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Methodist DeBakey Cardiovascular Journal 2023Vasoplegia is a condition characterized by persistent low systemic vascular resistance despite a normal or high cardiac index, resulting in profound and uncontrolled... (Review)
Review
Vasoplegia is a condition characterized by persistent low systemic vascular resistance despite a normal or high cardiac index, resulting in profound and uncontrolled vasodilation. Vasoplegia may occur due to various conditions, including cardiac failure, sepsis, and post-cardiac surgery. In the cardiac cohort, multiple risk factors for vasoplegia have been identified. Several factors contribute to the pathophysiology of this condition, and various mechanisms have been proposed, including nitric oxide, adenosine, prostanoids, endothelins, the renin-angiotensin-aldosterone system, and hydrogen sulfide. Early identification and prompt management of vasoplegia is crucial to prevent development of shock. This review expands upon the different vasopressors used in management of vasoplegia, including catecholamines such as norepinephrine, dopamine, epinephrine, phenylephrine, and other agents including vasopressin, methylene blue, angiotensin II, hydroxocobalamin, vitamin C, thiamine, and corticosteroids (ie, hydrocortisone). It also emphasizes the importance of conducting further research and making advancements in treatment regimens for vasoplegia.
Topics: Humans; Vasoplegia; Epinephrine; Norepinephrine; Phenylephrine; Sepsis
PubMed: 37547893
DOI: 10.14797/mdcvj.1245 -
Advanced Science (Weinheim,... Aug 2023Treatment of infected wounds remains a challenge owing to antibiotic resistance; thus, developing smart biomaterials for the healing of infected wounds is urgently...
Treatment of infected wounds remains a challenge owing to antibiotic resistance; thus, developing smart biomaterials for the healing of infected wounds is urgently needed. In this study, a microneedle (MN) patch system with antimicrobial and immunomodulatory properties is developed to promote and accelerate infected wound healing. In the MN patch (termed PFG/M MNs), a nanoparticle with polydopamine (PDA)-loaded iron oxide is grafted with glucose oxidase (GOx) and hyaluronic acid (HA) and then integrated into the tips, and amine-modified mesoporous silica nanoparticles (AP-MSNs) are incorporated into the bases. Results show that PFG/M MNs eradicate bacterial infections and modulate the immune microenvironment, combining the advantages of chemodynamic therapy, photothermal therapy, and M2 macrophage polarization from Fe/PDA@GOx@HA in the tips as well as anti-inflammatory effect of AP-MSNs from the MN bases. Thus, the PFG/M MN system is a promising clinical candidate for promoting infected wound healing.
Topics: Anti-Infective Agents; Amines; Biocompatible Materials; Drug Delivery Systems; Glucose Oxidase; Hyaluronic Acid
PubMed: 37202594
DOI: 10.1002/advs.202300576 -
Developmental Medicine and Child... Apr 2024Bachmann-Bupp syndrome (BABS) is a neurodevelopmental disorder characterized by developmental delay, hypotonia, and varying forms of non-congenital alopecia. The... (Review)
Review
Bachmann-Bupp syndrome (BABS) is a neurodevelopmental disorder characterized by developmental delay, hypotonia, and varying forms of non-congenital alopecia. The condition is caused by 3'-end mutations of the ornithine decarboxylase 1 (ODC1) gene, which produce carboxy (C)-terminally truncated variants of ODC, a pyridoxal 5'-phosphate-dependent enzyme. C-terminal truncation of ODC prevents its ubiquitin-independent proteasomal degradation and leads to cellular accumulation of ODC enzyme that remains catalytically active. ODC is the first rate-limiting enzyme that converts ornithine to putrescine in the polyamine pathway. Polyamines (putrescine, spermidine, spermine) are aliphatic molecules found in all forms of life and are important during embryogenesis, organogenesis, and tumorigenesis. BABS is an ultra-rare condition with few reported cases, but it serves as a convincing example for drug repurposing therapy. α-Difluoromethylornithine (DFMO, also known as eflornithine) is an ODC inhibitor with a strong safety profile in pediatric use for neuroblastoma and other cancers as well as West African sleeping sickness (trypanosomiasis). Patients with BABS have been treated with DFMO and have shown improvement in hair growth, muscle tone, and development.
Topics: Humans; Child; Putrescine; Spermidine; Polyamines; Spermine; Eflornithine
PubMed: 37469105
DOI: 10.1111/dmcn.15687 -
Nature Communications Aug 2023The incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota...
The incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota is causatively linked with the development of both metabolic dysfunctions and gastrointestinal disorders, thus gut dysbiosis in IBS may contribute to the development of metabolic syndrome. Here, we show that human gut bacterium Ruminococcus gnavus-derived tryptamine and phenethylamine play a pathogenic role in gut dysbiosis-induced insulin resistance in type 2 diabetes (T2D) and IBS. We show levels of R. gnavus, tryptamine, and phenethylamine are positively associated with insulin resistance in T2D patients and IBS patients. Monoassociation of R. gnavus impairs insulin sensitivity and glucose control in germ-free mice. Mechanistically, treatment of R. gnavus-derived metabolites tryptamine and phenethylamine directly impair insulin signaling in major metabolic tissues of healthy mice and monkeys and this effect is mediated by the trace amine-associated receptor 1 (TAAR1)-extracellular signal-regulated kinase (ERK) signaling axis. Our findings suggest a causal role for tryptamine/phenethylamine-producers in the development of insulin resistance, provide molecular mechanisms for the increased prevalence of metabolic syndrome in IBS, and highlight the TAAR1 signaling axis as a potential therapeutic target for the management of metabolic syndrome induced by gut dysbiosis.
Topics: Humans; Animals; Mice; Insulin Resistance; Metabolic Syndrome; Irritable Bowel Syndrome; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Dysbiosis; Phenethylamines; Tryptamines
PubMed: 37591886
DOI: 10.1038/s41467-023-40552-y -
Nature Feb 2024Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes; however, the bacterial gene(s)...
Bacteria in the gastrointestinal tract produce amino acid bile acid amidates that can affect host-mediated metabolic processes; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.
Topics: Humans; Acyltransferases; Amidohydrolases; Amines; Bacteroides fragilis; Bile Acids and Salts; Biocatalysis; Cohort Studies; Escherichia coli; Gastrointestinal Microbiome; Ligands; Pregnane X Receptor; Receptors, Aryl Hydrocarbon; Transcription Factors; Infant; Cell Culture Techniques
PubMed: 38326609
DOI: 10.1038/s41586-023-06990-w -
Cell Communication and Signaling : CCS Dec 2023Polyamines are essential for the growth and proliferation of mammalian cells and are intimately involved in biological mechanisms such as DNA replication, RNA... (Review)
Review
Polyamines are essential for the growth and proliferation of mammalian cells and are intimately involved in biological mechanisms such as DNA replication, RNA transcription, protein synthesis, and post-translational modification. These mechanisms regulate cellular proliferation, differentiation, programmed cell death, and the formation of tumors. Several studies have confirmed the positive effect of polyamines on the maintenance of health, while others have demonstrated that their activity may promote the occurrence and progression of diseases. This review examines a variety of topics, such as polyamine source and metabolism, including metabolism, transport, and the potential impact of polyamines on health and disease. In addition, a brief summary of the effects of oncogenes and signaling pathways on tumor polyamine metabolism is provided. Video Abstract.
Topics: Animals; Humans; Polyamines; Apoptosis; RNA; Neoplasms; Cell Proliferation; Mammals
PubMed: 38049863
DOI: 10.1186/s12964-023-01373-0 -
Marine Drugs Nov 2023A Chitosan is a copolymer of N-acetyl-D-glucose amine and D-glucose amine that can be easily produced. It is a polymer that is widely utilized to create nanoparticles... (Review)
Review
A Chitosan is a copolymer of N-acetyl-D-glucose amine and D-glucose amine that can be easily produced. It is a polymer that is widely utilized to create nanoparticles (NPs) with specific properties for applications in a wide range of human activities. Chitosan is a substance with excellent prospects due to its antibacterial, anti-inflammatory, antifungal, haemostatic, analgesic, mucoadhesive, and osseointegrative qualities, as well as its superior film-forming capacity. Chitosan nanoparticles (NPs) serve a variety of functions in the pharmaceutical and medical fields, including dentistry. According to recent research, chitosan and its derivatives can be embedded in materials for dental adhesives, barrier membranes, bone replacement, tissue regeneration, and antibacterial agents to improve the management of oral diseases. This narrative review aims to discuss the development of chitosan-containing materials for dental and implant engineering applications, as well as the challenges and future potential. For this purpose, the PubMed database (Medline) was utilised to search for publications published less than 10 years ago. The keywords used were "chitosan coating" and "dentistry". After carefully selecting according to these keywords, 23 articles were studied. The review concluded that chitosan is a biocompatible and bioactive material with many benefits in surgery, restorative dentistry, endodontics, prosthetics, orthodontics, and disinfection. Furthermore, despite the fact that it is a highly significant and promising coating, there is still a demand for various types of coatings. Chitosan is a semi-synthetic polysaccharide that has many medical applications because of its antimicrobial properties. This article aims to review the role of chitosan in dental implantology.
Topics: Humans; Chitosan; Biocompatible Materials; Dentistry; Anti-Bacterial Agents; Polymers; Amines; Glucose
PubMed: 38132934
DOI: 10.3390/md21120613 -
International Journal of Molecular... Nov 2023Polyamines (Pas) are short molecules that exhibit two or three amine groups that are positively charged at a physiological pH. These small molecules are present in high... (Review)
Review
Polyamines (Pas) are short molecules that exhibit two or three amine groups that are positively charged at a physiological pH. These small molecules are present in high concentrations in a wide variety of organisms and tissues, suggesting that they play an important role in cellular physiology. Polyamines include spermine, spermidine, and putrescine, which play important roles in age-related diseases that have not been completely elucidated. Aging is a natural process, defined as the time-related deterioration of the physiological functions; it is considered a risk factor for degenerative diseases such as cardiovascular, neurodegenerative, and musculoskeletal diseases; arthritis; and even cancer. In this review, we provide a new perspective on the participation of Pas in the cellular and molecular processes related to age-related diseases, focusing our attention on important degenerative diseases such as Alzheimerߣs disease, Parkinsonߣs disease, osteoarthritis, sarcopenia, and osteoporosis. This new perspective leads us to propose that Pas function as novel biomarkers for age-related diseases, with the main purpose of achieving new molecular alternatives for healthier aging.
Topics: Polyamines; Spermidine; Spermine; Putrescine
PubMed: 38003659
DOI: 10.3390/ijms242216469 -
Anesthesiology May 2024
Topics: Bupivacaine
PubMed: 38592361
DOI: 10.1097/ALN.0000000000004934 -
Journal of the American Chemical Society Nov 2023Aleutianamine is a recently isolated pyrroloiminoquinone natural product that displays potent and selective biological activity toward human pancreatic cancer cells with...
Aleutianamine is a recently isolated pyrroloiminoquinone natural product that displays potent and selective biological activity toward human pancreatic cancer cells with an IC of 25 nM against PANC-1, making it a potential candidate for therapeutic development. We report a synthetic approach to aleutianamine wherein the unique [3.3.1] ring system and tertiary sulfide of this alkaloid were constructed via a novel palladium-catalyzed dearomative thiophene functionalization. Other highlights of the synthesis include a palladium-catalyzed decarboxylative pinacol-type rearrangement of an allylic carbonate to install a ketone and a late-stage oxidative amination. This concise and convergent strategy will enable access to analogues of aleutianamine and further investigation of the biological activity of this unique natural product.
Topics: Humans; Palladium; Catalysis; Stereoisomerism; Amination; Biological Products
PubMed: 37967164
DOI: 10.1021/jacs.3c10212