Polyamine Levels Research Articles

Natural Product Quercetin-3-methyl ether Promotes Colorectal Cancer Cell Apoptosis by Downregulating Intracellular Polyamine Signaling.

Dysregulation of cellular metabolism is a key marker of cancer, and it is suggested that metabolism should be considered as a targeted weakness of colorectal cancer. Increased polyamine metabolism is a common metabolic change in tumors. Thus, targeting polyamine metabolism for anticancer therapy, particularly polyamine blockade therapy, has gradually become a hot topic. Quercetin-3-methyl ether is a natural compound existed in various plants with diverse biological activities like antioxidant and antiaging. Here, we reported that Quercetin-3-methyl ether inhibits colorectal cancer cell viability, and promotes apoptosis in a dose-dependent and time-dependent manner. Intriguingly, the polyamine levels, including spermidine and spermine, in colorectal cancer cells were reduced upon treatment of Quercetin-3-methyl ether. This is likely resulted from the downregulation of SMOX, a key enzyme in polyamine metabolism that catalyzes the oxidation of spermine to spermidine. These findings suggest Quercetin-3-methyl ether decreases cellular polyamine level by suppressing SMOX expression, thereby inducing colorectal cancer cell apoptosis. Our results also reveal a correlation between the anti-tumor activity of Quercetin-3-methyl ether and the polyamine metabolism modulation, which may provide new insights into a better understanding of the pharmacological activity of Quercetin-3-methyl ether and how it reprograms cellular polyamine metabolism.

The roles of polyamines in Malaysian herbs as a chemoprevention strategy: A scoping review

Maintaining normal polyamine levels is crucial for the physiological cellular process and differentiation because an imbalance of polyamine concentration affects the occurrence of neoplastic activities in many types of cancer diseases. Malaysian herbs have been purported to have anticancer properties that influence the polyamine’s bioavailability, leading to cancer cell death. Presently, the roles of polyamines in Malaysian herbs as chemoprevention have yet to be documented. Thus, this review aims to determine which Malaysian herbs have chemoprevention properties affecting polyamines and appraise the relationship between polyamine levels and Malaysian herbs and their cytotoxicity on cancer cells. The search, employing keywords like “Malaysian herbs”, “polyamines”, and “anticancer” or “chemoprevention”, yielded 256 articles. The articles were screened for their eligibility, befitting the objectives mentioned. The PRISMA-ScR checklist was employed to report the published findings from the databases. Thirteen articles meeting inclusion criteria were selected, highlighting 13 Malaysian herbs influencing the intracellular polyamines pathway. All herbs showed a significant reduction in ornithine decarboxylase (ODC) expression. In addition, Alpinia galanga and Aloe barbadensis showed an increase in catabolic polyamines expression, spermidine/spermine-N-acetyl transferase (SSAT) and spermine oxidase (SMO), respectively, leading to growth arrest and induction of apoptosis in cancer cells. The in vitro and in vivo studies demonstrated these herbs’ anti-proliferative effects on diverse cancer types, involving polyamine level modulation, intracellular dynamics, and chemopreventive mechanisms through apoptosis and anti-inflammatory responses. The findings underscore the potential of Malaysian herbs in cancer prevention by modulating the polyamine pathway.

Polyamines in Edible and Medicinal Fungi from Serbia: A Novel Perspective on Neuroprotective Properties.

The therapeutic effectiveness of current neurodegenerative disease treatments is still under debate because of problems with bioavailability and a range of side effects. Fungi, which are increasingly recognized as sources of natural antioxidants and acetylcholinesterase (AChE) enzyme inhibitors, may thus serve as potent neuroprotective agents. Previous studies have associated the anti-AChE and antioxidant activities of fungi mostly with polysaccharides and phenolic compounds, while other secondary metabolites such as polyamines (PAs) have been neglected. This study aimed to investigate eight edible and medicinal fungi from Serbia, marking the initial investigation into the neuroprotective capabilities of Postia caesia, Clitocybe odora, Clitopilus prunulus, and Morchella elata. Neuroprotective activity was examined using the Ellman assay, while the antioxidant capacity was tested by conducting DPPH, NO, ABTS, and FRAP tests. PA levels were determined by high-performance liquid chromatography (HPLC) coupled with fluorescent detection. Ganoderma applanatum and Lepista nuda exhibited the most robust anti-AChE (98.05 ± 0.83% and 99.94 ± 3.10%, respectively) and antioxidant activities, attributed to the synergistic effects of the total protein, total phenolic, and PA levels. Furthermore, P. caesia displayed significant AChE inhibition (88.21 ± 4.76%), primarily linked to the elevated spermidine (SPD) (62.98 ± 3.19 mg/kg d.w.) and putrescine (PUT) levels (55.87 ± 3.16 mg/kg d.w.). Our results highlight the need for thorough research to comprehend the intricate relationships between distinct fungus species and AChE inhibition. However, it is important to recognize that more research is required to identify the precise substances causing the reported inhibitory effects.

Exploring the interplay of phytohormones and polyamines in drought-stressed Cress (<i>Lepidium sativum</i> L.) leaves

The study investigated prolonged drought stress effects on phytohormone and polyamine levels in cress (Lepidium sativum L.) leaves, elucidating plant responses to harsh environments. Phytohormones, 12-oxophytodienoic acid (OPDA), Jasmonic acid (JA), Jasmonyl-Isoleucine (JA-Ile), Abscisic acid (ABA), and salicylic acid (SA) increased, especially ABA that rose consistently. Indole-3-acetic acid (IAA) responded akin to ABA and SA. Cytokinins such as zeatin (ZT) and isopentenyl adenine (iP) diversified drought tolerance, ZT fell sharply, and iP remained stable. Gibberellic acid (GA3) declined, while brassinolide (BL) surged with prolonged drought. Polyamines reduced, indicating sensitivity to severe drought. Findings uncovered intricate regulatory mechanisms for plant adaptation to water scarcity. Interaction of OPDA, JA, JA-Ile, ABA, SA, IAA, ZT, iP, GA3, BL, and polyamines contributes to drought coping and physiological balance. Insights into cress leaf response and drought tolerance mechanisms contribute significantly to plant drought adaptation understanding.

Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors.

S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.

Evaluation of Salt Stress-Induced Changes in Polyamine, Amino Acid, and Phytoalexin Profiles in Mature Fruits of Grapevine Cultivars Grown in Tunisian Oases

Salinity stress has become an increasing threat to viticulture in the Tunisian oasis, and more generally, the characterization of salinity tolerance markers can be of great interest for sustainable grape production. This study investigated some metabolic adaptations in different tissues of the ripe berries of indigenous grapevine cultivars after exposure to salt stress to identify the key traits of salt stress tolerance under oasis conditions. We especially focused on the adaptive responses occurring at the level of amino acids, polyamines, and stilbene phytoalexins in the grape berry skin, pulp, and seeds of six grapevine cultivars differing in phenotypic and ampelographic characteristics. Our data showed that amino acids accumulated strongly in the pulp and skin, while resveratrol, trans-piceid and trans-ε-viniferin, as major phytoalexins, significantly accumulated in the seeds. High salinity was also found to increase both the berry skin and pulp contents of essential amino acids such as threonine, valine, leucine, isoleucine, lysine, methionine, and phenylalanine. The amounts of stilbenes also increased under high salinity in the berry skin of all the studied cultivars. Polyamine homeostasis within the different berry tissues suggested enhanced polyamine biosynthesis rather than polyamine oxidation in response to high salinity. Our principal component analysis revealed a clear discrimination between the cultivars based on their metabolic profiles within the ripe berry tissues under high salinity.

DDR2-regulated arginase activity in ovarian cancer-associated fibroblasts promotes collagen production and tumor progression

Ovarian cancer has poor survival outcomes particularly for advanced stage, metastatic disease. Metastasis is promoted by interactions of stromal cells, such as cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), with tumor cells. CAFs play a key role in tumor progression by remodeling the TME and extracellular matrix (ECM) to result in a more permissive environment for tumor progression. It has been shown that fibroblasts, in particular myofibroblasts, utilize metabolism to support ECM remodeling. However, the intricate mechanisms by which CAFs support collagen production and tumor progression are poorly understood. In this study, we show that the fibrillar collagen receptor, Discoidin Domain Receptor 2 (DDR2), promotes collagen production in human and mouse omental CAFs through arginase activity. CAFs with high DDR2 or arginase promote tumor colonization in the omentum. In addition, DDR2-depleted CAFs had decreased ornithine levels leading to decreased collagen production and polyamine levels compared to WT control CAFs. Tumor cell invasion was decreased in the presence CAF conditioned media (CM) depleted of DDR2 or arginase-1, and this invasion defect was rescued in the presence of CM from DDR2-depleted CAFs that constitutively overexpressed arginase-1. Similarly, the addition of exogenous polyamines to CM from DDR2-depleted CAFs led to increased tumor cell invasion. We detected SNAI1 protein at the promoter region of the arginase-1 gene, and DDR2-depleted CAFs had decreased levels of SNAI1 protein at the arginase-1 promoter region. Furthermore, high stromal arginase-1 expression correlated with poor survival in ovarian cancer patients. These findings highlight how DDR2 regulates collagen production by CAFs in the tumor microenvironment by controlling the transcription of arginase-1, and CAFs are a major source of arginase activity and L-arginine metabolites in ovarian cancer models.

A simple, easy, and efficient HPTLC method for simultaneous determination of polyamines (putrescine, spermidine, and spermine) in plant tissues

Polyamine analysis has received a lot of attention in recent years because they are important in several physiological processes, including cell proliferation, differentiation, and growth. This study presents the development and validation of a user-friendly and convenient high-performance thin-layer chromatography (HPTLC) method, using benzoyl chloride as a derivatization agent for the analysis of three abundant polyamines. A comparative study with HPLC-MS/MS was performed to evaluate the putrescine, spermidine, and spermine content of plant tissues. The linear ranges for the determination of putrescine and spermine by HPTLC were lower than those of HPLC-MS/MS. Lower LODs were found for polyamine analysis using HPLC-MS/MS except for spermidine. The Pearson correlation coefficients of the two methods for putrescine, spermidine, and spermine were 0.982, 0.998, and 0.980, respectively, which confirms the applicability of both HPTLC-UV and LC-MS/MS methods. According to these results, the optimized HPTLC-UV method may be used as a practical analytical tool for screening polyamine levels in the horticultural, food, and pharmaceutical industries for quality control purposes.

Enriched endogenous free Spd and Spm in alfalfa (Medicago sativa L.) under drought stress enhance drought tolerance by inhibiting H2O2 production to increase antioxidant enzyme activity

Drought stress is a major factor limiting agricultural development, and exogenous polyamines (PAs) can increase plant drought resistance by enhancing antioxidant activity, but few studies have examined whether endogenous PAs enhance the plant antioxidant system. Here, to investigate the effects of endogenous PAs on the antioxidant system of alfalfa under drought stress and the underlying mechanisms, two alfalfa cultivars, Longzhong (drought resistant) and Gannong No. 3 (drought sensitive), were used as test materials, and their seedlings were treated with polyethylene glycol (PEG-6000) for 8 days at −1.2 MPa to simulate drought stress. The levels of free PAs [putrescine (Put), spermidine (Spd) and spermine (Spm)], hydrogen peroxide (H2O2), malondialdehyde (MDA), key PA metabolism enzyme [arginine decarboxylase (ADC), ornithine decarboxylase (ODC), S-adenosylmethionine decarboxylase (SAMDC), polyamine oxidase (PAO), and diamine oxidase (DAO)] activities, and antioxidant enzyme [superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD)] activities were measured. These physiological indicators were used for correlation analysis to investigate the relationship between PA metabolism and the antioxidant enzyme system. The results showed that PA synthesis in alfalfa under drought stress was dominated by the ADC pathway. Spd and Spm played an important role in improving drought tolerance. The high levels of ADC and SAMDC activities were facilitated by the conversion of Put to Spd and Spm. H2O2 generation by oxidative decomposition of PAs was mainly dependent on the oxidative decomposition of DAO but not PAO. Low DAO activity favored low H2O2 production. Spd, Spm, ADC, ODC and SAMDC were positively correlated with the antioxidant enzymes SOD, CAT and POD in both cultivars under drought. Therefore, we concluded that high ADC and SAMDC activities in alfalfa promoted the conversion of Put to Spd and Spm, leading to high accumulation of Spd and Spm and low Put accumulation. Low Put levels led to low H2O2 production through low DAO activity, and low H2O2 levels induced the expression of antioxidant enzyme-encoding genes to improve antioxidant enzyme activity and reduce MDA accumulation and thereby enhanced drought resistance in alfalfa.

Polyamine transport inhibition and cisplatin synergistically enhance tumor control through oxidative stress in murine head and neck cancer models

BackgroundSurgery and/or platinum-based chemoradiation remain standard of care for patients with head and neck squamous cell carcinoma (HNSCC). While these therapies are effective in a subset of patients, a substantial proportion experience recurrence or treatment resistance. As cisplatin mediates cytotoxicity through oxidative stress while polyamines play a role in redox regulation, we posited that combining cisplatin with polyamine transport inhibitor, AMXT-1501, would increase oxidative stress and tumor cell death in HNSCC cells. MethodsCell proliferation was measured in syngeneic mouse HNSCC cell lines treated with cisplatin ± AMXT-1501. Synergy was determined by administering cisplatin and AMXT-1501 at a ratio of 1:10 to cancer cells in vitro. Cancer cells were transferred onto mouse flanks to test the efficacy of treatments in vivo. Reactive oxygen species (ROS) were measured. Cellular apoptosis was measured with flow cytometry using Annexin V/PI staining. High-performance liquid chromatography (HPLC) was used to quantify polyamines in cell lines. Cell viability and ROS were measured in the presence of exogenous cationic amino acids. ResultsThe combination of cisplatin and AMXT-1501 synergize in vitro on HNSCC cell lines. In vivo combination treatment resulted in tumor growth inhibition greater than either treatment individually. The combination treatment increased ROS production and induced apoptotic cell death. HPLC revealed the synergistic mechanism was independent of intracellular polyamine levels. Supplementation of cationic amino acids partially rescued cancer cell viability and reduced ROS. ConclusionAMXT-1501 enhances the cytotoxic effects of cisplatin in vitro and in vivo in aggressive HNSCC cell lines through a polyamine-independent mechanism.

Hydrogen sulfide alleviates chilling injury of zucchini fruit by regulating antioxidant capacity, endogenous hydrogen sulfide, proline, and polyamine metabolism

Zucchini fruit was dipped in hydrogen sulfide (H2S) donor (1.0 mM NaHS) for 10 min and stored at 4 ± 1 °C to investigate the mechanism by which H2S treatment delays chilling injury (CI). The result showed that NaHS treatment inhibited the CI, and accumulations of malondialdehyde (MDA) and electrolyte leakage (EL), sustained hydrogen peroxide (H2O2) and superoxide anion (O2.−) production rate at a lower level, together with higher antioxidant enzyme activities of zucchini fruit. Furthermore, the research indicates that NaHS treatment can activate L-cysteine desulfhydrase (LCD) and D-cysteine desulfhydrase (DCD) to promote endogenous H2S accumulation which has a closely connection with alleviating chilling injury in zucchini. Meanwhile, the proline related synthetases enzyme was enhanced by NaHS treatment, which promoted proline accumulation. Likewise, higher polyamines (PAs) levels have been associated with inducing higher PAs related synthetases activities and lower PAs related degradation enzyme activities. Thus, NaHS treatment induced the antioxidant ability and improved cold stressed tolerance of zucchini by inducing endogenous H2S, proline, and PAs accumulation, maintaining membrane integrity and inhibiting oxidative stress to delay the CI of zucchini fruit.

Untargeted metabolomic profiling in children identifies novel pathways in asthma and atopy

BackgroundAsthma and other atopic disorders can present with varying clinical phenotypes marked by differential metabolomic manifestations and enriched biological pathways. ObjectiveTo identify these unique metabolomic profiles in atopy and asthma. MethodsWe analyzed baseline non-fasted plasma samples from a large multi-site pediatric population of 470 children < 13 years from three different sites in the US and France. Atopy (At+) was defined as skin prick test ≥ 3 mm and/or specific IgE ≥ 0.35 kUi/L, and/or total IgE ≥ 173 IU/mL. Asthma (As+) was based on physician’s diagnosis. The cohort was divided into four groups of varying combinations of As and At and six pairwise analyses were conducted to best assess differential metabolomic profiles between groups. Results210 children were classified as At-As-, 42 as At+As-, 74 as At-As+ and 144 as At+As+. Untargeted global metabolomic profiles were generated through Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy. We applied two independent machine learning classifiers and shortlisted 362 metabolites as discriminant features. Our analysis showed the most diverse metabolomic profile in the At+As+ / At-As- comparison, followed by the At-As+ / At-As- comparison, indicating that asthma is the most discriminant condition associated with metabolomic changes. At+As+ metabolomic profiles were characterized by higher levels of bile acids, sphingolipids, and phospholipids, and lower levels of polyamine, tryptophan, and gamma-glutamyl amino-acids. ConclusionAt+As+ phenotype displays a distinct metabolomic profile suggesting underlying mechanisms such as modulation of host-pathogen and gut microbiota interactions, epigenetic changes in T-cell differentiation, and lower antioxidant properties of the airway epithelium.

Impact of COVID-19 on sperm quality and the prostaglandin and polyamine systems in the seminal fluid.

The implications of SARS-CoV-2 infection on male fertility remain largely unknown. Besides their well-known pro- and anti-inflammatory actions, prostaglandins and polyamines are present in semen, where they play key roles in sperm quality. To analyze semen parameters, oxidative profile and the seminal fluid prostaglandin and polyamine systems in samples collected from individuals without coronavirus disease 2019 diagnosis and men who recovered from coronavirus disease 2019. This study compared semen collected from men without positive coronavirus disease 2019 diagnosis with samples obtained from individuals 1-6 months and 7-30 months post SARS-CoV-2 infection. Semen parameters, thiobarbituric acid reactive substances, cyclooxygenase 2 expression by fluorescence immunocytochemistry and immunoblotting, prostaglandin levels by enzyme immunoassay, ornithine decarboxylase activity by a radioactive assay, and polyamine and acetylated polyamine levels by thin-layer chromatography were assessed. In both groups of semen samples from coronavirus disease 2019 recovered men, sperm vitality, total and progressive sperm motility, and putrescine levels were significantly decreased when compared with samples from the uninfected group. In contrast, lipid peroxidation, leukocyte-associated cyclooxygenase 2 expression, and prostaglandin D2 levels were higher in semen from coronavirus disease 2019 recovered men than in samples from uninfected individuals. While sperm concentration and morphology, ornithine decarboxylase activity, and N-acetylputrescine levels were statistically diminished in semen obtained up to 6 months after coronavirus disease 2019 recovery, these parameters remained unchanged when samples were collected 7-30 months after coronavirus disease 2019 recovery. Coronavirus disease 2019 vaccination did not show negative effects on any of the parameters evaluated. Our work provides insights into the detrimental impact of coronavirus disease 2019 on several sperm parameters, in some cases, even more than a year after SARS-CoV-2 infection, which would be accompanied by alterations in the seminal fluid prostaglandin and polyamine profiles. Therefore, future treatments targeting the prostaglandin and polyamine pathways in coronavirus disease 2019 recovered men could lead to a successful reinstatement of semen parameters.

Polyamines in Ovarian Aging and Disease.

Ovarian aging and disease-related decline in fertility are challenging medical and economic issues with an increasing prevalence. Polyamines are a class of polycationic alkylamines widely distributed in mammals. They are small molecules essential for cell growth and development. Polyamines alleviate ovarian aging through various biological processes, including reproductive hormone synthesis, cell metabolism, programmed cell death, etc. However, an abnormal increase in polyamine levels can lead to ovarian damage and promote the development of ovarian disease. Therefore, polyamines have long been considered potential therapeutic targets for aging and disease, but their regulatory roles in the ovary deserve further investigation. This review discusses the mechanisms by which polyamines ameliorate human ovarian aging and disease through different biological processes, such as autophagy and oxidative stress, to develop safe and effective polyamine targeted therapy strategies for ovarian aging and the diseases.

Alleviation role of exogenous cadaverine on cell cycle, endogenous polyamines amounts and biochemical enzyme changes in barley seedlings under drought stress

Cadaverine (Cad), which has an independent synthesis pathway compared to other polyamine (PA) types, contributes to the health of plants by regulating plant growth and development, abiotic stress tolerance and antioxidant defense mechanisms. In this work, experiments were carried out to understand the effects of exogenous Cad (10 µM) application under drought stress (%22 PEG 6000) and without stress on cell cycle, total protein content, endogenous PA levels, and biochemical enzyme activities in barley (Hordeum vulgare cv. Burakbey) considering the potential of Cad to stimulate the drought-related tolerance system. Cad application in a stress-free environment showed an effect almost like low-impact drought stress, causing changes in all parameters examined compared to samples grown in distilled water environment (Control). The results clearly show that Cad applied against the negative effects of drought stress on all parameters creates a drought resistance mechanism of the plant. Accordingly, Cad applied together with drought stress increased the density of cells in the cell cycle (G1–S and S–G2 phases) and the amount of endogenous (spermidine 10% and spermine 40%) PAs. In addition, while superoxide dismutase (SOD) (5%), (CAT) (55%) and ascorbate peroxidase (APX) (18%) enzyme levels increased, a stress response mechanism occurred due to the decrease in total protein content (20%) and malondialdehyde (MDA) (80%). As a result, exogenous application of 10 µM Cad showed that it reduced the negative effects of drought stress on endogenous PA amounts, cell division and biochemical activities in barley.

Metabolic support by macrophages sustains colonic epithelial homeostasis

The intestinal epithelium has a high turnover rate and constantly renews itself through proliferation of intestinal crypt cells, which depends on insufficiently characterized signals from the microenvironment. Here, we showed that colonic macrophages were located directly adjacent to epithelial crypt cells in mice, where they metabolically supported epithelial cell proliferation in an mTORC1-dependent manner. Specifically, deletion of tuberous sclerosis complex 2 (Tsc2) in macrophages activated mTORC1 signaling that protected against colitis-induced intestinal damage and induced the synthesis of the polyamines spermidine and spermine. Epithelial cells ingested these polyamines and rewired their cellular metabolism to optimize proliferation and defense. Notably, spermine directly stimulated proliferation of colon epithelial cells and colon organoids. Genetic interference with polyamine production in macrophages altered global polyamine levels in the colon and modified epithelial cell proliferation. Our results suggest that macrophages act as "commensals" that provide metabolic support to promote efficient self-renewal of the colon epithelium.

Co-administration of curcumin and polyamines in high-fat diet induced obese rats: Assessment of changes in serum polyamine levels and some tissue parameters

Obesity is a non-communicable chronic disease that continues to increase around the world. Recently, it has been shown that curcumin positively affects lipid, energy metabolism, and body weight change. Moreover, polyamines are aliphatic polycations, which can be found in all mammalian cells and foods and have been shown to prevent obesity through many different mechanisms. However, whether the co-administration of curcumin and polyamines has synergistic effects has yet to be clarified. Our study aimed to examine the effects of curcumin and polyamines on obesity and to assess the changes in serum polyamine levels and tissue parameters. 28 Sprague-Dawley male rats were fed a high-fat diet for 10 weeks to develop obesity, and then they were randomly divided into 4 groups as the control group (CONT), curcumin group (CUR), polyamine group (POL), curcumin and polyamine group (CUR+POL) and supplements were administered for 6 weeks. As a result, the lowest feed consumption in rats was recorded in the CUR+POL group, and the group with the lowest weight after supplements was the POL group, then the CUR+POL, CONT, and CUR groups, respectively. N-acetyl putrescine and GABA levels increased significantly after obesity development. The total histopathological score in fat, liver, and kidney tissues increased significantly in the CONT group. In the CUR+POL group, damage to the tissues was in the direction of recovery compared to the other groups, and the expression of NF-κB was significantly low. These results suggest that combined curcumin and polyamines may have protective effects.

Polyamines in Canadian barley grains: Determination of their content and relationship with protein level

Barley is one of the important crops with diverse end-use purposes. In every use of barley grains, the protein fraction plays an important function impacting the quality of final products. Polyamines, having multiple nitrogen atoms in their chemical structure (e.g., putrescine, spermidine, and spermine), may be linked to the levels of protein and nitrogen reserves. In this study, thirteen Canadian barley varieties were characterized for their total polyamines and protein content. The effects of extractants on the extractability of polyamines were considered, and HCl (1 M) was found to be more effective than trichloroacetic acid (5% w/v) in extracting free polyamines from whole barley flour. The total polyamines content of barley grains varied from 6.46 to 11.47 mg/100 g dry basis and spermidine was the most abundant. Polyamine represented 0.045–0.071% w/w grain protein. Significant and positive correlations were found between protein content and levels of total polyamines (r = 0.798), putrescine (r = 0.771), and spermine (r = 0.668). Principal Component Analysis and K-Means Cluster Analysis divided the barley samples into one cluster (hulless barley for food) differentiated from the other (hulled barley for malting and feed) by their superiority in polyamine and protein content.

Comparative analysis of bile metabolic profile in patients with biliary obstruction complicated by Clonorchis sinensis infection.

Clonorchiasis is an important foodborne parasitic disease. However, eggs of Clonorchis sinensis (C. sinensis) cannot be detected in feces during biliary obstruction. Moreover, many diseases can cause biliary obstruction, such as gallstones, adenocarcinoma, cholangiocarcinoma and Ascaris lumbricoides infection. Therefore, it is of great significance to distinguish between patients of biliary obstruction and biliary obstruction with C. sinensis infection. A total of 48 biliary obstruction patients were enrolled, including 23 infected with C. sinensis (C. sinensis) (OB+C.s) and 25 non-infected subjects (OB). The bile samples were collected by endoscopic retrograde cholangiopancreatography and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). Additionally, multivariate statistical analysis methods were employed to identify differential metabolites. Next, bile amino acid levels were determined by targeted metabolomics analysis. A total of 146 and 132 significant metabolites were identified in electrospray ionization (ESI)+ and ESI- modes, respectively. The levels of amino acids (asparagine, glutamate, ornithine) and polyamines (spermidine and spermine) were significantly changed. Targeted analysis showed that the levels of amino acids (such as L-arginine, L-glutamine, L-lysine, L-propionic, and L-tyrosine) were lower in OB+C.s patients compared to those in OB patients. Marked metabolic pathways were involved in "Glutathione metabolism", "Caffeine metabolism", "Alanine, aspartate and glutamate metabolism", "Arginine and proline metabolism", "Purine metabolism", "Beta-Alanine metabolism", and "D-glutamine and D-glutamate metabolism". These results show that there were significant differences between OB+C.s and OB patients, especially in amino acids. The metabolic signature and perturbations in metabolic pathways may help to better distinguish OB+C.s and OB patients.

Synergistic antitumor efficacy of gemcitabine and cisplatin to induce ferroptosis in pancreatic ductal adenocarcinoma via Sp1-SAT1-polyamine metabolism pathway.

The combination of cisplatin and gemcitabine-based chemotherapy has been recommended as a preferred regimen for pancreatic ductal adenocarcinoma (PDAC) patients with germline-based mutations. However, the underlying mechanism remains poorly elucidated. Therefore, our study aimed to explore the mechanistic basis of the cell-killing activity of gemcitabine plus cisplatin and identify potential therapeutic targets. First, we explored the synergistic cytotoxic effects of gemcitabine and cisplatin on PDAC through in vitro and in vivo experiments. Then, we investigated ferroptosis-related biomarkers, to assess the impact of the combination therapy on ferroptosis. Using bioinformatics methods, we identified SAT1 as a potential key mediator of ferroptosis induced by gemcitabine and cisplatin. We tested the polyamine levels in PDAC cells by LC-MS after overexpressed or knocked down SAT1, and explored the role of polyamines in ferroptosis using exogenous supplementation. Finally, we explored the regulatory effect of Sp1 on SAT1 through ChIP-qPCR and dual-luciferase reporter assay. Gemcitabine plus cisplatin enhanced cell death and induced ferroptosis in PDAC. This combination upregulated SAT1 transcription by inhibiting Sp1. SAT1 activation promoted the catabolism of spermine and spermidine, leading to iron accumulation and lipid peroxide generation, ultimately resulting in ferroptosis. In summary, our findings suggested the gemcitabine and cisplatin combination therapy induced ferroptosis in a GSH-independent manner in PDAC. The combined treatment inhibited Sp1 and upregulated SAT1 transcription, leading to the breakdown of spermine and spermidine. Therefore, targeting SAT1-induced polyamine metabolism may represent a promising therapeutic strategy for PDAC.