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Oxidative Stress as a Commune Factor for the Interplay between, Neuropsychiatric and Gastrointestinal Disorders

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A special issue of Medicina (ISSN 1648-9144).

Deadline for manuscript submissions: closed (30 March 2021) | Viewed by 38120

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Special Issue Editor

Dr. Alin Ciobica

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Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University of Iasi, B dul Carol I, No. 11, 700506 Iasi, Romania
Interests: neuropsychiatry; oxidative stress
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lately, there has been increased interest in the understanding the connections that might exist between most neuropsychiatric disorders and their associated digestive dysfunctions. Thus, oxidative stress might represent one important communal aspect in the pathophysiology of these two types of disorders. For example, according to ROME IV criteria, functional gastrointestinal disorders are now disorders of gut–brain interaction impairments, which include common symptoms such as motility disturbance, visceral hypersensitivity, altered mucosal and immune function, dysregulated gut microbiota, and altered central nervous system processing. Considering the lack of specific biomarkers in the aforementioned context, oxidative stress parameters could represent an alternative in understanding the connections between digestive and neuropsychiatric manifestations. In this Special Issue, we invite researchers to submit original research, review articles, or clinical data, focused on recent advances on the main topics described below.

Keywords

Neuropsychiatric disorders
Associated digestive dysfunctions
Gastrointestinal disorders
Oxidative stress
ROME IV criteria
Functional gastrointestinal disorders
Gut–brain interaction impairments
Gut microbiota
Biomarkers

Published Papers (10 papers)

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Research

Jump to: Review

26 pages, 6799 KiB

Open AccessArticle

Testing the Accuracy of the ARIMA Models in Forecasting the Spreading of COVID-19 and the Associated Mortality Rate

by Ovidiu-Dumitru Ilie, Alin Ciobica and Bogdan Doroftei

Medicina 2020, 56(11), 566; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56110566 - 27 Oct 2020

Cited by 7 | Viewed by 4599

Abstract

Background and objectives: The current pandemic of SARS-CoV-2 has not only changed, but also affected the lives of tens of millions of people around the world in these last nine to ten months. Although the situation is stable to some extent within the developed countries, approximately one million have already died as a consequence of the unique symptomatology that these people displayed. Thus, the need to develop an effective strategy for monitoring, restricting, but especially for predicting the evolution of COVID-19 is urgent, especially in middle-class countries such as Romania. Material and Methods: Therefore, autoregressive integrated moving average (ARIMA) models have been created, aiming to predict the epidemiological course of COVID-19 in Romania by using two statistical software (STATGRAPHICS Centurion (v.18.1.13) and IBM SPSS (v.20.0.0)). To increase the accuracy, we collected data between the established interval (1 March, 31 August) from the official website of the Romanian Government and the World Health Organization. Results: Several ARIMA models were generated from which ARIMA (1,2,1), ARIMA (3,2,2), ARIMA (3,1,3), ARIMA (3,2,2), ARIMA (3,1,3), ARIMA (2,2,2) and ARIMA (1,2,1) were considered the best models. For this, we took into account the lowest value of mean absolute percentage error (MAPE) for March, April, May, June, July, and August (MAPE_March = 9.3225, MAPE_April = 0.975287, MAPE_May = 0.227675, MAPE_June = 0.161412, MAPE_July = 0.243285, MAPE_August = 0.163873, MAPE_{March – August} = 2.29175 for STATGRAPHICS Centurion (v.18.1.13) and MAPE_March = 57.505, MAPE_April = 1.152, MAPE_May = 0.259, MAPE_June = 0.185, MAPE_July = 0.307, MAPE_August = 0.194, and MAPE_{March – August} = 6.013 for IBM SPSS (v.20.0.0) respectively. Conclusions: This study demonstrates that ARIMA is a useful statistical model for making predictions and provides an idea of the epidemiological status of the country of interest. Full article

(This article belongs to the Special Issue Oxidative Stress as a Commune Factor for the Interplay between, Neuropsychiatric and Gastrointestinal Disorders)

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21 pages, 1574 KiB

Open AccessArticle

Oxytocin Differentiated Effects According to the Administration Route in a Prenatal Valproic Acid-Induced Rat Model of Autism

by Radu Lefter, Alin Ciobica, Iulia Antioch, Daniela Carmen Ababei, Luminita Hritcu and Alina-Costina Luca

Medicina 2020, 56(6), 267; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56060267 - 29 May 2020

Cited by 11 | Viewed by 3059

Abstract

Background and objectives: The hormone oxytocin (OXT) has already been reported in both human and animal studies for its promising therapeutic potential in autism spectrum disorder (ASD), but the comparative effectiveness of various administration routes, whether central or peripheral has been insufficiently studied. In the present study, we examined the effects of intranasal (IN) vs. intraperitoneal (IP) oxytocin in a valproic-acid (VPA) autistic rat model, focusing on cognitive and mood behavioral disturbances, gastrointestinal transit and central oxidative stress status. Materials and Methods: VPA prenatally-exposed rats (500 mg/kg; age 90 days) in small groups of 5 (n = 20 total) were given OXT by IP injection (10 mg/kg) for 8 days consecutively or by an adapted IN pipetting protocol (12 IU/kg, 20 μL/day) for 4 consecutive days. Behavioral tests were performed during the last three days of OXT treatment, and OXT was administrated 20 minutes before each behavioral testing for each rat. Biochemical determination of oxidative stress markers in the temporal area included superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA). A brief quantitative assessment of fecal discharge over a period of 24 hours was performed at the end of the OXT treatment to determine differences in intestinal transit. Results: OXT improved behavioral and oxidative stress status in both routes of administration, but IN treatment had significantly better outcome in improving short-term memory, alleviating depressive manifestations and mitigating lipid peroxidation in the temporal lobes. Significant correlations were also found between behavioral parameters and oxidative stress status in rats after OXT administration. The quantitative evaluation of the gastrointestinal (GI) transit indicated lower fecal pellet counts in the VPA group and homogenous average values for the control and both OXT treated groups. Conclusions: The data from the present study suggest OXT IN administration to be more efficient than IP injections in alleviating autistic cognitive and mood dysfunctions in a VPA-induced rat model. OXT effects on the cognitive and mood behavior of autistic rats may be associated with its effects on oxidative stress. Additionally, present results provide preliminary evidence that OXT may have a balancing effect on gastrointestinal motility. Full article

(This article belongs to the Special Issue Oxidative Stress as a Commune Factor for the Interplay between, Neuropsychiatric and Gastrointestinal Disorders)

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10 pages, 1389 KiB

Open AccessArticle

Systemic Oxidative Stress Markers in Cirrhotic Patients with Hepatic Encephalopathy: Possible Connections with Systemic Ammoniemia

by Cătălin Sfarti, Alin Ciobica, Ioana-Miruna Balmus, Ovidiu-Dumitru Ilie, Anca Trifan, Oana Petrea, Camelia Cojocariu, Irina Gîrleanu, Ana Maria Sîngeap and Carol Stanciu

Medicina 2020, 56(4), 196; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56040196 - 23 Apr 2020

Cited by 6 | Viewed by 3023

Abstract

Background and objectives: Oxidative stress shows evidence of dysregulation in cirrhotic patients with hepatic encephalopathy (HE), although there are still controversies regarding the connections between oxidative stress and ammonia in these patients. The aim of this study was to evaluate the oxidative stress implication in overt HE pathogenesis of cirrhotic patients. Materials and Methods: We performed a prospective case-control study, which included 40 patients divided into two groups: group A consisted of 20 cirrhotic patients with HE and increased systemic ammoniemia, and group B consisted of 20 cirrhotic patients with HE and normal systemic ammoniemia. The control group consisted of 21 healthy subjects matched by age and sex. The activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) levels (lipid peroxidation marker), and ammoniemia were evaluated. Results: We found a significant decrease in SOD and GPx activity and also a significant increase of MDA levels in cirrhotic patients with HE as compared to the healthy age-matched control group (1.35 ± 0.08 vs. 0.90 ± 0.08 U/mL, p = 0.002; 0.093 ± 0.06 vs. 0.006 ± 0.008 U/mL, p = 0.001; and 35.94 ± 1.37 vs. 68.90 ± 5.68 nmols/mL, p = 0.0001, respectively). Additionally, we found significant correlations between the main oxidative stress markers and the levels of systemic ammonia (r = 0.452, p = 0.005). Patients from group A had a significant increase of MDA as compared with those from group B (76.93 ± 5.48 vs. 50.06 ± 5.60 nmols/mL, p = 0.019). Also, there was a compensatory increase in the activity of both antioxidant enzymes (SOD and GPx) in patients with increased systemic ammoniemia (group A), as compared to HE patients from group B. Conclusions: Our results demonstrated a significant decrease in antioxidants enzymes activities (SOD and GPx), as well as a significant increase in MDA concentrations, adding new data regarding the influence of oxidative stress in HE pathogenesis in cirrhotic patients. Full article

(This article belongs to the Special Issue Oxidative Stress as a Commune Factor for the Interplay between, Neuropsychiatric and Gastrointestinal Disorders)

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Review

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15 pages, 2762 KiB

Open AccessReview

Serum BDNF Levels in Acute Stroke: A Systematic Review and Meta-Analysis

by Eleni Karantali, Dimitrios Kazis, Vasileios Papavasileiou, Angeliki Prevezianou, Symela Chatzikonstantinou, Foivos Petridis, Jack McKenna, Alina-Costina Luca, Constantin Trus, Alin Ciobica and Ioannis Mavroudis

Medicina 2021, 57(3), 297; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57030297 - 22 Mar 2021

Cited by 30 | Viewed by 3664

Abstract

Background and objectives: Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins. Low BDNF concentrations have been noted in patients with traditional cardiovascular disease risk factors and have been associated with the increased risk of stroke/transient ischemic attack (TIA). We aimed to study the correlation of BDNF serum levels with acute stroke severity and its potential role as a biomarker in predicting functional outcome. Materials and methods: We systematically searched PubMed, Web of Science, and the Cochrane database using specific keywords. The endpoints examined were the correlation of BDNF with functional outcome, the National Institute of Health stroke scale (NIHSS) measured at the acute phase, and stroke infarct volume. We also compared serum BDNF levels between stroke patients and healthy controls. Results: Twenty-six records were included from the initial 3088 identified. Twenty-five studies reported NIHSS and BDNF levels on the first day after acute stroke. Nine studies were further meta-analyzed. A statistically significant negative correlation between NIHSS and BDNF levels during the acute phase of stroke was noted (COR: −0.3013, 95%CI: (−0.4725; −0.1082), z = −3.01, p = 0.0026). We also noted that BDNF levels were significantly lower in patients with stroke compared to healthy individuals. Due to the heterogeneity of studies, we only conducted a qualitative analysis regarding serum BDNF and functional outcome, while no correlation between BDNF levels and stroke infarct volume was noted. Conclusions: We conclude that in the acute stroke phase, stroke severity is negatively correlated with BDNF levels. Concurrently, patients with acute stroke have significantly lower BDNF levels in serum compared to healthy controls. No correlations between BDNF and stroke infarct volume or functional outcome at follow-up were noted. Full article

(This article belongs to the Special Issue Oxidative Stress as a Commune Factor for the Interplay between, Neuropsychiatric and Gastrointestinal Disorders)

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10 pages, 2056 KiB

Open AccessReview

A Voxel-Wise Meta-Analysis on the Cerebellum in Essential Tremor

by Ioannis Mavroudis, Foivos Petrides, Eleni Karantali, Symela Chatzikonstantinou, Jack McKenna, Alin Ciobica, Alin-Constantin Iordache, Romeo Dobrin, Constantin Trus and Dimitrios Kazis

Medicina 2021, 57(3), 264; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57030264 - 14 Mar 2021

Cited by 11 | Viewed by 2414

Abstract

Background and Objectives: Essential tremor is a chronic progressive neurological condition. The clinical presentation of essential tremor is heterogeneous and includes involuntary tremor on hands or arms and progressively on head, jaw, and voice. More extensive and complex symptoms may also be noticed in several patients. Many studies have been carried out to identify biomarkers to help the diagnosis, however, all the efforts have not shown any substantial results yet. Materials and Methods: Here, we aimed to perform a voxel-based meta-analysis using a dedicated cerebellar mask to clarify whether the results from the previous studies are robust and have any clinical significance. We included studies with a total of 377 essential tremor patients and 338 healthy control individuals. Results: A significant regional decrease in the volume of the gray matter was detected in the right cerebellar hemispheric lobule IV/V, and in the cerebellar vermic lobule IV/V. Conclusions: This is the first study focused on the cerebellum and using a specific cerebellar mask, which increases the sensitivity. It showed regional statistically significant changes that could not be seen in the whole-brain analysis. Full article

(This article belongs to the Special Issue Oxidative Stress as a Commune Factor for the Interplay between, Neuropsychiatric and Gastrointestinal Disorders)

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22 pages, 1277 KiB

Open AccessReview

Mini-Review on Lipofuscin and Aging: Focusing on The Molecular Interface, The Biological Recycling Mechanism, Oxidative Stress, and The Gut-Brain Axis Functionality

by Ovidiu-Dumitru Ilie, Alin Ciobica, Sorin Riga, Nitasha Dhunna, Jack McKenna, Ioannis Mavroudis, Bogdan Doroftei, Adela-Magdalena Ciobanu and Dan Riga

Medicina 2020, 56(11), 626; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56110626 - 19 Nov 2020

Cited by 10 | Viewed by 4551

Abstract

Intra-lysosomal accumulation of the autofluorescent “residue” known as lipofuscin, which is found within postmitotic cells, remains controversial. Although it was considered a harmless hallmark of aging, its presence is detrimental as it continually accumulates. The latest evidence highlighted that lipofuscin strongly correlates with the excessive production of reactive oxygen species; however, despite this, lipofuscin cannot be removed by the biological recycling mechanisms. The antagonistic effects exerted at the DNA level culminate in a dysregulation of the cell cycle, by inducing a loss of the entire internal environment and abnormal gene(s) expression. Additionally, it appears that a crucial role in the production of reactive oxygen species can be attributed to gut microbiota, due to their ability to shape our behavior and neurodevelopment through their maintenance of the central nervous system. Full article

(This article belongs to the Special Issue Oxidative Stress as a Commune Factor for the Interplay between, Neuropsychiatric and Gastrointestinal Disorders)

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10 pages, 314 KiB

Open AccessReview

A Review of the Complex Relationship between Irritable Bowel Syndrome and Infertility

by Carmen Anton, Alin Ciobica, Bogdan Doroftei, Radu Maftei, Ciprian Ilea, Natalia Darii Plopa, Maria Bolota and Emil Anton

Medicina 2020, 56(11), 592; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56110592 - 06 Nov 2020

Cited by 4 | Viewed by 2632

Abstract

Irritable bowel syndrome (IBS) is a gastrointestinal disease that negatively affects up to 20% of the population. Infertility is defined as a disorder of the reproductive system described by lack of success in achieving pregnancy after more than a year of regular unprotected sexual intercourse. The main purpose of our review was to analyze the available literature regarding the IBS-infertility connection. Another secondary purpose of the present paper was to find out if oxidative stress may be the missing puzzle that may explain this possible correlation. After analyzing the available literature we concluded that oxidative stress is a plausible mediator of the connection between both female and male fertility and IBS. However, the data lacks in direct evidence to confirm this hypothesis. Nevertheless, it is recommended that certain levels of oxidative stress should not be exceeded in order to decrease IBS symptoms and increase the odds of conception given that generation of reactive oxygen species (ROS) is an aftermath of metabolically active cells. Therefore, reducing the oxidative stress by living a healthier lifestyle with a balanced diet, rich in micronutrients, limited in caffeine and alcohol, avoiding smoking and maintaining a normal body mass index with regular physical exercise may promote fertility and help diminishing IBS symptomatology. Studies with measurements of biological samples are needed in order to assess the complex relationship between oxidative stress, IBS and infertility. Full article

(This article belongs to the Special Issue Oxidative Stress as a Commune Factor for the Interplay between, Neuropsychiatric and Gastrointestinal Disorders)

32 pages, 506 KiB

Open AccessReview

Preclinical Considerations about Affective Disorders and Pain: A Broadly Intertwined, yet Often Under-Explored, Relationship Having Major Clinical Implications

by Iulia Antioch, Ovidiu-Dumitru Ilie, Alin Ciobica, Bogdan Doroftei and Michele Fornaro

Medicina 2020, 56(10), 504; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56100504 - 25 Sep 2020

Cited by 4 | Viewed by 2399

Abstract

Background: Pain, a distinctive undesirable experience, encompasses several different and fluctuating presentations across varying mood disorders. Therefore, the present narrative review aimed to shed further light on the matter, accounting for both experimental animal models and clinical observations about major depressive disorder (MDD) pathology. Method: Major databases were inquired from inception until April 2016 for records about MDD and pain. Results: Pain and MDD are tightly associated with each other in a bi-directional fashion. Several cross-sectional and retrospective studies indicated a high presence of pain in the context of mood disorders, including MDD (up to 65%), but also increased prevalence rates in the case of mood disorders documented among people with a primary diagnosis of either psychological or somatic pain (prevalence rates exceeding 45%). The clinical implications of these observations suggest the need to account for mood and pain manifestations as a whole rather than distinct entities in order to deliver more effective interventions. Limitations: Narrative review, lack of systematic control groups (e.g., people with the primary diagnosis at review, but not the associated comorbidity as a study) to allow reliable comparisons. Prevalence rates and clinical features associated with pain varied across different studies as corresponding operational definitions did. Conclusions: Pain may have a detrimental effect on the course of mood disorders—the opposite holds. Promoting a timely recognition and management of such an often neglected comorbidity would therefore represent a primary goal toward the delivery of effective, multi-disciplinary care. Full article

(This article belongs to the Special Issue Oxidative Stress as a Commune Factor for the Interplay between, Neuropsychiatric and Gastrointestinal Disorders)

12 pages, 729 KiB

Open AccessEditor’s ChoiceReview

Relationship between Vitamin Deficiencies and Co-Occurring Symptoms in Autism Spectrum Disorder

by Madalina-Andreea Robea, Alina-Costina Luca and Alin Ciobica

Medicina 2020, 56(5), 245; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56050245 - 20 May 2020

Cited by 20 | Viewed by 6312

Abstract

Recently, connections have been made between feeding and eating problems and autism spectrum disorder (ASD) and between autism pathophysiology and diet issues. These could explain some of the mechanisms which have not yet been discovered or are not sufficiently characterized. Moreover, there is an increased awareness for micronutrients in ASD due to the presence of gastrointestinal (GI) problems that can be related to feeding issues. For example, levels of vitamins B₁, B₆, B₁₂, A and D are often reported to be low in ASD children. Thus, in the present mini review we focused on describing the impact of some vitamins deficiencies and their relevance in ASD patients. Full article

(This article belongs to the Special Issue Oxidative Stress as a Commune Factor for the Interplay between, Neuropsychiatric and Gastrointestinal Disorders)

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18 pages, 615 KiB

Open AccessEditor’s ChoiceReview

Irritable Bowel Syndrome and Neurological Deficiencies: Is There A Relationship? The Possible Relevance of the Oxidative Stress Status

by Ioana-Miruna Balmus, Alin Ciobica, Roxana Cojocariu, Alina-Costina Luca and Lucian Gorgan

Medicina 2020, 56(4), 175; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina56040175 - 13 Apr 2020

Cited by 21 | Viewed by 3951

Abstract

Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, exhibiting complex and controversial pathological features. Both oxidative stress and inflammation-related reactive oxygen species production may be involved in IBS pathological development. Thus, we focused on several aspects regarding the causes of oxidative stress occurrence in IBS. Additionally, in the molecular context of oxidative changes, we tried to discuss these possible neurological implications in IBS. Methods: The literature search included the main available databases (e.g., ScienceDirect, Pubmed/Medline, Embase, and Google Scholar). Articles in the English language were taken into consideration. Our screening was conducted based on several words such as “irritable bowel syndrome”, “gut brain axis”, “oxidative stress”, “neuroendocrine”, and combinations. Results: While no consistent evidence suggests clear pathway mechanisms, it seems that the inflammatory response may also be relevant in IBS. The mild implication of oxidative stress in IBS has been described through clinical studies and some animal models, revealing changes in the main markers such as antioxidant status and peroxidation markers. Moreover, it seems that the neurological structures involved in the brain-gut axis may be affected in IBS rather than the local gut tissue and functionality. Due to a gut-brain axis bidirectional communication error, a correlation between neurological impairment, emotional over-responsiveness, mild inflammatory patterns, and oxidative stress can be suggested. Conclusions: Therefore, there is a possible correlation between neurological impairment, emotional over-responsiveness, mild inflammatory patterns, and oxidative stress that are not followed by tissue destruction in IBS patients. Moreover, it is not yet clear whether oxidative stress, inflammation, or neurological impairments are key determinants or in which way these three interact in IBS pathology. However, the conditions in which oxidative imbalances occur may be an interesting research lead in order to find possible explanations for IBS development. Full article

(This article belongs to the Special Issue Oxidative Stress as a Commune Factor for the Interplay between, Neuropsychiatric and Gastrointestinal Disorders)

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