INTRODUCTION With the expansion of the ageing population,cognitive decline has become an increas-ingly pressing challenge.1 As life expectancy increases,its socioeconomic burden is also increasing,highlighting the urg...INTRODUCTION With the expansion of the ageing population,cognitive decline has become an increas-ingly pressing challenge.1 As life expectancy increases,its socioeconomic burden is also increasing,highlighting the urgent need for effective interventions.Numerous studies suggest that specific dietary patterns and nutritional interventions may help mitigate cognitive decline associated with ageing.展开更多
Waterlogging stress significantly impairs plant growth and reduces crop yields.Spermidine(Spd),functioning as a second messenger,demonstrates positive effects on plant growth under waterlogging stress conditions.Howev...Waterlogging stress significantly impairs plant growth and reduces crop yields.Spermidine(Spd),functioning as a second messenger,demonstrates positive effects on plant growth under waterlogging stress conditions.However,the molecular mechanisms by which exogenous Spd application alleviates waterlogging stress remain unclear.This study employed physiological analysis and multi-omics approaches to investigate the effect of Spd application on waterlogging stress.The application of Spd enhanced the expression of genes related to light-harvesting complex(LHC),photosynthesis,and starch-related pathways,while inhibiting chlorophyll degradation and maintaining higher photosynthetic rates,thereby increasing biomass accumulation under waterlogging stress.The activation of genes associated with trehalose and Spd biosynthesis resulted in elevated accumulation of trehalose and endogenous Spd.The inhibition of 1-aminocyclopropane-1-carboxylic acid(ACC)oxidase(ACO)expression contributed to reduced ethylene emission,enhancing maize resistance to waterlogging.Following Spd application,auxin-related genes were up-regulated and indole acetic acid(IAA)content increased,promoting cell elongation in maize and maintaining normal growth under waterlogging stress.Additionally,the upregulation of lipid-related genes led to increased lipid content,protecting cell membranes under waterlogging conditions.These molecular and physiological modifications collectively enhanced resistance to waterlogging stress.These findings advance our understanding of Spd's regulatory roles in mitigating waterlogging damage and provide valuable insights for breeding waterlogging-tolerant maize varieties.展开更多
Diabetic wounds are among the most challenging chronic wounds to heal,due to the presence of multiple factors,including continuous oxidative stress,impaired vascular integrity,and biofilm formation.The development of ...Diabetic wounds are among the most challenging chronic wounds to heal,due to the presence of multiple factors,including continuous oxidative stress,impaired vascular integrity,and biofilm formation.The development of innovative treatment strategies is of paramount importance for the management of diabetic wounds.Stemmed from the pleiotropic physicochemical properties of ferrocene and spermidine,this essay reported the ferrocene-spermidine co-polymer(Fc S)for the first time through facile amidation reaction.Molecular dynamics simulation revealed its self-assembly through hydrogen bonds,van der Waals forces instead of traditional nanoprecipitation.The self-assembled nanoparticles were demonstrated to exhibit great antioxidant property on cells to facilitate their migration and angiogenesis.Moreover,the integration with photocuring hydrogel,gelatin methacrylate(Gel MA),to construct Fc S nanoparticles loaded wound dressing(Gel MA@Fc S)further confirmed the potential on promoting diabetic wound enclosure through enhancement of re-epithelization and collagen deposition.Together with its great biocompatibility and biosafety,Gel MA@Fc S is expected to be developed into a wound dressing for clinical diabetic wounds management.展开更多
Two wheat cultivars （Triticum aestivum L.） were used to evaluate the effects ofpost-anthesis severe water deficit （SD） on starch content and granule size distribution and their relations with ethylene and spermidi...Two wheat cultivars （Triticum aestivum L.） were used to evaluate the effects ofpost-anthesis severe water deficit （SD） on starch content and granule size distribution and their relations with ethylene and spermidine （Spd）. Comparison to the well-watered （WW） treatment, SD led to lower Spd and higher 1-aminocylopropane-l-carboxylic acid （ACC） concentrations and ethylene evolution rate （EER） in grains at the critical stage of forming starch granules. Application of Spd or aminoethoxyvinylglycine （AVG） significantly reduced ACC concentration and EER and increased Spd concentration, while ethephon or methylglyoxal-bis （MGBG） had an opposite impact. The volume and surface area distribution of starch granules showed a bimodal curve, while the number distribution exhibited a unimodal curve. SD caused a marked drop in grain weight, grain number and starch content, also led to a significant reduction in the proportion （both by volume and by surface area） of B-type starch granules （〈10 Ixm）, with an increase in those of A-type starch granules （〉10 ~tm）. Application of Spd or AVG increased the proportion （both by volume and by surface area） of B-type starch granules under SD. Correlation analysis suggested that ethylene and Spd showed an antagonism relation in the formation of B-type granules. These results suggested that it would be good for the formation of B-type starch granules to have the physiological traits of higher Spd and lower ACC concentrations and ethylene emission under SD.展开更多
In order to study how exogenous hormones in C.lanceolata(gymnosperm)regulate somatic embryogenesis,we measured the endogenous phytohormones of two genotypes with different somatic embryogenesis efficiency and found th...In order to study how exogenous hormones in C.lanceolata(gymnosperm)regulate somatic embryogenesis,we measured the endogenous phytohormones of two genotypes with different somatic embryogenesis efficiency and found that an increase in endogenous concentrations of IAA and ABA may be correlated to more efficient somatic embryogenesis.By applying exogenous spermidine,we found that exogenous hormones may affect somatic embryogenesis efficiency through affecting the endogenous phytohormone content.Based on these results,further studies can be conducted whereby the concentration of exogenous hormones or the levels of endogenous phytohormones by molecular methods are regulated to promote somatic embryogenesis.Our research may benefit the long-term economic output of the forestry industry and lays the foundation to studying the molecular mechanism that controls somatic embryogenesis efficiency.展开更多
The peppers which were treated at ice-temperature for 6 hours and 1 mmol/L spermidine for 10 min, followed by cold storage (4℃ ± 1℃) respectively were investigated. The results indicated that the chilling injur...The peppers which were treated at ice-temperature for 6 hours and 1 mmol/L spermidine for 10 min, followed by cold storage (4℃ ± 1℃) respectively were investigated. The results indicated that the chilling injury was delayed and reduced by ice-temperature and spermidine treatments. Comparing with control group, ice-temperature and spermidine exerted significant effects on reduction of ascorbic acid (Vc) and chlororphyll contents, relatively high activity of superoxide dismutase (SOD), accumulation of malondialdehyde (MDA) as well as the increase of cell membrane penetrability. The results indicated that the spermidine and ice-temperature induced the activity of antioxidant enzyme SOD and maintained higher defence-related compound Vc as well as lower levels of membrane lipid peroxidation, which may be associated with chilling injury alleviation. There was a difference between ice-temperature treatment and spermidine treatment after 30 days. The results suggested that spermidine was more effective in reducing chilling sensitivity and prolonging storage of peppers.展开更多
Exogenous application of spermidine（Spd） has been reported to modulate physiological processes and alleviate salt-induced damage to growth and productivity of several plants including rice. Employing a proteomic app...Exogenous application of spermidine（Spd） has been reported to modulate physiological processes and alleviate salt-induced damage to growth and productivity of several plants including rice. Employing a proteomic approach, we aimed at identifying rice leaf and grain proteins differentially expressing under salt stress, and in response to Spd prior to Na Cl treatment. A total of 9 and 20 differentially expressed protein spots were identified in the leaves of salt-tolerant（Pokkali） and saltsensitive（KDML105） rice cultivars, respectively. Differential proteins common to both cultivars included a photosynthetic light reaction protein（oxygen-evolving complex protein 1）, enzymes of Calvin cycle and glycolysis（fructose-bisphosphate aldolase and triose-phosphate isomerase）, malate dehydrogenase, superoxide dismutase and a hypothetical protein（Os I_18213）. Most proteins were present at higher intensities in Pokkali leaves. The photosynthetic oxygen-evolving enhancer protein 2 was detected only in Pokkali and was up-regulated by salt-stress and further enhanced by Spd treatment. All three spots identified as superoxide dismutase in KDML105 were up-regulated by Na Cl but down-regulated when treated with Spd prior to Na Cl, indicating that Spd acted directly as antioxidants. Important differential stress proteins detected in mature grains of both rice cultivars were late embryogenesis abundant proteins with protective roles and an antioxidant protein, 1-Cys-peroxiredoxin. Higher salt tolerance of Pokkali partly resulted from higher intensities and more responsiveness of the proteins relating to photosynthesis light reactions, energy metabolism, antioxidant enzymes in the leaves, and stress proteins with protective roles in the grains.展开更多
A monoclonal antibody was first prepared by fusion of mouse myeloma cells (SP2/0-Ag-14) with spleen cells isolated from male BALB/ c mice immunized with spermidine-bovine serum albumin conjugate (SPD- BSA). The hybrid...A monoclonal antibody was first prepared by fusion of mouse myeloma cells (SP2/0-Ag-14) with spleen cells isolated from male BALB/ c mice immunized with spermidine-bovine serum albumin conjugate (SPD- BSA). The hybridoma cell line producing antibody specific for spermidine was cultured in vitro and after i. p. into mice, the ascitic fluid gave suitably high dilution titres (1: 106) by enzyme immunoassay. This monoclonal antibody is of IgG1 class and the bimolecular compleex with molecular weight of 52KD and 27 KD. The monoclonal antibody was clearly specific to spermidine comparing with spermine or putriscine. Monclonal antibody may prove to be useful in the rapid diagnosis and evaluation of patients with cancer.展开更多
AIM:To test the growth-promoting activity of the polyamine spermidine bound to various polymeric compounds in supramolecular complexes.METHODS:A thiazolyl blue cell viability assay was used to determine the growth-pro...AIM:To test the growth-promoting activity of the polyamine spermidine bound to various polymeric compounds in supramolecular complexes.METHODS:A thiazolyl blue cell viability assay was used to determine the growth-promoting potency of spermidine-supramolecular complexes in a human skin fibroblast cell line exposed to spermidine and different spermidine-supramolecular complexes that were obtained by combining spermidine and polyanionic polymers or cyclodextrin.Reconstituted human vaginal epithelium was exposed to a specific spermidinesupramolecular complex,i.e.,spermidine-hyaluronan(HA)50,and cell proliferation was determined by Ki-67immunohistochemical detection.Transepithelial electrical resistance and histological analysis were also performed on reconstituted human vaginal epithelium to assess tissue integrity.RESULTS:The effect of spermidine and spermidinesupramolecular complexes was first tested in skin fi-broblasts.Spermidine displayed a reverse dose-related mode of activity with mmol/L growth inhibition,whereas 30%stimulation over basal levels was detected at mol/L and nmol/L levels.Novel spermidine-supramolecular complexes that formed between spermidine and polyanionic polymers,such as HA,alginate,and polymaleate,were then tested at variable spermidine concentrations and a fixed polymer level(0.1%w/v).Spermidine-supramolecular complexes stimulated the cell growth rate throughout the entire concentration range with maximal potency(up to 80%)at sub-mol/L levels.Similar results were obtained with spermidine-(-cyclodextrin),another type of spermidine-supramolecular complex.Moreover,the increased expression of Ki-67 in the reconstituted human vaginal epithelium exposed to spermidine-HA 50 showed that the mode of action behind the spermidine-supramolecular complexes was increased cell proliferation.Functional and morphological assessments of reconstituted human vaginal epithelium integrity did not show significant alterations after exposure to spermidine-HA,thus supporting its safety.CONCLUSION:Spermidine found in spermidine-supramolecular complexes displayed potentiated regenerative effects.Safety data on reconstituted human vaginal epithelium suggested that assessing spermidinesupramolecular complex efficacy in atrophic disorders is justified.展开更多
Serum spermidine was assayed by radioimmuno-assay in different stages of esophageal carcinogenesis in the population from high risk area of esophageal cancer, Linxian County. The serum spermidine values were 76.94+74....Serum spermidine was assayed by radioimmuno-assay in different stages of esophageal carcinogenesis in the population from high risk area of esophageal cancer, Linxian County. The serum spermidine values were 76.94+74.38 ng ml in 36 normal individuals; 115.71+113.45 ng/ml in 35 patients with marked epithelial hyperplasia (MEH) and 294.48+135.36 ng/ml in 31 patients with early esophageal cancer. Patients with MEH were given intervention treatment by Aminoretinoic Ester or Anticancer B or placebo (starch) as controls. One year later, samples from the population were collected again for serum spermidine msasurement. The values were 95.8+ 68.2 ng/ml in 27 normals; 125.1±72.9 ng/ml in 62 patients with MEH treated by Anticancer B; 125.6± 117.2 ng/ml in 64 patients with MEH treated by Aminoretinoic Ester; 162.4±76.6 ng/ml in 62 controls and 210.5±182.9 ng/ml in 44 patients with early esophageal cancer.The results showed that spermidine radioim-munoassay could reflect the tendency of esophageal precancerous changes toward cancer or back to normal. They can be taken as a mid-way monitor indicator for tumor-blocking drugs. Also, it could be of value in the early diagnosis of esophageal cancer.展开更多
Background: The most common subtype of chronic vulvar pain is provoked vestibulodynia. The entry of the vagina is the site of acute and recurrent pain in this highly prevalent and debilitating condition, which is char...Background: The most common subtype of chronic vulvar pain is provoked vestibulodynia. The entry of the vagina is the site of acute and recurrent pain in this highly prevalent and debilitating condition, which is characterized by pressure application or attempted vaginal penetration. The aim of this study was to determine the effectiveness of topical spermidine in patients with vestibulodynia. Methods: Topical gels containing spermidine in hyaluronate complexes Ubi1 and Ubi2 endowed with differentiated release ratio and viscosity were applied at 3 doses/week during 4-weeks, then at 2 doses/week during the next 4-weeks in two groups of patients. Pain relief was measured by visual analogic score (VAS) and dyspareunia score expressed as percent improvement from baseline to posttreatment. Results: Group 1 treated with Ubi1 provided improvement in pain (46%) and dyspareunia (27%). However, the treatment in Group 2 resulted in a superior amelioration: VAS of pain (76%) and dyspareunia (50%) as Ubi2 gel provided higher dose and viscosity along with improved local application. Conclusions: Our results demonstrated that preparation 2 resulted in greater reduction in symptoms as compared to preparation 1 as measured by the VAS and Marinoff scale. These early, yet outstanding clinical outcomes in vestibulodynia through to the stimulation of tissue mechanosensor and their relevant downstream effects are reviewed hereafter.展开更多
Tomato(Solanum lycopersicum)is an important crop but frequently experiences saline-alkali stress.Our previous studies have shown that exogenous spermidine(Spd)could significantly enhance the saline-alkali resistance o...Tomato(Solanum lycopersicum)is an important crop but frequently experiences saline-alkali stress.Our previous studies have shown that exogenous spermidine(Spd)could significantly enhance the saline-alkali resistance of tomato seedlings,in which a high concentration of Spd and jasmonic acid(JA)exerted important roles.However,the mechanism of Spd and JA accumulation remains unclear.Herein,SIWRKY42,a Group II WRKY transcription factor,was identified in response to saline-alkali stress.Overexpression of SIWRKY42 improved tomato saline-alkali tolerance.Meanwhile,SIWRKY42 knockout mutants,exhibited an opposite phenotype.RNA-sequencing data also indicated that SIWRKY42 regulated the expression of genes involved in JA signaling and Spd synthesis under saline-alkali stress.SIWRKY42 is directly bound to the promoters of SISPDS2 and SINHX4 to promote Spd accumulation and ionic balance,respectively.SIWRKY42 interacted with SIMYC2.Importantly,SIMYC2 is also bound to the promoter of SISPDS2to promote Spd accumulation and positively regulated saline-alkali tolerance.Furthermore,the interaction of SIMYC2 with SIWRKY42 boosted SIWRKY42's transcriptional activity on SISPDS2,ultimately enhancing the tomato's saline-alkali tolerance.Overall,our findings indicated that SIWRKY42 and SIMYC2 promoted saline-alkali tolerance by the Spd biosynthesis pathway.Thus,this provides new insight into the mechanisms of plant saline-alkali tolerance responses triggered by polyamines(PAs).展开更多
Tumor microenvironment governs various therapeutic tolerability of cancer such as ferroptosis and immuno-therapy through rewiring tumor metabolic reprogramming like Warburg metabolism.Highly expressed carbonic anhydra...Tumor microenvironment governs various therapeutic tolerability of cancer such as ferroptosis and immuno-therapy through rewiring tumor metabolic reprogramming like Warburg metabolism.Highly expressed carbonic anhydrases(CA)in tumor that maintaining the delicate metabolic homeostasis is thus the most potential target to be modulated to resolve the therapeutic tolerability.Hence,in this article,a self-healable and pH-responsive spermidine/ferrous ion hydrogel loaded with CA inhibitor(acetazolamide,ACZ)and glucose oxidase(ACZ/GOx@SPM-HA Gel)was fabricated through the Schiff-base reaction between spermidine-dextran and oxidized hyaluronic acid,along with ferrous coordination.Investigation on cancer cell lines(MOC-1)demonstrated ACZ/GOx@SPM-HA Gel may induce cellular oxidative stress and mitochondrial dysfunction through disrupting the cellular homeostasis.Moreover,with the facilitation of autophagy induced by spermidine,ACZ/GOx@SPM-HA Gel may trigger a positive feedback loop to maximally amplify cellular ferroptosis and promote DAMPs release.The anti-tumor evaluation on xenograft mice models furtherly proved the local injection of such hydrogel formulation could efficiently inhibit the tumor growth and distinctively promote the immunogenicity of tumor bed to provide a more favorable environment for immunotherapy.Overall,ACZ/GOx@SPM-HA Gel,with such feasible physiochemical properties and great biocompatibility,holds great potential in treating solid tumors with acidosis-mediated immunotherapy tolerance.展开更多
The elevated polyamines,amine-rich molecules with diverse functions in pathophysiology processes,are implicated in contributing to tumorigenesis and progression.Whether and how they affect the efficacy of chemotherapy...The elevated polyamines,amine-rich molecules with diverse functions in pathophysiology processes,are implicated in contributing to tumorigenesis and progression.Whether and how they affect the efficacy of chemotherapy is incompletely understood.Our screening assays reveal that the supplement with a low dose of spermidine(Spd),one of the polyamines,enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe^(2+)levels in vitro.Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice.Analysis of RNA-seq data indicates that heme oxygenase 1(HMOX1),an enzyme that catalyzes the cleavage of heme to release Fe^(2+),is significantly upregulated in response to Spd and erastin cotreatment.Spd mediated the hypusine modification of the eukaryotic initiation factor 5A(EIF5A)promotes the translation of the nuclear factor erythroid 2-related factor 2(NRF2),subsequently leading to elevation of HMOX1.Moreover,Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2,although many proteasomerelated genes are induced either by Spd or Spd plus erastin.Thus,in addition to its pro-oncogenic activity,the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.展开更多
Spermidine is a naturally occurring polyamine widely utilized in the prevention and treatment of various diseases.Current spermidine biosynthetic methods have problems such as low efficiency and complex multi-enzyme c...Spermidine is a naturally occurring polyamine widely utilized in the prevention and treatment of various diseases.Current spermidine biosynthetic methods have problems such as low efficiency and complex multi-enzyme catalysis.Based on sequence-structure-function relationships,we engineered the widely studied homospermidine synthase from Blastochloris viridis(BvHSS)and obtained mutants that could catalyze the production of spermidine from 1,3-diaminopropane and putrescine.The specific activities of BvHSS and the mutants D361E and E232D+D361E(E232D-D)were 8.72,46.04 and 48.30 U/mg,respectively.The optimal pH for both mutants was 9.0,and the optimal temperature was 50◦C.Molecular docking and dynamics simulations revealed that mutating aspartic acid at position 361 to glutamic acid narrowed the substrate binding pocket,promoting stable spermidine production.Conversely,mutating glutamic acid at position 232 to aspartic acid enlarged the substrate channel entrance,facilitating substrate entry into the active pocket and enhancing spermidine generation.In whole-cell catalysis lasting 6 h,D361E and E232D-D synthesized 725.3 and 933.5 mg/L of spermidine,respectively.This study offers a practical approach for single-enzyme catalyzed spermidine synthesis and sheds light on the crucial residues influencing homospermidine synthase catalytic activity in spermidine production.展开更多
: The effects of foliar spraying with spermidine (Spd), ranging in concentration from 0.25 to 0.50 mmol/L, on the antioxidant system under Cd2+ stress (range 0.1–0.2 mmol/L Cd2+) in Typha latifolia L. grown hydroponi...: The effects of foliar spraying with spermidine (Spd), ranging in concentration from 0.25 to 0.50 mmol/L, on the antioxidant system under Cd2+ stress (range 0.1–0.2 mmol/L Cd2+) in Typha latifolia L. grown hydroponically were investigated in order to offer a referenced evidence for an understanding of the mechanism by which polyamines (PAs) relieve the damage to plants by heavy metal and improve the phytoremediation efficiency of heavy metal-contaminated water. The results showed that Cd2+ stress induced oxidative injury, as evidenced by an increase in the generation of superoxide anion (O2-), as well as the hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents in both leaves and caudices. With the exception of superoxide dismutase (SOD) activity in the leaves, an increase in the activities of catalase (CAT), guaiacol peroxidase (GPX), and glutathione reductase (GR) was observed in both leaves and caudices, SOD activity was increased in caudices, and ascorbate peroxidase (APX) activity was increased in leaves following Cd2+ treatment. The reduced glutathione (GSH) content in both leaves and caudices and the reductive ascorbate content in leaves was obviously increased, which were prompted by the application of exogenous Spd. Spraying with Spd increased the activity of GR and APX in both leaves and caudices, whereas the activity of SOD, CAT, and GPX was increased only in caudices following spraying with Spd. The generation of O2 -. and the H2O2 and MDA content in both leaves and caudices decreased after spraying with Spd. The decrease in MDA was more obvious following the application of 0.25 than 0.50 mmol/L Spd. It is supposed that exogenous Spd elevated the tolerance of T. latifolia under Cd2+ stress primarily by increasing GR activity and the GSH level.展开更多
The effects of exogenous spermidine （Spd） on lipid peroxidation, relative plasma membrane permeability, photosystem Ⅱ （PSII） gene expression and PSII photochemical activity in water-stressed wheat seedlings were ...The effects of exogenous spermidine （Spd） on lipid peroxidation, relative plasma membrane permeability, photosystem Ⅱ （PSII） gene expression and PSII photochemical activity in water-stressed wheat seedlings were investigated. The decrease in relative water content （RWC）, Chl content, and 2,6-dichlorophenol indophenol （DCIP） photoreduction of PSII, and increases in electrolyte leakage of plasma membranes and malonyldialdehyde （MDA） in water-stressed leaves was alleviated by Spd pretreatment. Furthermore, Western and Northern blot analysis showed that decreases in the PSll major proteins D1, D2 and LHCII and the transcripts of corresponding genes psbA, psbD and cab were also alleviated by Spd pretreatment under water stress. These results suggest that the application of exogenous Spd protects PSII against water stress at both the transcriptional level and the translational level, and allows PSII to retain a higher activity level during water stress. The protective role of Spd in the photosynthetic apparatus also is discussed.展开更多
In vitro investigation on the condensation of DNA induced by naturally occurring polyamines can provide useful insights into the packaging state of DNA in vivo , which is closely related to the mechanism of the self r...In vitro investigation on the condensation of DNA induced by naturally occurring polyamines can provide useful insights into the packaging state of DNA in vivo , which is closely related to the mechanism of the self regulation or self switching of the gene expression. The present paper reports the high resolution AFM observations of the condensates of spermidine DNA complexes. It was found that the spermidine can directly condense the DNA into toroidal structures. The formation of this special structure is greatly influenced by the dynamic factors such as the concentrations and the reaction time. Close examination revealed that the toroids were constructed by many particles stacked and squeezed together. Our observations indicate that the dynamic process of the toroid formation may be a spiral wound process of the globular subunits.展开更多
Polyamines(putrescine,spermidine,and spermine)are aliphatic compounds ubiquitous in prokaryotes and eukaryotes.Positively charged polyamines bind to negatively charged macromolecules,such as nucleic acids and acidic p...Polyamines(putrescine,spermidine,and spermine)are aliphatic compounds ubiquitous in prokaryotes and eukaryotes.Positively charged polyamines bind to negatively charged macromolecules,such as nucleic acids and acidic phospholipids,and are involved in physiological activities including cell proliferation,differentiation,apoptosis and gene regulation.Intracellular polyamine levels are regulated by biosynthesis,catabolism and transport.Polyamines in the body originate from two primary sources:dietary intake and intestinal microbial metabolism.These polyamines are then transported into the bloodstream,through which they are distributed to various tissues and organs to exert their biological functions.Polyamines synthesized by intestinal microorganisms serve dual critical roles.First,they are essential for maintaining polyamine concentrations within the digestive tract.Second,through transcriptional and post-transcriptional mechanisms,these microbial-derived polyamines modulate the expression of genes governing key processes in intestinal epithelial cells-including proliferation,migration,apoptosis,and cell-cell interactions.Collectively,these regulatory effects help maintain intestinal epithelial homeostasis and ensure the integrity of the gut barrier.In addition,polyamines interact with the gut microbiota to maintain intestinal homeostasis by promoting microbial growth,biofilm formation,swarming,and endocytosis vesicle production,etc.Supplementation with polyamines has been demonstrated to be important in regulating host intestinal microbial composition,enhancing nutrient absorption,and improving metabolism and immunity.In this review,we will focus on recent advances in the study of polyamine metabolism and transport in intestinal microbes and intestinal epithelial cells.We then summarize the scientific understanding of their roles in intestinal homeostasis,exploring the advances in cellular and molecular mechanisms of polyamines and their potential clinical applications,and providing a rationale for polyamine metabolism as an important target for the treatment of intestinal-based diseases.展开更多
基金supported by the Shandong Second Medical University Overseas Visiting Scholar Programthe National Medical Research Council of Singapore (grant numbers NMRC/TA/0053/2016 and NMRC/CSA/INV/0009/2022)
文摘INTRODUCTION With the expansion of the ageing population,cognitive decline has become an increas-ingly pressing challenge.1 As life expectancy increases,its socioeconomic burden is also increasing,highlighting the urgent need for effective interventions.Numerous studies suggest that specific dietary patterns and nutritional interventions may help mitigate cognitive decline associated with ageing.
基金supported by the China Agriculture Research System(CARS-02-20)the Henan Province Agro-ecosystem Field Observation and Research Station,China(30602535)。
文摘Waterlogging stress significantly impairs plant growth and reduces crop yields.Spermidine(Spd),functioning as a second messenger,demonstrates positive effects on plant growth under waterlogging stress conditions.However,the molecular mechanisms by which exogenous Spd application alleviates waterlogging stress remain unclear.This study employed physiological analysis and multi-omics approaches to investigate the effect of Spd application on waterlogging stress.The application of Spd enhanced the expression of genes related to light-harvesting complex(LHC),photosynthesis,and starch-related pathways,while inhibiting chlorophyll degradation and maintaining higher photosynthetic rates,thereby increasing biomass accumulation under waterlogging stress.The activation of genes associated with trehalose and Spd biosynthesis resulted in elevated accumulation of trehalose and endogenous Spd.The inhibition of 1-aminocyclopropane-1-carboxylic acid(ACC)oxidase(ACO)expression contributed to reduced ethylene emission,enhancing maize resistance to waterlogging.Following Spd application,auxin-related genes were up-regulated and indole acetic acid(IAA)content increased,promoting cell elongation in maize and maintaining normal growth under waterlogging stress.Additionally,the upregulation of lipid-related genes led to increased lipid content,protecting cell membranes under waterlogging conditions.These molecular and physiological modifications collectively enhanced resistance to waterlogging stress.These findings advance our understanding of Spd's regulatory roles in mitigating waterlogging damage and provide valuable insights for breeding waterlogging-tolerant maize varieties.
基金supported by National Natural Science Foundation of China(Nos.52173150 and U22A20315)the Guangzhou Science and Technology Program City-University Joint Funding Project(No.2024A03J0604)+2 种基金the Science and Technology Program of Guangzhou(No.2024A03J0431)the start-up funding for the Seventh Affiliated Hospital of Sun Yat-sen University(Shenzhen)(No.ZSQYRSFPD0053)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515111126)。
文摘Diabetic wounds are among the most challenging chronic wounds to heal,due to the presence of multiple factors,including continuous oxidative stress,impaired vascular integrity,and biofilm formation.The development of innovative treatment strategies is of paramount importance for the management of diabetic wounds.Stemmed from the pleiotropic physicochemical properties of ferrocene and spermidine,this essay reported the ferrocene-spermidine co-polymer(Fc S)for the first time through facile amidation reaction.Molecular dynamics simulation revealed its self-assembly through hydrogen bonds,van der Waals forces instead of traditional nanoprecipitation.The self-assembled nanoparticles were demonstrated to exhibit great antioxidant property on cells to facilitate their migration and angiogenesis.Moreover,the integration with photocuring hydrogel,gelatin methacrylate(Gel MA),to construct Fc S nanoparticles loaded wound dressing(Gel MA@Fc S)further confirmed the potential on promoting diabetic wound enclosure through enhancement of re-epithelization and collagen deposition.Together with its great biocompatibility and biosafety,Gel MA@Fc S is expected to be developed into a wound dressing for clinical diabetic wounds management.
基金the National Natural Science Foundation of China(31271661,30871477)the National Basic Research Program of China(2009CB118602)+1 种基金the Special Fund for Agro-Scientific Research in the Public Interest of China(201203100)the Key Technologies R&D Program of China during the 12th Five-Year Plan period(2012BAD04B05)
文摘Two wheat cultivars （Triticum aestivum L.） were used to evaluate the effects ofpost-anthesis severe water deficit （SD） on starch content and granule size distribution and their relations with ethylene and spermidine （Spd）. Comparison to the well-watered （WW） treatment, SD led to lower Spd and higher 1-aminocylopropane-l-carboxylic acid （ACC） concentrations and ethylene evolution rate （EER） in grains at the critical stage of forming starch granules. Application of Spd or aminoethoxyvinylglycine （AVG） significantly reduced ACC concentration and EER and increased Spd concentration, while ethephon or methylglyoxal-bis （MGBG） had an opposite impact. The volume and surface area distribution of starch granules showed a bimodal curve, while the number distribution exhibited a unimodal curve. SD caused a marked drop in grain weight, grain number and starch content, also led to a significant reduction in the proportion （both by volume and by surface area） of B-type starch granules （〈10 Ixm）, with an increase in those of A-type starch granules （〉10 ~tm）. Application of Spd or AVG increased the proportion （both by volume and by surface area） of B-type starch granules under SD. Correlation analysis suggested that ethylene and Spd showed an antagonism relation in the formation of B-type granules. These results suggested that it would be good for the formation of B-type starch granules to have the physiological traits of higher Spd and lower ACC concentrations and ethylene emission under SD.
基金This research was supported by Foundation of Jiangsu forestry bureau(LYKJ[2017]42)Key research and development plan of Jiangsu Province(BE2017376)+2 种基金the Nature Science Foundation of China(31770715)the Qinglan project of Jiangsu province,Priority Academic Program Development of Jiangsu Higher Education Institutions,Natural Science Foundation of Jiangsu Province(BK20181176)the Joint Fund of the Natural Science Foundation of China and the Karst Science Research Center of Guizhou Province(Grant No.U1812401).
文摘In order to study how exogenous hormones in C.lanceolata(gymnosperm)regulate somatic embryogenesis,we measured the endogenous phytohormones of two genotypes with different somatic embryogenesis efficiency and found that an increase in endogenous concentrations of IAA and ABA may be correlated to more efficient somatic embryogenesis.By applying exogenous spermidine,we found that exogenous hormones may affect somatic embryogenesis efficiency through affecting the endogenous phytohormone content.Based on these results,further studies can be conducted whereby the concentration of exogenous hormones or the levels of endogenous phytohormones by molecular methods are regulated to promote somatic embryogenesis.Our research may benefit the long-term economic output of the forestry industry and lays the foundation to studying the molecular mechanism that controls somatic embryogenesis efficiency.
文摘The peppers which were treated at ice-temperature for 6 hours and 1 mmol/L spermidine for 10 min, followed by cold storage (4℃ ± 1℃) respectively were investigated. The results indicated that the chilling injury was delayed and reduced by ice-temperature and spermidine treatments. Comparing with control group, ice-temperature and spermidine exerted significant effects on reduction of ascorbic acid (Vc) and chlororphyll contents, relatively high activity of superoxide dismutase (SOD), accumulation of malondialdehyde (MDA) as well as the increase of cell membrane penetrability. The results indicated that the spermidine and ice-temperature induced the activity of antioxidant enzyme SOD and maintained higher defence-related compound Vc as well as lower levels of membrane lipid peroxidation, which may be associated with chilling injury alleviation. There was a difference between ice-temperature treatment and spermidine treatment after 30 days. The results suggested that spermidine was more effective in reducing chilling sensitivity and prolonging storage of peppers.
基金financially supported by Khon Kaen University Research Fund awarded to Salt-Tolerant Rice Research Group
文摘Exogenous application of spermidine（Spd） has been reported to modulate physiological processes and alleviate salt-induced damage to growth and productivity of several plants including rice. Employing a proteomic approach, we aimed at identifying rice leaf and grain proteins differentially expressing under salt stress, and in response to Spd prior to Na Cl treatment. A total of 9 and 20 differentially expressed protein spots were identified in the leaves of salt-tolerant（Pokkali） and saltsensitive（KDML105） rice cultivars, respectively. Differential proteins common to both cultivars included a photosynthetic light reaction protein（oxygen-evolving complex protein 1）, enzymes of Calvin cycle and glycolysis（fructose-bisphosphate aldolase and triose-phosphate isomerase）, malate dehydrogenase, superoxide dismutase and a hypothetical protein（Os I_18213）. Most proteins were present at higher intensities in Pokkali leaves. The photosynthetic oxygen-evolving enhancer protein 2 was detected only in Pokkali and was up-regulated by salt-stress and further enhanced by Spd treatment. All three spots identified as superoxide dismutase in KDML105 were up-regulated by Na Cl but down-regulated when treated with Spd prior to Na Cl, indicating that Spd acted directly as antioxidants. Important differential stress proteins detected in mature grains of both rice cultivars were late embryogenesis abundant proteins with protective roles and an antioxidant protein, 1-Cys-peroxiredoxin. Higher salt tolerance of Pokkali partly resulted from higher intensities and more responsiveness of the proteins relating to photosynthesis light reactions, energy metabolism, antioxidant enzymes in the leaves, and stress proteins with protective roles in the grains.
文摘A monoclonal antibody was first prepared by fusion of mouse myeloma cells (SP2/0-Ag-14) with spleen cells isolated from male BALB/ c mice immunized with spermidine-bovine serum albumin conjugate (SPD- BSA). The hybridoma cell line producing antibody specific for spermidine was cultured in vitro and after i. p. into mice, the ascitic fluid gave suitably high dilution titres (1: 106) by enzyme immunoassay. This monoclonal antibody is of IgG1 class and the bimolecular compleex with molecular weight of 52KD and 27 KD. The monoclonal antibody was clearly specific to spermidine comparing with spermine or putriscine. Monclonal antibody may prove to be useful in the rapid diagnosis and evaluation of patients with cancer.
基金Supported by Grants from the Italian Ministry of Education
文摘AIM:To test the growth-promoting activity of the polyamine spermidine bound to various polymeric compounds in supramolecular complexes.METHODS:A thiazolyl blue cell viability assay was used to determine the growth-promoting potency of spermidine-supramolecular complexes in a human skin fibroblast cell line exposed to spermidine and different spermidine-supramolecular complexes that were obtained by combining spermidine and polyanionic polymers or cyclodextrin.Reconstituted human vaginal epithelium was exposed to a specific spermidinesupramolecular complex,i.e.,spermidine-hyaluronan(HA)50,and cell proliferation was determined by Ki-67immunohistochemical detection.Transepithelial electrical resistance and histological analysis were also performed on reconstituted human vaginal epithelium to assess tissue integrity.RESULTS:The effect of spermidine and spermidinesupramolecular complexes was first tested in skin fi-broblasts.Spermidine displayed a reverse dose-related mode of activity with mmol/L growth inhibition,whereas 30%stimulation over basal levels was detected at mol/L and nmol/L levels.Novel spermidine-supramolecular complexes that formed between spermidine and polyanionic polymers,such as HA,alginate,and polymaleate,were then tested at variable spermidine concentrations and a fixed polymer level(0.1%w/v).Spermidine-supramolecular complexes stimulated the cell growth rate throughout the entire concentration range with maximal potency(up to 80%)at sub-mol/L levels.Similar results were obtained with spermidine-(-cyclodextrin),another type of spermidine-supramolecular complex.Moreover,the increased expression of Ki-67 in the reconstituted human vaginal epithelium exposed to spermidine-HA 50 showed that the mode of action behind the spermidine-supramolecular complexes was increased cell proliferation.Functional and morphological assessments of reconstituted human vaginal epithelium integrity did not show significant alterations after exposure to spermidine-HA,thus supporting its safety.CONCLUSION:Spermidine found in spermidine-supramolecular complexes displayed potentiated regenerative effects.Safety data on reconstituted human vaginal epithelium suggested that assessing spermidinesupramolecular complex efficacy in atrophic disorders is justified.
文摘Serum spermidine was assayed by radioimmuno-assay in different stages of esophageal carcinogenesis in the population from high risk area of esophageal cancer, Linxian County. The serum spermidine values were 76.94+74.38 ng ml in 36 normal individuals; 115.71+113.45 ng/ml in 35 patients with marked epithelial hyperplasia (MEH) and 294.48+135.36 ng/ml in 31 patients with early esophageal cancer. Patients with MEH were given intervention treatment by Aminoretinoic Ester or Anticancer B or placebo (starch) as controls. One year later, samples from the population were collected again for serum spermidine msasurement. The values were 95.8+ 68.2 ng/ml in 27 normals; 125.1±72.9 ng/ml in 62 patients with MEH treated by Anticancer B; 125.6± 117.2 ng/ml in 64 patients with MEH treated by Aminoretinoic Ester; 162.4±76.6 ng/ml in 62 controls and 210.5±182.9 ng/ml in 44 patients with early esophageal cancer.The results showed that spermidine radioim-munoassay could reflect the tendency of esophageal precancerous changes toward cancer or back to normal. They can be taken as a mid-way monitor indicator for tumor-blocking drugs. Also, it could be of value in the early diagnosis of esophageal cancer.
文摘Background: The most common subtype of chronic vulvar pain is provoked vestibulodynia. The entry of the vagina is the site of acute and recurrent pain in this highly prevalent and debilitating condition, which is characterized by pressure application or attempted vaginal penetration. The aim of this study was to determine the effectiveness of topical spermidine in patients with vestibulodynia. Methods: Topical gels containing spermidine in hyaluronate complexes Ubi1 and Ubi2 endowed with differentiated release ratio and viscosity were applied at 3 doses/week during 4-weeks, then at 2 doses/week during the next 4-weeks in two groups of patients. Pain relief was measured by visual analogic score (VAS) and dyspareunia score expressed as percent improvement from baseline to posttreatment. Results: Group 1 treated with Ubi1 provided improvement in pain (46%) and dyspareunia (27%). However, the treatment in Group 2 resulted in a superior amelioration: VAS of pain (76%) and dyspareunia (50%) as Ubi2 gel provided higher dose and viscosity along with improved local application. Conclusions: Our results demonstrated that preparation 2 resulted in greater reduction in symptoms as compared to preparation 1 as measured by the VAS and Marinoff scale. These early, yet outstanding clinical outcomes in vestibulodynia through to the stimulation of tissue mechanosensor and their relevant downstream effects are reviewed hereafter.
基金support from the Scientific&Technological Innovative Research Team of Shaanxi Province(Grant No.2021TD-34)the China Agriculture Research System(Grant No.CARS-23-D06)the National Natural Science Foundation of China(Grant No.32302531)。
文摘Tomato(Solanum lycopersicum)is an important crop but frequently experiences saline-alkali stress.Our previous studies have shown that exogenous spermidine(Spd)could significantly enhance the saline-alkali resistance of tomato seedlings,in which a high concentration of Spd and jasmonic acid(JA)exerted important roles.However,the mechanism of Spd and JA accumulation remains unclear.Herein,SIWRKY42,a Group II WRKY transcription factor,was identified in response to saline-alkali stress.Overexpression of SIWRKY42 improved tomato saline-alkali tolerance.Meanwhile,SIWRKY42 knockout mutants,exhibited an opposite phenotype.RNA-sequencing data also indicated that SIWRKY42 regulated the expression of genes involved in JA signaling and Spd synthesis under saline-alkali stress.SIWRKY42 is directly bound to the promoters of SISPDS2 and SINHX4 to promote Spd accumulation and ionic balance,respectively.SIWRKY42 interacted with SIMYC2.Importantly,SIMYC2 is also bound to the promoter of SISPDS2to promote Spd accumulation and positively regulated saline-alkali tolerance.Furthermore,the interaction of SIMYC2 with SIWRKY42 boosted SIWRKY42's transcriptional activity on SISPDS2,ultimately enhancing the tomato's saline-alkali tolerance.Overall,our findings indicated that SIWRKY42 and SIMYC2 promoted saline-alkali tolerance by the Spd biosynthesis pathway.Thus,this provides new insight into the mechanisms of plant saline-alkali tolerance responses triggered by polyamines(PAs).
基金supported by the Science and Technology Program of Guangzhou(2024A03J0431 and 2023A03J0488)National Natural Science Foundation of China(52173150 and U22A20315)+1 种基金the Guangzhou Science and Technology Program City-University Joint Funding Project(2024A03J0604)Guangdong Basic and Applied Basic Research Foundation(2023A1515111126).
文摘Tumor microenvironment governs various therapeutic tolerability of cancer such as ferroptosis and immuno-therapy through rewiring tumor metabolic reprogramming like Warburg metabolism.Highly expressed carbonic anhydrases(CA)in tumor that maintaining the delicate metabolic homeostasis is thus the most potential target to be modulated to resolve the therapeutic tolerability.Hence,in this article,a self-healable and pH-responsive spermidine/ferrous ion hydrogel loaded with CA inhibitor(acetazolamide,ACZ)and glucose oxidase(ACZ/GOx@SPM-HA Gel)was fabricated through the Schiff-base reaction between spermidine-dextran and oxidized hyaluronic acid,along with ferrous coordination.Investigation on cancer cell lines(MOC-1)demonstrated ACZ/GOx@SPM-HA Gel may induce cellular oxidative stress and mitochondrial dysfunction through disrupting the cellular homeostasis.Moreover,with the facilitation of autophagy induced by spermidine,ACZ/GOx@SPM-HA Gel may trigger a positive feedback loop to maximally amplify cellular ferroptosis and promote DAMPs release.The anti-tumor evaluation on xenograft mice models furtherly proved the local injection of such hydrogel formulation could efficiently inhibit the tumor growth and distinctively promote the immunogenicity of tumor bed to provide a more favorable environment for immunotherapy.Overall,ACZ/GOx@SPM-HA Gel,with such feasible physiochemical properties and great biocompatibility,holds great potential in treating solid tumors with acidosis-mediated immunotherapy tolerance.
基金supported by the National Natural Science Foundation of China(82293682,82173839,82373896)GXRC Program of Ji-Nan Science&Technology Bureau(2021GXRC102,China)+1 种基金ECCM Program of Clinical Research Center of Shandong University(2021SDUCRC003,China)Special Funding for Taishan Scholar Program(tstp20221159,China).
文摘The elevated polyamines,amine-rich molecules with diverse functions in pathophysiology processes,are implicated in contributing to tumorigenesis and progression.Whether and how they affect the efficacy of chemotherapy is incompletely understood.Our screening assays reveal that the supplement with a low dose of spermidine(Spd),one of the polyamines,enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe^(2+)levels in vitro.Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice.Analysis of RNA-seq data indicates that heme oxygenase 1(HMOX1),an enzyme that catalyzes the cleavage of heme to release Fe^(2+),is significantly upregulated in response to Spd and erastin cotreatment.Spd mediated the hypusine modification of the eukaryotic initiation factor 5A(EIF5A)promotes the translation of the nuclear factor erythroid 2-related factor 2(NRF2),subsequently leading to elevation of HMOX1.Moreover,Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2,although many proteasomerelated genes are induced either by Spd or Spd plus erastin.Thus,in addition to its pro-oncogenic activity,the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.
文摘Spermidine is a naturally occurring polyamine widely utilized in the prevention and treatment of various diseases.Current spermidine biosynthetic methods have problems such as low efficiency and complex multi-enzyme catalysis.Based on sequence-structure-function relationships,we engineered the widely studied homospermidine synthase from Blastochloris viridis(BvHSS)and obtained mutants that could catalyze the production of spermidine from 1,3-diaminopropane and putrescine.The specific activities of BvHSS and the mutants D361E and E232D+D361E(E232D-D)were 8.72,46.04 and 48.30 U/mg,respectively.The optimal pH for both mutants was 9.0,and the optimal temperature was 50◦C.Molecular docking and dynamics simulations revealed that mutating aspartic acid at position 361 to glutamic acid narrowed the substrate binding pocket,promoting stable spermidine production.Conversely,mutating glutamic acid at position 232 to aspartic acid enlarged the substrate channel entrance,facilitating substrate entry into the active pocket and enhancing spermidine generation.In whole-cell catalysis lasting 6 h,D361E and E232D-D synthesized 725.3 and 933.5 mg/L of spermidine,respectively.This study offers a practical approach for single-enzyme catalyzed spermidine synthesis and sheds light on the crucial residues influencing homospermidine synthase catalytic activity in spermidine production.
文摘: The effects of foliar spraying with spermidine (Spd), ranging in concentration from 0.25 to 0.50 mmol/L, on the antioxidant system under Cd2+ stress (range 0.1–0.2 mmol/L Cd2+) in Typha latifolia L. grown hydroponically were investigated in order to offer a referenced evidence for an understanding of the mechanism by which polyamines (PAs) relieve the damage to plants by heavy metal and improve the phytoremediation efficiency of heavy metal-contaminated water. The results showed that Cd2+ stress induced oxidative injury, as evidenced by an increase in the generation of superoxide anion (O2-), as well as the hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents in both leaves and caudices. With the exception of superoxide dismutase (SOD) activity in the leaves, an increase in the activities of catalase (CAT), guaiacol peroxidase (GPX), and glutathione reductase (GR) was observed in both leaves and caudices, SOD activity was increased in caudices, and ascorbate peroxidase (APX) activity was increased in leaves following Cd2+ treatment. The reduced glutathione (GSH) content in both leaves and caudices and the reductive ascorbate content in leaves was obviously increased, which were prompted by the application of exogenous Spd. Spraying with Spd increased the activity of GR and APX in both leaves and caudices, whereas the activity of SOD, CAT, and GPX was increased only in caudices following spraying with Spd. The generation of O2 -. and the H2O2 and MDA content in both leaves and caudices decreased after spraying with Spd. The decrease in MDA was more obvious following the application of 0.25 than 0.50 mmol/L Spd. It is supposed that exogenous Spd elevated the tolerance of T. latifolia under Cd2+ stress primarily by increasing GR activity and the GSH level.
基金Supported by the National Natural Science Foundation of China(30571119)the Sichuan Science and Technology Foundation(04ZQ026-036 and 05JY029-017)+1 种基金the Education Ministry Doctoral Foundation of China (20040610015)the Chengdu Science and Technology Foundation (05HJSW117)
文摘The effects of exogenous spermidine （Spd） on lipid peroxidation, relative plasma membrane permeability, photosystem Ⅱ （PSII） gene expression and PSII photochemical activity in water-stressed wheat seedlings were investigated. The decrease in relative water content （RWC）, Chl content, and 2,6-dichlorophenol indophenol （DCIP） photoreduction of PSII, and increases in electrolyte leakage of plasma membranes and malonyldialdehyde （MDA） in water-stressed leaves was alleviated by Spd pretreatment. Furthermore, Western and Northern blot analysis showed that decreases in the PSll major proteins D1, D2 and LHCII and the transcripts of corresponding genes psbA, psbD and cab were also alleviated by Spd pretreatment under water stress. These results suggest that the application of exogenous Spd protects PSII against water stress at both the transcriptional level and the translational level, and allows PSII to retain a higher activity level during water stress. The protective role of Spd in the photosynthetic apparatus also is discussed.
文摘In vitro investigation on the condensation of DNA induced by naturally occurring polyamines can provide useful insights into the packaging state of DNA in vivo , which is closely related to the mechanism of the self regulation or self switching of the gene expression. The present paper reports the high resolution AFM observations of the condensates of spermidine DNA complexes. It was found that the spermidine can directly condense the DNA into toroidal structures. The formation of this special structure is greatly influenced by the dynamic factors such as the concentrations and the reaction time. Close examination revealed that the toroids were constructed by many particles stacked and squeezed together. Our observations indicate that the dynamic process of the toroid formation may be a spiral wound process of the globular subunits.
基金supported by projects from the Xinjiang Production and Construction Corps Major Science and Technology"Revealing the List and Taking Command"Project(2023AB078)the Ministry of Science and Technology High-end Foreign Expert Project(G2023014066L)the Xinjiang Production and Construction Corps Agricultural Science and Technology Innovation Engineering Special Project(NCG202232).
文摘Polyamines(putrescine,spermidine,and spermine)are aliphatic compounds ubiquitous in prokaryotes and eukaryotes.Positively charged polyamines bind to negatively charged macromolecules,such as nucleic acids and acidic phospholipids,and are involved in physiological activities including cell proliferation,differentiation,apoptosis and gene regulation.Intracellular polyamine levels are regulated by biosynthesis,catabolism and transport.Polyamines in the body originate from two primary sources:dietary intake and intestinal microbial metabolism.These polyamines are then transported into the bloodstream,through which they are distributed to various tissues and organs to exert their biological functions.Polyamines synthesized by intestinal microorganisms serve dual critical roles.First,they are essential for maintaining polyamine concentrations within the digestive tract.Second,through transcriptional and post-transcriptional mechanisms,these microbial-derived polyamines modulate the expression of genes governing key processes in intestinal epithelial cells-including proliferation,migration,apoptosis,and cell-cell interactions.Collectively,these regulatory effects help maintain intestinal epithelial homeostasis and ensure the integrity of the gut barrier.In addition,polyamines interact with the gut microbiota to maintain intestinal homeostasis by promoting microbial growth,biofilm formation,swarming,and endocytosis vesicle production,etc.Supplementation with polyamines has been demonstrated to be important in regulating host intestinal microbial composition,enhancing nutrient absorption,and improving metabolism and immunity.In this review,we will focus on recent advances in the study of polyamine metabolism and transport in intestinal microbes and intestinal epithelial cells.We then summarize the scientific understanding of their roles in intestinal homeostasis,exploring the advances in cellular and molecular mechanisms of polyamines and their potential clinical applications,and providing a rationale for polyamine metabolism as an important target for the treatment of intestinal-based diseases.
