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Frontiers in Nutrition 2024Previous animal experiments have demonstrated the potential of spermidine to mitigate glucose intolerance, insulin resistance, and hyperinsulinemia. However, there...
BACKGROUND
Previous animal experiments have demonstrated the potential of spermidine to mitigate glucose intolerance, insulin resistance, and hyperinsulinemia. However, there remains a scarcity of epidemiological evidence supporting these findings. Therefore, we aimed to elucidate the associations of serum spermidine with T2DM and FPG.
MATERIALS AND METHODS
The cross-sectional study was conducted from June to August 2019 in the rural areas of Fuxin County, Liaoning Province, China. A total of 4,437 participants were included in the study. The serum spermidine was detected using high-performance liquid chromatography with a fluorescence detector. FPG was measured using the hexokinase method. T2DM was defined as participants with a FPG level of 7.0 mmol/L or greater, or self-reported diagnosis of diabetes by a doctor. Restricted cubic spline model and piecewise linear regression model were used to explore the associations of serum spermidine with T2DM and FPG, respectively.
RESULTS
The mean (SD) age of the participants was 59.3 (10.0) years, with 622 out of 4,437 participants being defined as T2DM. The serum spermidine in participants stratified by age and BMI categories was significantly different, with values of 0.006 and 0.001, respectively. Among all the participants, the association of serum spermidine with T2DM was J-shaped. The log (spermidine) was negatively associated with T2DM (OR = 0.68, 95% CI: 0.52 to 0.92, = 0.01) below the inflection point, while log (spermidine) was not significantly associated with T2DM (OR = 1.97, 95% CI: 0.93 to 4.15, = 0.07) above the inflection point. Among the participants without T2DM, the association of serum spermidine with FPG was inverted J-shaped. The log (spermidine) was positively associated with FPG ( = 0.13, 95% CI: 0.05 to 0.21, = 0.001) below the inflection point, while log (spermidine) was negatively associated with FPG ( = -0.29, 95% CI: -0.42 to -0.16, < 0.001) above the inflection point.
CONCLUSION
In conclusion, non-linear associations of serum spermidine with T2DM and FPG were found in the cross-sectional study in Chinese rural adults. This provided insights into the use of spermidine for the prevention of T2DM, highlighting the potential role in public health prevention strategies of spermidine.
PubMed: 38812932
DOI: 10.3389/fnut.2024.1393552 -
Communications Biology May 2024SMG9 is an essential component of the nonsense-mediated mRNA decay (NMD) machinery, a quality control mechanism that selectively degrades aberrant transcripts. Mutations...
SMG9 is an essential component of the nonsense-mediated mRNA decay (NMD) machinery, a quality control mechanism that selectively degrades aberrant transcripts. Mutations in SMG9 are associated with heart and brain malformation syndrome (HBMS). However, the molecular mechanism underlying HBMS remains unclear. We generated smg9 mutant zebrafish (smg9) that have a lifespan of approximately 6 months or longer, allowing for analysis of the in vivo function of Smg9 in adults in more detail. smg9 zebrafish display congenital brain abnormalities and reduced cardiac contraction. Additionally, smg9 zebrafish exhibit a premature aging phenotype. Analysis of NMD target mRNAs shows a trend toward increased mRNA levels in smg9 zebrafish. Spermidine oxidase (Smox) is increased in smg9 zebrafish, resulting in the accumulation of byproducts, reactive oxygen species, and acrolein. The accumulation of smox mRNA due to NMD dysregulation caused by Smg9 deficiency leads to increased oxidative stress, resulting in premature aging.
Topics: Animals; Zebrafish; Nonsense Mediated mRNA Decay; Aging, Premature; Zebrafish Proteins; RNA, Messenger; Oxidative Stress; Mutation
PubMed: 38806677
DOI: 10.1038/s42003-024-06356-6 -
Microorganisms Apr 2024is well known as a plant growth-promoting rhizobacteria (PGPR) and biocontrol agent. Nevertheless, there are very few reports on the study of on tomato early blight,...
is well known as a plant growth-promoting rhizobacteria (PGPR) and biocontrol agent. Nevertheless, there are very few reports on the study of on tomato early blight, especially the biocontrol effects among different inoculation concentrations. In this study, an IAA-producing strain, YXDHD1-7 was isolated from the tomato rhizosphere soil, which had the strongest inhibitory effect against . Inoculation with bacterial suspensions of this strain promoted the growth of tomato seedlings effectively. Furthermore, inoculations at 10, 10, and 10 cfu/mL resulted in control efficacies of 100%, 83.15%, and 69.90%, respectively. Genome sequencing showed that it possesses 22 gene clusters associated with the synthesis of antimicrobial metabolites and genes that are involved in the production of IAA. Furthermore, it may be able to produce spermidine and volatile compounds that also enhance plant growth and defense responses. Our results suggest that strain YXDHD1-7 prevents early blight disease by promoting growth and enhancing the defense enzyme activities in tomato plants. This strain is a promising candidate for an excellent microbial inoculant that can be used to enhance tomato production.
PubMed: 38792750
DOI: 10.3390/microorganisms12050921 -
Molecules (Basel, Switzerland) May 2024Infectious diseases caused by trypanosomatids, including African trypanosomiasis (sleeping sickness), Chagas disease, and different forms of leishmaniasis, are Neglected... (Review)
Review
Infectious diseases caused by trypanosomatids, including African trypanosomiasis (sleeping sickness), Chagas disease, and different forms of leishmaniasis, are Neglected Tropical Diseases affecting millions of people worldwide, mainly in vulnerable territories of tropical and subtropical areas. In general, current treatments against these diseases are old-fashioned, showing adverse effects and loss of efficacy due to misuse or overuse, thus leading to the emergence of resistance. For these reasons, searching for new antitrypanosomatid drugs has become an urgent necessity, and different metabolic pathways have been studied as potential drug targets against these parasites. Considering that trypanosomatids possess a unique redox pathway based on the trypanothione molecule absent in the mammalian host, the key enzymes involved in trypanothione metabolism, trypanothione reductase and trypanothione synthetase, have been studied in detail as druggable targets. In this review, we summarize some of the recent findings on the molecules inhibiting these two essential enzymes for and viability.
Topics: NADH, NADPH Oxidoreductases; Humans; Amide Synthases; Trypanosoma; Glutathione; Animals; Spermidine; Leishmania; Trypanocidal Agents; Leishmaniasis; Trypanosomatina; Protozoan Proteins; Chagas Disease
PubMed: 38792079
DOI: 10.3390/molecules29102214 -
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 -
Asian Journal of Surgery May 2024The gut microbiome is the entirety of microorganisms and their genomes residing in the gut, characterised by diversity, stability, and resilience. Disrupted gut... (Review)
Review
The gut microbiome is the entirety of microorganisms and their genomes residing in the gut, characterised by diversity, stability, and resilience. Disrupted gut microbiome has been implicated in multiple disease entities. The aim of this paper is to summarise the rapidly evolving contemporary evidence of gut dysbiosis on the development and progression of abdominal aortic aneurysm (AAA), discuss possible mechanisms, and explore potential microbiota-targeted interventions and prognostic markers for AAA. A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, using PubMed, ScienceDirect, Web of Science, Ovid, Embase. Search terms of "microbiome" OR "dysbiosis" OR "microorganism"; AND "aneurysm" OR "dilatation" OR "aorta" were used. Study endpoints included effects of microbiota on AAA formation, effects of specific type of bacteria and its metabolite on AAA formation, and pre- or post-treatment by novel small-molecules/inhibitors. From May to August 2023, a total of twelve animal studies and eight human studies were included. Akkermansia muciniphila, Lactobacillus acidophilus and species from the Bacteroidetes phylum were associated with lower AAA incidence in both animal and human studies, while Proteobacteria phylum, Campylobacter, Fusobacterium and Faecalibacterium prausnitzii were found to be in abundance in the AAA group and were associated with larger aneurysms. The diversity of gut microbiota was inversely correlated with AAA diameter. Three important mechanisms were identified: including trimethylamine N-oxide pathway, butyric acid pathway, and aberrant tryptophan metabolism. With our expanding knowledge of the downstream pathogenic mechanisms of gut dysbiosis, novel therapeutics such as short-chain fatty acids and spermidine, as well as prognostic biomarkers such as TMAO have yielded promising preclinical results. In conclusion, there is strong evidence corroborating the role of gut dysbiosis in the pathogenesis of AAA, wherein its therapeutic and prognostic potential deserves further exploration.
PubMed: 38772822
DOI: 10.1016/j.asjsur.2024.05.058 -
Rare : Open Research in Rare Diseases 2024Snyder-Robinson syndrome (SRS) is a rare X-linked recessive disorder characterized by a collection of clinical features including mild to severe intellectual disability,...
Snyder-Robinson syndrome (SRS) is a rare X-linked recessive disorder characterized by a collection of clinical features including mild to severe intellectual disability, hypertonia, marfanoid habitus, facial asymmetry, osteoporosis, developmental delay and seizures. Whole genome sequencing (WGS) identified a mutation in the spermine synthase () gene (c.746 A>G, p.Tyr249Cys) in a male with kyphosis, seizures, and osteoporosis. His phenotype is unique in that he does not have intellectual disability (ID) but does have a mild learning disability. This case demonstrates a milder presentation of SRS and expands the phenotype beyond the reported literature.
PubMed: 38770537
DOI: 10.1016/j.rare.2023.100017 -
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 -
Biomedicine & Pharmacotherapy =... May 2024Osteoporosis is a systemic bone disease characterized by decreased bone mass that is tightly regulated by the coordinated actions of osteoclasts and osteoblasts....
Osteoporosis is a systemic bone disease characterized by decreased bone mass that is tightly regulated by the coordinated actions of osteoclasts and osteoblasts. Apoptosis as a precise programmed cell death involves a cascade of gene expression events which are mechanistically linked to the regulation of bone metabolism. Nevertheless, the critical biomolecules involved in regulating cell apoptosis in osteoporosis remain unknown. To gain a deeper insight into the relationship between apoptosis and osteoporosis, this study integrated the sequencing results of human samples and using a machine learning workflow to overcome the limitations of a single study. Among all immune cell populations, we assessed the apoptotic level and portrayed the distinct subtypes and lineage differentiation of monocytic cells in osteoporotic tissues. Osteoclasts expressed a higher level of Spermidine/spermine-N1-Acetyltransferase1 (SAT1) during osteoclastogenesis which prevented osteoclasts apoptosis and facilitate osteoporosis progression. In addition, Berenil, one potent SAT1 inhibitor, increased osteoclast apoptosis and reversed the bone loss in the femurs of a murine ovariectomy model. In summary, Berenil promotes osteoclast apoptosis, inhibits the bone resorption and improves the abnormal bone structure in vitro and in vivo models by targeting SAT1, demonstrating its potential as a precise therapeutic strategy for clinical osteoporosis treatment.
PubMed: 38739990
DOI: 10.1016/j.biopha.2024.116732 -
Acta Naturae 2024The standardization of DNA fragment assembly methods for many tasks of synthetic biology is crucial. This is necessary for synthesizing a wider repertoire of sequences,...
The standardization of DNA fragment assembly methods for many tasks of synthetic biology is crucial. This is necessary for synthesizing a wider repertoire of sequences, as well as for further automation and miniaturization of such reactions. In this work, we proposed conditions for the assembly of DNA fragments from chemically synthesized oligonucleotides and we identified the errors occurring in the sequence under these conditions. Additionally, we proposed conditions for further combining synthetic fragments into larger DNA fragments. We showed that the optimized conditions are suitable for the assembly of a wide range of sequences.
PubMed: 38738632
DOI: 10.32607/actanaturae.27362