A comprehensive study of the genotoxic and anti-genotoxic effects of homocysteine in HUVECs and mouse bone marrow cells

Guo, Xihan; Qi, Yanmei; Li, Jianfei; Fan, Houhong; Yang, Limei; Wu, Xue; Ni, Juan; Wang, Han; Wang, Xu

doi:10.1016/j.fct.2021.112518

Cited by 5 publications

(5 citation statements)

References 79 publications

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“…While these two diet types are broadly similar in their overall content of carbohydrates (65.08% vs. 64.3%), they differed in the contents of proteins (23.07% vs. 20.3%), fats (11.8% vs. 15.8%), and other specific micronutrients. In supporting with this possibility, we have previously shown that restriction on micronutrients or calorie has a great influence on MN frequency (Guo et al., 2017 ; Guo, Dai, et al., 2019 ; Guo, Qi, et al., 2021 ; Guo, Su, et al., 2023 ; Hu et al., 2020 ; Li et al., 2022 ; Yan et al., 2020 ).…”

Section: Discussionmentioning

confidence: 77%

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Telomere length and micronuclei trajectories in APP/PS1 mouse model of Alzheimer's disease: Correlating with cognitive impairment and brain amyloidosis in a sexually dimorphic manner

Guo,

Li,

et al. 2024

Aging Cell

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Although studies have demonstrated that genome instability is accumulated in patients with Alzheimer's disease (AD), the specific types of genome instability linked to AD pathogenesis remain poorly understood. Here, we report the first characterization of the age‐ and sex‐related trajectories of telomere length (TL) and micronuclei in APP/PS1 mice model and wild‐type (WT) controls (C57BL/6). TL was measured in brain (prefrontal cortex, cerebellum, pituitary gland, and hippocampus), colon and skin, and MN was measured in bone marrow in 6‐ to 14‐month‐old mice. Variation in TL was attributable to tissue type, age, genotype and, to a lesser extent, sex. Compared to WT, APP/PS1 had a significantly shorter baseline TL across all examined tissues. TL was inversely associated with age in both genotypes and TL shortening was accelerated in brain of APP/PS1. Age‐related increase of micronuclei was observed in both genotypes but was accelerated in APP/PS1. We integrated TL and micronuclei data with data on cognition performance and brain amyloidosis. TL and micronuclei were linearly correlated with cognition performance or Aβ40 and Aβ42 levels in both genotypes but to a greater extent in APP/PS1. These associations in APP/PS1 mice were dominantly driven by females. Together, our findings provide foundational knowledge to infer the TL and micronuclei trajectories in APP/PS1 mice during disease progression, and strongly support that TL attrition and micronucleation are tightly associated with AD pathogenesis in a female‐biased manner.

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Section: Discussionmentioning

confidence: 77%

“…The bone marrow MN assay was conducted as previously described (Guo, Qi, et al., 2021 ; Guo, Su, et al., 2023 ). Briefly, after mouse was killed by cervical dislocation, both femurs of each mouse were dissected.…”

Section: Methodsmentioning

confidence: 99%

Telomere length and micronuclei trajectories in APP/PS1 mouse model of Alzheimer's disease: Correlating with cognitive impairment and brain amyloidosis in a sexually dimorphic manner

Guo,

Li,

et al. 2024

Aging Cell

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“…Slides were smeared and then stained using eosin staining solution (Beyotime, China). Using a double-blind procedure, 1,000 polychromatic erythrocytes cells were observed from each mouse ( OECD, 2016 ; Guo et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Safety and efficacy evaluation of halicin as an effective drug for inhibiting intestinal infections

Zhang,

Lin,

Han

et al. 2024

Front. Pharmacol.

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Halicin, the first antibacterial agent discovered by artificial intelligence, exerts broad-spectrum antibacterial effects and has a unique structure. Our study found that halicin had a good inhibitory effect on clinical isolates of drug-resistant strains and Clostridium perfringens (C. perfringens). The safety of halicin was evaluated by acute oral toxicity, genotoxicity and subchronic toxicity studies. The results of acute toxicity test indicated that halicin, as a low-toxicity compound, had an LD50 of 2018.3 mg/kg. The results of sperm malformation, bone marrow chromosome aberration and cell micronucleus tests showed that halicin had no obvious genotoxicity. However, the results of the 90-day subchronic toxicity test indicated that the test rats exhibited weight loss and slight renal inflammation at a high dose of 201.8 mg/kg. Teratogenicity of zebrafish embryos showed that halicin had no significant teratogenicity. Analysis of intestinal microbiota showed that halicin had a significant effect on the intestinal microbial composition, but caused a faster recovery. Furthermore, drug metabolism experiments showed that halicin was poorly absorbed and quickly eliminated in vivo. Our study found that halicin had a good therapeutic effect on intestinal infection model of C. perfringens. These results show the feasibility of developing oral halicin as a clinical candidate drug for treating intestinal infections.

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“…25 However, we have shown that a high concentration of H 2 S induces GIN in human cells. 23 Besides, we have found that metformin and resveratrol, two CR mimetics, induce GIN in human non-cancerous cells in a dose-dependent manner. 20,26 In addition, some metabolites may exert specific effects independent of total calorie intake.…”

Section: Introductionmentioning

confidence: 93%

“…10 One aspect of DR regimens is that inevitably one or more macro-/micronutrients are reduced or increased. We have previously shown that disrupting the balance of certain macro-/micronutrients or metabolites like folate, 18 sugars, 19,20 glutamine, 21 homocysteine 22,23 and bile acids 24 has harmful or beneficial effects on genome stability in human in vitro cells and/or in mice in a dose-dependent manner. Hydrogen sulfide (H 2 S) produced from an endogenous trans-sulfuration pathway is essential for DR-mediated stress resistance.…”

Section: Introductionmentioning

confidence: 99%

Effects of dietary restriction on genome stability are sex and feeding regimen dependent

Guo

Gao

et al. 2023

Food Funct.

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A comprehensive study of the genotoxic and anti-genotoxic effects of homocysteine in HUVECs and mouse bone marrow cells

Cited by 5 publications

References 79 publications

Telomere length and micronuclei trajectories in APP/PS1 mouse model of Alzheimer's disease: Correlating with cognitive impairment and brain amyloidosis in a sexually dimorphic manner

Telomere length and micronuclei trajectories in APP/PS1 mouse model of Alzheimer's disease: Correlating with cognitive impairment and brain amyloidosis in a sexually dimorphic manner

Safety and efficacy evaluation of halicin as an effective drug for inhibiting intestinal infections

Effects of dietary restriction on genome stability are sex and feeding regimen dependent

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