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Despite the well-known relevance of polyamines to many forms of life, little is known about how polyamines regulate osteogenesis and skeletal homeostasis. Here, we report a series of in vitro studies conducted with human-bone-marrow-derived pluripotent stromal cells (MSCs). First, we show that during osteogenic differentiation, mRNA levels of most polyamine-associated enzymes are relatively constant, except for the catabolic enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1), which is strongly increased at both mRNA and protein levels. As a result, the intracellular spermidine to spermine ratio is significantly reduced during the early stages of osteoblastogenesis. Supplementation of cells with exogenous spermidine or spermine decreases matrix mineralization in a dose-dependent manner. Employing N-cyclohexyl-1,3-propanediamine (CDAP) to chemically inhibit spermine synthase (SMS), the enzyme catalyzing conversion of spermidine into spermine, also suppresses mineralization. Intriguingly, this reduced mineralization is rescued with DFMO, an inhibitor of the upstream polyamine enzyme ornithine decarboxylase (ODC1). Similarly, high concentrations of CDAP cause cytoplasmic vacuolization and alter mitochondrial function, which are also reversible with the addition of DFMO. Altogether, these studies suggest that excess polyamines, especially spermidine, negatively affect hydroxyapatite synthesis of primary MSCs, whereas inhibition of polyamine synthesis with DFMO rescues most, but not all of these defects. These findings are relevant for patients with Snyder-Robinson syndrome (SRS), as the presenting skeletal defects-associated with SMS deficiency-could potentially be ameliorated by treatment with DFMO.

Metabolic dysregulation is a key driver of cellular senescence, contributing to the progression of systemic aging. The heterogeneity of senescent cells and their metabolic shifts are complex and unexplored. A microfluidic SlipChip integrated with surface‐enhanced Raman spectroscopy (SERS), termed SlipChip‐SERS, is developed for single‐cell metabolism analysis. This SlipChip‐SERS enables compartmentalization of single cells, parallel delivery of saponin and nanoparticles to release intracellular metabolites and to realize SERS detection with simple slipping operations. Analysis of different cancer cell lines using SlipChip‐SERS demonstrated its capability for sensitive and multiplexed metabolic profiling of individual cells. When applied to human primary fibroblasts of different ages, it identified 12 differential metabolites, with spermine validated as a potent inducer of cellular senescence. Prolonged exposure to spermine can induce a classic senescence phenotype, such as increased senescence‐associated β‐glactosidase activity, elevated expression of senescence‐related genes and reduced LMNB1 levels. Additionally, the senescence‐inducing capacity of spermine in HUVECs and WRL‐68 cells is confirmed, and exogenous spermine treatment increased the accumulation and release of H2O2. Overall, a novel SlipChip‐SERS system is developed for single‐cell metabolic analysis, revealing spermine as a potential inducer of senescence across multiple cell types, which may offer new strategies for addressing ageing and ageing‐related diseases. [ABSTRACT FROM AUTHOR]

Objective: Major depressive disorder (MDD) is common in childhood, but its etiopathogenesis is still unclear. Published neurochemical studies mostly focus on monoaminergic system, however, the pathophysiology of MDD cannot be explained by monoamine hypothesis only, medications that have effect on monoamines cannot have effect needed in all patients. We aimed to investigate the poliamine pathway of L-arginine metabolism which is proceeding by way of agmatine in adolescents with MDD. Methods: Our study involved 45 patients with MDD (case group), and 44 healthy controls (control group) between the ages of 13-17. Sociodemographic data form, Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version-DSM-5-Turkish, Beck Depression Inventory (BDI), Spielberger's State-Trait Anxiety Inventory were applied to all subjects. All subjects were evaluated in terms of the levels of serum agmatine, putrescine, spermidine, and spermine. Results: The levels of agmatine and spermine were significantly higher and putrescine and spermidine were significantly lower in case group compared with healthy controls. There was significant negative correlation with the levels of putrescine and spermidine between BDI scores, and there was significant positive correlation between the levels of spermine and BDI scores. No correlation found between the levels of agmatine and BDI scores. Conclusion: These differences that the levels of agmatine and polyamines in the MDD group seem to be a field that worth researching. In the future, the evaluation of the arginine/polyamine metabolism in MDD with larger sample and longitudinal studies is going to capable to contribute to a better understanding of the disorder. [ABSTRACT FROM AUTHOR]

Introduction: Alfalfa (Medicago sativa L.) is a globally important legume crop with high nutritional and ecological value. Drought poses a serious threat to alfalfa acreage and yields. Spermine (Spm) has been shown to protect plants from drought damage. The aim of this study was to clarify the mechanism of exogenous Spm to improve drought resistance of alfalfa. Methods: In this study, we root applied 0.1, 0.5, and 1mM Spm to Gannong No. 3 (G3) alfalfa under drought stress, and then determined their physiological and metabolic changes. Results: The results showed that exogenous Spm increased chlorophyll content, chlorophyll fluorescence parameters and gas exchange parameters, enhanced antioxidant enzymes activity, improved ascorbic acid-glutathione (AsA-GSH) cycle, increased osmoregulatory substances content, reduced hydrogen peroxide and superoxide anion levels, and inhibited malondialdehyde accumulation in alfalfa under drought stress, thereby increasing plant height and leaf relative water content and enhancing drought tolerance of alfalfa. The redundancy analysis of the above physiological indicators showed that the addition of the optimal Spm to improve drought tolerance of alfalfa under drought stress was mainly achieved by increasing catalase activity and improving the ASA-GSH cycle. In addition, metabolomics analysis revealed that exogenous Spm increased the content of oxobutanedioic acid, citric acid, fumaric acid and malic acid to enhance the tricarboxylic acid cycle. Meanwhile, exogenous Spm increased endogenous Spm and proline (Pro) content to resist drought stress by enhancing Spm and Pro metabolism. Moreover, exogenous Spm increased the accumulation of the signaling substance abscisic acid. Discussion: In conclusion, exogenous Spm enhanced drought resistance of alfalfa leaves under drought stress. [ABSTRACT FROM AUTHOR]

• Stevia is an industrially and medicinally valued herb from Asteraceae family. • First report on polyamine- and growth inducer-mediated mono-phasic regeneration in liquid medium. • meta -Topolin-putrescine combination enhanced in vitro growth and proliferation. • Cumulative impact on growth and development was assessed via multiple statistical analyses. • Successfully developed mono-phasic in vitro regenerationn protocol with reduced production time. In the present study, a high-frequency simultaneous muliple shoot-root regeneration protocol for stevia using a liquid medium was developed successfully. Shoot tip explants were grown in Murashige and Skoog liquid (MSL) medium supplemented with different cytokinins i.e. , 6-benzyladenine (BA), kinetin (KIN), and meta -Topolin (m T) in three varied concentrations in combination with 4.9 µM indole-3-butyric acid (IBA) to evaluate their performance on mono-phasic growth and development traits. The m T (6.2 µM) + IBA (4.9 µM) combination induced the highest number of de novo shoots, leaves, and roots (6.3, 30.7, and 5.3, respectively) compared to other treatments during the four-week culture. To assess the effect of polyamines and growth inducers on multiple shoot proliferation, shoot tips from optimized multiple shoot cultures were grown individually in putrescine (PUT), spermidine, spermine, silver nitrate, and salicylic acid (at 100–500 µM) supplemented medium for four weeks and compared against control (without polyamines or growth inducers). The cumulative and individual impact of these polyamines and growth inducers on in vitro growth parameters were comprehensively assessed by employing combined jitter plot and box plot, correlation, network plot, principal component analysis, and unweighted pair-group method with arithmetic mean clustering based on the Euclidean distance matrix. Among different treatments, 200 µM PUT exhibited the most promising results in terms of earliest shoot-root formation (4.7 days, 7.0 days), maximum shoot-root proliferation (counting 12.0, 11.0), and elongation (97.3 mm, 50.0 mm), having maximum leaf count (87). This protocol should be useful to meet the ever-increasing consumers' demand for stevia plantlets, a source of commercially valuable natural sweetener. [ABSTRACT FROM AUTHOR]

Nitrogen (N) is a macronutrient essential for plant growth and development; insufficient N availability has an extensive impact on the overall plant metabolism and productivity. Polyamines, short aliphatic amino-containing compounds naturally produced by living cells, have been widely reported to be beneficial for plant performance under several unfavorable conditions. In this work, the role of polyamine spermine (Spm) as a priming agent for wheat growing under N deficit was investigated. Wheat seeds were primed with 0.1 mM Spm for 3 h, germinated for 48 h, and then grown in N-sufficient or N-deficient media for 8 d. Spm treatment anticipated seed germination and, though priming with Spm did not result in any stimulatory effect on plants developed under an N-sufficient medium, under N limitation many of the studied traits improved compared with control plants. Under N deficit, wheat seedlings originated from Spm-primed seeds showed increased root length, developed the third leaf earlier, and maintained higher total N and protein contents and higher nitrate reductase (NR) and glutamine synthetase (GS) activities in their leaves, compared to control plants. Likewise, total amino acids increased in the roots of primed seedlings, and carbohydrates enhanced both in roots and leaves. Our findings indicate that seed priming with Spm promotes wheat germination and early seedling growth under N limitation, mainly by promoting root elongation and N allocation to the aerial part. [ABSTRACT FROM AUTHOR]

Oligoamines in cellular metabolism carry extremely diverse biological functions (i.e., regulating Ca2+-influx, neuronal nitric oxide synthase, membrane potential, Na+, K+-ATPase activity in synaptosomes, etc.). Furthermore, they also act as longevity agents and have a determinative role in autophagy, cell growth, proliferation, and death, while oligoamines dysregulation is a key in a variety of cancers. However, many of their mechanisms of actions have just begun to be understood. In addition to the numerous biosensing methods, only a very few simple small molecule-based tests are available for their selective but reversible tracking or fluorescent labeling. Motivated by this, we present herein a new fluorescent bis(acridino)-crown ether as a sensor molecule for biogenic oligoamines. The sensor molecule can selectively distinguish oligoamines from aliphatic mono- and diamino-analogues, while showing a reversible 1:2 (host:guest) complexation with a stepwise binding process accompanied by a turn-on fluorescence response. Both computational simulations on molecular docking and regression methods on titration experiments were carried out to reveal the oligoamine-recognition properties of the sensor molecule. The new fluorescent chemosensor molecule has a high potential for molecular-level functional studies on the oligoamine systems in cell processes (cellular uptake, transport, progression in cancers, etc.). [ABSTRACT FROM AUTHOR]

Polyamines are essential analytes due to their critical role in various biological processes and human health in general. Due to their role as regulators for cell growth and proliferation (putrescine and spermine), as neuroprotectors, gero‐, and cardiovascular protectors (spermidine), and as bacterial growth indicators (cadaverine), rapid, simple, and cost‐effective methods for polyamine detection in biofluids are in demand. The present study focuses on the development and investigation of self‐assembled and fluorescent host⋅dye chemo‐sensors based on sulfonated pillar[5]arene for the specific detection of polyamines. Binding studies, as well as stability and functionality assessments of the turn‐on chemosensors for selective polyamine detection in saline and biologically relevant media, are shown. Furthermore, the practical applicability of the developed chemo‐sensors is demonstrated in biofluids such as human urine and saliva. [ABSTRACT FROM AUTHOR]

Sugarcane smut fungus Sporisorium scitamineum produces polyamines putrescine (PUT), spermidine (SPD), and spermine (SPM) to regulate sexual mating/filamentous growth critical for pathogenicity. Besides de novo biosynthesis, intracellular levels of polyamines could also be modulated by oxidation. In this study, we identified two annotated polyamine oxidation enzymes (SsPAO and SsCuAO1) in S. scitamineum. Compared to the wild type (MAT‐1), the ss1paoΔ and ss1cuao1Δ mutants were defective in sporidia growth, sexual mating/filamentation, and pathogenicity. The addition of a low concentration of cAMP (0.1 mM) could partially or fully restore filamentation of ss1paoΔ × ss2paoΔ or ss1cuao1Δ × ss2cuao1Δ. cAMP biosynthesis and hydrolysis genes were differentially expressed in the ss1paoΔ × ss2paoΔ or ss1cuao1Δ × ss2cuao1Δ cultures, further supporting that SsPAO‐ or SsCuAO1‐based polyamine homeostasis regulates S. scitamineum filamentation by affecting the cAMP/PKA signalling pathway. During early infection, PUT promotes, while SPD inhibits, the accumulation of reactive oxygen species (ROS) in sugarcane, therefore modulating redox homeostasis at the smut fungus–sugarcane interface. Autophagy induction was found to be enhanced in the ss1paoΔ mutant and reduced in the ss1cuao1Δ mutant. Exogenous addition of cAMP, PUT, SPD, or SPM at low concentration promoted autophagy activity under a non‐inductive condition (rich medium), suggesting a cross‐talk between polyamines and cAMP signalling in regulating autophagy in S. scitamineum. Overall, our work proves that SsPAO‐ and SsCuAO1‐mediated intracellular polyamines affect intracellular redox balance and thus play a role in growth, sexual mating/filamentation, and pathogenicity of S. scitamineum. [ABSTRACT FROM AUTHOR]

A. Shoots of Gladiolus hybridus on masal MS medium; B. Shoots of Rosa damascena multiplied on MS medium containing 2.5 µM BAP. Rotted shoots of C. Gladiolus hybridus and D. Rosa damascena on MS medium supplemented with 2.5 µM IBA. [Display omitted] • IBA and putrescine both induced rooting individually in miroshoots of rosa damascena and gladiolus hybridus, and their synergistic effect was also observed. • Inhibition of diamine oxidase by l -aminoguanidine inhibited rooting in microshoots, which suggests the role of putrescine oxidation products in root induction, or the observed inhibition of rooting could be due to the accumulation of free putrescine. • When the endogenous synthesis of spermidine and spermine was blocked by methylglyoxal(bis) guanylhydrazone; the exogenous spermine application only induced rooting in microshoots, indicating its essential role in root induction. The effect of indole-3-butyric (IBA) acid and polyamines was investigated on in vitro rooting of microshoots of Rosa damascena Mill. (difficult-to-root) and Gladiolus hybridus Hort. (easy-to-root) plants. Both IBA and putrescine (PUT) individually induced rooting and showed a synergistic effect in the rooting of microshoots of both plant species. Maximum rooting of microshoots (%) was observed on Murashige and Skoog medium (MS medium) supplemented with 2.5 μM IBA and 100 μM PUT. The incorporation of methylglyoxal(bis) guanylhydrazone (MGBG: a competitive inhibitor of s-adenosyl methionine decarboxylase and is known to block spermidine and spermine synthesis) completely inhibited the rooting of microshoots of both plant species. Similarly, the incorporation of l -aminoguanidine (AG: an inhibitor of diamine oxidase) also inhibited the adventitious rooting of microshoots of both species, indicating the role of the oxidation product of PUT in rooting. Rooting was not observed in either species when a medium containing MGBG was supplemented with spermidine. In contrast, when spermine was incorporated in a MS medium with MGBG, the rooting was achieved in both species, thus establishing spermine's clear role in the rooting of microshoots. An increase in peroxidase activity was observed during IBA and PUT-induced rooting. The performance of plants rooted on a medium containing 2.5 μM IBA was significantly better than those rooted on a medium containing 2.5 μM IBA and 100 μM PUT. [ABSTRACT FROM AUTHOR]

In plant tissue culture, differences in endogenous levels of species-specific plant growth regulators (PGRs) may explain differences in regenerative capacity. In the case of polyamines (PAs), their dynamics and distribution may vary between species, genotypes, tissues, and developmental pathways, such as sexual reproduction and apomixis. In this study, for the first time, we aimed to assess the impact of varying endogenous PAs levels in seeds from distinct reproductive modes in Miconia spp. (Melastomataceae), on their in vitro regenerative capacity. We quantified the free PAs endogenous content in seeds of Miconia australis (obligate apomictic), Miconia hyemalis (facultative apomictic), and Miconia sellowiana (sexual) and evaluated their in vitro regenerative potential in WPM culture medium supplemented with a combination of 2,4-dichlorophenoxyacetic acid (2,4-D) and 6-benzylaminopurine (BAP). The morphogenic responses were characterized by light microscopy and scanning electron microscopy and discussed regarding the endogenous PAs profiles found. Seeds of M. sellowiana presented approximately eight times more putrescine than M. australis, which was associated with a higher percentage of regenerated calluses (76.67%) than M. australis (5.56%). On the other hand, spermine levels were significantly higher in M. australis. Spermine is indicated as an inhibitor of auxin-carrying gene expression, which may have contributed to its lower regenerative capacity under the tested conditions. These findings provide important insights into in vitro morphogenesis mechanisms in Miconia and highlight the significance of endogenous PA levels in plant regeneration. These discoveries can potentially optimize future regeneration protocols in Miconia, a plant group still underexplored in this area. [ABSTRACT FROM AUTHOR]

Herbaceous peony (Paeonia lactiflora Pall) is resistant to drought but not waterlogging. The main production areas of peony are prone to waterlogging, seriously affecting the growth and development of herbaceous peony. Polyamines have been observed to significantly enhance the ability of plants to defend and repair adverse damage and affect the synthesis and accumulation of the endogenous growth hormones indole-3-acetic acid (IAA) and abscisic acid (ABA). In this study, two herbaceous peony varieties ('Lihong', 'Qihualushuang') with different waterlogging tolerances were selected for artificial simulated waterlogging treatment to observe their morphological indexes and to determine their endogenous polyamine and hormone contents. Simultaneously, transcriptome sequencing and bioinformatics analysis were performed, focusing on screening differentially expressed genes in the polyamine metabolism pathway. The results showed that flood-tolerant varieties of herbaceous peony respond to waterlogging stress by continuously synthesizing spermidine (Spd) and spermine (Spm) through putrescine (Put) to counteract adversity. In the waterlogging-intolerant varieties, the expression of polyamine oxidase-related genes was annotated; their response to waterlogging stress was the simultaneous degradation of Spm and Spd to Put in the process of synthesis, and a decrease in the accumulation of Spm and Spd led to the early appearance of the symptoms of damage. In addition, polyamines influence key hormones that respond to plant adversity (IAA; ABA). The objective of this work was to initially analyze the mechanism of the polyamine signaling pathway in response to flooding in herbaceous peonies for further in-depth research on the mechanism of flooding tolerance in herbaceous peony, screen flood-tolerant varieties, and promote of their use. [ABSTRACT FROM AUTHOR]

The biosynthesis of antibiotics and other secondary metabolites (also named special metabolites) is regulated by multiple regulatory networks and cascades that act by binding transcriptional factors to the promoter regions of different biosynthetic gene clusters. The binding affinity of transcriptional factors is frequently modulated by their interaction with specific ligand molecules. In the last decades, it was found that the biosynthesis of penicillin is induced by two different molecules, 1,3-diaminopropane and spermidine, but not by putrescine (1,4-diaminobutane) or spermine. 1,3-diaminopropane and spermidine induce the expression of penicillin biosynthetic genes in Penicillium chrysogenum. Proteomic studies clearly identified two different proteins that respond to the addition to cultures of these inducers and are involved in β-alanine and pantothenic acid biosynthesis. These compounds are intermediates in the biosynthesis of phosphopantetheine that is required for the activation of non-ribosomal peptide synthetases, polyketide synthases, and fatty acid synthases. These large-size multidomain enzymes are inactive in the "apo" form and are activated by covalent addition of the phosphopantetheine prosthetic group by phosphopantetheinyl transferases. Both 1,3-diaminopropane and spermidine have a similar effect on the biosynthesis of cephalosporin by Acremonium chrysogenum and lovastatin by Aspergillus terreus, suggesting that this is a common regulatory mechanism in the biosynthesis of bioactive secondary metabolites/natural products. [ABSTRACT FROM AUTHOR]

Coordinated by intricate crosstalk between various phytohormones, petal senescence characterizes an extraordinary stage of flower development, involving precisely regulated biochemical and physiological reprogramming. The process involves a gradual deterioration of physiological processes and structural integrity, eventually leading to the death of the flowers. Polyamines are small organic compounds that play crucial roles in plant growth, development and stress. These compounds are involved in various physiological processes, including cell division, flowering, fruit set and maturation. Given this, the current study elucidates the potential role of polyamines in regulating the senescence of cut spikes of Antirrhinum majus. Spikes, harvested with a minimum of two buds at one day before the anthesis stage, were treated with different polyamines such as Putrescine (Put), Spermidine (Spd) and Spermine (Spm) at 0.25 and 0.75 mM concentrations. A separate set of flower spikes was maintained in distilled water, which served as the control. Our results indicated that polyamines delayed the senescence of A. majus significantly leading to an extended postharvest lifespan of flower spikes. Among these treatments, 0.75 mM Put was the most effective treatment in enhancing the longevity of A. majus. On the contrary, the control spikes showed early senescence. The study showed that polyamines accentuated the activity of antioxidant enzymes and enhanced membrane stability, besides reducing lipoxygenase activity and ethylene content in flowers. Moreover, polyamines significantly increased the content of soluble proteins, total phenols and sugar fractions in the floral tissues. Also, polyamines reduced bacterial growth and improved solution uptake in flowers. The investigation elucidated that the polyamines regulate the flower senescence of A. majus by orchestrating various physio-biochemical processes. [ABSTRACT FROM AUTHOR]

Soil salinization is a major abiotic stress that significantly impairs plant growth and development. This leads to various physiological disorders in plants, ultimately posing a threat to global food security. Polyamines are emerging as new plant growth regulators that can help promote salt stress tolerance in plants. Research has shown that application of polyamines, which are organic compounds containing multiple amine groups, can help alleviate the detrimental effects of salt stress on plants. Increasing the levels of polyamines, either naturally during salt stress or through exogenous application, helps establish homeostasis of polyamines within the plant. This polyamine homeostasis then leads to the homeostasis of reactive oxygen species (ROS) through several physiological processes such as hormonal regulation, ion channel regulation, activation of ROS scavenging enzymes, and antioxidant activity. Collectively, these polyamine-mediated physiological changes help the plant establish ROS homeostasis, which is a key mechanism underlying enhanced salt stress tolerance. The balanced regulation of polyamines and ROS is crucial for plant adaptive responses and survival under saline conditions. Overall, the use of polyamines represents a promising approach for developing more salt-tolerant crops and improving agricultural productivity in saline-affected regions. [ABSTRACT FROM AUTHOR]

Studies on the immune-regulatory roles played by the commensal microbes residing in the nasal mucosa consider the contribution of antiviral immune responses. Here, we sought to identify the nasal microbiome, Staphylococcus epidermidis-regulated antiviral immune responses and the alteration of polyamine metabolites in nasal epithelium. We found that polyamines were required for the life cycle of influenza A virus (IAV) and depletion of polyamines disturbed IAV replication in normal human nasal epithelial (NHNE) cells. Inoculation of S. epidermidis also suppressed IAV infection and the concentration of polyamines including putrescine, spermidine, and spermine was completely attenuated in S. epidermidis-inoculated NHNE cells. S. epidermidis activated the enzyme involved in the production of ornithine from arginine and downregulated the activity of the enzyme involved in the production of putrescine from ornithine in nasal epithelium. S. epidermidis also induced the activation of enzymes that promote the extracellular export of spermine and spermidine in NHNE cells. Our findings demonstrate that S. epidermidis is shown to be able of creating an intracellular environment lacking polyamines in the nasal epithelium and promote the balance of cellular polyamines in favor of the host to restrict influenza virus replication. Staphylococcus epidermidis, a nasal commensal in healthy mucus, can create an intracellular epithelium environment lacking polyamines and promote balance of cellular polyamines in favor of the host to restrict influenza virus replication. [ABSTRACT FROM AUTHOR]

Polyamines are ubiquitous biomolecules with a number of established functions in eukaryotic cells. In plant cells, polyamines have previously been linked to abiotic and biotic stress tolerance, as well as to the modulation of programmed cell death (PCD), with contrasting reports on their pro‐PCD and pro‐survival effects. Here, we used two well‐established platforms for the study of plant PCD, Arabidopsis thaliana suspension cultures cells and the root hair assay, to examine the roles of the polyamines spermine and spermidine in the regulation of PCD. Using these systems for precise quantification of cell death rates, we demonstrate that both polyamines can trigger PCD when applied exogenously at higher doses, whereas at lower concentrations they inhibit PCD induced by both biotic and abiotic stimuli. Furthermore, we show that concentrations of polyamines resulting in inhibition of PCD generated a transient ROS burst in our experimental system, and activated the expression of oxidative stress‐ and pathogen response‐associated genes. Finally, we examined PCD responses in existing Arabidopsis polyamine synthesis mutants, and identified a subtle PCD phenotype in Arabidopsis seedlings deficient in thermo‐spermine. The presented data show that polyamines can have a role in PCD regulation; however, that role is dose‐dependent and consequently they may act as either inhibitors, or inducers, of PCD in Arabidopsis. [ABSTRACT FROM AUTHOR]

Natural polyamines, including spermidine (SPD), spermine (SPM) and putrescine (PUT), are evolutionarily conserved endogenous molecules crucially involved in central cellular processes. Their physiological importance may extend to the maintenance of cognitive function during aging. However, limited population-based epidemiological studies have explored the link between dietary polyamines and dementia risk. This study was a prospective analysis of 77,092 UK Biobank participants aged ≥ 60 years without dementia at baseline. We used Cox proportional hazard regression models to explore the associations between dietary polyamines and the risk of dementia, and restricted cubic splines to test the non-linear relationships. During a median follow-up of 12 years, 1087 incidents of all-cause dementia cases occurred, including 450 Alzheimer's disease (AD) cases and 206 vascular dementia (VD) cases. The fully adjusted hazard ratios (HRs) for the upper fourth quintile of dietary SPD, in comparison with the lowest quintile of intake, were 0.68 (95% confidence interval [95% CI]: 0.66–0.83) for the risk of all-cause dementia, 0.62 (95% CI: 0.45–0.85) for AD and 0.56 (95% CI: 0.36–0.88) for VD, respectively. A 26% reduction in dementia risk [HR: 0.74, (95% CI: 0.61–0.89)] and a 47% reduction in AD [HR: 0.53, (95%CI: 0.39–0.72)] were observed comparing the third with the lowest quintiles of dietary SPM. Dietary PUT was only associated with a reduced risk of all-cause dementia in the fourth quintile [HR (95% CI): 0.82 (0.68–0.99)]. Reduced risk was not found to be significant across all quintiles. There were 'U'-shaped relationships found between dietary polyamines and all-cause dementia, AD and VD. Stratification by genetic predisposition showed no significant effect modification. Optimal intake of polyamines was linked to a decreased risk of dementia, with no modification by genetic risk. This potentially suggests cognitive benefits of dietary natural polyamines in humans. [ABSTRACT FROM AUTHOR]

Decreased plasma spermine levels are associated with kidney dysfunction. However, the role of spermine in kidney disease remains largely unknown. Herein, it is demonstrated that spermine oxidase (SMOX), a key enzyme governing polyamine metabolism, is predominantly induced in tubular epithelium of human and mouse fibrotic kidneys, alongside a reduction in renal spermine content in mice. Moreover, renal SMOX expression is positively correlated with kidney fibrosis and function decline in patients with chronic kidney disease. Importantly, supplementation with exogenous spermine or genetically deficient SMOX markedly improves autophagy, reduces senescence, and attenuates fibrosis in mouse kidneys. Further, downregulation of ATG5, a critical component of autophagy, in tubular epithelial cells enhances SMOX expression and reduces spermine in TGF‐β1‐induced fibrogenesis in vitro and kidney fibrosis in vivo. Mechanically, ATG5 readily interacts with SMOX under physiological conditions and in TGF‐β1‐induced fibrogenic responses to preserve cellular spermine levels. Collectively, the findings suggest SMOX/spermine axis is a potential novel therapy to antagonize renal fibrosis, possibly by coordinating autophagy and suppressing senescence. [ABSTRACT FROM AUTHOR]

Mammalian polyamines, including putrescine, spermidine, and spermine, are positively charged amines that are essential for all living cells including neoplastic cells. An increasing understanding of polyamine metabolism, its molecular functions, and its role in cancer has led to the interest in targeting polyamine metabolism as an anticancer strategy, as the metabolism of polyamines is frequently dysregulated in neoplastic disease. In addition, due to compensatory mechanisms, combination therapies are clinically more promising, as agents can work synergistically to achieve an effect beyond that of each strategy as a single agent. In this article, the nature of polyamines, their association with carcinogenesis, and the potential use of targeting polyamine metabolism in treating and preventing cancer as well as combination therapies are described. The goal is to review the latest strategies for targeting polyamine metabolism, highlighting new avenues for exploiting aberrant polyamine homeostasis for anticancer therapy and the mechanisms behind them. [ABSTRACT FROM AUTHOR]

Potential toxic element (PTE) pollution has emerged as a significant environmental and social concern in global agriculture. Chromium (Cr) occurs in different oxidation states naturally, among them Cr(VI), which is highly toxic. This study carried out biochemical and molecular tests to elucidate the accumulation of total soluble phenolics (TSPs) in rice plants exposed to Cr(VI) at 2.0, 8.0, and 16.0 mg Cr/L, emphasizing the interaction between polyamines (PAs) and abscisic acid (ABA). The results revealed significant Cr accumulation in different tissues of rice plants, which hindered their growth. Cr(VI) exposure increased the ABA concentration, with higher levels detected in the shoots than in the roots. The TSP concentration in rice tissues showed a positive relationship with the supplied concentrations of Cr(VI). The measured PAs, including spermine (Spm), putrescine (Put), and spermidine (Spd), exhibited varied responses to Cr(VI) stress, with only Spm concentration increasing with Cr(VI) concentrations. Real-time qRT-PCR showed PAs and ABA synthesis-associated genes such as OsADC1, OsAIH, OsCPA1, and OsCPA4 were significantly up-regulated in shoot of rice plants treated with Cr(VI). These genes are associated with the second pathway of Put synthesis, originating from Arg. Almost all genes activated in the Met pathway were significantly up-regulated as well. Moreover, the genes involved in the interconversion among the three species of PAs exhibited completely different responses to Cr(VI) exposure. Overall, the biochemical analysis and gene expression data indicate that the interaction between ABA and Spm is likely to enhance the TSP levels in rice plants subjected to Cr(VI) toxicity. [ABSTRACT FROM AUTHOR]

We report a method to modulate the formation and stability of nano- and micro-assemblies of bovine serum albumin (BSA) formed with CB[7] using the treatment of a biogenic polyamine such as spermine (SPM). Our findings show that SPM impacts the size and surface charge of BSA-CB[7] assemblies, effectively reducing the size of nanoscale particles and making their surface charges more positive. Conversely, for larger particles spanning more than a few micrometres in diameter, SPM treatment is less effective in reducing their size. This ineffectiveness is attributed to the interaction between the external surface of CB[7] and BSA, which remains relatively unaffected by SPM. Over time, with an excess of CB[7], this interaction becomes more pronounced, resulting in aggregation of large particles and subsequent sedimentation. Since SPM is a biogenic polyamine found at elevated levels in cancerous tissues, this result may offer a strategic direction for designing supramolecular systems to control protein assemblies in oncological environments, highlighting the significant potential of supramolecular chemistry in biomedical applications. [ABSTRACT FROM AUTHOR]

The fabrication of an all-in-one solid-state ECL sensing platform is beneficial not only for expediting the miniaturization of sensing devices, but also, more importantly, for enabling point-of-care applications. In the present work, a self-enhanced solid-state ECL sensing platform is fabricated using newly synthesised silica polyethylene nanoparticles (SiO2-PEI NPs) which generate a co-reactant in situ and easily self-assemble with Ru(bpy)32+ and shows selective and sensitive detection of spermine at physiological pH (7.4). Spermine induces the maximum ECL emission intensity compared to other biogenic amines due to the presence of two secondary amines. A possible ECL reaction mechanism has been proposed based on CV and ECL experiments, DFT calculations, and in situ ECL spectrum analysis. The developed solid-state sensor showed a linear increase in ECL intensity with increasing spermine concentration in the range of 10 nM to 100 nM with an LOD of 12.2 nM. Compared to other biogenic amines in previous works, chemically synthesised SiO2-PEI NPs used in the present study act as an effective label- and enzyme-free sensor, and the new method is observed to be simple and cost-effective, to overcome various limitations of solution-phase ECL and to avoid the usage of any noble metals. [ABSTRACT FROM AUTHOR]

Plant growth‐promoting rhizobacteria (PGPR) are known for their role in ameliorating plant stress, including alkaline stress, yet the mechanisms involved are not fully understood. This study investigates the impact of various inoculum doses of Bacillus licheniformis Jrh14‐10 on Arabidopsis growth under alkaline stress and explores the underlying mechanisms of tolerance enhancement. We found that all tested doses improved the growth of NaHCO3‐treated seedlings, with 109 cfu/mL being the most effective. Transcriptome analysis indicated downregulation of ethylene‐related genes and an upregulation of polyamine biosynthesis genes following Jrh14‐10 treatment under alkaline conditions. Further qRT‐PCR analysis confirmed the suppression of ethylene biosynthesis and signaling genes, alongside the activation of polyamine biosynthesis genes in NaHCO3‐stressed seedlings treated with Jrh14‐10. Genetic analysis showed that ethylene signaling‐deficient mutants (etr1‐3 and ein3‐1) exhibited greater tolerance to NaHCO3 than the wild type, and the growth‐promoting effect of Jrh14‐10 was significantly diminished in these mutants. Additionally, Jrh14‐10 was found unable to produce 1‐aminocyclopropane‐1‐carboxylic acid (ACC) deaminase, indicating it does not reduce the ethylene precursor ACC in Arabidopsis. However, Jrh14‐10 treatment increased the levels of polyamines (putrescine, spermidine, and spermine) in stressed seedlings, with spermidine particularly effective in reducing H2O2 levels and enhancing Fv/Fm under NaHCO3 stress. These findings reveal a novel mechanism of PGPR‐induced alkaline tolerance, highlighting the crosstalk between ethylene and polyamine pathways, and suggest a strategic redirection of S‐adenosylmethionine towards polyamine biosynthesis to combat alkaline stress. [ABSTRACT FROM AUTHOR]

Biogenic polyamines are ubiquitous compounds. Dysregulation of their metabolism is associated with the development of various pathologies, including cancer, hyperproliferative diseases, and infections. The canonical pathway of polyamine catabolism includes acetylation of spermine and spermidine and subsequent acetylpolyamine oxidase (PAOX)-mediated oxidation of acetylpolyamines (back-conversion) or their direct efflux from the cell. PAOX is considered to catalyze a non-rate-limiting catabolic step. Here, we show that PAOX transcription levels are extremely low in various tumor- and non-tumor cell lines and, in most cases, do not change in response to altered polyamine metabolism. Its enzymatic activity is undetectable in the majority of cell lines except for neuroblastoma and low passage glioblastoma cell lines. Treatment of A549 cells with N1,N11-diethylnorspermine leads to PAOX induction, but its contribution to polyamine catabolism remains moderate. We also describe two alternative enzyme isoforms and show that isoform 4 has diminished oxidase activity and isoform 2 is inactive. PAOX overexpression correlates with the resistance of cancer cells to genotoxic antitumor drugs, indicating that PAOX may be a useful therapeutic target. Finally, PAOX is dispensable for the replication of various viruses. These data suggest that a decrease in polyamine levels is achieved predominantly by the secretion of acetylated spermine and spermidine rather than by back-conversion. [ABSTRACT FROM AUTHOR]

Kukoamine A has been known for decades as an anti-inflammatory and hypotensive principle of Chinese medicinal plant extract from Lycium root, bark, and fruit. The recent pharmacological significance of this alkaloid makes it a potential therapeutic target for the pharmaceutical industry. We accomplished the synthesis of kukoamine A in a 73% yield over four steps starting from cheaper commercial reagents, ambient reaction conditions, and minimal purification efforts. [ABSTRACT FROM AUTHOR]

medium supplemented with exogenous putrescine(Put), spermidine(Spd), and spermine(Spm). The results were as follows:(1)Exogenous Put, Spd and Spm treatments significantly increased the EC proliferation rate and reduced the amount of induced somatic embryos and number of germinations. The proliferated EC cells after exogenous PA treatments were more consistent in size and stained deeply and evenly. Furthermore, multicellular proembryos in EC were reduced, and fully differentiated early cotyledon embryos could be seen. (2)All the exogenous PA treatments significantly increased the endogenous PA content in EC. Among them, Put treatment had the highest content of each endogenous PA component and total PA. When the EC proliferated on the medium containing exogenous PAs was transferred to the medium without exogenous PAs(recovery culture)for proliferating, the Put content in the EC was still significantly higher than the control, however, the endogenous Spd and Spm were significantly decreased. (3)Exogenous Put treatment significantly increased the activities of ornithine decarboxylase(ODC), arginine decarboxylase(ADC), and diamine oxidase(DAO)in EC, while exogenous Spd and Spm treatments significantly reduced the activities of ODC and ADC in EC, and exogenous Spd significantly increased the polyamine oxidase(PAO)activity. When transferred to the recovery culture medium, the ADC and DAO activities of newly proliferated EC were significantly lower than those of EC cultured with exogenous PAs, but there was no significant difference in ODC and PAO activities. In summary, the exogenous PAs can affect endogenous PAs content by regulating the activities of enzymes related to PAs metabolism, thereby affecting EC proliferation and somatic embryo induction in litchi. These results provide a basis for further study on the mechanism of PAs regulating embryogenesis, and improve litchi regeneration efficiency in vitro. [ABSTRACT FROM AUTHOR]

We studied the effects of some nitrogen-containing, heterocyclic, and cyclic compounds on the rate of oxidative deamination of polyamines and putrescine in tissues with a high proliferation rate. For this purpose, the specific activities of the main enzymes of polyamine oxidative degradation — spermine oxidase (SMO), polyamine oxidase (PAO), and diamine oxidase (DAO) were determined using a cell-free test system from regenerating rat liver. The compounds methyl 2-(5-formylfuran-2-yl)benzoate and 2,7-bis-[2-(diethylamino)ethoxy]-9H-fluoren-9-one (and in the form of dihydrochloride) showed mainly activating effect on oxidative degradation of putrescine, spermidine, and spermine, which indirectly indicates their antiproliferative effect. Nitrogen-free compounds inhibited this process, thus exhibiting potentially carcinogenic properties. Correlations were calculated for activity of DAO, PAO, and SMO with 5 topological indices: Wiener (W), Rouvray (R), Balaban (J) in the Trinaistich modification, detour (Ip), and electropy (Ie). The highest dependence was noted for DAO and the Balaban index (R=-0.55), for PAO and the detour index (R=0.78), and for SMO and the electropy index (R=0.53). The remaining dependencies showed insignificant correlation strength. [ABSTRACT FROM AUTHOR]

Polyamine metabolism dysregulation is a hallmark of many cancers, offering a promising avenue for early tumor theranostics. This study presents the development of a nuclear probe derived from spermidine (SPM) for dual-purpose tumor PET imaging and internal radiation therapy. The probe, radiolabeled with either [68Ga]Ga for diagnostic applications or [177Lu]Lu for therapeutic use, was synthesized with exceptional purity, stability, and specific activity. Extensive testing involving 12 different tumor cell lines revealed remarkable specificity towards B16 melanoma cells, showcasing outstanding tumor localization and target-to-non-target ratio. Mechanistic investigations employing polyamines, non-labeled precursor, and polyamine transport system (PTS) inhibitor, consistently affirmed the probe 's targetability through recognition of the PTS. Notably, while previous reports indicated PTS upregulation in various tumor types for targeted therapy, this study observed no positive signals, highlighting a concentration-dependent discrepancy between targeting for therapy and diagnosis. Furthermore, when labeled with [177Lu], the probe demonstrated its therapeutic potential by effectively controlling tumor growth and extending mouse survival. Investigations into biodistribution, excretion, and biosafety in healthy humans laid a robust foundation for clinical translation. This study introduces a versatile SPM-based nuclear probe with applications in precise tumor theranostics, offering promising prospects for clinical implementation. [ABSTRACT FROM AUTHOR]

Cultivated and processed white button mushrooms are widely used in the menu of the Slovak consumers. However, these food items can potentially contain biogenic amines, attributed to the presence of precursor compounds and their susceptibility to microbial spoilage. Biogenic amines significantly influence food quality and can pose health risks to consumers. This study is focused on determination of spermidine, putrescine, tyramine, cadaverine, histamine, spermine, and 2-phenylethylamine in processed mushroom products available in the Slovak market. The findings revealed considerable variability in biogenic amine content across individual products, influenced by the producer. Spermidine, putrescine and spermine emerged as the predominant biogenic amines with concentration ranges 2349.8 -7412.8, 37.2 - 607.5 and 74.2 - 267.6 mg/kg DW, respectively. Tyramine and histamine were detected in 22.2% of processed mushroom samples with one product exceeding concentration 200 mg/kg DW. Cadaverine was identified in 44.4% samples. The presence of histamine has to be concerned regarding potential health risks for consumers. Comparison of the mushroom products showed significant differences between the groups of products with whole mushrooms vs. sliced mushrooms in brine in case of the content of spermine (p<0.001), water content (p<0.01), putrescine, histamine and tyramine (p<0.05 for all these BAs). No significant differences were found between the groups for the cadaverine, spermidine and total content of biogenic amines. In house rapid validation was performed in term of determination of limits of detection and limits of quantification and intraday precision of retention time for individual biogenic amines in this study. Limits of detection ranged from 0.013 to 0.029 µg/mL and limits for quantification were in the range from 0.039 to 0.087 µg/mL. The RSD for the retention time in standard solutions did not exceed 0.12%. [ABSTRACT FROM AUTHOR]

Background: Some studies have reported that polyamine levels may influence immune system programming. The aim of this study was to evaluate the polyamine profile during gestation and its associations with maternal allergy and cytokine production in cord blood cells in response to different allergenic stimuli. Methods: Polyamines were determined in plasma of pregnant women (24 weeks, N = 674) and in umbilical cord samples (N = 353 vein and N = 160 artery) from the Mediterranean NELA birth cohort. Immune cell populations were quantified, and the production of cytokines in response to different allergic and mitogenic stimuli was assessed in cord blood. Results: Spermidine and spermine were the most prevalent polyamines in maternal, cord venous, and cord arterial plasma. Maternal allergies, especially allergic conjunctivitis, were associated with lower spermine in umbilical cord vein. Higher levels of polyamines were associated with higher lymphocyte number but lower Th2‐related cells in cord venous blood. Those subjects with higher levels of circulating polyamines in cord showed lower production of inflammatory cytokines, especially IFN‐α, and lower production of Th2‐related cytokines, mainly IL‐4 and IL‐5. The effects of polyamines on Th1‐related cytokines production were uncertain. Conclusions: Spermidine and spermine are the predominant polyamines in plasma of pregnant women at mid‐pregnancy and also in umbilical cord. Maternal allergic diseases like allergic conjunctivitis are related to lower levels of polyamines in cord vein, which could influence the immune response of the newborn. Cord polyamine content is related to a decreased Th2 response and inflammatory cytokines production, which might be important to reduce an allergenic phenotype in the neonate. [ABSTRACT FROM AUTHOR]

This paper presents new colloidal systems that have prospects for use as carriers of medicinal compounds and are polymer complexes based on polyacrylic acid molecules of various molecular weights and biogenic polyamine, additionally modified with magnetic iron oxide nanoparticles. The main physicochemical characteristics of the resulting polycomplexes are determined. The possibility of incorporating a doxorubicin medicinal compound in the polycomplexes is demonstrated, and the magnetic properties of the polycomplexes functionalized with magnetic iron oxide nanoparticles are studied. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Challenges Associated with Byproducts Valorization—Comparison Study of Safety Parameters of Ultrasonicated and Fermented Plant-Based Byproducts." The correction addresses mistakes in Figures 2 and 3a of the original publication, stating that not all names of the samples were visible in Figure 2 and that mg/kg should be used instead of mg/g in Figure 3a. The corrected figures are provided, and the authors assure that the scientific conclusions remain unaffected. The original publication has been updated accordingly. [Extracted from the article]

N-methyl-D-aspartate receptors (NMDARs emerging from GRIN genes) are tetrameric receptors that form diverse channel compositions in neurons, typically consisting of two GluN1 subunits combined with two GluN2(A-D) subunits. During prenatal stages, the predominant channels are di-heteromers with two GluN1 and two GluN2B subunits due to the high abundance of GluN2B subunits. Postnatally, the expression of GluN2A subunits increases, giving rise to additional subtypes, including GluN2A-containing di-heteromers and tri-heteromers with GluN1, GluN2A, and GluN2B subunits. The latter emerge as the major receptor subtype at mature synapses in the hippocampus. Despite extensive research on purely di-heteromeric receptors containing two identical GRIN variants, the impact of a single variant on the function of other channel forms, notably tri-heteromers, is lagging. In this study, we systematically investigated the effects of two de novo GRIN2B variants (G689C and G689S) in pure, mixed di- and tri-heteromers. Our findings reveal that incorporating a single variant in mixed di-heteromers or tri-heteromers exerts a dominant negative effect on glutamate potency, although 'mixed' channels show improved potency compared to pure variant-containing di-heteromers. We show that a single variant within a receptor complex does not impair the response of all receptor subtypes to the positive allosteric modulator pregnenolone-sulfate (PS), whereas spermine completely fails to potentiate tri-heteromers containing GluN2A and -2B-subunits. We examined PS on primary cultured hippocampal neurons transfected with the variants, and observed a positive impact over current amplitudes and synaptic activity. Together, our study supports previous observations showing that mixed di-heteromers exhibit improved glutamate potency and extend these findings towards the exploration of the effect of Loss-of-Function variants over tri-heteromers. Notably, we provide an initial and crucial demonstration of the beneficial effects of GRIN2B-relevant potentiators on tri-heteromers. Our results underscore the significance of studying how different variants affect distinct receptor subtypes, as these effects cannot be inferred solely from observations made on pure di-heteromers. Overall, this study contributes to ongoing efforts to understand the pathophysiology of GRINopathies and provides insights into potential treatment strategies. [ABSTRACT FROM AUTHOR]

This review describes a 50-year-long research study on the characteristics of Helianthus tuberosus L. tuber dormancy, its natural release and programmed cell death (PCD), as well as on the ability to change the PCD so as to return the tuber to a life program. The experimentation on the tuber over the years is due to its particular properties of being naturally deficient in polyamines (PAs) during dormancy and of immediately reacting to transplants by growing and synthesizing PAs. This review summarizes the research conducted in a unicum body. As in nature, the tuber tissue has to furnish its storage substances to grow vegetative buds, whereby its destiny is PCD. The review's main objective concerns data on PCD, the link with free and conjugated PAs and their capacity to switch the destiny of the tuber from a program of death to one of new life. PCD reversibility is an important biological challenge that is verified here but not reported in other experimental models. Important aspects of PA features are their capacity to change the cell functions from storage to meristematic ones and their involvement in amitosis and differentiation. Other roles reported here have also been confirmed in other plants. PAs exert multiple diverse roles, suggesting that they are not simply growth substances, as also further described in other plants. [ABSTRACT FROM AUTHOR]

Polyamines, such as putrescine, spermidine, and spermine, are crucial for plant defense against both abiotic and biotic stresses. Putrescine is also known as a significant inducer of deoxynivalenol (DON) production in Fusarium graminearum, the primary causal agent of Fusarium head blight (FHB). However, the impact of other polyamines on DON production and whether modifying polyamine biosynthesis could improve wheat resistance to FHB are currently unknown. In this study, we demonstrate that key precursor components of putrescine synthesis, including arginine, ornithine, and agmatine, can induce DON production, albeit to a lesser extent than putrescine in trichothecene biosynthesis-inducing (TBI) culture under the same total nitrogen conditions. Intriguingly, spermidine and spermine, downstream products of putrescine in the polyamine biosynthesis pathway, do not induce DON production under the same conditions. Additionally, externally applying either spermidine or spermine to wheat heads significantly reduces the diseased spikelet number caused by F. graminearum. Furthermore, our results show that overexpression of the wheat spermidine synthase (SPDS) gene TaSPDS-7D1 significantly enhances the spermidine content and wheat resistance to FHB. In addition, the TaSPDS-7D1-overexpressing line OE3 exhibited a 1000-grain weight and plant height increase compared to the wild type. Our findings reveal that overexpression of the spermidine synthase gene can enhance wheat resistance to FHB without compromising wheat yield. [ABSTRACT FROM AUTHOR]

Objective: To investigate damaging effects of clomifene citrate (CC) on endometrial stromal cells (hEndoSCs), and to study effects of spermidine on autophagy and inflammatory cytokine expression in damaged endometrial stromal cells. Methods: Groups were firstly divided into control group, spermidine group, clomiphene group (CC group), CC+Spermidine group. MTT assay was used to detect cell survival rate of hEndoSCs after co-incubation with different concentrations of CC or Spermidine for 24 h. Content of intracellular reactive oxygen species (ROS) and level of apoptosis in cells of the 4 groups were detected by flow cytometry technique. Western blot was used to detect expressions of autophagy pathway-related proteins ULK1, p-ULK1, LC-3 H, and apoptosis-related proteins Bax, Bcl-2, Cleaved-caspase 3. RT-qPCR was used to detect mRNA expressions of IL-6, IL-1β and TNF-α. Results: Compared with control group, CC group showed decreased cell survival, increased apoptosis rate, ROS content, Bax, Cleaved-caspase 3 expressions, decreased Bcl-2 expression, decreased levels of autophagy-related proteins p-ULK1 and LC-3 II/I, and elevated expressions of inflammatory factors IL-6, IL-1β and TNF-α mRNA (P<0.01). There was no significant changes viability of cells in spermidine group compared with control group (P>0.05). Compared with CC group, cell survival rate in CC+spermidine group was significantly increased, apoptosis rate, ROS content, Bax and Cleaved-caspase 3 expressions were decreased, Bcl-2 expression was increased, expressions of autophagy-related proteins p-ULK1 and LC-3 H/I were elevated, while expressions of inflammatory factors IL-6, IL-1β and TNF-α mRNA were decreased (P<0.01). Conclusion: CC can inhibit endometrial stromal cell proliferation, promote apoptosis, and increase the transcript levels of inflammatory factors IL-6, IL-1β and TNF-α. Spermidine can reduce intracellular ROS in clomiphene-injured endometrial stromal cells by activating cellular autophagy, increase cell survival, and inhibit the expressions of inflammatory factors IL-6, IL-1β and TNF-α. [ABSTRACT FROM AUTHOR]

Spermine synthase is an aminopropyltransferase that adds an aminopropyl group to the essential polyamine spermidine to form tetraamine spermine, needed for normal human neural development, plant salt and drought resistance, and yeast CoA biosynthesis. We functionally identify for the first time bacterial spermine synthases, derived from phyla Bacillota, Rhodothermota, Thermodesulfobacteriota, Nitrospirota, Deinococcota, and Pseudomonadota. We also identify bacterial aminopropyltransferases that synthesize the spermine same mass isomer thermospermine, from phyla Cyanobacteriota, Thermodesulfobacteriota, Nitrospirota, Dictyoglomota, Armatimonadota, and Pseudomonadota, including the human opportunistic pathogen Pseudomonas aeruginosa. Most of these bacterial synthases were capable of synthesizing spermine or thermospermine from the diamine putrescine and so possess also spermidine synthase activity. We found that most thermospermine synthases could synthesize tetraamine norspermine from triamine norspermidine, that is, they are potential norspermine synthases. This finding could explain the enigmatic source of norspermine in bacteria. Some of the thermospermine synthases could synthesize norspermidine from diamine 1,3-diaminopropane, demonstrating that they are potential norspermidine synthases. Of 18 bacterial spermidine synthases identified, 17 were able to aminopropylate agmatine to form N¹ -aminopropylagmatine, including the spermidine synthase of Bacillus subtilis, a species known to be devoid of putrescine. This suggests that the N¹ -aminopropylagmatine pathway for spermidine biosynthesis, which bypasses putrescine, may be far more widespread than realized and may be the default pathway for spermidine biosynthesis in species encoding L-arginine decarboxylase for agmatine production. Some thermospermine synthases were able to aminopropylate N¹ -aminopropylagmatine to form N12- guanidinothermospermine. Our study reveals an unsuspected diversification of bacterial polyamine biosynthesis and suggests a more prominent role for agmatine. [ABSTRACT FROM AUTHOR]

Trypsin, a novel superoxide scavenger, significantly enhances the storage quality of Hylocereus undatus (H. undatus). To elucidate the preservation mechanism of trypsin on H. undatus, a widely targeted metabolomic analysis, and transcriptomics analysis were conducted. Firstly, a total of 453 metabolites were identified, with organic acids and their derivatives constituting the largest proportion (25%). Amino acids and their metabolites, prominent among organic acids, were further analyzed. Among them, 73 metabolites were associated with amino acids, and 37 exhibited significant differences. The most enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was arginine biosynthesis (map00220), with polyamine metabolites showing the most pronounced differences, particularly spermine (FC = 1.7594). Compared with the control group, 4-hydroxy-2-oxoglutaric acid was significantly upregulated (FC = 2.117) in the process of spermine biosynthesis. Furthermore, the results of Gene Ontology (GO) and KEGG enrichment analysis of the H. undatus transcriptome profile revealed that trypsin treatment led to 187 differentially expressed genes associated with arginine. Both GO and KEGG analyses exhibited significant enrichment in the spermine biosynthetic process (GO:0006597) (map:00220) within the arginine biosynthesis pathway. Moreover, most enzymes and metabolites within the spermine biosynthesis pathway in H. undatus were upregulated. The results of the PPI network highlighted that ADC, SPDS, and SAMDC, among others, were pivotal proteins involved in trypsin-regulated arginine metabolism and spermine synthesis. This study revealed that trypsin could significantly delay postharvest senescence of H. undatus at room temperature. This effect might be attributed to trypsin triggering the synthesis of 4-hydroxy-2-oxoglutaric acid in the fruit peel, thereby promoting the biosynthesis of spermine and other polyamines. [ABSTRACT FROM AUTHOR]

This study investigated the effect of polycationic and uncharged polymers (and oligomers) on the catalytic parameters and thermostability of L-asparaginase from Thermococcus sibiricus (TsA). This enzyme has potential applications in the food industry to decrease the formation of carcinogenic acrylamide during the processing of carbohydrate-containing products. Conjugation with the polyamines polyethylenimine and spermine (PEI and Spm) or polyethylene glycol (PEG) did not significantly affect the secondary structure of the enzyme. PEG contributes to the stabilization of the dimeric form of TsA, as shown by HPLC. Furthermore, neither polyamines nor PEG significantly affected the binding of the L-Asn substrate to TsA. The conjugates showed greater maximum activity at pH 7.5 and 85 °C, 10–50% more than for native TsA. The pH optima for both TsA-PEI and TsA-Spm conjugates were shifted to lower pH ranges from pH 10 (for the native enzyme) to pH 8.0. Additionally, the TsA-Spm conjugate exhibited the highest activity at pH 6.5–9.0 among all the samples. Furthermore, the temperature optimum for activity at pH 7.5 shifted from 90–95 °C to 80–85 °C for the conjugates. The thermal inactivation mechanism of TsA-PEG appeared to change, and no aggregation was observed in contrast to that of the native enzyme. This was visually confirmed and supported by the analysis of the CD spectra, which remained almost unchanged after heating the conjugate solution. These results suggest that TsA-PEG may be a more stable form of TsA, making it a potentially more suitable option for industrial use. [ABSTRACT FROM AUTHOR]

In recent decades, extensive research has been conducted on nano drug delivery systems for treating inflammation. Despite this, the lack of specificity in many carriers and materials has hindered their effectiveness in enhancing treatment efficiency. To address this challenge, among numerous candidate biomaterials, stimuli-responsive biopolymers have received significant interest for precisely delivering their payload to inflamed tissues. Herein, to overcome this deficiency, pH-responsive magnetic nanocarriers were fabricated. A cationic dextran was synthesized based on the oxidation of glucose ring and conjugation of spermine. Drug-loaded magnetic dextran-spermine nanoparticles (DS-NPs) were prepared by in situ drug loading via ionic gelation. Fabricated nanoparticles have smaller size (60–100 nm), with relatively narrow size distribution (pdI = 0.175–0.251), and a positive surface charge (+ 17.1 to + 29.0 mV). The in vitro release study in simulated normal and inflamed organ environments confirmed the pH sensitivity of the drug release with a slight burst effect in normal conditions and accelerated release in acidic pH (final release < 70% and < 50% of the total encapsulated drug for pH 7.4 and pH 5.0, respectively). Antibacterial study on Staphylococcus aureus showed no changes in the bactericidal activity of encapsulated vancomycin. Cytotoxicity studies on HUVEC cells confirmed that drug-free nanoparticles exhibited no toxicity, even up to 1 mg/mL. Furthermore, the cytotoxicity of encapsulated vancomycin against HUVEC cells was lower than that of free vancomycin in all incubation times (24 h, 48 h, 72 h). [ABSTRACT FROM AUTHOR]

Salinity stress was imposed on Calendula officinalis L. by potassium chloride (KCl) and sodium chloride (NaCl) salts. This study evaluated the ameliorative effects of polyamine foliar application on growth indices and physiological traits of Calendula officinalis L. under salinity stress. A factorial experiment was arranged in a completely randomized design with three replications. The experiment was conducted in a commercial greenhouse in Pakdasht, Iran (2021). The treatments included salinity stress induced by NaCl and KCl salts (0, 50 and 100 mg L-1) and putrescine and spermine foliar applications (0, 1 and 2 mM). The results showed that the treatments had a significant effect on the measured variables. Increasing NaCl and KCl levels decreased the value of each variable, except for proline and superoxide dismutase activity. Putrescine and spermine foliar applications mitigated the effects of salt stress and improved the evaluated traits. The highest fresh and dry shoot weight (15.59-3.58 g), plant height (38.70 cm), leaf count (23), and flower count (12.50) were observed in the control. Also, the highest root fresh weight (5.17 g) and root volume (4.60 cm3) were obtained in response to NaCl 50 mg L-1 + spermidine 2 mM. The effects of NaCl 50 mg L-1 + putrescine 2 mM caused the highest root dry weight (1.42 g). The highest carotenoid content in petals (0.69 mg g-1 FW) and leaf chlorophyll content (14.54 mg g-1 FW) were obtained in response to KCl 50 mg L-1 + spermidine 2 mM. Also, the highest superoxide dismutase enzyme activity (85.90 unit of enzyme g-1 FW) and proline (8.4 mg g-1 FW) were obtained in response to NaCl 50 and 100 mg L-1, respectively. In summary, this research showed that polyamine foliar application, especially spermine, most significantly increased the growth indices and physiological traits in pot marigold under salinity stress. [ABSTRACT FROM AUTHOR]

Exogenous polyamines can elevate postharvest fruit cold resistance and alleviate cold injury. However, the mechanism, by which polyamines mediate cold tolerance, is still to be explored. So in this paper, the conjugated polyamines in tonoplast and vacuole conformation were illuminated in the flesh cells of peach fruit subjected to cold stress, which were pretreated with exogenous putrescine. The results showed that under cold condition, fruit firmness decreased and flesh browning area increased, and vacuole conformation changed. The cold injury could be alleviated by pretreatment with exogenous putrescine, as judged by stabilization of the vacuole conformation, increased fruit firmness and reduced flesh browning area. Furthermore, the cold alleviation was coupled with the increases in the levels of covalently conjugated putrescine and non-covalently conjugated spermidine and spermine in the tonoplast. The results suggested that these conjugated polyamines in tonoplast and vacuole conformation might be involved in putrescine-mediated cold tolerance. The suggestion was further verified by applications with inhibitors, phenanthroline and methylglyoxal-bis (guanylhydrazone) (MGBG). Phenanthroline and MGBG could restrain the putrescine-induced increases in covalently and non-covalently conjugated polyamines mentioned above in the tonoplast, respectively, and increase flesh browning area, decrease fruit firmness and vacuole conformation stabilization. So, we can conclude that exogenous putrescine alleviates cold injury in peach fruit via elevating the contents of the polyamines conjugated to the tonoplast and thereby maintaining vacuole conformation. [ABSTRACT FROM AUTHOR]

Background: It was previously shown that GlnA3sc enabled Streptomyces coelicolor to survive in excess polyamines. However, subsequent studies revealed that Rv1878, the corresponding Mycobacterium tuberculosis (M.tb) ortholog, was not essential for the detoxification of spermine (Spm), in M.tb. On the other hand, the multi-drug efflux pump Rv1877 was previously shown to enable export of a wide range of compounds, while Rv0191 was shown to be more specific to chloramphenicol. Rationale: Therefore, we first wanted to determine if detoxification of Spm by efflux can be achieved by any efflux pump, or if that was dependent upon the function of the pump. Next, since Rv1878 was found not to be essential for the detoxification of Spm, we sought to follow-up on the investigation of the physiological role of Rv1878 along with Rv1877 and Rv0191. Approach: To evaluate the specificity of efflux pumps in the mycobacterial tolerance to Spm, we generated unmarked ∆rv1877 and ∆rv0191 M.tb mutants and evaluated their susceptibility to Spm. To follow up on the investigation of any other physiological roles they may have, we characterized them along with the ∆rv1878 M.tb mutant. Results: The ∆rv1877 mutant was sensitive to Spm stress, while the ∆rv0191 mutant was not. On the other hand, the ∆rv1878 mutant grew better than the wild-type during iron starvation yet was sensitive to cell wall stress. The proteins Rv1877 and Rv1878 seemed to play physiological roles during hypoxia and acidic stress. Lastly, the ∆rv0191 mutant was the only mutant that was sensitive to oxidative stress. Conclusion: The multidrug MFS-type efflux pump Rv1877 is required for Spm detoxification, as opposed to Rv0191 which seems to play a more specific role. Moreover, Rv1878 seems to play a role in the regulation of iron homeostasis and the reconstitution of the cell wall of M.tb. On the other hand, the sensitivity of the ∆rv0191 mutant to oxidative stress, suggests that Rv0191 may be responsible for the transport of low molecular weight thiols. [ABSTRACT FROM AUTHOR]

The objective of this study was to quantify biogenic amines and to adapt equations for the calculation of the biogenic amine index (BAI) in rendered pig carcass meals (RPCM). Samples of RPCM from three different origins were evaluated: Group 1—experimentally produced meal; Group 2—meal produced in a plant dedicated to rendering pigs dead on the farm due to non-infectious causes; and Group 3—meal produced in commercial rendering plants. Group 1 meals were produced from sow carcasses that were stored either under environmental temperature (ET = 25 °C) or refrigeration temperature (RT = −6 °C), and their biogenic amine contents were analyzed at 0, 24, 48, and 72 h of storage. The levels of the biogenic amines phenylethylamine, putrescine, cadaverine, histamine, tyramine, spermidine, and spermine of all meals were determined by high-performance liquid chromatography, and their BAIs were calculated. Group 1 meals stored at ET presented higher phenylethylamine, putrescine, cadaverine, and tyramine contents compared with those stored at RT after 24 h storage, whereas spermidine and spermine contents decreased after 24 h of storage at ET. The adapted BAI can be used as a quality indicator of RPCM. [ABSTRACT FROM AUTHOR]

Osteoporosis is a prevalent metabolic bone disease. While drug therapy is essential to prevent bone loss in osteoporotic patients, current treatments are limited by side effects and high costs, necessitating the development of more effective and safer targeted therapies. Utilizing a zebrafish (Danio rerio) larval model of osteoporosis, we explored the influence of the metabolite spermine on bone homeostasis. Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption. Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity. Notably, spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae. At the molecular level, Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine, with P53 potentially acting downstream of Rac1. These findings were confirmed using mouse (Mus musculus) models, in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions, suggesting strong potential as a bone strengthening agent. This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development, highlighting pivotal molecular mediators. Given their efficacy and safety, human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents. [ABSTRACT FROM AUTHOR]

Abstract Decreased plasma spermine levels are associated with kidney dysfunction. However, the role of spermine in kidney disease remains largely unknown. Herein, it is demonstrated that spermine oxidase (SMOX), a key enzyme governing polyamine metabolism, is predominantly induced in tubular epithelium of human and mouse fibrotic kidneys, alongside a reduction in renal spermine content in mice. Moreover, renal SMOX expression is positively correlated with kidney fibrosis and function decline in patients with chronic kidney disease. Importantly, supplementation with exogenous spermine or genetically deficient SMOX markedly improves autophagy, reduces senescence, and attenuates fibrosis in mouse kidneys. Further, downregulation of ATG5, a critical component of autophagy, in tubular epithelial cells enhances SMOX expression and reduces spermine in TGF‐β1‐induced fibrogenesis in vitro and kidney fibrosis in vivo. Mechanically, ATG5 readily interacts with SMOX under physiological conditions and in TGF‐β1‐induced fibrogenic responses to preserve cellular spermine levels. Collectively, the findings suggest SMOX/spermine axis is a potential novel therapy to antagonize renal fibrosis, possibly by coordinating autophagy and suppressing senescence.

Background Polyamines have been reported to be associated with neurological function, but the associations between polyamines and the prognosis of ischemic stroke remain unclear. We aimed to prospectively investigate whether elevated plasma polyamine levels are associated with adverse outcomes in patients with ischemic stroke. Methods and Results Plasma polyamine levels were measured at admission in 3570 patients with acute ischemic stroke, and clinical outcomes were assessed at 3 months after stroke onset. The primary outcome was a composite outcome of death and major disability (modified Rankin Scale score≥3), and secondary outcomes included the individual outcomes of death and major disability. During a 3‐month follow‐up period, 877 participants (25.1%) experienced the primary outcome. Increased putrescines were associated with a decreased risk of the primary outcome (the highest versus the lowest tertile: odds ratio, 0.72 [95% CI, 0.58–0.91]; P=0.005) and major disability (odds ratio, 0.59 [95% CI, 0.47–0.74]; P

Objective: To evaluate the relationship between dietary polyamine intake and all-cause and cardiovascular disease (CVD)-related mortality in Korean population. Methods: A total of 37,715 participants were included in a population-based cohort study. Dietary polyamine intake (µmol/d) were calculated using the average spermidine and spermine content (µmol/g) and daily consumed food components (mg/d) from 12 food groups. Cox proportional hazards examined associations between dietary polyamine and all-cause and CVD-related mortality. Results: Among the participants, 2,080 all-cause and 483 CVD-related deaths occurred. The lowest risk of all-cause and CVD-related mortality was found in the highest tertile of fruit, vegetables, legume, nut and seafood-derived spermidine and spermine intake, after adjusting covariates. The relationship between dietary polyamine intake and all-cause and CVD-related mortality was more pronounced in men and older individuals than in their counterparts. Conclusions: Higher intake of mediterranean-like diet derived polyamine was associated with lower CVD-related and all-cause mortality in Korean adults.