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Urinary Microbiome Dysbiosis in Children With Congenital Uropathies at Varying Risk for Urinary Tract Infections.

INTRODUCTION: Febrile urinary tract infections (UTIs) may occur in 30% to 50% of children with vesicoureteral reflux (VUR) or posterior uret … ns became dominant. Control-associated microbiomes favored short- and branched-chain fatty acid and spermidine production; high-risk microbiomes overproduced ammonia, putrescine, and cadaverine. Resistance to 18 of 22 routinely tested antibiotics was almost confined to the 31 risk-associated microbiomes (P = 0.001). During the median (interquartile range) fo …

Fictibacillus phosphorivorans gen. nov., sp. nov. and proposal to reclassify Bacillus arsenicus, Bacillus barbaricus, Bacillus macauensis, Bacillus nanhaiensis, Bacillus rigui, Bacillus solisalsi and Bacillus gelatini in the genus Fictibacillus.

A Gram-positive-staining, aerobic, endospore-forming bacterium (Ca7(T)) was isolated from a bioreactor showing extensive phosphorus removal. … of the peptidoglycan was meso-diaminopimelic acid and the polyamine pattern contained predominantly spermidine and spermine. The major fatty acids, which were iso-C15 : 0, anteiso-C15 : 0 and C16 : 0, supported the grouping of strain Ca7(T) in the family Bacillaceae. The strain showed DNA-DNA similarities of 48 % (reciprocal 47 %) to B. nanhaiensis DSM 23009 …

Chondroprotection and Molecular Mechanism of Action of Phytonutraceuticals on Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease and an important cause of incapacitation. There is a lack of drugs and effective treatments that stop or slow the OA progression. Modern pharmacological treatments, such as analgesics, have analgesic effects but do not affect the course of OA. Long-term use of these drugs can lead to serious side effects. Given the OA nature, it is likely that lifelong treatment will be required to stop or slow its progression. Therefore, there is an urgent need for disease-modifying OA treatments that are also safe for clinical use over long periods. Phytonu

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… Spermidine Role in OA Inhibition The natural polyamine spermidine has a cardioprotective effect, dietary spermidine can reduce TNF-α in plasma [ 117 ] and further increase the bioavailability of NO by reducing oxidative stress in cardiomyocytes [ 120 ]. … The studies [ 122 ] focused on the role of spermidine in TNF-α-induced inflammation in OA. It was shown that spermidine significantly increased the expression of aggrecan and collagen II and decreased the expression of MMP13 in mice treated with spermidine. …

Manipulating Macrophage/Microglia Polarization to Treat Glioblastoma or Multiple Sclerosis.

Macrophages and microglia are implicated in several diseases with divergent roles in physiopathology. This discrepancy can be explained by their capacity to endorse different polarization states. Theoretical extremes of these states are called M1 and M2. M1 are pro-inflammatory, microbicidal, and cytotoxic whereas M2 are anti-inflammatory, immunoregulatory cells in favor of tumor progression. In pathological states, these polarizations are dysregulated, thus restoring phenotypes could be an interesting treatment approach against diseases. In this review, we will focus on compounds targeting ma

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… The first example is spermidine, a polyamine found in most organisms. It is biosynthesized from putrescine, which is obtained in the body from the amino-acid ornithine. Spermidine has been shown in vitro to inhibit pro-inflammatory cytokine secretion by LPS-stimulated microglia. … Spermidine has also been tested for effects in vivo with the EAE model. After treatment with spermidine, the mice showed decreased EAE clinical scores and the severity of the disease was diminished in both preventive and curative treatment schemes. …

Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: A targeted metabolomic and transcriptomic study.

BACKGROUND: There is growing evidence that Alzheimer disease (AD) is a pervasive metabolic disorder with dysregulation in multiple biochemic … p < 0.001; reduced glutathione [GSH]: higher in AD, p < 0.001); (3) polyamine synthesis/catabolism (spermidine: higher in AD, p = 0.004); (4) urea cycle (N-acetyl glutamate: lower in AD, p < 0.001); (5) glutamate-aspartate metabolism (N-acetyl aspartate: lower in AD, p = 0.002); and (6) neurotransmitter metabolism (gamma-amino-butyric acid: lower in AD, p < …

Fate and effects of acrolein.

Acrolein is a highly toxic, reactive, and irritating aldehyde that occurs as a product of organic pyrolysis, as a metabolite of a number of … reactive aldehyde also occurs in organisms as a metabolite of allyl alcohol, allylamine, spermine, spermidine, and the anticancer drug cyclophosphamide, and as a product of UV radiation of the skin lipid triolein. Furthermore, small amounts are found in foods; when animal or vegetable fats are overheated, however, large amounts are produced. Most human cont …

Multiple Facets of Autophagy and the Emerging Role of Alkylphosphocholines as Autophagy Modulators.

Autophagy is a highly conserved multistep process and functions as passage for degrading and recycling protein aggregates and defective organelles in eukaryotic cells. Based on the nature of these materials, their size and degradation rate, four types of autophagy have been described, i.e. chaperone mediated autophagy, microautophagy, macroautophagy, and selective autophagy. One of the major regulators of this process is mTOR, which inhibits the downstream pathway of autophagy following the activation of its complex 1 (mTORC1). Alkylphosphocholine (APC) derivatives represent a novel class of a

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… Aging and associated atherosclerotic cardiovascular diseases may be slowed down by increasing autophagic flux through calorie restriction, fasting, exercise, and nutritional support such as with spermidine-rich food ( Maiuri and Kroemer, 2019 ). … Spermidine, a natural polyamine, triggers autophagy by inducing the acetylation or deacetylation of autophagy-related genes ( Yang et al., 2017 ). …

[Arginase activity in plasma and erythrocytes in children with hematologic diseases].

INTRODUCTION: Arginase (EC 3.5.3.1) is one of the essential enzymes in the terminal stages of the urea cycle in the liver which participates in the elimination of ammonia from the human body [1, 7]. Except in liver tissue arginase is also present in many human tissues and in the circulating blood cells, especially in erythrocytes and leukocytes. Arginase splits arginase to urea and ornithine that serve for biosynthesis of amino acid proline, glutamic acid and biosynthesis of polyamines-spermine, spermidine and putrescine. Arginase activity is high during the mitotic cycle, with the function in…

Effects of source of supplementary trace minerals in pre- and postpartum diets on reproductive biology and performance in dairy cows.

Our objectives were to evaluate the effects of complete replacement of inorganic salts of trace minerals (STM) with organic trace minerals ( … M group. In pregnant cows, 24 metabolites were more abundant in the uterine fluid of OTM, including spermidine, sucrose, and cholesterol. In conclusion, replacing STM with OTM caused modest improvements to resumption of ovarian cyclicity and important changes in preimplantation conceptus development, but it did not alter conception risk and pregnancy rate.

Communication between gut microbiota-derived metabolites and the tumor microenvironment.

The gut microbiota has been increasingly recognized as a critical player in maintaining human health and influencing disease development. The tumor microenvironment (TME) is pivotal in tumor development and progression, comprising immune cells, stromal elements, extracellular matrix components, and cytokines. Recent studies have highlighted the promising potential of gut microbiota-derived metabolites (e.g., short-chain fatty acids, bile acids, polyamines, and tryptophan derivatives) to reshape the TME in various ways, generating significant interest for the development of novel therapeutic st

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… Polyamines (e.g., spermidine) derived from whole grains and fermented foods help to modulate T cell differentiation and contribute to gut immunity ( 118 ). … Regulating T-cell differentiation through the polyamine spermidine. J Allergy Clin Immunol. (2021) 147:335–48.e11. doi: 10.1016/j.jaci.2020.04.037, PMID: 119. Fan L, Xia Y, Wang Y, Han D, Liu Y, Li J, et al. Gut microbiota bridges dietary nutrients and host immunity. …

Myeloid Cell-Derived Arginase in Cancer Immune Response.

Amino acid metabolism is a critical regulator of the immune response, and its modulating becomes a promising approach in various forms of immunotherapy. Insufficient concentrations of essential amino acids restrict T-cells activation and proliferation. However, only arginases, that degrade L-arginine, as well as enzymes that hydrolyze L-tryptophan are substantially increased in cancer. Two arginase isoforms, ARG1 and ARG2, have been found to be present in tumors and their increased activity usually correlates with more advanced disease and worse clinical prognosis. Nearly all types of myeloid

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… ODC catalyzes the conversion of L-ornithine into putrescine, which is then metabolized to spermidine by spermidine synthase and spermine by spermine synthase ( 260 ). At physiological pH polyamines are positively charged and bind to acidic sites in DNA and RNA, controlling gene expression ( 261 ). … IDO1 activity in TGF-β-treated DCs requires ARG-1-dependent spermidine synthesis that activates Src tyrosine kinase, which participates in IDO1 phosphorylation ( 267 ). …

Targeting immunosenescence for improved tumor immunotherapy.

Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed "immunosenescence," which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underly

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… . | 180 | IGF‐1 signaling inhibitor | IGF‐1 signaling | Spermidine | Induces autophagy; Lengthen lifespan in mice; Attenuate B‐cell senescence in mice. | 181 , 182 | Polyphenols | – | Flavonoid‐rich cocoa polyphenols | Reduce expression of adhesion molecules and pro‐inflammatory markers on monocytes … Immunosenescent B lymphocytes could induct decreased levels of autophagy and obstructed B‐cell responses, but treatment with spermidine could restore their functions instead. 236 Inspiringly, B‐cell subpopulations, repertoire, cellular functions in vitro, and immune responses in vivo were analyzed using …

Autophagic mechanisms in longevity intervention: role of natural active compounds.

The term 'autophagy' literally translates to 'self-eating' and alterations to autophagy have been identified as one of the several molecular changes that occur with aging in a variety of species. Autophagy and aging, have a complicated and multifaceted relationship that has recently come to light thanks to breakthroughs in our understanding of the various substrates of autophagy on tissue homoeostasis. Several studies have been conducted to reveal the relationship between autophagy and age-related diseases. The present review looks at a few new aspects of autophagy and speculates on how they m

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… Different groups of natural compounds including berberine, tanshinone IIA, oridanin, hesperidin, icariin, luteolin, nobiletin, puerarin, melatonin, hinokitiol, thymoquinone, gallic acid, spermidine, curcumin, allicin, resveratrol, ginsenoside Rg3, cucurbitacin B were reported to display cardioprotective … in vivo High-salt-induced congestive heart failure Autophagy induction Enhances autophagic flux (Ref. 193 ) Polyamines Spermidine in vivo Myocardial infarction-induced myocardial injury Autophagy induction Promotes AMPK/mTOR (Ref. 194 ) Polyphenolics Curcumin in vitro Isoproterenol (ISO)-induced cardiac …

Нацеливание SMOX сохраняет оптический нерв Myelin, аксонская целостность и визуальные функции в мультиклерозе.

Множественный склероз (MS) — хроническое неврологическое состояние, затрагивающее молодых людей. Воспаление, обезвоживание и повреждение аксона являются ключевыми патологическими особенностями MS и его животной модели, экспериментального аутоиммунного энцефаломиелита (EAE). Наша предыдущая работа показала, что ингибирование сперматозоидной оксиды (SMOX) MDL72527, селективный необратимый фармакологический ингибитор, значительно сокращенные клинические симптомы, потеря клеток сетчатки (RGC) и воспаление зрительного нерва в мышах EAE. В настоящем исследовании изучался более широкий терапевтически

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… Polyamines, including putrescine, spermidine, and spermine, are ubiquitous polycationic molecules involved in various cellular functions, such as cell growth, differentiation, and stress response [ 34 , 35 ]. … Supplementation of spermidine, a product of SMOX activity, demonstrated neuroprotective effects in Alzheimer’s disease [ 104 ], aging [ 105 , 106 ], neuropathy [ 107 ], optic nerve injury [ 108 ], etc. …

Microbiota-Driven Mechanism in Multical Sclerosis: патогенез, терапевтические стратегии и биомаркерский потенциал.

Множественный склероз (MS) — известное хроническое аутоиммунное расстройство центральной нервной системы (КНС), связанное с демиэлированием и нейродегенерацией. Исследования, ранее проведенные в области кишечного микробиома, показали, что он является важнейшим источником патогенеза MS. Изменения в комменсовом микробиоте, или дисбиозе, оказывают воздействие на иммунный гомеостаз, что приводит к повышению уровней провоспалительных цитокинов и нарушению оси кишечника. В этом обзоре мы представляем всеобъемлющий обзор взаимодействия между кишечной микробиотой и MS с уделением особого внимания имму

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… Spermidine enhances arginase 1 (Arg-1) expression in macrophages and downregulates NF-κB pathway activity, limiting the release of pro-inflammatory cytokines and co-stimulatory molecules. … Spermidine reduces astrocyte production of TNF-α, IL-6, and CCL2 ( Figure 2 ) [ 120 ]. Some food-derived metabolites that can influence the immune and nervous systems include short-chain fatty acids (SCFAs), the amino acid tryptophan, urolithins, and polyamines . …

Новое понимание механизма нейрохимического несбалансированности при множественном склерозе: ненормальный перенос внеклеточного пространства мозга.

Нейрохимический дисбаланс является фактором, способствующим возникновению неврологических симптомов при множественном склерозе (МС). Взрослая милиновая оболочка имеет решающее значение для транспортировки веществ в внеклеточном пространстве (ЭКС) и для поддержания местного гомеостаза. Поэтому мы предположим, что нарушение переноса ЭКС после демиелионирующих повреждений может привести к нейрохимическому дисбалансу в MS. В рамках нынешнего исследования для изучения пространственных нейрохимических изменений использовалась односторонняя модель MS, вызванная лизофосфатидилхолином. Результаты показ

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… Spermidine increased only in the internal capsule, and lipid dysregulation was also observed solely in the internal capsule. … AFADESI showed neuroactive substances changes in various substances, with pathway enrichment in the striatum, internal capsule, and thalamus . ( A ) Representative changes in dopamine, adenosine, glutamine, spermidine, proline, and betaine after ECS partitioning barrier disruption. …

Antiaging Strategies and Remedies: A Landscape of Research Progress and Promise.

Aging is typified by a gradual loss of physiological fitness and accumulation of cellular damage, leading to deteriorated functions and enhanced vulnerability to diseases. Antiaging research has a long history throughout civilization, with many efforts put forth to understand and prevent the effects of aging. Multiple strategies aiming to promote healthy aging and extend the lifespan have been developed including lifestyle adjustments, medical treatments, and social programs. A multitude of antiaging medicines and remedies have also been explored. Here, we use data from the CAS Content Collect

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… Examples of the most widely examined caloric restriction mimetics include rapamycin, metformin, resveratrol, acarbose, aspirin, glucosamine, nicotinamide riboside, and spermidine. 193 , 282 , 293 Rapamycin (CAS RN 53123-88-9) represents one of the best-known caloric restriction mimetics. 282 It is a … . 315 Furthermore, spermidine is able to promote mitophagy. 316 Aspirin (acetylsalicylic acid, CAS RN 50-78-2), a nonsteroidal anti-inflammatory drug, has been in widespread medical use for a long time. …

Food-derived compounds targeting ferroptosis for cancer therapy: from effects to mechanisms.

Ferroptosis is distinctive type programmed cell death. Tumor cells, with their higher iron levels, render them more susceptible to ferroptosis Inducing ferroptosis can activate immune cells, regulate immune evasion, and inhibit the biology activity of cancer cells. Therefore, ferroptosis-induced cancer cell death could become a promising approach for cancer treatment. Dietary compounds are an important source for drug discovery, and there has been an increasing amount of literature on food-derived ferroptosis inducers and their applications in cancer treatment. This review provides an overview

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… Recent findings have shown that P53 affects ferroptosis by regulating spermidine/spermine N1-acetyltransferase 1 (SAT1) ( 57 ). SAT1 overexpression rapidly depletes putrescine and spermidine, leading to mitochondria-mediated apoptosis and a slowdown in cell growth ( 58 ). … nicotinamide adenine dinucleotide phosphate Coenzyme Q10 dihydrofolate to tetrahydrofolate nuclear factor erythroid 2-related factor 2 Kelch-like ECH-associated protein 1 antioxidant response elements glutamate cysteine ligase glutathione synthetase heme oxygenase-1 ubiquitin-specific protease 7 spermidine …

Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update.

In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biolo

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… Several structurally related polyamines such as spermine, spermidine, putrescine and cadaverine, may be retained in uremia [ 1 ]. Most experimental toxicity data (summarized below) have been accumulated with spermine and spermidine. … Recent data indeed show a decrease rather than an increase of concentration in CKD, especially for spermine and spermidine [ 5 , 88 ]. Some of these polyamines may be conjugated to proteins [ 90 ]. …

Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.

Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Unders

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… SAM is also involved in polyamine biosynthesis, generating spermidine and 5′-methylthioadenosine (MTA), which can further regenerate Met [ 111 ]. … Spermidine is a metabolite specifically enriched in LSCs, and reducing the spermidine or total polyamine concentrations could impair LSC function by downregulating the expression of lysine acetyltransferase 7 (KAT7). …