Potential therapeutic role of spermine via Rac1 in osteoporosis:Insights from zebrafish and mice

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

Enhancing the radiosensitivity of colorectal cancer cells by reducing spermine synthase through promoting autophagy and DNA damage

BACKGROUND Colorectal cancer(CRC),the third most common cancer worldwide,has increasingly detrimental effects on human health.Radiotherapy resistance diminishes treatment efficacy.Studies suggest that spermine synthase(SMS)may serve as a potential target to enhance the radiosensitivity.AIM To investigate the association between SMS and radiosensitivity in CRC cells,along with a detailed elucidation of the underlying mechanisms.METHODS Western blot was adopted to assess SMS expression in normal colonic epithelial cells and CRC cell lines.HCT116 cells were transfected with control/SMS-specific shRNA or control/pcDNA3.1-SMS plasmids.Assessments included cell viability,colony formation,and apoptosis via MTT assays,colony formation assays,and flow cytometry.Radiosensitivity was studied in SMS-specific shRNA-transfected HCT116 cells post-4 Gy radiation,evaluating cell viability,colony formation,apoptosis,DNA damage(comet assays),autophagy(immunofluorescence),and mammalian target of rapamycin(mTOR)pathway protein expression(western blot).RESULTS Significant up-regulation of SMS expression levels was observed in the CRC cell lines.Upon down-regulation of SMS expression,cellular viability and colonyforming ability were markedly suppressed,concomitant with a notable increase in apoptotic indices.Furthermore,attenuation of SMS expression significantly augmented the sensitivity of HCT116 cells to radiation therapy,evidenced by a pronounced elevation in levels of cellular DNA damage and autophagy.Impor tantly,down-regulation of SMS corresponded with a marked reduction in the expression levels of proteins associated with the mTOR signaling pathway.CONCLUSION Knocking down SMS attenuates the mTOR signaling pathway,thereby promoting cellular autophagy and DNA damage to enhance the radiosensitivity of CRC cells.

Effect of spermine on the melting curve and melting temperature of some tRNAs

Using purified bovine liver tRNA￣(Ile) and yeast tRNA￣(Phe), we studied the effects of spermine on the melting curve and melting temperature(Tm) of the tRNAs. The results showed that the absorbance at 260 nm of tRNAs decreases with the increase of temperature in the presence of 2 mmol/L spermine. We called this phenomenon hypochromism and reverse-Tm of the tRNAs. It is suggested that spermine binds to tRNAs and stabilizes the secondary structure of the tRNAs.

Casein kinase G may be the target of spermine during progesterone-induced oocyte maturation

Casein kinase G (CKG) with more than 2500-fold enrichment was purified from Bufo bufo gargarizans ovaries. The catalytic activity of the enzyme was found to be associated with its 42 kD subunit, and its 26 kD subunit was found to be the major target for the enzyme auto-phosphorylation. Each full-grown oocyte contained 1.9 units of CKG corresponding to an intracellular concentration of 93 nM. After injecting an amount of 0.38 units of the enzyme into the oocyte, approximately 50% of the progesterone-induced maturation was inhibited. The inhibitory effect was enhanced in oocytes pretreated with spermine, which was consistent with the results that the enzyme was activated in vitro in the presence of spermine. The MPF-induced oocyte maturation was delayed and even prohibited in the kinase-microinjected oocytes. A 55 kD oocyte protein was identified as an substrate of CKG both in vivo and in vitro, and the enhancement of the 55 kD protein phosphorylation was associated with kinase inhibition on maturation and on protein synthesis in kinase-microinjected oocytes. As the endogenous spermine level decreased in the course of progesterone-induced oocyte maturation, 55 kD protein was dephospho-rylated. Heparin, a specific inhibitor of CKG, potentiated the progesterone-induced oocyte maturation. Altogether the experimental results indicated strongly that CKG may be the physiological target of spermine.

Studies on the physiological function of spermine in the process of progesterone induced toad oocyte maturation

Spermidine or spermine but not putrescine inhibited progesterone induced Bufo bufo gargarizans oocyte maturation. The ID50 for spermine inhibition via intra - oocyte mi-croinjection on maturation induced by progesterone was 6. 8 mM(100 nl). Spermine could inhibit MPF induced toad oocyte maturation with a much higher ID50.A 55 kD protein was dephosphorylated during the process of progesterone induced oocyte maturation. Spermine selectively promoted the level of phosphorylation of ?this protein in both progesterone - stimulated and hormone - untreated oocytes. The extent of its dephosphorylation was fairly correlated with the percentage of GVBD in the hormone stimulated oocytes.The level of endogenous spermine was reduced by 28% between the period of 0. 40 GVBD50 and 0. 60 GVBD50, at which 55 kD protein was dephosphorylated.Spermine inhibited progesterone - stimulated protein synthesis in almost the same dose dependent manner as its inhibitory effect on the hormone - induced maturation. The endogenous spermine regulated 55 kD protein dephosphorylation which may trigger the increase of protein synthesis and in turn promote the activation of MPF. It is possible that 55 kD protein may be one of the components of messenger ribonucleoprotein (mRNP) particles.

High Concentration of Spermine Induces the Dedifferentiation of Somatic Cells into Pluripotent Stem Cells

Cancer tissues contain cancer stem cells (CSCs), which play important roles in cancer metastasis. However, the mechanisms through which cancer cells dedifferentiate into stem cells have not yet been elucidated. In this study, the effects of high concentrations of polyamines produced in cancer cells on dedifferentiation were examined. The results showed that when normal human fibroblasts were cultured with high concentrations of spermine, the obtained polyamine-induced cells expressed alkaline phosphatase and marker proteins of pluripotent stem cells, although apoptosis occurred in most cells. In contrast, another polyamine-induced stem (PIS) cell line (Spe-2 PIS cells), obtained by culture in medium containing Rock, p53, and Bax inhibitors plus spermine, did not show signs of apoptosis. These Spe-2 PIS cells expressed marker proteins of pluripotent stem cells and differentiated into cardiomyocytes, brown adipocytes, and nerve cells. These results suggest that a high concentration of spermine, which often induces apoptosis in normal cells, has the capacity to dedifferentiate somatic cells into pluripotent stem cells and may be associated with the dedifferentiation of cancer cells, which continuously produce high concentrations of spermine. Moreover, the procedure to obtain Spe-2 PIS cells, which is simple and efficient, may have potential applications in regenerative medicine.

Supramolecular cyclization induced emission enhancement in a pillar[5]arene probe for discrimination of spermine

Early diagnosis and treatment of cancer requires the development of tools that are both sensitive and selective in detecting spermine.In this study,we presented a"supramolecular cyclization-induced emission enhancement"strategy for the sensitive and selective detection of spermine.A new pillar[5]arene probe(P1)demonstrated excellent solution/solid dual-state emission properties,and the addition of certain spermine(Spm)resulted in fluorescence enhancement due to the synergy of multiple weak interactions that restricted the free motion of P1 in the P1⊃Spm complex.This mechanism was further confirmed by time-resolved spectroscopy,DFT calculations,and IGM analysis.With its low limit of detection and high selectivity,P1 is a promising tool for measuring spermine in artificial urine samples.

New insights into the role of spermine in enhancing the antioxidant capacity of rat spleen and liver under oxidative stress

Oxidative stress can damage cellular antioxidant defense and reduce livestock production efficiency.Spermine is a ubiquitous cellular component that plays important roles in stabilizing nucleic acids,modulating cell growth and differentiation, and regulating ion channel activities. Spermine has the potential to alleviate the effects of oxidative stress. However, to date no information is available about the effect of spermine administration on antioxidant property of the liver and spleen in any mammalian in vivo system. This study aims to investigate the protective effect of spermine on rat liver and spleen under oxidative stress. Rats received intragastric administration of either 0.4 μmol/g body weight of spermine or saline once a day for 3 days. The rats in each treatment were then injected with either diquat or sterile saline at 12 mg/kg body weight. Liver and spleen samples were collected 48 h after the last spermine ingestion.Results showed that regardless of diquat treatment, spermine administration significantly reduced the malondialdehyde(MDA) content by 23.78% in the liver and by 5.75% in the spleen, respectively(P < 0.05).Spermine administration also enhanced the catalase(CAT) activity, anti-hydroxyl radical(AHR) capacity and glutathione(GSH) content by 38.68%, 15.53% and 1.32% in the spleen, respectively(P< 0.05). There were interactions between spermine administration and diquat injection about anti-superoxide anion(ASA),AHR capacity, CAT activity, GSH content, and total antioxidant capacity(T-AOC) in the liver and about ASA capacity and T-AOC in the spleen of weaned rats(P < 0.05). Compared with the control group, spermine administration significantly increased the AHR capacity, CAT activity, GSH content, and T-AOC by 40.23%,31.15%, 30.25%, 35.37% in the liver, respectively(P < 0.05) and increased the T-AOC by 8% in the spleen of weaned rats(P < 0.05). Compared with the diquat group, spermine + diquat group significantly increased ASA capacity by 15.63% in the liver and by 73.41% in the spleen of weaned rats, respectively(P < 0.05).Results demonstrate that spermine administration can increase the antioxidant capacity in the liver and spleen and can enhance the antioxidant status in the spleen and liver under oxidative stress.

Effects of spermine supplementation on the morphology, digestive enzyme activities, and antioxidant capacity of intestine in weaning rats

The main objective of this study was to investigate the effects of different doses of spermine and its extended supplementation on the morphology, digestive enzyme activities, and intestinal antioxidant capacity in weaning rats. Nineteen-day-old male rats received intragastric spermine at doses of 0.2 and0.4 μmol/g BW for 3 or 7 d, whereas control rats received similar doses of saline. The results are as follows: 1) In the jejunum, the seven-day supplementation with both doses of spermine significantly increased crypt depth(P < 0.05) compared with the control group; the supplementation extension of the high spermine dose increased villus height and crypt depth(P < 0.05); in the ileum, the low spermine dose significantly increased villus height and crypt depth compared with the control group for 7 days(P < 0.05). 2) The 3-day supplementation with high spermine dose increased alkaline phosphatase activity in the jejunum(P < 0.05). 3) In the jejunum, the anti-hydroxyl radical(AHR), total superoxide dismutase(T-SOD), catalase(CAT), and total antioxidant capacity(T-AOC) activities were increased(P < 0.05); however, the malondialdehyde(MDA) content was reduced(P < 0.05) in groups supplemented with the high spermine dose relative to those in the control groups after 3 and 7 d; moreover, the anti-superoxide anion(ASA) and glutathione(GSH) contents increased with the high spermine dose that lasted for 3 days(P < 0.05). Furthermore, the T-SOD and CAT activities(after 3 and 7 d), ASA(after 3 d),and AHR(after 7 d) increased with the high spermine dose compared with those of the low spermine dose(P < 0.05). Extending the supplementation duration(7 d) of the high spermine dose decreased the MDA content and ASA and T-AOC activities(P < 0.05). These results suggested that spermine supplementation can modulate gut development and enhance the antioxidant status of the jejunum in weaning rats, and a dosage of 0.4 μmol spermine/g BW had better effects than the dosage of 0.2 μmol spermine/g BW on accelerating gut development and increasing antioxidant capacity.

Spermine induced reversible collapse of deoxyribonucleic acid-bridged nanoparticle-based assemblies

DNA-linked 2D and 3D nano-assemblies find use in a diverse set of applications, ranging from DNA-origami in drug delivery and medical imaging, to DNA-linked nanoparticle structures for use in plasmonics and （bio）sensing. However, once these structures have been fully assembled, few options are available to modulate structure geometry. Here, we investigated the use of the polycation spermine to induce DNA collapse in small oligonucleotide-linked （54 bp） gold nanoparticle structures by monitoring shifts in the localized surface plasmon resonance （LSPR） peak and by comparing the data with finite-difference time-domain （FDTD） simulations. Our data shows that low concentrations of spermine can be applied to induce large changes in DNA conformation, leading to a significant reduction in interparticle distance （from - 25 to - 3 nm） and enhanced plasmonic coupling. The DNA collapse is near-instantaneous and reversible, and its application at low and high DNA densities is demonstrated with surface plasmon resonance imaging （SPRi）, showing the potential of spermine to dynamically modulate distances and geometry in DNA-based nano-assemblies.

Spermine protects intestinal barrier integrity through ras-related C3 botulinum toxin substrate 1/phospholipase C-γ1 signaling pathway in piglets

Weaning stress can cause tight junctions damage and intestinal permeability enhancement,which leads to intestinal imbalance and growth retardation,thereby causing damage to piglet growth and development.Spermine can reduce stress.However,the mechanism of spermine modulating the intestinal integrity in pigs remains largely unknown.This study aims to examine whether spermine protects the intestinal barrier integrity of piglets through ras-related C3 botulinum toxin substrate 1(Rac1)/phospholipase C-g1(PLC-γ1)signaling pathway.In vivo,80 piglets were categorised into 4 control groups and 4 spermine groups(10 piglets per group).The piglets were fed with normal saline or spermine at 0.4 mmol/kg BW for 7 h and 3,6 and 9 d.In vitro,we investigated whether spermine protects the intestinal barrier after a tumor necrosis factor a(TNF-a)challenge through Rac1/PLC-γ1 signaling pathway.The in vivo study found that spermine supplementation increased tight junction protein mRNA levels and Rac1/PLC-γ1 signaling pathway gene expression in the jejunum of piglets.The serum D-lactate content was significantly decreased after spermine supplementation(P<0.05).The in vitro study found that 0.1 mmol/L spermine increased the levels of tight junction protein expression,Rac1/PLC-γ1 signaling pathway and transepithelial electrical resistance,and decreased paracellular permeability(P<0.05).Further experiments demonstrated that spermine supplementation enhanced the levels of tight junction protein expression,Rac1/PLC-γ1 signaling pathway and transepithelial electrical resistance,and decreased paracellular permeability compared with the NSC-23766 and U73122 treatment with spermine after TNF-a challenge(P<0.05).Collectively,spermine protects intestinal barrier integrity through Rac1/PLC-γ1 signaling pathway in piglets.

Spermine increases bactericidal activity of silver-nanoparticles against clinical methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus(MRSA) has emerged worldwide as a major multidrugresistant pathogen that causes notable morbidity and mortality. Fast emerging of MRSA prevalence requires special attention for strengthening the inventory of antimicrobial compounds. Silver nanoparticles(AgNPs) have been widely used to treat multi-drug resistant pathogens due to the unique antibacterial properties, meanwhile spermine has been proven to exert outstanding inhibition effect to S.aureus with not yet fully understood mechanisms. The aim of this study was to investigate the synergistic effect of AgNPs and spermine as well as to determine the antibacterial activity of their combination against MRSA strains. Several clinical MRSA isolates and ATCC BAA-1026 were used to determine minimum inhibitory concentration(MIC) and fractional inhibitory concentration indices(FICI) of AgNPs and spermine, and a synergistic effect was observed. This phenomenon was further confirmed by growth curve and time-killing assays, showed that spermine could be used as an adjuvant for AgNPs in the treatment of MRSA infections.

SPERMINE——AN INHIBITION OF in vitro CAPACITATION AND FERTILIZATION IN HAMSTER SPERM

I. INTRODUCTION The polyamines, putrescine, spermidine and spermine exist in all mammalian tissues and fluids. In semen, spermine is frequently present in high concentrations. However, the

Changes in the sugars,amino acids and organic acids of postharvest sperminetreated immature vegetable soybean(Glycine max L.Merr.)as determined by^(1)H NMR spectroscopy

^(1)H NMR spectroscopy was adopted to determine compositional changes(mainly sugars,organic acids and amino acids)involved in cold-stored immature soybean grains after exogenous spermine treatment.Significant changes of sugars,including sucrose,galactose,myo-inositol,glucose and fructose were detected in soybean after spermine treatment.As for the organic acids related to tricarboxylic acid cycle,the levels of malic and fumaric acids decreased but the level of citric acid increased.However,no significant changes were observed for amino acids in spermine-treated soybeans.By using metabolic profile analysis,a difference was observed between the aging of soybean grains as such and those treated with spermine.This study provides an insight into the accumulation of metabolites in postharvest immature soybeans after exogenous spermine-treatment.

三种多胺对隐秘小环藻生长及藻壳结构的影响

为了探究外源多胺的添加能否使硅藻壳的结构特征发生变化,本研究在实验室条件下比较了3种多胺(亚精胺、精胺和腐胺)不同浓度处理对隐秘小环藻(Cyclotella cryptica)生长、藻壳细微结构及主要物理特性的影响。研究显示,1000μmol/L精胺表现出致死效应,600、800及1000μmol/L的腐胺处理组中,细胞密度峰值分别在培养的第4、3、2天出现,显示出典型的“时间剂量效应”。其中100μmol/L亚精胺、1000μmol/L精胺以及200μmol/L腐胺处理组的硅质壳,在管状突出结构分布的位置和数量、壳孔区孔的排列、藻壳中心孔的分布、孔容孔径等方面发生较为明显的变化,如200μmol/L腐胺处理组藻壳总孔体积和比表面积仅为对照组的52.7%和53.6%。上述结果说明这3种多胺分子可以造成硅藻壳结构的改变。

亚精胺对人子宫内膜基质细胞自噬和炎症细胞因子表达的影响

目的:探讨克罗米芬(CC)对子宫内膜基质细胞(hEndoSCs)的损伤作用,并研究亚精胺对受损子宫内膜基质细胞自噬和炎症细胞因子表达的影响。方法:实验分为对照组、亚精胺组、克罗米芬组(CC组)、CC+亚精胺组。MTT法检测hEndoSCs与不同浓度CC或亚精胺共同孵育24 h后细胞的存活率;流式细胞技术检测4组细胞内活性氧(ROS)含量和细胞凋亡水平。Western blot检测自噬途径相关蛋白ULK1、p-ULK1、LC-3Ⅱ和凋亡相关蛋白Bax、Bcl-2、Cleaved-caspase 3的表达。采用RT-qPCR检测IL-6、IL-1β、TNF-αmRNA表达量。结果:与对照组相比,CC组细胞存活率下降,细胞凋亡率、ROS含量、Bax、Cleaved-caspase 3表达量升高,Bcl-2表达量降低,自噬相关蛋白p-ULK1、LC-3Ⅱ/Ⅰ水平降低,炎症因子IL-6、IL-1β、TNF-αmRNA表达升高(P<0.01)。与对照组相比,亚精胺组细胞的存活率无明显变化(P>0.05)。与CC组相比,CC+亚精胺组细胞存活率显著提高,细胞凋亡率、ROS含量、Bax和Cleaved-caspase 3表达量降低,Bcl-2表达量升高,自噬相关蛋白p-ULK1、LC-3Ⅱ/Ⅰ表达升高,炎症因子IL-6、IL-1β、TNF-αmRNA表达降低(P<0.01)。结论:CC能够抑制子宫内膜基质细胞增殖,促进细胞凋亡,提高炎症因子IL-6、IL-1β、TNF-α的转录水平。亚精胺可通过激活细胞自噬,降低CC损伤的子宫内膜基质细胞胞内ROS水平,提高细胞存活率,并抑制炎症因子IL-6、IL-1β、TNF-α表达。

A PET probe targeting polyamine transport system for precise tumor diagnosis and therapy

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

精胺氧化酶靶向调控硫氧还蛋白还原酶1促进结肠癌恶性进展

目的探讨精胺氧化酶(spermine oxidase,SMOX)靶向调控硫氧还蛋白还原酶1(thioredoxin reductase 1,TR1)对结肠癌恶性进展的影响。方法收集2018年9月至2019年6月就诊于南京市第一医院的30例结肠癌患者的结肠癌组织及其癌旁组织。采用免疫组织化学染色检测组织中的SMOX表达。采用Western blot实验检测结肠癌细胞株(HCT116、SW480、DLD-1、SW620、Caco-2、HCT-15、T84和LS123)和正常结肠细胞株NCM460的SMOX表达。利用基因表达谱互作分析(Gene Expression Profiling Interactive Analysis,GEPIA)网站查询SMOX在结肠癌组织与癌旁组织中的表达情况和SMOX表达水平与患者总生存的关系。采用Western blot实验检测上述细胞和组织中代谢产物亚精胺合成酶的水平。利用2',7'-二氯二氢荧光素二乙酸酯(2',7'-dichlorodihydrofluorescein diacetate,DCFH-DA)结合流式细胞术和组织免疫荧光实验分别检测结肠细胞和组织中代谢副产物活性氧(reactive oxygen species,ROS)水平。选取SMOX表达水平最高的结肠癌细胞株HCT116和SW480为实验对象,构建慢病毒载体,用PLKO.1-puro-shCtrl、PLKO.1-puro-shSMOX、PLKO.1-puro-shSMOX+pcDNA3.1和PLKO.1-puro-shSMOX+pcDNA3.1-TR1分别转染细胞,分别为shCtrl组、shSMOX组、shSMOX+pcDNA3.1组和shSMOX+TR1组。Western blot实验检测HCT116和SW480细胞shCtrl组和shSMOX组SMOX与TR1的表达情况,以及HCT116细胞shSMOX+pcDNA3.1组和shSMOX+TR1组的TR1表达水平。利用细胞计数试剂盒(Cell Counting Kit-8,CCK-8)检测细胞增殖活力。碘化丙啶(propidium iodide,PI)单染结合流式细胞术检测肿瘤细胞周期变化。PI/异硫氰酸荧光素-膜连蛋白(PI/fluorescein isothiocyanate-Annexin V,PI/FITC-Annexin V)双染结合流式细胞术检测细胞凋亡/坏死情况。Transwell体外侵袭实验分析细胞侵袭能力。shCtrl组、shSMOX组、shSMOX+pcDNA3.1组和shSMOX+TR1组的HCT116细胞稀释至浓度为1×107个/mL的细胞悬液分别向裸鼠右侧腋窝皮下注射0.2 mL细胞悬液,建立裸鼠结肠癌移植瘤模型。4周后处死裸鼠,分离组织,剥取肿瘤称重。运用免疫组织化学染色检测裸鼠结肠肿瘤组织中Ki-67阳性细胞数。结果SMOX在8种结肠癌细胞株和结肠癌组织中的表达水平均高于正常结肠细胞株和癌旁组织,且与不良预后有关(均P<0.05)。与正常结肠细胞和癌旁组织比较,8种结肠癌细胞和结肠癌组织中的代谢产物亚精胺合成酶和ROS水平随SMOX的高表达同步升高(均P<0.05)。与shCtrl组比较,shSMOX组G_(0)/G_(1)期细胞数目增多,PI/Annexin V双阳性细胞数目增加,细胞增殖活性降低,侵袭数量减少,SMOX和TR1表达水平降低(均P<0.05)。与shSMOX组和shSMOX+pcDNA3.1组比较,shSMOX+TR1组TR1表达水平升高,S期细胞数目增多,PI/Annexin V双阳性细胞数目减少,细胞增殖活性升高(均P<0.05)。裸鼠结肠癌移植瘤模型显示,注射后14 d,与shCtrl组比较,shSMOX组和shSMOX+pcDNA3.1组肿瘤体积和重量均降低,结肠肿瘤组织中Ki-67阳性细胞数减少,而shSMOX+TR1组肿瘤体积、重量和结肠肿瘤组织中Ki-67阳性细胞数则较shSMOX+pcDNA3.1组增加(均P<0.05)。结论SMOX在结肠癌细胞和组织中表达上调,可能通过靶向提高TR1的表达促进细胞周期运转,抑制细胞凋亡,促进细胞增殖和侵袭能力及肿瘤生长,进而促进结肠癌恶性进展。

多胺在肿瘤发生发展中的作用及其干预研究进展

多胺在肿瘤发生发展、靶向治疗和免疫治疗方面发挥着重要的作用。多胺包括腐胺、精胺和亚精胺等,临床研究和实验结果显示肿瘤存在多种形式的多胺代谢异常,且多胺代谢异常的研究对于肿瘤靶向治疗、免疫治疗生化标志物研究具有重要价值。随着对多胺在肿瘤发生发展和肿瘤治疗中作用的认识不断加深,人们对以多胺代谢为靶点的抗肿瘤干预策略的兴趣日益加深。本文综述多胺及其代谢与不同类型肿瘤进展的关系,旨在总结多胺代谢调控的药物靶点和临床防治药物开发策略。

外源精胺对盐胁迫下草莓钠钾稳态和光合作用的影响

本试验以‘红颜’为材料,采用盆栽方式,研究不同浓度(0、0.3、0.6、0.9mmol·L^(-1))外源精胺(Spermine)对盐胁迫(150mmol·L^(-1)NaCl)下草莓幼苗生长、Na^(+)和K^(+)含量、光合特性的影响。结果表明:外源喷施不同浓度精胺,与NaCl处理相比,显著提高地上部和地下部鲜重、地下部干重、K^(+)含量、叶绿素含量、净光合速率、可溶性糖含量、可溶性蛋白含量和抗氧化酶活性,显著降低Na^(+)含量、丙二醛含量。根据隶属函数综合评价,0.6 mmol·L^(-1)精胺处理的草莓幼苗耐盐性最好,D值为0.27。