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Veličković M, Kadam L, Kim J, Zemaitis KJ, Veličković D, Gao Y, Wu R, Fillmore TL, Orton D, Williams SM, Monroe ME, Moore RJ, Piehowski PD, Bramer LM, Myatt L, Burnum-Johnson KE. Advanced multi-modal mass spectrometry imaging reveals functional differences of placental villous compartments at microscale resolution. Nat Commun 2025; 16:2061. [PMID: 40021619 PMCID: PMC11871073 DOI: 10.1038/s41467-025-57107-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 02/12/2025] [Indexed: 03/03/2025] Open
Abstract
The placenta is a complex and heterogeneous organ that links the mother and fetus, playing a crucial role in nourishing and protecting the fetus throughout pregnancy. Integrative spatial multi-omics approaches can provide a systems-level understanding of molecular changes underlying the mechanisms leading to the histological variations of the placenta during healthy pregnancy and pregnancy complications. Herein, we advance our metabolome-informed proteome imaging (MIPI) workflow to include lipidomic imaging, while also expanding the molecular coverage of metabolomic imaging by incorporating on-tissue chemical derivatization (OTCD). The improved MIPI workflow advances biomedical investigations by leveraging state-of-the-art molecular imaging technologies. Lipidome imaging identifies molecular differences between two morphologically distinct compartments of a placental villous functional unit, syncytiotrophoblast (STB) and villous core. Next, our advanced metabolome imaging maps villous functional units with enriched metabolomic activities related to steroid and lipid metabolism, outlining distinct molecular distributions across morphologically different villous compartments. Complementary proteome imaging on these villous functional units reveals a plethora of fatty acid- and steroid-related enzymes uniquely distributed in STB and villous core compartments. Integration across our advanced MIPI imaging modalities enables the reconstruction of active biological pathways of molecular synthesis and maternal-fetal signaling across morphologically distinct placental villous compartments with micrometer-scale resolution.
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Affiliation(s)
- Marija Veličković
- The Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Leena Kadam
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, USA
| | - Joonhoon Kim
- Energy and Environment Directorate, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Kevin J Zemaitis
- The Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Dušan Veličković
- The Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Yuqian Gao
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Ruonan Wu
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Thomas L Fillmore
- The Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Daniel Orton
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Sarah M Williams
- The Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Matthew E Monroe
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Ronald J Moore
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Paul D Piehowski
- The Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Lisa M Bramer
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
| | - Leslie Myatt
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, USA.
| | - Kristin E Burnum-Johnson
- The Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, USA.
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2
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Sriraam N, Chinta B, Suresh S, Sudharshan S. Ultrasound imaging based recognition of prenatal anomalies: a systematic clinical engineering review. PROGRESS IN BIOMEDICAL ENGINEERING (BRISTOL, ENGLAND) 2024; 6:023002. [PMID: 39655845 DOI: 10.1088/2516-1091/ad3a4b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 04/03/2024] [Indexed: 12/18/2024]
Abstract
For prenatal screening, ultrasound (US) imaging allows for real-time observation of developing fetal anatomy. Understanding normal and aberrant forms through extensive fetal structural assessment enables for early detection and intervention. However, the reliability of anomaly diagnosis varies depending on operator expertise and device limits. First trimester scans in conjunction with circulating biochemical markers are critical in identifying high-risk pregnancies, but they also pose technical challenges. Recent engineering advancements in automated diagnosis, such as artificial intelligence (AI)-based US image processing and multimodal data fusion, are developing to improve screening efficiency, accuracy, and consistency. Still, creating trust in these data-driven solutions is necessary for integration and acceptability in clinical settings. Transparency can be promoted by explainable AI (XAI) technologies that provide visual interpretations and illustrate the underlying diagnostic decision making process. An explanatory framework based on deep learning is suggested to construct charts depicting anomaly screening results from US video feeds. AI modelling can then be applied to these charts to connect defects with probable deformations. Overall, engineering approaches that increase imaging, automation, and interpretability hold enormous promise for altering traditional workflows and expanding diagnostic capabilities for better prenatal care.
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Affiliation(s)
- Natarajan Sriraam
- Center for Medical Electronics and Computing, Dept of Medical Electronics, Ramaiah Institute of Technology (RIT), Bangalore, India
| | - Babu Chinta
- Center for Medical Electronics and Computing, Dept of Medical Electronics, Ramaiah Institute of Technology (RIT), Bangalore, India
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Lubrano C, Parisi F, Cetin I. Impact of Maternal Environment and Inflammation on Fetal Neurodevelopment. Antioxidants (Basel) 2024; 13:453. [PMID: 38671901 PMCID: PMC11047368 DOI: 10.3390/antiox13040453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 03/29/2024] [Accepted: 04/02/2024] [Indexed: 04/28/2024] Open
Abstract
During intrauterine life, external stimuli including maternal nutrition, lifestyle, socioeconomic conditions, anxiety, stress, and air pollution can significantly impact fetal development. The human brain structures begin to form in the early weeks of gestation and continue to grow and mature throughout pregnancy. This review aims to assess, based on the latest research, the impact of environmental factors on fetal and neonatal brain development, showing that oxidative stress and inflammation are implied as a common factor for most of the stressors. Environmental insults can induce a maternal inflammatory state and modify nutrient supply to the fetus, possibly through epigenetic mechanisms, leading to significant consequences for brain morphogenesis and neurological outcomes. These risk factors are often synergic and mutually reinforcing. Fetal growth restriction and preterm birth represent paradigms of intrauterine reduced nutrient supply and inflammation, respectively. These mechanisms can lead to an increase in free radicals and, consequently, oxidative stress, with well-known adverse effects on the offspring's neurodevelopment. Therefore, a healthy intrauterine environment is a critical factor in supporting normal fetal brain development. Hence, healthcare professionals and clinicians should implement effective interventions to prevent and reduce modifiable risk factors associated with an increased inflammatory state and decreased nutrient supply during pregnancy.
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Affiliation(s)
- Chiara Lubrano
- Nutritional Sciences, Doctoral Programme (PhD), Università degli Studi di Milano, 20157 Milan, Italy;
- Department of Mother, Child and Neonate, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Francesca Parisi
- Department of Mother, Child and Neonate, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, 20157 Milan, Italy;
| | - Irene Cetin
- Department of Mother, Child and Neonate, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, 20157 Milan, Italy;
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Fan J, Yin M. Offspring of women with hyperemesis gravidarum are more likely to have cardiovascular abnormalities. BMC Pregnancy Childbirth 2024; 24:119. [PMID: 38331740 PMCID: PMC10854153 DOI: 10.1186/s12884-024-06293-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 01/26/2024] [Indexed: 02/10/2024] Open
Abstract
BACKGROUND Hyperemesis gravidarum (HG) is a severe form of pregnancy-related nausea and vomiting affecting 0.3-2.3% of pregnancies, which can lead to fluid, electrolyte, and acid-base imbalances, nutritional deficiencies, and weight loss, and is usually severe enough to require hospitalization. Abnormally elevated urinary ketones are commonly seen in patients with HG, and ketone bodies are free to pass through the placenta, and maternal hyperketonemia, with or without acidosis, is associated with an increased rate of stillbirth, an increased incidence of congenital anomalies, and impaired neurophysiologic development of the infant. This study investigates the obstetric outcomes of patients with HG and whether HG increases the incidence of cardiovascular disease in the offspring. METHODS This study included 1020 pregnant women who were hospitalized in our hospital for HG and ultimately delivered in our hospital as well as pregnant women without HG in early gestation and delivered in our hospital from January 2019-January 2020, and we collected and followed up the clinical information of the pregnant women and their offspring. RESULTS Pregnant women with HG were more likely to have severe urinary ketones, the rate of early miscarriage and mid-term miscarriage was significantly higher in women with HG compared to pregnant women without HG. Fetal and neonatal head and abdominal circumferences were smaller in HG group than in control group. Neonatal birth weight and length were also lower in the HG group and cardiovascular anomalies were more likely to occur in the offspring of women with HG when all births were followed up for 3 years. CONCLUSIONS HG may cause poor obstetric outcomes and was associated with the development of cardiovascular disease in the offspring of women with HG.
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Affiliation(s)
- Jiao Fan
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Minghong Yin
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
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5
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Firman CH, Mellor DD, Unwin D, Brown A. Does a Ketogenic Diet Have a Place Within Diabetes Clinical Practice? Review of Current Evidence and Controversies. Diabetes Ther 2024; 15:77-97. [PMID: 37966583 PMCID: PMC10786817 DOI: 10.1007/s13300-023-01492-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 10/10/2023] [Indexed: 11/16/2023] Open
Abstract
Carbohydrate restriction has gained increasing popularity as an adjunctive nutritional therapy for diabetes management. However, controversy remains regarding the long-term suitability, safety, efficacy and potential superiority of a very low carbohydrate, ketogenic diet compared to current recommended nutritional approaches for diabetes management. Recommendations with respect to a ketogenic diet in clinical practice are often hindered by the lack of established definition, which prevents its capacity to be most appropriately prescribed as a therapeutic option for diabetes. Furthermore, with conflicted evidence, this has led to uncertainty amongst clinicians on how best to support and advise their patients. This review will explore whether a ketogenic diet has a place within clinical practice by reviewing current evidence and controversies.
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Affiliation(s)
- Chloe H Firman
- Centre for Obesity Research, University College London, London, UK
| | - Duane D Mellor
- Aston Medical School, Aston University, Birmingham, UK
- Centre for Health and Society, Aston University, Birmingham, UK
| | - David Unwin
- Edge Hill Medical School, Edge Hill, Ormskirk, UK
- Norwood Avenue Surgery, Southport, UK
- NNEdPro Global Institute for Food, Nutrition and Health, Cambridge, UK
| | - Adrian Brown
- Centre for Obesity Research, University College London, London, UK.
- National Institute of Health Research, London, UK.
- Bariatric Centre for Weight Management and Metabolic Surgery, University College London Hospital NHS Trust, London, UK.
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Peshevska-Sekulovska M, Gulinac M, Rangelov R, Docheva D, Velikova T, Sekulovski M. Navigating the Challenges of Gluten Enteropathy and Infertility: The Role of Celiac-Related Antibodies and Dietary Changes. Antibodies (Basel) 2023; 12:79. [PMID: 38131801 PMCID: PMC10741221 DOI: 10.3390/antib12040079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 11/09/2023] [Accepted: 11/28/2023] [Indexed: 12/23/2023] Open
Abstract
Celiac disease (CD) is an autoimmune condition that is initiated in genetically susceptible individuals by the exposure of the intestines to gluten, and the early start of symptoms is related to malabsorption. Atypical variants of the illness are often identified in adulthood and are frequently associated with manifestations outside of the intestines, including metabolic osteopathy, anemia, and dermatitis herpetiformis. But also, empirical data suggest a correlation between CD and reproductive abnormalities, including repeated abortions. Infertility and repeated miscarriages frequently manifest in women diagnosed with CD and may serve as the initial clinical indication of a subclinical form. Furthermore, the condition may manifest as amenorrhea, infertility, and the delivery of infants with a low birth weight. Regarding the mechanisms of CD in infertility, along with the anti-tTG action to hinder the invasiveness of trophoblast, these antibodies could damage endometrial angiogenesis, which has been shown in in vitro models with human endometrial cells and in vivo in murine models. Another important aspect is the role of nutrient deficiencies, such as zinc deficiency (connected to impaired hormone production, secondary amenorrhea, and pre-eclampsia) and folic acid, etc. Therefore, our objective was to conduct a comprehensive review of the existing literature pertaining to this specific topic and to elucidate the role of the autoantibodies in its pathogenesis.
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Affiliation(s)
- Monika Peshevska-Sekulovska
- Medical Faculty, Sofia University St. Kliment Ohridski, Kozyak 1 Str., 1407 Sofia, Bulgaria; (M.P.-S.); (T.V.)
- Department of Gastroenterology, University Hospital Lozenetz, 1407 Sofia, Bulgaria
| | - Milena Gulinac
- Department of General and Clinical Pathology, Medical University of Plovdiv, 15A Vasil Aprilov Bul. 4000 Plovdiv, Bulgaria;
| | - Radoslav Rangelov
- Medical Center Neovitro OOD, 20 Petko Yu. Todorov Bul., 1408 Sofia, Bulgaria; (R.R.); (D.D.)
| | - Desislava Docheva
- Medical Center Neovitro OOD, 20 Petko Yu. Todorov Bul., 1408 Sofia, Bulgaria; (R.R.); (D.D.)
| | - Tsvetelina Velikova
- Medical Faculty, Sofia University St. Kliment Ohridski, Kozyak 1 Str., 1407 Sofia, Bulgaria; (M.P.-S.); (T.V.)
| | - Metodija Sekulovski
- Medical Faculty, Sofia University St. Kliment Ohridski, Kozyak 1 Str., 1407 Sofia, Bulgaria; (M.P.-S.); (T.V.)
- Medical Center Neovitro OOD, 20 Petko Yu. Todorov Bul., 1408 Sofia, Bulgaria; (R.R.); (D.D.)
- Department of Anesthesiology and Intensive Care, University Hospital Lozenetz, 1 Kozyak Str., 1407 Sofia, Bulgaria
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Cooper ID, Kyriakidou Y, Edwards K, Petagine L, Seyfried TN, Duraj T, Soto-Mota A, Scarborough A, Jacome SL, Brookler K, Borgognoni V, Novaes V, Al-Faour R, Elliott BT. Ketosis Suppression and Ageing (KetoSAge): The Effects of Suppressing Ketosis in Long Term Keto-Adapted Non-Athletic Females. Int J Mol Sci 2023; 24:15621. [PMID: 37958602 PMCID: PMC10650498 DOI: 10.3390/ijms242115621] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 10/16/2023] [Accepted: 10/23/2023] [Indexed: 11/15/2023] Open
Abstract
Most studies on ketosis have focused on short-term effects, male athletes, or weight loss. Hereby, we studied the effects of short-term ketosis suppression in healthy women on long-standing ketosis. Ten lean (BMI 20.5 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9) maintaining nutritional ketosis (NK) for > 1 year (3.9 years ± 2.3) underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). Adherence to each phase was confirmed with daily capillary D-beta-hydroxybutyrate (BHB) tests (P1 = 1.9 ± 0.7; P2 = 0.1 ± 0.1; and P3 = 1.9 ± 0.6 pmol/L). Ageing biomarkers and anthropometrics were evaluated at the end of each phase. Ketosis suppression significantly increased: insulin, 1.78-fold from 33.60 (± 8.63) to 59.80 (± 14.69) pmol/L (p = 0.0002); IGF1, 1.83-fold from 149.30 (± 32.96) to 273.40 (± 85.66) µg/L (p = 0.0045); glucose, 1.17-fold from 78.6 (± 9.5) to 92.2 (± 10.6) mg/dL (p = 0.0088); respiratory quotient (RQ), 1.09-fold 0.66 (± 0.05) to 0.72 (± 0.06; p = 0.0427); and PAI-1, 13.34 (± 6.85) to 16.69 (± 6.26) ng/mL (p = 0.0428). VEGF, EGF, and monocyte chemotactic protein also significantly increased, indicating a pro-inflammatory shift. Sustained ketosis showed no adverse health effects, and may mitigate hyperinsulinemia without impairing metabolic flexibility in metabolically healthy women.
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Affiliation(s)
- Isabella D. Cooper
- Ageing Biology and Age-Related Diseases, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK; (Y.K.); (L.P.); (A.S.); (S.L.J.); (V.B.); (V.N.); (R.A.-F.); (B.T.E.)
| | - Yvoni Kyriakidou
- Ageing Biology and Age-Related Diseases, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK; (Y.K.); (L.P.); (A.S.); (S.L.J.); (V.B.); (V.N.); (R.A.-F.); (B.T.E.)
| | - Kurtis Edwards
- Cancer Biomarkers and Mechanisms Group, School of Life Sciences, University of Westminster, London W1W 6UW, UK;
| | - Lucy Petagine
- Ageing Biology and Age-Related Diseases, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK; (Y.K.); (L.P.); (A.S.); (S.L.J.); (V.B.); (V.N.); (R.A.-F.); (B.T.E.)
| | - Thomas N. Seyfried
- Biology Department, Boston College, Chestnut Hill, MA 02467, USA; (T.N.S.); (T.D.)
| | - Tomas Duraj
- Biology Department, Boston College, Chestnut Hill, MA 02467, USA; (T.N.S.); (T.D.)
| | - Adrian Soto-Mota
- Metabolic Diseases Research Unit, National Institute of Medical Sciences and Nutrition Salvador Zubiran, Mexico City 14080, Mexico;
- Tecnologico de Monterrey, School of Medicine, Mexico City 14380, Mexico
| | - Andrew Scarborough
- Ageing Biology and Age-Related Diseases, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK; (Y.K.); (L.P.); (A.S.); (S.L.J.); (V.B.); (V.N.); (R.A.-F.); (B.T.E.)
| | - Sandra L. Jacome
- Ageing Biology and Age-Related Diseases, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK; (Y.K.); (L.P.); (A.S.); (S.L.J.); (V.B.); (V.N.); (R.A.-F.); (B.T.E.)
| | - Kenneth Brookler
- Retired former Research Collaborator, Aerospace Medicine and Vestibular Research Laboratory, Mayo Clinic, Scottsdale, AZ 85259, USA;
| | - Valentina Borgognoni
- Ageing Biology and Age-Related Diseases, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK; (Y.K.); (L.P.); (A.S.); (S.L.J.); (V.B.); (V.N.); (R.A.-F.); (B.T.E.)
| | - Vanusa Novaes
- Ageing Biology and Age-Related Diseases, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK; (Y.K.); (L.P.); (A.S.); (S.L.J.); (V.B.); (V.N.); (R.A.-F.); (B.T.E.)
| | - Rima Al-Faour
- Ageing Biology and Age-Related Diseases, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK; (Y.K.); (L.P.); (A.S.); (S.L.J.); (V.B.); (V.N.); (R.A.-F.); (B.T.E.)
| | - Bradley T. Elliott
- Ageing Biology and Age-Related Diseases, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK; (Y.K.); (L.P.); (A.S.); (S.L.J.); (V.B.); (V.N.); (R.A.-F.); (B.T.E.)
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Veneti S, Grammatikopoulou MG, Kintiraki E, Mintziori G, Goulis DG. Ketone Bodies in Diabetes Mellitus: Friend or Foe? Nutrients 2023; 15:4383. [PMID: 37892458 PMCID: PMC10609881 DOI: 10.3390/nu15204383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 10/12/2023] [Accepted: 10/14/2023] [Indexed: 10/29/2023] Open
Abstract
In glucose-deprived conditions, ketone bodies are produced by the liver mitochondria, through the catabolism of fatty acids, and are used peripherally, as an alternative energy source. Ketones are produced in the body under normal conditions, including during pregnancy and the neonatal period, when following a ketogenic diet (KD), fasting, or exercising. Additionally, ketone synthesis is also augmented under pathological conditions, including cases of diabetic ketoacidosis (DKA), alcoholism, and several metabolic disorders. Nonetheless, diet is the main regulator of total body ketone concentrations. The KDs are mimicking the fasting state, altering the default metabolism towards the use of ketones as the primary fuel source. Recently, KD has gained recognition as a medical nutrition therapy for a plethora of metabolic conditions, including obesity and diabetes mellitus (DM). The present review aims to discuss the role of ketones, KDs, ketonemia, and ketonuria in DM, presenting all the available new evidence in a comprehensive manner.
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Affiliation(s)
- Stavroula Veneti
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
| | - Maria G. Grammatikopoulou
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
- Unit of Immunonutrition and Clinical Nutrition, Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, GR-41110 Larissa, Greece
| | - Evangelia Kintiraki
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
| | - Gesthimani Mintziori
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
| | - Dimitrios G. Goulis
- Unit of Reproductive Endocrinology, 1st Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; (S.V.); (E.K.)
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Guevara-Ramírez P, Paz-Cruz E, Cadena-Ullauri S, Ruiz-Pozo VA, Tamayo-Trujillo R, Felix ML, Simancas-Racines D, Zambrano AK. Molecular pathways and nutrigenomic review of insulin resistance development in gestational diabetes mellitus. Front Nutr 2023; 10:1228703. [PMID: 37799768 PMCID: PMC10548225 DOI: 10.3389/fnut.2023.1228703] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 09/01/2023] [Indexed: 10/07/2023] Open
Abstract
Gestational diabetes mellitus is a condition marked by raised blood sugar levels and insulin resistance that usually occurs during the second or third trimester of pregnancy. According to the World Health Organization, hyperglycemia affects 16.9% of pregnancies worldwide. Dietary changes are the primarily alternative treatment for gestational diabetes mellitus. This paper aims to perform an exhaustive overview of the interaction between diet, gene expression, and the metabolic pathways related to insulin resistance. The intake of foods rich in carbohydrates can influence the gene expression of glycolysis, as well as foods rich in fat, can disrupt the beta-oxidation and ketogenesis pathways. Furthermore, vitamins and minerals are related to inflammatory processes regulated by the TLR4/NF-κB and one carbon metabolic pathways. We indicate that diet regulated gene expression of PPARα, NOS, CREB3L3, IRS, and CPT I, altering cellular physiological mechanisms and thus increasing or decreasing the risk of gestational diabetes. The alteration of gene expression can cause inflammation, inhibition of fatty acid transport, or on the contrary help in the modulation of ketogenesis, improve insulin sensitivity, attenuate the effects of glucotoxicity, and others. Therefore, it is critical to comprehend the metabolic changes of pregnant women with gestational diabetes mellitus, to determine nutrients that help in the prevention and treatment of insulin resistance and its long-term consequences.
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Affiliation(s)
- Patricia Guevara-Ramírez
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genética y Genómica, Universidad UTE, Quito, Ecuador
| | - Elius Paz-Cruz
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genética y Genómica, Universidad UTE, Quito, Ecuador
| | - Santiago Cadena-Ullauri
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genética y Genómica, Universidad UTE, Quito, Ecuador
| | - Viviana A. Ruiz-Pozo
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genética y Genómica, Universidad UTE, Quito, Ecuador
| | - Rafael Tamayo-Trujillo
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genética y Genómica, Universidad UTE, Quito, Ecuador
| | - Maria L. Felix
- Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, Quito, Ecuador
| | - Daniel Simancas-Racines
- Centro de Investigación de Salud Pública y Epidemiología Clínica (CISPEC), Universidad UTE, Quito, Ecuador
| | - Ana Karina Zambrano
- Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genética y Genómica, Universidad UTE, Quito, Ecuador
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10
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Management of Diabetic Ketoacidosis in Pregnancy. Clin Obstet Gynecol 2023; 66:186-195. [PMID: 36657054 DOI: 10.1097/grf.0000000000000758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Diabetic ketoacidosis (DKA) is a rare, but potentially life-threatening complication of diabetes. Certain physiological changes during pregnancy predispose pregnant individuals to developing DKA. Early recognition and aggressive treatment are essential to avoid maternal and fetal morbidity and mortality. Although laboratory values can help to support, pregnant patients with DKA may not meet the usual criteria and the diagnosis can be made clinically. The key components to treatment include volume replacement, insulin infusion, correction of serum potassium, and fetal monitoring. With appropriate treatment, maternal mortality is low. After recovery, steps should be taken to avoid recurrence.
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11
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Noshiro K, Umazume T, Hattori R, Kataoka S, Yamada T, Watari H. Changes in Serum Levels of Ketone Bodies and Human Chorionic Gonadotropin during Pregnancy in Relation to the Neonatal Body Shape: A Retrospective Analysis. Nutrients 2022; 14:nu14091971. [PMID: 35565938 PMCID: PMC9099686 DOI: 10.3390/nu14091971] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 05/02/2022] [Accepted: 05/05/2022] [Indexed: 12/10/2022] Open
Abstract
Among the physiological changes occurring during pregnancy, the benefits of morning sickness, which is likely mediated by human chorionic gonadotropin (HCG) and induces serum ketone production, are unclear. We investigated the relationship between serum levels of ketone bodies and HCG in the first, second, and third trimesters and neonatal body shape (i.e., birth weight, length, head circumference, and chest circumference) in 245 pregnant women. Serum levels of 3-hydroxybutyric acid peaked in late-stage compared with early stage pregnancy (27.8 [5.0−821] vs. 42.2 [5.0−1420] μmol/L, median [range], p < 0.001). However, serum levels of ketone bodies and HCG did not correlate with neonatal body shape. When weight loss during pregnancy was used as an index of morning sickness, a higher pre-pregnancy body mass index was associated with greater weight loss. This study is the first to show that serum ketone body levels are maximal in the third trimester of pregnancy. As the elevation of serum ketone bodies in the third trimester is a physiological change, high serum levels of ketone bodies may be beneficial for mothers and children. One of the possible biological benefits of morning sickness is the prevention of diseases that have an increased incidence due to weight gain during pregnancy.
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Affiliation(s)
- Kiwamu Noshiro
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (K.N.); (H.W.)
| | - Takeshi Umazume
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (K.N.); (H.W.)
- Correspondence: ; Tel.: +81-11-706-5941
| | - Rifumi Hattori
- Department of Obstetrics and Gynecology, Obihiro-Kosei General Hospital, Obihiro 080-0024, Japan;
| | - Soromon Kataoka
- Department of Obstetrics and Gynecology, Hakodate Central General Hospital, Hakodate 040-8585, Japan;
| | - Takashi Yamada
- Department of Obstetrics and Gynecology, Japan Community Health Care Organization Hokkaido Hospital, Sapporo 062-8618, Japan;
| | - Hidemichi Watari
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan; (K.N.); (H.W.)
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12
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Maternal and Fetal Metabolites in Gestational Diabetes Mellitus: A Narrative Review. Metabolites 2022; 12:metabo12050383. [PMID: 35629887 PMCID: PMC9143359 DOI: 10.3390/metabo12050383] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 04/11/2022] [Accepted: 04/20/2022] [Indexed: 02/05/2023] Open
Abstract
Gestational diabetes mellitus (GDM) is a major public health issue of our century due to its increasing prevalence, affecting 5% to 20% of all pregnancies. The pathogenesis of GDM has not been completely elucidated to date. Increasing evidence suggests the association of environmental factors with genetic and epigenetic factors in the development of GDM. So far, several metabolomics studies have investigated metabolic disruptions associated with GDM. The aim of this review is to highlight the usefulness of maternal metabolites as diagnosis markers of GDM as well as the importance of both maternal and fetal metabolites as prognosis biomarkers for GDM and GDM’s transition to type 2 diabetes mellitus T2DM.
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13
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Mosher LT, Seabrook JA, Twynstra J. Identifiable Dietary Patterns of Pregnant Women: A Canadian Sample. CAN J DIET PRACT RES 2022; 83:104-111. [PMID: 35014558 DOI: 10.3148/cjdpr-2021-040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Purpose: To estimate the percentage of a sample of pregnant women in Canada following a vegetarian, vegan, low-carbohydrate, gluten-free, Mediterranean, or well-balanced diet, before and during pregnancy and to explore if pregnant women received and were satisfied with nutrition information received from health care providers (HCPs).Methods: Participants were conveniently sampled through Facebook and Twitter. An online survey collected data on sociodemographic characteristics, maternal diet, and whether women received and were satisfied with nutrition information from their HCPs. The McNemar test assessed changes in the proportion of diets followed before and during pregnancy.Results: Of 226 women, most followed a well-balanced diet before (76.9%) and during (72.9%) pregnancy (p = 0.26). Vegetarian, gluten-free, vegan, and low-carbohydrate diets were the least followed diets before and during pregnancy (vegetarian: 7.6% vs 5.3%; gluten-free: 4.9% vs 4.0%; vegan: 2.7% vs 2.2%; low-carbohydrate:4.0% vs 0.4%). Overall, the number of women following restrictive diets before pregnancy was significantly reduced throughout pregnancy (19.1% vs 12.0%, p < 0.001). Only 52.0% of women received nutrition information from their primary HCP, and 35.6% were satisfied with the nutrition information received.Conclusions: Most women followed a well-balanced diet before and during pregnancy and approximately one-third were satisfied with the information received from HCPs.
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Affiliation(s)
- Lydia Tegwyn Mosher
- School of Food and Nutritional Sciences, Brescia University College, London, ON
| | - Jamie A Seabrook
- School of Food and Nutritional Sciences, Brescia University College, London, ON.,Department of Paediatrics, Western University, London, ON.,Department of Epidemiology and Biostatistics, Western University, London, ON.,Children's Health Research Institute, London, ON.,Lawson Health Research Institute, London, ON.,Human Environments Analysis Laboratory, Western University, London, ON
| | - Jasna Twynstra
- School of Food and Nutritional Sciences, Brescia University College, London, ON.,Department of Medical Biophysics, Western University, London, ON
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14
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Raczkowska BA, Mojsak P, Rojo D, Telejko B, Paczkowska-Abdulsalam M, Hryniewicka J, Zielinska-Maciulewska A, Szelachowska M, Gorska M, Barbas C, Kretowski A, Ciborowski M. Gas Chromatography-Mass Spectroscopy-Based Metabolomics Analysis Reveals Potential Biochemical Markers for Diagnosis of Gestational Diabetes Mellitus. Front Pharmacol 2021; 12:770240. [PMID: 34867398 PMCID: PMC8640240 DOI: 10.3389/fphar.2021.770240] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 10/28/2021] [Indexed: 12/14/2022] Open
Abstract
Due to many adverse effects of gestational diabetes mellitus (GDM) on the mother and fetus, its diagnosis is crucial. The presence of GDM can be confirmed by an abnormal fasting plasma glucose level (aFPG) and/or oral glucose tolerance test (OGTT) performed mostly between 24 and 28 gestational week. Both aFPG and abnormal glucose tolerance (aGT) are used to diagnose GDM. In comparison to measurement of FPG, OGTT is time-consuming, usually inconvenient for the patient, and very often needs to be repeated. Therefore, it is necessary to seek tests that will be helpful and convenient to diagnose GDM. For this reason, we investigated the differences in fasting serum metabolites between GDM women with abnGM and normal FPG (aGT-GDM group), with aFPG and normal glucose metabolism (aFPG-GDM group) as well as pregnant women with normal glucose tolerance (NGT) being a control group. Serum metabolites were measured by an untargeted approach using gas chromatography–mass spectrometry (GC–MS). In the discovery phase, fasting serum samples collected from 79 pregnant women (aFPG-GDM, n = 24; aGT-GDM, n = 26; NGT, n = 29) between 24 and 28 weeks of gestation (gwk) were fingerprinted. A set of metabolites (α–hydroxybutyric acid (α–HB), β–hydroxybutyric acid (β–HB), and several fatty acids) significant in aGT-GDM vs NGT but not significant in aFPG-GDM vs NGT comparison in the discovery phase was selected for validation. These metabolites were quantified by a targeted GC–MS method in a validation cohort consisted of 163 pregnant women (aFPG-GDM, n = 51; aGT-GDM, n = 44; and NGT, n = 68). Targeted analyses were also performed on the serum collected from 92 healthy women in the first trimester (8–14 gwk) who were NGT at this time, but in the second trimester (24–28 gwk) they were diagnosed with GDM. It was found that α–HB, β–HB, and several fatty acids were associated with aGT-GDM. A combination of α–HB, β–HB, and myristic acid was found highly specific and sensitive for the diagnosis of GDM manifested by aGT-GDM (AUC = 0.828) or to select women at a risk of aGT-GDM in the first trimester (AUC = 0.791). Our findings provide new potential markers of GDM and may have implications for its early diagnosis.
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Affiliation(s)
- Beata A Raczkowska
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - Patrycja Mojsak
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
| | - David Rojo
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe, Madrid, Spain
| | - Beata Telejko
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | | | - Justyna Hryniewicka
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Anna Zielinska-Maciulewska
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Malgorzata Szelachowska
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Maria Gorska
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Coral Barbas
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe, Madrid, Spain
| | - Adam Kretowski
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.,Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
| | - Michal Ciborowski
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
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15
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Wang QY, You LH, Xiang LL, Zhu YT, Zeng Y. Current progress in metabolomics of gestational diabetes mellitus. World J Diabetes 2021; 12:1164-1186. [PMID: 34512885 PMCID: PMC8394228 DOI: 10.4239/wjd.v12.i8.1164] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 05/20/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders of pregnancy and can cause short- and long-term adverse effects in both pregnant women and their offspring. However, the etiology and pathogenesis of GDM are still unclear. As a metabolic disease, GDM is well suited to metabolomics study, which can monitor the changes in small molecular metabolites induced by maternal stimuli or perturbations in real time. The application of metabolomics in GDM can be used to discover diagnostic biomarkers, evaluate the prognosis of the disease, guide the application of diet or drugs, evaluate the curative effect, and explore the mechanism. This review provides comprehensive documentation of metabolomics research methods and techniques as well as the current progress in GDM research. We anticipate that the review will contribute to identifying gaps in the current knowledge or metabolomics technology, provide evidence-based information, and inform future research directions in GDM.
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Affiliation(s)
- Qian-Yi Wang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 21000, Jiangsu Province, China
| | - Liang-Hui You
- Nanjing Maternity and Child Health Care Institute, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 21000, Jiangsu Province, China
| | - Lan-Lan Xiang
- Department of Clinical Laboratory, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 21000, Jiangsu Province, China
| | - Yi-Tian Zhu
- Department of Clinical Laboratory, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 21000, Jiangsu Province, China
| | - Yu Zeng
- Department of Clinical Laboratory, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 21000, Jiangsu Province, China
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16
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Dini S, Zakeri M, Ebrahimpour S, Dehghanian F, Esmaeili A. Quercetin‑conjugated superparamagnetic iron oxide nanoparticles modulate glucose metabolism-related genes and miR-29 family in the hippocampus of diabetic rats. Sci Rep 2021; 11:8618. [PMID: 33883592 PMCID: PMC8060416 DOI: 10.1038/s41598-021-87687-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Accepted: 03/25/2021] [Indexed: 02/02/2023] Open
Abstract
Quercetin (QC) is a dietary bioflavonoid that can be conjugated with nanoparticles to facilitate its brain bioavailability. We previously showed that quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) reduced the level of blood glucose in diabetic rats. Glucose transporters (GLUTs), insulin-like growth factor-1 (IGF-1), and microRNA-29 (miR-29) play a critical role in brain glucose homeostasis. In the current study, we examined the effects of QCSPION on the expression of glucose metabolism-related genes, and the miR-29 family as a candidate regulator of glucose handling in the hippocampus of diabetic rats. Our in silico analyses introduce the miR-29 family as potential regulators of glucose transporters and IGF-1 genes. The expression level of the miR-29 family, IGF-1, GLUT1, GLUT2, GLUT3, and GLUT4 were measured by qPCR. Our results indicate that diabetes significantly results in upregulation of the miR-29 family and downregulation of the GLUT1, 2, 3, 4, and IGF-1 genes. Interestingly, QCSPIONs reduced miR-29 family expression and subsequently enhanced GLUT1, 2, 3, 4, and IGF-1expression. In conclusion, our findings suggest that QCSPION could regulate the expression of the miR-29 family, which in turn increases the expression of glucose transporters and IGF-1, thereby reducing diabetic complications.
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Affiliation(s)
- Solmaz Dini
- grid.411750.60000 0001 0454 365XDepartment of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Mansoureh Zakeri
- grid.411750.60000 0001 0454 365XDepartment of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Shiva Ebrahimpour
- grid.411750.60000 0001 0454 365XDepartment of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Fariba Dehghanian
- grid.411750.60000 0001 0454 365XDepartment of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Abolghasem Esmaeili
- grid.411750.60000 0001 0454 365XDepartment of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
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17
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Insights into intrauterine growth restriction based on maternal and umbilical cord blood metabolomics. Sci Rep 2021; 11:7824. [PMID: 33837233 PMCID: PMC8035183 DOI: 10.1038/s41598-021-87323-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 03/26/2021] [Indexed: 11/08/2022] Open
Abstract
Intrauterine growth restriction (IUGR) is a fetal adverse condition, ascribed by limited oxygen and nutrient supply from the mother to the fetus. Management of IUGR is an ongoing challenge because of its connection with increased fetal mortality, preterm delivery and postnatal pathologies. Untargeted nuclear magnetic resonance (1H NMR) metabolomics was applied in 84 umbilical cord blood and maternal blood samples obtained from 48 IUGR and 36 appropriate for gestational age (AGA) deliveries. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) followed by pathway and enrichment analysis generated classification models and revealed significant metabolites that were associated with altered pathways. A clear association between maternal and cord blood altered metabolomic profile was evidenced in IUGR pregnancies. Increased levels of the amino acids alanine, leucine, valine, isoleucine and phenylalanine were prominent in IUGR pregnancies indicating a connection with impaired amino acid metabolism and transplacental flux. Tryptophan was individually connected with cord blood discrimination while 3-hydroxybutyrate assisted only maternal blood discrimination. Lower glycerol levels in IUGR samples ascribed to imbalance between gluconeogenesis and glycolysis pathways, suggesting poor glycolysis. The elevated levels of branched chain amino acids (leucine, isoleucine and valine) in intrauterine growth restricted pregnancies were linked with increased insulin resistance.
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18
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Bordeleau M, Fernández de Cossío L, Chakravarty MM, Tremblay MÈ. From Maternal Diet to Neurodevelopmental Disorders: A Story of Neuroinflammation. Front Cell Neurosci 2021; 14:612705. [PMID: 33536875 PMCID: PMC7849357 DOI: 10.3389/fncel.2020.612705] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 12/07/2020] [Indexed: 12/13/2022] Open
Abstract
Providing the appropriate quantity and quality of food needed for both the mother's well-being and the healthy development of the offspring is crucial during pregnancy. However, the macro- and micronutrient intake also impacts the body's regulatory supersystems of the mother, such as the immune, endocrine, and nervous systems, which ultimately influence the overall development of the offspring. Of particular importance is the association between unhealthy maternal diet and neurodevelopmental disorders in the offspring. Epidemiological studies have linked neurodevelopmental disorders like autism spectrum disorders, attention-deficit-hyperactivity disorder, and schizophrenia, to maternal immune activation (MIA) during gestation. While the deleterious consequences of diet-induced MIA on offspring neurodevelopment are increasingly revealed, neuroinflammation is emerging as a key underlying mechanism. In this review, we compile the evidence available on how the mother and offspring are both impacted by maternal dietary imbalance. We specifically explore the various inflammatory and anti-inflammatory effects of dietary components and discuss how changes in inflammatory status can prime the offspring brain development toward neurodevelopmental disorders. Lastly, we discuss research evidence on the mechanisms that sustain the relationship between maternal dietary imbalance and offspring brain development, involving altered neuroinflammatory status in the offspring, as well as genetic to cellular programming notably of microglia, and the evidence that the gut microbiome may act as a key mediator.
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Affiliation(s)
- Maude Bordeleau
- Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada
- Axe Neurosciences, Centre de Recherche du CHU de Québec-Université Laval, Québec, QC, Canada
| | | | - M. Mallar Chakravarty
- Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada
- Cerebral Imaging Centre, Douglas Mental Health University, McGill University, Montréal, QC, Canada
- Department of Psychiatry, McGill University, Montréal, QC, Canada
- Department of Biological and Biomedical Engineering, McGill University, Montréal, QC, Canada
| | - Marie-Ève Tremblay
- Axe Neurosciences, Centre de Recherche du CHU de Québec-Université Laval, Québec, QC, Canada
- Département de Médecine Moléculaire, Université Laval, Québec, QC, Canada
- Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada
- Division of Medical Sciences, University of Victoria, Victoria, BC, Canada
- Biochemistry and Molecular Biology, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada
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19
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Rudland VL, Price SAL, Hughes R, Barrett HL, Lagstrom J, Porter C, Britten FL, Glastras S, Fulcher I, Wein P, Simmons D, McIntyre HD, Callaway L. ADIPS 2020 guideline for pre-existing diabetes and pregnancy. Aust N Z J Obstet Gynaecol 2020; 60:E18-E52. [PMID: 33200400 DOI: 10.1111/ajo.13265] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 09/14/2020] [Indexed: 02/07/2023]
Abstract
This is the full version of the Australasian Diabetes in Pregnancy Society (ADIPS) 2020 guideline for pre-existing diabetes and pregnancy. The guideline encompasses the management of women with pre-existing type 1 diabetes and type 2 diabetes in relation to pregnancy, including preconception, antepartum, intrapartum and postpartum care. The management of women with monogenic diabetes or cystic fibrosis-related diabetes in relation to pregnancy is also discussed.
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Affiliation(s)
- Victoria L Rudland
- Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, New South Wales, Australia.,Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Sarah A L Price
- Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.,Department of Diabetes, Royal Women's Hospital, Melbourne, Victoria, Australia.,Mercy Hospital for Women, Melbourne, Victoria, Australia.,Faculty of Medicine, University of Melbourne, Melbourne, Victoria, Australia
| | - Ruth Hughes
- Department of Obstetrics and Gynaecology, University of Otago, Christchurch, New Zealand
| | - Helen L Barrett
- Department of Endocrinology, Mater Health, Brisbane, Queensland, Australia.,Mater Research, The University of Queensland, Brisbane, Queensland, Australia
| | - Janet Lagstrom
- Green St Specialists Wangaratta, Wangaratta, Victoria, Australia.,Denis Medical Yarrawonga, Yarrawonga, Victoria, Australia.,Corowa Medical Clinic, Corowa, New South Wales, Australia.,NCN Health, Numurkah, Victoria, Australia
| | - Cynthia Porter
- Geraldton Diabetes Clinic, Geraldton, Western Australia, Australia
| | - Fiona L Britten
- Department of Obstetric Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.,Mater Private Hospital and Mater Mother's Private Hospital, Brisbane, Queensland, Australia.,Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Sarah Glastras
- Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.,Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, Sydney, New South Wales, Australia
| | - Ian Fulcher
- Liverpool Hospital, Sydney, New South Wales, Australia
| | - Peter Wein
- Mercy Hospital for Women, Melbourne, Victoria, Australia.,Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia
| | - David Simmons
- Western Sydney University, Sydney, New South Wales, Australia.,Campbelltown Hospital, Sydney, New South Wales, Australia
| | - H David McIntyre
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Mater Health, Brisbane, Queensland, Australia
| | - Leonie Callaway
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Women's and Children's Services, Metro North Hospital and Health Service District, Brisbane, Queensland, Australia.,Women's and Newborn Services, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
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20
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Wood TR, Stubbs BJ, Juul SE. Exogenous Ketone Bodies as Promising Neuroprotective Agents for Developmental Brain Injury. Dev Neurosci 2019; 40:451-462. [PMID: 31085911 DOI: 10.1159/000499563] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Accepted: 03/12/2019] [Indexed: 11/19/2022] Open
Abstract
Ketone bodies are a promising area of neuroprotection research that may be ideally suited to the injured newborn. During normal development, the human infant is in significant ketosis for at least the first week of life. Ketone uptake and metabolism is upregulated in the both the fetus and neonate, with ketone bodies providing at least 10% of cerebral metabolic energy requirements, as well as being the preferred precursors for the synthesis of fatty acids and cholesterol. At the same time, ketone bodies have been shown to have multiple neuroprotective effects, including being anticonvulsant, decreasing oxidative stress and inflammation, and epigenetically upregulating the production of neurotrophic factors. While ketogenic diets and exogenous ketosis are largely being investigated in the setting of adult brain injury, the adaptation of the neonate to ketosis suggests that developmental brain injury may be the area most suited to the use of ketones for neuroprotection. Here, we describe the mechanisms by which ketone bodies exert their neuroprotective effects, and how these may translate to benefits within each of the phases of neonatal asphyxial brain injury.
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Affiliation(s)
- Thomas R Wood
- Division of Neonatology, Department of Pediatrics, University of Washington, Seattle, Washington, USA, .,Institute for Human and Machine Cognition, Pensacola, Florida, USA,
| | - Brianna J Stubbs
- HVMN Inc., San Francisco, California, USA.,Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
| | - Sandra E Juul
- Division of Neonatology, Department of Pediatrics, University of Washington, Seattle, Washington, USA
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21
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Huang SY, Yu B, He X, Chen Y. Intrapartum Results on Differing Degrees of Ketonuria in Nulliparous Women with Gestational Diabetes Mellitus during Spontaneous Labor. Int J Endocrinol 2019; 2019:7207012. [PMID: 31827509 PMCID: PMC6885219 DOI: 10.1155/2019/7207012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 09/26/2019] [Indexed: 12/21/2022] Open
Abstract
To compare intrapartum results associated with differing degrees of ketonuria in nulliparous women with gestational diabetes mellitus (GDM), we implemented a retrospective cohort study comparing clinical characteristics among differing degrees of ketonuria and the duration and distribution of ketonuria at different stages of labor. We also analyzed adverse maternal and neonatal outcomes for each group. A total of 570 GDM deliveries were included; of these, 238 had negative ketonuria (41.8%), 180 had moderate ketonuria (31.6%), and 152 had ketosis (26.6%). The proportion of patients with a family history of diabetes significantly increased as the degree of ketonuria increased (P < 0.001). Moreover, a significantly lower level of HOMA-IR (the insulin resistance index) was observed for the Negative group (P < 0.001). The triglyceride (TG) level was significantly higher in the Ketosis group (P < 0.001), and the total cholesterol (TC) levels significantly increased as the degree of ketonuria progressed (P < 0.001). There were also higher maternal blood sugar levels and a significantly higher proportion of oxytocin augmentation in ketonuria cases (P < 0.001). Over three-fourths of patients (75.6%) had a ketonuria duration of ≤2 hours in the Moderate group, 61.2% had a ketonuria duration of between 3 and 4 h in the Ketosis group, and most of the ketonuria cases resolved in the first stage of labor. As the degree of ketonuria progressed, we observed a significantly higher number of cases with fetal heart rate pattern III (FHR pattern III), meconium-stained amniotic fluid III (MSAF III), postpartum hemorrhages, prolonged labor, neonatal hypoglycemia, an umbilical cord arterial pH of <7.2, low Apgar scores, increased neonatal intensive care admissions, augmented forceps-assisted deliveries, and conversions to cesarean sections. The results showed that ketonuria is common during the intrapartum period and that the risk of adverse maternal and neonatal outcomes may increase when complicated with ketonuria.
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Affiliation(s)
- Shi-Yun Huang
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
| | - Bo Yu
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
| | - Xin He
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
| | - Yi Chen
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
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