surface-enhanced Raman spectroscopy (SERS) and machine learning (ML) can distinguish among multiple pathogen species, but processing complex fluid samples to sensitively and specifically detect pathogens remains an outstanding challenge. Here, we develop an acoustic bioprinter to digitize samples into millions of droplets, each containing just a few cells, which are identified with SERS and ML.

E2F1-Deficient Adipose-Derived Stem Cells Improve Wound Closure in Mice by Up-Regulating Expression of VEGF and TGF-β1.

Background: Wound healing is a widespread health problem that imposes a financial burden on health systems. Cell therapy with genetically modified adipose-derived stem cells (ADSCs) is a promising strategy for dysregulated wound repair. E2F transcription factor 1 (E2F1) is a bidirectional regulator of cytokines.