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  • 1
    Online Resource
    Online Resource
    Maternal Iron Deficiency Programs Offspring Cognition and Its Relationship with Gastrointestinal Microbiota and Metabolites
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 17, No. 17 ( 2020-08-20), p. 6070-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 17 ( 2020-08-20), p. 6070-
    Abstract: Iron is an essential micronutrient for the brain development of the fetus. Altered intestinal microbiota might affect behavior and cognition through the so-called microbiota-gut-brain axis. We used a Sprague-Dawley rat model of a maternal low-iron diet to explore the changes in cognition, dorsal hippocampal brain-derived neurotrophic factor (BDNF) and related pathways, gut microbiota, and related metabolites in adult male offspring. We established maternal iron-deficient rats by feeding them a low-iron diet (2.9 mg/kg), while the control rats were fed a standard diet (52.3 mg/kg). We used a Morris water maze test to assess spatial learning and long-term memory. Western blot (WB) assays and a quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to detect the BDNF concentration and related signaling pathways. We collected fecal samples for microbiota profiling and measured the concentrations of plasma short-chain fatty acids. The adult male offspring of maternal rats fed low-iron diets before pregnancy, during pregnancy and throughout the lactation period had (1) spatial deficits, (2) a decreased BDNF mRNA expression and protein concentrations, accompanied by a decreased TrkB protein abundance, (3) a decreased plasma acetate concentration, and (4) an enrichment of the Bacteroidaceae genus Bacteroides and Lachnospiraceae genus Marvinbryantia. Maternal iron deficiency leads to an offspring spatial deficit and is associated with alternations in gastrointestinal microbiota and metabolites.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph17176070
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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  • 2
    Online Resource
    Online Resource
    Increased Circulating ADMA in Young Male Rats Caused Cognitive Deficits and Increased Intestinal and Hippocampal NLRP3 Inflammasome Expression and Microbiota Composition Alterations: Effects of Resveratrol
    MDPI AG ; 2023
    In:  Pharmaceuticals Vol. 16, No. 6 ( 2023-05-31), p. 825-
    Details
    In: Pharmaceuticals, MDPI AG, Vol. 16, No. 6 ( 2023-05-31), p. 825-
    Abstract: Endothelial dysfunction is characterized by disturbances in nitric oxide (NO) bioavailability and increased circulating asymmetric dimethylarginine (ADMA) due to the enormous release of free radicals. Increased circulating ADMA may cause endothelial dysfunction and a variety of clinical disorders, such as liver and kidney disease. Young male Sprague-Dawley rats at postnatal day 17 ± 1 received continuous ADMA infusion via an intraperitoneal pump to induce endothelial dysfunction. Four groups of rats (n = 10 per group) were allocated: control, control and resveratrol, ADMA infusion, and ADMA infusion and resveratrol groups. Spatial memory, NLR family pyrin-domain-containing 3 (NLRP3) inflammasome, cytokine expression, tight junction proteins in the ileum and dorsal hippocampus, and microbiota composition were examined. We found cognitive deficits; increased NLRP3 inflammasome in the plasma, ileum, and dorsal hippocampus; decreased ileum and dorsal hippocampal cytokine activation and tight junction proteins; and microbiota composition alterations in the ADMA-infusion young male rats. Resveratrol had beneficial effects in this context. In conclusion, we observed NLRP3 inflammasome activation in peripheral and central dysbiosis in young male rats with increased circulating ADMA, and found that resveratrol had beneficial effects. Our work adds to the mounting evidence that inhibiting systemic inflammation is a promising therapeutic avenue for cognition impairment, probably via the gut-brain axis.
    Type of Medium: Online Resource
    ISSN: 1424-8247
    URL: Article
    DOI: 10.3390/ph16060825
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2193542-7
    SSG: 15,3
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  • 3
    Online Resource
    Online Resource
    Methotrexate Neurotoxicity Is Related to Epigenetic Modification of the Myelination Process
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 13 ( 2021-06-23), p. 6718-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 13 ( 2021-06-23), p. 6718-
    Abstract: With the improvement of the survival rate of acute lymphoblastic leukemia (ALL) in children, some children ALL survivors reveal inferior intellectual and cognition outcome. Methotrexate (MTX), while serving as an essential component in ALL treatment, has been reported to be related to various neurologic sequelae. Using combined intrathecal (IT) and intraperitoneal (IP) MTX model, we had demonstrated impaired spatial memory function in developing rats, which can be rescued by melatonin treatment. To elucidate the impact of MTX treatment on the epigenetic modifications of the myelination process, we examined the change of neurotrophin and myelination-related transcriptomes in the present study and found combined IT and IP MTX treatment resulted in altered epigenetic modification on the myelination process, mainly in the hippocampus. Further, melatonin can restore the MTX effect through alterations of the epigenetic pathways.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22136718
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Effects of Maternal Resveratrol on Maternal High-Fat Diet/Obesity with or without Postnatal High-Fat Diet
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 10 ( 2020-05-12), p. 3428-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 10 ( 2020-05-12), p. 3428-
    Abstract: To examine the effects of maternal resveratrol in rats borne to dams with gestational high-fat diet (HFD)/obesity with or without postnatal high-fat diet. We first tested the effects of maternal resveratrol intake on placenta and male fetus brain in rats borne to dams with gestational HFD/obesity. Then, we assessed the possible priming effect of a subsequent insult, male offspring were weaned onto either a rat chow or a HFD. Spatial learning and memory were assessed by Morris water maze test. Blood pressure and peripheral insulin resistance were examined. Maternal HFD/obesity decreased adiponectin, phosphorylation alpha serine/threonine-protein kinase (pAKT), sirtuin 1 (SIRT1), and brain-derived neurotrophic factor (BDNF) in rat placenta, male fetal brain, and adult male offspring dorsal hippocampus. Maternal resveratrol treatment restored adiponectin, pAKT, and BDNF in fetal brain. It also reduced body weight, peripheral insulin resistance, increased blood pressure, and alleviated cognitive impairment in adult male offspring with combined maternal HFD and postnatal HFD. Maternal resveratrol treatment restored hippocampal pAKT and BDNF in rats with combined maternal HFD and postnatal HFD in adult male offspring dorsal hippocampus. Maternal resveratrol intake protects the fetal brain in the context of maternal HFD/obesity. It effectively reduced the synergistic effects of maternal HFD/obesity and postnatal HFD on metabolic disturbances and cognitive impairment in adult male offspring. Our data suggest that maternal resveratrol intake may serve as an effective therapeutic strategy in the context of maternal HFD/obesity.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21103428
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    The Influence of Helium Dielectric Barrier Discharge Jet (DBDjet) Plasma Treatment on Bathocuproine (BCP) in p-i-n-Structure Perovskite Solar Cells
    MDPI AG ; 2021
    In:  Polymers Vol. 13, No. 22 ( 2021-11-20), p. 4020-
    Details
    In: Polymers, MDPI AG, Vol. 13, No. 22 ( 2021-11-20), p. 4020-
    Abstract: A bathocuproine (BCP) layer is typically used as the hole-blocking layer in p-i-n-structure perovskite solar cells (PSCs) between PC61BM and Ag electrodes. Before evaporating the Ag, we used a low-temperature ( 〈 40 °C) atmospheric-pressure dielectric barrier discharge jet (DBDjet) to treat the BCP with different scan rates. The main purpose of this was to change the contact resistance between the BCP layer and the Ag electrodes through surface modification using a DBDjet. The best power conversion efficiency (PCE) of 13.11% was achieved at a DBDjet scan rate of 2 cm/s. The He DBDjet treatment introduced nitrogen to form C−N bonds and create pits on the BCP layer. This deteriorated the interface between the BCP and the follow-up deposited-Ag top electrode. Compared to the device without the plasma treatment on the BCP layer, the He DBDjet treatment on the BCP layer reduced photocurrent hysteresis but deteriorated the fill factor and the efficiency of the PSCs.
    Type of Medium: Online Resource
    ISSN: 2073-4360
    URL: Article
    DOI: 10.3390/polym13224020
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527146-5
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  • 6
    Online Resource
    Online Resource
    Melatonin Alleviates Liver Apoptosis in Bile Duct Ligation Young Rats
    MDPI AG ; 2016
    In:  International Journal of Molecular Sciences Vol. 17, No. 8 ( 2016-08-20), p. 1365-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 17, No. 8 ( 2016-08-20), p. 1365-
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms17081365
    Language: English
    Publisher: MDPI AG
    Publication Date: 2016
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Epileptiform Discharge and Electrographic Seizures during the Hypothermia Phase as Predictors of Rewarming Seizures in Children after Resuscitation
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 7 ( 2020-07-08), p. 2151-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 7 ( 2020-07-08), p. 2151-
    Abstract: The aim of this study was to determine the frequency, timing, and predictors of rewarming seizures in a cohort of children undergoing therapeutic hypothermia after resuscitation. We retrospectively reviewed consecutive pediatric patients undergoing therapeutic hypothermia after resuscitation admitted to our pediatric intensive care unit between January 2000 and December 2019. Continuous electroencephalographic monitoring was performed during hypothermia (24 h for cardiac aetiologies and 72 h for asphyxial aetiologies), rewarming (72 h), and then an additional 12 h of normothermia. Thirty comatose children undergoing therapeutic hypothermia after resuscitation were enrolled, of whom 10 (33.3%) had rewarming seizures. Two (20%) of these patients had their first seizure during the rewarming phase. Four (40%) patients had electroclinical seizures, and six (60%) had nonconvulsive seizures. The median time from starting rewarming to the onset of rewarming seizures was 37.3 h (range 6 to 65 h). The patients with interictal epileptiform activity and electrographic seizures during the hypothermia phase were more likely to have rewarming seizures compared to those without interictal epileptiform activity or electrographic seizures (p = 0.019 and 0.019, respectively). Therefore, in high-risk patients, continuous electroencephalographic monitoring for a longer duration may help to detect rewarming seizures and guide clinical management.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9072151
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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  • 8
    Online Resource
    Online Resource
    An Examination of Serum Acylcarnitine and Amino Acid Profiles at Different Time Point of Ketogenic Diet Therapy and Their Association of Ketogenic Diet Effectiveness
    MDPI AG ; 2020
    In:  Nutrients Vol. 13, No. 1 ( 2020-12-23), p. 21-
    Details
    In: Nutrients, MDPI AG, Vol. 13, No. 1 ( 2020-12-23), p. 21-
    Abstract: Background: This study aimed to identify metabolic parameters at different time points of ketogenic diet therapy (KDT) and investigate their association with response to KDT in pediatric drug-resistant epilepsy (DRE). Methods: Prospectively, twenty-nine patients (0.67~20 years old) with DRE received classic ketogenic diet with non-fasting, gradual KD initiation protocol (GRAD-KD) for 1 year were enrolled. A total of 22 patients remaining in study received blood examinations at baseline, 3rd, 6th, 9th, and 12th months of KDT. β-hydroxybutyrate, free carnitine, acylcarnitines, and amino acids were compared between responders (seizure reduction rate ≥ 50%) and non-responders (seizure reduction rate 〈 50%) to identify the effectiveness of KDT. Results: The 12-month retention rate was 76%. The responders after 12 months of KDT were 59% (13/22). The free carnitine level decreased significantly at 9th months (p 〈 0.001) but increased toward baseline without symptoms. Propionyl carnitine (C3), Isovaleryl carnitine (C5), 3-Hydroxyisovalerylcarnitine (C5:OH) and methylmalonyl carnitine (C4-DC) decreased but 3-hydroxybutyrylcarnitine (C4:OH) increased significantly at 12th months of KDT. The glycine level was persistently higher than baseline after KDT. KDT responders had lower baseline C3 and long-chain acylcarnitines, C14 and C18, as well as lower C5, C18, and leucine/isoleucine. Conclusions: KDT should be avoided in patients with non-ketotic hyperglycemia. Routine carnitine supplementation is not recommended because hypocarnitinemia was transient and asymptomatic during KDT. Better mitochondrial βoxidation function associates with greater KDT response.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu13010021
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2518386-2
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  • 9
    Online Resource
    Online Resource
    Inhibition of Neddylation Suppresses Osteoclast Differentiation and Function In Vitro and Alleviates Osteoporosis In Vivo
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 10 ( 2022-09-21), p. 2355-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 10 ( 2022-09-21), p. 2355-
    Abstract: Neddylation, or the covalent addition of NEDD8 to specific lysine residue of proteins, is a reversible posttranslational modification, which regulates numerous biological functions; however, its involvement and therapeutic significance in osteoporosis remains unknown. Our results revealed that during the soluble receptor activator of nuclear factor-κB ligand (sRANKL)-stimulated osteoclast differentiation, the neddylation and expression of UBA3, the NEDD8-activating enzyme (NAE) catalytic subunit, were dose- and time-dependently upregulated in RAW 264.7 macrophages. UBA3 knockdown for diminishing NAE activity or administering low doses of the NAE inhibitor MLN4924 significantly suppressed sRANKL-stimulated osteoclast differentiation and bone-resorbing activity in the macrophages by inhibiting sRANKL-stimulated neddylation and tumor necrosis factor receptor-associated factor 6 (TRAF6)-activated transforming growth factor-β-activated kinase 1 (TAK1) downstream signaling for diminishing nuclear factor-activated T cells c1 (NFATc1) expression. sRANKL enhanced the interaction of TRAF6 with the neddylated proteins and the polyubiquitination of TRAF6’s lysine 63, which activated TAK1 downstream signaling; however, this process was inhibited by MLN4924. MLN4924 significantly reduced osteoporosis in an ovariectomy- and sRANKL-induced osteoporosis mouse model in vivo. Our novel finding was that NAE-mediated neddylation participates in RANKL-activated TRAF6–TAK1–NFATc1 signaling during osteoclast differentiation and osteoporosis, suggesting that neddylation may be a new target for treating osteoporosis.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10102355
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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  • 10
    Online Resource
    Online Resource
    Maternal Obesity Programs Offspring Development and Resveratrol Potentially Reprograms the Effects of Maternal Obesity
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 17, No. 5 ( 2020-03-02), p. 1610-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 5 ( 2020-03-02), p. 1610-
    Abstract: Maternal obesity during pregnancy is a now a public health burden that may be the culprit underlying the ever-increasing rates of adult obesity worldwide. Understanding the association between maternal obesity and adult offspring’s obesity would inform policy and practice regarding offspring health through available resources and interventions. This review first summarizes the programming effects of maternal obesity and discusses the possible underlying mechanisms. We then summarize the current evidence suggesting that maternal consumption of resveratrol is helpful in maternal obesity and alleviates its consequences. In conclusion, maternal obesity can program offspring development in an adverse way. Maternal resveratrol could be considered as a potential regimen in reprogramming adverse outcomes in the context of maternal obesity.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph17051610
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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