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Agaricus bisporus, the most widely cultivated mushroom, is safe to eat and enriched with protein and secondary metabolites. We prepared silver nanoparticles (AgNPs) from two varieties of A. bisporus and tested their antibacterial activity The synthesized AgNPs were initially confirmed by UV-Vis spectroscopy peaks at 420 and 430 nm for white and brown mushrooms AgNPs, respectively. AgNPs were further characterized by zeta sizer, transmission electronic microscopy (TEM), Fourier transform infrared (FTIR), and energy-dispersive X-ray spectroscopy (EDX) prior to antibacterial activity by the well diffusion method against six bacterial strains which include Staphylococcus aureus, Staphylococcus epidermis, Bacillus subtilis, Escherichia coli, Salmonella typhi, and Pseudomonas aeruginosa. TEM results revealed a spherical shape with an average diameter of about 11 nm in the white mushroom extract and 5 nm in the brown mushroom extract. The presence of elemental silver in the prepared AgNPs was confirmed by EDS. The IR spectrum of the extract confirmed the presence of phenols, flavonoids, carboxylic, or amide groups which aided in the reduction and capping of synthesized AgNPs. The AgNPs from both extracts showed almost the same results; however, nanoparticles prepared from brown mushrooms were smaller in size with strong antibacterial activity.

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.

A substantial interest has been manifested in utilizing oil/metal oxide hybrid bionanocomposite, especially organic/ inorganic to design different biomedical applications. The present study reports the synthesis, characterization, antibacterial and anticancer properties of biogenic silver nanoparticles (AgNPs) and L.satiVum oil/PEG/Ag-MgO bionanocomposite. The fabricated AgNPs and L.sativum oil/PEG/Ag-MgO bionanocomposite were characterized by employing different spectroscopic (UV, FTIR, XRD) and microscopic (TEM, SEM) techniques. The particle size analysis showed that the mean size of 16.32 nm for AgNPS and 13.45 nm L.satiVum oil/PEG/Ag-MgO, indicating the excellent dispersion of Ag-MgO nanoparticles in the PEG- L.satiVum oil matrix. The antimicrobial activity of AgNPs and polymeric bionanocomposite was investigated against two pathogenic bacteria. The highest antibacterial effect was observed for bionanocomposite towards Gram-positive Staphylococcus aureus (27 mm) and Gram-negative Escherichia coli (25 mm) at 40 µg/well. The bionanocomposite completely vanished the bacterial growth (100%) at 80 µgmL-1 concentrations. Moreover, the AgNPs and polymeric bionanocomposite was evaluated for anticancer activity against human cervical cancer cells (HeLa cells) at different doses (50, 250, 500, and 1000 µgmL-1). The results showed polymeric bionanocomposite was stronger in inducing the HeLa cancer cell death than AgNPs. Overall, the fabricated L.satiVum oil/PEG/Ag-MgO bionanocomposite serve as a potential antimicrobial and anticancer agent and could be used in the development of novel drugs and health care products in near future.

Background: Lipid homeostasis and gut flora can be related to many metabolic diseases, especially autism. Lipid metabolism in the brain can control neuronal structure and function and can also take part in signal transduction pathways to control metabolism in peripheral tissues, especially in the liver. Impaired phospholipid metabolism promotes oxidative stress and neuroinflammation and is, therefore, directly related to autism. Objective: The effect of propionic acid (PPA) toxicity on lipid homeostasis in the gut-liver-brain axis was evaluated to understand their inter-connection. Cytosolic phospholipase A2 (cPLA2) concentration and activity was measured in autistic model and protective role of omega-3 (ω-3) and vitamin B12 was evaluated. Methods: Animals were divided into five groups: Group I (control group); Group II (autistic model treated with neurotoxic dose of PPA); Group III (treated with vitamin B12 (16.7 mg/kg/day) for 30 days post PPA treatment); Group IV (treated with ω-3 (200 mg/kg body weight/day) for 30 days post PPA treatment; Group V (combined dose of ω-3 and Vitamin B12, for 30 days post PPA treatment). Phospholipase A2 activity and protein expression level in the liver homogenate of all the groups was analyzed by western blotting and was compared to brain cPLA2. Results: PPA increased the levels of liver and brain cPLA2. However, independent or combined treatment with ω-3 and vitamin B12 was effective in neutralizing its effect. Moreover, PPA-induced dysbiosis, which was ameliorated with the above treatments. Conclusions: This study showed the role of cPLA2 as a lipid metabolism marker, related to PPA-induced inflammation through a highly interactive gut-liver-brain axis.

Background: Autism spectrum disorders (ASDs) comprise a heterogeneous group of pathological conditions, mainly of genetic origin, characterized by stereotyped behavior, marked impairment in verbal and nonverbal communication, social skills, and cognition. Excitatory/inhibitory (E/I) imbalances have been recorded as an etiological mechanism of ASD. Furthermore, GABA, the main inhibitory neurotransmitter in adult life is known to be much lower in both patients and rodent models of ASD. Methods: In the present study, forty young male western Albino rats, 3–4 weeks in age, weighing about 60–70 g were used. The animals were randomly assigned into six experimental groups; each of them included eight rats. Group (I) serves as control orally given phosphate-buffered saline. Groups (II, III) serve as a rodent model of ASD, orally administered a neurotoxic dose of PPA. The rats in the three therapeutic groups (IV, V, and IV) received the same doses of PPA followed by 0.2 g/kg body weight of pure Bifidobacterium infantis, the probiotic mixture of (ProtexinR), and pure Lactobacillus bulgaricus respectively for three weeks. Selected variables related to oxidative stress, glutamate excitotoxicity, and gut bacteria were measured in the six studied groups. Results: Both pure or mixed Lactobacillus and Bifidobacterium were effective in ameliorating glutamate excitotoxicity as an autistic feature developed in the PPA-induced rodent model. Their therapeutic effects were mostly through, the correction of oxidative stress, restoring the depleted GABA neurotransmitter, and up-regulating the gene expression of GABA receptors. Pure Bifidobacterium was the most effective followed by the mixture of probiotics, and finally lactobacillus. Conclusion: Bifidobacteria and lactobacilli could be used either independently or in combination as psycho-biotics to ameliorate oxidative stress and glutamate excitotoxicity as two confirmed etiological mechanisms through the gut-brain axis.

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.

Silver nanoparticles (AgNPs) are toxic to various microbes, but the mechanism of action is not fully understood. The present report explores Azadirachta indica leaf extract as a reducing agent for the rapid biosynthesis of AgNPs. The effects of AgNPs on the growth, glutathione-S-transferase (GST) activity, and total protein concentration in Staphylococcus aureus were investigated, as was its antibacterial activity against seven other bacterial strains. Nanoparticle synthesis was confirmed by the UV-Vis spectrum and colour change of the solution. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, and infrared spectroscopy were used to characterise the synthesised nanoparticles. The UV-Visible spectrograph showed an absorbance peak at 420 nm. DLS analysis showed an average AgNP size of 159 nm and a Polydispersity Index of 0.373. SEM analysis showed spherical particle shapes, while TEM established an average AgNP size of 7.5 nm. The element analysis profile showed small peaks for calcium, potassium, zinc, chlorine, with the presence of oxygen and silver. AgNPs markedly affected the growth curves and GST activity in treated bacteria, and produced moderate antibacterial activity. Thus AgNPs synthesised from A. indica leaves can interrupt the growth curve and total protein concentration in bacterial cells.

Arbuscular mycorrhizal fungi (AMF) inoculation and biochar amendment has been reported to improve growth of several crop plants however their role in stress amelioration individually as well as in combination has not been worked out. This experiment was conducted to evaluate the application of AMF and biochar on the performance of chickpea under drought stress. The treatments included the individual as well as combined treatment of AMF and biochar to drought stressed and normal chickpea plants. Plants inoculation improved growth in terms of shoot and root length, leaf area and number of branches which was observed to show a steep decline due to drought stress. Drought declined the AMF colonization potential though biochar amendment ameliorated the negative effects of drought significantly by improving the spore population, number of mycelium, vesicle and arbuscules and the percentage of colonization as well. Increased chlorophyll synthesis in biochar and AMF treated plants was obvious, which lead to significant enhancement in the net photosynthetic efficiency. Drought stress also declined the relative water content (RWC) and membrane stability index (MSI), while treatment of biochar and AMF either individually or in combination mitigated the deleterious effects to considerable extent and caused a significant enhancement in RWC and MSI under normal conditions. Amendments with biochar and AMF inoculation increased the nitrogen fixation attributes including the number and weight of nodules, leghemoglobin content and activity of nitrate reductase enzyme leading to greater uptake and assimilation of nitrogen in them when compared to drought stressed plants. Drought stressed chickpea plants exhibited considerable reduction in uptake of nitrogen and phosphorous which was ameliorated by biochar and AMF treatments. It could be suggested that increase in growth and physiological attributes in chickpea due to biochar amendments and AMF inoculation under drought stress were plausibly due to their involvement in nitrogen and phosphorous uptake, chlorophyll synthesis and photosynthesis. Keywords: Biochar, Arbuscular mycorrhizal fungi, Membrane stability index, Nitrogen fixation, Photosynthesis, Drought, Cicer arietinum

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 gut and the liver are closely linked to each other, as changes in the gut microbiota can play a significant role in the development of many liver diseases. Gut bacteria respond rapidly to changes in diet and thus can affect the liver through their metabolites. The impact of a high lipid diet on the liver in the presence of an altered gut flora modulated by ampicillin was investigated. The study was performed on 30 male Western albino rats randomly divided into 3 groups: control (phosphate buffered saline treated), group II (ampicillin 50 mg/kg for three weeks to induce microbiota alterations and fed on standard diet) and group III (same dose of ampicillin and fed on a lipid rich diet). Stool samples were collected for qualitative determination of bacteria. Serum hepato-specific markers, in addition to Glutathione (GSH), Lipid peroxidase (MDA), Glutathione-S- transferase(GST), and vitamin C in liver tissues, were measured. Altered gut microbiota significantly increased the level of the hepato-specific marker MDA and reduced the GST, GSH and vitamin C levels. However, animals fed a lipid rich diet displayed a more significant shift in hepatic markers and antioxidants. Moreover, a new switch in composition of the gut bacteria was observed by feeding the lipid rich diet. Our study showed that bacterial overgrowth in the gut can be associated with liver dysfunction and that a high lipid diet can promote the overgrowth of some liver damaging microflora during antibiotic treatment.

Eye lenses are exposed to thermal, solar radiations, dryness that enhances cataractogenesis. Some animal lenses contain novel proteins in bulk quantities. ζ-crystallin occurred in three ecologically divergent species, but it's physiological role not known. The truncated variant of ζ-crystallin causes hereditary cataract. Guinea pig ζ-crystallin is temperature-sensitive and rapidly aggregates at 41°C. Camels adopted to survive above 50°C, which raises an interesting question about how it retains lens proteins in the soluble state? Here, we have optimized expression and purification of recombinant camel ζ-crystallin. We have studied thermodynamic and spectroscopic properties using orthogonal techniques. Dynamic multimode spectroscopy results showed that camel ζ-crystallin unfolds via single transition with Tm value of 60.8±0.1°C and van't Hoff enthalpy of 714.7±7.1kJ/mol. Thermal-shift assay calculates Tm value of 62°C at pH 7. Additionally, the conformational stability of ζ-crystallin increases with ionic-strength. The influence of pH on ζ-crystallin was evaluated where the protein was found to be stable in the pH range of 6-9, but its stability drastically decreases below pH 6. Our results also showed that quaternary structure of ζ-crystallin drastically changed as a result of lowering pH. This study provides significant understandings onto the conformational, thermodynamic and unfolding pathway of camel ζ-crystallin.

Background Rodent models may guide investigations towards identifying either environmental neuro-toxicants or drugs with neuro-therapeutic effects. This work aims to study the therapeutic effects of bee pollen on brain glutamate excitotoxicity and the impaired glutamine-glutamate- gamma amino butyric acid (GABA) circuit induced by propionic acid (PPA), a short chain fatty acid, in rat pups. Methods Twenty-four young male Western Albino rats 3–4 weeks of age, and 45–60 g body weight were enrolled in the present study. They were grouped into four equal groups: Group 1, the control received phosphate buffered saline at the same time of PPA adminstration; Group 2, received 750 mg/kg body weight divided into 3 equal daily doses and served as acute neurotoxic dose of PPA; Group 3, received 750 mg/kg body weight divided in 10 equal doses of 75 mg/kg body weight/day, and served as the sub-acute group; and Group 4, the therapeutic group, was treated with bee pollen (50 mg/kg body weight) for 30 days after acute PPA intoxication. GABA, glutamate and glutamine were measured in the brain homogenates of the four groups. Results The results showed that PPA caused multiple signs of excitotoxicity, as measured by the elevation of glutamate and the glutamate/glutamine ratio and the decrease of GABA, glutamine and the GABA/glutamate ratio. Bee pollen was effective in counteracting the neurotoxic effects of PPA to a certain extent. Conclusion In conclusion, bee pollen demonstrates ameliorating effects on glutamate excitotoxicity and the impaired glutamine-glutamate-GABA circuit as two etiological mechanisms in PPA-induced neurotoxicity.

Overexpression of nuclear factor (NF-κB) or activation of Smad3 by transforming growth factor β (TGF-β1) induced by oncogenes results in overexpression of fibrotic processes and hence cell death. The objective of this study is to examine whether Silymarin (Sil) alone or in combination with Vitamin E (Vit E) and/or Curcumin (Cur) plays a modulatory role against the overexpression of NF-κB, and TGF-β that induced in response to carbon tetrachloride (CCl4) administration. The present work revealed that CCl4 induced elevation of in serum alanine aminotransferase (ALT), Apoptosis regulator (Bax), Smad3, TGF-β, and NF-kB hepatic mRNA expression (using Real-time PCR), administration of Sil alone downregulated these expressions. Treatment with Vit E acid and/ or Cur along with Sil produced best results in this concern. B-cell lymphoma 2 (Bcl-2) expressions were downregulated by CCl4; whereas concurrent treatment of Vit E and/or Cur along with Sil increased its expression. On conclusion, the use of Vit E a...

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.

BackgroundGlutamate excitotoxicity can cause DNA damage and is linked to many retinal and neurological disorders. In mammals, the visual signal from the eyes to the brain is conducted only by retinal ganglion cells (RGCs), which can be damaged by overstimulation of glutamate receptors.MethodologyWe examined the protective effects ofMoringa oleiferaseed extract against glutamate-induced DNA damage in RGCs. RGCs cells were treated with 5, 10, 50, or 100 µg/ml ofM. oleiferaseed extract and glutamate separately and then assessed for DNA damage using the comet assay. We also evaluated the viability of the RGCs after both treatments using the MTT test. Additionally, RGCs were pretreated withM.oleiferaseed extract (50 or 100 µg/ml) for 2 h before glutamate treatment (100 µg/ml) to determine the potential protective effects ofM. oleifera. We performed a phytochemical analysis of theM. oleiferaseed extract using standard reactions.ResultsTheM. oleiferaseed extract was found to be rich in many phytochemicals. We observed a significant dose-dependent elevation in all comet assay variables in glutamate-treated RGCs, whereasM. oleiferaseed extract treatments did not show any significant change in DNA integrity.ConclusionM. oleiferaseed extract demonstrates neuroprotective effects, which suggests it may help to prevent the development of many neurodegenerative disorders.

Background Abnormal phospholipid metabolism is a major component of many neurodevelopmental disorders including autism. Oral administration of propionic acid (PPA) can produce behavioral abnormalities and biochemical features in rodents similar to those observed in autism and can thus be used as a model to understand impaired brain fatty acid metabolism in autism. Methods The present study was designed to understand alterations in phospholipid metabolism in the brain of a rodent model of autism and to explore omega-3 and vitamin B12 as remedies. Five groups of rats were selected: Group 1 was the control. Group 2 was the rodent model of autism treated with a neurotoxic dose of PPA. Group 3 was given vitamin B12 cobalamin (16.7 mg/kg/day) for 30 days after PPA treatment. Group 4 was given pharmaceutical grade Omega-3 (200 mg cholesterol free-DHA/kg body weight/day), a product of Madre lab, Germany, for 30 days after PPA treatment for 3 days. Group 5 was given a combined dose of ω-3 + Vitamin B12 for the same duration post-PPA treatment. Phospholipid levels and Phospholipase A2 were measured in the brain homogenates of all the groups. ELISA and western blotting were used to detect the cPLA2 protein level. Results A significant decrease in phospholipid levels and a significant increase in cPLA2 were found in brain tissue of PPA-treated rats; however, both ω-3 and vitamin B12 were efficient in ameliorating the neurotoxic effect of PPA. Conclusion Both ω-3 and vitamin B12 may play a role in ameliorating impaired phospholipid metabolism in autism; however, proper clinical trials are needed.

Background Colorectal cancer is the leading cause of cancer-related deaths in Saudi Arabia. Cancer has a multifactorial nature and can be described as a disease of altered gene expression. The profiling of gene expression has been used to identify cancer subtypes and to predict patients' responsiveness. Telomere-associated proteins that regulate telomere biology are essential molecules in cancer development. Thus, the present study examined their contributions to colorectal cancer progression in Saudi patients. Methods The expression of hTERT, TRF1, TRF2, POT1, ATR, ATM, Chk1 and Chk2 were measured via real-time PCR in matched cancerous and adjacent tissues of CRC patients. The protein level of hTERT, TRF1, TRF2, ATR, ATM, Chk1 and Chk2 were measured using immunohistochemistry. A region of hTERT core promoter was sequenced via Sanger sequencing. Methylation of CTCF binding site was examined via methylation-specific PCR. Finally, the length of telomere was estimated using q-PCR. Results Our results showed that POT1, ATR, Chk1 and Chk2 show increased expression in CRC relative to the adjacent mucosa. The expression levels of each gene were associated with clinicopathological characteristics of patients with CRC. There was a positive correlation between the age of the patients and hTERT expression. Regarding tumor site, telomere length, ATR, ATM and Chk1 were shown to be altered. No somatic mutation was detected in hTERT core promoter, and no differences in methylation patterns at CTCF binding site in the promoter between normal and cancer tissues. Conclusion Analysis of targeted genes expression in colorectal cancer based on the clinical variables revealed that tumor location and age could have a role in gene expression and telomere length variations and this could be taken under consideration during CRC diagnosis and therapy. Other epigenetic mechanisms could influence hTERT expression in cancers. Our findings warrant further validation through experiments involving a larger number of patients.

Purpose: To investigate the potency of ampicillin in altering gut flora in the presence of a high-sucrose diet in rat pups, and to determine its effect on selected neurotransmitters and a cytokine as markers of the persistent autistic features repeatedly induced in orally administered propionic acid rat pups.. Methods: Twenty-eight young male Wistar albino rats were divided into four equal groups. The first group served as a control. The second group received an oral neurotoxic dose of propionic acid (PPA, 250 mg/kg body weight/day) for 3 days. The third group was treated with ampicillin (50 mg/kg for 3 weeks) with a standard diet. The fourth group was given the same dose of ampicillin with a high-sucrose diet for 10 weeks. Results: The results showed a significant ( p < 0.001) decrease in the investigated neurotransmitters in PPA- and ampicillin-treated rat pups (norepinephrine by 32.49 and 14.58 %, dopamine by 31.45 and 20.22 %, serotonin by 35.99 and 29.09 %), as well as a remarkable increase ( p < 0.001) in the proinflammatory cytokine, IL-6 (30.07and 6.07 %). The high-sucrose diet also significantly ( p < 0.001) enhanced the neurotoxic effect of ampicillin. Conclusion: The observed dietary modulation of the gut microbiota, coupled with the subsequent modulation of brain neurochemistry and inflammation, demonstrates the considerable potential of dietary intervention through the elimination of highly refined sugar as a treatment strategy to prevent and treat autism. Keywords: Neurotoxicity, Ampicillin, Propionic acid, Neurotransmitters, Cytokines, High-sucrose diet