Bee Pollen Phytochemicals and Nutrients as Unequaled Pool of Epigenetic Regulators: Implications for Age-Related Diseases

Foods, Год журнала: 2025, Номер 14(3), С. 347 - 347

Опубликована: Янв. 21, 2025

Bee pollen is characterized by an exceptional diversity and abundance of micronutrients bioactive phytochemicals. This richness remains very sparsely investigated, but accumulating evidence strongly supports a promising future for bee in human nutrition medicine. Epigenetic regulation among the most compelling biomedical topics that remain completely untapped derivative research. In our current research, we identified numerous ubiquitous compounds are consistently present this matrix, regardless its botanical geographical origins, have been well studied documented as epigenetic regulators recent years. Given relative newness both research studies within nutritional, pharmaceutical, medical sciences, review aims to bridge these valuable fields advance related experimental investigations. To best knowledge, first work has aimed comprehensively investigate modulatory potential compounds. Our findings also unveiled several intriguing phenomena, such dual effect same compound depending on cellular context or some cross-generational heritability traits. Although whole extract still lacking, study clearly indicates avenue worth further We hope constitutes foundational cornerstone investigations

Язык: Английский

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Integrative bioinformatics approach identifies novel drug targets for hyperaldosteronism, with a focus on SHMT1 as a promising therapeutic candidate

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 11, 2025

Primary aldosteronism (PA), characterized by autonomous aldosterone overproduction, is a major cause of secondary hypertension with significant cardiovascular complications. Current treatments mainly focus on symptom management rather than addressing underlying mechanisms. This study aims to discover novel therapeutic targets for PA using integrated bioinformatics and experimental validation approaches. We employed systematic approach combining: gene identification through transcriptome-wide association studies (TWAS); causal inference summary data-based Mendelian randomization (SMR) two-sample (MR) analyses; additional analyses included phenome-wide analysis, enrichment protein-protein interaction (PPI) networks, drug repurposing, molecular docking clinical aldosterone-producing adenomas (APAs) tissue. Through screening prioritization, we identified 163 PA-associated genes, which seven emerged as potential targets: CEP104, HIP1, TONSL, ZNF100, SHMT1, two long non-coding RNAs (AC006369.2 MRPL23-AS1). SHMT1 was the most promising target, showing significantly elevated expression in APAs compared adjacent non-tumorous tissues. Drug repurposing analysis four SHMT1-targeting compounds (Mimosine, Pemetrexed, Leucovorin, Irinotecan), supported studies. The integration multiple methods successfully hyperaldosteronism. particular, represents candidate future development. These findings provide new opportunities developing causative PA, though further warranted.

Язык: Английский

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Mapping the metabolic reprogramming induced by sodium-glucose cotransporter 2 inhibition

JCI Insight, Год журнала: 2023, Номер 8(7)

Опубликована: Фев. 21, 2023

Diabetes is associated with increased risk for kidney disease, heart failure, and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) prevent these adverse outcomes; however, the mechanisms involved are not clear. We generated a roadmap of metabolic alterations that occur in different organs diabetes response to SGLT2i. In vivo labeling 13C-glucose normoglycemic diabetic mice treated or without dapagliflozin, followed by metabolomics flux analyses, showed that, diabetes, glycolysis glucose oxidation impaired kidney, liver, heart. Treatment dapagliflozin failed rescue glycolysis. SGLT2 inhibition all organs; this was modulation redox state. altered methionine cycle metabolism, evident decreased betaine levels, whereas treatment SGLT2i hepatic along homocysteine levels. mTORC1 activity inhibited stimulation AMPK both animals, possibly explaining protective effects against diseases. Collectively, our findings suggest induces reprogramming orchestrated AMPK-mTORC1 signaling common distinct various tissues, implications aging.

Язык: Английский

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Exploring the complexities of 1C metabolism: implications in aging and neurodegenerative diseases

Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 15

Опубликована: Янв. 4, 2024

The intricate interplay of one-carbon metabolism (OCM) with various cellular processes has garnered substantial attention due to its fundamental implications in several biological processes. OCM serves as a pivotal hub for methyl group donation vital biochemical reactions, influencing DNA methylation, protein synthesis, and redox balance. In the context aging, dysregulation can contribute epigenetic modifications aberrant states, accentuating senescence age-associated pathologies. Furthermore, OCM’s involvement cancer progression is evident through capacity provide essential units crucial nucleotide synthesis thereby fueling uncontrolled cell proliferation tumor development. neurodegenerative disorders like Alzheimer’s Parkinson’s, perturbations pathways are implicated neurotransmitter mitochondrial dysfunction, contributing disease pathophysiology. This review underscores profound impact diverse contexts, reinforcing need comprehensive understanding molecular complexities pave way targeted therapeutic interventions across inflammation, aging disorders.

Язык: Английский

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

Nutrients, Год журнала: 2024, Номер 16(5), С. 678 - 678

Опубликована: Фев. 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.

Язык: Английский

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Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 27, 2024

SUMMARY Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family defensive deacylases. During aging, levels NAD + can decrease by up to 50% some tissues, repletion which provides range health benefits both mice humans. Whether or not precursor nicotinamide mononucleotide (NMN) extends lifespan mammals known. Here we investigate effect long-term administration NMN on health, cancer burden, frailty male female mice. Without increasing tumor counts severity any tissue, treatment males females increased activity, maintained more youthful gene expression patterns, reduced overall frailty. Reduced with was associated increases Anerotruncus colihominis, gut bacterium lower inflammation longevity slowed accumulation adipose tissue later life improved metabolic but mice, while males, median 8.5%, possible due sex-specific effects metabolism. Together, these data show that chronic delays frailty, alters microbiome, improves mouse lifespan, without burden. These results highlight potential boosters treating age-related conditions importance using sexes interventional studies.

Язык: Английский

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Unveiling the Therapeutic Potential of Folate-Dependent One-Carbon Metabolism in Cancer and Neurodegeneration

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9339 - 9339

Опубликована: Авг. 28, 2024

Cellular metabolism is crucial for various physiological processes, with folate-dependent one-carbon (1C) playing a pivotal role. Folate, B vitamin, key cofactor in this pathway, supporting DNA synthesis, methylation and antioxidant defenses. In dividing cells, folate facilitates nucleotide biosynthesis, ensuring genomic stability preventing carcinogenesis. Additionally, neurodevelopment, essential neural tube closure central nervous system formation. Thus, dysregulation of can contribute to pathologies such as cancer, severe birth defects, neurodegenerative diseases. Epidemiological evidence highlights folate's impact on disease risk its potential therapeutic target. antifolate drugs that inhibit enzymes 1C strategies targeting receptors are current options. However, cancer complex, varying among types dietary contexts. conditions, including Alzheimer's Parkinson's diseases, deficiency exacerbates cognitive decline through elevated homocysteine levels, contributing neuronal damage. Clinical trials folic acid supplementation show mixed outcomes, underscoring the complexities neuroprotective effects. This review integrates knowledge neurodegeneration, exploring molecular mechanisms, clinical implications, strategies, which provide information advancing treatments.

Язык: Английский

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The integrated stress response as a key pathway downstream of mitochondrial dysfunction

Current Opinion in Physiology, Год журнала: 2022, Номер 27, С. 100555 - 100555

Опубликована: Май 26, 2022

Язык: Английский

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The role of maternal choline, folate and one‐carbon metabolism in mediating the impact of prenatal alcohol exposure on placental and fetal development

The Journal of Physiology, Год журнала: 2023, Номер 601(6), С. 1061 - 1075

Опубликована: Фев. 9, 2023

Prenatal alcohol consumption (PAE) may be associated with a broad spectrum of impacts, ranging from no overt effects, to miscarriage, fetal growth restriction and disorder. A major mechanism underlying the effects PAE is considered altered DNA methylation gene expression. Maternal nutritional status an important factor in determining extent which impacts pregnancy outcomes, particularly dietary micronutrients folate choline because they provide methyl groups for via one carbon metabolism. This review summarises roles development blastocyst, placenta brain, examines evidence that maternal intake these can modify on development. Studies or deficiency have found reduced blastocyst implantation, placental invasion, vascularisation nutrient transport capability, impaired brain development, abnormal neurodevelopmental outcomes. has been shown reduce absorption and/or metabolism produce similar outcomes choline/folate deficiency. few studies demonstrated ameliorated by supplementation; however, there very limited supplementation early placenta. Further are required support findings determine optimal parameters.

Язык: Английский

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Network-level analysis of ageing and its relationship with diseases and tissue regeneration in the mouse liver

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Март 21, 2023

The liver plays a vital role in maintaining whole-body metabolic homeostasis, compound detoxification and has the unique ability to regenerate itself post-injury. Ageing leads functional impairment of predisposes non-alcoholic fatty disease (NAFLD) hepatocellular carcinoma (HCC). Mapping molecular changes with ageing may help understand crosstalk different diseases. A systems-level analysis ageing-induced its liver-associated conditions is lacking. In present study, we performed network-level analyses using mouse transcriptomic data protein-protein interaction (PPI) network. sample-wise network entropy measure was performed, which showed an increasing trend helped identify genes based on local changes. To gain further insights, also integrated differentially expressed (DEGs) between young age groups PPI identified core modules nodes associated ageing. Finally, computed proximity networks diseases regeneration quantify effect Our revealed complex interplay immune, cancer signalling, liver. We found significant proximities NAFLD, HCC, damage conditions, early phase common including NLRP12, TRP53, GSK3B, CTNNB1, MAT1 FASN. Overall, our study maps their interconnections physiology pathology

Язык: Английский

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