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Silver nanoparticles (AgNPs) are extensively studied as potent antibacterial agents targeting antibiotic-resistant pathogens. Cellular damage induced through various mechanisms that can affect multiple cell components like the outer membrane, enzymes, and proteins is closely linked to their chemical and morphological characteristics. We investigated the impact of AgNPs’ size on their antibacterial effectiveness using two differently sized nanoparticles: silver nanoparticle-Citrus limon (AgCL) with an average size of 21 nm and silver nanoparticle-Citrus sinensis (AgCS) with an average size of 13 nm, derived from C. limon and C. sinensis through environmentally friendly methods. The study evaluated their antibacterial effects by assessing morphology changes via scanning electron microscopy, metabolic alterations using Fourier transform infrared (FT-IR) spectroscopy, and oxidative stress responses through biochemical markers in Klebsiella pneumoniae cells exposed to AgNPs. The results showed that both AgCL and AgCS exhibited remarkable antibacterial activity, evidenced by inhibition zones of 14 ± 1.5 and 16 ± 1.0 mm, respectively. Morphological changes in K. pneumoniae cells treated with AgNPs were size dependent, with notable alterations noted. FT-IR spectroscopy revealed size and concentration-dependent biochemical changes, particularly in shifts in functional groups involved in the fluidity of cell wall lipid, and protein structure. Exposure to AgNPs led to increased oxidative stress markers like lipid peroxides and reduced levels of enzymatic and non-enzymatic antioxidants, more prominently observed with smaller AgCS nanoparticles (13 nm). AgNPs induce oxidative stress and morphological changes in K. pneumoniae strains, with smaller nanoparticles demonstrating greater efficacy. These findings underscore the importance of nanoparticle size in optimizing the antibacterial properties against pathogens.

Rodent models may help investigations on the possible link between autism spectrum disorder and increased permeability of the gastrointestinal (GI) tract since autistic patients frequently manifested GI troubles as comorbidities.

Abstract Backgrounds The investigation of the environmental contribution for developmental neurotoxicity is very important. Many environmental chemical exposures are now thought to contribute to the development of neurological disorders, especially in children. Results from animal studies may guide investigations of human populations toward identifying environmental contaminants and drugs that produce or protect from neurotoxicity and may help in the treatment of neurodevelopmental disorders. Objective To study the protective effects of omega-3 polyunsaturated fatty acid on brain intoxication induced by propionic acid (PPA) in rats. Methods 24 young male Western Albino rats were enrolled in the present study. They were grouped into three equal groups; oral buffered PPA-treated group given a nuerotoxic dose of 250 mg/Kg body weight/day for 3 days; omega-3 - protected group given a dose of 100 mg/kg body weight/day omega-3 orally daily for 5 days followed by PPA for 3 days, and a third group as control given only phosphate buffered saline. Tumor necrosis factor-α, caspase-3, interlukin-6, gamma amino-buteric acid (GABA), serotonin, dopamine and phospholipids were then assayed in the rats brain's tissue of different groups. Results The obtained data showed that PPA caused multiple signs of brain toxicity as measured by depletion of gamaaminobyteric acid (GABA), serotonin (5HT) and dopamine (DA) as three important neurotransmitters that reflect brain function. A high significant increase of interlukin-6 (Il-6), tumor necrosis factor-α (TNF-α) as excellent markers of proinflammation and caspase-3 as a proapotic marker were remarkably elevated in the intoxicated group of rats. Moreover, brain phospholipid profile was impaired in PPA-treated young rats recording lower levels of phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylcholine (PC). Conclusions Omega-3 fatty acids showed a protective effects on PPA - induced changes in rats as there was a remarkable amelioration of most of the measured parameters (i.e. higher GABA, 5HT, DA, PE, PS and PC) and lower Il-6, TNF-α and caspase-3.

Understanding the factors driving SARS-CoV-2 infection progression and severity is complex due to the dynamic nature of human physiology. Therefore, we aimed to explore the severity risk indicators of SARS-CoV-2 through demographic data, clinical manifestations, and the profile of laboratory parameters. The study included 175 patients either hospitalized at King Abdulaziz Medical City-Riyadh or placed in quarantine at designated hotels in Riyadh, Saudi Arabia, from June 2020 to April 2021. Hospitalized patients were followed up through the first week of admission. Demographic data, clinical presentations, and laboratory results were retrieved from electronic patient records. Our results revealed that older age (OR: 1.1, CI: [1.1-1.12]; p < 0.0001), male gender (OR: 2.26, CI: [1.0-5.1]; p = 0.047), and blood urea nitrogen level (OR: 2.56, CI: [1.07-6.12]; p = 0.034) were potential predictors of severity level. In conclusion, the study showed that apart from laboratory parameters, age and gender could potentially predict the severity of SARS-CoV-2 infection in the early stages. To our knowledge, this study is the first in Saudi Arabia to explore the longitudinal profile of laboratory parameters among risk factors, shedding light on SARS-CoV-2 infection progression parameters.

The mechanisms underlying selective serotonin reuptake inhibitor (SSRI) use during pregnancy as a major autism risk factor are unclear. Here, brain neurochemical changes following fluoxetine exposure and in an autism model were compared to determine the effects on autism risk. The study was performed on neonatal male western albino rats which were divided into Groups one (control), two (propionic acid [PPA]-induced autism model), and three (prenatal SSRI-exposed newborn rats whose mothers were exposed to 5 mg/kg of fluoxetine over gestation days 10-20). SSRI (fluoxetine) induced significant neurochemical abnormalities in the rat brain by increasing lipid peroxide (MDA), Interferon-gamma (IFN-γ), and caspase-3 levels and by depleting Glutathione (GSH), Glutathione S-transferases (GST), Catalase, potassium (K+), and Creatine kinase (CK) levels, similarly to what has been discovered in the PPA model of autism when compared with control. Prenatal fluoxetine exposure plays a significant role in asset brain damage in newborns; further investigation of fluoxetine as an autism risk factor is thus warranted.

Genetic polymorphism in proinflammatory cytokine genes may be associated with the etiology of preterm birth (PTB). The current study was designed with the aim to explore the association of genetic polymorphisms and mRNA expression of IL-1α, IL-1β, and TNF-α gene with preterm birth in the Saudi population. Genotyping of genomic DNA of 50 PTB patients and an equal number of controls were carried out using TaqMan Genotyping assay kits. Gene expression of each gene was carried out using quantitative RT-PCR. The cytokine levels in the serum of PTB patients and controls were measured by ELISA. A statistically significant association was observed between the rs361525 alleles (G and A) of TNF-α and PTB, where the mutant A allele was significantly protective against PTB development (OR= 0.362; χ2=4.31; p=0.038). The gene expression of all studied genes (IL1α, IL-1β, IL-6, and TNF-α) was higher in the PTB patients, but the results reached significance only for IL-1β (p=0.035). Elevated gene expression was also evident from the level of these proteins in plasma, where the level of IL1α, IL-β were significantly higher in the serum of PTB patients compared to the controls, however, IL6 and TNF-α were significantly lower despite higher gene expression. For IL6, the lower level could be due to tocolytic treatment that was given to all women suffering from PTB. Receiver operating curves (ROC) were drawn for the studied cytokines. In conclusion, this study revealed that rs361525 polymorphism plays a role as a protective marker for PTB and the levels of IL-1α, IL-6, TNF- α can be used as predicative biomarkers for PTB I Saudi women.

MeHg is a widely distributed environmental toxicant with harmful effects on the developing and adult nervous system. This study aimed to evaluate the therapeutic and protective efficacy of pollen grain in improving the toxic effects of MeHg, through the measurement of selected biochemical parameters linked to oxidative stress, energy metabolism, and neurotransmission in brain homogenates of male pups' neonates. Forty healthy pregnant female rats were randomly divided into five groups, and after delivery, each group was consisting of 10 male neonates: (1) neonates delivered by control mothers, (2) neonates delivered by bee pollen treated mothers who received bee pollen at the dose of 200-mg/kg body weight from postnatal day 0 for 4 weeks, (3) neonates delivered by MeHg-treated mothers who received MeHg at the dose of 0.5 mg/kg/day via drinking water from gestational day 7 till postnatal day 7 of delivery, (4) therapeutic group: neonates delivered by MeHg-treated mothers followed by bee pollen treatment who received bee pollen at the dose of 200-mg/kg body weight from postnatal day 0 for 4 weeks, and (5) protective group: neonates delivered by MeHg and bee pollen-treated mothers. Mothers continued receiving the bee pollen at the same dose until day 21. Biochemical parameters linked to oxidative stress and energy metabolism and neurotransmission were investigated in brain homogenates of neonates from all the five groups. MeHg treatment showed an increase in oxidative stress markers like lipid peroxidation and catalase activity coupled with a non-significant decrease in glutathione level. Impaired energy metabolism was ascertained via the inhibition of creatine kinase and lactate dehydrogenase activities. Dramatic decrease of Mg 2+ and K + concentrations confirmed the neurotransmission defect. Interestingly, the bee pollen treatment was highly effective in restoring the catalase, lactate dehydrogenase, and creatine kinase activities in addition to normalizing the levels of Mg 2+ , K + , lipid peroxidation, and glutathione. Overall, the exposure to MeHg during the developing brain stages was highly effective to show signs and symptoms of neuronal toxicity. Furthermore, it has been concluded that bee pollen can be used safely to ameliorate oxidative stress, poor detoxification as well as metal ion defects, and neuronal death as a critical mechanisms involved in the etiology of numerous neurological disorders.

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.

Background: Abnormalities in fatty acid metabolism and membrane fatty acid composition play a part in a wide range of neurodevelopmental and psychiatric disorders. Altered fatty acid homeostasis as a result of insufficient dietary supplementation, genetic defects, the function of enzymes involved in their metabolism, or mitochondrial dysfunction contributes to the development of autism., Objective: This study evaluates the association of altered brain lipid composition and neurotoxicity related to autism spectrum disorders in propionic acid (PA)-treated rats., Design: Forty-eight young male western albino rats were used in this study. They were grouped into six equal groups with eight rats in each. The first group received only phosphate buffered saline (control group). The second group received a neurotoxic dose of buffered PA (250 mg/kg body weight/day for 3 consecutive days). The third and fourth groups were intoxicated with PA as described above followed by treatment with either coenzyme Q (4.5 mg/kg body weight) or melatonin (10 mg/kg body weight) for 1 week (therapeutically treated groups). The fifth and sixth groups were administered both compounds for 1 week prior to PA (protected groups). Methyl esters of fatty acid were extracted with hexane, and the fatty acid composition of the extract was analyzed on a gas chromatography., Results: The obtained data proved that fatty acids are altered in brain tissue of PA-treated rats. All saturated fatty acids were increased while all unsaturated fatty acids were significantly decreased in the PA-treated group and relatively ameliorated in the pre-post melatonin and coenzyme Q groups., Conclusions: Melatonin and coenzyme Q were effective in restoring normal level of most of the impaired fatty acids in PA-intoxicated rats which could help suggest both as supplements to ameliorate the autistic features induced in rat pups.

Propionic acid (PA) is a short chain fatty acid, a common food preservative and metabolic end product of enteric bacteria in the gut. The present study was undertaken to investigate the effect of PA on liver injury in male rats. Male western albino rats were divided into two groups. The first group served as normal control, the second was treated with PA. The activities of serum hepatospecific markers such as aspartate transaminase, alanine transaminase, and alkaline phosphatase were estimated. Antioxidant status in liver tissues was estimated by determining the level of lipid peroxidation and activities of enzymatic and non-enzymatic antioxidants. Sodium and potassium levels were also measured in liver tissue. PA treatment caused significant changes in all hepatospecific markers. Biochemical analysis of liver homogenates from PA-treated rats showed an increase in oxidative stress markers like lipid peroxidation and lactate dehydrogenase, coupled with a decrease in glutathione, vitamin C and glutathione S- transferase. However, PA exposure caused no change in sodium and potassium levels in liver tissue. Our study demonstrated that PA persuade hepatic damage in rats.

Hypothesis: A healthy gut with normal intestinal microflora is completely disrupted by oral antibiotics. The byproducts of harmful gut bacteria can interfere with brain development and may contribute to autism. Strategies to improve the gut microflora profile through dietary modification may help to alleviate gut disorders in autistic patients., Method: Sixty young male western albino rats were divided into six equal groups. The first group served as the control; the second group was given an oral neurotoxic dose of propionic (PPA) (250 mg/kg body weight/day) for three days. The third group received an orogastric dose of ampicillin (50 mg/kg for three weeks) with a standard diet. Groups 4, 5 and 6 were given an orogastric dose of ampicillin and fed high-carbohydrate, high-protein and high-lipid diets, respectively, for 10 weeks. Biochemical parameters related to oxidative stress were investigated in brain homogenates from each group., Result: The microbiology results revealed descriptive changes in the fecal microbiota of rats treated with ampicillin either alone or with the three dietary regimens. The results of PPA acid and ampicillin treatment showed significant increases in lipid peroxidation and catalase with decreases in glutathione and potassium compared with levels in the control group. A protein-rich diet was effective at restoring the glutathione level, while the carbohydrate-rich diet recovered lipid peroxidation and catalase activity. In addition, the three dietary regimens significantly increase the potassium level in the brain tissue of the test animals. Lactate dehydrogenase was remarkably elevated in all groups relative to the control. No outstanding effects were observed in glutathione S-transferase and creatine kinase., Conclusion: The changes observed in the measured parameters reflect the neurotoxic effects of PPA and ampicillin. Lipid peroxide and catalase activity and the levels of glutathione and potassium are satisfactory biomarkers of PPA and ampicillin neurotoxicity. Based on the effects of the three dietary regimens, a balanced diet can protect against PPA or ampicillin-induced neurotoxicity that might induce autistic traits. These outcomes will help efforts directed at controlling the prevalence of autism, a disorder that has recently been associated with PPA neurotoxicity.

Objective: To investigate the antibacterial activity and photochemicals of five green leafy vegetables against a panel of five bacteria strains., Methods: Disc diffusion method was used to determine the antibacterial activity, while kanamycin was used as a reference antibiotic. The phytochemical screening of the extracts was performed using standard methods., Results: All methanol extracts were found active against all the test bacterial strains. Overall maximum extracts shows antibacterial activity which range from 6 to 15 mm. Proteins and carbohydrates was found in all the green leaves, whereas alkaloid, steroids, saponins, flavonoids, tannins were found in most of the test samples., Conclusions: The obtain result suggests that green leafy vegetables have moderate antibacterial activity and contain various pharmacologically active compounds and thus provide the scientific basis for the traditional uses of the studied vegetables in the treatment of bacterial infections.

Nanotechnology involves the creation and manipulation of materials at nanoscale levels (1-100 nm) to create products that exhibit novel properties. While this motivation has driven nanoscience and technology in physics and engineering, it is not the main reason that nanoparticles are useful for systemic applications in the human body. The application of nanotechnology to medicine, known as nanomedicine, concerns the use of precisely engineered materials at this length scale to develop novel therapeutic and diagnostic modalities. A number of nanotherapeutic formulations are already approved for medical use and more are in the approval pipeline currently. This chapter is intended to provide an overview of the toxicity of these therapeutic nanoparticles and to summarize the current state of the field. We begin with background on the sources of exposure to nanoparticles, followed by reviewing different forms of nanosized therapeutic tools as quantum dots, nanoshells, nanocapsules, echogenic bubble, and "nanoshuttles." Moreover, cytotoxic effects of nanoparticles on cell membrane, mitochondrial function, prooxidant/antioxidant status, enzyme leakage, DNA, and other biochemical endpoints were elucidated. We highlight the need for caution during the use and disposal of such manufactured nanomaterials to prevent unintended environmental impacts. Moreover, different strategies which could be used to minimize or eliminate nanotoxicity were also discussed in detail. Understanding of how to tune size and surface properties to provide safety will permit the creation of new, more effective nanomedicines for systemic use.

Schistosomisis is endemic in many rural areas of developing countries. The life cycle of schistosomes is complex with two hosts, an intermediate snail host and a definitive human host. Biomphalaria arabica is the intermediate host for Schistosoma mansoni in Saudi Arabia. One method of controlling the disease is to break the life cycle at the intermediate host snail stage using molluscicides. Snails kill schistosomes by a mechanism involving production of reactive oxygen species. In this study malondialdehyde (MDA), and the antioxidants glutathione (GSH), catalase (CAT) and glutathione peroxidase (GP(x)) were determined in tissue homogenates of B. arabica treated with sublethal concentration (LC25) of the plant molluscicide Solanum nigrum. MDA, GSH and CAT were significantly increased in molluscicide-treated snails compared to controls (p < 0.000). GP(x) was decreased in treated snails. It therefore appears that a sublethal concentration of S. nigrum increases both ability of snail tissue to generate cytotoxic ROS and antioxidants for protection of the tissue against the cytotoxicity. The increase in the level of ROS would decrease snail- schistosome compatibility.

Schistosomiasis is one of the most important human parasitic diseases. One of the possible methods for the control is through the molluscan intermediate host of the parasite. Biomphalaria arabica, molluscan hosts to Schistosoma mansoni in Saudi Arabia were treated with sublethal concentrations (LC25) of dry powdered leaves Solanum nigrum. Effect of plant on ectonucleotidases (NTPdases) (ADPase & ATPase), sodium/potassium adenosine triphosphatase (Na+/K+ ATPase) and creatine kinase (CK) was traced. The plant molluscicide was potent in inhibiting the four investigated enzymes giving a percentage inhibition range between 45-55%. The effect of the inhibited enzymes on the compatibility of the snail hosts to schistosome parasite was discussed. In conclusion, the use of sublethal concentration of S. nigrum to disturb the biochemical profile of the snail hosts could be a promising and safe strategy to control the disease.

The Biomphalaria species are freshwater snails which have a wide distribution and are significant both medically and economically as intermediate hosts for the schistosome parasite, a digenetic trematode causing schistosomiasis, a disease that infects 200 million people, and domestic animals throughout the tropics. The host-parasite relationship is, in principle, a powerful determinant of the biology of infection and disease. Research on snail-schistosome interactions has the potential for making an important contribution to the study of co-evolution or reciprocal adaptation. The association between Biomphalaria and Schistosoma mansoni could well be an excellent model for studies aimed at elucidating some aspects of the compatibility or resistance of this species to schistosomes. Snail hosts and schistosomes appear to have effects on each other's phenotype and genotype. The objective of this review is to clarify the nature of the relationship between schistosome parasites and their freshwater snail hosts. Aspects of snail-schistosome interactions will be traced in relation to behavioral (growth, reproduction, locomotion), immunological, and biochemical changes induced in the host's tissues by the developing intramolluscan stages of the parasite. This may help to identify biochemical or genetic targets for drug design. Manipulation of the intermediate host through these targets could break the cycle of human and snail infection by schistosomes.

Digenetic trematodes have evolved behavioral adaptations to their complex life cycles. They have their own strategies to find hosts, locate sites of infection within final and intermediate hosts, escape immune responses, etc. Many of these strategies are highly complex, but they are sometimes quite subtle. While the mechanisms or processes involved in a few parasites are understood, most are not. Schistosoma mansoni parasites inhabit three distinct environments: water, intermediate molluscan hosts, and a definitive vertebrate host. Although targeted chemotherapy and other public health measures are employed to control schistosomiasis and its spread, there is a need for the development of vaccine and new anti-schistosome drugs. Determining how schistosomes interact with different environments may be one mechanism by which suitable vaccine or chemotherapeutic drugs could be developed. Genes expressed in a stage-specific manner may help us to understand the molecular events controlling the complex life cycle of schistosomes. Various proteins are expressed during the life cycle of schistosomes which are essential for its miracidial infection of molluscan hosts, cercarial penetration of vertebrate skin, evasion of the immune responses of both hosts, and other biological activities needed by schistosomes to complete their complex life cycle. Identifying these stage-specific proteins may uncover hidden aspects of parasite biology and provide useful leads for the development of novel intervention strategies.

5-Aminolevulinic acid synthase (ALAS), the first enzyme of the heme biosynthesis pathway, catalyses the pyridoxal 5'-phosphate-dependent condensation between glycine and succinyl-CoA to yield 5-aminolevulinic acid (5-amino-4-oxopentanoate). A three-dimensional structural model of Rhodobacter spheroides ALAS has been constructed and used to identify amino acid residues at the active site that are likely to be important for the recognition of glycine, the only amino acid substrate. Several residues have been investigated by site-directed mutagenesis and enzyme variants have been generated that are able to use alanine, serine or threonine. A three-dimensional structure model of 5-aminolevulinic acid synthase from human erythrocytes (ALAS 2) has also been constructed and used to map a range of naturally occurring human mutants that give rise to X-linked sideroblastic anemia. A number of these anemias respond favourably to vitamin B(6) (pyridoxine) therapy, whereas others are either partially responsive or completely refractory. Detailed investigations with selected human mutants have highlighted the importance of arginine-517 that is implicated in glycine carboxyl group binding.