BackgroundNon-polio Enteroviruses (EV) are important neonatal CNS pathogens. Multiple EV genotype... more BackgroundNon-polio Enteroviruses (EV) are important neonatal CNS pathogens. Multiple EV genotypes have been detected in pediatric CSF, e.g. Echovirus (E) 6 and E30. CSF innate immune responses to EV genotypes remain poorly defined. Most data are from EV-A71 or E30 CNS infections and do not compare responses between these or other EV types. We sought to better define innate immune responses to EV genotypes in CSF.MethodsSalvaged standard of care CSF samples from ≤6 month olds (real time EV PCR(+) or EV PCR(-) controls) from Jan 2010 - Dec 2020 were tested in duplicate on a 21- cytokine bead panel (MilliporeSigma). EV positive samples were previously genotyped by sequencing the viral capsid gene. Cytokine levels calculated from the standard curve were compared by Kruskal-Wallis and post-hoc analysis (GraphPad Prism 8.4.3). Natural partitioning of participants was explored using principal component analysis and cluster analysis (IBM SPSS v27). The utility of cytokine signatures in predicting EV status was explored using discriminant analysis and ROC analysis (IBM SPSS v27).ResultsData from 72 CSF with E6 (N=16), E9 (N= 9), E18 (N=9), and E30 (N=21) showed significant differences among EV genotypes vs. controls for 20 cytokines (IL-17 was excluded). Significant differences in cytokine levels in EV CSF vs controls were seen: E6 for all 20 cytokines; E9 for Fractalkine, IP10, and MCP1; E18 for Fractalkine and MCP1; E30 19 cytokines (not GM-CSF). PCA revealed only minor overlap of controls and EV positives; EV types overlapped, except E30, differing most from E9 and E18 but overlapping E6. The most important type-differentiating cytokines by PCA were MCP1, Fractalkine, IL-8, and IL-10. Patterns in DA resembled PCA; controls clearly separated from EV CSF, E30 being the most distinct. Overall, the discriminant model correctly classified EV type or controls at a 63% rate - highest for controls (94.1%) and E30 (74.1%). In the DA model, the most important cytokines were IP-10, IL-2, IL-1Ra, and Fractalkine. Discriminant scores had the largest area under the curve (AUC), 0.990. Among cytokines, IFNa2 had the largest AUC, 0.987. Open in a separate windowConclusionPreliminary data show significant EV-genotype differences in innate immune response to CNS infections. Cytokine patterns may serve as a key predictor for discerning EV genotypes.Disclosures Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.
<p>Set 1 (a) and 2 (b) data obtained from autistic and healthy control participants were an... more <p>Set 1 (a) and 2 (b) data obtained from autistic and healthy control participants were analyzed with PCA. Screen plots show Eigen values of raw data (blue), as well as the 50<sup>th</sup> (green) and 95<sup>th</sup> percentile (yellow) simulated data. A principal component was considered statistically significant (circled in red) whenever its raw data Eigen value lay above the corresponding 95<sup>th</sup> percentile simulated data Eigen value.</p
<p>(a) Rates of correct assignment of autistic and control groups. Control and autistic lib... more <p>(a) Rates of correct assignment of autistic and control groups. Control and autistic library units were composed, respectively, of 39 and 35 participants when using set 1 biomarkers; and 16 and 29 participants when using set 2 biomarkers. (b) Rates of correct assignment in autstic patients with mild-to-moderate sensory profile impairment and those with high impairment. Severe and mild-to-moderate library units wre composed of 12 and 17 participants, respectively. Biomarkers used in the identification process were set 1: PE, PS, PC, MAP2K1, IL-10, IL-12, and NFκB; set 2: PGE2, PGE2-EP2, PGES, cPLA2, 8-isoprostane, and COX-2; set 3: PGE2, PGES, cPLA2, 8-isoprostane, COX-2, and PE; and set 4: PGE2, PGES, and PE.</p
<p>Correlation between sensory profile scores and each of the variables was calculated usin... more <p>Correlation between sensory profile scores and each of the variables was calculated using Pearson and Spearman Correlation Coefficients to evaluate linear and monotonic nonlinear correlations, respectively. P values (in parenthesis) indicate the likelihood of obtaining the corresponding correlation value or a higher value due to random sampling alone. A linear regression line is shown with 95% confidence intervals (dotted lines).</p
<p>Autistic patients were classified into two groups, one with severe impairment of sensory... more <p>Autistic patients were classified into two groups, one with severe impairment of sensory profiles (purple squares) and the other with mild or moderate impairment (magenta squares). Principal component analysis (a&b) and multidimensional scaling (c&d) scatter plots based on set 1 (a&c) do not show separation between groups, while set 2 biomarkers (b&d) show visually discernible—although not complete—separation. Hierarchical clustering failed to show separation of autistic patient groups based on either set 1 (e) or 2 (f) biomarkers. Dendrograms were constructed from Canberra distances data using Neighbor joining algorithm. Heat maps depict marker values with darker grey indicative of higher values. Heat map variables from left to right are (e) PE, PS, PC, MAP2K1, IL-10, IL-12, and NFκB, and (f) PGE2, PGE2-EP2, PGES, cPLA2, 8-isoprostane, and COX-2.</p
Obesity prevalence is rising globally, as are the number of chronic disorders connected with obes... more Obesity prevalence is rising globally, as are the number of chronic disorders connected with obesity, such as diabetes, non-alcoholic fatty liver disease, dyslipidemia, and hypertension. Bariatric surgery is also becoming more common, and it remains the most effective and long-term treatment for obesity. This study will assess the influence of Laparoscopic Sleeve Gastrectomy (LSG) on gut microbiota in people with obesity before and after surgery. The findings shed new light on the changes in gut microbiota in Saudi people with obesity following LSG. In conclusion, LSG may improve the metabolic profile, resulting in decreased fat mass and increased lean mass, as well as improving the microbial composition balance in the gastrointestinal tract, but this is still not equivalent to normal weight microbiology. A range of factors, including patient characteristics, geographic dispersion, type of operation, technique, and nutritional and caloric restriction, could explain differences in ab...
We report the first case of pericarditis exacerbation due to influenza B viral infection while em... more We report the first case of pericarditis exacerbation due to influenza B viral infection while emphasizing the importance of cardiac magnetic resonance (CMR) for the timely diagnosis and ruling out of non-effusive pericarditis in a patient with compatible, unexplained chest pain. The patient presented with left-sided chest pain that was partially relieved by leaning backward and noted persistent fatigue for several days. Pericardial friction rub, electrocardiogram (ECG), and echocardiogram abnormalities were not detected. After discharge on the morning following admission, fatigue and fever several minutes after physical exertion continued. The patient contracted influenza type B, leading to pneumonia and a second hospitalization, during which echocardiography showed moderate pericardial effusion. We conclude that the patient had pericarditis on the first admission because other compatible causes of chest pain were ruled out, symptoms were compatible with non-effusive pericarditis and could not be ruled out since CMR was not done, and the patient tested positive during his second admission for multiple known etiologic agents of pericarditis. We highlight the importance of CMR in screening patients presenting with chest pain of unknown origin to facilitate early detection and intervention.
The novel coronavirus pandemic continues to cause significant morbidity and mortality around the ... more The novel coronavirus pandemic continues to cause significant morbidity and mortality around the world. Diverse clinical presentations prompted numerous attempts to predict disease severity to improve care and patient outcomes. Equally important is understanding the mechanisms underlying such divergent disease outcome. Multivariate modeling was used here to define the most distinctive features that separate COVID-19 from healthy controls and those that separate severe from moderate disease. Using discriminant analysis and binary logistic regression models we could distinguish between COVID-19 patients with severe disease, those with moderate disease, and controls with rates of correct classifications ranging from 71-100%. The distinction of severe and moderate disease was most reliant on the depletion of natural killer cells and activated, class-switched memory B cells, increased frequency of neutrophils, and decreased expression of the activation marker HLA-DR on monocytes in patie...
This study aims to explore the effects of Garcinia mangostana (mangosteen) and Curcuma longa inde... more This study aims to explore the effects of Garcinia mangostana (mangosteen) and Curcuma longa independently and synergistically in modulating induced inflammation and impaired brain neurotransmitters commonly observed in high-fat diet-induced obesity in rodent models. Male albino Wistar rats were divided into four experimental groups. Group I, control, obese, fed on a high-fat diet (HFD), and Group II-IV, fed on HFD then given mangosteen extract (400 mg/kg/day) and/or Curcuma (80 mg/kg/day), or a mixture of both for 6 weeks. Plasma pro-inflammatory cytokines, leptin, and brain serotonin, dopamine, and glutamate were measured in the five studied groups. G. mangostana and Curcuma longa extracts demonstrate antioxidant and DPPH radical scavenging activities. Both induced a significant reduction in the weight gained, concomitant with a non-significant decrease in the BMI (from 0.86 to 0.81 g/cm2). Curcuma either alone or in combination with MPE was more effective. Both extracts demonstra...
Autism spectrum disorders (ASDs) are neurodevelopmental disorders that clinically presented as im... more Autism spectrum disorders (ASDs) are neurodevelopmental disorders that clinically presented as impaired social interaction, repetitive behaviors, and weakened communication. The use of bee pollen as a supplement rich in amino acids amino acids, vitamins, lipids, and countless bioactive substances may lead to the relief of oxidative stress, neuroinflammation, glutamate excitotoxicity, and impaired neurochemistry as etiological mechanisms autism. Thirty young male Western albino rats were randomly divided as: Group I-control; Group II, in which autism was induced by the oral administration of 250 mg propionic acid/kg body weight/day for three days followed by orally administered saline until the end of experiment and Group III, the bee pollen-treated group, in which the rats were treated with 250 mg/kg body weight of bee pollen for four weeks before autism was induced as described for Group II. Markers related to oxidative stress, apoptosis, inflammation, glutamate excitotoxicity, and...
Neuropeptides play a major role in maintaining normal brain development in children. Dysfunction ... more Neuropeptides play a major role in maintaining normal brain development in children. Dysfunction of some specific neuropeptides can lead to autism spectrum disorders (ASD) in terms of social interaction and repetitive behavior, but the exact underlying etiological mechanisms are still not clear. In this study, we used an animal model of autism to investigate the role of bee pollen and probiotic in maintaining neuropeptide levels in the brain. We measured the Alpha-melanocyte-stimulating hormone (α-MSH), Beta-endorphin (β-End), neurotensin (NT), and substance P (SP) in brain homogenates of six studied groups of rats. Group I served as control, given only PBS for 30 days; Group II as an autistic model treated with 250 mg PPA/kg BW/day for 3 days after being given PBS for 27 days. Groups III-VI were denoted as intervention groups. G-III was treated with bee pollen (BP) 250 mg/kg body weight/day; G-IV with Lactobacillus paracaseii (LB) (109 CFU/mL) suspended in PBS; G-V with 0.2 g/kg bo...
2017 IEEE International Conference on Bioinformatics and Biomedicine (BIBM), 2017
It is critical to be able to identify longitudinally changing genes in temporal data so that stud... more It is critical to be able to identify longitudinally changing genes in temporal data so that studies can be focused on how gene expression changes in a dynamic way. While biological networks continue to play a significant role in modeling and characterizing complex relationships in biological systems, most network modeling studies in biomedical research focus on snapshot or “static” network-based analysis to identify genes of interest. In this study, we use a temporal non-sampling network-based approach to identify and rank genes that exhibit significant co-expression variation over time. We use in the C. elegans gene correlation network obtained from mRNA expression profiles to illustrate the value of the proposed approach. We compare the results of this method to results obtained from traditional statistical analysis that focuses on identifying simple differentially expressed genes. We show that rank-based temporal network analysis can identify genes that contribute to changes in the network structure and consequently contribute to changes in the genetic regulatory machine.
2017 IEEE International Conference on Bioinformatics and Biomedicine (BIBM), 2017
It is critical to be able to identify longitudinally changing genes in temporal data so that stud... more It is critical to be able to identify longitudinally changing genes in temporal data so that studies can be focused on how gene expression changes in a dynamic way. While biological networks continue to play a significant role in modeling and characterizing complex relationships in biological systems, most network modeling studies in biomedical research focus on snapshot or “static” network-based analysis to identify genes of interest. In this study, we use a temporal non-sampling network-based approach to identify and rank genes that exhibit significant co-expression variation over time. We use in the C. elegans gene correlation network obtained from mRNA expression profiles to illustrate the value of the proposed approach. We compare the results of this method to results obtained from traditional statistical analysis that focuses on identifying simple differentially expressed genes. We show that rank-based temporal network analysis can identify genes that contribute to changes in the network structure and consequently contribute to changes in the genetic regulatory machine.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social ... more 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 perform...
Multiple neurodegenerative diseases are causally linked to aggregation-prone proteins. Cellular m... more Multiple neurodegenerative diseases are causally linked to aggregation-prone proteins. Cellular mechanisms involving protein turnover may be key defense mechanisms against aggregating protein disorders. We have used a transgenic Caenorhabditis elegans Alzheimer’s disease model to identify cellular responses to pro-teotoxicity resulting from expression of the human beta amyloid peptide (Ab). We show up-regulation of aip-1 in Ab-expressing animals. Mammalian homologues of AIP-1 have been shown to associate with, and regulate the function of, the 26S proteasome, leading us to hypothesize that induction of AIP-1 may be a pro-tective cellular response directed toward modulating proteasomal function in response to toxic protein aggregation. Using our transgenic model, we show that overexpression of AIP-1 protected against, while RNAi knockdown of AIP-1 exacerbated, Ab toxicity. AIP-1 overexpression also reduced accumulation of Ab in this model, which is consistent with AIP-1 enhancing pro...
BackgroundNon-polio Enteroviruses (EV) are important neonatal CNS pathogens. Multiple EV genotype... more BackgroundNon-polio Enteroviruses (EV) are important neonatal CNS pathogens. Multiple EV genotypes have been detected in pediatric CSF, e.g. Echovirus (E) 6 and E30. CSF innate immune responses to EV genotypes remain poorly defined. Most data are from EV-A71 or E30 CNS infections and do not compare responses between these or other EV types. We sought to better define innate immune responses to EV genotypes in CSF.MethodsSalvaged standard of care CSF samples from ≤6 month olds (real time EV PCR(+) or EV PCR(-) controls) from Jan 2010 - Dec 2020 were tested in duplicate on a 21- cytokine bead panel (MilliporeSigma). EV positive samples were previously genotyped by sequencing the viral capsid gene. Cytokine levels calculated from the standard curve were compared by Kruskal-Wallis and post-hoc analysis (GraphPad Prism 8.4.3). Natural partitioning of participants was explored using principal component analysis and cluster analysis (IBM SPSS v27). The utility of cytokine signatures in predicting EV status was explored using discriminant analysis and ROC analysis (IBM SPSS v27).ResultsData from 72 CSF with E6 (N=16), E9 (N= 9), E18 (N=9), and E30 (N=21) showed significant differences among EV genotypes vs. controls for 20 cytokines (IL-17 was excluded). Significant differences in cytokine levels in EV CSF vs controls were seen: E6 for all 20 cytokines; E9 for Fractalkine, IP10, and MCP1; E18 for Fractalkine and MCP1; E30 19 cytokines (not GM-CSF). PCA revealed only minor overlap of controls and EV positives; EV types overlapped, except E30, differing most from E9 and E18 but overlapping E6. The most important type-differentiating cytokines by PCA were MCP1, Fractalkine, IL-8, and IL-10. Patterns in DA resembled PCA; controls clearly separated from EV CSF, E30 being the most distinct. Overall, the discriminant model correctly classified EV type or controls at a 63% rate - highest for controls (94.1%) and E30 (74.1%). In the DA model, the most important cytokines were IP-10, IL-2, IL-1Ra, and Fractalkine. Discriminant scores had the largest area under the curve (AUC), 0.990. Among cytokines, IFNa2 had the largest AUC, 0.987. Open in a separate windowConclusionPreliminary data show significant EV-genotype differences in innate immune response to CNS infections. Cytokine patterns may serve as a key predictor for discerning EV genotypes.Disclosures Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.
<p>Set 1 (a) and 2 (b) data obtained from autistic and healthy control participants were an... more <p>Set 1 (a) and 2 (b) data obtained from autistic and healthy control participants were analyzed with PCA. Screen plots show Eigen values of raw data (blue), as well as the 50<sup>th</sup> (green) and 95<sup>th</sup> percentile (yellow) simulated data. A principal component was considered statistically significant (circled in red) whenever its raw data Eigen value lay above the corresponding 95<sup>th</sup> percentile simulated data Eigen value.</p
<p>(a) Rates of correct assignment of autistic and control groups. Control and autistic lib... more <p>(a) Rates of correct assignment of autistic and control groups. Control and autistic library units were composed, respectively, of 39 and 35 participants when using set 1 biomarkers; and 16 and 29 participants when using set 2 biomarkers. (b) Rates of correct assignment in autstic patients with mild-to-moderate sensory profile impairment and those with high impairment. Severe and mild-to-moderate library units wre composed of 12 and 17 participants, respectively. Biomarkers used in the identification process were set 1: PE, PS, PC, MAP2K1, IL-10, IL-12, and NFκB; set 2: PGE2, PGE2-EP2, PGES, cPLA2, 8-isoprostane, and COX-2; set 3: PGE2, PGES, cPLA2, 8-isoprostane, COX-2, and PE; and set 4: PGE2, PGES, and PE.</p
<p>Correlation between sensory profile scores and each of the variables was calculated usin... more <p>Correlation between sensory profile scores and each of the variables was calculated using Pearson and Spearman Correlation Coefficients to evaluate linear and monotonic nonlinear correlations, respectively. P values (in parenthesis) indicate the likelihood of obtaining the corresponding correlation value or a higher value due to random sampling alone. A linear regression line is shown with 95% confidence intervals (dotted lines).</p
<p>Autistic patients were classified into two groups, one with severe impairment of sensory... more <p>Autistic patients were classified into two groups, one with severe impairment of sensory profiles (purple squares) and the other with mild or moderate impairment (magenta squares). Principal component analysis (a&b) and multidimensional scaling (c&d) scatter plots based on set 1 (a&c) do not show separation between groups, while set 2 biomarkers (b&d) show visually discernible—although not complete—separation. Hierarchical clustering failed to show separation of autistic patient groups based on either set 1 (e) or 2 (f) biomarkers. Dendrograms were constructed from Canberra distances data using Neighbor joining algorithm. Heat maps depict marker values with darker grey indicative of higher values. Heat map variables from left to right are (e) PE, PS, PC, MAP2K1, IL-10, IL-12, and NFκB, and (f) PGE2, PGE2-EP2, PGES, cPLA2, 8-isoprostane, and COX-2.</p
Obesity prevalence is rising globally, as are the number of chronic disorders connected with obes... more Obesity prevalence is rising globally, as are the number of chronic disorders connected with obesity, such as diabetes, non-alcoholic fatty liver disease, dyslipidemia, and hypertension. Bariatric surgery is also becoming more common, and it remains the most effective and long-term treatment for obesity. This study will assess the influence of Laparoscopic Sleeve Gastrectomy (LSG) on gut microbiota in people with obesity before and after surgery. The findings shed new light on the changes in gut microbiota in Saudi people with obesity following LSG. In conclusion, LSG may improve the metabolic profile, resulting in decreased fat mass and increased lean mass, as well as improving the microbial composition balance in the gastrointestinal tract, but this is still not equivalent to normal weight microbiology. A range of factors, including patient characteristics, geographic dispersion, type of operation, technique, and nutritional and caloric restriction, could explain differences in ab...
We report the first case of pericarditis exacerbation due to influenza B viral infection while em... more We report the first case of pericarditis exacerbation due to influenza B viral infection while emphasizing the importance of cardiac magnetic resonance (CMR) for the timely diagnosis and ruling out of non-effusive pericarditis in a patient with compatible, unexplained chest pain. The patient presented with left-sided chest pain that was partially relieved by leaning backward and noted persistent fatigue for several days. Pericardial friction rub, electrocardiogram (ECG), and echocardiogram abnormalities were not detected. After discharge on the morning following admission, fatigue and fever several minutes after physical exertion continued. The patient contracted influenza type B, leading to pneumonia and a second hospitalization, during which echocardiography showed moderate pericardial effusion. We conclude that the patient had pericarditis on the first admission because other compatible causes of chest pain were ruled out, symptoms were compatible with non-effusive pericarditis and could not be ruled out since CMR was not done, and the patient tested positive during his second admission for multiple known etiologic agents of pericarditis. We highlight the importance of CMR in screening patients presenting with chest pain of unknown origin to facilitate early detection and intervention.
The novel coronavirus pandemic continues to cause significant morbidity and mortality around the ... more The novel coronavirus pandemic continues to cause significant morbidity and mortality around the world. Diverse clinical presentations prompted numerous attempts to predict disease severity to improve care and patient outcomes. Equally important is understanding the mechanisms underlying such divergent disease outcome. Multivariate modeling was used here to define the most distinctive features that separate COVID-19 from healthy controls and those that separate severe from moderate disease. Using discriminant analysis and binary logistic regression models we could distinguish between COVID-19 patients with severe disease, those with moderate disease, and controls with rates of correct classifications ranging from 71-100%. The distinction of severe and moderate disease was most reliant on the depletion of natural killer cells and activated, class-switched memory B cells, increased frequency of neutrophils, and decreased expression of the activation marker HLA-DR on monocytes in patie...
This study aims to explore the effects of Garcinia mangostana (mangosteen) and Curcuma longa inde... more This study aims to explore the effects of Garcinia mangostana (mangosteen) and Curcuma longa independently and synergistically in modulating induced inflammation and impaired brain neurotransmitters commonly observed in high-fat diet-induced obesity in rodent models. Male albino Wistar rats were divided into four experimental groups. Group I, control, obese, fed on a high-fat diet (HFD), and Group II-IV, fed on HFD then given mangosteen extract (400 mg/kg/day) and/or Curcuma (80 mg/kg/day), or a mixture of both for 6 weeks. Plasma pro-inflammatory cytokines, leptin, and brain serotonin, dopamine, and glutamate were measured in the five studied groups. G. mangostana and Curcuma longa extracts demonstrate antioxidant and DPPH radical scavenging activities. Both induced a significant reduction in the weight gained, concomitant with a non-significant decrease in the BMI (from 0.86 to 0.81 g/cm2). Curcuma either alone or in combination with MPE was more effective. Both extracts demonstra...
Autism spectrum disorders (ASDs) are neurodevelopmental disorders that clinically presented as im... more Autism spectrum disorders (ASDs) are neurodevelopmental disorders that clinically presented as impaired social interaction, repetitive behaviors, and weakened communication. The use of bee pollen as a supplement rich in amino acids amino acids, vitamins, lipids, and countless bioactive substances may lead to the relief of oxidative stress, neuroinflammation, glutamate excitotoxicity, and impaired neurochemistry as etiological mechanisms autism. Thirty young male Western albino rats were randomly divided as: Group I-control; Group II, in which autism was induced by the oral administration of 250 mg propionic acid/kg body weight/day for three days followed by orally administered saline until the end of experiment and Group III, the bee pollen-treated group, in which the rats were treated with 250 mg/kg body weight of bee pollen for four weeks before autism was induced as described for Group II. Markers related to oxidative stress, apoptosis, inflammation, glutamate excitotoxicity, and...
Neuropeptides play a major role in maintaining normal brain development in children. Dysfunction ... more Neuropeptides play a major role in maintaining normal brain development in children. Dysfunction of some specific neuropeptides can lead to autism spectrum disorders (ASD) in terms of social interaction and repetitive behavior, but the exact underlying etiological mechanisms are still not clear. In this study, we used an animal model of autism to investigate the role of bee pollen and probiotic in maintaining neuropeptide levels in the brain. We measured the Alpha-melanocyte-stimulating hormone (α-MSH), Beta-endorphin (β-End), neurotensin (NT), and substance P (SP) in brain homogenates of six studied groups of rats. Group I served as control, given only PBS for 30 days; Group II as an autistic model treated with 250 mg PPA/kg BW/day for 3 days after being given PBS for 27 days. Groups III-VI were denoted as intervention groups. G-III was treated with bee pollen (BP) 250 mg/kg body weight/day; G-IV with Lactobacillus paracaseii (LB) (109 CFU/mL) suspended in PBS; G-V with 0.2 g/kg bo...
2017 IEEE International Conference on Bioinformatics and Biomedicine (BIBM), 2017
It is critical to be able to identify longitudinally changing genes in temporal data so that stud... more It is critical to be able to identify longitudinally changing genes in temporal data so that studies can be focused on how gene expression changes in a dynamic way. While biological networks continue to play a significant role in modeling and characterizing complex relationships in biological systems, most network modeling studies in biomedical research focus on snapshot or “static” network-based analysis to identify genes of interest. In this study, we use a temporal non-sampling network-based approach to identify and rank genes that exhibit significant co-expression variation over time. We use in the C. elegans gene correlation network obtained from mRNA expression profiles to illustrate the value of the proposed approach. We compare the results of this method to results obtained from traditional statistical analysis that focuses on identifying simple differentially expressed genes. We show that rank-based temporal network analysis can identify genes that contribute to changes in the network structure and consequently contribute to changes in the genetic regulatory machine.
2017 IEEE International Conference on Bioinformatics and Biomedicine (BIBM), 2017
It is critical to be able to identify longitudinally changing genes in temporal data so that stud... more It is critical to be able to identify longitudinally changing genes in temporal data so that studies can be focused on how gene expression changes in a dynamic way. While biological networks continue to play a significant role in modeling and characterizing complex relationships in biological systems, most network modeling studies in biomedical research focus on snapshot or “static” network-based analysis to identify genes of interest. In this study, we use a temporal non-sampling network-based approach to identify and rank genes that exhibit significant co-expression variation over time. We use in the C. elegans gene correlation network obtained from mRNA expression profiles to illustrate the value of the proposed approach. We compare the results of this method to results obtained from traditional statistical analysis that focuses on identifying simple differentially expressed genes. We show that rank-based temporal network analysis can identify genes that contribute to changes in the network structure and consequently contribute to changes in the genetic regulatory machine.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social ... more 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 perform...
Multiple neurodegenerative diseases are causally linked to aggregation-prone proteins. Cellular m... more Multiple neurodegenerative diseases are causally linked to aggregation-prone proteins. Cellular mechanisms involving protein turnover may be key defense mechanisms against aggregating protein disorders. We have used a transgenic Caenorhabditis elegans Alzheimer’s disease model to identify cellular responses to pro-teotoxicity resulting from expression of the human beta amyloid peptide (Ab). We show up-regulation of aip-1 in Ab-expressing animals. Mammalian homologues of AIP-1 have been shown to associate with, and regulate the function of, the 26S proteasome, leading us to hypothesize that induction of AIP-1 may be a pro-tective cellular response directed toward modulating proteasomal function in response to toxic protein aggregation. Using our transgenic model, we show that overexpression of AIP-1 protected against, while RNAi knockdown of AIP-1 exacerbated, Ab toxicity. AIP-1 overexpression also reduced accumulation of Ab in this model, which is consistent with AIP-1 enhancing pro...
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Papers by Wail Hassan