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Journal of Nutritional Science 2023Preeclampsia (PE) affects up to five times more women with pre-existing diabetes mellitus (PDM) than women without it. The present study aimed to identify the effect of... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of the Dietary Approaches to Stop Hypertension (DASH) diet on the development of preeclampsia and metabolic outcomes in pregnant women with pre-existing diabetes mellitus: a randomised, controlled, single-blind trial.
Preeclampsia (PE) affects up to five times more women with pre-existing diabetes mellitus (PDM) than women without it. The present study aimed to identify the effect of the DASH diet on PE incidence (primary outcome) and blood pressure, glycated haemoglobin (GH), serum lipids, glutathione peroxidase (GP), C-reactive protein (CRP - secondary outcomes) in pregnant with PDM. This randomised, controlled, single-blind trial studied sixty-eight pregnant women with PDM throughout prenatal care until delivery (18 weeks) at a public maternity hospital, Brazil. The standard diet group (SDG) received a diet containing 45-65 % carbohydrates, 15-20 % protein and 25-30 % lipids. The DASH diet group (DDG) received the adapted DASH diet with a similar macronutrient distribution, but with a higher concentration of fibres, unsaturated fats, calcium, magnesium and potassium as well as lower saturated fat. Student's , Mann-Whitney and the Chi-square tests were used to compare outcomes. PE incidence was 22⋅9 % in the SDG and 12⋅1 % in the DDG ( = 0⋅25). GP levels significantly increased in the DDG (intra-group analysis; mean difference = 1588 [CI 181, 2994], = 0⋅03) and tended to be different from the variation in the SDG (mean difference = -29⋅5 [CI -1305; 1⋅365]; . DDG: 1588 [CI 181; 2994], = 0⋅09). GH levels decreased significantly and similarly between groups (SDG: -0⋅61 [CI -0⋅26, -0⋅96], = 0⋅00) . DDG: -1⋅1 [CI -0⋅57, -1⋅62], = 0⋅00). There was no evidence of a difference in PE incidence at the end of the intervention between the two diets. The DASH diet seems to favour PE-related biochemical markers.
Topics: Dietary Approaches To Stop Hypertension; Humans; Female; Pregnancy; Pre-Eclampsia; Pregnancy in Diabetics; Diabetes Mellitus; Brazil; Adult; Blood Pressure; Glycated Hemoglobin; Lipids; Glutathione Peroxidase; C-Reactive Protein
PubMed: 37457679
DOI: 10.1017/jns.2023.54 -
Indian Journal of Dental Research :... 2023It had been found that passive smoking may have the same harmful effect as tobacco cigarettes smoking. Aims: This study was conducted to determine the effect of passive...
BACKGROUND
It had been found that passive smoking may have the same harmful effect as tobacco cigarettes smoking. Aims: This study was conducted to determine the effect of passive smoking on salivary glutathione peroxidase and selenium in relation to dental caries severity.
SETTINGS AND DESIGN
The sample consisted of 120 children aged 5 years old, classified into four groups according to the number of cigarettes smoked by their fathers daily: Passive smoking children of 5-10 cigarettes, those of 10-15 cigarettes daily, those of 15-20 cigarettes daily and non-passive smoking children of no smokers indoor (the control group). The sample was further classified according to dental caries severity into three groups: mild (DMFS values <4), moderate (DMFS values from 4 to 8) and severe (DMFS values >8).
METHODS AND MATERIAL
Stimulated saliva was collected, and salivary glutathione peroxidase and selenium were chemically analysed.
RESULTS AND CONCLUSIONS
Glutathione peroxidase and selenium were higher among non-passive smoking children than passive smoking children and they were higher among children with mild caries severity than in children with moderate or severe caries severity (p < 0.01). Passive smoking had significant effect in both salivary glutathione peroxidase and selenium (p < 0.01), while dental caries had non-significant effect on them (p > 0.05). In conclusion, passive smoking had deleterious effect in salivary glutathione peroxidase and selenium, while dental caries did not have effect on these two variables. There is no interaction between both passive smoking and dental caries in neither glutathione peroxidase nor selenium, so the effect of passive smoking on these two variables can exceed the effect of dental caries on them.
Topics: Child; Humans; Child, Preschool; Selenium; Tobacco Smoke Pollution; Dental Caries; Smoking; Glutathione Peroxidase
PubMed: 38197345
DOI: 10.4103/ijdr.ijdr_969_22 -
The Journal of Biological Chemistry Dec 2023Eosinophil peroxidase (EPO) is the most abundant granule protein exocytosed by eosinophils, specialized human phagocytes. Released EPO catalyzes the formation of...
Eosinophil peroxidase (EPO) is the most abundant granule protein exocytosed by eosinophils, specialized human phagocytes. Released EPO catalyzes the formation of reactive oxidants from bromide, thiocyanate, and nitrite that kill tissue-invading parasites. However, EPO also plays a deleterious role in inflammatory diseases, making it a potential pharmacological target. A major hurdle is the high similarity to the homologous myeloperoxidase (MPO), which requires a detailed understanding of the small structural differences that can be used to increase the specificity of the inhibitors. Here, we present the first crystal structure of mature leukocyte EPO at 1.6 Å resolution together with analyses of its posttranslational modifications and biochemical properties. EPO has an exceptionally high number of positively charged surface patches but only two occupied glycosylation sites. The crystal structure further revealed the existence of a light (L) and heavy (H) chain as a result of proteolytic cleavage. Detailed comparison with the structure of human MPO allows us to identify differences that may contribute to the known divergent enzymatic properties. The crystal structure revealed fully established ester links between the prosthetic group and the protein, the comparably weak imidazolate character of the proximal histidine, and the conserved structure of the catalytic amino acids and Ca-binding site. Prediction of the structure of unprocessed proeosinophil peroxidase allows further structural analysis of the three protease cleavage sites and the potential pro-convertase recognition site in the propeptide. Finally, EPO biosynthesis and its biochemical and biophysical properties are discussed with respect to the available data from the well-studied MPO.
Topics: Humans; Eosinophil Peroxidase; Eosinophils; Heme; Protein Processing, Post-Translational
PubMed: 38229400
DOI: 10.1016/j.jbc.2023.105402 -
PeerJ 2023Maize is one of the major crops in the world and the most productive member of the family. Since cold stress affects the germination, growth, and productivity of corn...
Maize is one of the major crops in the world and the most productive member of the family. Since cold stress affects the germination, growth, and productivity of corn seeds, the present study aimed to investigate the effect of seed biopriming with on the tolerance of two genotypes of maize seedlings to cold stress. This study was conducted in triplicates in factorial experiment with a complete randomized block design (CRBD). The study was conducted in the greenhouse and laboratory of the University of Mohaghegh Ardabili, Ardabil, Iran. Experimental factors include two cultivars (AR68 cold-resistant and KSC703 cold-sensitive maize cultivars), four pretreatment levels (control, biopriming with , exogenous and hydropriming), and two levels of cold stress (control and cold at 5 °C) in a hydroponic culture medium. The present study showed that maize leaves' establishment rate and maximum fluorescence (Fm) are affected by triple effects (C*, P*, S). The highest establishment (99.66%) and Fm (994 units) rates were observed in the KP3 control treatment. Moreover, among the pretreatments, the highest (0.476 days) and the lowest (0.182 days) establishment rates were related to P0 and P3 treatments, respectively. Cultivar A showed higher chlorophyll a and b, carotenoid content, and establishment rate compared to cultivar K in both optimal and cold conditions. The highest root dry weight (11.84 units) was obtained in cultivar A with P3 pretreatment. The pretreatments with increased physiological parameters and seedling emergence of maize under cold and optimal stress conditions. Pretreatment and cultivar improved catalase activity in roots and leaves. Higher leaf and root catalase activity was observed in the roots and leaves of cultivar K compared to cultivar A. The cold treatment significantly differed in peroxidase activity from the control treatment. Cultivar K showed higher catalase activity than cultivar A. The main effects of pretreatment and cold on polyphenol oxidase activity and proline content showed the highest polyphenol oxidase activity and proline content in hydropriming (H) treatment. Cold treatment also showed higher polyphenol oxidase activity and proline content than cold-free conditions.
Topics: Zea mays; Cold-Shock Response; Catalase; Chlorophyll A; Catechol Oxidase
PubMed: 37645014
DOI: 10.7717/peerj.15644 -
Advanced Science (Weinheim,... Jul 2023Preventing islet β-cells death is crucial for treating type 2 diabetes mellitus (T2DM). Currently, clinical drugs are being developed to improve the quality of T2DM...
Selenium Nanodots (SENDs) as Antioxidants and Antioxidant-Prodrugs to Rescue Islet β Cells in Type 2 Diabetes Mellitus by Restoring Mitophagy and Alleviating Endoplasmic Reticulum Stress.
Preventing islet β-cells death is crucial for treating type 2 diabetes mellitus (T2DM). Currently, clinical drugs are being developed to improve the quality of T2DM care and self-care, but drugs focused on reducing islets β-cell death are lacking. Given that β-cell death in T2DM is dominated ultimately by excessive reactive oxygen species (ROS), eliminating excessive ROS in β-cells is a highly promising therapeutic strategy. Nevertheless, no antioxidants have been approved for T2DM therapy because most of them cannot meet the long-term and stable elimination of ROS in β-cells without eliciting toxic side-effects. Here, it is proposed to restore the endogenous antioxidant capacity of β-cells to efficiently prevent β-cell death using selenium nanodots (SENDs), a prodrug of the antioxidant enzyme glutathione peroxidase 1 (GPX1). SENDs not only scavenge ROS effectively, but also "send" selenium precisely to β-cells with ROS response to greatly enhance the antioxidant capacity of β-cells by increasing GPX1 expression. Therefore, SENDs greatly rescue β-cells by restoring mitophagy and alleviating endoplasmic reticulum stress (ERS), and demonstrate much stronger efficacy than the first-line drug metformin for T2DM treatment. Overall, this strategy highlights the great clinical application prospects of SENDs, offering a paradigm for an antioxidant enzyme prodrug for T2DM treatment.
Topics: Humans; Antioxidants; Selenium; Diabetes Mellitus, Type 2; Prodrugs; Reactive Oxygen Species; Mitophagy; Oxidative Stress; Glutathione Peroxidase GPX1; Endoplasmic Reticulum Stress
PubMed: 37408520
DOI: 10.1002/advs.202300880 -
Rheumatology (Oxford, England) Apr 2024Data on ANCA-associated vasculitis (AAV) induced by anti-thyroid drugs (ATD) are scarce. We aimed to describe the characteristics and outcome of these patients in...
OBJECTIVE
Data on ANCA-associated vasculitis (AAV) induced by anti-thyroid drugs (ATD) are scarce. We aimed to describe the characteristics and outcome of these patients in comparison to primary AAV.
METHODS
We performed a retrospective multicentre study including patients with ATD-induced AAV. We focused on ATD-induced microscopic polyangiitis (MPA) and compared them with primary MPA by matching each case with four controls by gender and year of diagnosis.
RESULTS
Forty-five patients with ATD-induced AAV of whom 24 MPA were included. ANCA were positive in 44 patients (98%), including myeloperoxidase (MPO)-ANCA in 21 (47%), proteinase 3 (PR3)-ANCA in six (13%), and double positive MPO- and PR3-ANCA in 15 (33%). Main clinical manifestations were skin involvement (64%), arthralgia (51%) and glomerulonephritis (20%). ATD was discontinued in 98% of cases, allowing vasculitis remission in seven (16%). All the remaining patients achieved remission after glucocorticoids, in combination with rituximab in 11 (30%) or cyclophosphamide in four (11%). ATD were reintroduced in seven cases (16%) without any subsequent relapse. Compared with 96 matched primary MPA, ATD-induced MPA were younger at diagnosis (48 vs 65 years, P < 0.001), had more frequent cutaneous involvement (54 vs 25%, P = 0.007), but less frequent kidney (38 vs 73%, P = 0.02), and a lower risk of relapse (adjusted HR 0.07; 95% CI 0.01, 0.65, P = 0.019).
CONCLUSION
ATD-induced AAV were mainly MPA with MPO-ANCA, but double MPO- and PR3-ANCA positivity was frequent. The most common manifestations were skin and musculoskeletal manifestations. ATD-induced MPA were less severe and showed a lower risk of relapse than primary MPA.
Topics: Humans; Granulomatosis with Polyangiitis; Retrospective Studies; Antibodies, Antineutrophil Cytoplasmic; Case-Control Studies; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Myeloblastin; Microscopic Polyangiitis; Recurrence; Peroxidase
PubMed: 37354498
DOI: 10.1093/rheumatology/kead319 -
World Journal of Gastroenterology Mar 2024Acute liver failure (ALF) has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis. The silent information regulator sirtuin 1...
BACKGROUND
Acute liver failure (ALF) has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis. The silent information regulator sirtuin 1 (SIRT1)-mediated deacetylation affects multiple biological processes, including cellular senescence, apoptosis, sugar and lipid metabolism, oxidative stress, and inflammation.
AIM
To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.
METHODS
This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) testing. C57BL/6 mice were also intraperitoneally pretreated with SIRT1, p53, or glutathione peroxidase 4 (GPX4) inducers and inhibitors and injected with lipopolysaccharide (LPS)/D-galactosamine (D-GalN) to induce ALF. Gasdermin D (GSDMD) mice were used as an experimental group. Histological changes in liver tissue were monitored by hematoxylin and eosin staining. ALT, AST, glutathione, reactive oxygen species, and iron levels were measured using commercial kits. Ferroptosis- and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction. SIRT1, p53, and GSDMD were assessed by immunofluorescence analysis.
RESULTS
Serum AST and ALT levels were elevated in patients with ALF. SIRT1, solute carrier family 7a member 11 (SLC7A11), and GPX4 protein expression was decreased and acetylated p5, p53, GSDMD, and acyl-CoA synthetase long-chain family member 4 (ACSL4) protein levels were elevated in human ALF liver tissue. In the p53 and ferroptosis inhibitor-treated and GSDMD groups, serum interleukin (IL)-1β, tumour necrosis factor alpha, IL-6, IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated. In mice with GSDMD knockout, p53 was reduced, GPX4 was increased, and ferroptotic events (depletion of SLC7A11, elevation of ACSL4, and iron accumulation) were detected. , knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels, the cytostatic rate, and GSDMD expression, restoring SLC7A11 depletion. Moreover, SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group, accompanied by reduced p53, GSDMD, and ACSL4, and increased SLC7A11 and GPX4. Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalN-induced and models.
CONCLUSION
SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.
Topics: Animals; Humans; Mice; Gasdermins; Iron; Lipopolysaccharides; Liver Failure, Acute; Mice, Inbred C57BL; Phospholipid Hydroperoxide Glutathione Peroxidase; Sirtuin 1; Tumor Suppressor Protein p53
PubMed: 38617450
DOI: 10.3748/wjg.v30.i11.1588 -
Molecules (Basel, Switzerland) Nov 2023Aging and age-related diseases are important study topics due to their associations with progressive physiological damage to genes, cells, tissues, and the entire...
Aging and age-related diseases are important study topics due to their associations with progressive physiological damage to genes, cells, tissues, and the entire organism, which ultimately affects the functional efficiency of organs. Murr. is a functional food that is known for its high contents of anthocyanins and spermidines, both of which have been demonstrated to have positive effects on anti-aging activity and anti-oxidation. In this study, we used HPLC-MS to analyze the constituents of Murr. Extract (LRM) and investigated their potential mechanism for exerting antioxidative effects in D-galactose (D-Gal) aging model mice. LRM (25 mg/kg, 50 mg/kg, and 100 mg/kg) improved cognitive function in D-Gal-treated mice, as shown by reduced escape latencies and increased platform crossings in behavioral tests. We measured the contents of lipid peroxidation (LPO) and malondialdehyde (MDA) and the enzyme activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in mice serum and brain after 6 weeks of D-Gal treatment. LRM decreased the contents of LPO and MDA and increased the enzyme activities of SOD and GSH-Px, indicating the protection effect of LRM against D-Gal-induced oxidative stress. Additionally, LRM can inhibit oxidative stress in cells by reducing intracellular ROS levels and restoring mitochondrial membrane potential, thereby inhibiting paraquat (PQ)-induced cellular senescence and delaying cell aging. Therefore, LRM has the potential to be a healthcare product for the treatment of age-related diseases.
Topics: Mice; Animals; Lycium; Anthocyanins; Oxidative Stress; Antioxidants; Glutathione Peroxidase; Ethanol; Superoxide Dismutase; Plant Extracts; Galactose; Malondialdehyde
PubMed: 38005337
DOI: 10.3390/molecules28227615 -
Oncology Reports Nov 2023As a newly identified circular RNA (circRNA), the role of circBLNK in cancer progression has not been probed. The objective of the present study was to functionally...
As a newly identified circular RNA (circRNA), the role of circBLNK in cancer progression has not been probed. The objective of the present study was to functionally dissect the role of circBLNK in osteosarcoma (OS) tumorigenesis and progression. With regards of the experimental procedure, the levels of mRNAs and proteins were assessed using reverse transcription‑quantitative PCR and western blot analysis, respectively. The subcellular location of circBLNK in OS cells was determined by cell cytosolic/nuclear fractionation assay. Cell ferroptosis ability was assessed through MTT assay. Cell proliferative abilities were assessed by clonogenic and Cell Counting Kit‑8 assays, and cell apoptosis was measured using flow cytometry. The relationships among circBLNK, miR‑188‑3p, and glutathione peroxidase 4 (GPX4) were validated by luciferase reporter and RNA pull‑down assays, as well as RNA immunoprecipitation. The stability of circBLNK and linear BLNK was confirmed using RNase R treatment assay. The association between circBLNK expression and overall survival rate was assessed by Kaplan‑Meier plot. The correlation between the expression levels of circBLNK, miR‑188‑3p, and GPX4 in OS tissues was assessed by Pearson's χ test. The results revealed that CircBLNK and GPX4 were significantly upregulated in OS tissues, which predicted the poor prognosis. CircBLNK knockdown led to suppressed cell proliferation and enhanced cell apoptosis, an effect that could be reversed by the inhibition of miR‑188‑3p. In an circBLNK deficiency model, tumor growth was observed to be markedly suppressed. Moreover, circBLNK deficiency elevated levels of intracellular free iron (Fe), malondialdehyde, lipid reactive oxygen species and mitochondrial superoxide, while diminishing mitochondrial membrane potential in Erastin‑treated OS cells, which were eliminated by overexpressing GPX4. Furthermore, mechanistic investigations revealed that circBLNK sponged miR‑188‑3p to regulate the expression of GPX4, thereby affecting OS progression. In conclusion, the present study delineated a new regulatory axis involving circBLNK/miR‑188‑3p/GPX4 in OS progression, adding to the growing evidence that circRNAs are critical gene regulators in cancer progression.
Topics: Humans; RNA, Circular; Phospholipid Hydroperoxide Glutathione Peroxidase; Ferroptosis; Osteosarcoma; Bone Neoplasms; MicroRNAs
PubMed: 37711054
DOI: 10.3892/or.2023.8629 -
International Journal of Molecular... Aug 2023Age and sex influence serum cholesterol levels, but the underlying mechanisms remain unclear. To investigate further, we measured cholesterol, precursors (surrogate...
Age and sex influence serum cholesterol levels, but the underlying mechanisms remain unclear. To investigate further, we measured cholesterol, precursors (surrogate synthesis markers), degradation products (oxysterols and bile acid precursors) in serum, the liver, jejunum, and ileum, as well as serum plant sterols (intestinal absorption markers) in male and female Wistar rats (4 and 24 months old). The analysis of histomorphometric and oxidative stress parameters (superoxide dismutase, catalase, glutathione-related enzyme activities, lipid peroxide, and protein carbonyl concentrations) in the liver and jejunum offered further insights into the age- and sex-related differences. The hepatic gene expression analysis included AR, ERα, and sex-specific growth hormone-regulated (Cyp2c11 and Cyp2c12) and thyroid-responsive (Dio1, Tbg, and Spot 14) genes by qPCR. We observed age-related changes in both sexes, with greater prominence in females. Aged females had significantly higher serum cholesterol ( < 0.05), jejunum cholesterol ( < 0.05), and serum plant sterols ( < 0.05). They exhibited poorer hepato-intestinal health compared with males, which was characterized by mild liver dysfunction (hydropic degeneration, increased serum ALT, < 0.05, and decreased activity of some antioxidant defense enzymes, < 0.05), mononuclear inflammation in the jejunal lamina propria, and age-related decreases in jejunal catalase and glutathione peroxidase activity ( < 0.05). Aged females showed increased levels of 27-hydroxycholesterol ( < 0.05) and upregulated ERα gene expression ( < 0.05) in the liver. Our study suggests that the more significant age-related increase in serum cholesterol in females is associated with poorer hepato-intestinal health and increased jejunal cholesterol absorption. The local increase in 27-hydroxycholesterol during aging might reduce the hepatoprotective effects of endogenous estrogen in the female liver.
Topics: Female; Male; Rats; Animals; Catalase; Estrogen Receptor alpha; Rats, Wistar; Liver; Aging
PubMed: 37628805
DOI: 10.3390/ijms241612624