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Amino Acids Jun 2024Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine...
Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine decarboxylase (ODC) of polyamine biosynthesis, α-difluoromethylornithine (DFMO), are implicated as stimulants for bone formation. We demonstrate in this study the osteogenic potential of exogenous polyamines and DFMO in human osteoblasts (hOBs), murine monocyte cell line RAW 264.7, and an ovariectomized rat model. The effect of polyamines and DFMO on hOBs and RAW 264.7 cells was studied by analyzing gene expression, alkaline phosphatase (ALP) activity, tartrate-resistant acid phosphatase (TRAP) activity, and matrix mineralization. Ovariectomized rats were treated with polyamines and DFMO and analyzed by micro computed tomography (micro CT). The mRNA level of the early onset genes of osteogenic differentiation, Runt-related transcription factor 2 (Runx2) and ALP, was significantly elevated in hOBs under osteogenic conditions, while both ALP activity and matrix mineralization were enhanced by exogenous polyamines and DFMO. Under osteoclastogenic conditions, the gene expression of both receptor activator of nuclear factor-κB (RANK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) was reduced, and TRAP activity was suppressed by exogenous polyamines and DFMO in RAW 264.7 cells. In an osteoporotic animal model of ovariectomized rats, SPM and DFMO were found to improve bone volume in rat femurs, while trabecular thickness was increased in all treatment groups. Results from this study provide in vitro and in vivo evidence indicating that polyamines and DFMO act as stimulants for bone formation, and their osteogenic effect may be associated with the suppression of osteoclastogenesis.
Topics: Animals; Mice; Osteoclasts; Osteogenesis; Rats; Humans; Cell Differentiation; Eflornithine; Female; Polyamines; Osteoblasts; RAW 264.7 Cells; Ovariectomy; Rats, Sprague-Dawley; Spermidine
PubMed: 38935136
DOI: 10.1007/s00726-024-03403-8 -
Cancer Research Communications Jun 2024Escherichia coli that harbor the polyketide synthase (pks) genomic island produce colibactin and are associated with sporadic colorectal cancer development (CRC). Given...
Escherichia coli that harbor the polyketide synthase (pks) genomic island produce colibactin and are associated with sporadic colorectal cancer development (CRC). Given the considerable prevalence of pks+ bacteria in healthy individuals, we sought to identify strategies to limit the growth and expansion of pks+ E. coli. We found that culture supernatants of the probiotic strain E. coli Nissle 1917 were able to inhibit the growth of the murine pathogenic strain pks+ E. coli NC101 (EcNC101). We performed a non-targeted analysis of the metabolome in supernatants from several E. coli strains and identified putrescine as a potential postbiotic capable of suppressing EcNC101 growth in vitro. The effect of putrescine supplementation was then evaluated in the azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of CRC in mice colonized with EcNC101. Putrescine supplementation inhibited the growth of pks+ E. coli; reduced the number and size of colonic tumors; and downmodulated the release of inflammatory cytokines in the colonic lumen. Additionally, putrescine supplementation led to shifts in the composition and function of gut microbiota, characterized by an increase of the Firmicutes/Bacteroidetes ratio and enhanced acetate production. The effect of putrescine was further confirmed in vitro using a pks+ E. coli strain isolated from a CRC patient. These results suggest that probiotic-derived metabolites can be used as an alternative to live bacteria in individuals at risk of developing CRC due to the presence of pks+ bacteria in their colon.
PubMed: 38934090
DOI: 10.1158/2767-9764.CRC-23-0355 -
International Journal of Molecular... Jun 2024Polyamine (PA) spermidine (SPD) plays a crucial role in aging. Since SPD accumulates in glial cells, particularly in Müller retinal cells (MCs), the expression of the...
Polyamine (PA) spermidine (SPD) plays a crucial role in aging. Since SPD accumulates in glial cells, particularly in Müller retinal cells (MCs), the expression of the SPD-synthesizing enzyme spermidine synthase (SpdS) in Müller glia and age-dependent SpdS activity are not known. We used immunocytochemistry, Western blot (WB), and image analysis on rat retinae at postnatal days 3, 21, and 120. The anti-glutamine synthetase (GS) antibody was used to identify glial cells. In the neonatal retina (postnatal day 3 (P3)), SpdS was expressed in almost all progenitor cells in the neuroblast. However, by day 21 (P21), the SpdS label was pronouncedly expressed in multiple neurons, while GS labels were observed only in radial Müller glial cells. During early cell adulthood, at postnatal day 120 (P120), SpdS was observed solely in ganglion cells and a few other neurons. Western blot and semi-quantitative analyses of SpdS labeling showed a dramatic decrease in SpdS at P21 and P120 compared to P3. In conclusion, the redistribution of SpdS with aging indicates that SPD is first synthesized in all progenitor cells and then later in neurons, but not in glia. However, MCs take up and accumulate SPD, regardless of the age-associated decrease in SPD synthesis in neurons.
Topics: Animals; Rats; Spermidine Synthase; Retina; Ependymoglial Cells; Aging; Spermidine; Neuroglia; Animals, Newborn
PubMed: 38928162
DOI: 10.3390/ijms25126458 -
PloS One 2024This study investigated the mitigating effects of spermidine on salinity-stressed yarrow plants (Achillea millefolium L.), an economically important medicinal crop....
This study investigated the mitigating effects of spermidine on salinity-stressed yarrow plants (Achillea millefolium L.), an economically important medicinal crop. Plants were treated with four salinity levels (0, 30, 60, 90 mM NaCl) and three spermidine concentrations (0, 1.5, 3 μM). Salinity induced electrolyte leakage in a dose-dependent manner, increasing from 22% at 30 mM to 56% at 90 mM NaCl without spermidine. However, 1.5 μM spermidine significantly reduced leakage across salinities by 1.35-11.2% relative to untreated stressed plants. Photosynthetic pigments (chlorophyll a, b, carotenoids) also exhibited salinity- and spermidine-modulated responses. While salinity decreased chlorophyll a, both spermidine concentrations increased chlorophyll b and carotenoids under most saline conditions. Salinity and spermidine synergistically elevated osmoprotectants proline and total carbohydrates, with 3 μM spermidine augmenting proline and carbohydrates up to 14.4% and 13.1% at 90 mM NaCl, respectively. Antioxidant enzymes CAT, POD and APX displayed complex regulation influenced by treatment factors. Moreover, salinity stress and spermidine also influenced the expression of linalool and pinene synthetase genes, with the highest expression levels observed under 90 mM salt stress and the application of 3 μM spermidine. The findings provide valuable insights into the responses of yarrow plants to salinity stress and highlight the potential of spermidine in mitigating the adverse effects of salinity stress.
Topics: Spermidine; Achillea; Salt Stress; Chlorophyll; Photosynthesis; Carotenoids; Proline; Gene Expression Regulation, Plant; Salinity; Antioxidants; Sodium Chloride; Chlorophyll A
PubMed: 38923971
DOI: 10.1371/journal.pone.0304831 -
Applied and Environmental Microbiology Jun 2024Microbial community adaptability to pH stress plays a crucial role in biofilm formation. This study aims to investigate the regulatory mechanisms of exogenous putrescine...
Microbial community adaptability to pH stress plays a crucial role in biofilm formation. This study aims to investigate the regulatory mechanisms of exogenous putrescine on pH stress, as well as enhance understanding and application for the technical measures and molecular mechanisms of biofilm regulation. Findings demonstrated that exogenous putrescine acted as a switch-like distributor affecting microorganism pH stress, thus promoting biofilm formation under acid conditions while inhibiting it under alkaline conditions. As pH decreases, the protonation degree of putrescine increases, making putrescine more readily adsorbed. Protonated exogenous putrescine could increase cell membrane permeability, facilitating its entry into the cell. Subsequently, putrescine consumed intracellular H by enhancing the glutamate-based acid resistance strategy and the γ-aminobutyric acid metabolic pathway to reduce acid stress on cells. Furthermore, putrescine stimulated ATPase expression, allowing for better utilization of energy in H transmembrane transport and enhancing oxidative phosphorylation activity. However, putrescine protonation was limited under alkaline conditions, and the intracellular H consumption further exacerbated alkali stress and inhibits cellular metabolic activity. Exogenous putrescine promoted the proportion of fungi and acidophilic bacteria under acidic stress and alkaliphilic bacteria under alkali stress while having a limited impact on fungi in alkaline biofilms. Increasing under alkali conditions with putrescine further aggravated the biofilm decomposition. This research shed light on the unclear relationship between exogenous putrescine, environmental pH, and pH stress adaptability of biofilm. By judiciously employing putrescine, biofilm formation could be controlled to meet the needs of engineering applications with different characteristics.IMPORTANCEThe objective of this study is to unravel the regulatory mechanism by which exogenous putrescine influences biofilm pH stress adaptability and understand the role of environmental pH in this intricate process. Our findings revealed that exogenous putrescine functioned as a switch-like distributor affecting the pH stress adaptability of biofilm-based activated sludge, which promoted energy utilization for growth and reproduction processes under acidic conditions while limiting biofilm development to conserve energy under alkaline conditions. This study not only clarified the previously ambiguous relationship between exogenous putrescine, environmental pH, and biofilm pH stress adaptability but also offered fresh insights into enhancing biofilm stability within extreme environments. Through the modulation of energy utilization, exerting control over biofilm growth and achieving more effective engineering goals could be possible.
PubMed: 38916292
DOI: 10.1128/aem.00569-24 -
International Journal of Molecular... May 2024The associations of plasma metabolites with adverse cardiovascular (CV) outcomes are still underexplored and may be useful in CV risk stratification. We performed a... (Meta-Analysis)
Meta-Analysis Review
The associations of plasma metabolites with adverse cardiovascular (CV) outcomes are still underexplored and may be useful in CV risk stratification. We performed a systematic review and meta-analysis to establish correlations between blood metabolites and adverse CV outcomes in patients with heart failure (HF). Four cohorts were included, involving 83 metabolites and 37 metabolite ratios, measured in 1158 HF patients. Hazard ratios (HR) of 42 metabolites and 3 metabolite ratios, present in at least two studies, were combined through meta-analysis. Higher levels of histidine (HR 0.74, 95% CI [0.64; 0.86]) and tryptophan (HR 0.82 [0.71; 0.96]) seemed protective, whereas higher levels of symmetric dimethylarginine (SDMA) (HR 1.58 [1.30; 1.93]), N-methyl-1-histidine (HR 1.56 [1.27; 1.90]), SDMA/arginine (HR 1.38 [1.14; 1.68]), putrescine (HR 1.31 [1.06; 1.61]), methionine sulfoxide (HR 1.26 [1.03; 1.52]), and 5-hydroxylysine (HR 1.25 [1.05; 1.48]) were associated with a higher risk of CV events. Our findings corroborate important associations between metabolic imbalances and a higher risk of CV events in HF patients. However, the lack of standardization and data reporting hampered the comparison of a higher number of studies. In a future clinical scenario, metabolomics will greatly benefit from harmonizing sample handling, data analysis, reporting, and sharing.
Topics: Humans; Heart Failure; Metabolomics; Biomarkers; Cardiovascular Diseases; Metabolome; Heart Disease Risk Factors
PubMed: 38891881
DOI: 10.3390/ijms25115693 -
Polymers May 2024Only 0.1% of polyurethanes available on the market are from renewable sources. With increasing concern about climate change, the substitution of monomers derived from...
Only 0.1% of polyurethanes available on the market are from renewable sources. With increasing concern about climate change, the substitution of monomers derived from petrochemical sources and the application of eco-friendly synthesis processes is crucial for the development of biomaterials. Therefore, polyhydroxyurethanes have been utilized, as their synthesis route allows for the carbonation of vegetable oils with carbon dioxide and the substitution of isocyanates known for their high toxicity, carcinogenicity, and petrochemical origin. In this study, polyhydroxyurethanes were obtained from carbonated soybean oil in combination with two diamines, one that is aliphatic (1,4-butadiamine (putrescine)) and another that is cycloaliphatic (1,3-cyclohexanobis(methylamine)). Four polyhydroxyurethanes were obtained, showing stability in hydrolytic and oxidative media, thermal stability above 200 °C, tensile strength between 0.9 and 1.1 MPa, an elongation at break between 81 and 222%, a water absorption rate up 102%, and contact angles between 63.70 and 101.39. New formulations of bio-based NIPHUs can be developed with the inclusion of a cycloaliphatic diamine (CHM) for the improvement of mechanical properties, which represents a more sustainable process for obtaining NIPHUs with the physicochemical, mechanical, and thermal properties required for the preparation of wound dressings.
PubMed: 38891461
DOI: 10.3390/polym16111514 -
IMeta Apr 2024The gut microbiota is a complex community of microorganisms inhabiting the intestinal tract, which plays a vital role in human health. It is intricately involved in the... (Review)
Review
The gut microbiota is a complex community of microorganisms inhabiting the intestinal tract, which plays a vital role in human health. It is intricately involved in the metabolism, and it also affects diverse physiological processes. The gut-lung axis is a bidirectional pathway between the gastrointestinal tract and the lungs. Recent research has shown that the gut microbiome plays a crucial role in immune response regulation in the lungs and the development of lung diseases. In this review, we present the interrelated factors concerning gut microbiota and the associated metabolites in pulmonary hypertension (PH), a lethal disease characterized by elevated pulmonary vascular pressure and resistance. Our research team explored the role of gut-microbiota-derived metabolites in cardiovascular diseases and established the correlation between metabolites such as putrescine, succinate, trimethylamine N-oxide (TMAO), and N, N, N-trimethyl-5-aminovaleric acid with the diseases. Furthermore, we found that specific metabolites, such as TMAO and betaine, have significant clinical value in PH, suggesting their potential as biomarkers in disease management. In detailing the interplay between the gut microbiota, their metabolites, and PH, we underscored the potential therapeutic approaches modulating this microbiota. Ultimately, we endeavor to alleviate the substantial socioeconomic burden associated with this disease. This review presents a unique exploratory analysis of the link between gut microbiota and PH, intending to propel further investigations in the gut-lung axis.
PubMed: 38882495
DOI: 10.1002/imt2.159 -
American Journal of Physiology. Cell... Jun 2024Polyamines are molecules with multiple amino groups that are essential for cellular function. The major polyamines are putrescine, spermidine, spermine, and cadaverine.... (Review)
Review
Polyamines are molecules with multiple amino groups that are essential for cellular function. The major polyamines are putrescine, spermidine, spermine, and cadaverine. Polyamines are important for posttranscriptional regulation, autophagy, programmed cell death, proliferation, redox homeostasis, and ion channel function; their levels are tightly controlled. High levels of polyamines are associated with proliferative pathologies such as cancer, while low polyamine levels are observed in aging, and elevated polyamine turnover enhances oxidative stress. Polyamine metabolism is implicated in a variety of pathophysiological processes in the nervous, immune, and cardiovascular systems. Currently, manipulating polyamine levels is under investigation as a potential preventive treatment in several pathologies, including aging, ischemia/reperfusion injury, pulmonary hypertension, and cancer. Although polyamines have been implicated in a plethora of intracellular mechanisms, our understanding of these processes remains incomplete and is a topic of ongoing investigations. Here, we discuss the regulation and cellular functions of polyamines, their role in physiology and pathology, and emphasize the current gaps in knowledge and potential future research directions.
PubMed: 38881422
DOI: 10.1152/ajpcell.00074.2024 -
Food Chemistry May 2024Reducing nitrites tends to increase the accumulation of hazardous biogenic amines (BAs) in Chinese fermented sausages (CFSs). Gallic acid (GA) has emerged as a potential...
The metabolic regulation mechanism of gallic acid on biogenic amines and nitrosamines in reduced-nitrite Chinese fermented sausages: A perspective of metabolomics and metagenomics.
Reducing nitrites tends to increase the accumulation of hazardous biogenic amines (BAs) in Chinese fermented sausages (CFSs). Gallic acid (GA) has emerged as a potential alternative to reduce nitrite usage and control BAs. This study explored how GA inhibits BAs and nitrosamines accumulation in reduced-nitrite CFSs. Results demonstrated that combining 0.05% (w/w) GA with reduced nitrite effectively curbed BAs and N-nitrosodimethylamine, decreasing total BA from 271.48 to 125.46 mg/kg. Fifty-one metabolites associated with the metabolism of BAs and N-nitrosodimethylamine were identified. GA boosted Lactococcus while reducing spoilage bacteria and Macrococcus. This dual regulation suppressed BAs and dimethylamine accumulation by regulating amino acids and trimethylamine pathways. Consequently, GA achieved an 89.86% reduction in N-nitrosodimethylamine by decreasing the key precursors like putrescine, dimethylamine, and nitrite. These findings offer new insights into utilizing GA and similar plant polyphenols to manage BAs and nitrosamines in meat products with reduced nitrite usage.
PubMed: 38878551
DOI: 10.1016/j.foodchem.2024.139900