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The objective of the research is to know the extent to which Islamic education courses include the following dimensions of intellectual security: Religious dimension, national dimension, social dimension, after dialogue and acceptance of opinions, after positive thinking (critical thinking), and to achieve this goal the researcher used the descriptive approach based on the method of content analysis, the researcher also designed the study tool that consisted of the content analysis card, the research sample was determined in the book Hadith 1 course for high school students (curriculum system) in to: there is a disparity in the degree of inclusion of dimensions of intellectual security in the course of Hadith 1 for high school students, where it came in the following order: in the first degree the religious dimension by the percentage of repetitions reached (13,002%) to the total content of the course, in the second degree the social dimension by the percentage of repetitions reached (10%) to the total content of the course, in the third degree the national dimension by the percentage of repetitions reached (5%) to the total content of the course, in the fourth: Review the content planning of Hadith course 1 for high school students (courses system), in a way that allows in achieving parity and balance between the depth of content and its organization, in including the dimensions of intellectual security and distribution in an appropriate manner among its subjects, in addition to including the activities of the content of the course on the dimensions of intellectual security.

Benzylidene chromanones are small molecules, structurally similar to active phytochemicals. Herein, we report one novel benzylidene chromanone, TMF 104, for its bio-efficacies. Its computational docking for Vanin-1, antioxidant, free radical scavenging capacities, antimicrobial effects, and anticancer efficacy were analyzed. TMF 104 predicated strong binging to Vanin-1 protein with a docking energy of -8.1 kcal/mol. The compound dose-dependently exhibited free-radical scavenging and antioxidant activities when tested in vitro. The compound also had remarkable activity against Salmonella typhimurium, Enterococcus faecalis, Staphylococcus aureus, and Escherichia coli with minimum inhibitory concentration values of 1.5, 2.0, 12.5, and 13.5 μg/ml, respectively. The compound was also effective against Bacillus cereus and Pseudomonas aeruginosa albeit at higher concentrations. TMF 104 dose-dependently inhibited the proliferation of MCF-7, NCI H460, and Caki-1 cells with respective GI

Background and aimDespite the fact that the chikungunya viral infection is a neglected disease, complications such as hemorrhagic fever, arthritis, and lymphopenia remain a health concern. The aim of this study was to determine the prevalence of the chikungunya virus in the Southern Region, Saudi Arabia. Enzyme immunoassay and polymerase chain reaction have been compared between samples.Materials and methodsForty samples from two southern hospitals in Saudi Arabia were collected between December 2019 and February 2020 and screened for chikungunya virus IgG antibodies and for viral RNA. Selection criteria were based on hematological parameters and rheumatological profiles such as rheumatoid factor, c-reactive protein, anti-nuclear antibody, and anti-cyclic citrullinated peptide (anti-CCP) of out-patients.ResultsOne confirmed case of chikungunya virus was detected using the ELISA test. However, no viral RNA was detected in any of the samples. This suggests that the virus is cleared rapidly in patients.ConclusionChikungunya is a neglected viral disease in Saudi Arabia. Future work should focus on detailed investigation of this viral infection and its vectors.

Objectives: To investigate trends in hemoglobinopathies following the establishment of a mandatory premarital screening program (MPMSP) in the southern region of Saudi Arabia, where they are considered highly predominant. Methods: A retrospective analysis was performed on data from 32,130 high-performance liquid chromatography (HPLC) tests between November 2017 and October 2020. The data was obtained from the Hematology section, Laboratory Department, Armed Forces Hospital, Southern Region. Results: Despite the establishment of the MPMSP, our data showed that sickle cell disease remains a predominant hemoglobinopathy accounting for more than 7% of total tests in Southern Saudi Arabia. Observed HPLC hemoglobin fractions among the tested population showed a reduction in Hb A mean indicating a high rate of hemoglobin abnormalities. In addition, the prevalence of hemoglobin variants, including sickle cell and thalassemia, was higher in the younger population born after the MPMSP than in older subjects. Conclusion: Even with the implementation of the MPMSP, hemoglobin abnormalities remain prevalent in southern Saudi Arabia. A longer time frame is recommended to verify the validity of the program.

Objectives: To explore the antibacterial activity of thymoquinone (TQ), a quinone extracted from Nigella sativa. Methods: This study was conducted from May 2019 to March 2020 at the Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia. The antimicrobial activity, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of TQ were determined using an agar well diffusion method and broth microdilution assays, and the synergistic effect was evaluated using antibiotics in parallel. The disruptive effect of TQ on bacterial cell membranes was determined using scanning electron microscopy. The antivirulence properties of TQ, which include adherence and biofilm formation, were also investigated using adherence and biofilm formation assays, respectively. Results: Thymoquinone demonstrated bactericidal efficacy against 4/14 bacterial strains, with MIC range of 1.04-8.3 µg/mL and and MBC range of 10.41–66.66 µg/mL. Thymoquinone showed synergism against Klebsiella pneumoniae, Staphylococcus epidermidis (American Type Culture Collection 12228), Staphylococcus aureus, and Staphylococcus epidermidis in combination with the tested antibiotics. Thymoquinone inhibited bacterial adhesion by 39%-54%, 48%-68%, and 61%-81% at 0.5 × MIC, 1 × MIC, and 2 × MIC, respectively. The tested bacterial strains significantly inhibited biofilm formation after treatment with various concentrations of TQ for 24 and 48 hours. Conclusion: The combinatory effect of TQ with antimicrobials should be considered when developing new antimicrobial therapy regimens to overcome multidrug-resistant.

Dihydroorotate dehydrogenase (DHODH) remains as an active target at the preclinical level against acute myeloid leukemia (AML). Herein we report potent second generation benzylidene chromanone (SBL-105) analogues to inhibit DHODH in AML cells. Virtual docking and molecular dynamic simulations were performed. Human-recombinant (rh)DHODH, THP-1, TF-1 and HL-60 cell lines were used. MTT assay was used for cell viability. Flow cytometry was used for differentiation analysis. Computational modeling and simulations predict, SBL-105 analogs bind efficiently to DHODH with improved binding energies. While all tested analogues of SBL-105 inhibited rh DHODH enzyme, SBL-105-4 and SBL-105-6 more effectively inhibited rh DHODH with an IC

Background The molecular drivers of early sporadic Parkinson’s disease (PD) remain unclear, and the presence of widespread end stage pathology in late disease masks the distinction between primary or causal disease-specific events and late secondary consequences in stressed or dying cells. However, early and mid-stage Parkinson’s brains (Braak stages 3 and 4) exhibit alpha-synuclein inclusions and neuronal loss along a regional gradient of severity, from unaffected-mild-moderate-severe. Here, we exploited this spatial pathological gradient to investigate the molecular drivers of sporadic PD. Methods We combined high precision tissue sampling with unbiased large-scale profiling of protein expression across 9 brain regions in Braak stage 3 and 4 PD brains, and controls, and verified these results using targeted proteomic and functional analyses. Results We demonstrate that the spatio-temporal pathology gradient in early-mid PD brains is mirrored by a biochemical gradient of a changing proteome. Importantly, we identify two key events that occur early in the disease, prior to the occurrence of alpha-synuclein inclusions and neuronal loss: (i) a metabolic switch in the utilisation of energy substrates and energy production in the brain, and (ii) perturbation of the mitochondrial redox state. These changes may contribute to the regional vulnerability of developing alpha-synuclein pathology. Later in the disease, mitochondrial function is affected more severely, whilst mitochondrial metabolism, fatty acid oxidation, and mitochondrial respiration are affected across all brain regions. Conclusions Our study provides an in-depth regional profile of the proteome at different stages of PD, and highlights that mitochondrial dysfunction is detectable prior to neuronal loss, and alpha-synuclein fibril deposition, suggesting that mitochondrial dysfunction is one of the key drivers of early disease.

Background Pneumocystis pneumonia (PCP) is a fatal infectious disease caused by Pneumocystis jirovecii (PJP). The major factor relevant to morbidity and mortality seems to be the host inflammatory reaction. The objective of this study was to evaluate the role of IL-2, IL-4, IL-10, and IL-13 cytokine mRNA expression among suspected P. jirovecii infection. Methods This was a cross-sectional analytical study undertaken in Aseer region, Saudi Arabia. One hundred suspected PCP cases and 100 healthy controls were included in the study. Basic clinical manifestations, radiological findings, microbiological and immunological findings were extracted from the hospital records from January 2019 to August 2019, Pneumocystis detection was done by immune-fluorescent staining (IFAT, Gomorimethanamine silver staining (GMSS), Giemsa staining, Toluidine blue O (TBO), and Pneumocystis RT-PCR. Results Increased more than 5 fold, 3 fold, 4 fold, and 7 fold of IL-2, IL-4, IL-10, and IL-13 mRNA expression were observed in PCP cases compared to controls. Higher expression of IL-2 mRNA was connected with crept, wheezing and chest X-ray findings like central perihilar infiltrate, patchy infiltrate, consolidation, hilar lymphadenopathy, pneumothorax, pleural effusion which showed higher expression compared to counterpart (pp=0.002), dyspnea (p=0.003), crept (p=0.01), and chest X-ray findings (p Conclusion Confirmed cases of P. jirovecii showed higher IL-2, IL-4, IL-10, and IL-13 mRNA expression comparatively to negative cases. Increased expression of cytokines may be indicative of infection severity and could help in patients’ management.

Punica granatum (Pomegranate fruit) and its constituents are proven effective against various cancer types. However, a kinome-wide screening for the active phytochemicals against kinases is not reported. This study aims in validating pomegranate fruit extract (PFE) against acute myeloid leukemia (AML) cells, and computationally identifying the phytochemicals interacting with active kinases. PFE was made with Soxhlet extractor using absolute ethanol. Gas-chromatography-mass spectroscopy (GC-MS) for phytochemical identification and MTT assay for cytotoxicity in AML (THP-1, TF-1 and HL-60) cells were performed. Apoptosis, CDK5 and CDK8 were assessed with flow cytometry. Kinase profiling was performed using In silico kinome screening. GC-MS analysis revealed 38 bioactive phytochemicals in PFE including pyrazoles, aldehydes, phenols, esters, pyranosides, and octadecadienoic acids. The extract inhibited the AML cell proliferations with GI

The coronavirus pandemic, known as COVID-19, is an evolving pandemic caused by a coronavirus, the SARS-CoV-2. The virus was first detected in Wuhan, China, in December 2019. In January 2020, the World Health Organization (WHO) notified this upsurge as an international emergency concerning public health. It was declared a pandemic later in March 2020. By May 12, 2021, 160,363,284 cases had been registered, and 3,332,762 deaths have been reported, caused by COVID-19, characterized as a horrific pandemic in the history of humankind. Scientists have reached a consensus about the origin of COVID-19, a zoonotic virus arising from bats or other animals in a natural habitat. The economic impact of this outbreak has left far-reaching repercussions on world business transactions, along with bond, commodity, and stock markets. One of the crucial incidents that popped up was the oil price war among OPEC countries. It caused plummeting oil prices and the collapse of stock markets globally in March 2020, as the OPEC agreement failed. However, COVID-19 plays a crucial role in the economic recession. The monetary deficit impact on the travel and trade industries is likely to be huge, in billions of pounds, increasing daily. Other sectors have also suffered significantly.

Diabetic nephropathy (DN) is the most common manifestation of high glucose induced diabetes mellitus. In this study, we report the effects of Cassia auriculata ethanol leaf extract (CALE) on DN-associated cell toxicity and complications. The effects of CALE were screened in vitro using RGE cells. Cell viability was assessed using MTT and flow cytometry. Male Sprague-Dawley rats were divided into control, DN and treatment groups (n = 8). The DN and treatment groups received 60 mg/kg/bw of streptozotocin in citrate buffer, while the treatment group was administered 150 mg/kg/bw of CALE for 10 weeks. Biochemical analysis was conducted using spectrophotometry. Kidney tissues were analyzed using hematoxylin and eosin staining and transmission electron microscopy. CD365-KIM-1 expression was assessed using flow cytometry and signalling proteins were detected using western blotting. Treatment with 30-mM glucose reduced the viability of RGE cells in a time-dependent manner and increased the population of dead RGE cells. Cotreatment with CALE reduced cell death and glucose induced protein expression of LC3-II, RIP-1 and RIP-3 in a dose-dependent manner. In addition, CALE improved the biochemical complications, renal dysfunction and pathophysiology of rats with DN and partially or fully restored the expression of key DN-associated signalling proteins, such as KIM-1 LC3-II, RIP-1, RIP-3 and p-p38MAPK in kidney cells. CALE showed protective effects, and improved DN-associated complications in RGE cells under high glucose stress conditions, potentially by inhibiting autophagic-necroptosis signals. Additionally, CALE improved the biochemical and pathological features of kidney injury while reducing autophagic-necroptosis in rat renal cells via the LC3-II-RIP-p38MAPK pathway. PRACTICAL APPLICATIONS: Results from the current investigation will add information to the literature on glucose induced renal toxicity and the protective effects of CALE over the complications of diabetic nephropathy (DN). The mechanistic investigations of the study will add light on the autophagic/necroptosis signals in DN and open new routes of investigations to study the efficacy of CALE in diabetes-related complications.

Mycobacterium tuberculosis (Mtb) is a deadly tuberculosis (TB)-causing pathogen. The proteasome is vital to the survival of Mtb and is therefore validated as a potential target for anti-TB therapy. Mtb resistance to existing antibacterial agents has enhanced drastically, becoming a worldwide health issue. Therefore, new potential therapeutic agents need to be developed that can overcome the complications of TB. With this purpose, in the present study, 224,205 natural compounds from the ZINC database have been screened against the catalytic site of Mtb proteasome by the computational approach. The best scoring hits, ZINC3875469, ZINC4076131, and ZINC1883067, demonstrated robust interaction with Mtb proteasome with binding energy values of −7.19, −7.95, and −7.21 kcal/mol for the monomer (K-chain) and −8.05, −9.10, and −7.07 kcal/mol for the dimer (both K and L chains) of the beta subunit, which is relatively higher than that of reference compound HT1171 (−5.83 kcal/mol (monomer) and −5.97 kcal/mol (dimer)). In-depth molecular docking of top-scoring compounds with Mtb proteasome reveals that amino acid residues Thr1, Arg19, Ser20, Thr21, Gln22, Gly23, Asn24, Lys33, Gly47, Asp124, Ala126, Trp129, and Ala180 are crucial in binding. Furthermore, a molecular dynamics study showed steady-state interaction of hit compounds with Mtb proteasome. Computational prediction of physicochemical property assessment showed that these hits are non-toxic and possess good drug-likeness properties. This study proposed that these compounds could be utilized as potential inhibitors of Mtb proteasome to combat TB infection. However, there is a need for further bench work experiments for their validation as inhibitors of Mtb proteasome.

This study evaluates a novel benzylidene-chromanone derivative, FNF-12, for efficacy in in vitro and in vivo asthma models. Rat basophilic leukemia (RBL-2H3) and acute monocytic leukemia (THP-1)-derived M2 macrophages were used. Human whole blood-derived neutrophils and basophils were employed. Flow cytometry was used for studying key signalling proteins. Platelet activation factor (PAF)-induced asthma model in guinea pigs was used for in vivo studies. The chemical structure of FNF-12 was confirmed with proton-nuclear mass resonance (NMR) and mass spectroscopy. FNF-12 controlled degranulation in RBL-2H3 cells with an IC50 value of 123.7 nM and inhibited TNF-α release from these cells in a dose-responsive way. The compound effectively controlled the migration and elastase release in activated neutrophils. IC50 value in the FceRI-basophil activation assay was found to be 205 nM. FNF-12 controlled the release of lipopolysaccharide (LPS)-induced interleukin-10, I-309/CCL1 and MDC/CCL22 in THP-1 derived M2 macrophages. The compound suppressed LPS-induced mitogen activated protein kinase (MAPK)-p-p38 and nuclear factor kappa B(NF-kB)-p-p65 expression in these cells. A dose-dependent decrease in the accumulation of total leucocytes, eosinophils, neutrophils and macrophages was observed in PAF-induced animal models. FNF-12 was able to control the inflammatory responses in in vitro and in vivo asthma models, which may be driven by controlling M2-related Th2 cytokines via MAPK and NF-kB signaling.

We consider a new mathematical model for the COVID-19 disease with Omicron variant mutation. We formulate in details the modeling of the problem with omicron variant in classical differential equations. We use the definition of the Atangana-Baleanu derivative and obtain the extended fractional version of the omicron model. We study mathematical results for the fractional model and show the local asymptotical stability of the model for infection-free case if

Predicting novel dual inhibitors to combat adverse effects such as the development of resistance to vemurafenib in melanoma treatment due to the reactivation of MAPK and PI3K/AKT signaling pathways is studied to help in reversal of cancer symptoms.Reversal of cancer symptoms in melanoma associated with vemurafenib resistance is driven by reactivation of MAPK and PI3K/Akt signaling pathways. Novel dual inhibitors targeting these proteins would be beneficial to combat resistance.High-throughput virtual screening of the ChemBridge library against B-RAFV600E and Akt was performed using an automated protocol with the AutoDock VINA program. Luminescence and time-resolved fluorescence kits were used to measure enzyme activities. The MTT assay was used to determine proliferation in normal and vemurafenib-resistant A375 cells. Flow cytometry was used to examine apoptosis, cell cycle, and phosphorylation of ERK/Akt signaling pathway.High-throughput screening from the ChemBridge library identified 15 compounds with high binding energy towards B-RAFV600E; among these, CB-RAF600E-1 had the highest ΔGCB-RAF600E-1, identified as a novel dual inhibitor effective against normal and vemurafenib-resistant melanoma cells, requires further attention for development as an effective chemotherapeutic agent for melanoma management.

The mitochondrial respiratory chain (MRC) and ATP synthase (complex V) play an essential role in cellular energy production by the process of oxidative phosphorylation. In addition to inborn errors of metabolism, as well as secondary causes from disease pathophysiology, an impairment of oxidative phosphorylation can result from drug toxicity. These 'off-target' pharmacological effects can occur from a direct inhibition of MRC enzyme activity, an induction of mitochondrial oxidative stress, an uncoupling of oxidative phosphorylation, an impairment of mitochondrial membrane structure or a disruption in the replication of mitochondrial DNA. The purpose of this review is to focus on the off-target mitochondrial toxicity associated with both commonly used pharmacotherapies and a topical 'weight loss' agent. The mechanisms of drug-induced mitochondrial impairment will be discussed together with putative therapeutic strategies to counteract the adverse effects of the pharmacotherapy.

Introduction. To investigate the association of high Body Mass Index (BMI) with semen parameters and reproductive hormones in men of reproductive age. Setting. The Saudi Center for Assisted Reproduction. Method. This study was conducted during the period from February 2009 to February 2011. Subjects were exposed through medical history evaluation as well as physical examination. BMI was calculated. Two semen samples about 1 week apart were taken from each participant by masturbation after 2–5 days of abstinence. The samples were assessed according to the WHO Criteria. Blood samples (5 ml) were withdrawn; centrifuged and the resulting sera were preserved at −4 degrees Centigrade. Serum FSH, LH, PRL, and Testosterone levels were estimated by the ELISA method. Results. There was no significant correlation between BMI and any of semen and hormonal parameters. There was significant negative correlation between age and total motility. Only the advanced paternal age has shown significant association with low motility ( 𝑃 = 0 . 0 0 7 ). Conclusion. Our study showed a significant effect of aging on sperm motility and concentration.

Background: Initial low maternal serum β-human chorionic gonadotropin (β-hCG) is a good predictor of early pregnancy demise. Our objective was to determine it s predictive value in determining the long-term outcome in ICSI pregnancies. Methods: A retrospective cohort study was designed at the Saudi Center for Assisted Reproduction. Two hundred and sixty-one women with ICSI pregnancies were followed up from initial β-hCG level determination till the end of pregnancy. Accuracy of early β-hCG in predicting the occurrence of a live-birth, ongoing pregnancy, late miscarriage, ectopic pregnancy and early miscarriage following ICSI was measured. Results: β-hCG levels were significantly different in pregnancies that reached the stage of an ongoing pregnancy and live-birth as compared to early pregnancy loss. The ROC curves demonstrated a high sensitivity for identifying patients with ectopic pregnancies and early miscarriage (100% and 93.33% respectively). The remaining results ranged from a sensitivity of 69% to 79% and specificity of 62% to 75%. Conclusions: In ICSI pregnancies, a single early β-hCG may help to identify pregnancies that will reach full-term and delivery. doi:10.4021/jocmr477e

Intracytoplasmic sperm injection (ICSI) procedures have become accepted worldwide and their effect on society is well-known. However, the full extent of the possible complications of these procedures on maternal and neonatal outcome is still unclear.This is a retrospective case controlled study from January 2003 to December 2007 which compared 253 women that had conceived using assisted reproduction (ICSI) and delivered 327 children at our center (study group) with a matched group of 349 women who naturally conceived and delivered 354 children at Abha General Hospital (control group) during the same period. The obstetrical and neonatal characteristics of the women and their children were assessed to determine any significant differences between the groups.The number of gestations per pregnancy (1.34 +/- 0.57 vs. 1.01 +/- 0.12) and number of children born per woman (1.28 +/- 0.49 vs. 1.01 +/- 0.12) was significantly higher in the ICSI group (p0.001). In addition, the gestational age at delivery (37.23 +/- 2.68 vs. 38.56 +/- 1.89) was significantly shorter in the ICSI group (p0.001) and this led to an increased number of obstetrical interventions, as well as the incidence of cesarean deliveries. Examination of the new-born children revealed similar incidence of congenital anomalies in both groups.ICSI conceived pregnancies were characterized by an increased number of gestations and live-born, and there was no increase in congenital malformations compared to naturally conceived pregnancies.

The objective was to determine if symptoms of obstructive voiding correlate with post-void residual urine volume measured by catheterization. A cross-sectional study of 134 consecutive women referred to a tertiary urogynecology clinic was performed. Subjects were interviewed regarding three types of obstructive voiding symptoms: a sensation of incomplete emptying, straining to void, and slow urine stream. Post-void residual urine volume was measured by catheterization as the gold standard. Data for each symptom were analyzed using Cohen’s kappa test, sensitivity, specificity, likelihood ratios for a positive of negative test, and positive and negative predictive values. A total of 11 out of 134 patients (8%) had a post-void residual volume greater than 100 ml. Of these 11, 1 had symptoms of incomplete emptying (9%), 1 had symptoms of straining to void (9%), and 2 had symptoms of slow urine stream (18%). Sensitivity, specificity, likelihood ratio for a positive symptom, likelihood ratio for a negative symptom, positive predictive value, negative predictive value, and Cohen’s kappa, respectively, were 9%, 80%, 0.47, 1.13, 4%, 91%, and 0.05 for the symptom of incomplete emptying, 9%, 91%, 1.12, 1.0, 8%, 92%, and 0.01 for straining to void, and 18%, 89%, 1.6, 0.92, 13%, 92%, and 0.07 for the symptom of slow urine stream. It was concluded that symptoms of obstructive voiding do not correlate with measured post-void urine volume. In clinically important situations, these symptoms cannot substitute for measurement of post-void residual urine volume.