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OBJECTIVE: Folic acid (FA) may contribute to the development of gestational diabetes mellitus (GDM), but available studies are inconsistent. We studied the genotype distribution and allele frequencies of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C, and methionine synthase reductase (MTRR) A66G polymorphisms in pregnant Chinese women and compared the effects of individualized and traditional FA supplementation on GDM. METHODS: In this retrospective study, genotype distribution and allele frequencies in 968 pregnant women were tested. FA metabolism was tested by dividing patients into four groups, each of which was supplemented with different doses of FA at different times. Pregnancy complications were followed up and compared to 1940 pregnant women traditionally supplemented with FA in the same hospital as a control group. RESULTS: The allele frequencies were 63.3% (C) and 36.7% (T) for MTHFR C677T, 79.3% (A) and 20.7% (C) for MTHFR A1298C and 75.0% (A) and 25.0% (G) for MTRR A66G. The incidence of GDM after FA supplementation was significantly lower in the case group compared to the control group, especially in high-risk pregnancies. CONCLUSION: Using genetic polymorphisms to elucidate FA metabolism in pregnant women and providing appropriate FA supplementation can be effective in reducing GDM, especially in high-risk groups.
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BACKGROUND: Lead (Pb) is a highly toxic and persistent substance that easily accumulates in living organisms, eliciting cellular toxicity and oxidative stress. Some selenium-containing proteins and peptides prepared from plant extracts are beneficial for protecting the body's health and resisting external disturbances. In the present study, selenium-containing peptide species were prepared from selenium-enriched Pleurotus eryngii protein hydrolysates and to evaluate the benefits of selenium-containing peptides on Pb-induced oxidative stress in NCTC1469 hepatocytes. RESULTS: Trypsin was selected as primary enzyme to hydrolyze the selenium-enriched protein (SPH). The optimal hydrolysis conditions were: hydrolysis time, 1.5 h; initial pH 8.0. The SPH was digested by trypsin and then purified by ultrafiltration, gel filtration chromatography and reversed-phase HPLC to obtain the selenium-containing peptides SPH-I-2. Furthermore, SPH-I-2 was analyzed and a number of total 12 selenium-containing peptides were identified by liquid chromatography-tandem mass spectroscopy. The NCTC1469 cell culture study showed that selenium-containing peptides were capable of reducing reactive oxygen species levels and regulating the Keap1/Nrf2 pathway by upregulating Nrf2, HO-1, GCLC, GCLM and NQO1 genes and downregulating Keap1 genes. Moreover, selenium-containing peptides were also able to suppress Pb-induced elevated levels of nitric oxide (NO), lactate dehydrogenase (LDH), malondialdehyde (MDA), increase antioxidant enzyme activity and alleviate cell apoptosis. CONCLUSION: The present study indicated that the selenium-containing peptides could protect cells from Pb2+ -induced oxidative stress. © 2023 Society of Chemical Industry.
Assuntos
Selênio , Selênio/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Chumbo/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Tripsina/metabolismo , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Peptídeos/farmacologia , Peptídeos/metabolismo , Hepatócitos/metabolismoRESUMO
It is of great significance to develop safe and efficient dietary selenium sources to improve lead toxicity. In this study, selenate, selenite, SeMet and Se-yeast were supplied to investigate the Se biofortification and bioaccessibility in Pleurotus eryngii. The effects of Se-enriched P. eryngii on lead binding bacteria were investigated via in vitro fermentation. With 40 mg/kg Se in the substrate, the total Se contents of P. eryngii treated with selenite and Se-yeast were 145.22 ± 8.00 mg/kg and 90.01 ± 7.01 mg/kg, respectively. Compared with selenite, Se-yeast treatment significantly increased the organic Se proportion in P. eryngii (SeCys2 2.85 ± 0.17%, MeSeCys 2.33 ± 0.21% and SeMet 78.19 ± 1.58%), which led to higher bioaccessibility. With 1 mg/L lead treatment during in vitro fermentation, Se-enriched P. eryngii promoted the growth of Desulfovibrio, which contributed to the increase of gut microbiota lead adsorption. Se-enriched P. eryngii cultivated with Se-yeast could be used as dietary Se sources for lead toxicity improvement.
Assuntos
Microbioma Gastrointestinal , Selênio , Adsorção , Biofortificação , Fermentação , Chumbo , Pleurotus , Saccharomyces cerevisiae/metabolismo , Ácido Selenioso , Selênio/metabolismoRESUMO
The main mechanism of pyroptosis is Caspase-1-mediated GSDMD cleavage, and GSDMD is also the executive protein of pyroptosis. Our previous study has shown that mafenide can inhibit pyroptosis by inhibiting the GSDMD-Asp275 site to suppress cleavage. In this study, sulfonamide was used as the parent nucleus structure to synthesize sulfa-4 and sulfa-20. Screening of drug activity in the pyroptosis model of BV2 and iBMDM cell lines revealed the efficacy of five compounds were superior to mafenide, which exerted a better inhibitory effect on the occurrence of pyroptosis. For in vivo assay, Sulfa-4 and Sulfa-22 were intervened in the neuroinflammation APP/PS1 mice. As a result, the administration of Sulfa-4 and Sulfa-22 could significantly inhibit the activation of microglia, decrease the expression of inflammatory factors in the central nervous system and simultaneously suppress the production of p30-GSDMD as well as the expression of upstream NLRP3 inflammasome and Caspase-1 protein. Immunoprecipitation and Biotin-labelled assay confirmed the targeted binding relationship of Sulfa-4 and Sulfa-22 with GSDMD protein in the iBMDM model in vitro. In this study, we investigated a new type inhibitor of GSDMD cleavage, which exerted a good inhibitory effect on pyroptosis and provided new references for the development of inflammatory drugs in the future.