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Foods (Basel, Switzerland) Mar 2024The influence of different levels of sodium chloride, sodium nitrite, and glucose on the quality characteristics of spontaneously fermented goat meat sausage was...
The influence of different levels of sodium chloride, sodium nitrite, and glucose on the quality characteristics of spontaneously fermented goat meat sausage was investigated. The amounts of total biogenic amines in all the sausages ranged from 324.70 to 388.77 mg/kg; among them, spermine was the most abundant, with amounts ranging from 230.96 to 275.78 mg/kg. Increasing sodium chloride from 15 to 35 g/kg, the content of cadaverine, putrescine, tyramine, phenylethylamine, tryptamine, and total amines decreased, and Enterobacteriaceae counts decreased at the same time. Increasing sodium nitrite from 150 to 250 mg/kg, the content of cadaverine, histamine, and total amines decreased, while Enterobacteriaceae counts decreased simultaneously. Increasing glucose from 10 to 40 g/kg, the content of cadaverine, spermidine, and total amines decreased. was the most abundant genus across all the samples, and the relative abundance of was reduced obviously by increasing sodium nitrite and glucose levels. The top 10 differential bacterial taxa for each additive group were respectively obtained, and microbial biomarkers for each level of additive within its group were acquired, respectively. Through Pearson correlation, was positively correlated with phenylethylamine, tryptamine, tyramine, and cadaverine, and were positively correlated with phenylethylamine and putrescine, respectively, suggesting they have the potential to produce biogenic amines. The results provided references for controlling the accumulation of biogenic amines in fermented goat meat sausage via the addition of auxiliary additives during the processing.
PubMed: 38540808
DOI: 10.3390/foods13060817 -
Biomedicines Mar 2024Cisplatin, a chemotherapeutic agent, can cause nephrotoxic and ototoxic injuries. Using a mouse model of repeated low dose cisplatin (RLDC), we compared the kidneys of...
Cisplatin, a chemotherapeutic agent, can cause nephrotoxic and ototoxic injuries. Using a mouse model of repeated low dose cisplatin (RLDC), we compared the kidneys of cisplatin- and vehicle-treated mice on days 3 (early injury phase) and 35 (late injury/recovery phase) after the final treatment. RNA-seq analyses revealed increases in the expression of markers of kidney injury (e.g., lipocalin 2 and kidney injury molecule 1) and fibrosis (e.g., collagen 1, fibronectin, and vimentin 1) in RLDC mice. In addition, we observed increased expression of polyamine catabolic enzymes (spermidine/spermine N-acetyltransferase, , and spermine oxidase, ) and decreased expression of ornithine decarboxylase (), a rate-limiting enzyme in polyamine synthesis in mice subjected to RLDC. Upon confirmation of the RNA-seq results, we tested the hypothesis that enhanced polyamine catabolism contributes to the onset of renal injury and development of fibrosis. To test our hypothesis, we compared the severity of RLDC-induced renal injury and fibrosis in wildtype (WT), -KO, and -KO mice. Our results suggest that the ablation of polyamine catabolic enzymes reduces the severity of renal injury and that modulation of the activity of these enzymes may protect against kidney damage and fibrosis caused by cisplatin treatment.
PubMed: 38540254
DOI: 10.3390/biomedicines12030640 -
Journal of Translational Medicine Mar 2024Due to their complexity and to the presence of common clinical features, differentiation between asthma and chronic obstructive pulmonary disease (COPD) can be a...
BACKGROUND
Due to their complexity and to the presence of common clinical features, differentiation between asthma and chronic obstructive pulmonary disease (COPD) can be a challenging task, complicated in such cases also by asthma-COPD overlap syndrome. The distinct immune/inflammatory and structural substrates of COPD and asthma are responsible for significant differences in the responses to standard pharmacologic treatments. Therefore, an accurate diagnosis is of central relevance to assure the appropriate therapeutic intervention in order to achieve safe and effective patient care. Induced sputum (IS) accurately mirrors inflammation in the airways, providing a more direct picture of lung cell metabolism in comparison to those specimen that reflect analytes in the systemic circulation.
METHODS
An integrated untargeted metabolomics and lipidomics analysis was performed in IS of asthmatic (n = 15) and COPD (n = 22) patients based on Ultra-High-Pressure Liquid Chromatography-Mass Spectrometry (UHPLC-MS) and UHPLC-tandem MS (UHPLC-MS/MS). Partial Least Squares-Discriminant Analysis (PLS-DA) was applied to resulting dataset. The analysis of main enriched metabolic pathways and the association of the preliminary metabolites/lipids pattern identified to clinical parameters of asthma/COPD differentiation were explored. Multivariate ROC analysis was performed in order to determine the discriminatory power and the reliability of the putative biomarkers for diagnosis between COPD and asthma.
RESULTS
PLS-DA indicated a clear separation between COPD and asthmatic patients. Among the 15 selected candidate biomarkers based on Variable Importance in Projection scores, putrescine showed the highest score. A differential IS bio-signature of 22 metabolites and lipids was found, which showed statistically significant variations between asthma and COPD. Of these 22 compounds, 18 were decreased and 4 increased in COPD compared to asthmatic patients. The IS levels of Phosphatidylethanolamine (PE) (34:1), Phosphatidylglycerol (PG) (18:1;18:2) and spermine were significantly higher in asthmatic subjects compared to COPD.
CONCLUSIONS
This is the first pilot study to analyse the IS metabolomics/lipidomics signatures relevant in discriminating asthma vs COPD. The role of polyamines, of 6-Hydroxykynurenic acid and of D-rhamnose as well as of other important players related to the alteration of glycerophospholipid, aminoacid/biotin and energy metabolism provided the construction of a diagnostic model that, if validated on a larger prospective cohort, might be used to rapidly and accurately discriminate asthma from COPD.
Topics: Humans; Lipidomics; Tandem Mass Spectrometry; Sputum; Diagnosis, Differential; Reproducibility of Results; Pilot Projects; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Asthma; Biomarkers; Metabolomics; Lipids
PubMed: 38521955
DOI: 10.1186/s12967-024-05100-2 -
Frontiers in Microbiology 2024It was previously shown that GlnA3 enabled to survive in excess polyamines. However, subsequent studies revealed that Rv1878, the corresponding (M.tb) ortholog, was...
BACKGROUND
It was previously shown that GlnA3 enabled to survive in excess polyamines. However, subsequent studies revealed that Rv1878, the corresponding (M.tb) ortholog, was not essential for the detoxification of spermine (Spm), in M.tb. On the other hand, the multi-drug efflux pump Rv1877 was previously shown to enable export of a wide range of compounds, while Rv0191 was shown to be more specific to chloramphenicol.
RATIONALE
Therefore, we first wanted to determine if detoxification of Spm by efflux can be achieved by any efflux pump, or if that was dependent upon the function of the pump. Next, since Rv1878 was found not to be essential for the detoxification of Spm, we sought to follow-up on the investigation of the physiological role of Rv1878 along with Rv1877 and Rv0191.
APPROACH
To evaluate the specificity of efflux pumps in the mycobacterial tolerance to Spm, we generated unmarked ∆ and ∆ M.tb mutants and evaluated their susceptibility to Spm. To follow up on the investigation of any other physiological roles they may have, we characterized them along with the ∆ M.tb mutant.
RESULTS
The ∆ mutant was sensitive to Spm stress, while the ∆ mutant was not. On the other hand, the ∆ mutant grew better than the wild-type during iron starvation yet was sensitive to cell wall stress. The proteins Rv1877 and Rv1878 seemed to play physiological roles during hypoxia and acidic stress. Lastly, the ∆ mutant was the only mutant that was sensitive to oxidative stress.
CONCLUSION
The multidrug MFS-type efflux pump Rv1877 is required for Spm detoxification, as opposed to Rv0191 which seems to play a more specific role. Moreover, Rv1878 seems to play a role in the regulation of iron homeostasis and the reconstitution of the cell wall of M.tb. On the other hand, the sensitivity of the ∆ mutant to oxidative stress, suggests that Rv0191 may be responsible for the transport of low molecular weight thiols.
PubMed: 38516013
DOI: 10.3389/fmicb.2024.1359188 -
ACS Omega Mar 2024Advances in chemotherapeutic strategies are urgently required to improve antitumor efficiency. Herein, a carboxylated pillar[6]arene (CP6A) was employed to load...
Supramolecular Chemotherapy: Complexation by Carboxylated Pillar[6]arene for Decreasing Cytotoxicity of Nitrogen Mustard to Normal Cells and Enhancing Its Antitumor Efficiency against Breast Cancer.
Advances in chemotherapeutic strategies are urgently required to improve antitumor efficiency. Herein, a carboxylated pillar[6]arene (CP6A) was employed to load chemotherapy medication, nitrogen mustard (NM), via forming a direct host-guest complex, as this helps to decrease the cytotoxicity of NM on normal mammary epithelial cells. Attributed to the stronger complexation ability of CP6A for endogenous spermine (SPM) than for NM, the complexed NM could be competitively released from the CP6A cavity via replacement with SPM. This chemotherapy strategy performed well in vitro and in vivo for SPM-overexpressed cancers. In comparison with free NM, antitumor efficiency of NM/CP6A was significantly enhanced, which originated from the synergistic effect of competitive release of NM and simultaneous trapping of SPM. This strategy might guide expansion to other first-line antitumor agents to improve therapeutic efficacy and decrease side effects, thereby replenishing the possibilities of supramolecular chemotherapy.
PubMed: 38497008
DOI: 10.1021/acsomega.3c09353 -
Journal of Alzheimer's Disease : JAD 2024A hypothesis of Alzheimer's disease etiology is proposed describing how cellular stress induces excessive polyamine synthesis and recycling which can disrupt nucleoli....
A hypothesis of Alzheimer's disease etiology is proposed describing how cellular stress induces excessive polyamine synthesis and recycling which can disrupt nucleoli. Polyamines are essential in nucleolar functions, such as RNA folding and ribonucleoprotein assembly. Changes in the nucleolar pool of anionic RNA and cationic polyamines acting as counterions can cause significant nucleolar dynamics. Polyamine synthesis reduces S-adenosylmethionine which, at low levels, triggers tau phosphorylation. Also, polyamine recycling reduces acetyl-CoA needed for acetylcholine, which is low in Alzheimer's disease. Extraordinary nucleolar expansion and/or contraction can disrupt epigenetic control in peri-nucleolar chromatin, such as chromosome 14 with the presenilin-1 gene; chromosome 21 with the amyloid precursor protein gene; chromosome 17 with the tau gene; chromosome 19 with the APOE4 gene; and the inactive X chromosome (Xi; aka "nucleolar satellite") with normally silent spermine synthase (polyamine synthesis) and spermidine/spermine-N1-acetyltransferase (polyamine recycling) alleles. Chromosomes 17, 19 and the Xi have high concentrations of Alu elements which can be transcribed by RNA polymerase III if positioned nucleosomes are displaced from the Alu elements. A sudden flood of Alu RNA transcripts can competitively bind nucleolin which is usually bound to Alu sequences in structural RNAs that stabilize the nucleolar heterochromatic shell. This Alu competition leads to loss of nucleolar integrity with leaking of nucleolar polyamines that cause aggregation of phosphorylated tau. The hypothesis was developed with key word searches (e.g., PubMed) using relevant terms (e.g., Alzheimer's, lupus, nucleolin) based on a systems biology approach and exploring autoimmune disease tautology, gaining synergistic insights from other diseases.
Topics: Humans; Polyamines; Alzheimer Disease; Cell Nucleolus; Autoimmune Diseases; RNA
PubMed: 38489184
DOI: 10.3233/JAD-231184 -
Zoological Research Mar 2024Osteoporosis is a prevalent metabolic bone disease. While drug therapy is essential to prevent bone loss in osteoporotic patients, current treatments are limited by side...
Osteoporosis 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 ( ) 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 anti-osteoporotic effects of spermine, with P53 potentially acting downstream of Rac1. These findings were confirmed using mouse ( ) models, in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions, suggesting strong potential as a bone-strengthening 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.
Topics: Humans; Mice; Animals; Zebrafish; Spermine; Osteoporosis; Prednisolone; Glucocorticoids; Rodent Diseases
PubMed: 38485506
DOI: 10.24272/j.issn.2095-8137.2023.371 -
International Journal of Molecular... Feb 2024The work presents the synthesis of a series of linear polyamidoamines by polycondensation of sebacoyl dichloride with endogenous polyamines: putrescine, spermidine,...
The work presents the synthesis of a series of linear polyamidoamines by polycondensation of sebacoyl dichloride with endogenous polyamines: putrescine, spermidine, spermine, and norspermidine-a biogenic polyamine not found in the human body. During the synthesis carried out via interfacial reaction, hydrophilic, semi-crystalline polymers with an average viscosity molecular weight of approximately 20,000 g/mol and a melting point of approx. 130 °C were obtained. The structure and composition of the synthesized polymers were confirmed based on NMR and FTIR studies. The cytotoxicity tests performed on human fibroblasts and keratinocytes showed that the polymers obtained with spermine and norspermidine were strongly cytotoxic, but only in high concentrations. All the other examined polymers did not show cytotoxicity even at concentrations of 2000 µg/mL. Simultaneously, the antibacterial activity of the obtained polyamides was confirmed. These polymers are particularly active against , and virtually all the polymers obtained demonstrated a strong inhibitory effect on the growth of cells of this strain. Antimicrobial activity of the tested polymer was found against strains like , , and . The broadest spectrum of bactericidal action was demonstrated by polyamidoamines obtained from spermine, which contains two amino groups in the repeating unit of the chain. The obtained polymers can be used as a material for forming drug carriers and other biologically active compounds in the form of micro- and nanoparticles, especially as a component of bactericidal creams and ointments used in dermatology or cosmetology.
Topics: Humans; Spermine; Escherichia coli; Polyamines; Anti-Bacterial Agents; Polymers; Spermidine
PubMed: 38473823
DOI: 10.3390/ijms25052576 -
International Journal of Molecular... Feb 2024Despite the well-known relevance of polyamines to many forms of life, little is known about how polyamines regulate osteogenesis and skeletal homeostasis. Here, we...
Despite the well-known relevance of polyamines to many forms of life, little is known about how polyamines regulate osteogenesis and skeletal homeostasis. Here, we report a series of in vitro studies conducted with human-bone-marrow-derived pluripotent stromal cells (MSCs). First, we show that during osteogenic differentiation, mRNA levels of most polyamine-associated enzymes are relatively constant, except for the catabolic enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1), which is strongly increased at both mRNA and protein levels. As a result, the intracellular spermidine to spermine ratio is significantly reduced during the early stages of osteoblastogenesis. Supplementation of cells with exogenous spermidine or spermine decreases matrix mineralization in a dose-dependent manner. Employing N-cyclohexyl-1,3-propanediamine (CDAP) to chemically inhibit spermine synthase (SMS), the enzyme catalyzing conversion of spermidine into spermine, also suppresses mineralization. Intriguingly, this reduced mineralization is rescued with DFMO, an inhibitor of the upstream polyamine enzyme ornithine decarboxylase (ODC1). Similarly, high concentrations of CDAP cause cytoplasmic vacuolization and alter mitochondrial function, which are also reversible with the addition of DFMO. Altogether, these studies suggest that excess polyamines, especially spermidine, negatively affect hydroxyapatite synthesis of primary MSCs, whereas inhibition of polyamine synthesis with DFMO rescues most, but not all of these defects. These findings are relevant for patients with Snyder-Robinson syndrome (SRS), as the presenting skeletal defects-associated with SMS deficiency-could potentially be ameliorated by treatment with DFMO.
Topics: Humans; Spermidine; Spermine; Spermine Synthase; Ornithine Decarboxylase; Osteogenesis; Polyamines; Mesenchymal Stem Cells; RNA, Messenger
PubMed: 38473716
DOI: 10.3390/ijms25052463 -
Disease Models & Mechanisms Jun 2024Snyder-Robinson syndrome (SRS) is a rare X-linked recessive disorder caused by a mutation in the SMS gene, which encodes spermine synthase, and aberrant polyamine...
Snyder-Robinson syndrome (SRS) is a rare X-linked recessive disorder caused by a mutation in the SMS gene, which encodes spermine synthase, and aberrant polyamine metabolism. SRS is characterized by intellectual disability, thin habitus, seizure, low muscle tone/hypotonia and osteoporosis. Progress towards understanding and treating SRS requires a model that recapitulates human gene variants and disease presentations. Here, we evaluated molecular and neurological presentations in the G56S mouse model, which carries a missense mutation in the Sms gene. The lack of SMS protein in the G56S mice resulted in increased spermidine/spermine ratio, failure to thrive, short stature and reduced bone density. They showed impaired learning capacity, increased anxiety, reduced mobility and heightened fear responses, accompanied by reduced total and regional brain volumes. Furthermore, impaired mitochondrial oxidative phosphorylation was evident in G56S cerebral cortex, G56S fibroblasts and Sms-null hippocampal cells, indicating that SMS may serve as a future therapeutic target. Collectively, our study establishes the suitability of the G56S mice as a preclinical model for SRS and provides a set of molecular and functional outcome measures that can be used to evaluate therapeutic interventions for SRS.
Topics: Animals; Disease Models, Animal; Mental Retardation, X-Linked; Behavior, Animal; Spermine Synthase; Polyamines; Mitochondria; Male; Mice; Fibroblasts; Oxidative Phosphorylation; Hippocampus; Anxiety; Bone Density; Brain; Fear; Humans; Organ Size
PubMed: 38463005
DOI: 10.1242/dmm.050639