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Initiation of colorectal carcinogenesis may be induced by chromosomal instability caused by oxidative stress or indirectly by bacterial infections. Moreover, proliferating tumor cells are characterized by reprogrammed glucose metabolism, which is associated with upregulation of PDK1 and LDHA enzymes. In the present study, some 4,5,6,7-tetrahydrobenzo[b]thiophene derivatives in addition to Fe3O4 and Fe3O4/SiO2 nanoparticles (NPs) supported with a new Schiff base were synthesized for biological evaluation as PDK1 and LDHA inhibitors as well as antibacterial, antioxidant, and cytotoxic agents on LoVo and HCT-116 cells of colorectal cancer (CRC). The results showed that compound 1b is the most active as PDK1 and LDHA inhibitor with IC50 values (μg/mL) of 57.10 and 64.10 compared to 25.75 and 15.60, which were produced by the standard inhibitors sodium dichloroacetate and sodium oxamate, respectively. NPs12a,b and compound 1b exhibited the strongest antioxidant properties with IC50 values (μg/mL) of 80.0, 95.0, and 110.0 μg/mL, respectively, compared to 54.0 μg/mL, which was produced by butylated hydroxy toluene. Moreover, NPs12a and carbamate derivative 3b exhibited significant cytotoxic activities with IC50 values (μg/mL) of 57.15 and 81.50 (LoVo cells) and 60.35 and 71.00 (HCT-116 cells). Thus, NPs12a and compound 3b would be considered as promising candidates suitable for further optimization to develop new chemopreventive and chemotherapeutic agents against these types of CRC cell lines. Besides, molecular docking in the colchicine binding site of the tubulin (TUB) domain revealed a good binding affinity of 3b to the protein; in addition, the absorption, distribution, metabolism, and excretion (ADME) analyses showed its desirable drug-likeness and oral bioavailability characteristics.

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.

Traditional wastewater treatments involve expensive mechanical and physiochemical methods, so researchers have been developing cost-effective, sustainable technologies that use enzymes to produce higher quality effluents and recover more energy and nutrients from wastewater. A thermostable, alkaline, and solvent-tolerant lipase was partially purified from thermophilic Bacillus stearothermophilus. The lipase displayed maximum activity at 50 °C and pH 11.0 and catalyzed both short- and long-chain triacylglycerols at similar rates. B. stearothermophilus lipase also exhibited high stability when incubated at 40 °C for 1 h with anionic and non-ionic surfactants. Studies show that thermostable enzymes can be improved through immobilization and modification of other reaction conditions. Therefore, B. stearothermophilus lipase was immobilized through adsorption on CaCO3, Celite 545, and silica gel with the CaCO3 support producing the best adsorption rate (89.33%). The optimal initial lipase activity was approximately 4500 U.g−1 after 60 min. Interestingly, 93% of the initial lipase activity was retained after six cycles, and almost 50% of the initial activity remained after 12 cycles. Furthermore, immobilization improved storage stability with 98.85% of the initial lipase activity retained after 60 days of storage at 4 °C. The biochemical characteristics of immobilized lipase shifted toward a slightly alkaline region, reaching maximum activity at pH 12. The optimal temperature of immobilized lipase was 60 °C. Immobilization also improved enzymatic stability by widening the pH range from 5–9 (for free lipase) to 4–11, and thermostability by reaching 65 °C. The application of immobilized lipase in wastewater treatment was observed through oil layer biodegradation. Notably, treating wastewater for 10 days with immobilized lipase almost removed the chemical oxygen demand (COD) from 1950.1 down to 4.04 mg.L−1. Similarly, lipid content was almost removed from 15,500 ± 546 mg.L−1 down to 12 mg.L−1. All results highlight the potential value of CaCO3-immobilized lipase as an effective biocatalyst for hydrolyzing wastewater.

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.

Brain inflammation and apoptosis play crucial roles in the pathogenesis of various neurodevelopmental disorders. Probiotics have been shown to confer protection against many stresses, including apoptosis and inflammation, by modulating the gut function. The short‐chain fatty acid, propionic acid (PPA), plays an important intermediate of cellular metabolism. Although PPA exhibits numerous beneficial biological effects, its accumulation is neurotoxic. This study focused on the therapeutic potency of probiotics against PPA‐induced apoptosis and neuroinflammation in hamsters. Five groups of male golden Syrian hamsters were treated as follows: Group I as control; Group II as PPA‐treated with three doses of 250 mg PPA/kg/day; Group III as clindamycin‐treated with a single dose of 30 mg clindamycin/kg; Group IV as PPA–probiotic; and Group V as clindamycin–probiotic were two therapeutic groups which were treated with the same doses of PPA and clindamycin, respectively, followed by treatment with 0.2 g kg‐1 d−1 of probiotic (ProtexinR, Probiotics International Limited) for three weeks. Proapoptotic markers, such as caspases 3 and 7; neuroinflammation markers, such as interleukins 1β and 8; and heat shock protein 70 were measured in the brain. Significant increase of all measured markers (p ˂ .001) was observed in PPA and clindamycin‐treated hamsters compared with controls. Probiotics significantly reduced the damages and ameliorated all the test markers in both therapeutic groups compared with the control. Our results confirmed that probiotics can be utilized as a feasible strategy for managing apoptotic and inflammation‐related stresses in brain disorders by retaining the gut function., This study ascertained the role of neuroinflammation and apoptosis as neurotoxic effects in the PPA‐induced rodent model of autism. Clindamycin showed relatively fewer neurotoxic effects compared with orally administered PPA. Moreover, our study showed that probiotics exert ameliorative effects and may be used as a novel noninvasive and safe treatment strategy.

There are limited data on inflammatory cytokines and chemokines; the humoral immune response; and main clinical laboratory parameters as indicators for disease severity and mortality in patients with critical and mild COVID-19 without comorbidities or immune-mediated diseases in Saudi Arabia. We determined the expression levels of major proinflammatory cytokines and chemokines; C-reactive protein (CRP); procalcitonin; SARS-CoV-2 IgM antibody and twenty-two clinical laboratory parameters and assessed their usefulness as indicators of disease severity and in-hospital death. Our results showed a significant increase in the expression levels of SARS-CoV-2 IgM antibody; IL1-β; IL-6; IL-8; TNF-α and CRP in critical COVID-19 patients; neutrophil count; urea; creatinine and troponin were also increased. The elevation of these biomarkers was significantly associated and positively correlated with in-hospital death in critical COVID-19 patients. Our results suggest that the levels of IL1-β; IL-6; IL-8; TNF-α; and CRP; neutrophil count; urea; creatinine; and troponin could be used to predict disease severity in COVID-19 patients without comorbidities or immune-mediated diseases. These inflammatory mediators could be used as predictive early biomarkers of COVID-19 disease deterioration; shock and death among COVID-19 patients without comorbidities or immune-mediated diseases.

In this study, the chemical compositions of the ethanolic and aqueous extracts of the leaves of Origanum syriacum and Salvia lanigera were identified based on GC-MS spectrometric analyses. The in vitro anti-inflammatory potential of the different extracts was evaluated by determining the membrane stabilization of human red blood cells and the percent inhibition of the COX1/2, 5LOX, and sPLA2-V enzymes. Both ethanolic extracts showed maximum membrane stabilization (≤ 91%, at 100 μg/mL) compared to the aqueous extracts (≤ 45%) and the reference drug diclofenac sodium (90.75%). The membrane-stabilizing effects of the ethanolic extracts could be directly correlated to their anti-inflammatory activity. While both ethanolic fractions strongly inhibited the 5LOX and COX-1 enzymes at 100 μg/mL, only the O. syriacum ethanolic extract selectively inhibited sPLA2-V (99.35%, at 50 μg/mL). The differences in the pharmacological efficiencies of the different extracts could be attributed to the variation in their chemical compositions particularly the content of oxygenated monoterpenoids. Additionally, none of the ethanolic extracts demonstrated cytotoxicity to human colorectal cancer cell lines (HCT-116 and Lovo), even at the highest concentration tested (200 μg/mL). The safe profiles of these extracts towards the tested cell lines may be due to the absence of the toxic phthalic acid ester substances. Collectively, these findings clearly suggest that the studied ethanolic extracts of O. syriacum and S. lanigera can be considered interesting candidates for the treatment of human inflammatory diseases related to oxidative stress and microbial infections.

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.

Aging and age-related disorders are prominent issues. Aging is associated with a gradual impairment of physiology at the genetic, cellular, tissue, and whole organism level that directly influences the development of chronic diseases and organ failure. Blueberries, on the other hand, are well known for their high content of bioactive compounds and have demonstrated positive impacts on metabolic factors that influence health and general well-being. This study is aimed at evaluating the ameliorating the effects of blueberry on the liver of aged rats by monitoring changes in metabolic disturbances, oxidative stress, and inflammatory disruption. The aged group of rats was orally administered with blueberry extract (200 mg/kg) for a period of 4 weeks. The results revealed that aging was associated with an increase in body weight, liver weight, and metabolic parameters like serum insulin, triglycerides, total cholesterol, and liver function markers accompanied with a decrease in vitamin D levels. Furthermore, the results showed a significant diminish in the activities of antioxidant enzymes, glutathione content with an elevation in lipid peroxidation, inflammatory mediators (tumor necrosis factor alpha, interleukin 6, and nuclear factor kappa-light-chain-enhancer of activated B cells) as well as fibrotic markers (TGF-β1) in the liver of aged rats. Compared to the young rats (control group), blueberry effectively reversed age-mediated disruption of the aforementioned parameters. Hence, blueberries can be used as a potential therapeutic strategy for the management of age-related liver dysfunction and disease.

Introduction Nanoparticles are at the forefront of rapidly developing nanotechnology and have gained much attention for their application as an effective drug delivery system and as a mediated therapeutic agent for cancer. However, the cytotoxicity of nanoparticles is still relatively unknown and, therefore, additional study is required in order to elucidate the potential toxicity of these nanoparticles on cells. Materials and methods Thus, the following work aimed to investigate the capability of Beta vulgaris (beetroot) water extract (BWE; 200 mg/kg) to protect hepatic tissue following silver nanoparticles (AgNPs; 80 mg/kg; >100 nm) intoxication in male rats. Results AgNPs-intoxication elevated the liver function markers - including serum transaminases and alkaline phosphatase activities - and decreased serum levels of albumin and total proteins, in addition to disturbing the oxidation homeostasis. This is evidenced by the increased lipid peroxidation, the depleted glutathione, and the suppressed activity of superoxide dismutase and catalase. In addition, an apoptotic reaction was observed following AgNPs treatment, as indicated by the up-regulation of p53 and down-regulating Bcl-2 expressions, examined by the immunohistochemistry method. Furthermore, AgNPs exhibited a marked elevation in liver DNA damage that was indicated by an increase in tail length, tail DNA% and tail movement. However, BWE eliminated the biochemical and histological alterations, reflecting its hepatoprotection effect in response to AgNPs. Discussion Collectively, the present data suggest that BWE could be used following AgNPs as a potential therapeutic intervention to minimize AgNPs-induced liver toxicity.

We aimed in the current study, the identification of a marine bacterial amylase produced by Bacillus pacificus, which was associated with Turbinaria ornata. Cultural conditions were optimized for the highest amylase production on Tryptic soy broth media supplemented with starch 1% at initial pH 9, 55 &deg, C for 24 h. The newly purified amylase was characterized for a possible biotechnological application. Data indicated that the obtained amylase with a molecular weight of 40 kD and the N-terminal sequence of the first 30 amino acids of amBp showed a high degree of homology with known alpha amylase, and was stable at 60 &deg, C of pH 11. Among the tested substrate analogs, amBp was almost fully active on Alylose and Alylopectine (97%), but moderately hydrolyzed glycogen &lt, sucrose &lt, maltose &lt, lactose. Therefore, the current amylase mainly generated maltohexaose from starch. Mg2+ and Zn2+ improved amylase activity up to 170%. While ethylenediamine tetraacetic acid (EDTA) similarly induced the greatest activity with purified amylase, PCMB had the least effect. Regarding all these characteristics, amylase from marine bacterial symbionts amBp has a new promising feature for probable therapeutic, industrial, and nutritional applications.

Obesity is a global epidemic disease that is closely associated with various health problems as Diabetes mellitus, cardiovascular, and metabolic disorders. Lycopene (LYC), a red-colored carotenoid, has demonstrated various promising therapeutic effects. Hence, the potential of LYC was studied against high fat diet (HFD)-induced obesity and metabolic disturbances in rats. Animals fed on HFD and orally supplemented with LYC (25 and 50 mg/kg) or simvastatin (10 mg/kg) every day for 3 months. The results revealed that long-term consumption of HFD significantly increased weight gain, liver weight, cholesterol, triglycerides (TG), apolipoprotein-B (Apo-B), low-density lipoprotein-cholesterol (LDL-c) levels, as well as decreasing the high-density lipoprotein-cholesterol (HDL-c) levels. Moreover, high blood glucose and insulin levels accompanied by low peroxisome proliferator activated receptor gamma (PPAR-γ) were recorded in HFD group. Further, HFD rats displayed lower levels of antioxidant biomarkers (SOD, CAT, GPx, GR and GSH), in addition to higher levels of MDA, NO and inflammatory mediators (IL-1β, TNF-α, and MPO). Marked increases were observed in atherogenic index, lactate dehydrogenase and creatine kinase together with fibrosis markers (TGF-β1 and α-SMA) in rats fed on HFD. Comparing to model group, LYC was able to effectively reverse HFD-mediated alterations at dose dependent manner. Altogether, dietary supplementation of LYC successfully reversed HFD-induced alterations through its antioxidant, anti-inflammatory, and anti-fibrotic properties. Hence, LYC displayed a therapeutic potential to manage obesity and its associated pathologies.

The pathogenesis of colorectal cancer is a multifactorial process. Dysbiosis and the overexpression of COX-2 and LDHA are important effectors in the initiation and development of the disease through chromosomal instability, PGE2 biosynthesis, and induction of the Warburg effect, respectively. Herein, we report the in vitro testing of some new quinoxalinone and quinazolinone Schiff’s bases as: antibacterial, COX-2 and LDHA inhibitors, and anticolorectal agents on HCT-116 and LoVo cells. Moreover, molecular docking and SAR analyses were performed to identify the structural features contributing to the biological activities. Among the synthesized molecules, the most active cytotoxic agent, (6d) was also a COX-2 inhibitor. In silico ADMET studies predicted that (6d) would have high Caco-2 permeability, and %HIA (99.58%), with low BBB permeability, zero hepatotoxicity, and zero risk of sudden cardiac arrest, or mutagenicity. Further, (6d) is not a potential P-gp substrate, instead, it is a possible P-gpI and II inhibitor, therefore, it can prevent or reverse the multidrug resistance of the anticancer drugs. Collectively, (6d) can be considered as a promising lead suitable for further optimization to develop anti-CRC agents or glycoproteins inhibitors.

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.

SARS CoV-2 is still considered a global health issue, and its threat keeps growing with the emergence of newly evolved strains. Despite the success in developing some vaccines as a protective measure, finding cost-effective treatments is urgent. Accordingly, we screened a number of phenolic natural compounds for their in vitro anti-SARS CoV-2 activity. We found sinapic acid (SA) selectively inhibited the viral replication in vitro with an half-maximal inhibitory concentration (IC50) value of 2.69 µg/mL with significantly low cytotoxicity (CC50 = 189.3 µg/mL). Subsequently, we virtually screened all currently available molecular targets using a multistep in silico protocol to find out the most probable molecular target that mediates this compound’s antiviral activity. As a result, the viral envelope protein (E-protein) was suggested as the most possible hit for SA. Further in-depth molecular dynamic simulation-based investigation revealed the essential structural features of SA antiviral activity and its binding mode with E-protein. The structural and experimental results presented in this study strongly recommend SA as a promising structural motif for anti-SARS CoV-2 agent development.

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.

This study was conducted to identify a new alkaline and thermophilic protease (Ba.St.Pr) produced from Bacillus stearothermophilus isolated from olive oil mill sols and to evaluate its culture conditions, including temperature, pH, carbon and nitrogen sources, and incubation time. The optimum culture conditions for cell growth (10 g/L) and protease production (5050 U/mL) were as follows: temperature 55 °C, pH 10, inoculation density 8 × 108 CFU/mL, and incubation time 24 h. The use of 3% yeast extract as the nitrogen sources and galactose (7.5 g/L) as the carbon sources enhanced both cell growth and protease production. Using reversed-phase analytical HPLC on C-8 column, the new protease was purified with a molecular mass of approximately 28 kDa. The N-terminal sequence of Ba.St.Pr exhibited a high level of identity of approximately 95% with those of Bacillus strains. Characterization under extreme conditions revealed a novel thermostable and alkaline protease with a half-life time of 187 min when incubated with combined Ca2+/mannitol. Ba.St.Pr demonstrated a higher stability in the presence of surfactant, solvent, and Ca2+ ions. Consequently, all the evaluated activity parameters highlighted the promising properties of this bacterium for industrial and biotechnological applications.

Many venomous species, especially snakes, contain a variety of secreted phospholipases A2 that contribute to venom toxicity and prey digestion. We characterized a novel highly toxic phospholipase A2 of group II, WaPLA2-II, from the snake venom of Saudi Walterinnesia aegyptia (W. aegyptia). The enzyme was purified using a reverse phase C18 column. It is a monomeric protein with a molecular weight of approximately 14 kDa and an NH2-terminal amino acid sequence exhibiting similarity to the PLA2 group II enzymes. WaPLA2-II, which contains 2.5% (w/w) glycosylation, reached a maximal specific activity of 1250 U/mg at pH 9.5 and 55 &deg, C in the presence of Ca2+ and bile salts. WaPLA2-II was also highly stable over a large pH and temperature range. A strong correlation between antimicrobial and indirect hemolytic activities of WaPLA2 was observed. Additionally, WaPLA2-II was found to be significantly cytotoxic only on cancerous cells. However, chemical modification with para-Bromophenacyl bromide (p-BPB) inhibited WaPLA2-II enzymatic activity without affecting its antitumor effect, suggesting the presence of a separate &lsquo, pharmacological site&rsquo, in snake venom phospholipase A2 via its receptor binding affinity. This enzyme is a candidate for applications including the treatment of phospholipid-rich industrial effluents and for the food production industry. Furthermore, it may represent a new therapeutic lead molecule for treating cancer and microbial infections.

Plants of the Euphorbia genus present a wide range of therapeutic applications. This study is aimed at investigating new antidigestive enzyme agents from Euphorbia cyparissias through inhibition of lipid and carbohydrate absorption, to evaluate their potential applications for the treatment of metabolic syndrome. Lipase, phospholipase, protease, α-amylase, β-glucosidase, and xanthine oxidase activities under treatment with aqueous and ethanolic extracts of Euphorbia cyparissias were observed to evaluate the inhibitory effect of these extracts, as well as their antioxidant and cytotoxic effects. Results showed that ethanolic and aqueous extracts exhibited important inhibitory activity in a concentration-related manner on digestive enzymes, which is more effective than the commercial drugs used as controls. Results also showed that, out of the two extracts tested, the ethanolic extract presented the most promising results in inhibiting the activities of all digestive enzymes used. Moreover, the two extracts displayed a higher reducing power than that of the positive control used. The obtained results, together with previous reports in the literature, strongly suggest that Euphorbia cyparissias extracts may be natural inhibitors of the digestive enzymes and thus a potential new drug for metabolic syndrome treatment.