-
Circulation Oct 2023In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory... (Review)
Review
2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, β-adrenergic receptor antagonists (also known as β-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.
Topics: Humans; Adrenergic beta-Antagonists; American Heart Association; Benzodiazepines; Cardiopulmonary Resuscitation; Digoxin; Heart Arrest; United States
PubMed: 37721023
DOI: 10.1161/CIR.0000000000001161 -
Cell Death & Disease Mar 2021Chemotherapeutic agents have been linked to immunogenic cell death (ICD) induction that is capable of augmenting anti-tumor immune surveillance. The cardiac glycoside...
Chemotherapeutic agents have been linked to immunogenic cell death (ICD) induction that is capable of augmenting anti-tumor immune surveillance. The cardiac glycoside oleandrin, which inhibits Na/K-ATPase pump (NKP), has been shown to suppress breast cancer growth via inducing apoptosis. In the present study, we showed that oleandrin treatment triggered breast cancer cell ICD by inducing calreticulin (CRT) exposure on cell surface and the release of high-mobility group protein B1 (HMGB1), heat shock protein 70/90 (HSP70/90), and adenosine triphosphate (ATP). The maturation and activation of dendritic cells (DCs) were increased by co-culturing with the oleandrin-treated cancer cells, which subsequently enhanced CD8 T cell cytotoxicity. Murine breast cancer cell line EMT6 was engrafted into BALB/c mice, and tumor-bearing mice were administered with oleandrin intraperitoneally every day. Oleandrin inhibited tumor growth and increased tumor infiltrating lymphocytes including DCs and T cells. Furthermore, the differential mRNA expression incurred by oleandrin was investigated by mRNA sequencing and subsequently confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Mechanistically, oleandrin induced endoplasmic reticulum (ER) stress-associated, caspase-independent ICD mainly through PERK/elF2α/ATF4/CHOP pathway. Pharmacological and genetic inhibition of protein kinase R-like ER kinase (PERK) suppressed oleandrin-triggered ICD. Taken together, our findings showed that oleandrin triggered ER stress and induced ICD-mediated immune destruction of breast cancer cells. Oleandrin combined with immune checkpoint inhibitors might improve the efficacy of immunotherapy.
Topics: Activating Transcription Factor 4; Animals; Breast Neoplasms; Cardenolides; Cardiac Glycosides; Cell Line, Tumor; Disease Models, Animal; Female; Humans; Immunogenic Cell Death; Mice
PubMed: 33762577
DOI: 10.1038/s41419-021-03605-y -
Nature Metabolism Nov 2019Senescence is a cellular stress response that results in the stable arrest of old, damaged or preneoplastic cells. Oncogene-induced senescence is tumor suppressive but...
Senescence is a cellular stress response that results in the stable arrest of old, damaged or preneoplastic cells. Oncogene-induced senescence is tumor suppressive but can also exacerbate tumorigenesis through the secretion of pro-inflammatory factors from senescent cells. Drugs that selectively kill senescent cells, termed senolytics, have proved beneficial in animal models of many age-associated diseases. Here, we show that the cardiac glycoside, ouabain, is a senolytic agent with broad activity. Senescent cells are sensitized to ouabain-induced apoptosis, a process mediated in part by induction of the pro-apoptotic Bcl2-family protein NOXA. We show that cardiac glycosides synergize with anti-cancer drugs to kill tumor cells and eliminate senescent cells that accumulate after irradiation or in old mice. Ouabain also eliminates senescent preneoplastic cells. Our findings suggest that cardiac glycosides may be effective anti-cancer drugs by acting through multiple mechanism. Given the broad range of senescent cells targeted by cardiac glycosides their use against age-related diseases warrants further exploration.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cardiac Glycosides; Cellular Senescence; Humans; Mice; Ouabain; Quercetin; Rats
PubMed: 31799499
DOI: 10.1038/s42255-019-0122-z -
International Journal of Molecular... Mar 2022Among carbohydrate active enzymes, glycoside phosphorylases (GPs) are valuable catalysts for white biotechnologies, due to their exquisite capacity to efficiently... (Review)
Review
Among carbohydrate active enzymes, glycoside phosphorylases (GPs) are valuable catalysts for white biotechnologies, due to their exquisite capacity to efficiently re-modulate oligo- and poly-saccharides, without the need for costly activated sugars as substrates. The reversibility of the phosphorolysis reaction, indeed, makes them attractive tools for glycodiversification. However, discovery of new GP functions is hindered by the difficulty in identifying them in sequence databases, and, rather, relies on extensive and tedious biochemical characterization studies. Nevertheless, recent advances in automated tools have led to major improvements in GP mining, activity predictions, and functional screening. Implementation of GPs into innovative in vitro and in cellulo bioproduction strategies has also made substantial advances. Herein, we propose to discuss the latest developments in the strategies employed to efficiently discover GPs and make the best use of their exceptional catalytic properties for glycoside bioproduction.
Topics: Biotechnology; Cardiac Glycosides; Catalysis; Glycoside Hydrolases; Glycosides; Phosphorylases
PubMed: 35328479
DOI: 10.3390/ijms23063043 -
Planta Medica Aug 2017This review provides a renewed look at the genus . Emphasis will be put on those issues that attracted the most attention or even went through paradigmatic changes since... (Review)
Review
This review provides a renewed look at the genus . Emphasis will be put on those issues that attracted the most attention or even went through paradigmatic changes since the turn of the millennium. PubMed and Google Scholar were used ("" and "Foxglove" were the key words) to identify research from 2000 till 2017 containing data relevant enough to be presented here. Intriguing new results emerged from studies related to the phylogeny and taxonomy of the genus as well as to the biosynthesis and potential medicinal uses of the key active compounds, the cardiac glycosides. Several Eastern and Western Foxgloves were studied with respect to their propagation In this context, molecular biology tools were applied and phytochemical analyses were conducted. Structure elucidation and analytical methods, which have experienced less exciting progress, will not be considered here in great detail.
Topics: Cardiac Glycosides; Digitalis; Phytochemicals; Plant Extracts; Plants, Medicinal
PubMed: 28561136
DOI: 10.1055/s-0043-111240 -
Toxins May 2021Cardiac glycosides (CGs), toxins well-known for numerous human and cattle poisoning, are natural compounds, the biosynthesis of which occurs in various plants and... (Review)
Review
Cardiac glycosides (CGs), toxins well-known for numerous human and cattle poisoning, are natural compounds, the biosynthesis of which occurs in various plants and animals as a self-protective mechanism to prevent grazing and predation. Interestingly, some insect species can take advantage of the CG's toxicity and by absorbing them, they are also protected from predation. The mechanism of action of CG's toxicity is inhibition of Na/K-ATPase (the sodium-potassium pump, NKA), which disrupts the ionic homeostasis leading to elevated Ca concentration resulting in cell death. Thus, NKA serves as a molecular target for CGs (although it is not the only one) and even though CGs are toxic for humans and some animals, they can also be used as remedies for various diseases, such as cardiovascular ones, and possibly cancer. Although the anticancer mechanism of CGs has not been fully elucidated, yet, it is thought to be connected with the second role of NKA being a receptor that can induce several cell signaling cascades and even serve as a growth factor and, thus, inhibit cancer cell proliferation at low nontoxic concentrations. These growth inhibitory effects are often observed only in cancer cells, thereby, offering a possibility for CGs to be repositioned for cancer treatment serving not only as chemotherapeutic agents but also as immunogenic cell death triggers. Therefore, here, we report on CG's chemical structures, production optimization, and biological activity with possible use in cancer therapy, as well as, discuss their antiviral potential which was discovered quite recently. Special attention has been devoted to digitoxin, digoxin, and ouabain.
Topics: Animals; Antineoplastic Agents; Cardiac Glycosides; Cattle; Digitoxin; Digoxin; Humans; Molecular Targeted Therapy; Neoplasms; Ouabain; Sodium-Potassium-Exchanging ATPase
PubMed: 34064873
DOI: 10.3390/toxins13050344 -
Biomolecules Apr 2021Cardiac glycosides (CGs) are natural steroid compounds occurring both in plants and animals. They are known for long as cardiotonic agents commonly used for various... (Review)
Review
Cardiac glycosides (CGs) are natural steroid compounds occurring both in plants and animals. They are known for long as cardiotonic agents commonly used for various cardiac diseases due to inhibition of Na/K-ATPase (NKA) pumping activity and modulating heart muscle contractility. However, recent studies show that the portfolio of diseases potentially treatable with CGs is much broader. Currently, CGs are mostly studied as anticancer agents. Their antiproliferative properties are based on the induction of multiple signaling pathways in an NKA signalosome complex. In addition, they are strongly connected to immunogenic cell death, a complex mechanism of induction of anticancer immune response. Moreover, CGs exert various immunomodulatory effects, the foremost of which are connected with suppressing the activity of T-helper cells or modulating transcription of many immune response genes by inhibiting nuclear factor kappa B. The resulting modulations of cytokine and chemokine levels and changes in immune cell ratios could be potentially useful in treating sundry autoimmune and inflammatory diseases. This review aims to summarize current knowledge in the field of immunomodulatory properties of CGs and emphasize the large area of potential clinical use of these compounds.
Topics: Animals; Antineoplastic Agents; Cardiac Glycosides; Cell Proliferation; Cytokines; Gene Expression Regulation, Neoplastic; Humans; Immunologic Factors; Neoplasms; Signal Transduction; Sodium-Potassium-Exchanging ATPase
PubMed: 33947098
DOI: 10.3390/biom11050659 -
Journal of the American College of... May 1985Clinical manifestations of digitalis toxicity were clearly described by Withering in 1785. One hundred years later, certain digitalis-induced arrhythmias were inscribed... (Review)
Review
Clinical manifestations of digitalis toxicity were clearly described by Withering in 1785. One hundred years later, certain digitalis-induced arrhythmias were inscribed on the smoked drum, and shortly thereafter with the introduction of the electrocardiograph, manifestations of digitalis toxicity as recognized today were recorded in animals and human beings. With popularization of the direct-writing electrocardiograph in the late 1940s and the introduction of digitoxin in recommended doses (that in retrospect appear inappropriately high), the documented prevalence of digitalis toxicity increased rapidly. With increased understanding of the interaction of electrolytes and digitalis and perhaps, and more importantly, the widespread use of digoxin in doses derived largely from its inotropic action and, thus, inappropriately low for the management of many of the arrhythmias, the prevalence of digitalis toxicity began to decline again. In addition, the advent of serum level determinations and the widespread acceptance of the concept of "therapeutic" levels which, although frequently falling short of the desired clinical end point, served to preclude digitalis toxicity. With the decline in the incidence of digitalis toxicity consequent to these factors, some of the digitalis-related arrhythmias that were common are now rarely observed. This report focuses on arrhythmias that are highly specific for digitalis toxicity and on those that now are less commonly encountered. The discussion and classification of the arrhythmias are based on their most probable electrophysiologic mechanism.
Topics: Animals; Arrhythmias, Cardiac; Digitalis Glycosides; Electrocardiography; Electrophysiology; Heart Block; Heart Conduction System; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Pacemaker, Artificial
PubMed: 3886755
DOI: 10.1016/s0735-1097(85)80467-8 -
Nutrients Apr 2023β-glucans are a polymeric dietary fiber characterized by β-(1,3) and β-(1,4) glycosidic bonds between glucose monomers. They are often used as thickeners,... (Review)
Review
β-glucans are a polymeric dietary fiber characterized by β-(1,3) and β-(1,4) glycosidic bonds between glucose monomers. They are often used as thickeners, stabilizers, and fat substitutes in foods. The functional and technological quality of β-glucans is attributed to their origin/source, molecular weight, and structural properties. In particular, physical treatments such as drying, cooking, freezing, and refrigeration influence their molecular, morphological, and rheological characteristics. In addition to their useful technical qualities, β-glucans are recognized for their numerous beneficial impacts on human health. For this reason, the European Food Safety Authority (EFSA) has provided a positive opinion on health claims such as cholesterol lowering and hypoglycemic properties relating to oats and barley β-glucans. This paper provides insight into the properties of β-glucans and different treatments affecting their characteristics and then reviews the latest research on β-glucans as a functional ingredient for people with type 2 diabetes mellitus (T2DM).
Topics: Humans; Edible Grain; Diabetes Mellitus, Type 2; Avena; Cardiac Glycosides; Cooking
PubMed: 37432266
DOI: 10.3390/nu15092124 -
Cells Nov 2021Drug repositioning is one of the leading strategies in modern therapeutic research. Instead of searching for completely novel substances and demanding studies of their... (Review)
Review
Drug repositioning is one of the leading strategies in modern therapeutic research. Instead of searching for completely novel substances and demanding studies of their biological effects, much attention has been paid to the evaluation of commonly used drugs, which could be utilized for more distinct indications than they have been approved for. Since treatment approaches for cancer, one of the most extensively studied diseases, have still been very limited, great effort has been made to find or repurpose novel anticancer therapeutics. One of these are cardiac glycosides, substances commonly used to treat congestive heart failure or various arrhythmias. Recently, the antitumor properties of cardiac glycosides have been discovered and, therefore, these compounds are being considered for anticancer therapy. Their mechanism of antitumor action seems to be rather complex and not fully uncovered yet, however, autophagy has been confirmed to play a key role in this process. In this review article, we report on the up-to-date knowledge of the anticancer activity of cardiac glycosides with special attention paid to autophagy induction, the molecular mechanisms of this process, and the potential employment of this phenomenon in clinical practice.
Topics: Animals; Apoptosis; Autophagy; Biomarkers; Cardiac Glycosides; Humans; Models, Biological; Sodium-Potassium-Exchanging ATPase
PubMed: 34943848
DOI: 10.3390/cells10123341