Interplay of Demographic Influences, Clinical Manifestations, and Longitudinal Profile of Laboratory Parameters in the Progression of SARS-CoV-2 Infection: Insights from the Saudi Population.

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.

Prenatal SSRI Exposure Increases the Risk of Autism in Rodents via Aggravated Oxidative Stress and Neurochemical Changes in the Brain.

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.

Polymorphisms in proinflammatory cytokine genes, effect on gene expression and association with preterm delivery in Saudi females.

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-1ß, 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-1ß, IL-6, and TNF-α) was higher in the PTB patients, but the results reached significance only for IL-1ß (p=0.035). Elevated gene expression was also evident from the level of these proteins in plasma, where the level of IL1α, IL-ß 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.

Therapeutic and Protective Potency of Bee Pollen Against Neurotoxic Effects Induced by Prenatal Exposure of Rats to Methyl Mercury.

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 Mg2+ 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 Mg2+, 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.

High-fat diet stimulates the gut pathogenic microbiota and maintains hepatic injury in antibiotic-treated rats.

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.

CYP19A1 gene polymorphism and colorectal cancer etiology in Saudi population: case-control study.

BACKGROUND: Considerable interest is directed toward the enzyme aromatase (CYP19A1) and the development of cancer, due to CYP19A1's role in estrogen biosynthesis. Several cancers display excessive intra-tumor accumulation of estrogens, and aromatase inhibitors are used for treatment. The CYP19A1 gene exhibits polymorphism and mutations that can alter its expression or aromatase activity and influence estrogen production. We designed this study to investigate the link between CYP19A1 polymorphism and susceptibility to colorectal cancer (CRC) development in Saudis. PATIENTS AND METHODS: Blood samples from 100 CRC patients and 100 healthy controls were drawn for DNA extractions. Three polymorphic sites, rs4774585, rs936308, and rs4775936, were genotyped using Taqman genotyping by real-time polymerase chain reaction. Allelic and genotype frequencies were calculated and compared in the two groups. RESULTS: All single nucleotide polymorphisms (SNPs) were polymorphic in Saudis, and comparison of allele frequencies showed several differences when compared to other populations. None of the SNPs were associated with the risk of CRC development in Saudis (P>0.05). Some gender and location (colon or rectal) differences were observed. DISCUSSION: The results of this study highlighted the genetic heterogeneity existing between populations in the prevalence of different SNPs and their relation to disease state. It showed that, although rs4774585, rs936308, and rs4775936 are involved in CRC development in several populations, their role is not significant in the etiology of CRC in Saudis; however, some SNPs do increase susceptibility or resistance to CRC development as judged from the odds ratio. Further large-scale studies are warranted to clarify the role of the CYP19A1 development in CRC.

Potency of pre-post treatment of coenzyme Q10 and melatonin supplement in ameliorating the impaired fatty acid profile in rodent model of autism.

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.

Impact of Propionic Acid on Liver Damage in Rats.

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.

The neurotoxic effects of ampicillin-associated gut bacterial imbalances compared to those of orally administered propionic acid in the etiology of persistent autistic features in rat pups: effects of various dietary regimens.

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.

Protective effects of quercetin on cadmium fluoride induced oxidative stress at different intervals of time in mouse liver.

Quercetin, a member of the flavonoid family is a major antioxidant acquired in humans by food consumption, while Cadmium fluoride (CdF2) is one of the naturally occurring chemicals having adverse effects. The protective effect of quercetin on time dependent oxidative damage induced in mice liver by CdF2 was studied in the following groups of mice consisting of six mice each: (i) control group; (ii) mice treated with single i.p injection of 2 mg/kg bw CdF2 for 24 h; (iii) mice treated with single i.p injection of 2 mg/kg bw CdF2 for 48 h; (iv) mice treated with single i.p injection of quercetin (100 mg/kg bw); (v) mice treated with i.p injection of 100 mg/kg bw of quercetin followed by i.p injection of CdF2 (2 mg/kg bw) for 24 h; and (vi) mice treated with i.p injection of 100mg/kg bw of quercetin followed by CdF2 (2 mg/kg bw) for 48 h. Administration of quercetin two hours before CdF2 significantly reduced the biochemical alterations in reduced glutathione, ascorbic acid, lipid peroxidation, super oxide dismutase, catalase and total protein (p<0.05). Histopathology also showed the protective effect of quercetin. The livers treated with CdF2 were atrophic, markedly nodular, inflamed and necrotic. However, this effect was reduced to a minimum in the mice pre-treated for two hours with quercetin.

Is consanguinity prevalence decreasing in Saudis?: A study in two generations.

BACKGROUND: Saudi population is unique in that there is a strong preference for cousin marriages in the general population. We studied the prevalence of consanguinity in educated Saudi females and compared the results with the results obtained in their parents, to access if a generation difference in which extensive educational activities have prevailed to inform the people of the influence of cousin marriages on health, has made any difference in prevalence of consanguineous marriages. METHOD: A total of 600 Saudi women (421 university students and 179 women attending outpatients' clinics) were interviewed about their own and their parents' consanguinity. RESULTS: The total consanguinity (first and second cousins) was 29.7% in the parents. Consanguinity was significantly higher among the daughters than the parents, where 37.9% of the 293 married women had consanguineous marriages. The prevalence of consanguinity was studied in different age groups, though no significant pattern was observed. A strong correlation was found between consanguinity of parents and their daughters; consanguinity was highest (52.3%) in the daughters of parents who were themselves consanguineous. CONCLUSION: The results did not reveal any decrease in the prevalence of consanguinity over a generation. This shows that the tradition of marrying within the family is a preferred practice, despite the awareness that certain genetic disorders occur at a higher frequency in cousin marriages. There is a need at the primary health care level to inform the public of the consequences of this common practice.

Phytochemical constituents and antibacterial activity of some green leafy vegetables.

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.

Phytochemical constituents and antibacterial activity of some green leafy vegetables

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.

Toxicity of novel nanosized formulations used in medicine.

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.

Purification, characterization and bactericidal activities of phospholipase A2 from the dromedary intestine.

We purified a protein from the dromedary small intestine that displayed potent bactericidal activity against Gram-positive bacteria, and identified it as group-IIA phospholipase A2 (DrPLA2-IIA) by NH2-terminal sequencing and enzymatic measurements. In fact, our findings revealed that the purified PLA2-IIA was a monomeric protein with a molecular mass of about 14 kDa. Pure enzyme has a specific activity of 329 ± 25 U/mg at optimal conditions (pH 9.5 and 45 °C) in the presence of 6 mM NaDC and 7 mM CaCl2 with egg yolk emulsion as substrate and binds with a higher affinity to PE than PS and PC. Furthermore, the DrPLA2-IIA activity was dependent on Ca(2+); other cations (Cd(2+), Co(2+), Fe(2+), Mg(2+), Mn(2+), and Zn(2+)) reduced the enzymatic activity notably, suggesting that the arrangement of the catalytic site presents an exclusive structure for Ca(2+). On the other hand, DrPLA2-IIA was highly bactericidal against Gram-positive bacteria with inhibition zones and IC50 values in the range of 21-27 mm and 3.7-8 µg/ml, respectively, whereas Gram-negative bacteria exhibited a much higher resistance. These observations suggest that the main physiological role of DrPLA2-IIA could be the defense of the intestine against bacterial infections.

Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats.

Agaricus blazei Murill is one of the very popular edible medicinal mushrooms. The present study investigated the protective effect of this biologically active mushroom on the tissue peroxidative damage and abnormal antioxidant levels in carbon tetrachloride induced hepatotoxicity in male albino rats. Male albino rats of Sprague-Dawley strain weighting (120-150 g) were categorized into five groups. The first group served as the normal control, the second and the third groups were treated with Agaricus blazei Mushroom extract and carbon tetrachloride dose, respectively. Fourth group (protective group) was first treated with Agaricus blazei Mushroom extract followed by carbon tetrachloride treatment and fifth (therapeutic group) with carbon tetrachloride first followed by Agaricus blazei Mushroom treatment. The wet fruiting bodies of mushroom Agaricus blazei Murill, crushed and suspended in distilled water was administered orally to the treated groups of male albino rats. The activities of various enzymes (aspartate and alanine transaminase, lactate dehydrogenase, glutathione reductase), levels of non-enzymatic antioxidants (glutathione, vitamin C, vitamin E) and level of lipid peroxidation (malondialdehyde) were determined in the serum of all the experimental animals. Decrease in all the enzymes and non-enzymatic antioxidant, along with an increase in the lipid peroxidative index (malondialdehyde) was found in all the carbon tetrachloride treated rats as compared with normal controls. Also increase level of non-enzymatic antioxidant along with the decrease level in malondialdehyde was found in all experimental animals which were treated with Agaricus blazei Mushroom extract as compared with normal controls. The findings indicate that the extract of Agaricus blazei Murill can protect the liver against carbon tetrachloride induced oxidative damage in rats and is an efficient hepatoprotective and antioxidant agent against carbon tetrachloride induced liver injury.

On the protective effect of omega-3 against propionic acid-induced neurotoxicity in rat pups.

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.

TP53 genetic alterations in Arab breast cancer patients: Novel mutations, pattern and distribution.

Breast cancer remains a worldwide public health concern. The incidence and mortality of breast cancer varies significantly in ethnically and geographically distinct populations. In the Kingdom of Saudi Arabia (KSA) breast cancer has shown an increase in incidence and is characterized by early onset and aggressiveness. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. Furthermore, studies have shown a correlation between certain p53 mutations and response to therapy in breast cancer. In the present study, TP53 mutations were identified by direct sequencing of the gene (exons 4-9) from 119 breast cancer tissues. The prevalence of TP53 mutations in Arab breast cancer patients living in the KSA is among the highest in the world (40%). Notably, 73% of the patients whose tumors harbored p53 mutations were less than 50 years of age. Furthermore, for the first time, we identified 7 novel mutations and 16 mutations in breast cancer tissues. Notably, all the novel point mutations were found in exon 4, wherein 29% of the mutations were localized. Furthermore, an excess of G:C→A:T transitions (49%) at non-CpG sites was noted, suggesting exposure to particular environmental carcinogens such as N-nitroso compounds. The results indicate that the TP53 gene plays a significant role in breast carcinogenesis and the early onset of the disease among Arab female individuals.

Effect of plant molluscicides on selected enzymes related to energy metabolism in Biomphalaria arabica snails molluscan hosts to Schistosoma mansoni in Saudi Arabia.

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 effect of a sublethal concentration of Solanum nigrum on some antioxidants in Biomphalaria arabica.

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.