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Considerable disturbances in post-translational protein phosphorylation have recently been discovered in multiple neurological disorders. Casein kinase-2 (CK2) is a tetrameric Ser/Thr protein kinase that phosphorylates a large number of substrates and contributes in several cellular physiological and pathological processes. CK2 is highly expressed in the mammalian brain and catalyzes the phosphorylation of a large number of substrates that are crucial in neuronal or glial homeostasis and inflammatory signaling processes across synapses. In this study, we investigated the impact of auditory integration therapy (AIT) for the treatment of sensory processing abnormalities in autism on plasma CK2 levels. A total of 25 ASD children, aged between 5 and 12 years, were enrolled and participated in the present research study. AIT was performed for two weeks, for a period of 30 min, twice a day, with a 3 h interval between sessions. Before and after AIT, the Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Short Sensory Profile (SSP) scores were calculated, and plasma CK2 levels were assayed using an ELISA test. The CARS and SRS indices of autism severity improved as a result of AIT, which could be related to the decreased level of plasma CK2. However, the mean value of the SSP scores was not significantly increased after AIT. The relationship between CK2 downregulation and glutamate excitotoxicity, neuro-inflammation, and leaky gut, as etiological mechanisms in ASD, was proposed and discussed. Further research, conducted on a larger scale and with a longer study duration, are required to assess whether the cognitive improvement in ASD children after AIT is related to the downregulation of CK2.

The essential oil and macroelemental composition of different parts of flower bud (petal, choke, and heart) of Cynara scolymus L. were explored and compared using gas chromatography mass spectrometry (GC-MS) and inductively coupled plasma mass spectrometry (ICP-MS). Overall, 62 organic components were detected in the flower bud based on mass spectra characteristics and retention indices. The essential oil extracted from the petals, choke, and bud showed the presence of thirty-one, twenty-one, and twenty-one compounds, respectively, with linoleic acid and palmitic acid as the major components. 21 components were identified in the oil of the petals, comprising 94.45% of the total oil, in which linoleic acid methyl ester, palmitic acid methyl ester, octadecanoic acid methyl ester, O-α-d-glucopyranoside, and heptyl oct-3-yl ester were the major constituents. Twenty-one compounds, representing 89.13% of the total oil, were detected in the choke oil. Linoleic acid methyl ester, palmitic acid methyl ester, and 2-methyl-1-hexadecanol were the main components. However, the edible heart oil contains twenty compounds, comprising 86.84% of the total oil. Cyclopropane butanoic acid, linoleic acid, methyl ester, and palmitic acid were the major constituents. The analysis executed by ICP-MS revealed the presence of significant amounts of various inorganic elements in all the three samples. The extracted essential oils were tested for antibacterial, antioxidant, and anticancer activities. The results showed that the oil extracted from the petals of C. scolymus flower bud displayed the highest antibacterial, antioxidant, anti-inflammatory, and anticancer effects, as compared to choke and heart oils.

Background: Inflammation plays a major role in dry eye diseases and is the prime target in clinical treatments of the disease. Objective: To determine whether the inflammatory cytokines in the tear film of patients with dry eye correlate with parameters such as Tear Break-Up Time (TBUT) and Tear Meniscus Height (TMH) and could be used together as predictive biomarkers of disease severity. Methods: This study included 58 eyes (29 female subjects; age, 19–25 years) comprising 20 normal eyes (control), 20 eyes (level 1 dryness), and 18 eyes (level 2 dryness). Dryness level 1 or 2 is keratographic diagnosis according to the tear break-up time cut-off value obtained. After ophthalmic examinations, including determination of non-invasive TBUT average and first second and TMH using Keratograph 4 (to measure dryness level), tears of all participants were collected. Five cytokines, including interleukin 6, 10, 12, interferon-γ, and tumor necrosis factor-α, were measured using ELISA. Results: Significant changes were observed in all measured cytokines and these changes correlated with eye dryness severity scores. Both groups (levels 1 & 2) showed remarkable changes related to ocular surface alterations in clinical examinations. Significantly, shorter TBUT and TMH were recorded in both groups and were positively correlated with the dryness severity. Conclusion: Cytokines could be used as predictive markers for pre-clinical diagnosis of dry eye diseases and as prognostic markers to monitor treatment effectiveness.

Background: In utero exposure to Selective serotonin reuptake inhibitors (SSRI) is considered as a risk factor for many neurodevelopmental diseases. Objective: The aim of this study was to investigate whether prenatal SSRI exposure changes newborn brain chemistry. Method: An animal based study was designed in which utero SSRI exposed rat’s pups were compared to one without drug exposure. Neurochemical changes of the infants were assessed after 2 days of birth by estimating the levels of inflammatory cytokines, neurotransmitters and caspases in the brain exposed to SSRI at prenatal stage and compared to normal unexposed newborn. Results: Our results showed significant neurochemical changes in SSRI-exposed newborns. A significant decrease in dopamine, and serotonin levels with a remarkable decrease in noradrenaline in addition to remarkable increase of IFN-γ and caspase-3 levels was observed in the brain tissues of prenatal exposed SSRIs rat pups. Conclusion: The results suggest that prenatal SSRI treatment may affect brain development of newborn hence should be used warily during gestation period.

The present study investigated that maternal type 1 diabetes may contribute to autism pathogenesis in offspring, and that insulin therapy during pregnancy may prevent the onset of autism. As evidenced, selected brain biomarkers representing the accepted etiological mechanism of autism in newborn rats from diabetic mothers and diabetic mothers receiving insulin therapy compared to the propionic acid (PPA) rodent model of autism were screened. Female Wistar rats with a controlled fertility cycle were randomly divided into three groups: a control group, a group treated with a single dose of 65 mg/kg streptozotocin (STZ) to induce type 1 diabetes (T1D), and a group treated with a single dose of STZ to induce T1D along with insulin therapy. Neonatal rats from these groups were divided into four experimental groups of six animals each: the control group, oral buffered PPA-treated group administered a neurotoxic dose of 250 mg/kg PPA for 3 days to induce autism, neonatal rats from mothers with T1D, and neonatal rats from mothers with T1D receiving insulin therapy. Biochemical parameters of oxidative stress, neuroinflammation, and glutamate excitotoxicity were examined in brain homogenates from all neonatal rats. The development of pathogenic bacteria was monitored in stool samples from all rat groups. Descriptive analyses of changes in fecal microbiota and overgrowth of Clostridium species were performed in diabetic mothers, diabetic mothers treated with insulin therapy, and their offspring. Clostridium species may induce autism-relevant behaviors in offspring from mothers with T1D. Maternal T1D without insulin therapy increased lipid peroxidation levels, reduced GST activity, and lower offspring’ vitamin C and GSH levels. Increased IL-6 levels and reduced GABA levels were detected in brain homogenates from neonatal rats whose mothers had T1D. Interestingly, insulin therapy reduced MDA and IL-6 levels and increased GST, GSH, and vitamin C levels in brain homogenates of neonatal rats from mothers with T1D receiving insulin therapy compared to the PPA-treated group. Based on our results, the PPA-treated group and neonatal rats from mothers with T1D exhibited similar results. These findings suggest that neonatal rats from mothers with T1D may develop autism-relevant biochemical autistic features and that insulin therapy may ameliorate oxidative stress, poor detoxification, inflammation, and excitotoxicity as ascertained mechanisms involved in the etiology of autism.

This study aims to explore the effects of

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficiencies in social interaction and repetitive behaviors. Multiple studies have reported abnormal cell membrane composition and autoimmunity as known mechanisms associated with the etiopathogenesis of ASD. In this study, multiple regression and combined receiver operating characteristic (ROC) curve as statistic tools were done to clarify the relationship between phospholipase A2 and phosphatidylethanolamine (PE) ratio (PLA2/PE) as marker of lipid metabolism and membrane fluidity, and antihistone-autoantibodies as marker of autoimmunity in the etiopathology of ASD. Furthermore, the study intended to define the linear combination that maximizes the partial area under an ROC curve for a panel of markers. Forty five children with ASD and forty age- and sex-matched controls were enrolled in the study. Using ELISA, the levels of antihistone-autoantibodies, and PLA2 were measured in the plasma of both groups. PE was measured using HPLC. Statistical analyses using ROC curves and multiple and logistic regression models were performed. A notable rise in the area under the curve was detected using combined ROC curve models. Additionally, higher specificity and sensitivity of the combined markers were documented. The present study indicates that the measurement of the predictive value of selected biomarkers related to autoimmunity and lipid metabolism in children with ASD using a ROC curve analysis should lead to a better understanding of the pathophysiological mechanism of ASD and its link with metabolism. This information may enable the early diagnosis and intervention.

Rodent models may help investigations on the possible link between autism spectrum disorder (ASD) and gut microbiota since autistic patients frequently manifested gastrointestinal troubles as co-morbidities. Thirty young male rats were divided into five groups: Group 1 serves as control; Group 2, bee pollen and probiotic-treated; and Group 3, propionic acid (PPA)-induced rodent model of autism; Group 4 and Group 5, the protective and therapeutic groups were given bee pollen and probiotic combination treatment either before or after the neurotoxic dose of PPA, respectively. Serum occludin, zonulin, lipid peroxides (MDA), glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPX), catalase, and gut microbial composition were assessed in all investigated groups. Recorded data clearly indicated the marked elevation in serum occludin (1.23 ± 0.15 ng/mL) and zonulin (1.91 ± 0.13 ng/mL) levels as potent biomarkers of leaky gut in the PPA- treated rats while both were normalized to bee pollen/probiotic-treated rats. Similarly, the high significant decrease in catalase (3.55 ± 0.34 U/dL), GSH (39.68 ± 3.72 µg/mL), GST (29.85 ± 2.18 U/mL), and GPX (13.39 ± 1.54 U/mL) concomitant with a highly significant increase in MDA (3.41 ± 0.12 µmoles/mL) as a marker of oxidative stress was also observed in PPA-treated animals. Interestingly, combined bee pollen/probiotic treatments demonstrated remarkable amelioration of the five studied oxidative stress variables as well as the fecal microbial composition. Overall, our findings demonstrated a new approach to the beneficial use of bee pollen and probiotic combination as a therapeutic intervention strategy to relieve neurotoxic effects of PPA, a short-chain fatty acid linked to the pathoetiology of autism.

This study tested the anti-hyperlipidemic, hypoglycemic, hepatoprotective, and anti-inflammatory effects of whole pearl millet grain powder (MPG) and its ethanol extract (MPGethaolE) in obese rats fed a high-fat diet. The rats were divided into eight groups based on the treatments they received: control, high fat diet (HFD), HFD + MGE (25 mg/Kg), HFD + MPGethaolE (50 mg/Kg), HFD + MPGethaolE (100 mg/Kg), HFD + MPG (10%), HFD + MPG (20%), and HFD + MPG (30%). The final body weight, visceral, epididymal fat pads, and the liver weight were significantly decreased, in a dose-dependent manner, in HFD fed rats that were co-administered either the MPG powder or MPGethaolE. In the same line, serum levels of triglycerides (TGs), cholesterol (CHOL), and low-density lipoprotein-cholesterol (LDL-c), as well as fasting glucose, insulin, HOMA-IR, and serum levels of lipopolysaccharides (LPS), interleukine-6 (IL-6), interleukine-10 (IL-10), C-reactive protein (CRP), tumor necrosis factor (TNF-α), and adiponectin were progressively decreased while serum levels of high-density lipoproteins (HDL-c) were significantly increased when increasing the doses of both treatments. In conclusion, both the raw powder and ethanolic extract of MP have a comparative dose-dependent anti-obesity, hypoglycemic, hypolipidemic, anti-inflammatory, and anti-steatotic in HFD-fed rats.

This study aimed to evaluate the protective and therapeutic potency of bee pollen and probiotic mixture on brain intoxication caused by propionic acid (PPA) in juvenile rats. Five groups of six animals each, were used: the control group only receiving phosphate-buffered saline; the bee pollen and probiotic-treated group receiving a combination of an equal quantity of bee pollen and probiotic (0.2 kg/kg body weight); the PPA group being treated for 3 days with an oral neurotoxic dose of PPA (0.25 kg/kg body weight); the protective and therapeutic groups receiving bee pollen and probiotic mixture treatment right before and after the neurotoxic dose of PPA, respectively. The levels of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor α, and interferon γ (IFN-γ) were investigated to evaluate the neuroinflammatory responses in brain tissues from different animal groups. The much higher IL-1β, IL-8, and IFN-γ, as pro-inflammatory cytokines (P < 0.001), together with much lower IL-10, as anti-inflammatory cytokine (P < 0.001) compared to controls clearly demonstrated the neurotoxic effects of PPA. Interestingly, the mixture of bee pollen and probiotics was effective in alleviating PPA neurotoxic effects in both therapeutic and protective groups demonstrating highly significant changes in IL-1β, IL-8, IL-10, and IFN-γ levels together with non-significant reduction in IL-6 levels compared to PPA-treated rats. Overall, our findings demonstrated a new approach to the beneficial use of psychobiotics presenting as bee pollen and probiotic combination in neuroinflammation through cytokine changes as a possible role of glial cells in gut–brain axis.

Autism spectrum disorder (ASD) is a progressively prevalent neurodevelopmental disorder with substantial clinical heterogeneity. Despite the considerable interest in dietary interventions, no consensus has been reached regarding the optimal nutritional therapy. The present study aimed to investigate the possible positive effect of goat’s milk (GM) compared to cow’s milk (CM) on ASD autistic features in a valproic acid (VPA; 600 mg/kg)-induced white albino rat model of autism. All tests were conducted on rats that were divided into four groups (n = 15/group): control with goat milk (GM) treatment, control with cow milk (CM) treatment, autistic with goat milk (GM) treatment, and autistic with cow milk treatment. The casein levels were also measured in GM and CM. Social behavior was assessed by three-chambered sociability to test social interaction after the intervention. After 15 days of intervention, selected biomarkers, such as glutathione (GSH), thiobarbituric acid reactive substance (TBARS), interleukin-6 (IL-6), neurotransmitter dopamine (DA), serotonin (5-hydroxytryptamine, 5-HT), and glutamate (GLU), were measured in blood serum and brain homogenates. The results showed a significant positive effect on social interaction in the VPA rat ASD model fed GM. Blood serum and brain samples showed a positive increase in TBARS in the VPA rat model fed GM, but brain and serum serotonin levels were lower in both VPA-GM and VPA-CM groups. Dopamine in serum was also lower in the VPA-CM group than in the VPA-GM group. IL-6 levels were slightly lower in the VPA-GM group than in the VPA-CM group. In comparison with cow’s milk, goat’s milk was effective in ameliorating the neurotoxic effects of VPA. Goat’s milk may be considered a suitable source of dairy for children diagnosed with ASD. Autistic children with allergies to cow’s milk could possibly convert to goat’s milk. Nevertheless, more in-depth studies and clinical trials are recommended.

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 abundance between studies. This information could point to a novel and, most likely, tailored strategy in obesity therapy, which could eventually be incorporated into health evaluations and monitoring in preventive health care or clinical medicine.

Gut microbiota plays a major role in neurological disorders, including autism. Modulation of the gut microbiota through fecal microbiota transplantation (FMT) or probiotic administration, such as Bifidobacteria, is suggested to alleviate autistic symptoms; however, their effects on the brain are not fully examined. We tested both approaches in a propionic acid (PPA) rodent model of autism as treatment strategies. Autism was induced in Sprague-Dawley rats by administering PPA orally (250 mg/kg) for 3 days. Animals were later treated with either saline, FMT, or Bifidobacteria for 22 days. Control animals were treated with saline throughout the study. Social behavior and selected brain biochemical markers related to stress hormones, inflammation, and oxidative stress were assessed. PPA treatment induced social impairments, which was rescued by the treatments. In the brain, Bifidobacteria treatment increased oxytocin relative to control and PPA groups. Moreover, Bifidobacteria treatment rescued the PPA-induced increase in IFN-γ levels. Both treatments increased GST levels, which was diminished by the PPA treatment. These findings indicate the potential of gut microbiota-targeted therapeutics in ameliorating behavioral deficit and underlying neural biochemistry.

In relation to dietary intervention in individuals with autism spectrum disorder (ASD), certain food constituents especially gluten and casein are recognized to be challenging and should be restricted. In this study, levels of glutathione S-transferase, glutathione, lipid peroxides, serotonin (5-HT), interleukin-6 (IL-6), glutamate, and gamma aminobutyric acid (GABA) were measured in the brain homogenates of ASD rodent model. Rats were treated either with single dose clindamycin (30 mg/kg) or with propionic acid (PPA) (250 mg/kg) for 3 days and then fed a standard diet, casein-rich diet (CRD), or gluten-rich diet (GRD). The obtained data demonstrates that clindamycin and PPA induced oxidative stress, which was slightly affected by CRD. A marked increase in the proinflammatory cytokine (IL-6) concentration found in clindamycin- and PPA-treated groups was lower in CRD fed rats. Both CRDs and GRDs produced similar trends in glutamate levels. 5-HT levels were higher in the clindamycin- and PPA-treated groups and increased with a GRD but were less affected by a CRD. CRD could be less deleterious compared to GRD. Although the underlying cause of gastrointestinal symptoms in patients with ASD is not exactly known, the most widely accepted one is the opioid theory which is related to GRD and CRD.

Autism spectrum disorders (ASD) express as impaired social interactions and stereotypes. The gut microbiome which is remarkably different in ASD compared with controls may contribute to the sex bias of this disorder, with females being less vulnerable to clinically present autism. This review aims to understand the role of gut microbiota and female sex hormone in the sex bias of autism. Recent evidence proved that transplanted gut microbiota from autistic donors but not healthy controls into germ-free mice were effective in inducing autistic features. Moreover selective probiotic known to be more abundant in females than males was effective as a treatment strategy. The higher autistic phenotypes in males compared with females could be attributed to the protective effect of estrogen, the higher diversity and predominance of probiotics in females, the lower liability of females to develop leaky gut, neuroinflammation, and excitotoxicity as etiological mechanisms.

The marked heterogeneity of autism spectrum disorders is a challenge for research into biomarkers of these disorders. The present study aimed to assess the association of the thioredoxin (TRX) system and vasopressin with autism in children. Thirty-five autistic children were recruited with thirty-one healthy controls children matched for age and gender. Total antioxidant capacity (TAC), vasopressin, peroxiredoxin (PRDX1, PRDX3), phox domain-containing protein kinase-like protein, and TRX1 levels were measured in plasma and mercury and lead levels were measured in red blood cells. Children with autism had significantly lower levels of PRDX1 and TRX1 and significantly higher levels of lead and mercury compared with controls. Significantly higher levels of vasopressin were also observed in more severe cases of autism. Receiver operating characteristics analysis demonstrated satisfactory specificity and sensitivity of TAC, PRDX1, PRDX3, and TRX1 for the diagnosis of autism. The optimal cut-off value for plasma TRX1 levels, as an indicator of autism, was 10.6 ng/mL. Significant positive correlations existed between TRX system components, lead, and mercury. A negative correlation was found between vasopressin and TRX1, but positive correlations were found between vasopressin and mercury and lead. In conclusion, TAC, PRDX1, PRDX3, and TRX1 may be useful biomarkers for the diagnosis of autism in Saudi populations. Vasopressin-resistance in autistic patients may be due to an increased oxidative burden.

The current study evaluated the protective and therapeutic potency of bee pollen in ameliorating the toxic effects of methylmercury (MeHg), by measuring certain biochemical parameters related to neurotransmission, neuroinflammation, apoptosis, and glutamate excitotoxicity in the male neonate brain. Healthy, pregnant female rats (N = 40) were randomly divided into 5 groups, each comprising10 male neonates, as follows: (i) neonates delivered by control mothers; (ii) neonates delivered by MeHg-treated mothers who received 0.5 mg/kg BW/day MeHg via drinking water from gestational day 7 till postnatal day 7; (iii) neonates delivered by bee pollen treated mothers who received 200-mg/kg BW bee pollen from postnatal day 0 for 4 weeks; (iv) protective group of neonates delivered by MeHg and bee pollen-treated mothers, who continued to receive bee pollen until day 21 at the same dose, and (v) therapeutic group of neonates delivered by MeHg- treated mothers followed by bee pollen treatment, wherein they received 200-mg/kg BW bee pollen from postnatal day 0 for 4 weeks. Selected biochemical parameters in brain homogenates from each group were measured. MeHg-treated groups exhibited various signs of brain toxicity, such as a marked reduction in neurotransmitters (serotonin (5-HT), nor-adrenalin (NA), dopamine (DA)) and gamma aminobutyric acid (GABA) and elevated levels of interferon gamma (IFN-γ), caspase-3, and glutamate (Glu). Bee pollen effectively reduced the neurotoxic effects of MeHg. Minimal changes in all measured parameters were observed in MeHg-treated animals compared to the control group. Therefore, bee pollen may safely improve neurotransmitter defects, inflammation, apoptosis, and glutamate excitotoxicity.

It is proposed that gluten- and casein-rich diets (GRD and CRD) can synergistically exacerbate dysbiosis as comorbidity in autism by worsening leaky gut that affects the brain through the gut–brain axis. In this study, 35 young male rats were divided into 7 groups, Group 1 serves as control; Group 2, clindamycin (CL)-treated; and Group 3, propionic acid (PPA)-induced rodent model of autism. These three groups were fed standard diet until the end of the experiment. Groups 4–7 are rats treated similarly with CL and PPA, then fed on CRD or GRD until the end of the experiment. Serum zonulin, glutathione (GSH), lipid peroxides, and gut microbial composition were measured in the seven studied groups. Data demonstrate the significant increase in serum zonulin as marker of leaky gut in the CL-treated groups fed on CRD or GRD. Lipid peroxides were significantly higher in the serum of GRD-fed rats compared to CRD-fed or normal diet-fed rats. GSH was much lower in CL-treated groups fed on CRD or GRD compared to PPA-treated rats fed on both diets. Both diets differentially affected the diversity of the gut microbiota. This study demonstrates that CRD and GRD exacerbates leaky gut, according to serum zonulin, which was used as marker for increased gut permeability.

The present study investigated that maternal type 1 diabetes may contribute to autism pathogenesis in offspring, and that insulin therapy during pregnancy may prevent the onset of autism. As evidenced, selected brain biomarkers representing the accepted etiological mechanism of autism in newborn rats from diabetic mothers and diabetic mothers receiving insulin therapy compared to the propionic acid (PPA) rodent model of autism were screened. Female Wistar rats with a controlled fertility cycle were randomly divided into three groups: a control group, a group treated with a single dose of 65 mg/kg streptozotocin (STZ) to induce type 1 diabetes (T1D), and a group treated with a single dose of STZ to induce T1D along with insulin therapy. Neonatal rats from these groups were divided into four experimental groups of six animals each: the control group, oral buffered PPA-treated group administered a neurotoxic dose of 250 mg/kg PPA for 3 days to induce autism, neonatal rats from mothers with T1D, and neonatal rats from mothers with T1D receiving insulin therapy. Biochemical parameters of oxidative stress, neuroinflammation, and glutamate excitotoxicity were examined in brain homogenates from all neonatal rats. The development of pathogenic bacteria was monitored in stool samples from all rat groups. Descriptive analyses of changes in fecal microbiota and overgrowth of Clostridium species were performed in diabetic mothers, diabetic mothers treated with insulin therapy, and their offspring. Clostridium species may induce autism-relevant behaviors in offspring from mothers with T1D. Maternal T1D without insulin therapy increased lipid peroxidation levels, reduced GST activity, and lower offspring' vitamin C and GSH levels. Increased IL-6 levels and reduced GABA levels were detected in brain homogenates from neonatal rats whose mothers had T1D. Interestingly, insulin therapy reduced MDA and IL-6 levels and increased GST, GSH, and vitamin C levels in brain homogenates of neonatal rats from mothers with T1D receiving insulin therapy compared to the PPA-treated group. Based on our results, the PPA-treated group and neonatal rats from mothers with T1D exhibited similar results. These findings suggest that neonatal rats from mothers with T1D may develop autism-relevant biochemical autistic features and that insulin therapy may ameliorate oxidative stress, poor detoxification, inflammation, and excitotoxicity as ascertained mechanisms involved in the etiology of autism.

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.

Excess glutamate in the central nervous system may be a major cause of neurodegenerative diseases with gradual loss and dysfunction of neurons. Primary or secondary metabolites from medicinal plants and algae show potential for treatment of glutamate-induced excitotoxicity. Three plant extracts were evaluated for impact on glutamate excitotoxicity-induced in primary cultures of retinal ganglion cells. These cells were treated separately in seven groups: control; Plicosepalus. curviflorus treated; Saussurea lappa treated; Cladophora glomerate treated. Cells were treated independently with 5, 10, 50, or 100 µg/ml of extracts of plant or alga material, respectively, for 2 h. Glutamate-treated cells (48 h with 5, 10, 50, or 100 µM glutamate); and P. curviflorus/glutamate; S. lappa/glutamate; C. glomerata/glutamate [pretreatment with extract for 2 h (50 and 100 µg/ml) before glutamate treatment with 100 µM for 48 h]. Comet and MTT assays were used to assess cell damage and cell viability. The number of viable cells fell significantly after glutamate exposure. Exposure to plant extracts caused no notable effect of viability. All tested plants extracts showed a protective effect against glutamate excitotoxicity-induced RGC death. Use of these extracts for neurological conditions related to excitotoxicity and oxidative stress might prove beneficial.

The present study investigated the combined effects of mixed probiotic and bee pollen on brain intoxication induced by propionic acid (PPA) in rat pups. Thirty western albino rats were divided into five groups, six animals each: (1) Control group receiving phosphate‐buffered saline; (2) Probiotic and bee pollen‐treated group being administered at the same dose with 200 mg/kg body weight; (c) PPA‐treated group receiving a neurotoxic dose 250 mg/kg body weight of PPA for 3 days; (d) Therapeutic group being administered the neurotoxic dose of PPA followed by probiotic and bee pollen treatment 200 mg/kg body weight; (e) Protective group receiving probiotic and bee pollen mixture treatment followed by neurotoxic dose of PPA. Selected biochemical parameters linked to oxidative stress, energy metabolism, and neurotransmission were investigated in brain homogenates from all the five groups. PPA treatment showed an increase in oxidative stress markers like lipid peroxidation coupled with a significant decrease in glutathione level. Impaired energy metabolism was ascertained via the alteration of creatine kinase (CK) and lactate dehydrogenase (LDH) activities. Dramatic increase of Na+ and K+ concentrations together with a decrease of GABA and IL‐6 and an elevation of glutamate levels in PPA‐treated rat's pups confirmed the neurotoxicity effect of PPA. Interestingly, the mixed probiotic and bee pollen treatment were effective in restoring the levels of glutamate, GABA, and IL‐6 in addition to normalizing the levels of lipid peroxidation and glutathione and the activities of CK and LDH. The present study indicates that mixed probiotic and bee pollen treatment can improve poor detoxification, oxidative stress, and neuroinflammation as mechanisms implicated in the etiology of autism., The present study indicates that mixed probiotic and bee pollen treatment can improve poor detoxification, oxidative stress, and neuroinflammation as mechanisms implicated in the etiology of autism.

Background:Obesity is a risk factor for several diseases related to oxidative stress, hyperlipidemia, and hyperglycemia. Several pharmacological agents have been used to treat obesity, but these commonly exhibit undesirable side effects. The aim of this study was to explore the effects of Garcinia mangostana (mangosteen) and Curcuma longa independently and synergistically in modulating selected biochemical markers of oxidative stress, dyslipidemia, and hyperglycemia commonly observed in high-fat diet-induced obesity in rodent models. Methods: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 body weight/day) and/or curcumin (80 mg/kg body weight/day) for 6 weeks. Oxidative stress markers, glucose, and lipid fractions were measured in the sera. Results:Curcumin was found to be more effective in reducing BMI, while mangosteen extract was found to induce a significant increase in anti-atherogenic marker HDL-C, but was ineffective in reducing dyslipidemia. Mangosteen extract and curcumin effectively reduced blood glucose. Mangosteen did not exhibit any anti-oxidative effects in normal weight rats; however, it induced a significant increase in glutathione in obese rats. Conclusion:The present study demonstrated that mangosteen pericarp extract and curcumin were independently and synergistically effective in treating obesity-induced atherogenesis.

Dietary polyphenols in plant extracts are being widely investigated due to their great health-promoting activities and effect on modulating gut ecology. In turn, gut microbiota, plays a vital role in the biological activities of phenolic metabolites, particularly after the intake of food rich in polyphenols, such as plant extracts. However, this two-way relationship between polyphenols and microbiota is poorly understood. We prepared curcuma and mangosteen methanol extracts and fed them to healthy, lean, and obese rats over a period of 10 weeks. Subsequent alterations in the gut microbiota were determined. Overall, Firmicutes were more abundant than Bacteroidetes throughout the experiment. A particular increase of gram-positive cocci species and a significant decrease in both Clostridium and Bacteroides species were noted primarily in the first weeks of both plant extract intake in the control and lean rats. Compared to obese rats fed a regular diet, obese rats fed plant extracts showed an increase in Enterobacteriacea, Clostridium, and Bacteroides species and a decrease in gram-positive cocci in the first weeks of treatment with the last weeks of treatment the results at the species level were inverted.

Background: Due to the prevalence of Hepatocellular carcinoma (HCC) in Saudi Arabia, using new markers to give best diagnostic performance than alpha-feto protein (AFP) are important in early diagnosis. The aim of this work was to compare the significance between serum and mRNA Golgi glypican73 (GP-73) as newly identified diagnostic and prognostic markers for HCC among Saudi patients. Materials and Methods: A total of 300 subjects were divided into: 250 blood samples where 145 samples from HCC, 105 samples from chronic liver cirrhosis (CLC) and 50 normal controls were investigated for serum GP73 (sGP73) by ELISA. GP-73 mRNA from peripheral blood mononuclear cells was amplified by RT-PCR. The sensitivity and specificity of both techniques was compared. Results: Serum Golgi glypican 73 was significantly higher in HCC group compared to cirrhotic and normal controls (p

A high extracellular concentration of glutamate has the potential to induce autism. Presently no appropriate treatment is available to modulate glutamate-mediated injury; however, increased levels of glutamate transporters, which aid in glutamate clearance, may potentially limit and prevent glutamate excitotoxicity, and β-lactam antibiotics have been found to activate the expression of a glutamate transporter. To identify the beneficial role of β-lactam in autism, we used an animal model of autism by administrating propionic acid (PPA) to juvenile rats and then treated these animals with this antibiotic. Animals were divided into three groups: (1) an untreated control group, (2) a PPA-intoxicated group and (3) a PPA-intoxicated group treated with β-lactam. Selected parameters related to glutamate signaling were measured in brain homogenates of all groups. The obtained data demonstrated neurotoxicity of PPA through glutamate (GLU) excitotoxicity. Moreover, the rats treated with β-lactam exhibited higher glutamate transporter 1 (Glt-1) levels than the control group (p = 0.044). Furthermore, compared to the expression in the control group and the untreated autism model group, Glt-1 gene expression was much higher in brain samples from β-lactam-treated autism model rats (p < 0.056). Receiver operating characteristic (ROC) analyses revealed that measured parameters such as GLU and GLU/γ-aminobutyric acid, Glt-1, and GLU/Glt-1 were found to be predictive markers of the protective effect of β-lactam against GLU excitotoxicity. Immediate upregulation of Glt-1 may reduce extracellular GLU levels and thereby prevent damage to neurons. Therefore, increasing Glt-1 expression could be a potential approach to prevent excitotoxicity in the brain.

This study tested the anti-hyperlipidemic, hypoglycemic, hepatoprotective, and anti-inflammatory effects of whole pearl millet grain powder (MPG) and its ethanol extract (MPGethaolE) in obese rats fed a high-fat diet. The rats were divided into eight groups based on the treatments they received: control, high fat diet (HFD), HFD + MGE (25 mg/Kg), HFD + MPGethaolE (50 mg/Kg), HFD + MPGethaolE (100 mg/Kg), HFD + MPG (10%), HFD + MPG (20%), and HFD + MPG (30%). The final body weight, visceral, epididymal fat pads, and the liver weight were significantly decreased, in a dose-dependent manner, in HFD fed rats that were co-administered either the MPG powder or MPGethaolE. In the same line, serum levels of triglycerides (TGs), cholesterol (CHOL), and low-density lipoprotein-cholesterol (LDL-c), as well as fasting glucose, insulin, HOMA-IR, and serum levels of lipopolysaccharides (LPS), interleukine-6 (IL-6), interleukine-10 (IL-10), C-reactive protein (CRP), tumor necrosis factor (TNF-α), and adiponectin were progressively decreased while serum levels of high-density lipoproteins (HDL-c) were significantly increased when increasing the doses of both treatments. In conclusion, both the raw powder and ethanolic extract of MP have a comparative dose-dependent anti-obesity, hypoglycemic, hypolipidemic, anti-inflammatory, and anti-steatotic in HFD-fed rats.

In Saudi Arabia AFP considered the main serum marker for diagnostic Hepatocellular carcinoma (HCC), due to the continuous detection of HCC in Saudi Arabia, using new biomarkers for early surveillance are essential to control in prevalence of HCC. The present study depend on compare the significant between serum and mRNA Glypican-3 (GPC-3) as newly identified diagnostic and prognostic biomarkers for HCC between study cases. And combined sensitivity of AFP and GPC-3. Three hundred study cases, divided into: 250 blood samples were 145 samples from HCC , 105 samples from chronic liver cirrhosis (CLC) and 50 normal controls were investigated for serum GPC-3 (sGPC-3) by Sandwich ELISA. Glypican-3 mRNA from whole blood cells was detected by quantitative RT-PCR. The comparison between two techniques was by sensitivity and specificity. The results of sGPC-3 showed higher significant in HCC group than CLC and normal controls (p

Metabolites of proper fatty acids modulate the inflammatory response and are essential for normal brain development; equally, abnormal fatty acid metabolism plays a critical role in the pathology of autism. Currently, dietary supplements are often used to improve the core symptoms of Autism spectrum disorder (ASD). The present study analyzed the effects of orally supplemented omega-3 (ω-3) and vitamin B12 on ameliorating oxidative stress and impaired lipid metabolism in a propionic acid (PPA)-induced rodent model of autism, together with their effect on the gut microbial composition, where great fluctuations in the bacterial number and strains were observed; interestingly, polyunsaturated fatty acids such as omega-3 induced higher growth of the gram-positive bacterium Staphylococcus aureus and decreased the survival rates of Clostridia sp. as well as other enteric bacterial strains. Thirty-five young male western albino rats were divided into five equal groups. The first group served as the control; the second group was given an oral neurotoxic dose of PPA (250 mg/kg body weight/day) for 3 days. The third group received an oral dose of ω-3 (200 mg/kg body weight/day) for 30 days after the 3-day PPA treatment. Group four was given an oral dose of vitamin B12 (16.7 mg/kg/day) for 30 days after PPA treatment. Finally, group five was given a combination of both ω-3 and vitamin B12 at the same dose for the same duration after PPA treatment. Biochemical parameters related to oxidative stress and impaired fatty acid metabolism were investigated in the brain homogenates of each group. The effects of the dietary supplements on the gut microbiota were also observed. The PPA-treated autistic model expressed significantly higher levels of lipid peroxides and 5-lipoxygenase (5-LOX) and significantly less glutathione (GSH), glutathione S-transferase (GST), and cyclooxygenase 2 (COX2) than the control group. However, a remarkable amelioration of most of the impaired markers was observed with oral supplementation with ω-3 and vitamin B12, either alone or in combination. Our results concluded that impairment at various steps of the lipid metabolic pathways may contribute to the development of autism; however, supplementation with ω-3 and vitamin B12 can result in a positive therapeutic effect.

Human cytomegalovirus (CMV) is the leading infectious cause of congenital infection in developing countries. However, the pathogenesis of CMV infection is poorly understood. Worldwide, CMV seropositivity varies with age and sex, but data related to these variations are lacking. Here, we examined the variation in CMV seroprevalence in three different age groups of Saudi population in an attempt to understand the variation in the relationship between CMV infection seroprevalence with age and study the risk factor liver dysfunction. Serum samples for 455 patients with elevation of liver profiles (ALT, AST, ALP and GGT) were screened for CMV- IgG and IgM and categorized in different age groups. A correlation between CMV seropositivity measured with IgG and IgMand liver enzymes were tested. Receiver operating characteristics (ROC) analysis and multiple regressions were used for data analysis. Our study shows that young people (18-25 years) had much higher IgG and IgM compared to elderly people (26 -35 and 36-45 years). A significant correlation between both antibodies and liver enzymes (AST, ALT) was recorded. Receiver operating characteristics (ROC) analysis revealed that both IgG and IgM can be used as excellent predictive markers for CMV infection as both recorded 100% specificity and sensitivity together with area under the curve of 1 in the three studied research groups. Multiple regression analysis ascertain the correlation between both antibodies as dependent variables and liver enzymes as independent variables with ALT being the most affected enzyme with CMV seropositivity. This study strongly ascertains that CMV is indeed capable of initiating and accelerating liver dysfunction especially in young people. Serological screening of individuals who are asymptomatic based on a detection of CMV-IgG and IgMmight help in early diagnosis and intervention to avoid liver disorder as cirrhosis and other complications related to CMV infection, which are associated with ALT, AST and GGT elevation.

The present study investigated the therapeutic effects of probiotics on brain intoxication induced by clindamycin and propionic acid (PPA) in hamsters. Fifty golden Syrian hamsters were randomly divided into five experimental groups of ten animals each: (A) control group receiving phosphate buffered saline; (B) oral buffered PPA-treated group being administered with a neurotoxic dose of 250 mg/kg PPA during three days; (C) oral clindamycin-treated group receiving a single dose of 30 mg clindamycin/kg; and (D, E) the two therapeutic groups being administered the same doses of clindamycin and PPA followed by probiotics for three weeks at a daily dose of 0.2 g/kg. Biochemical parameters of energy metabolism and oxidative stress were examined in brain homogenates from all hamsters. The development of pathogenic bacteria was monitored on stool samples from all hamsters. Descriptive changes in fecal microbiota and overgrowth of Clostridium species in clindamycin and PPA treated hamsters were recorded. Interestingly, probiotics were shown effective to restore normal gut microbiota. Clindamycin and PPA treatments caused an elevation in lipid peroxidation and catalase activity, as oxidative stress markers, together with a reduction in GST activity and GSH level. Energy metabolism impairment was ascertained via the activation of creatine kinase and a decrease of lactate dehydrogenase. These findings suggest that bacteria overgrowth caused by PPA and clindamycin was efficient to illustrate signs of neuronal toxicity. The present study indicates that probiotic treatment can improve poor detoxification, oxidative stress, and altered gut microbiota as mechanisms implicated in the etiology of many neurological disorders.

Autism spectrum disorder (ASD) is a multifactorial disorder caused by an interaction between environmental risk factors and a genetic background. It is characterized by impairment in communication, social interaction, repetitive behavior, and sensory processing. The etiology of ASD is still not fully understood, and the role of neuroinflammation in autism behaviors needs to be further investigated. The aim of the present study was to test the possible association between prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), prostaglandin PGE2 EP2 receptors and nuclear kappa B (NF-κB) and the severity of cognitive disorders, social impairment, and sensory dysfunction. PGE2, COX-2, mPGES-1, PGE2-EP2 receptors and NF-κB as biochemical parameters related to neuroinflammation were determined in the plasma of 47 Saudi male patients with ASD, categorized as mild to moderate and severe as indicated by the Childhood Autism Rating Scale (CARS) or the Social Responsiveness Scale (SRS) or the Short Sensory Profile (SSP) and compared to 46 neurotypical controls. The data indicated that ASD patients have remarkably higher levels of the measured parameters compared to neurotypical controls, except for EP2 receptors that showed an opposite trend. While the measured parameter did not correlate with the severity of social and cognitive dysfunction, PGE2, COX-2, and mPGES-1 were remarkably associated with the dysfunction in sensory processing. NF-κB was significantly increased in relation to age. Based on the discussed data, the positive correlation between PGE2, COX-2, and mPGES-1 confirm the role of PGE2 pathway and neuroinflammation in the etiology of ASD, and the possibility of using PGE2, COX-2 and mPGES-1 as biomarkers of autism severity. NF-κB as inflammatory inducer showed an elevated level in plasma of ASD individuals. Receiver operating characteristic analysis together with predictiveness diagrams proved that the measured parameters could be used as predictive biomarkers of biochemical correlates to ASD.

Aim Autism is a heterogeneous neurological disorder that is characterized by impairments in communication and social interactions, repetitive behaviors, and sensory abnormalities. The etiology of autism remains unclear. Animal, genetic, and post-mortem studies suggest that an imbalance exists in the neuronal excitation and inhibition system in autism. The aim of this study was to determine whether alterations of the measured parameters in children with autism are significantly associated with the risk of a sensory dysfunction. Methods The glutamine synthetase (GS), kidney-type glutaminase (GLS1), and glutamic acid decarboxylase autoantibody levels were analyzed in 38 autistic children and 33 age- and sex-matched controls using enzyme-linked immunosorbent assays. Results The obtained data demonstrated significant alterations in glutamate and glutamine cycle enzymes, as represented by GS and GLS1, respectively. While the glutamic acid decarboxylase autoantibodies levels were remarkably increased, no significant difference was observed compared to the healthy control participants. Conclusion The obtained data indicate that GS and GLS1 are promising indicators of a neuronal excitation and inhibition system imbalance and that combined measured parameters are good predictive biomarkers of autism.

Autism spectrum disorder (ASD) is a neurodevelopmental pathology characterized by an impairment in social interaction, communication difficulties, and repetitive behaviors. Glutamate signaling abnormalities are thought to be considered as major etiological mechanisms leading to ASD. The search for amino-acidic catabolytes related to glutamate in patients with different levels of ASD might help current research to clarify the mechanisms underlying glutamate signaling and its disorders, particularly in relation to ASD. In the present study, plasma levels of the amino acids and their derivatives glutamate, glutamine, and γ-aminobutyric acid (GABA), associated with their relative ratios, were evaluated using an enzyme-linked immunosorbent assay (ELISA) technique in 40 male children with ASD and in 38 age- and gender-matched neurotypical health controls. The Social Responsiveness Scale (SRS) was used to evaluate social cognition, and the Childhood Autism Rating Scale (CARS) was used to assess subjects' behaviors. Children with ASD exhibited a significant elevation of plasma GABA and glutamate/glutamine ratio, as well as significantly lower levels of plasma glutamine and glutamate/GABA ratios compared to controls. No significant correlation was found between glutamate levels and the severity of autism, measured by CARS and SRS. In receiver operating characteristic (ROC) curve analysis, the area under the curve for GABA compared to other parameters was close to one, indicating its potential use as a biomarker. Glutamine appeared as the best predictive prognostic markers in the present study. The results of the present study indicate a disturbed balance between GABAergic and glutamatergic neurotransmission in ASD. The study also indicates that an increased plasma level of GABA can be potentially used as an early diagnostic biomarker for ASD.

Females have been found to be at lower risk for the development of neurodevelopmental disorders than males. The greater neuroprotection in females is mostly due to female sex hormones. Estrogen is hypothesized to provide neuroprotection by suppressing the neuro-excitotoxicity induced by glutamate (Glu). This study was conducted to understand the effect of sex in modulating Glu signaling in juvenile rats. Brain tissue homogenate of 15 Wistar albino rats (9 males, 6 females) weighing 60 to 80 g and aged approximately 28 days was used. Biochemical parameters related to Glu signaling, such as the absolute and relative concentrations of Glu, gamma aminobutyric acid (GABA), and glutamine, as well as glutamate transporter 1 (GLT1), glutamine synthetase (GS), glutaminase (GLN), and glutamate decarboxylase-67 (GAD-67), were measured by ELISA. The data obtained demonstrated that compared with the levels in males, female rats exhibited significantly lower levels of Glu (p = .001) and GLN/GS (p = .021). The Glu/GABA and Glu/GLT1 ratios as well as the levels of GAD-67 were also lower in female rats, although the difference was not significant. The GLN/GAD-67 ratio (p = .027) and levels of GS (p = .019) were significantly higher in female rats than in males. Multiple regression analysis confirmed the role of GLN/GS, together with the much higher affinity of GLT1 to Glu, in avoiding excitotoxicity in females. In conclusion, there was a significant difference in Glu signaling between female and male rats. The females exhibited a lower susceptibility to develop Glu-induced excitotoxicity, an etiological mechanism for multiple neurodevelopmental disorders.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is behaviorally defined by social and communication impairments and restricted interests and repetitive behaviors. There is currently no biomarkers that can help in the diagnosis. Several studies suggest that mitochondrial dysfunction is commonly involved in ASD pathophysiology, but standard mitochondrial biomarkers are thought to be very variable. In the present study we examine a wide variety of plasma biomarkers of mitochondrial metabolism and the related abnormalities of oxidative stress and apoptosis in 41 ASD patients assessed for ASD severity using the Childhood Autism Rating Scales and 41 non-related age and sex matched healthy controls. Our findings confirm previous studies indicating abnormal mitochondrial and related biomarkers in children with ASD including pyruvate, creatine kinase, Complex 1, Glutathione S-Transferase, glutathione and Caspase 7. As a novel finding, we report that lactate dehydrogenase is abnormal in children with ASD. We also identified that only the most severe children demonstrated abnormalities in Complex 1 activity and Glutathione S-Transferase. Additionally, we find that several biomarkers could be candidates for differentiating children with ASD and typically developing children, including Caspase 7, gluthatione and Glutathione S-Transferase by themselves and lactate dehydrogenase and Complex I when added to other biomarkers in combination. Caspase 7 was the most discriminating biomarker between ASD patients and healthy controls suggesting its potential use as diagnostic marker for the early recognition of ASD pathophysiology. This study confirms that several mitochondrial biomarkers are abnormal in children with ASD and suggest that certain mitochondrial biomarkers can differentiate between ASD and typically developing children, making them possibly useful as a tool to diagnosis ASD and identify ASD subgroups.

Autism, a neurodevelopmental disorder, is characterized by a high level of social interaction insufficiency, impairment in language, and repetitive behavior. The gut–brain axis (GBA) is considered a bidirectional communication pathway between the gut and the brain. Growing evidence shows that the GBA contributes to the etiology of autism. The phenotypic behaviors of autism and the gastrointestinal problems that are comorbidity in autism are associated with modified gut microbiota. Understanding the role of the gut microbiota in oxidative stress, heavy metal toxicity, glutamate excitotoxicity, impaired lipid metabolism, and neuroinflammation as pathological mechanisms of autism might support the use of nutritional and dietary interventions through the supplementation of probiotics for the amelioration of unhealthy perinatal and postnatal gut microbiota. This could lead to strategies to prevent, or at least control, autism through the correction of these pathological mechanisms. The aim of this chapter is to understand how autism is responsive to the composition of the gut microbiota, which can be targeted to treat this disorder.

BackgroundNeuroinflammation plays a major role in the pathogenesis of autism because the cytokine levels are typically disturbed in the brain in autistic patients. Prebiotics-rich diet maintains the healthy gut microbiota and hence can regulate the neuroinflammation indirectly. The study aimed to investigate the role of bee pollen and propolis in ameliorating neuroinflammation, including cytokine levels, in an animal model of autism.MethodsHamsters were classified as four groups: Group I, control; Group II, autistic model/animals treated with 250 mg propionic acid (PPA)/kg body weight (BW)/day for 3 days; Group III, animals treated with bee pollen at a dose of 250 mg/kg BW/day for 4 weeks; and Group IV, animals treated with propolis at a dose of 250 mg/kg BW/day for 4 weeks. Neuroinflammatory responses were evaluated using the levels of interferon γ (IFN-γ), interleukin 1 alpha (IL-1α), IL-6, IL-10, IL-12 (p70), vascular endothelial growth factor (VEGF), and tumor necrosis factor α (TNFα).ResultsSignificant decrease of IL-10 (PPPPPPPPConclusionsOur findings indicate that both bee pollen and propolis protect against neuroinflammation in the rodent model of autism. However, further studies are needed to investigate the clinical benefits of prebiotics-rich diet in neurodevelopmental disorders, such as autism.

Autism spectrum disorder (ASD) is a complex neurodevelopmental syndrome commonly diagnosed in early childhood; it is usually characterized by impairment in reciprocal communication and speech, repetitive behaviors, and social withdrawal with loss in communication skills. Its development may be affected by a variety of environmental and genetic factors. Trained physicians diagnose and evaluate the severity of ASD based on clinical evaluations of observed behaviors. As such, this approach is inevitably dependent on the expertise and subjective assessment of those administering the clinical evaluations. There is a need to identify objective biological markers associated with diagnosis or clinical severity of the disorder. Several important issues and concerns exist regarding the diagnostic competence of the many abnormal plasma metabolites produced in the different biochemical pathways evaluated in individuals with ASD. The search for high-performing bio-analytes to diagnose and follow-up ASD development is still a major target in medicine. Dysregulation in the oxidative stress response and proinflammatory processes are major etiological causes of ASD pathogenesis. Furthermore, dicarboxylic acid metabolites, cholesterol-related metabolites, phospholipid-related metabolites, and lipid transporters and mediators are impaired in different pathological conditions that have a role in the ASD etiology. A mechanism may exist by which pro-oxidant environmental stressors and abnormal metabolites regulate clinical manifestations and development of ASD.

Background Autism spectrum disorder (ASD) is a complex group of heterogeneous neurodevelopmental disorders the prevalence of which has been in the rise in the past decade. In an attempt to better target the basic causes of ASD for diagnosis and treatment, efforts to identify reliable biomarkers related to the body’s metabolism are increasing. Despite an increase in identifying biomarkers in ASD, there are none so far with enough evidence to be used in routine clinical examination, unless medical illness is suspected. Promising biomarkers include those of mitochondrial dysfunction, oxidative stress, energy metabolism, and apoptosis. Methods and participants Sodium (Na+), Potassium (K+), glutathione (GSH), glutathione-s-transferase (GST), Creatine kinase (CK), lactate dehydrogenase (LDH), Coenzyme Q10, and melatonin (MLTN) were evaluated in 13 participants with ASD and 24 age-matched healthy controls. Additionally, five ratios, which include Na+/K+, GSH:GST, CK:Cas7, CoQ10: Cas 7, and Cas7:MLTN, were tested to measure their predictive values in discriminating between autistic individuals and controls. These markers, either in absolute values, as five ratios, or combined (9 markers + 5 ratios) were subjected to a principal component analysis and multidimensional scaling (MDS), and hierarchical clustering, which are helpful statistical tools in the field of biomarkers. Results Our data demonstrated that both PCA and MDS analysis were effective in separating autistic from control subjects completely. This was also confirmed through the use of hierarchical clustering, which showed complete separation of the autistic and control groups based on nine biomarkers, five biomarker ratios, or a combined profile. Excellent predictive value of the measured profile was obtained using the receiver operating characteristics analysis, which showed an area under the curve of 1. Conclusion The availability of an improved predictive profile, represented by nine biomarkers plus the five ratios, inter-related different etiological mechanisms in ASD and would be valuable in providing greater recognition of the altered biological pathways in ASD. Our predictive profile could be used for the diagnosis and intervention of ASD.