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Biomedical Materials (Bristol, England) Jun 2024Oral cancer accounts for 50%-70% of all cancer-related deaths in India and ranks sixth among the most frequent cancers globally. Roughly 90% of oral malignancies are...
Oral cancer accounts for 50%-70% of all cancer-related deaths in India and ranks sixth among the most frequent cancers globally. Roughly 90% of oral malignancies are histologically arise from squamous cells and are therefore called oral squamous cell carcinoma. Organic polycations known as biogenic polyamines, for example, putrescine (Put), spermidine (Spd), and spermine (Spm), are vital for cell proliferation, including gene expression control, regulation of endonuclease-mediated fragmentation of DNA, and DNA damage inhibition. Higher Spm and Spd levels have been identified as cancer biomarkers for detecting tumour development in various cancers. The current study utilises tannic acid, a polyphenolic compound, as a reducing and capping agent to fabricate AuNPs via a one-step microwave-assisted synthesis. The fabricated TA@AuNPs were utilised as a nanoprobe for colourimetric sensing of polyamines in PBS. When TA@AuNPs are added to the polyamine, the amine groups in polyamines interact with the phenolic groups of TA@AuNPs via hydrogen bonding or electrostatic interactions. These interactions cause the aggregation of TA@AuNPs, resulting in a red shift of the Surface Plasmon Resonance band of TA@AuNPs from 530 nm to 560 nm. The nanoprobe was found to be highly specific for Spm at low concentrations. TA@AuNPs were able to detect Spm successfully in artificial saliva samples. On recording the RGB values of the sensing process using a smartphone app, it was found that as the nanoparticles aggregated due to the presence of Spm, the intensity of the-value decreased, indicating the aggregation of TA@AuNPs due to interaction with the polyamine.
Topics: Mouth Neoplasms; Humans; Metal Nanoparticles; Polyamines; Gold; Spermine; Smartphone; Putrescine; Spermidine; Tannins; Surface Plasmon Resonance; Colorimetry; Biomarkers, Tumor; Carcinoma, Squamous Cell
PubMed: 38871001
DOI: 10.1088/1748-605X/ad581a -
Journal of Agricultural and Food... Jun 2024Rapeseed ( L.) is extremely sensitive to excessive NH toxicity. There remains incomplete knowledge of the causal factors behind the growth suppression in NH-nourished...
Rapeseed ( L.) is extremely sensitive to excessive NH toxicity. There remains incomplete knowledge of the causal factors behind the growth suppression in NH-nourished plants, with limited studies conducted specifically on field crop plants. In this study, we found that NH toxicity significantly increased salicylic acid (SA) accumulation by accelerating the conversion of SA precursors. Moreover, exogenous SA application significantly aggravated NH toxicity symptoms in the rapeseed shoots. Genome-wide differential transcriptomic analysis showed that NH toxicity increased the expression of genes involved in the biosynthesis, transport, signaling transduction, and conversion of SA. SA treatment significantly increased shoot NH concentrations by reducing the activities of glutamine synthase and glutamate synthase in NH-treated rapeseed plants. The application of an SA biosynthesis inhibitor, ABT, alleviated NH toxicity symptoms. Furthermore, SA induced putrescine (Put) accumulation, resulting in an elevated ratio of Put to [spermidine (Spd) + spermine (Spm)] in the NH-treated plants, while the opposite was true for ABT. The application of exogenous Put and its biosynthesis inhibitor DFMA induced opposite effects on NH toxicity in rapeseed shoots. These results indicated that the increased endogenous SA contributed noticeably to the toxicity caused by the sole NH-N supply in rapeseed shoots. This study provided fresh perspectives on the mechanism underlying excessive NH-induced toxicity and the corresponding alleviating strategies in plants.
Topics: Brassica napus; Salicylic Acid; Ammonium Compounds; Plant Proteins; Gene Expression Regulation, Plant; Putrescine; Plant Shoots
PubMed: 38869198
DOI: 10.1021/acs.jafc.4c00238 -
Biomacromolecules Jun 2024After RNAi was first discovered over 20 years ago, siRNA-based therapeutics are finally becoming reality. However, the delivery of siRNA has remained a challenge. In our...
After RNAi was first discovered over 20 years ago, siRNA-based therapeutics are finally becoming reality. However, the delivery of siRNA has remained a challenge. In our previous research, we found that spermine-based poly(β-amino ester)s are very promising for siRNA delivery. However, the role of hydrophobic modification in siRNA delivery of spermine-based poly(β-amino ester)s is not fully understood yet. In the current work, we synthesized spermine-based poly(β-amino ester)s with different percentages of oleylamine side chains, named P(SpOABAE). The chemical structures of the polymers were characterized by H NMR. The polymers showed efficient siRNA encapsulation determined by SYBR Gold assays. The hydrodynamic diameters of the P(SpOABAE) polyplexes from charge ratio N/P 1 to 20 were 30-100 nm except for aggregation phenomena observed at N/P 3. Morphology of the polyplexes was visualized by atomic force microscopy, and cellular uptake was determined by flow cytometry in H1299 cells, where all the polyplexes showed significantly higher cellular uptake than hyperbranched polyethylenimine (25 kDa). The most hydrophobic P(SpOABAE) polyplexes were able to achieve more than 90% GFP knockdown in H1299/eGFP cells. The fact that gene silencing efficacy increased with hydrophobicity but cellular uptake was affected by both charge and hydrophobic interactions highlights the importance of endosomal escape. For pulmonary administration and improved storage stability, the polyplexes were spray-dried. Results confirmed the maintained siRNA activity after storage for 3 months at room temperature, indicating potential for dry powder inhalation.
PubMed: 38866384
DOI: 10.1021/acs.biomac.4c00283 -
Pediatric Allergy and Immunology :... Jun 2024Some studies have reported that polyamine levels may influence immune system programming. The aim of this study was to evaluate the polyamine profile during gestation...
BACKGROUND
Some studies have reported that polyamine levels may influence immune system programming. The aim of this study was to evaluate the polyamine profile during gestation and its associations with maternal allergy and cytokine production in cord blood cells in response to different allergenic stimuli.
METHODS
Polyamines were determined in plasma of pregnant women (24 weeks, N = 674) and in umbilical cord samples (N = 353 vein and N = 160 artery) from the Mediterranean NELA birth cohort. Immune cell populations were quantified, and the production of cytokines in response to different allergic and mitogenic stimuli was assessed in cord blood.
RESULTS
Spermidine and spermine were the most prevalent polyamines in maternal, cord venous, and cord arterial plasma. Maternal allergies, especially allergic conjunctivitis, were associated with lower spermine in umbilical cord vein. Higher levels of polyamines were associated with higher lymphocyte number but lower Th2-related cells in cord venous blood. Those subjects with higher levels of circulating polyamines in cord showed lower production of inflammatory cytokines, especially IFN-α, and lower production of Th2-related cytokines, mainly IL-4 and IL-5. The effects of polyamines on Th1-related cytokines production were uncertain.
CONCLUSIONS
Spermidine and spermine are the predominant polyamines in plasma of pregnant women at mid-pregnancy and also in umbilical cord. Maternal allergic diseases like allergic conjunctivitis are related to lower levels of polyamines in cord vein, which could influence the immune response of the newborn. Cord polyamine content is related to a decreased Th2 response and inflammatory cytokines production, which might be important to reduce an allergenic phenotype in the neonate.
Topics: Humans; Female; Pregnancy; Infant, Newborn; Fetal Blood; Cytokines; Polyamines; Hypersensitivity; Adult; Pregnancy Complications; Th2 Cells; Spermidine
PubMed: 38860435
DOI: 10.1111/pai.14167 -
Biochimica Et Biophysica Acta. General... Jun 2024Mitochondria play a crucial role in maintaining Ca homeostasis in cells. Due to the critical regulatory role of the products of oxidative and non-oxidative metabolism of...
Mitochondria play a crucial role in maintaining Ca homeostasis in cells. Due to the critical regulatory role of the products of oxidative and non-oxidative metabolism of L-arginine, it is essential to clarify their effect on Ca transport in smooth muscle mitochondria. Experiments were performed on the uterine myocytes of rats and isolated mitochondria. The possibility of NO synthesis by mitochondria was demonstrated by confocal microscopy and spectrofluorimetry methods using the NO-sensitive fluorescent probe DAF-FM and Mitotracker Orange CM-H2TMRos. It was shown that 50 μM L-arginine stimulates the energy-dependent accumulation of Ca in mitochondria using the fluorescent probe Fluo-4 AM. A similar effect occurred when using nitric oxide donors 100 μM SNP, SNAP, and sodium nitrite (SN) directly. The stimulating effect was eliminated in the presence of the NO scavenger C-PTIO. Nitric oxide reduces the electrical potential in mitochondria without causing them to swell. The stimulatory effect of spermine on the accumulation of Ca by mitochondria is attributed to the enhancement of NO synthesis, which was demonstrated with the use of C-PTIO, NO-synthase inhibitors (100 μM NA and L-NAME), as well as by direct monitoring of NO synthesis fluorescent probe DAF-FM. A conclusion was drawn about the potential regulatory effect of the product of the oxidative metabolism of L-arginine - NO on the transport of Ca in the mitochondria of the myometrium, as well as the corresponding effect of the product of non-oxidative metabolism -spermine by increasing the synthesis of NO in these subcellular structures.
PubMed: 38857773
DOI: 10.1016/j.bbagen.2024.130652 -
BMC Genomics Jun 2024Expansion of genomic resources for the Pacific white shrimp (Litopenaeus vannamei), such as the construction of dense genetic linkage maps, is crucial for the...
BACKGROUND
Expansion of genomic resources for the Pacific white shrimp (Litopenaeus vannamei), such as the construction of dense genetic linkage maps, is crucial for the application of genomic tools in order to improve economically relevant traits. Sexual dimorphism exists in Pacific white shrimp, and the mapping of the sex-determination region in this species may help in future reproductive applications. We have constructed male, female, and sex-averaged high-density genetic maps using a 50 K single-nucleotide polymorphism (SNP) array, followed by a genome-wide association study (GWAS) to identify genomic regions associated with sex in white shrimp.
RESULTS
The genetic map yielded 15,256 SNPs assigned to 44 linkage groups (LG). The lengths of the male, female, and sex-averaged maps were 5,741.36, 5,461.20 and 5,525.26 cM, respectively. LG18 was found to be the largest for both sexes, whereas LG44 was the shortest for males and LG31 for females. A sex-determining region was found in LG31 with 21 statistically significant SNPs. The most important SNP was previously identified as a sex-linked marker and was able to identify 99% of the males and 88% of the females. Although other significant markers had a lower ability to determine sex, putative genes were intercepted or close to them. The oplophorus-luciferin 2-monooxygenase, serine/arginine repetitive matrix protein and spermine oxidase genes were identified as candidates with possible participation in important processes of sexual differentiation in shrimp.
CONCLUSIONS
Our results provide novel genomic resources for shrimp, including a high-density linkage map and new insights into the sex-determining region in L. vannamei, which may be usefulfor future genetics and reproduction applications.
Topics: Animals; Penaeidae; Polymorphism, Single Nucleotide; Female; Male; Chromosome Mapping; Sex Determination Processes; Genetic Linkage; Genome-Wide Association Study
PubMed: 38840101
DOI: 10.1186/s12864-024-10431-x -
Communications Biology Jun 2024Ferroptosis, a type of iron-dependent non-apoptotic cell death, plays a vital role in both tumor proliferation and resistance to chemotherapy. Here, our study...
Ferroptosis, a type of iron-dependent non-apoptotic cell death, plays a vital role in both tumor proliferation and resistance to chemotherapy. Here, our study demonstrates that MAX's Next Tango (MNT), by involving itself in the spermidine/spermine N1-acetyltransferase 1 (SAT1)-related ferroptosis pathway, promotes the proliferation of lung adenocarcinoma (LUAD) cells and diminishes their sensitivity to chemotherapy. Initially, an RNA-sequence screen of LUAD cells treated with ferroptosis inducers (FINs) reveals a significant increase in MNT expression, suggesting a potential link between MNT and ferroptosis. Overexpression of MNT in LUAD cells hinders changes associated with ferroptosis. Moreover, the upregulation of MNT promotes cell proliferation and suppresses chemotherapy sensitivity, while the knockdown of MNT has the opposite effect. Through the intersection of ChIP-Seq and ferroptosis-associated gene sets, and validation by qPCR and western blot, SAT1 is identified as a potential target of MNT. Subsequently, we demonstrate that MNT binds to the promoter sequence of SAT1 and suppresses its transcription by ChIP-qPCR and dual luciferase assays. Restoration of SAT1 levels antagonizes the efficacy of MNT to inhibit ferroptosis and chemosensitivity and promote cell growth in vitro as well as in vivo. In the clinical context, MNT expression is elevated in LUAD and is inversely connected with SAT1 expression. High MNT expression is also associated with poor patient survival. Our research reveals that MNT inhibits ferroptosis, and impairing chemotherapy effectiveness of LUAD.
Topics: Ferroptosis; Humans; Lung Neoplasms; Adenocarcinoma of Lung; Acetyltransferases; Mice; Cell Line, Tumor; Animals; Drug Resistance, Neoplasm; Mice, Nude; Gene Expression Regulation, Neoplastic; Cell Proliferation; Antineoplastic Agents; Xenograft Model Antitumor Assays; Female; Mice, Inbred BALB C; Male
PubMed: 38831092
DOI: 10.1038/s42003-024-06373-5 -
Plant Physiology and Biochemistry : PPB Jul 2024The mulberry fruit is prized for its superior nutrition value and abundant color due to its high flavone content. To enhance comprehension of flavone biogenesis induced...
The mulberry fruit is prized for its superior nutrition value and abundant color due to its high flavone content. To enhance comprehension of flavone biogenesis induced by external hormones, we sprayed exogenous ethylene (ETH), indoleacetic acid (IAA) and spermine (SPM) on mulberry fruit (Hongguo 2) during its color-changed period. The levels of anthocyanin, titratable acid, soluble sugar and endogenous hormones were determined after hormone treatment, integrated transcriptome and metabolome analysis were performed for mechanism exploration. Our results indicated that exogenous ETH, SPM, and IAA play important roles in mulberry ripening, including acid reduction, sugar increase and flavonoid synthesis.
Topics: Morus; Fruit; Flavonoids; Plant Growth Regulators; Indoleacetic Acids; Transcriptome; Gene Expression Regulation, Plant; Ethylenes; Spermine; Gene Expression Profiling; Metabolome; Metabolomics
PubMed: 38820912
DOI: 10.1016/j.plaphy.2024.108773 -
The FEBS Journal May 2024Polyamines are ubiquitous biomolecules with a number of established functions in eukaryotic cells. In plant cells, polyamines have previously been linked to abiotic and...
Polyamines are ubiquitous biomolecules with a number of established functions in eukaryotic cells. In plant cells, polyamines have previously been linked to abiotic and biotic stress tolerance, as well as to the modulation of programmed cell death (PCD), with contrasting reports on their pro-PCD and pro-survival effects. Here, we used two well-established platforms for the study of plant PCD, Arabidopsis thaliana suspension cultures cells and the root hair assay, to examine the roles of the polyamines spermine and spermidine in the regulation of PCD. Using these systems for precise quantification of cell death rates, we demonstrate that both polyamines can trigger PCD when applied exogenously at higher doses, whereas at lower concentrations they inhibit PCD induced by both biotic and abiotic stimuli. Furthermore, we show that concentrations of polyamines resulting in inhibition of PCD generated a transient ROS burst in our experimental system, and activated the expression of oxidative stress- and pathogen response-associated genes. Finally, we examined PCD responses in existing Arabidopsis polyamine synthesis mutants, and identified a subtle PCD phenotype in Arabidopsis seedlings deficient in thermo-spermine. The presented data show that polyamines can have a role in PCD regulation; however, that role is dose-dependent and consequently they may act as either inhibitors, or inducers, of PCD in Arabidopsis.
PubMed: 38808914
DOI: 10.1111/febs.17165 -
Aging Cell May 2024Recent studies have demonstrated the remarkable potential of early life intervention strategies at influencing the course of postnatal development, thereby offering...
Recent studies have demonstrated the remarkable potential of early life intervention strategies at influencing the course of postnatal development, thereby offering exciting possibilities for enhancing longevity and improving overall health. Metformin (MF), an FDA-approved medication for type II diabetes mellitus, has recently gained attention for its promising anti-aging properties, acting as a calorie restriction mimetic, and delaying precocious puberty. Additionally, trodusquemine (MSI-1436), an investigational drug, has been shown to combat obesity and metabolic disorders by inhibiting the enzyme protein tyrosine phosphatase 1b (Ptp1b), consequently reducing hepatic lipogenesis and counteracting insulin and leptin resistance. In this study, we aimed to further explore the effects of these compounds on young, developing mice to uncover biomolecular signatures that are central to liver metabolic processes. We found that MSI-1436 more potently alters mRNA and miRNA expression in the liver compared with MF, with bioinformatic analysis suggesting that cohorts of differentially expressed miRNAs inhibit the action of phosphoinositide 3-kinase (Pi3k), protein kinase B (Akt), and mammalian target of rapamycin (Mtor) to regulate the downstream processes of de novo lipogenesis, fatty acid oxidation, very-low-density lipoprotein transport, and cholesterol biosynthesis and efflux. In summary, our study demonstrates that administering these compounds during the postnatal window metabolically reprograms the liver through induction of potent epigenetic changes in the transcriptome, potentially forestalling the onset of age-related diseases and enhancing longevity. Future studies are necessary to determine the impacts on lifespan and overall quality of life.
PubMed: 38798180
DOI: 10.1111/acel.14227