Search Results (108)

L-asparaginase (L-ASNase) remains a vital chemotherapeutic agent for acute lymphoblastic leukemia (ALL), primarily due to its mechanism of depleting circulating asparagine essential for leukemic cell proliferation. However, existing ASNases (including pegylated ones) face limitations including immunogenicity, rapid clearance, and off-target toxicities. Earlier, we have shown that the conjugation of L-ASNase with the polyamines and their copolymers results in significant enhancement of the antiproliferative activity due to accumulation in tumor cells. We suggested that this effect is probably mediated by polyamine transport system (PTS) receptors that are overexpressed in ALL cells. Here, we investigated the effect of competitive inhibitors of PTS receptors to the L-ASNase interaction with cancer cells (L5178Y, K562 and A549). L-ASNase from Rhodospirillum rubrum (RrA), Erwinia carotovora (EwA), and Escherichia coli (EcA) were conjugated with natural polyamines (spermine—spm, spermidine—spd, putrescine—put) and a synthetic branched polymer, polyethyleneimine 2 kDa (PEI2 ), using carbodiimide chemistry. Polyamine conjugation with L-ASNase significantly increased enzyme binding and cellular uptake, as quantified by fluorimetry and confocal microscopy. This increased cellular uptake translated into increased cytotoxicity of L-ASNase conjugates. The presence of competitive ligands to PTS receptors decreased the uptake of polyamine-conjugated enzymes-fatty acid derivatives of polyamines produced the strongest suppression. Simultaneously with this suppression, in some cases, competitive ligands to PTS significantly promoted the uptake of the native unconjugated enzymes, “equalizing” the cellular access for native vs conjugated ASNase. The screening for competing inhibitors of PTS receptor-mediated endocytosis revealed spermine and caproate/lipoate derivatives as the most potent inhibitors or antagonists, significantly reducing the cytostatic efficacy of polyamine-conjugated ASNases. The results obtained emphasize the complex, cell-type-dependent and inhibitor-specific nature of these interactions, which highlights the profound involvement of PTS in L-ASNase internalization and cytotoxic activity. These findings support the viability of polyamine conjugation as a strategy to enhance L-ASNase delivery and therapeutic efficacy by targeting the PTS. Full article

Fomes fomentarius (L.) Fr. has been valued since the 15th century across Europe, including the Balkan region, for its medicinal and traditional uses such as tinder production, spiritual practices, wound healing, and hemostasis. This study analyzes three Balkan strains, focusing on micro- and macroelements, polyamines (PAs), and phenolic compounds in hot water (H₂O), chloroform (CHCl₃), hydroethanolic (EtOH), and hydromethanolic (MeOH) extracts. Micro- and macroelements were determined using atomic absorption spectrophotometry (AAS), while PAs were quantified using high-performance liquid chromatography with fluorescence detection (HPLC-FD). Phenolic profiles were determined using liquid chromatography–mass spectrometry (LC-MS/MS), with total phenolic content (TPC) assessed using the Folin–Ciocalteu method. Antioxidant activity was evaluated via DPPH, ABTS, NO scavenging, lipid peroxidation inhibition, and FRAP assays, alongside anti-acetylcholinesterase and antiproliferative activity assessments. This study represents the first investigation of PA profiles in F. fomentarius, with total PA levels ranging from 32.67 to 2910.09 nmol/g dry weight (d.w.). The Bosnian strain exhibited the highest PA levels, with spermidine (SPD) concentrations ranging from 899.96 to 2910.09 nmol/g d.w. LC-MS/MS analysis identified several bioactive phenolics, including amentoflavone, baicalein, chrysoeriol, esculetin, and scopoletin—reported here for the first time in this fungus. The H₂O and EtOH extracts from the Croatian and Serbian strains showed higher TPC levels, correlating with notable antioxidant activity. The EtOH and MeOH extracts demonstrated significant anti-acetylcholinesterase and antiproliferative activities, emphasizing their medicinal potential. These findings highlight the therapeutic potential of polar extracts from Balkan F. fomentarius. Full article

Populus alba clone ‘Villafranca’ (white poplar), highly suitable for biomass production and ecosystem restoration, is a model system for molecular and physiological studies, but no reports are available concerning seed quality. Although clonal propagation is the preferred approach for commercial purposes, attention should be given to face genetic variability losses in the existing germplasm. To address this challenge, new populations should be developed starting from seeds, overcoming the issues of low germinability and viability during storage. This study proposes to develop tailored treatments to improve the germination of long-term stored white poplar seeds. Priming and soaking protocols, based on the use of water or spermidine (Spd, 50 and 100 μM), were tested. Treatment efficacy was assessed based on germination parameters, reactive oxygen species (ROS) profiles, and the expression patterns of genes with key roles in early seed germination. Soaking with 100 μM Spd for 4 h significantly enhanced germination percentage and speed. Low ROS levels were evidenced in the Spd-treated seeds, compared to water-soaked seeds. High expression of genes involved in desiccation tolerance acquisition, polyamine biosynthesis, and antioxidant defense was observed only in dry seeds. The results are discussed in view of the potential protective role of Spd. Full article

Tomato (Solanum lycopersicum L.) is one of the most widely consumed vegetables globally and plays a crucial role in food security. However, rising temperatures due to climate change pose a significant threat to tomato cultivation by reducing yield and fruit quality. Among various abiotic stresses, heat stress (HS) can severely impair tomato growth, reproduction, and physiological functions. Polyamines (PAs), such as spermidine (Spd), putrescine (Put), and spermine (Spm), are natural compounds that play vital roles in plant stress tolerance by modulating growth and physiological responses. This review evaluates the effects of HS on tomatoes and examines the potential of exogenously applied PAs to mitigate HS. Through detailed analysis of agronomic, physiological, and biochemical responses, the review highlights how PAs can enhance heat tolerance by improving antioxidant activity, stabilizing cellular membranes, and maintaining photosynthetic efficiency. Understanding these mechanisms can aid in developing strategies to improve tomato resilience under climate stress and ensure sustainable production. Full article

Viral infections of the reproductive tract and testis in male yaks, often resulting from natural mating under grazing conditions, can lead to infertility due to Leydig cell (LC) apoptosis, immune activation, oxidative stress, and reduced testosterone production. Spermidine (SPD), a potential therapeutic agent with antioxidant and anti-aging properties, might alleviate oxidant stress, immune response, and virus infection caused by apoptosis. In this study, firstly testicular Leydig cells of yak were induced with Poly(I:C), the pathogen-associated molecular pattern of the dsRNA virus, as a pathogenic model at the cellular level. Secondly, immune response, apoptosis, oxidative stress, and testosterone synthesis were measured in LC with or without SPD culture medium. Finally, transcriptomic sequencing was utilized to investigate the molecular mechanisms underlying the protective effects of SPD. These results suggested Poly(I:C) damaged the function of Leydig cells, significantly decreased the concentration of testosterone, and induced immune response, oxidative stress, and cell apoptosis, while SPD significantly alleviated the immune response and oxidative stress, and then significantly inhibited cell apoptosis and restores testosterone production in LCs. Transcriptomic analysis revealed that SPD significantly alleviates inflammation and apoptosis induced by Poly(I:C), reducing immune response and cellular damage through the regulation of several key gene expressions. These findings suggest SPD has the potential ability to mitigate Poly(I:C)-induced immune response, oxidative stress, and apoptosis, and then restore testosterone production in Leydig cells, offering a promising strategy to protect and enhance male yak fertility after infection with dsRNA virus. Full article

In this study, a method for the determination of eight biogenic amines (BAs), including tyramine (Tyr), 2-phenylethylamine (2-Phe), histamine (His), tryptamine (Trp), spermidine (Spd), spermine (Spm), cadaverine (Cad), and putrescine (Put), in crab was established using ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS), using a magnetic solid-phase extraction (MSPE) pretreatment, without derivatization, and the content changes in regard to these eight biogenic amines in the traditional Chinese dish, pickled swimming crabs, were investigated. The samples were purified via MSPE, using C nanofiber-coated magnetic nanoparticles (Fe₃O₄@C-NFs) as sorbents. The experimental variables involved in the MSPE, including the solution pH, adsorption and desorption time, adsorbent usage, and type and volume of the eluent, were investigated and optimized. Method validation indicated that the developed method showed good linearity (R² > 0.995); the average recovery rates were 84.7% to 115%, with the intra-day and inter-day relative standard deviations (RSD, n = 6) ranging from 3.7% to 7.5% and 4.2% to 7.7%, respectively. The limit of detection (LOD) and limit of quantification (LOQ) for the eight BAs were 0.1 mg/kg~1.0 mg/kg and 0.3 mg/kg~3.0 mg/kg, respectively. Finally, this method was applied to determine the changes in the eight biogenic amines in pickled swimming crabs (Portunus trituberculatus) during storage at 20 °C and 400 BAC. Among the BAs evaluated, Cad, Put, and Tyr were the predominant amines formed during storage. The final content of Cad, Put, and Tyr reached 22.9, 20.1, and 29.0 mg/100 g at 4 °C for 16 d, and 47.1, 52.3, and 72.0 mg/100 g at 20 °C for 96 h, respectively. The results from this study can be used to expand the application range of magnetic materials in biogenic amine pretreatment and to strengthen the quality control of the traditional Chinese dish, pickled swimming crabs. Full article

Seed aging has adverse effects on agricultural production, mainly because seed vigor is inhibited. Spermidine can improve seed vitality and germination ability to a certain extent and is essential for plant growth and plant response to stress. This study explored how spermidine counteracted aging effects on sorghum seed germination through antioxidant metabolism regulation. Aged seeds showed decreased vigor due to heightened reactive oxygen species (ROS) and diminished antioxidants. Applying spermidine notably enhanced aged seeds’ germination and vigor by boosting antioxidant enzyme activity and curbing ROS. Integrated transcriptomic, proteomic, and metabolomic analyses demonstrated that the majority of differentially expressed genes following exogenous spermidine treatment in aged sorghum seeds were significantly enriched in pathways related to glutathione metabolism, phenylpropanoid, and flavonoid biosynthesis, resulting in increased expression of genes encoding peroxidase, chalcone synthase, and glutathione s-transferase. Exogenous spermidine facilitated the synthesis of peroxidases and glutathione transferases. Analysis of flavonoid pathway intermediates showed a notable increase in antioxidant metabolites like isoquercitrin, underscoring their role in oxidative stress resistance. This multi-omics strategy underscores Spd’s role in boosting aged seeds’ antioxidants, highlighting the molecular basis of seed aging and Spd’s rejuvenating impact. Full article

Polyamines (PAs) are low-molecular-weight compounds that contain amino groups. PAs are present in a variety of organisms, including plants, animals and microorganisms. In plants, the main PAs are putrescine (PUT), spermidine (SPD) and spermine (SPM). They play crucial physiological roles in plant development, including flowering, fruit set, growth, ripening and metabolic processes. In addition, PAs are components of the diet and have a role in health and disease. Furthermore, PAs have been demonstrated to help overcome the negative effects of adverse environmental factors of both biotic and abiotic stresses. Thus, the main objective of this review was to examine the recent literature regarding the mentioned effects of PAs apart from the impact of preharvest PAs treatments, applied at different stages of fruit development, on fresh fruit crop yield and fruit quality properties at harvest, and in their maintenance during storage, with a special emphasis on the fruit content in bioactive compounds with antioxidant activity. Moreover, this review addressed the impact of PAs on other physiological processes affecting crop yield such as flowering and fruit set. Full article

Background: Polyamines, including spermidine (SPD), spermine (SPM) and putrescine (PUT), are essential for cellular physiology and various cellular processes. This study aimed to examine the associations of dietary polyamines intake and all-cause mortality and incident cardiovascular disease (CVD). Methods: This prospective cohort study included 184,732 participants without CVD at baseline from the UK Biobank who had completed at least one dietary questionnaire. Diet was assessed using Oxford WebQ, a web-based 24 h recall questionnaire, with polyamines intakes estimated from previous studies. Cox proportional models with restricted cubic splines were employed to investigate nonlinear associations. The primary endpoint was all-cause mortality or incident CVD (including CVD death, coronary heart disease and stroke). Results: During a median follow-up period of 11.5 years, 7348 (3.9%) participants died and 12,316 (6.5%) developed incident CVD. Polyamines intake showed nonlinear associations with all-cause mortality and incident CVD (P for nonlinear < 0.01). Compared to the lowest quintile group of dietary polyamines intake (≤17.4 mg/day), the quintile 2 to 5 groups demonstrated a reduced risk of all-cause mortality, with the lowest risk in quintile 2 group (>17.4–22.3 mg/day) (HR:0.82, 95% CI: 0.76–0.88). Similar results were observed for incident CVD, with the lowest risk in the quintile 4 group (>27.1–33.5 mg/day) (HR: 0.86, 95% CI: 0.82–0.92). Conclusions: We found that dietary polyamines intake was associated with a lower risk of all-cause mortality or incident CVD. Furthermore, our study identified an optimal range of dietary polyamines intake. Full article

The anti-cancer potential of eugenol (EUG) is well recognized, whereas that of spermidine (SPD) is subject to dispute and requires further research. The anti-tumorigenic potential of wheat germ SPD (150 µM) and clove EUG (100 µM), alone, in combination as SPD+EUG (50 µM + 100 µM) and, as a supplement (SUPPL; 0.6 µM SPD + 50 µM EUG), was investigated on both metastatic SW620 and primary Caco-2 colorectal cancer (CRC) spheroids. Compared to untreated controls, all treatments significantly reduced the vitality and spheroid area, increased the necrotic area, and induced apoptosis on both cell-type spheroids after 96 h, with a reduced migration evident in 2D (two-dimensional) cultures after 48 h. The comparable anti-CRC effects of the SPD+EUG and the SUPPL reflected a wide-range dose efficacy of SPD and EUG. It is of note that SPD+EUG induced a synergistic effect on the increased caspase-3 expression and reduced the migration percentage in SW620. In more physiologically relevant intestinal equivalents (healthy enterocytes [NCM460], fibroblasts [L929], and monocytes [U937]) containing embedded SW620/Caco-2 spheroids, SPD+EUG administration significantly reduced the spheroid CEA marker and proliferation, whilst simultaneously increasing occludin, autophagy LC3-II expression, and monocyte differentiation, compared to the control models. Exogenous SPD, alone and in combination with EUG, displayed an anti-CRC potential on tumor growth and metastasis, and warrants further investigation. Full article

Lisianthus (Eustoma grandiflorum Raf. Shinn.) is a valued plant known for its diverse flower colors and long vase life. Despite considerable research on the physiological roles of osmolytes, polyamines, and phenolic compounds, there is a lack of understanding regarding their specific accumulation patterns across various lisianthus cultivars and organs. This study aims to compare eleven lisianthus cultivars with varying flowering periods according to their accumulation of osmolytes, polyamines, phenolic content, and antioxidant capacities and measure their resistance to abiotic stress factors. High-performance liquid chromatography coupled with fluorescent detection was employed to quantify putrescine (PUT), spermidine (SPD), and spermine (SPM). In addition, proline (PRO), glycine betaine (GB), antioxidant capacities, phenolic content, and flavonoid contents were assessed spectrophotometrically. This comprehensive analysis allowed for a detailed understanding of the biochemical markers. The result indicates a significant genotype and organ-dependent variation in accumulation patterns of inspected metabolites and antioxidant activities. The petals of Rosita Green exhibited the highest levels of phenols and flavonoids, whereas the petals of Rosita Blue Picote demonstrated the highest concentrations of osmolytes. Polyamines were found to be more concentrated in the petals than in the leaves. The average values indicated high levels of polyamines in the Mariachi Carmine (PUT 186.72 nmol g⁻¹ DW) and Mariachi Pink (SPD 227.4 nmol g⁻¹ DW) cultivars. These findings underscore the significance of inspected compounds in stress tolerance among cultivars with different flowering periods, providing insights for optimizing cultivation strategies for lisianthus. Full article

This paper aims to clarify the effects of different exogenous phytohormones on the physiological traits of rice (Oryza sativa L.) at the early stage of irrigation under low-temperature stress. In this study, two types of rice varieties with different temperature sensitivities screened out previously, namely, a cold-tolerant variety (Nan Jing 9108) and a low-temperature-sensitive variety (Hui Liang You 898), were used in pots to simulate the process of low-temperature stress in rice at the early stage of grouting (6–9 days after anthesis) with artificial low-temperature treatments. The experimental treatments were 450 mg L⁻¹ Methyl jasmine acid (MJ), 46 mg L⁻¹ Melatonin (MT), 69 mg L⁻¹ Salicylate (SA), 40 mg L⁻¹ Erythromycin (GA₃), 25 mg L⁻¹ Zeatin (Z), 145 mg L⁻¹ Spermidine (SPD), and 5 mg L⁻¹ Abscisic acid (ABA) sprayed on rice before low-temperature stress, while low-temperature treatment without spraying (DK) and conventional planting without spraying (CK) were added as the control. The results showed that compared with the room temperature control (CK, sprayed with deionized water), the low-temperature control (DK, low-temperature treatment, and sprayed with deionized water) all significantly reduced the rice grain yield. Different exogenous hormones sprayed before low-temperature stress could increase rice yield, among which, Z and SPD spraying treatments had a better effect on the yield of Hui Liang You 898, while different exogenous hormone treatments increased the yield of Nan Jing 9108 in an average manner. The Z and SPD treatments increased the yield of Hui Liang You 898 by 24.87% and 26.16% and that of Nan Jing 9108 by 15.87% and 17.80%, respectively. This was mainly attributed to the significant increase in thousand-grain weight and fruiting rate, while there was no significant difference in the number of spikes and number of grains. The different exogenous hormone treatments were able to delay leaf senescence, enhance the photosynthetic production capacity of plants by increasing leaf chlorophyll content, and thus increase the accumulation of photosynthetic assimilation products and population growth rate after flowering. Among them, both Z and SPD treatments resulted in a population growth rate of more than 30% from spike flushing to maturity, which led to a higher dry matter accumulation of the plant at maturity. In addition, in the dry matter distribution of the plant at maturity, the seeds occupied a higher accumulation amount and proportion compared with the respective DK; the SPD treatment resulted in the maximum distribution rate of seeds at maturity of Hui Liang You 898, with an increase of 8.27%, and the Z treatment resulted in the maximum distribution rate of seeds at maturity of Nan Jing 9108, with an increase of 7.34%. At the same time, the Z treatment significantly increased the activities of adenosine diphosphate glucose phosphorylated enzyme (AGP) and starch branching enzyme (SBE) in the grains of both varieties, which resulted in the accumulation of more starch and ultimately increased the rice grain yield. The results verified that different exogenous phytohormones could be used to regulate the insufficiency of grouting caused by low-temperature stress during the grouting and fruiting stages of rice and enriched their agronomic and physiological traits in response at the same time. Full article

Rhodamine 6G (R6G) and 4-nitro-2,1,3-benzoxadiazole (NBD) linked through a spacer molecule spermidine (spd), R6G-spd-NBD, produces a fluorescent probe with pH-sensitive FRET (Förster (fluorescence) resonance energy transfer) effect that can be useful in a variety of diagnostic applications. Specifically, cancer cells can be spotted due to a local decrease in pH (Warburg effect). In this research, we applied this approach to intracellular infectious diseases—namely, leishmaniasis, brucellosis, and tuberculosis, difficult to treat because of their localization inside macrophages. R6G-spd-NBD offers an opportunity to detect such bacteria and potentially deliver therapeutic targets to treat them. The nanogel formulation of the R6G-spd-NBD probe (nanoparticles based on chitosan or heparin grafted with lipoic acid residues, Chit-LA and Hep-LA) was obtained to improve the pH sensitivity in the desired pH range (5.5–7.5), providing selective visualization and targeting of bacterial cells, thereby enhancing the capabilities of CLSM (confocal laser scanning microscopy) imaging. According to AFM (atomic force microscopy) data, nanogel particles containing R6G-spd-NBD of compact structure and spherical shape are formed, with a diameter of 70–100 nm. The nanogel formulation of the R6G-spd-NBD further improves absorption and penetration into bacteria, including those located inside macrophages. Due to the negative charge of the bacteria surface, the absorption of positively charged R6G-spd-NBD, and even more so in the chitosan derivatives’ nanogel particles, is pronounced. Additionally, with a pH-sensitive R6G-spd-NBD fluorescent probe, the macrophages’ lysosomes can be easily distinguished due to their acidic pH environment. CLSM was used to visualize samples of macrophage cells containing absorbed bacteria. The created nanoparticles showed a significant selectivity to model E. coli vs. Lactobacillus bacterial cells, and the R6G-spd-NBD agent, being a mild bactericide, cleared over 50% E.coli in conditions where Lactobacillus remained almost unaffected. Taken together, our data indicate that R6G-spd-NBD, as well as similar compounds, can have value not only for diagnostic, but also for theranostic applications. Full article

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. Full article

Low temperature is a common abiotic stress that causes significant damage to crop production. Polyamines (PAs) are a class of aliphatic amine compounds that serve as regulatory molecules involved in plant growth, development, and response to abiotic and biotic stresses. In this study, we found that the exogenous application of two concentrations of spermidine (Spd) significantly enhanced the freezing tolerance of three differently matured rapeseed (Brassica napus L.) varieties, as manifested by higher survival rates, lower freezing injury indexes, and reduced H₂O₂ content. RNA-seq and qRT-PCR analyses showed that Spd enhanced the freezing tolerance of rapeseed by regulating genes related to the PA metabolic pathway and antioxidant mechanism, and generally inhibited the expression of genes related to the JA signaling pathway. This study provides a reference basis for understanding the functionality and molecular mechanisms of polyamines in the response of rapeseed to freezing stress. Full article