The Pharmacology of Vitamin C DOI Creative Commons
Jens Lykkesfeldt,

Anitra C. Carr,

Pernille Tveden‐Nyborg

et al.

Pharmacological Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 100043 - 100043

Published: Jan. 1, 2025

Ascorbic acid, the reduced form of vitamin C, is a ubiquitous small carbohydrate. Despite decades focused research, new metabolic functions this universal electron donor are still being discovered and add to complexity our view C in human health. Although praised as an unsurpassed water-soluble antioxidant plasma cells, most interesting seem be its roles specific numerous biological reactions ranging from well-known hydroxylation proline cofactor for epigenetic master regulators ten-eleven translocation enzymes Jumonji domain-containing histone-lysine demethylases. Some these may have important implications disease prevention treatment spiked renewed interest in, eg, C's potential cancer therapy. Moreover, some fundamental pharmacokinetic properties remain established including if other mechanisms than passive diffusion governs efflux ascorbate anions cell. Taken together, there seems much learn about pharmacology role health disease. This review explores avenues integrates present knowledge pharmacology. SIGNIFICANCE STATEMENT: Vitamin involved multiple which essential Hundreds millions people considered deficient according accepted guidelines, but little known long-term consequences. physiology has been widely disregarded clinical studies decades, it clear that deeper understanding particularly holds key unravel possibly exploit

Language: Английский

TET (Ten-eleven translocation) family proteins: structure, biological functions and applications DOI Creative Commons

Xinchao Zhang,

Yue Zhang, Chaofu Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 11, 2023

Abstract Ten-eleven translocation (TET) family proteins (TETs), specifically, TET1, TET2 and TET3, can modify DNA by oxidizing 5-methylcytosine (5mC) iteratively to yield 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), 5-carboxycytosine (5caC), then two of these intermediates (5fC 5caC) be excised return unmethylated cytosines thymine-DNA glycosylase (TDG)-mediated base excision repair. Because methylation demethylation play an important role in numerous biological processes, including zygote formation, embryogenesis, spatial learning immune homeostasis, the regulation TETs functions is complicated, dysregulation their implicated many diseases such as myeloid malignancies. In addition, recent studies have demonstrated that able catalyze hydroxymethylation RNA perform post-transcriptional regulation. Notably, catalytic-independent certain contexts been identified, further highlighting multifunctional roles. Interestingly, reactivating expression selected target genes, accumulated evidences support potential therapeutic use TETs-based editing tools disorders associated with epigenetic silencing. this review, we summarize key findings functions, activity regulators at various levels, technological advances detection 5hmC, main oxidative product, emerging applications editing. Furthermore, discuss existing challenges future directions field.

Language: Английский

Citations

95
Emerging evidence that the mammalian sperm epigenome serves as a template for embryo development DOI Creative Commons
Ariane Lismer, Sarah Kimmins

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

Published: April 14, 2023

Abstract Although more studies are demonstrating that a father’s environment can influence child health and disease, the molecular mechanisms underlying non-genetic inheritance remain unclear. It was previously thought sperm exclusively contributed its genome to egg. More recently, association have shown various environmental exposures including poor diet, toxicants, stress, perturbed epigenetic marks in at important reproductive developmental loci were associated with offspring phenotypes. The cellular routes underlie how transmitted fertilization, resist reprogramming embryo, drive phenotypic changes only now beginning be unraveled. Here, we provide an overview of state field intergenerational paternal mammals present new insights into relationship between embryo development three pillars inheritance: chromatin, DNA methylation, non-coding RNAs. We evaluate compelling evidence sperm-mediated transmission retention embryo. Using landmark examples, discuss sperm-inherited regions may escape impact via implicate transcription factors, chromatin organization, transposable elements. Finally, link paternally functional pre- post-implantation Understanding factors will permit greater understanding related origins disease.

Language: Английский

Citations

82
Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy DOI Creative Commons
Xi Lu,

Qingxing Xie,

Xiaohui Pan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 2, 2024

Language: Английский

Citations

65
Lachnospiraceae -derived butyrate mediates protection of high fermentable fiber against placental inflammation in gestational diabetes mellitus DOI Creative Commons
Shuangbo Huang, Jianzhao Chen, Zhijuan Cui

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(44)

Published: Nov. 3, 2023

Inflammation-associated insulin resistance is a key trigger of gestational diabetes mellitus (GDM), but the underlying mechanisms and effective interventions remain unclear. Here, we report association placental inflammation (tumor necrosis factor–α) abnormal maternal glucose metabolism in patients with GDM, high fermentable dietary fiber (HFDF; konjac ) could reduce GDM development through gut flora–short-chain fatty acid–placental axis mouse model. Mechanistically, HFDF increases abundances Lachnospiraceae butyrate, reduces placental-derived by enhancing barrier inhibiting transfer bacterial-derived lipopolysaccharide, ultimately resists high-fat diet–induced resistance. butyrate have similar anti-GDM anti–placental effects, they can ameliorate function pregnancy outcome effects probably dampening immune dysfunction. These findings demonstrate involvement important inflammation–related progression great potential HFDFs to susceptibility gut-flora-placenta axis.

Language: Английский

Citations

58
Caloric restriction prevents inheritance of polycystic ovary syndrome through oocyte-mediated DNA methylation reprogramming DOI
Yue Liu,

Yi Dong,

Yonghui Jiang

et al.

Cell Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

4
Dynamic metabolism during early mammalian embryogenesis DOI Creative Commons
Jing Zhao,

Wenjie Wang,

Ling Zhang

et al.

Development, Journal Year: 2023, Volume and Issue: 150(20)

Published: Oct. 15, 2023

Dynamic metabolism is exhibited by early mammalian embryos to support changing cell fates during development. It widely acknowledged that metabolic pathways not only satisfy cellular energetic demands, but also play pivotal roles in the process of signalling, gene regulation, proliferation and differentiation. Recently, various new technological advances have been made metabolomics computational analysis, deepening our understanding crucial role dynamic embryogenesis. In this Review, we summarize recent studies on oocyte embryo its with a particular focus association key developmental events such as fertilization, zygote genome activation fate determination. addition, discuss mechanisms certain metabolites that, addition serving energy sources, contribute epigenetic modifications.

Language: Английский

Citations

20
Host genetics and gut microbiota jointly regulate blood biochemical indicators in chickens DOI Creative Commons
Xinwei Jiang,

Boxuan Zhang,

Fangren Lan

et al.

Applied Microbiology and Biotechnology, Journal Year: 2023, Volume and Issue: 107(24), P. 7601 - 7620

Published: Oct. 4, 2023

Blood biochemical indicators play a crucial role in assessing an individual's overall health status and metabolic function. In this study, we measured five blood indicators, including total cholesterol (CHOL), low-density lipoprotein (LDL-CH), triglycerides (TG), high-density (HDL-CH), glucose (BG), as well 19 growth traits of 206 male chickens. By integrating host whole-genome information 16S rRNA sequencing the duodenum, jejunum, ileum, cecum, feces microbiota, assessed contributions genetics gut microbiota to their interrelationships. Our results demonstrated significant negative phenotypic genetic correlations (r = - 0.20 ~ 0.67) between CHOL LDL-CH with such body weight, abdominal fat content, muscle shin circumference. The heritability microbiability indicated that were jointly regulated by microbiota. Notably, HDL-CH was estimated be 0.24, while jejunal for BG TG reached 0.45 0.23. Furthermore, conducting genome-wide association study (GWAS) single-nucleotide polymorphism (SNPs), insertion/deletion (indels), structural variation (SV), identified RAP2C, member RAS oncogene family (RAP2C), dedicator cytokinesis 11 (DOCK11), neurotensin (NTS) BOP1 ribosomal biogenesis factor (BOP1) regulators HDL-CH, glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5), dihydrodiol dehydrogenase (DHDH), potassium voltage-gated channel interacting protein 1 (KCNIP1) candidate genes BG. Moreover, our findings suggest cecal RF39 Clostridia_UCG_014 may linked regulation CHOL, Streptococcaceae involved TG. Additionally, microbial GWAS presence under regulation. provide valuable insights into complex interaction shaping profile KEY POINTS: • Multiple RF39, Clostridia_UCG_014, implicated modulation. composition is influenced genetics.

Language: Английский

Citations

16
Developmental origins of diabetes mellitus: Environmental epigenomics and emerging patterns DOI Creative Commons
Hong Zhu, Guolian Ding,

Xinmei Liu

et al.

Journal of Diabetes, Journal Year: 2023, Volume and Issue: 15(7), P. 569 - 582

Published: May 16, 2023

Abstract Mounting epidemiological evidence indicates that environmental exposures in early life have roles diabetes susceptibility later life. Additionally, environmentally induced diabetic could be transmitted to subsequent generations. Epigenetic modifications provide a potential association with the factors and altered gene expression might cause disease phenotypes. Here, we bring increasing development are linked through epigenetic modifications. This review first summarizes targets, including metastable epialleles imprinting genes, by which can modify epigenome. Then epigenetics changes response challenge during critical developmental windows, gametogenesis, embryogenesis, fetal postnatal period, specific example of susceptibility. Although mechanisms still largely unknown, especially humans, new research methods now gradually available, animal models more in‐depth study mechanisms. These implications for investigating link phenomena human diabetes, providing perspective on triggered risk.

Language: Английский

Citations

15
Maternal Western diet mediates susceptibility of offspring to Crohn’s-like colitis by deoxycholate generation DOI Creative Commons
Chongyang Huang,

Huishi Tan,

Mengyao Song

et al.

Microbiome, Journal Year: 2023, Volume and Issue: 11(1)

Published: May 2, 2023

Abstract Background The Western dietary pattern, characterized by high consumption of fats and sugars, has been strongly associated with an increased risk developing Crohn’s disease (CD). However, the potential impact maternal obesity or prenatal exposure to a diet on offspring’s susceptibility CD remains unclear. Herein, we investigated effects underlying mechanisms high-fat/high-sugar Western-style (WD) 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced Crohn’s-like colitis. Methods Maternal dams were fed either WD normal control (ND) for eight weeks prior mating continued throughout gestation lactation. Post-weaning, offspring subjected ND create four groups: ND-born (N–N) (N-W), WD-born (W–N) (W-W). At age, they administered TNBS induce model. Results Our findings revealed that W–N group exhibited more severe intestinal inflammation than N–N group, as demonstrated lower survival rate, weight loss, shorter colon length. displayed significant increase in Bacteroidetes , which was accompanied accumulation deoxycholic (DCA). Further experimentation confirmed generation DCA mice colonized gut microbes from group. Moreover, administration aggravated TNBS-induced colitis promoting Gasdermin D (GSDMD)-mediated pyroptosis IL-1beta (IL-1β) production macrophages. Importantly, deletion GSDMD effectively restrains effect Conclusions study demonstrates can alter microbiota composition bile metabolism mouse offspring, leading CD-like These highlight importance understanding long-term consequences health may have implications prevention management disease.

Language: Английский

Citations

14
Auto-suppression of Tet dioxygenases protects the mouse oocyte genome from oxidative demethylation DOI
Xiaojie Zhang,

Binbin Han,

Zhenyu Shao

et al.

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: 31(1), P. 42 - 53

Published: Jan. 1, 2024

Language: Английский

Citations

6