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Mohammedsaeed W, Alharbi M. Biochemical Markers as Predictors of Health Outcomes in Autism Spectrum Disorder: A Comprehensive Systematic Review and Meta-analysis. J Mol Neurosci 2025; 75:17. [PMID: 39913064 DOI: 10.1007/s12031-024-02306-3] [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: 11/25/2024] [Accepted: 12/26/2024] [Indexed: 02/07/2025]
Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with an increasing prevalence worldwide, including in Saudi Arabia. Emerging evidence suggests that biochemical markers, such as oxidative stress indicators, neurotransmitter levels, and lipid profiles, play a significant role in ASD's pathology and may also elevate cardiovascular and metabolic risks in affected individuals. This systematic review and meta-analysis synthesize current findings on these biomarkers, with a particular focus on the Saudi population, to elucidate their relationship with ASD pathology and associated health outcomes. Following the PRISMA guidelines, data from 41 studies on oxidative stress markers, neurotransmitters, lipid profiles, and immune markers were analyzed. Searches were conducted across major databases, including PubMed, Scopus, Web of Science, and Embase, and effect sizes were calculated using standardized mean differences with a 95% confidence interval. To further interpret the data, bioinformatics tools such as Reactome, Panther, and STRING were employed to analyze biomarker pathways. The results highlight a significant association between elevated oxidative stress and mitochondrial dysfunction in individuals with ASD, with profound effects on gastrointestinal and mitochondrial health. These biochemical abnormalities disrupt synaptic plasticity and drive chronic neuroinflammation, which impairs neurodevelopmental processes, contributing to the pathology of ASD. The meta-analysis reveals minimal heterogeneity (I2 = 0.02%) and limited publication bias, supporting the reliability of these associations. The findings underscore the need for a multidisciplinary approach to ASD management in Saudi Arabia, emphasizing biomarker-based diagnostics and personalized treatment strategies. Future research directions include developing individualized diagnostic and therapeutic frameworks utilizing these biomarkers to enhance ASD-related health outcomes.
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Affiliation(s)
- Walaa Mohammedsaeed
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Science, Taibah University, Al-Madinah, Saudi Arabia.
| | - Mohammed Alharbi
- Department of Speech and Language Disorders, Faculty of Medical Rehabilitation Sciences, Taibah University, Al-Madinah, Saudi Arabia
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El-Ansary A, Alfawaz HA, Ben Bacha A, Al-Ayadhi L. Assessing the COX-2/PGE2 Ratio and Anti-Nucleosome Autoantibodies as Biomarkers of Autism Spectrum Disorders: Using Combined ROC Curves to Improve Diagnostic Values. Curr Issues Mol Biol 2024; 46:8699-8709. [PMID: 39194730 DOI: 10.3390/cimb46080513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 08/05/2024] [Accepted: 08/06/2024] [Indexed: 08/29/2024] Open
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by restricted and repetitive behaviors as well as difficulties with social interaction. Numerous studies have revealed aberrant lipid mediators and autoimmunity as a recognized etiological cause of ASD that is amenable to therapeutic intervention. In this study, the relationship between the relative cyclooxygenase-2/prostaglandin E2 ratio (COX-2/PGE2) as a lipid mediator marker and anti-nucleosome autoantibodies as an autoimmunity marker of ASD was investigated using multiple regression and combined receiver operating characteristic (ROC) curve analyses. The study also sought to identify the linear combination of these variables that optimizes the partial area under the ROC curves. There were forty ASD children and forty-two age- and gender-matched controls included in the current study. Using combined ROC curve analysis, a notable increase in the area under the curve was seen in the patient group, using the control group as a reference group. Additionally, it was reported that the combined markers had improved specificity and sensitivity. This study demonstrates how the predictive value of particular biomarkers associated with lipid metabolism and autoimmunity in children with ASD can be measured using a ROC curve analysis. This technique should help us better understand the etiological mechanism of ASD and how it may adversely affect cellular homeostasis, which is essential to maintaining healthy metabolic pathways. Early diagnosis and intervention may be facilitated by this knowledge.
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Affiliation(s)
- Afaf El-Ansary
- Autism Center, Lotus Holistic Alternative Medical Center, P.O. Box 110281, Abu Dhabi 23251, United Arab Emirates
| | - Hanan A Alfawaz
- Department of Food Science and Nutrition, College of Food & Agriculture Sciences, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia
| | - Abir Ben Bacha
- Department of Biochemistry, College of Science, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia
| | - Laila Al-Ayadhi
- Department of Physiology, Faculty of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Saudi Arabia
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Ferencova N, Visnovcova Z, Ondrejka I, Hrtanek I, Bujnakova I, Kovacova V, Macejova A, Tonhajzerova I. Peripheral Inflammatory Markers in Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder at Adolescent Age. Int J Mol Sci 2023; 24:11710. [PMID: 37511467 PMCID: PMC10380731 DOI: 10.3390/ijms241411710] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/03/2023] [Accepted: 07/18/2023] [Indexed: 07/30/2023] Open
Abstract
Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are associated with immune dysregulation. We aimed to estimate the pro- and anti-inflammatory activity/balance in ASD and ADHD patients at a little-studied adolescent age with respect to sex. We evaluated 20 ASD patients (5 girls, average age: 12.4 ± 1.9 y), 20 ADHD patients (5 girls, average age: 13.4 ± 1.8 y), and 20 age- and gender-matched controls (average age: 13.2 ± 1.9 y). The evaluated parameters included (1) white blood cells (WBCs), neutrophils, monocytes, lymphocytes, platelets, platelet distribution width (PDW), mean platelet volume, and derived ratios, as well as (2) cytokines-interferon-gamma, interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10, tumor necrosis factor-alpha (TNF-α), and derived profiles and ratios. ASD adolescents showed higher levels of WBC, monocytes, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10, macrophages (M)1 profile, and anti-inflammatory profile than the controls, with ASD males showing higher monocytes, IL-6 and IL-10, anti-inflammatory profile, and a lower T-helper (Th)1/Th2+T-regulatory cell ratio than control males. The ADHD adolescents showed higher levels of PDW, IL-1β and IL-6, TNF-α, M1 profile, proinflammatory profile, and pro-/anti-inflammatory ratio than the controls, with ADHD females showing a higher TNF-α and pro-/anti-inflammatory ratio than the control females and ADHD males showing higher levels of IL-1β and IL-6, TNF-α, and M1 profile than the control males. Immune dysregulation appeared to be different for both neurodevelopmental disorders in adolescence.
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Affiliation(s)
- Nikola Ferencova
- Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Zuzana Visnovcova
- Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
| | - Igor Ondrejka
- Psychiatric Clinic, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, University Hospital Martin, 03601 Martin, Slovakia
| | - Igor Hrtanek
- Psychiatric Clinic, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, University Hospital Martin, 03601 Martin, Slovakia
| | - Iveta Bujnakova
- Society to Help People with Autism (SPOSA-Turiec), 03601 Martin, Slovakia
| | - Veronika Kovacova
- Psychiatric Clinic, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, University Hospital Martin, 03601 Martin, Slovakia
| | - Andrea Macejova
- Psychiatric Clinic, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, University Hospital Martin, 03601 Martin, Slovakia
| | - Ingrid Tonhajzerova
- Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia
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Hassan WM, Al-Dbass A, Al-Ayadhi L, Bhat RS, El-Ansary A. Discriminant analysis and binary logistic regression enable more accurate prediction of autism spectrum disorder than principal component analysis. Sci Rep 2022; 12:3764. [PMID: 35260688 PMCID: PMC8904630 DOI: 10.1038/s41598-022-07829-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 01/31/2022] [Indexed: 12/04/2022] Open
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction and restricted, repetitive behavior. Multiple studies have suggested mitochondrial dysfunction, glutamate excitotoxicity, and impaired detoxification mechanism as accepted etiological mechanisms of ASD that can be targeted for therapeutic intervention. In the current study, blood samples were collected from 40 people with autism and 40 control participants after informed consent and full approval from the Institutional Review Board of King Saud University. Sodium (Na+), Potassium (K+), lactate dehydrogenase (LDH), glutathione-s-transferase (GST), and mitochondrial respiratory chain complex I (MRC1) were measured in plasma of both groups. Predictive models were established to discriminate individuals with ASD from controls. The predictive power of these five variables, individually and in combination, was compared using the area under a ROC curve (AUC). We compared the performance of principal component analysis (PCA), discriminant analysis (DA), and binary logistic regression (BLR) as ways to combine single variables and create the predictive models. K+ had the highest AUC (0.801) of any single variable, followed by GST, LDH, Na+, and MRC1, respectively. Combining the five variables resulted in higher AUCs than those obtained using single variables across all models. Both DA and BLR were superior to PCA and comparable to each other. In our study, the combination of Na+, K+, LDH, GST, and MRC1 showed the highest promise in discriminating individuals with autism from controls. These results provide a platform that can potentially be used to verify the efficacy of our models with a larger sample size or evaluate other biomarkers.
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Affiliation(s)
- Wail M Hassan
- Department of Biomedical Sciences, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA
| | - Abeer Al-Dbass
- Biochemistry Department, College of Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Laila Al-Ayadhi
- Department of Physiology, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia.,Autism Research and Treatment Center, Riyadh, Saudi Arabia
| | - Ramesa Shafi Bhat
- Biochemistry Department, College of Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Afaf El-Ansary
- Autism Research and Treatment Center, Riyadh, Saudi Arabia. .,Central Research Laboratory, Female Centre for Scientific and Medical Studies, King Saud University, Riyadh, Saudi Arabia.
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Zaheer J, Kim H, Ko IO, Jo EK, Choi EJ, Lee HJ, Shim I, Woo HJ, Choi J, Kim GH, Kim JS. Pre/post-natal exposure to microplastic as a potential risk factor for autism spectrum disorder. ENVIRONMENT INTERNATIONAL 2022; 161:107121. [PMID: 35134716 DOI: 10.1016/j.envint.2022.107121] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 01/04/2022] [Accepted: 01/26/2022] [Indexed: 06/14/2023]
Abstract
In common with the increase in environmental pollution in the past 10 years, there has also been a recent increase in the prevalence of autism spectrum disorder (ASD). In this regard, we hypothesized that exposure to microplastics is a potential risk factor for ASD. To evaluate the validity of this hypothesis, we initially examined the accumulation of polyethylene (PE) in the brains of mice and then assessed the behavioral effects using mouse models at different life stages, namely, prenatal, post-weaning, puberty, and adult models. Based on typical behavioral assessments of autistic traits in the model mice, we established that ASD-like traits were induced in mice after PE feeding. In addition, we examined the induction of ASD-like traits in response to microplastic exposure using positron emission tomography, magnetic resonance spectroscopy, quantitative real-time polymerase chain reaction, microarray, and microbiome analysis. We believe these findings provide evidence in microplastics as a potential risk factor for ASD.
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Affiliation(s)
- Javeria Zaheer
- Division of RI Application, Korea Institute Radiological and Medical Sciences, Seoul 01812, Republic of Korea; Radiological and Medico-Oncological Sciences, University of Science and Technology (UST), Seoul 01812, Republic of Korea
| | - Hyeongi Kim
- Division of RI Application, Korea Institute Radiological and Medical Sciences, Seoul 01812, Republic of Korea; Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea
| | - In Ok Ko
- Division of RI Application, Korea Institute Radiological and Medical Sciences, Seoul 01812, Republic of Korea
| | - Eun-Kyeong Jo
- School of Health & Environmental Science, College of Health Science, Korea University Seoul 02841, Republic of Korea
| | - Eui-Ju Choi
- Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea
| | - Hae-June Lee
- Division of Radiation Biomedical Research, Korea Institute Radiological and Medical Sciences, Seoul 01812, Republic of Korea
| | - Insop Shim
- Department of Physiology, College of Medicine, Kyung Hee University, Seoul 02453, Republic of Korea
| | - Hyun-Jeong Woo
- Department of Biomedical Engineering, School of Integrative Engineering, College of ICT Engineering, Chung-Ang University, Seoul 06974, Republic of Korea
| | - Jonghoon Choi
- Department of Biomedical Engineering, School of Integrative Engineering, College of ICT Engineering, Chung-Ang University, Seoul 06974, Republic of Korea
| | - Gun-Ha Kim
- Department of Pediatrics, Korea Cancer Center Hospital, Korea Institute Radiological and Medical Sciences, Seoul 01812, Republic of Korea
| | - Jin Su Kim
- Division of RI Application, Korea Institute Radiological and Medical Sciences, Seoul 01812, Republic of Korea; Radiological and Medico-Oncological Sciences, University of Science and Technology (UST), Seoul 01812, Republic of Korea.
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Al-hadlaq SM, Balto HA, Hassan WM, Marraiki NA, El-Ansary AK. Biomarkers of non-communicable chronic disease: an update on contemporary methods. PeerJ 2022; 10:e12977. [PMID: 35233297 PMCID: PMC8882335 DOI: 10.7717/peerj.12977] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 01/31/2022] [Indexed: 01/11/2023] Open
Abstract
Chronic diseases constitute a major global burden with significant impact on health systems, economies, and quality of life. Chronic diseases include a broad range of diseases that can be communicable or non-communicable. Chronic diseases are often associated with modifications of normal physiological levels of various analytes that are routinely measured in serum and other body fluids, as well as pathological findings, such as chronic inflammation, oxidative stress, and mitochondrial dysfunction. Identification of at-risk populations, early diagnosis, and prediction of prognosis play a major role in preventing or reducing the burden of chronic diseases. Biomarkers are tools that are used by health professionals to aid in the identification and management of chronic diseases. Biomarkers can be diagnostic, predictive, or prognostic. Several individual or grouped biomarkers have been used successfully in the diagnosis and prediction of certain chronic diseases, however, it is generally accepted that a more sophisticated approach to link and interpret various biomarkers involved in chronic disease is necessary to improve our current procedures. In order to ensure a comprehensive and unbiased coverage of the literature, first a primary frame of the manuscript (title, headings and subheadings) was drafted by the authors working on this paper. Second, based on the components drafted in the preliminary skeleton a comprehensive search of the literature was performed using the PubMed and Google Scholar search engines. Multiple keywords related to the topic were used. Out of screened papers, only 190 papers, which are the most relevant, and recent articles were selected to cover the topic in relation to etiological mechanisms of different chronic diseases, the most recently used biomarkers of chronic diseases and finally the advances in the applications of multivariate biomarkers of chronic diseases as statistical and clinically applied tool for the early diagnosis of chronic diseases was discussed. Recently, multivariate biomarkers analysis approach has been employed with promising prospect. A brief discussion of the multivariate approach for the early diagnosis of the most common chronic diseases was highlighted in this review. The use of diagnostic algorithms might show the way for novel criteria and enhanced diagnostic effectiveness inpatients with one or numerous non-communicable chronic diseases. The search for new relevant biomarkers for the better diagnosis of patients with non-communicable chronic diseases according to the risk of progression, sickness, and fatality is ongoing. It is important to determine whether the newly identified biomarkers are purely associations or real biomarkers of underlying pathophysiological processes. Use of multivariate analysis could be of great importance in this regard.
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Affiliation(s)
- Solaiman M. Al-hadlaq
- Department of Restorative Dental Sciences, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | - Hanan A. Balto
- Department of Restorative Dental Sciences, College of Dentistry, King Saud University, Riyadh, Saudi Arabia,Central Research Laboratory, Female Campus, King Saud University, Riyadh, Saudi Arabia
| | - Wail M. Hassan
- Department of Biomedical Sciences, University of Missouri-Kansas City School of Medicine, Kansas City, KS, United States of America
| | - Najat A. Marraiki
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Afaf K. El-Ansary
- Central Research Laboratory, Female Campus, King Saud University, Riyadh, Saudi Arabia
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Jenabi E, Bashirian S, Khazaei S, Farhadi Nasab A, Maleki A. The Association between Assisted Reproductive Technology and the Risk of Autism Spectrum Disorders among Offspring: A Meta-analysis. Curr Pediatr Rev 2022; 19:83-89. [PMID: 35410610 DOI: 10.2174/1573396318666220410231435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 01/21/2022] [Accepted: 02/02/2022] [Indexed: 02/02/2023]
Abstract
BACKGROUND This review aimed to determine the association between assisted reproductive technology (ART) and increased chances of having an autistic child. METHODS The Web of Science, PubMed, and Scopus databases were systematically searched for studies published until December 2020 with the restricted English language. The Newcastle-Ottawa Scale (NOS) for cohort and case-control studies has been used for the evaluation of quality in individual studies. We evaluated the heterogeneity among the studies using I-squared. Publication bias was assessed using the funnel plot and Egger's and Begg's tests. We presented results using odds ratio (OR) and relative ratio (RR) estimates with its 95% confidence intervals (CI) using a randomeffects model. RESULTS In total, 18 articles were included in the present study. The overall findings of the present meta-analysis show that the use of ART didn't associate with the risk of autism spectrum disorders (ASD) among offspring based on OR and RR (OR = 1.04, 95% CI: 0.88-1.21) and (RR = 1 .26, 95% CI: 0.96- 1 .55), respectively. We showed a significant association between ART and the risk of ASD in Asia than in the other regions without heterogeneity. CONCLUSION Our result showed that the risk of ASD was not increased in children born from ART. Possible interaction between ART and other regions with increased risk of ASD is important to point and future studies of this topic were recommended.
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Affiliation(s)
- Ensiyeh Jenabi
- Autism Spectrum Disorders Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Saeid Bashirian
- Social Determinants of Health Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Salman Khazaei
- Research Center for Health Sciences, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Abdollah Farhadi Nasab
- Psychiatry, Behavioral Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azam Maleki
- Social Determinants of Health Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
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El-Ansary A, Alhakbany M, Aldbass A, Qasem H, Al-Mazidi S, Bhat RS, Al-Ayadhi L. Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values. Lipids Health Dis 2021; 20:155. [PMID: 34742290 PMCID: PMC8571879 DOI: 10.1186/s12944-021-01578-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 10/12/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and restricted and repetitive behaviors. Neuroinflammation and abnormal lipid mediators have been identified in multiple investigations as an acknowledged etiological mechanism of ASD that can be targeted for therapeutic intervention. METHODS In this study, multiple regression and combined receiver operating characteristic (ROC) curve analyses were used to determine the relationship between the neuroinflammatory marker α-synuclein and lipid mediator markers related to inflammation induction, such as cyclooxygenase-2 and prostaglandin-EP2 receptors, in the etiology of ASD. Additionally, the study aimed to determine the linear combination that maximizes the partial area under ROC curves for a set of markers. Forty children with ASD and 40 age- and sex-matched controls were enrolled in the study. Using ELISA, the levels of α-synuclein, cyclo-oxygenase-2, and prostaglandin-EP2 receptors were measured in the plasma of both groups. Statistical analyses using ROC curves and multiple and logistic regression models were performed. RESULTS A remarkable increase in the area under the curve was observed using combined ROC curve analyses. Moreover, higher specificity and sensitivity of the combined markers were reported. CONCLUSIONS The present study indicates that measurement of the predictive value of selected biomarkers related to neuroinflammation and lipid metabolism in children with ASD using a ROC curve analysis should lead to a better understanding of the etiological mechanism of ASD and its link with metabolism. This information may facilitate early diagnosis and intervention.
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Affiliation(s)
- Afaf El-Ansary
- Central Laboratory, Female Center for Medical Studies and Scientific Section, King Saud University, P. O Box 22452, Riyadh, KSA, 11495, Saudi Arabia.
- Autism Research and Treatment Center, Riyadh, Saudi Arabia.
| | - Manan Alhakbany
- Department of Physiology, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Abeer Aldbass
- Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Hanan Qasem
- Department of Physiology, College of Medicine, Al-Imam Mohammed Bin Saud Islamic University, Riyadh, Saudi Arabia
| | - Sarah Al-Mazidi
- Department of Physiology, College of Medicine, Al-Imam Mohammed Bin Saud Islamic University, Riyadh, Saudi Arabia
| | - Ramesa Shafi Bhat
- Department of Physiology, College of Medicine, Al-Imam Mohammed Bin Saud Islamic University, Riyadh, Saudi Arabia
| | - Laila Al-Ayadhi
- Autism Research and Treatment Center, Riyadh, Saudi Arabia
- Department of Physiology, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia
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Abstract
OBJECTIVE The aim of the study was to perform a systematic review assessing the research investigating the association between celiac disease (CD) and autism spectrum disorder (ASD). METHODS A literature search of MEDLINE and EMBASE was performed without limits placed on year or language. Observational studies reporting on the occurrence of CD among patients with ASD and/or the occurrence of ASD among patients with CD were included. Study design, characteristics, diagnostic criteria for ASD and CD, and the frequency of positive cases in the studied sample were recorded. Study quality was assessed using an adapted Newcastle-Ottawa Quality Assessment Scale. Due to substantial heterogeneity between studies, a meta-analysis was not performed. RESULTS Of the 298 unique citations identified within our search strategy, 17 articles evaluating the association between CD and ASD were included. Of those articles, 13 observed samples of patients with ASD, and 6 observed samples of patients with CD. Overall, most studies had small sample sizes and reported no evidence for an association between the 2 conditions. However, a limited number of population-based studies of higher quality suggested a potential association between CD and ASD. CONCLUSIONS Most studies assessing an association between CD and ASD are at risk for systematic and/or random error. A potential link has, however, been shown in a handful of high-quality studies, and, therefore, this comorbidity cannot be ruled out. Future studies should recruit larger sample sizes, include precise definitions of CD and ASD, and exclude patients with ASD on a gluten-free diet.
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Labban RSM, Alfawaz HA, Almnaizel AT, Al-Muammar MN, Bhat RS, El-Ansary A. Garcinia mangostana extract and curcumin ameliorate oxidative stress, dyslipidemia, and hyperglycemia in high fat diet-induced obese Wistar albino rats. Sci Rep 2021; 11:7278. [PMID: 33790313 PMCID: PMC8012579 DOI: 10.1038/s41598-021-86545-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Accepted: 03/08/2021] [Indexed: 12/15/2022] Open
Abstract
The aim of this study was to explore the effects of Garcinia mangostana (mangosteen) and Curcuma longa independently and synergistically in modulating oxidative stress, dyslipidemia, and hyperglycemia commonly observed in high-fat diet-induced obesity in rodent models. Male albino Wistar rats were divided into eight experimental groups, fed on a normal diet or high-fat diet (HFD), then given mangosteen extract (400 mg /kg /day) and/or curcumin (80 mg/kg /day) for 6 weeks. Oxidative stress markers, glucose, and lipid fractions were measured in the sera. Mangosteen pericarp extract (MPE) induced a remarkable decrease in BMI (from 0.86 to 0.81 gm/cm2), while curcuma either alone or in combination was more effective, as treated rats recorded BMIs of 0.78 and 0.79 gm/cm2, respectively. Regarding the antioxidant effects, MPE induced a significant increase of GSH in obese rats (123.86 ± 15.53 μg/ml vs 288.72 ± 121.37 μg/ml). As anti-atherogenic agents MPE demonstrate significant effect recorded higher level of HDL-C in treated animals, but ineefective as anti-dyslipidemic agent. Curcumin was more effective in reducing LDL-C levels in obese rats. Both extracts effectively reduced blood glucose. The present study demonstrated that MPE and curcumin were independently and synergistically effective in treating obesity-induced atherogenesis.
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Affiliation(s)
- Ranyah Shaker M Labban
- Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia
- Ministry of Health, General Administration of Nutrition, Riyadh, Saudi Arabia
| | - Hanan A Alfawaz
- Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Ahmed T Almnaizel
- Prince Naif for Health Research Center, King Saud University, Riyadh, Saudi Arabia
| | - May N Al-Muammar
- Department of Community Health, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Ramesa Shafi Bhat
- Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Afaf El-Ansary
- Central Laboratory, Female Centre for Scientific and Medical Studies, King Saud University, Riyadh, Saudi Arabia.
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Song Y, Loor JJ, Zhao C, Huang D, Du X, Li X, Wang Z, Liu G, Li X. Potential hemo-biological identification markers to the left displaced abomasum in dairy cows. BMC Vet Res 2020; 16:470. [PMID: 33267889 PMCID: PMC7709353 DOI: 10.1186/s12917-020-02676-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 11/13/2020] [Indexed: 11/18/2022] Open
Abstract
Background Left displaced abomasum (LDA) occurs at high frequency in the early postpartum period and can affect production performance of dairy cows. Clinical diagnosis of LDA is usually done by abdominal auscultation and percussion. The purpose of this study was to explore the potential applicability of blood biomarkers for early warning and diagnosis of LDA in dairy cows. Results Twenty early postpartum healthy cows and thirty early postpartum LDA cows of similar parity were used. A receiver operating characteristic curve (ROC) method was used to analyze the sensitivity of hematological biomarkers to LDA including energy balance metabolic biomarkers, liver/kidney function biomarkers, and minerals. A cut-off point was defined for each of the selected hematological biomarkers deemed sensitive markers of LDA. Compared with healthy cows, body condition score (BCS), dry matter intake (DMI) and milk production were lower in LDA cows. Among energy metabolism markers, serum non-esterified fatty acid (NEFA), β-hydroxybutyric acid (BHBA), insulin (INS), and revised quantitative insulin sensitivity check index (RQUICKI) levels were lower while serum glucagon (GC) was greater in LDA cows. Among the liver/kidney function biomarkers, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), the ratio of AST/ALT and levels of total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), albumin (ALB), blood urea nitrogen (BUN), creatinine, and total protein (TP) were greater in LDA cows. Among minerals analyzed, serum Cl, Ca, and K were lower in LDA cows. After ROC analysis, it was determined that serum Ca, INS, RQUICKI, ALT, GGT, and creatinine are potential indicators for early warning and diagnosis of LDA for early postpartum dairy cows. Conclusions Dairy cows with LDA were under severe negative energy balance (NEB), had signs of liver damage and potentially lower insulin sensitivity. A combination of multi-hematological biomarkers including Ca, INS, RQUICKI, ALT, GGT and creatinine has the potential to help identify cows at risk of LDA in the early postpartum period.
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Affiliation(s)
- Yuxiang Song
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Jilin, 130062, Changchun, China
| | - Juan J Loor
- Mammalian NutriPhysioGenomics, Department of Animal Sciences, Division of Nutritional Sciences, University of Illinois, 61801, Urbana, USA
| | - Chenchen Zhao
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Jilin, 130062, Changchun, China
| | - Dan Huang
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Jilin, 130062, Changchun, China
| | - Xiliang Du
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Jilin, 130062, Changchun, China
| | - Xiaobing Li
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Jilin, 130062, Changchun, China
| | - Zhe Wang
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Jilin, 130062, Changchun, China
| | - Guowen Liu
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Jilin, 130062, Changchun, China
| | - Xinwei Li
- Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Jilin, 130062, Changchun, China.
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12
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Konečná B, Radošinská J, Keményová P, Repiská G. Detection of disease-associated microRNAs - application for autism spectrum disorders. Rev Neurosci 2020; 31:757-769. [PMID: 32813679 DOI: 10.1515/revneuro-2020-0015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 04/15/2020] [Indexed: 12/12/2022]
Abstract
Autism spectrum disorders (ASD) diagnostic procedure still lacks a uniform biological marker. This review gathers the information on microRNAs (miRNAs) specifically as a possible source of biomarkers of ASD. Extracellular vesicles, and their subset of exosomes, are believed to be a tool of cell-to-cell communication, and they are increasingly considered to be carriers of such a marker. The interest in studying miRNAs in extracellular vesicles grows in all fields of study and therefore should not be omitted in the field of neurodevelopmental disorders. The summary of miRNAs associated with brain cells and ASD either studied directly in the tissue or biofluids are gathered in this review. The heterogeneity in findings from different studies points out the fact that unified methods should be established, beginning with the determination of the accurate patient and control groups, through to sample collection, processing, and storage conditions. This review, based on the available literature, proposes the standardized approach to obtain the results that would not be affected by technical factors. Nowadays, the method of high-throughput sequencing seems to be the most optimal to analyze miRNAs. This should be followed by the uniformed bioinformatics procedure to avoid misvalidation. At the end, the proper validation of the obtained results is needed. With such an approach as is described in this review, it would be possible to obtain a reliable biomarker that would characterize the presence of ASD.
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Affiliation(s)
- Barbora Konečná
- Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University in Bratislava, 811 08 Bratislava, Slovakia
| | - Jana Radošinská
- Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, 813 72 Bratislava, Slovakia
- Institute for Heart Research, Centre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia
| | - Petra Keményová
- Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, 813 72 Bratislava, Slovakia
| | - Gabriela Repiská
- Institute of Physiology, Faculty of Medicine, Comenius University in Bratislava, 813 72 Bratislava, Slovakia
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13
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Scassellati C, Bonvicini C, Benussi L, Ghidoni R, Squitti R. Neurodevelopmental disorders: Metallomics studies for the identification of potential biomarkers associated to diagnosis and treatment. J Trace Elem Med Biol 2020; 60:126499. [PMID: 32203724 DOI: 10.1016/j.jtemb.2020.126499] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 01/10/2020] [Accepted: 03/13/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Diagnosis and treatment of complex diseases such as Neurodevelopmental Disorders (NDDs) can be resolved through the identification of biomarkers. Metallomics (research on biometals) and metallomes (metalloproteins/metalloenzymes/chaperones) along with genomics, proteomics and metabolomics, can contribute to accelerate and improve this process. AIM This review focused on four NDDs pathologies (Schizophrenia, SZ; Attention Deficit Hyperactivity Disorder, ADHD; Autism, ADS; Epilepsy), and we reported, for the first time, different studies on the role played by the principal six essential trace elements (Cobalt, Co; Copper, Cu; Iron, Fe; Manganese, Mn; Selenium, Se; Zinc, Zn) that can influence diagnosis/treatment. RESULTS in light of the literature presented, based on meta-analyses, we suggest that Zn (glutamatergic neurotransmission, inflammation, neurodegeneration, autoimmunity alterations), could be a potential diagnostic biomarker associated to SZ. Moreover, considering the single association studies going in the same direction, increased Cu (catecholamine alterations, glucose intolerance, altered lipid metabolism/oxidative stress) and lower Fe (dopaminergic dysfunctions) levels were associated with a specific negative symptomatology. Lower Mn (lipid metabolism/oxidative stress alterations), and lower Se (metabolic syndrome) were linked to SZ. From the meta-analyses in ADHD, it is evidenced that Fe (and ferritin in particular), Mn, and Zn (oxidative stress dysfunctions) could be potential diagnostic biomarkers, mainly associated to severe hyperactive or inattentive symptoms; as well as Cu, Fe, Zn in ADS and Zn in Epilepsy. Fe, Zn and Mn levels seem to be influenced by antipsychotics treatment in SZ; Mn and Zn by methylphenidate treatment in ADHD; Cu and Zn by antiepileptic drugs in Epilepsy. CONCLUSIONS Although there is controversy and further studies are needed, this work summarizes the state of art of the literature on this topic. We claim to avoid underreporting the impact of essential trace elements in paving the way for biomarkers research for NDDs.
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Affiliation(s)
- Catia Scassellati
- Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
| | - Cristian Bonvicini
- Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Luisa Benussi
- Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Roberta Ghidoni
- Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Rosanna Squitti
- Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
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Ogruc Ildiz G, Bayari S, Karadag A, Kaygisiz E, Fausto R. Fourier Transform Infrared Spectroscopy Based Complementary Diagnosis Tool for Autism Spectrum Disorder in Children and Adolescents. Molecules 2020; 25:molecules25092079. [PMID: 32365644 PMCID: PMC7249117 DOI: 10.3390/molecules25092079] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 04/11/2020] [Accepted: 04/21/2020] [Indexed: 11/16/2022] Open
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that begins early in life and continues lifelong with strong personal and societal implications. It affects about 1%-2% of the children population in the world. The absence of auxiliary methods that can complement the clinical evaluation of ASD increases the probability of false identification of the disorder, especially in the case of very young children. In this study, analytical models for auxiliary diagnosis of ASD in children and adolescents, based on the analysis of patients' blood serum ATR-FTIR (Attenuated Total Reflectance-Fourier Transform Infrared) spectra, were developed. The models use chemometrics (either Principal Component Analysis (PCA) or Partial Least Squares Discriminant Analysis (PLS-DA)) methods, with the infrared spectra being the X-predictor variables. The two developed models exhibit excellent classification performance for samples of ASD individuals vs. healthy controls. Interestingly, the simplest, unsupervised PCA-based model results to have a global performance identical to the more demanding, supervised (PLS-DA)-based model. The developed PCA-based model thus appears as the more economical alternative one for use in the clinical environment. Hierarchical clustering analysis performed on the full set of samples was also successful in discriminating the two groups.
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Affiliation(s)
- Gulce Ogruc Ildiz
- Department of Physics, Faculty of Sciences and Letters, Istanbul Kultur University, 34158 Istanbul, Turke
- Department of Chemistry, CQC, University of Coimbra, P-3004-535 Coimbra, Portugal;
- Correspondence:
| | - Sevgi Bayari
- Department of Physics Engineering, Hacettepe University, 06800 Ankara, Turkey;
| | - Ahmet Karadag
- Department of Physics, Faculty of Sciences and Letters, Istanbul Kultur University, 34158 Istanbul, Turke
| | - Ersin Kaygisiz
- Department of Geological Engineering, Istanbul University-Cerrahpasa, 34320 Istanbul, Turkey;
| | - Rui Fausto
- Department of Chemistry, CQC, University of Coimbra, P-3004-535 Coimbra, Portugal;
- Department of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran 34463, Saudi Arabia
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15
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Longitudinal EEG power in the first postnatal year differentiates autism outcomes. Nat Commun 2019; 10:4188. [PMID: 31519897 PMCID: PMC6744476 DOI: 10.1038/s41467-019-12202-9] [Citation(s) in RCA: 102] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Accepted: 08/23/2019] [Indexed: 12/11/2022] Open
Abstract
An aim of autism spectrum disorder (ASD) research is to identify early biomarkers that inform ASD pathophysiology and expedite detection. Brain oscillations captured in electroencephalography (EEG) are thought to be disrupted as core ASD pathophysiology. We leverage longitudinal EEG power measurements from 3 to 36 months of age in infants at low- and high-risk for ASD to test how and when power distinguishes ASD risk and diagnosis by age 3-years. Power trajectories across the first year, second year, or first three years postnatally were submitted to data-driven modeling to differentiate ASD outcomes. Power dynamics during the first postnatal year best differentiate ASD diagnoses. Delta and gamma frequency power trajectories consistently distinguish infants with ASD diagnoses from others. There is also a developmental shift across timescales towards including higher-frequency power to differentiate outcomes. These findings reveal the importance of developmental timing and trajectory in understanding pathophysiology and classifying ASD outcomes. Brain oscillations may be disrupted in children with autism spectrum disorder. The authors performed a longitudinal study of electroencephalography recordings and found that EEG recordings from the first year after birth can distinguish healthy children from children with autism spectrum disorder.
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16
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Thuringer D, Garrido C. Molecular chaperones in the brain endothelial barrier: neurotoxicity or neuroprotection? FASEB J 2019; 33:11629-11639. [PMID: 31348679 DOI: 10.1096/fj.201900895r] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Brain microvascular endothelial cells (BMECs) interact with astrocytes and pericytes to form the blood-brain barrier (BBB). Their compromised function alters the BBB integrity, which is associated with early events in the pathogenesis of cancer, neurodegenerative diseases, and epilepsy. Interestingly, these conditions also induce the expression of heat shock proteins (HSPs). Here we review the contribution of major HSP families to BMEC and BBB function. Although investigators mainly report protective effects of HSPs in brain, contrasted results were obtained in BMEC, which depend both on the HSP and on its location, intra- or extracellular. The therapeutic potential of HSPs must be scrupulously analyzed before targeting them in patients to reduce the progression of brain lesions and improve neurologic outcomes in the long term.-Thuringer, D., Garrido, C. Molecular chaperones in the brain endothelial barrier: neurotoxicity or neuroprotection?
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Affiliation(s)
- Dominique Thuringer
- INSERM Unité Mixte de Recherche (UMR) 1231, Institut Fédératif de Recherche en Santé-Sciences et Techniques de l'Information et de la Communication (IFR Santé-STIC), Faculté de Médecine, Université de Bourgogne Franche-Comté, Dijon, France
| | - Carmen Garrido
- INSERM Unité Mixte de Recherche (UMR) 1231, Institut Fédératif de Recherche en Santé-Sciences et Techniques de l'Information et de la Communication (IFR Santé-STIC), Faculté de Médecine, Université de Bourgogne Franche-Comté, Dijon, France
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17
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Waugh DT. Fluoride Exposure Induces Inhibition of Sodium-and Potassium-Activated Adenosine Triphosphatase (Na +, K +-ATPase) Enzyme Activity: Molecular Mechanisms and Implications for Public Health. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:E1427. [PMID: 31010095 PMCID: PMC6518254 DOI: 10.3390/ijerph16081427] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Revised: 04/02/2019] [Accepted: 04/08/2019] [Indexed: 12/24/2022]
Abstract
In this study, several lines of evidence are provided to show that Na + , K + -ATPase activity exerts vital roles in normal brain development and function and that loss of enzyme activity is implicated in neurodevelopmental, neuropsychiatric and neurodegenerative disorders, as well as increased risk of cancer, metabolic, pulmonary and cardiovascular disease. Evidence is presented to show that fluoride (F) inhibits Na + , K + -ATPase activity by altering biological pathways through modifying the expression of genes and the activity of glycolytic enzymes, metalloenzymes, hormones, proteins, neuropeptides and cytokines, as well as biological interface interactions that rely on the bioavailability of chemical elements magnesium and manganese to modulate ATP and Na + , K + -ATPase enzyme activity. Taken together, the findings of this study provide unprecedented insights into the molecular mechanisms and biological pathways by which F inhibits Na + , K + -ATPase activity and contributes to the etiology and pathophysiology of diseases associated with impairment of this essential enzyme. Moreover, the findings of this study further suggest that there are windows of susceptibility over the life course where chronic F exposure in pregnancy and early infancy may impair Na + , K + -ATPase activity with both short- and long-term implications for disease and inequalities in health. These findings would warrant considerable attention and potential intervention, not to mention additional research on the potential effects of F intake in contributing to chronic disease.
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Affiliation(s)
- Declan Timothy Waugh
- EnviroManagement Services, 11 Riverview, Doherty's Rd, P72 YF10 Bandon, Co. Cork, Ireland.
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18
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Drozd HP, Karathanasis SF, Molosh AI, Lukkes JL, Clapp DW, Shekhar A. From bedside to bench and back: Translating ASD models. PROGRESS IN BRAIN RESEARCH 2018; 241:113-158. [PMID: 30447753 DOI: 10.1016/bs.pbr.2018.10.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Autism spectrum disorders (ASD) represent a heterogeneous group of disorders defined by deficits in social interaction/communication and restricted interests, behaviors, or activities. Models of ASD, developed based on clinical data and observations, are used in basic science, the "bench," to better understand the pathophysiology of ASD and provide therapeutic options for patients in the clinic, the "bedside." Translational medicine creates a bridge between the bench and bedside that allows for clinical and basic science discoveries to challenge one another to improve the opportunities to bring novel therapies to patients. From the clinical side, biomarker work is expanding our understanding of possible mechanisms of ASD through measures of behavior, genetics, imaging modalities, and serum markers. These biomarkers could help to subclassify patients with ASD in order to better target treatments to a more homogeneous groups of patients most likely to respond to a candidate therapy. In turn, basic science has been responding to developments in clinical evaluation by improving bench models to mechanistically and phenotypically recapitulate the ASD phenotypes observed in clinic. While genetic models are identifying novel therapeutics targets at the bench, the clinical efforts are making progress by defining better outcome measures that are most representative of meaningful patient responses. In this review, we discuss some of these challenges in translational research in ASD and strategies for the bench and bedside to bridge the gap to achieve better benefits to patients.
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Affiliation(s)
- Hayley P Drozd
- Program in Medical Neurobiology, Stark Neurosciences Institute, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Sotirios F Karathanasis
- Program in Medical Neurobiology, Stark Neurosciences Institute, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Andrei I Molosh
- Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Jodi L Lukkes
- Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States
| | - D Wade Clapp
- Department of Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Anantha Shekhar
- Program in Medical Neurobiology, Stark Neurosciences Institute, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United States; Indiana Clinical and Translation Sciences Institute, Indiana University School of Medicine, Indianapolis, IN, United States.
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19
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Bolotta A, Visconti P, Fedrizzi G, Ghezzo A, Marini M, Manunta P, Messaggio E, Posar A, Vignini A, Abruzzo PM. Na + , K + -ATPase activity in children with autism spectrum disorder: Searching for the reason(s) of its decrease in blood cells. Autism Res 2018; 11:1388-1403. [PMID: 30120881 PMCID: PMC6221099 DOI: 10.1002/aur.2002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 05/24/2018] [Accepted: 06/03/2018] [Indexed: 12/27/2022]
Abstract
Na+ , K+ -ATPase (NKA) activity, which establishes the sodium and potassium gradient across the cell membrane and is instrumental in the propagation of the nerve impulses, is altered in a number of neurological and neuropsychiatric disorders, including autism spectrum disorders (ASD). In the present work, we examined a wide range of biochemical and cellular parameters in the attempt to understand the reason(s) for the severe decrease in NKA activity in erythrocytes of ASD children that we reported previously. NKA activity in leukocytes was found to be decreased independently from alteration in plasma membrane fluidity. The different subunits were evaluated for gene expression in leukocytes and for protein expression in erythrocytes: small differences in gene expression between ASD and typically developing children were not apparently paralleled by differences in protein expression. Moreover, no gross difference in erythrocyte plasma membrane oxidative modifications was detectable, although oxidative stress in blood samples from ASD children was confirmed by increased expression of NRF2 mRNA. Interestingly, gene expression of some NKA subunits correlated with clinical features. Excess inhibitory metals or ouabain-like activities, which might account for NKA activity decrease, were ruled out. Plasma membrane cholesterol, but not phosphatidylcholine and phosphatidlserine, was slighty decreased in erythrocytes from ASD children. Although no compelling results were obtained, our data suggest that alteration in the erytrocyte lipid moiety or subtle oxidative modifications in NKA structure are likely candidates for the observed decrease in NKA activity. These findings are discussed in the light of the relevance of NKA in ASD. Autism Res 2018, 11: 1388-1403. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The activity of the cell membrane enzyme NKA, which is instrumental in the propagation of the nerve impulses, is severely decreased in erythrocytes from ASD children and in other brain disorders, yet no explanation has been provided for this observation. We strived to find a biological/biochemical cause of such alteration, but most queries went unsolved because of the complexity of NKA regulation. As NKA activity is altered in many brain disorders, we stress the relevance of studies aimed at understanding its regulation in ASD.
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Affiliation(s)
- Alessandra Bolotta
- From the Department of Experimental, Diagnostic, and Specialty MedicineUniversity of BolognaBolognaItaly
- IRCCS Fondazione Don Carlo GnocchiMilanItaly
| | - Paola Visconti
- IRCCS Istituto delle Scienze Neurologiche di BolognaBolognaItaly
| | - Giorgio Fedrizzi
- Chemical DepartmentIZSLER Zooprophylactic Experimental Institute for Lombardy and Emilia RomagnaBolognaItaly
| | - Alessandro Ghezzo
- From the Department of Experimental, Diagnostic, and Specialty MedicineUniversity of BolognaBolognaItaly
| | - Marina Marini
- From the Department of Experimental, Diagnostic, and Specialty MedicineUniversity of BolognaBolognaItaly
- IRCCS Fondazione Don Carlo GnocchiMilanItaly
| | - Paolo Manunta
- University and Hospital Vita‐SaluteMilanItaly
- Chair of NephrologyUniversity Vita Salute San Raffaele, IRCCS San Raffaele Scientific InstituteMilanItaly
| | | | - Annio Posar
- IRCCS Istituto delle Scienze Neurologiche di BolognaBolognaItaly
- Department of Biomedical and Neuromotor SciencesUniversity of BolognaBolognaItaly
| | - Arianna Vignini
- Department of Clinical Sciences – Section of Biochemistry, Biology and PhysicsPolytechnic University of MarcheAnconaItaly
| | - Provvidenza Maria Abruzzo
- From the Department of Experimental, Diagnostic, and Specialty MedicineUniversity of BolognaBolognaItaly
- IRCCS Fondazione Don Carlo GnocchiMilanItaly
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The Use of Multi-parametric Biomarker Profiles May Increase the Accuracy of ASD Prediction. J Mol Neurosci 2018; 66:85-101. [PMID: 30112624 DOI: 10.1007/s12031-018-1136-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 07/20/2018] [Indexed: 12/12/2022]
Abstract
Effective biomarkers are urgently needed to facilitate early diagnosis of autism spectrum disorder (ASD), permitting early intervention, and consequently improving prognosis. In this study, we evaluate the usefulness of nine biomarkers and their association (combination) in predicting ASD onset and development. Data were analyzed using multiple independent mathematical and statistical approaches to verify the suitability of obtained results as predictive parameters. All biomarkers tested appeared useful in predicting ASD, particularly vitamin E, glutathione-S-transferase, and dopamine. Combining biomarkers into profiles improved the accuracy of ASD prediction but still failed to distinguish between participants with severe versus mild or moderate ASD. Library-based identification was effective in predicting the occurrence of disease. Due to the small sample size and wide participant age variation in this study, we conclude that the use of multi-parametric biomarker profiles directly related to autism phenotype may help predict the disease occurrence more accurately, but studies using larger, more age-homogeneous populations are needed to corroborate our findings.
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21
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Noroozi R, Omrani MD, Sayad A, Taheri M, Ghafouri-Fard S. Cytoplasmic FMRP interacting protein 1/2 (CYFIP1/2) expression analysis in autism. Metab Brain Dis 2018; 33:1353-1358. [PMID: 29752658 DOI: 10.1007/s11011-018-0249-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 05/06/2018] [Indexed: 11/26/2022]
Abstract
Cytoplasmic FMRP interacting proteins 1 and 2 (CYFIP1/2) have been previously shown to be associated with central nervous system (CNS) disorders such as autism spectrum disorder (ASD). Moreover, dysregulation of their expression levels results in disturbances in CNS maturation and neuronal interconnections. In the present study, we compared expression levels of CYFIP1/2 in peripheral blood of 30 ASD patients and 41 healthy subjects by means of real time PCR. Expression analysis showed significant over-expression of CYFIP1/2 in ASD patients compared with healthy subjects (Fold change = 3.252, P < 0.0001 and Fold change = 4.14, P = 0.001 respectively). Such over-expression was also seen for CYFIP1 in male and female patients when compared with the corresponding control subjects. In addition, a significant correlation was found between CYFIP1 transcript levels and age in female subjects. A significant correlation was detected between expression levels of these genes in control subjects. The current study provides further supports for contribution of CYFIP1/2 in the pathogenesis of ASD and potentiates it as a peripheral marker for ASD diagnosis. Future studies in larger sample sizes are needed to confirm the results of the current study.
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Affiliation(s)
- Rezvan Noroozi
- Department of medical genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mir Davood Omrani
- Department of medical genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arezou Sayad
- Department of medical genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Department of medical genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Soudeh Ghafouri-Fard
- Department of medical genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Coenzyme Q 10 supplementation reduces oxidative stress and decreases antioxidant enzyme activity in children with autism spectrum disorders. Psychiatry Res 2018; 265:62-69. [PMID: 29684771 DOI: 10.1016/j.psychres.2018.03.061] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 03/02/2018] [Accepted: 03/22/2018] [Indexed: 12/22/2022]
Abstract
Antioxidants and oxidative stress can participate in pathobiochemical mechanisms of autism spectrum disorders (ASDs). The aim was to identify the effects of early CoQ10 supplementation on oxidative stress in children with ASDs. Ninety children with ASDs were included in this study, based on DSM-IV criteria and using Childhood Autism Rating Scale (CARS) scores. Concentrations of CoQ10, MDA, total antioxidant status (TAS) assay, and antioxidant enzymes (superoxide dismutase or SOD and glutathione peroxidase or GPx) activity were determined in serum before and after 100 days of supportive therapy with CoQ10 at daily doses of 30 and 60 mg. Data on children's behavior were collected from parents and babysitters. CoQ10 supportive therapy was determined after three months with daily dose 2 ͯ 30 mg improved oxidative stress in the children with ASDs. A relation was seen between serum MDA (r2 = 0.668) and TAS (r2 = 0.007), and antioxidant enzymes (SOD [r2 = 0.01] and GPx [r2 = 0.001]) activity and CARS score. Based on the results, high doses of CoQ10 can improve gastrointestinal problems (P = 0.004) and sleep disorders (P = 0.005) in children with ASDs with an increase in the CoQ10 of the serum. We concluded that the serum concentration of CoQ10 and oxidative stress could be used as relevant biomarkers in helping the improvement of ASDs.
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Bitar T, Mavel S, Emond P, Nadal-Desbarats L, Lefèvre A, Mattar H, Soufia M, Blasco H, Vourc’h P, Hleihel W, Andres CR. Identification of metabolic pathway disturbances using multimodal metabolomics in autistic disorders in a Middle Eastern population. J Pharm Biomed Anal 2018; 152:57-65. [DOI: 10.1016/j.jpba.2018.01.007] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 12/17/2017] [Accepted: 01/06/2018] [Indexed: 12/21/2022]
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Anwar A, Abruzzo PM, Pasha S, Rajpoot K, Bolotta A, Ghezzo A, Marini M, Posar A, Visconti P, Thornalley PJ, Rabbani N. Advanced glycation endproducts, dityrosine and arginine transporter dysfunction in autism - a source of biomarkers for clinical diagnosis. Mol Autism 2018; 9:3. [PMID: 29479405 PMCID: PMC5817812 DOI: 10.1186/s13229-017-0183-3] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Accepted: 12/19/2017] [Indexed: 12/21/2022] Open
Abstract
Background Clinical chemistry tests for autism spectrum disorder (ASD) are currently unavailable. The aim of this study was to explore the diagnostic utility of proteotoxic biomarkers in plasma and urine, plasma protein glycation, oxidation, and nitration adducts, and related glycated, oxidized, and nitrated amino acids (free adducts), for the clinical diagnosis of ASD. Methods Thirty-eight children with ASD (29 male, 9 female; age 7.6 ± 2.0 years) and 31 age-matched healthy controls (23 males, 8 females; 8.6 ± 2.0 years) were recruited for this study. Plasma protein glycation, oxidation, and nitration adducts and amino acid metabolome in plasma and urine were determined by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. Machine learning methods were then employed to explore and optimize combinations of analyte data for ASD diagnosis. Results We found that children with ASD had increased advanced glycation endproducts (AGEs), Nε-carboxymethyl-lysine (CML) and Nω-carboxymethylarginine (CMA), and increased oxidation damage marker, dityrosine (DT), in plasma protein, with respect to healthy controls. We also found that children with ASD had increased CMA free adduct in plasma ultrafiltrate and increased urinary excretion of oxidation free adducts, alpha-aminoadipic semialdehyde and glutamic semialdehyde. From study of renal handling of amino acids, we found that children with ASD had decreased renal clearance of arginine and CMA with respect to healthy controls. Algorithms to discriminate between ASD and healthy controls gave strong diagnostic performance with features: plasma protein AGEs—CML, CMA—and 3-deoxyglucosone-derived hydroimidazolone, and oxidative damage marker, DT. The sensitivity, specificity, and receiver operating characteristic area-under-the-curve were 92%, 84%, and 0.94, respectively. Conclusions Changes in plasma AGEs were likely indicative of dysfunctional metabolism of dicarbonyl metabolite precursors of AGEs, glyoxal and 3-deoxyglucosone. DT is formed enzymatically by dual oxidase (DUOX); selective increase of DT as an oxidative damage marker implicates increased DUOX activity in ASD possibly linked to impaired gut mucosal immunity. Decreased renal clearance of arginine and CMA in ASD is indicative of increased arginine transporter activity which may be a surrogate marker of disturbance of neuronal availability of amino acids. Data driven combination of these biomarkers perturbed by proteotoxic stress, plasma protein AGEs and DT, gave diagnostic algorithms of high sensitivity and specificity for ASD. Electronic supplementary material The online version of this article (10.1186/s13229-017-0183-3) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Attia Anwar
- Warwick Medical School, University of Warwick, Clinical Sciences Research Laboratories, University Hospital, Coventry, UK
| | - Provvidenza Maria Abruzzo
- 2Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Via Belmeloro 8, 40126 Bologna, Italy.,4Don Carlo Gnocchi Foundation ONLUS, IRCCS "S. Maria Nascente", Via Alfonso Capecelatro 66, 20148 Milan, Italy
| | - Sabah Pasha
- Warwick Medical School, University of Warwick, Clinical Sciences Research Laboratories, University Hospital, Coventry, UK
| | - Kashif Rajpoot
- 3Department of Computer Science, University of Birmingham, Birmingham, UK
| | - Alessandra Bolotta
- 2Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Via Belmeloro 8, 40126 Bologna, Italy.,4Don Carlo Gnocchi Foundation ONLUS, IRCCS "S. Maria Nascente", Via Alfonso Capecelatro 66, 20148 Milan, Italy
| | - Alessandro Ghezzo
- 2Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Via Belmeloro 8, 40126 Bologna, Italy
| | - Marina Marini
- 2Department of Experimental, Diagnostic and Specialty Medicine, School of Medicine, University of Bologna, Via Belmeloro 8, 40126 Bologna, Italy.,4Don Carlo Gnocchi Foundation ONLUS, IRCCS "S. Maria Nascente", Via Alfonso Capecelatro 66, 20148 Milan, Italy
| | - Annio Posar
- Child Neurology and Psychiatry Unit, IRCCS Institute of Neurological Sciences, Via Altura, 3, 40139 Bologna, Italy.,6Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Altura 3, 40139 Bologna, Italy
| | - Paola Visconti
- Child Neurology and Psychiatry Unit, IRCCS Institute of Neurological Sciences, Via Altura, 3, 40139 Bologna, Italy
| | - Paul J Thornalley
- Warwick Medical School, University of Warwick, Clinical Sciences Research Laboratories, University Hospital, Coventry, UK.,7Zeeman Institute for Systems Biology & Infectious Disease Epidemiology Research, Senate House, University of Warwick, Coventry, CV4 7AL UK
| | - Naila Rabbani
- Warwick Medical School, University of Warwick, Clinical Sciences Research Laboratories, University Hospital, Coventry, UK.,7Zeeman Institute for Systems Biology & Infectious Disease Epidemiology Research, Senate House, University of Warwick, Coventry, CV4 7AL UK.,8Research Technology Platform-Proteomics, University of Warwick, Coventry, UK
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Bara TS, Farias AC, Felden EPG, Cordeiro ML. Receiver operating characteristic curve analysis of the Child Behavior Checklist and Teacher's Report Form for assessing autism spectrum disorder in preschool-aged children. Neuropsychiatr Dis Treat 2017; 14:95-102. [PMID: 29343961 PMCID: PMC5749382 DOI: 10.2147/ndt.s151185] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social, behavioral, and communication impairments with an estimated prevalence of 1 in 68 school-aged children. There is a need for objective and easily applicable instruments for early identification of autistic children to enable initiation of early interventions during a very sensitive period of brain development and, consequently, optimize prognosis. Here, we tested the utility of the Child Behavior Checklist (CBCL) and the Caregiver-Teacher's Report Form (C-TRF) scales for assessing ASD in Brazil, where ASD screening research is emergent. SUBJECTS AND METHODS A total of 70 children (2-5 years old, both sexes) were enrolled, including an ASD group (n=39) and a non-ASD control group (n=31). The preschool versions of the CBCL and C-TRF were applied. The CBCL and C-TRF results were compared between the ASD and non-ASD control groups with Mann-Whitney U tests and receiver operating characteristic analyses. RESULTS The CBCL and C-TRF were found to have moderate accuracy for the dimensions withdrawn and autism spectrum problems, and to correlate with each other. CONCLUSION The CBCL and C-TRF may aid in early ASD detection.
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Affiliation(s)
- Tiago S Bara
- Neurosciences Core, Pelé Pequeno Príncipe Research Institute
- Faculdades Pequeno Príncipe
| | - Antonio C Farias
- Neurosciences Core, Pelé Pequeno Príncipe Research Institute
- Faculdades Pequeno Príncipe
- Department of Neuropediatrics, Children’s Hospital, Pequeno Príncipe
- School of Medicine, University Positivo, Curitiba
| | - Erico PG Felden
- Centro de Ciências da Saúde e do Esporte (CEFID) da Universidade do Estado de Santa Catarina, Florianópolis, Brazil
| | - Mara L Cordeiro
- Neurosciences Core, Pelé Pequeno Príncipe Research Institute
- Faculdades Pequeno Príncipe
- Department of Psychiatry and Biobehavior Sciences, David Geffen School of Medicine, Semel Institute for Neusroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA
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Chiu KH, Dong CD, Chen CF, Tsai ML, Ju YR, Chen TM, Chen CW. NMR-based metabolomics for the environmental assessment of Kaohsiung Harbor sediments exemplified by a marine amphipod (Hyalella azteca). MARINE POLLUTION BULLETIN 2017; 124:714-724. [PMID: 28267993 DOI: 10.1016/j.marpolbul.2017.02.067] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 02/21/2017] [Accepted: 02/24/2017] [Indexed: 05/08/2023]
Abstract
Inflow of wastewater from upstream causes a large flux of pollutants to enter Kaohsiung Harbor in Taiwan daily. To reveal the ecological risk posed by Kaohsiung Harbor sediments, an ecological metabolomic approach was employed to investigate environmental factors pertinent to the physiological regulation of the marine amphipod Hyalella azteca. The amphipods were exposed to sediments collected from different stream inlets of the Love River (LR), Canon River (CR), Jen-Gen River (JR), and Salt River (SR). Harbor entrance 1 (E1) was selected as a reference site. After 10-day exposure, metabolomic analysis of the Hyalella azteca revealed differences between two groups: {E1, LR, CR} and {JR, SR}. The metabolic pathways identified in the two groups of amphipods were significantly different. The results demonstrated that NMR-based metabolomics can be effectively used to characterize metabolic response related to sediment from polluted areas.
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Affiliation(s)
- K H Chiu
- Department and Graduate Institute of Aquaculture, National Kaohsiung Marine University, Kaohsiung, Taiwan
| | - C D Dong
- Department of Marine Environmental Engineering, National Kaohsiung Marine University, Kaohsiung, Taiwan; Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan
| | - C F Chen
- Department of Marine Environmental Engineering, National Kaohsiung Marine University, Kaohsiung, Taiwan
| | - M L Tsai
- Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung, Taiwan
| | - Y R Ju
- Department of Marine Environmental Engineering, National Kaohsiung Marine University, Kaohsiung, Taiwan
| | - T M Chen
- Department and Graduate Institute of Aquaculture, National Kaohsiung Marine University, Kaohsiung, Taiwan
| | - C W Chen
- Department of Marine Environmental Engineering, National Kaohsiung Marine University, Kaohsiung, Taiwan.
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High predictive values of RBC membrane-based diagnostics by biophotonics in an integrated approach for Autism Spectrum Disorders. Sci Rep 2017; 7:9854. [PMID: 28852136 PMCID: PMC5574882 DOI: 10.1038/s41598-017-10361-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Accepted: 08/09/2017] [Indexed: 12/13/2022] Open
Abstract
Membranes attract attention in medicine, concerning lipidome composition and fatty acid correlation with neurological diseases. Hyperspectral dark field microscopy (HDFM), a biophotonic imaging using reflectance spectra, provides accurate characterization of healthy adult RBC identifying a library of 8 spectral end-members. Here we report hyperspectral RBC imaging in children affected by Autism Spectrum Disorder (ASD) (n = 21) compared to healthy age-matched subjects (n = 20), investigating if statistically significant differences in their HDFM spectra exist, that can comprehensively map a membrane impairment involved in disease. A significant difference concerning one end-member (spectrum 4) was found (P value = 0.0021). A thorough statistical treatment evidenced: i) diagnostic performance by the receiving operators curve (ROC) analysis, with cut-offs and very high predictive values (P value = 0.0008) of spectrum 4 for identifying disease; ii) significant correlations of spectrum 4 with clinical parameters and with the RBC membrane deficit of the omega-3 docosahexaenoic acid (DHA) in ASD patients; iii) by principal component analysis, very high affinity values of spectrum 4 to the factor that combines behavioural parameters and the variable “cc” discriminating cases and controls. These results foresee the use of biophotonic methodologies in ASD diagnostic panels combining with molecular elements for a correct neuronal growth.
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28
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Serologic Markers of Autism Spectrum Disorder. J Mol Neurosci 2017; 62:420-429. [PMID: 28730336 DOI: 10.1007/s12031-017-0950-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Accepted: 07/12/2017] [Indexed: 12/27/2022]
Abstract
According to WHO data, about 67 million people worldwide are affected by autism, and this number grows by 14% annually. Among the possible causes of autism are genetic modifications, organic lesions of the central nervous system, metabolic disorders, influence of viral and bacterial infections, chemical influence to the mother's body during pregnancy, etc. The conducted research shows that research papers published until today do not name any potential protein markers that meet the requirements of the basic parameters for evaluating the efficiency of disease diagnostics, in particular high sensitivity, specificity, and accuracy. Conducting proteomic research on a big scale in order to detect serologic markers of protein nature associated with development of autism spectrum disorders seems to be highly relevant.
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Spierling SR, Zorrilla EP. Don't stress about CRF: assessing the translational failures of CRF 1antagonists. Psychopharmacology (Berl) 2017; 234:1467-1481. [PMID: 28265716 PMCID: PMC5420464 DOI: 10.1007/s00213-017-4556-2] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2016] [Accepted: 01/27/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Dr. Athina Markou sought treatments for a common neural substrate shared by depression and drug dependence. Antagonists of corticotropin-releasing factor (CRF) receptors, a target of interest to her, have not reached the clinic despite strong preclinical rationale and sustained translational efforts. METHODS We explore potential causes for the failure of CRF1 antagonists and review recent findings concerning CRF-CRF1 systems in psychopathology. RESULTS Potential causes for negative outcomes include (1) poor safety and efficacy of initial drug candidates due to bad pharmacokinetic and physicochemical properties, (2) specificity problems with preclinical screens, (3) the acute nature of screens vs. late-presenting patients, (4) positive preclinical results limited to certain models and conditions with dynamic CRF-CRF1 activation not homologous to tested patients, (5) repeated CRF1 activation-induced plasticity that reduces the importance of ongoing CRF1 agonist stimulation, and (6) therapeutic silencing which may need to address CRF2 receptor or CRF-binding protein molecules, constitutive CRF1 activity, or molecules that influence agonist-independent activity or to target structural regions other than the allosteric site bound by all drug candidates. We describe potential markers of activation towards individualized treatment, human genetic, and functional data that still implicate CRF1 systems in emotional disturbance, sex differences, and suggestive clinical findings for CRF1 antagonists in food craving and CRF-driven HPA-axis overactivation. CONCLUSION The therapeutic scope of selective CRF1 antagonists now appears narrower than had been hoped. Yet, much remains to be learned about CRF's role in the neurobiology of dysphoria and addiction and the potential for novel anti-CRF therapies therein.
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Affiliation(s)
- Samantha R Spierling
- Committee on the Neurobiology of Addictive Disorders, SP30-2400, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA.
| | - Eric P Zorrilla
- Committee on the Neurobiology of Addictive Disorders, SP30-2400, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA.
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