Polyamines: their significance for maintaining health and contributing to diseases

Xuan, Mengjuan; Gu, Xinyu; Li, Juan; Huang, Di; Xue, Chen; He, Yuting

doi:10.1186/s12964-023-01373-0

Cited by 31 publications

(10 citation statements)

References 242 publications

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“…In rat brain homogenates, it acted as free radical scavengers to lessen lipid peroxidation brought on by prooxidant agents like quinolinic acid, iron (Fe 2+ ), and sodium nitroprusside [ 70 , 71 ]. Due to the capacity of PA to raise nitric oxide bioavailability, lower oxidative stress, change structural variables, and promote autophagy, it might improve EC function [ 72 ]. 4-acetamidobutanoate was also reported to be a derivative of gamma-aminobutyric acid (GABA) [ 73 ], a crucial inhibitory neurotransmitter in the human CNS.…”

Section: Discussionmentioning

confidence: 99%

SGLT1 and SGLT2 inhibition, circulating metabolites, and cerebral small vessel disease: a mediation Mendelian Randomization study

Lv,

Cheng,

Dong

2024

Cardiovasc Diabetol

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Background Sodium-glucose cotransporter 2 (SGLT2) and SGLT1 inhibitors may have additional beneficial metabolic effects on circulating metabolites beyond glucose regulation, which could contribute to a reduction in the burden of cerebral small vessel disease (CSVD). Accordingly, we used Mendelian Randomization (MR) to examine the role of circulating metabolites in mediating SGLT2 and SGLT1 inhibition in CSVD. Methods Genetic instruments for SGLT1/2 inhibition were identified as genetic variants, which were both associated with the expression of encoding genes of SGLT1/2 inhibitors and glycated hemoglobin A1c (HbA1c) level. A two-sample two-step MR was used to determine the causal effects of SGLT1/2 inhibition on CSVD manifestations and the mediating effects of 1400 circulating metabolites linking SGLT1/2 inhibition with CSVD manifestations. Results A lower risk of deep cerebral microbleeds (CMBs) and small vessel stroke (SVS) was linked to genetically predicted SGLT2 inhibition. Better white matter structure integrity was also achieved, as evidenced by decreased mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), as well as lower deep (DWMH) and periventrivular white matter hyperintensity (PWMH) volume. Inhibiting SGLT2 could also lessen the incidence of severe enlarged perivascular spaces (EPVS) located at white matter, basal ganglia (BG) and hippocampus (HIP). SGLT1 inhibition could preserve white matter integrity, shown as decreased MD of white matter and DWMH volume. The effect of SGLT2 inhibition on SVS and MD of white matter through the concentration of 4-acetamidobutanoate and the cholesterol to oleoyl-linoleoyl-glycerol (18:1 to 18:2) ratio, with a mediated proportion of 30.3% and 35.5% of the total effect, respectively. Conclusions SGLT2 and SGLT1 inhibition play protective roles in CSVD development. The SGLT2 inhibition could lower the risk of SVS and improve the integrity of white matter microstructure via modulating the level of 4-acetamidobutanoate and cholesterol metabolism. Further mechanistic and clinical studies research are needed to validate our findings.

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Section: Discussionmentioning

confidence: 99%

SGLT1 and SGLT2 inhibition, circulating metabolites, and cerebral small vessel disease: a mediation Mendelian Randomization study

Lv,

Cheng,

Dong

2024

Cardiovasc Diabetol

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“…Its high expression in tumors correlates positively with immune cell activation, suggesting its role as an immune-related gene 46 . Finally, SRM plays a pivotal role in spermidine biosynthesis, a natural polyamine with diverse functions including antioxidant properties, regulation of cell division, protein synthesis, tissue growth and reduction of lipid accumulation in adipose tissue 47 , 48 . However, the role of these gene families and genes in vultures should be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive genome assembly reveals genetic diversity and carcass consumption insights in critically endangered Asian king vultures

Buthasane,

Shotelersuk,

Chetruengchai

et al. 2024

Sci Rep

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The Asian king vulture (AKV), a vital forest scavenger, is facing globally critical endangerment. This study aimed to construct a reference genome to unveil the mechanisms underlying its scavenger abilities and to assess the genetic relatedness of the captive population in Thailand. A reference genome of a female AKV was assembled from sequencing reads obtained from both PacBio long-read and MGI short-read sequencing platforms. Comparative genomics with New World vultures (NWVs) and other birds in the Family Accipitridae revealed unique gene families in AKV associated with retroviral genome integration and feather keratin, contrasting with NWVs’ genes related to olfactory reception. Expanded gene families in AKV were linked to inflammatory response, iron regulation and spermatogenesis. Positively selected genes included those associated with anti-apoptosis, immune response and muscle cell development, shedding light on adaptations for carcass consumption and high-altitude soaring. Using restriction site-associated DNA sequencing (RADseq)-based genome-wide single nucleotide polymorphisms (SNPs), genetic relatedness and inbreeding status of five captive AKVs were determined, revealing high genomic inbreeding in two females. In conclusion, the AKV reference genome was established, providing insights into its unique characteristics. Additionally, the potential of RADseq-based genome-wide SNPs for selecting AKV breeders was demonstrated.

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“…Lactic acid correlates well with long-recognized resting energy expenditure in cancer cachexia, which has been related to futile metabolic cycling including an overactivation of the Cori cycle ( 7 , 31 , 32 ). Ornithine and methionine contribute to the urea cycle, glutathione synthesis with interconnection to one-carbon metabolism, and polyamine production ( 44 – 46 , 69 , 90 ). Research on the relationship between maltose and cancer cachexia is limited, necessitating further investigation to establish potential connections.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics analysis reveals novel serum metabolite alterations in cancer cachexia

More,

Hiller,

Seifert

et al. 2024

Front. Oncol.

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BackgroundCachexia is a body wasting syndrome that significantly affects well-being and prognosis of cancer patients, without effective treatment. Serum metabolites take part in pathophysiological processes of cancer cachexia, but apart from altered levels of select serum metabolites, little is known on the global changes of the overall serum metabolome, which represents a functional readout of the whole-body metabolic state. Here, we aimed to comprehensively characterize serum metabolite alterations and analyze associated pathways in cachectic cancer patients to gain new insights that could help instruct strategies for novel interventions of greater clinical benefit.MethodsSerum was sampled from 120 metastatic cancer patients (stage UICC IV). Patients were grouped as cachectic or non-cachectic according to the criteria for cancer cachexia agreed upon international consensus (main criterium: weight loss adjusted to body mass index). Samples were pooled by cachexia phenotype and assayed using non-targeted gas chromatography-mass spectrometry (GC-MS). Normalized metabolite levels were compared using t-test (p < 0.05, adjusted for false discovery rate) and partial least squares discriminant analysis (PLS-DA). Machine-learning models were applied to identify metabolite signatures for separating cachexia states. Significant metabolites underwent MetaboAnalyst 5.0 pathway analysis.ResultsComparative analyses included 78 cachectic and 42 non-cachectic patients. Cachectic patients exhibited 19 annotable, significantly elevated (including glucose and fructose) or decreased (mostly amino acids) metabolites associating with aminoacyl-tRNA, glutathione and amino acid metabolism pathways. PLS-DA showed distinct clusters (accuracy: 85.6%), and machine-learning models identified metabolic signatures for separating cachectic states (accuracy: 83.2%; area under ROC: 88.0%). We newly identified altered blood levels of erythronic acid and glucuronic acid in human cancer cachexia, potentially linked to pentose-phosphate and detoxification pathways.ConclusionWe found both known and yet unknown serum metabolite and metabolic pathway alterations in cachectic cancer patients that collectively support a whole-body metabolic state with impaired detoxification capability, altered glucose and fructose metabolism, and substrate supply for increased and/or distinct metabolic needs of cachexia-associated tumors. These findings together imply vulnerabilities, dependencies and targets for novel interventions that have potential to make a significant impact on future research in an important field of cancer patient care.

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Polyamines: their significance for maintaining health and contributing to diseases

Cited by 31 publications

References 242 publications

SGLT1 and SGLT2 inhibition, circulating metabolites, and cerebral small vessel disease: a mediation Mendelian Randomization study

SGLT1 and SGLT2 inhibition, circulating metabolites, and cerebral small vessel disease: a mediation Mendelian Randomization study

Comprehensive genome assembly reveals genetic diversity and carcass consumption insights in critically endangered Asian king vultures

Metabolomics analysis reveals novel serum metabolite alterations in cancer cachexia

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