Package delivered: folate receptor-mediated transporters in cancer therapy and diagnosis

Chemical Science, Journal Year: 2024, Volume and Issue: 15(6), P. 1966 - 2006

Published: Jan. 1, 2024

Neoplasias pose a significant threat to aging society, underscoring the urgent need overcome limitations of traditional chemotherapy through pioneering strategies. Targeted drug delivery is an evolving frontier in cancer therapy, aiming enhance treatment efficacy while mitigating undesirable side effects. One promising avenue utilizes cell membrane receptors like folate receptor guide transporters precisely malignant cells. Based on cellular as hallmark, targeted nanocarriers and small molecule-drug conjugates have been developed that comprise different (bio) chemistries and/or mechanical properties with individual advantages challenges. Such modern folic acid-conjugated stimuli-responsive provide systemic controlled release, enabling reduced dosages, circumvention resistance, diminished adverse Since transporters' structure-based

Language: Английский

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One-Carbon Metabolism: Pulling the Strings behind Aging and Neurodegeneration

Cells, Journal Year: 2022, Volume and Issue: 11(2), P. 214 - 214

Published: Jan. 9, 2022

One-carbon metabolism (OCM) is a network of biochemical reactions delivering one-carbon units to various biosynthetic pathways. The folate cycle and methionine are the two key modules this that regulate purine thymidine synthesis, amino acid homeostasis, epigenetic mechanisms. Intersection with transsulfuration pathway supports glutathione production regulation cellular redox state. Dietary intake micronutrients, such as folates acids, directly contributes OCM, thereby adapting metabolic state environmental inputs. contribution OCM proliferation during development in adult proliferative tissues well established. Nevertheless, accumulating evidence reveals pivotal role homeostasis non-proliferative coordination signaling cascades energy longevity. In review, we summarize current knowledge on related pathways discuss how may impact longevity neurodegeneration across species.

Language: Английский

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Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review

Nutrients, Journal Year: 2023, Volume and Issue: 15(21), P. 4699 - 4699

Published: Nov. 6, 2023

This review delves into the intricate relationship between excess folate (vitamin B9) intake, especially its synthetic form, namely, folic acid, and implications on health disease. While plays a pivotal role in one-carbon cycle, which is essential for DNA synthesis, repair, methylation, concerns arise about excessive intake. The literature underscores potential deleterious effects, such as an increased risk of carcinogenesis; disruption methylation; impacts embryogenesis, pregnancy outcomes, neurodevelopment, disease risk. Notably, these consequences stretch beyond immediate potentially influencing future generations through epigenetic reprogramming. molecular mechanisms underlying effects were examined, including altered metabolism, accumulation unmetabolized vitamin-B12-dependent mechanisms, methylation patterns, interactions with critical receptors signaling pathways. Furthermore, differences mediated by acid compared natural are highlighted. Given widespread supplementation, it imperative to further research optimal intake levels pathways impacted ensuring well-being global population.

Language: Английский

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FMO rewires metabolism to promote longevity through tryptophan and one carbon metabolism in C. elegans

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 2, 2023

Abstract Flavin containing monooxygenases (FMOs) are promiscuous enzymes known for metabolizing a wide range of exogenous compounds. In C. elegans , fmo-2 expression increases lifespan and healthspan downstream multiple longevity-promoting pathways through an unknown mechanism. Here, we report that, beyond its classification as xenobiotic enzyme, leads to rewiring endogenous metabolism principally changes in one carbon (OCM). These likely relevant, find that genetically modifying OCM enzyme alterations longevity interact with expression. Using computer modeling, identify decreased methylation the major flux modified by FMO-2 is sufficient recapitulate benefits. We further tryptophan mammalian FMO overexpression models validated substrate FMO-2. Our resulting model connects single two previously unconnected key metabolic provides framework interconnectivity such dietary restriction. FMOs well-conserved also induced lifespan-extending interventions mice, supporting conserved important role promoting health remodeling.

Language: Английский

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The Role of Microbiota-Derived Vitamins in Immune Homeostasis and Enhancing Cancer Immunotherapy

Cancers, Journal Year: 2023, Volume and Issue: 15(4), P. 1300 - 1300

Published: Feb. 18, 2023

Not all cancer patients who receive immunotherapy respond positively and emerging evidence suggests that the gut microbiota may be linked to treatment efficacy. Though mechanisms of microbial contributions immune response have been postulated, one likely function is supply basic co-factors host including selected vitamins. Bacteria, fungi, plants can produce their own vitamins, whereas humans primarily obtain vitamins from exogenous sources, yet despite significance microbial-derived as crucial system modulators, an overlooked source these nutrients in humans. Microbial-derived are often shared by bacteria, stabilizing bioenergetic pathways amongst communities. Compositional changes affect metabolic alter function. Similarly, plays a pivotal role maintaining microbiota, which parenthetically affects vitamin biosynthesis. Here we elucidate immune-interactive underlying effects microbially derived how they potentially enhance activity immunotherapies cancer.

Language: Английский

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MoS₂ Nanosheets–Cyanobacteria Interaction: Reprogrammed Carbon and Nitrogen Metabolism

ACS Nano, Journal Year: 2021, Volume and Issue: 15(10), P. 16344 - 16356

Published: Sept. 27, 2021

Fully understanding the environmental implications of engineered nanomaterials is crucial for their safe and sustainable use. Cyanobacteria, as pioneers planet earth, play important roles in global carbon nitrogen cycling. Here, we evaluated biological effects molybdenum disulfide (MoS2) nanosheets on a N2-fixation cyanobacteria (Nostoc sphaeroides) by monitoring growth metabolome changes. MoS2 did not exert overt toxicity to Nostoc at tested doses (0.1 1 mg/L). On contrary, intrinsic enzyme-like activities semiconducting properties promoted metabolic processes Nostoc, including enhancing CO2-fixation-related Calvin cycle pathway. Meanwhile, boosted production range biochemicals, sugars, fatty acids, amino other valuable end products. The altered metabolism subsequently drove proportional changes Nostoc. These intracellular could potentially alter C N cycles. findings this study shed light nature underlying mechanisms bio-nanoparticle interactions, offer prospect utilization bio-nanomaterials efficient CO2 sequestration biochemical production.

Language: Английский

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Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics

GeroScience, Journal Year: 2022, Volume and Issue: 45(1), P. 85 - 103

Published: July 21, 2022

Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes metabolic processes that lead to elevated cf-DNA levels. We sought analyse the relationship circulating level age, sex, smoking, physical activity, vegetable consumption, (physical functioning, number diseases, frailty) an extensive panel biomarkers including blood urine metabolites inflammatory markers in three human cohorts (N = 5385; 17-82 years). The relationships were assessed using correlation statistics, linear penalised regressions (the Lasso), also stratified by sex.cf-DNA levels significantly higher men than women, especially middle-aged women who smoke, older more frail individuals. Correlation statistics data showed was with inflammation (C-reactive protein, interleukin-6), homocysteine, proportion red cells lower ascorbic acid. Inflammation glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), ketogenesis (3-hydroxybutyrate) included level-related profiles at least two cohorts.In conclusion, different related behaviour, decline common disease. These results can inform future studies where epidemiological biological pathways are be analysed details, for evaluating potential clinical marker.

Language: Английский

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Epigenetic Genome Modifications during Pregnancy: The Impact of Essential Nutritional Supplements on DNA Methylation

Nutrients, Journal Year: 2024, Volume and Issue: 16(5), P. 678 - 678

Published: Feb. 28, 2024

Pregnancy is an extremely stressful period in a pregnant woman’s life. Currently, women’s awareness of the proper course pregnancy and its possible complications constantly growing. Therefore, significant percentage women increasingly reach for various dietary supplements during gestation. Some most popular substances included multi-ingredient are folic acid choline. Those associated with positive effects on fetal intrauterine development fewer pregnancy-associated complications. Recently, more attention has been paid to impacts specific environmental factors, such as diet, stress, physical activity, etc., epigenetic modifications, understood changes occurring gene expression without direct alteration DNA sequences. Substances choline may participate modifications by acting via one-carbon cycle, leading methyl-group donor formation. nutrients indirectly impact genome phenotype influencing process methylation. This review article presents current state knowledge use supplementation pregnancy, taking into account their maternal–fetal unit outcomes, determining mechanisms action, particular emphasis modifications.

Language: Английский

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Distinct electrochemical and metabolic responses of anode respiring bacteria to sulfamethoxazole in microbial fuel cells coupled with constructed wetlands

Bioresource Technology, Journal Year: 2024, Volume and Issue: 406, P. 131079 - 131079

Published: July 5, 2024

Language: Английский

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S‐adenosyl‐L‐homocysteine extends lifespan through methionine restriction effects

Aging Cell, Journal Year: 2022, Volume and Issue: 21(5)

Published: April 7, 2022

Abstract Methionine restriction (MetR) can extend lifespan and delay the onset of aging‐associated pathologies in most model organisms. Previously, we showed that supplementation with metabolite S ‐adenosyl‐L‐homocysteine (SAH) extends activates energy sensor AMP‐activated protein kinase (AMPK) budding yeast Saccharomyces cerevisiae . However, mechanism involved whether SAH metazoan have remained unknown. Here, show reduces Met levels recapitulates many physiological molecular effects MetR. In yeast, leads to inhibition target rapamycin complex 1 (TORC1) activation autophagy. Furthermore, Caenorhabditis elegans treatment by activating AMPK providing benefits Therefore, propose be used as an intervention lower intracellular confer

Language: Английский

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