Cardiomyocyte engineering: The meeting point of transcription factors, signaling networks, metabolism and function.

Direct cardiac reprogramming or transdifferentiation is a relatively new and promising area in regenerative therapy, cardiovascular disease modeling, and drug discovery. Effective reprogramming of fibroblasts is limited by their plasticity, that is, their ability to reprogram, and depends on solving several levels of tasks: inducing cardiomyocyte-like cells and obtaining functionally and metabolically mature cardiomyocytes. Currently, in addition to the use of more classical approaches such as overexpression of exogenous transcription factors, activation of endogenous cardiac transcription factors via controlled nucleases, such as CRISPR, represents another interesting way to obtain cardiomyocytes.

Pyridoxal-5-phosphate mitigates age-related metabolic imbalances in the rat heart through the HS/AKT/GSK3β signaling axis.

Pyridoxal-5-phosphate (PLP) enhances the synthesis of endogenous hydrogen sulfide, a potent regulator of cell metabolism. We used 24-month-old rats to investigate the PLP mitoprotective function in the aging heart. We demonstrated improvement of mitochondrial bioenergetic functions, inhibition of mPTP opening after PLP administration.

The resilience of Ukrainian scientists.

We have asked Ukrainian scientists how they have been able to persist in pursuing their research since the beginning of the full-scale invasion of Ukraine by the Russian Federation in February of 2022. We thank the scientists who were willing to share their thoughts and experiences; the views expressed are those of the contributors alone.

WNT/β-catenin pathway is a key regulator of cardiac function and energetic metabolism.

The WNT/β-catenin pathway is a master regulator of cardiac development and growth, and its activity is low in healthy adult hearts. However, even this low activity is essential for maintaining normal heart function. Acute activation of the WNT/β-catenin signaling cascade is considered to be cardioprotective after infarction through the upregulation of prosurvival genes and reprogramming of metabolism.

Influence of Natural and Climatic Conditions on the Distribution and Forms of Contagious Agalactia in Sheep in Bessarabia, Ukraine.

Introduction: Contagious agalactia of ruminants is an endemic disease caused by in flicting significant losses on farms in deaths and forced slaughter of sick animals, abortions, births of sick young animals, and reduced milk and wool production. The aim of the study was to determine the influence of hydrometeorological conditions on the distribution and forms of contagious agalactia in sheep in Bessarabia, Ukraine.

Material And Methods: The epizootic situation regarding contagious agalactia was studied during 2011-2021 on sheep farms in the south of the Odesa region in Bessarabia.

Cardiac-specific β-catenin deletion dysregulates energetic metabolism and mitochondrial function in perinatal cardiomyocytes.

β-Catenin signaling pathway regulates cardiomyocytes proliferation and differentiation, though its involvement in metabolic regulation of cardiomyocytes remains unknown. We used one-day-old mice with cardiac-specific knockout of β-catenin and neonatal rat ventricular myocytes treated with β-catenin inhibitor to investigate the role of β-catenin metabolism regulation in perinatal cardiomyocytes. Transcriptomics of perinatal β-catenin-ablated hearts revealed a dramatic shift in the expression of genes involved in metabolic processes.

Induction of Glutathione Synthesis Provides Cardioprotection Regulating NO, AMPK and PPARa Signaling in Ischemic Rat Hearts.

Glutathione (GSH) is essential for antioxidant defence, and its depletion is associated with tissue damage during cardiac ischemia-reperfusion (I/R). GSH is synthesized by the glutamate-cysteine ligase enzyme (GCL) from L-cysteine, which alternatively might be used for hydrogen sulfide production by cystathionine-gamma-lyase (CSE). Here, we have investigated whether in vivo treatment with L-cysteine and an inhibitor of CSE,D,L-propargylglycine (PAG), can modulate cardiac glutathione and whether this treatment can influence heart resistance to I/R in a Langendorff isolated rat hearts model.

β-Catenin Regulates Cardiac Energy Metabolism in Sedentary and Trained Mice.

The role of canonical Wnt signaling in metabolic regulation and development of physiological cardiac hypertrophy remains largely unknown. To explore the function of β-catenin in the regulation of cardiac metabolism and physiological cardiac hypertrophy development, we used mice heterozygous for cardiac-specific knockout that were subjected to a swimming training model. haploinsufficient mice subjected to endurance training displayed a decreased β-catenin transcriptional activity, attenuated cardiomyocytes hypertrophic growth, and enhanced activation of AMP-activated protein kinase (AMPK), phosphoinositide-3-kinase-Akt (Pi3K-Akt), and mitogen-activated protein kinase/extracellular signal-regulated kinases 1/2 (MAPK/Erk1/2) signaling pathways compared to trained wild type mice.

Correction to: Cardiospecific deletion of αE-catenin leads to heart failure and lethality in mice.

The original version of this article unfortunately contained a mistake. The published paper presented an incorrect version of Table 1. The corrected Table is given here.

Cardiospecific deletion of αE-catenin leads to heart failure and lethality in mice.

αE-catenin is a component of adherens junctions that link the cadherin-catenin complex to the actin cytoskeleton. The signaling function of this protein was recently revealed. In the present study, we investigated the role of αE-catenin in the pathogenesis of heart failure.

The canonical way to make a heart: β-catenin and plakoglobin in heart development and remodeling.

The main mediator of the canonical Wnt pathway, β-catenin, is a major effector of embryonic development, postnatal tissue homeostasis, and adult tissue regeneration. The requirement for β-catenin in cardiogenesis and embryogenesis has been well established. However, many questions regarding the molecular mechanisms by which β-catenin and canonical Wnt signaling regulate these developmental processes remain unanswered.

Possible mechanisms of Leukoagglutinin induced apoptosis in human cells in vitro.

Leukoagglutinin is one of the phytohemagglutinin isolectins isolated from Phaseolus vulgaris. In our recent study, we showed that this lectin is able to influence the growth of human cancer cells in vitro. In addition, using the acridine orange and ethidium bromide staining, we found that leukoagglutinin can induce apoptosis.

Isolectins of phytohemagglutinin are able to induce apoptosis in HEp-2 carcinoma cells in vitro.

Aim: To study the effects of total phytohemagglutinin (PHA) and its isolectins on cell death and apoptosis in human HEp-2 carcinoma cells and to analyze the possible molecular mechanisms of lectin induced apoptosis.

Materials And Methods: The commercial preparation of the kidney beans (Phaseolus vulgaris) lectins and HEp-2 cells were used. Apoptosis index was determined using acridine orange and ethidium bromide staining.

[Proapoptotic properties of total phytohemagglutinine and its individual isolectins in human cell culture 4BL].

Phytohemagglutinine (PHA) is widely investigated lectin with mitogenic properties. Recently it was shown that PHA is not only cell proliferation inducer, but also has a toxic or cytostatic effect. However concentration dependence and molecular mechanisms of this effect are not enough investigated.

[The Wnt/beta-catenin signaling in embryonic cardiogenesis, postnatal development and myocardium reconstruction].

Wnt/beta-catenin signaling exerts great and diverse influence on the formation, development and vital activity of a great number of vertebrate tissues, including heart tissue. The role of Wnt/beta-catenin signaling and beta-catenin itself in the processes of cardiogenesis and adult myocardium functioning is not fully elucidated to date. In the current review we made the attempt to generalize data from up-to-date literature dealing with participation of this signaling pathway in embryogenesis and postnatal heart development as well as in adult myocardium functioning in normal conditions and during stress adaptation, aging, resulting in hypertrophy and heart remodeling.

Requirement for N-cadherin-catenin complex in heart development.

Cell adhesion, mediated by N-cadherin, is critical for embryogenesis since N-cadherin-null embryos die during mid-gestation with multiple developmental defects. To investigate the role of N-cadherin in heart muscle development, N-cadherin was specifically deleted from myocardial cells in mice. The structural integrity of the myocardial cell wall was compromised in the N-cadherin mutant embryos, leading to a malformed heart and a delay in embryonic development.

[Influence of exogeneous proteins on mutagenic process].

Mutagenic factors of biological origin by the example of carbohydrate-binding proteins are observed. An attempt of summarizing the existing data concerning participation of exogenous macromolecules in mutagenic process is made. The mechanisms of the influence of exogenous macromolecules on mutagenesis, proliferation, and surviving of mammalian cells are discussed.

[The influence of lectins on some repair processes in mammalian cells in vitro].

The influence of plant lectins on primary DNA damage repair and on expression of repair enzyme alkylguanine-DNA alkyltransferase (MGMT) in mammalian cells in vitro has been investigated. Those lectins have been shown to modify DNA damage repair process, and to induce the MGMT expression increasing its level in the used model system.