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International Journal of Molecular... May 2024This review describes a 50-year-long research study on the characteristics of L. tuber dormancy, its natural release and programmed cell death (PCD), as well as on the... (Review)
Review
This review describes a 50-year-long research study on the characteristics of L. tuber dormancy, its natural release and programmed cell death (PCD), as well as on the ability to change the PCD so as to return the tuber to a life program. The experimentation on the tuber over the years is due to its particular properties of being naturally deficient in polyamines (PAs) during dormancy and of immediately reacting to transplants by growing and synthesizing PAs. This review summarizes the research conducted in a unicum body. As in nature, the tuber tissue has to furnish its storage substances to grow vegetative buds, whereby its destiny is PCD. The review's main objective concerns data on PCD, the link with free and conjugated PAs and their capacity to switch the destiny of the tuber from a program of death to one of new life. PCD reversibility is an important biological challenge that is verified here but not reported in other experimental models. Important aspects of PA features are their capacity to change the cell functions from storage to meristematic ones and their involvement in amitosis and differentiation. Other roles reported here have also been confirmed in other plants. PAs exert multiple diverse roles, suggesting that they are not simply growth substances, as also further described in other plants.
Topics: Helianthus; Apoptosis; Polyamines; Plant Tubers
PubMed: 38791426
DOI: 10.3390/ijms25105386 -
Journal of Fungi (Basel, Switzerland) May 2024The effect of dimethyl sulfoxide (DMSO) on fungal metabolism has not been well studied. This study aimed to evaluate, by metabolomics, the impact of DMSO on the central...
The effect of dimethyl sulfoxide (DMSO) on fungal metabolism has not been well studied. This study aimed to evaluate, by metabolomics, the impact of DMSO on the central carbon metabolism of . Biofilms of SC5314 were grown on paper discs, using minimum mineral (MM) medium, in a dynamic continuous flow system. The two experimental conditions were control and 0.03% DMSO (/). After 72 h of incubation (37 °C), the biofilms were collected and the metabolites were extracted. The extracted metabolites were subjected to gas chromatography-mass spectrometry (GC/MS). The experiment was conducted using five replicates on three independent occasions. The GC/MS analysis identified 88 compounds. Among the 88 compounds, the levels of 27 compounds were markedly different between the two groups. The DMSO group exhibited enhanced levels of putrescine and glutathione and decreased levels of methionine and lysine. Additionally, the DMSO group exhibited alterations in 13 metabolic pathways involved in primary and secondary cellular metabolism. Among the 13 altered pathways, seven were downregulated and six were upregulated in the DMSO group. These results indicated a differential intracellular metabolic profile between the untreated and DMSO-treated biofilms. Hence, DMSO was demonstrated to affect the metabolic pathways of . These results suggest that DMSO may influence the results of laboratory tests when it is used as a solvent. Hence, the use of DMSO as a solvent must be carefully considered in drug research, as the effect of the researched drugs may not be reliably translated into clinical practice.
PubMed: 38786692
DOI: 10.3390/jof10050337 -
Chemico-biological Interactions Jun 2024Chronic inflammation, oxidative stress, and airway remodelling represent the principal pathophysiological features of chronic respiratory disorders. Inflammation stimuli...
Chronic inflammation, oxidative stress, and airway remodelling represent the principal pathophysiological features of chronic respiratory disorders. Inflammation stimuli like lipopolysaccharide (LPS) activate macrophages and dendritic cells, with concomitant M1 polarization and release of pro-inflammatory cytokines. Chronic inflammation and oxidative stress lead to airway remodelling causing irreversible functional and structural alterations of the lungs. Airway remodelling is multifactorial, however, the hormone transforming growth factor-β (TGF-β) is one of the main contributors to fibrotic changes. The signalling pathways mediating inflammation and remodelling rely both on the transcription factor nuclear factor-κB (NFκB), underlying the potential of NFκB inhibition as a therapeutic strategy for chronic respiratory disorders. In this study, we encapsulated an NFκB-inhibiting decoy oligodeoxynucleotide (ODN) in spermine-functionalized acetalated dextran (SpAcDex) nanoparticles and tested the in vitro anti-inflammatory and anti-remodelling activity of this formulation. We show that NF-κB ODN nanoparticles counteract inflammation by reversing LPS-induced expression of the activation marker CD40 in myeloid cells and counteracts remodelling features by reversing the TGF-β-induced expression of collagen I and α-smooth muscle actin in human dermal fibroblast. In summary, our study highlights the great potential of inhibiting NFκB via decoy ODN as a therapeutic strategy tackling multiple pathophysiological features underlying chronic respiratory conditions.
Topics: Oligodeoxyribonucleotides; Humans; Nanoparticles; Anti-Inflammatory Agents; NF-kappa B; Spermine; Lipopolysaccharides; Transforming Growth Factor beta; Fibroblasts; Fibrosis
PubMed: 38761875
DOI: 10.1016/j.cbi.2024.111059 -
Cell Death & Disease May 2024Precise polyamine metabolism regulation is vital for cells and organisms. Mutations in spermine synthase (SMS) cause Snyder-Robinson intellectual disability syndrome...
Precise polyamine metabolism regulation is vital for cells and organisms. Mutations in spermine synthase (SMS) cause Snyder-Robinson intellectual disability syndrome (SRS), characterized by significant spermidine accumulation and autophagy blockage in the nervous system. Emerging evidence connects polyamine metabolism with other autophagy-related diseases, such as Tauopathy, however, the functional intersection between polyamine metabolism and autophagy in the context of these diseases remains unclear. Here, we altered SMS expression level to investigate the regulation of autophagy by modulated polyamine metabolism in Tauopathy in Drosophila and human cellular models. Interestingly, while complete loss of Drosophila spermine synthase (dSms) impairs lysosomal function and blocks autophagic flux recapitulating SRS disease phenotype, partial loss of dSms enhanced autophagic flux, reduced Tau protein accumulation, and led to extended lifespan and improved climbing performance in Tauopathy flies. Measurement of polyamine levels detected a mild elevation of spermidine in flies with partial loss of dSms. Similarly, in human neuronal or glial cells, partial loss of SMS by siRNA-mediated knockdown upregulated autophagic flux and reduced Tau protein accumulation. Importantly, proteomics analysis of postmortem brain tissue from Alzheimer's disease (AD) patients showed a significant albeit modest elevation of SMS level. Taken together, our study uncovers a functional correlation between polyamine metabolism and autophagy in AD: SMS reduction upregulates autophagy, suppresses Tau accumulation, and ameliorates neurodegeneration and cell death. These findings provide a new potential therapeutic target for AD.
Topics: Autophagy; Animals; tau Proteins; Humans; Spermine Synthase; Drosophila melanogaster; Drosophila Proteins; Tauopathies; Neurons; Alzheimer Disease; Spermidine; Disease Models, Animal; Lysosomes; Drosophila; Mental Retardation, X-Linked
PubMed: 38740758
DOI: 10.1038/s41419-024-06720-8 -
Plants (Basel, Switzerland) Apr 2024Five putrescine and spermidine derivatives (-) together with five rotenoids (-) were isolated from a methanolic extract of the flowers of that displayed promising...
Five putrescine and spermidine derivatives (-) together with five rotenoids (-) were isolated from a methanolic extract of the flowers of that displayed promising inhibition of 76.0 ± 1.9% for AChE and 90.0 ± 4.0% for BuChE at a concentration of 1 mg/mL. Although the anticholinesterase activities of the isolated compounds did not reach that of galantamine, molecular docking revealed that all--tri--coumaroylspermidine and ---tri--coumaroylspermidine showed binding poses mimicking the known inhibitor galantamine and thus could serve as model molecules in future searches for new AChE and BuChE inhibitors.
PubMed: 38732396
DOI: 10.3390/plants13091181 -
Food Chemistry Sep 2024Rye leaven, the basic constituent of sour rye soup ('żurek' or white borsch), was obtained through three methods of initiating lacto-fermentation of rye flour. Optimal...
Rye leaven, the basic constituent of sour rye soup ('żurek' or white borsch), was obtained through three methods of initiating lacto-fermentation of rye flour. Optimal concentrations of NaCl (1.5%) and garlic (0.5%) were selected by utilizing the response surface methodology. During the production and storage of leaven at 10 °C and 20 °C, the secalin proteins of rye flour degraded significantly and the concentration of free amino acids increased, making the rye leaven an environment potentially conducive to the formation of biogenic amines. Putrescine (max. conc: 116.7 mg kg) and tyramine (max. conc: 63.4 mg kg) were the amines that occurred in the largest amounts in the leavens. The final concentration of histamine (after 150 days of storage) did not exceed 22 mg kg. Regardless of the method of initiation of fermentation, the products that contained fewer biogenic amines better retained their sensory characteristics (r ≤ -0.89, p < 0.05) and had a higher number of lactic acid bacteria (r ≤ -0.66, p < 0.05).
Topics: Biogenic Amines; Secale; Food Storage; Fermentation; Flour; Humans; Taste
PubMed: 38728889
DOI: 10.1016/j.foodchem.2024.139523 -
RSC Chemical Biology May 2024The enzymatic synthesis of xenobiotic nucleic acids (XNA), which are artificially sugar-modified nucleic acids, is essential for the preparation of XNA libraries. XNA...
The enzymatic synthesis of xenobiotic nucleic acids (XNA), which are artificially sugar-modified nucleic acids, is essential for the preparation of XNA libraries. XNA libraries are used in the selection of XNA aptamers and enzymes (XNAzymes). Efficient enzymatic synthesis of various XNAs can enable the screening of high-quality XNA aptamers and XNAzymes by expanding the diversity of XNA libraries and adding a variety of properties to XNA aptamers and XNAzymes. However, XNAs that form unstable duplexes with DNA, such as arabino nucleic acid (ANA), may dissociate during enzyme synthesis at temperatures suitable for thermophilic polymerases. Thus, such XNAs are not efficiently synthesised by the thermophilic polymerase mutants at the end of the sequence. This undesirable bias reduces the possibility of generating high-quality XNA aptamers and XNAzymes. Here, we demonstrate that polyamine-induced DNA/ANA duplex stabilisation promotes ANA synthesis that is catalysed by thermophilic polymerase mutants. Several polyamines, including spermine, spermidine, cadaverine, and putrescine promote ANA synthesis. The negative effect of polyamines on the fidelity of ANA synthesis was negligible. We also showed that polyamines promote the synthesis of other XNAs, including 2'-amino-RNA/2'-fluoro-RNA mixture and 2'--methyl-RNA. In addition, we found that polyamine promotes DNA synthesis from the 2'--methyl-RNA template. Polyamines, with the use of thermophilic polymerase mutants, may allow further development of XNA aptamers and XNAzymes by promoting the transcription and reverse transcription of XNAs.
PubMed: 38725908
DOI: 10.1039/d4cb00017j -
Spectrochimica Acta. Part A, Molecular... Sep 2024Over the years, osteosarcoma therapy has had a significative improvement with the use of a multidrug regime strategy, increasing the survival rates from less than 20 %...
Over the years, osteosarcoma therapy has had a significative improvement with the use of a multidrug regime strategy, increasing the survival rates from less than 20 % to circa 70 %. Different types of development of new antineoplastic agents are critical to achieve irreversible damage to cancer cells, while preserving the integrity of their healthy counterparts. In the present study, complexes with two and three Pd(II) centres linked by the biogenic polyamines: spermine (PdSpmCl) and spermidine (PdSpdCl) were tested against non-malignant (osteoblasts, HOb) and cancer (osteosarcoma, MG-63) human cell lines. Either alone or in combination according to the EURAMOS-1 protocol, they were used versus cisplatin as a drug reference. By evaluating the cytotoxic effects of both therapeutic approaches (single and drug combination) in HOb and MG-63 cell lines, the selective anti-tumoral potential is assessed. To understand the different treatments at a molecular level, Synchrotron Radiation Fourier Transform Infrared and Raman microspectroscopies were applied. Principal component analysis and hierarchical cluster analysis are applied to the vibrational data, revealing the major metabolic changes caused by each drug, which were found to rely on DNA, lipids, and proteins, acting as biomarkers of drug-to-cell impact. The main changes were observed for the B-DNA native conformation to either Z-DNA (higher in the presence of polynuclear complexes) or A-DNA (preferably after cisplatin exposure). Additionally, a higher effect upon variation in proteins content was detected in drug combination when compared to single drug administration proving the efficacy of the EURAMOS-1 protocol with the new drugs tested.
Topics: Humans; Osteosarcoma; Spectrum Analysis, Raman; Antineoplastic Agents; Cell Line, Tumor; Spectroscopy, Fourier Transform Infrared; Vibration; Spermine; Bone Neoplasms; Spermidine; Principal Component Analysis; Cell Survival
PubMed: 38710137
DOI: 10.1016/j.saa.2024.124389 -
ACS Omega Apr 2024This study aimed to verify the presence of biogenic amines (BAs) and evaluate the microbiological activity of some food samples collected from retail stores in the...
This study aimed to verify the presence of biogenic amines (BAs) and evaluate the microbiological activity of some food samples collected from retail stores in the Kingdom of Saudi Arabia. A total of thirty-five dairy and fish products were collected and analyzed for BAs, including putrescine (PUT), cadaverine (CAD), spermidine (SPE), histamine (HIS), spermine (SPR), and tyramine (TYR), as well as for total colony count (TCC), lactic acid bacteria (LAB), Enterobacteriaceae, yeast and mold (Y and M), coliforms, and aerobic sporulation count (ASF). The thin layer chromatography (TLC) method was used in the analytical methodology to identify the BAs. The results showed the presence of BAs in all dairy products, but their concentration did not exceed the maximum permissible limit, which in contrast was established by the Food and Drug Administration (FDA) at 10 mg/100 g. The amounts of BAs in fish products varied significantly. All fish product samples contained levels of BAs below the permissible limit. Results of an independent study also indicated potential toxicity at levels of BAs (>10 mg/100 g) in Egyptian herring. Enterobacteriaceae and the coli group were present in higher concentrations in the Egyptian herring samples, whereas other samples (particularly frozen shrimp) showed increased TCC levels with a higher concentration of histamine-producing bacteria. From a consumer safety perspective, this study also indicated that food samples generally contained acceptable levels of BAs. In conclusion, there is a need to improve and standardize food quality and hygiene practices during production and storage to ensure human safety and prevent HIS formation.
PubMed: 38708229
DOI: 10.1021/acsomega.3c10347 -
Synthetic and Systems Biotechnology Sep 2024Spermidine is a naturally occurring polyamine widely utilized in the prevention and treatment of various diseases. Current spermidine biosynthetic methods have problems...
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 (HSS) and obtained mutants that could catalyze the production of spermidine from 1,3-diaminopropane and putrescine. The specific activities of HSS 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.
PubMed: 38699566
DOI: 10.1016/j.synbio.2024.04.012