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8 result(s) for "Marghani, Dina"
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Comprehensive pharmacokinetic profiling and molecular docking analysis of natural bioactive compounds targeting oncogenic biomarkers in breast cancer
Breast cancer is one of the leading causes of death in women worldwide, highlighting the crucial need for novel and effective treatments. In this study, we look at the ability of four natural compounds i.e. Berberine, Curcumin, Withaferin A, and Ellagic Acid to target important breast cancer biomarkers such as B-cell lymphoma 2 (BCL-2), programmed death-ligand 1 (PDL-1), cyclin-dependent kinase 4/6 (CDK4/6) and fibroblast growth factor receptor (FGFR). These indicators have important roles in tumor development, survival, immune response, and cell cycle control, making them potential targets for future cancer treatments. Our study employs a variety of techniques, including pharmacokinetic profiling (ADME), molecular docking, and molecular dynamics simulations, to determine how successful these drugs could be in therapy. The pharmacokinetic investigation found that Berberine and Ellagic Acid stand out due to their high absorption and solubility, implying that they could be suitable for clinical application. When we ran docking simulations, we discovered substantial connections between these chemicals and the target proteins. Additionally, Berberine has a binding affinity of − 9.3 kcal/mol for BCL-2, indicating that it can impair the protein’s cancer cell-protective activities. Ellagic Acid, on the other hand, has an even higher binding affinity for PDL-1 of − 9.8 kcal/mol, showing that it may be able to increase immune responses against tumors. Molecular dynamics simulations over 100 ns demonstrated the stability of these protein–ligand complexes. Interestingly, Ellagic Acid was found to be more structurally stable than Berberine throughout these simulations. We found consistent interactions between the chemicals and key residues in the target proteins. For example, Ellagic Acid (CID: 5281855) established persistent linkages with LYS43, ASP163, and VAL27, whereas Berberine (CID: 2353) interacted with VAL27, ALA41, and LEU152 throughout the simulation. In conclusion, the combination of good pharmacokinetics, robust interactions with cancer biomarkers, and stable complexes makes Berberine and Ellagic Acid interesting candidates for further investigation as natural inhibitors in breast cancer treatment. These findings establish the framework for future research into novel and inventive techniques to effectively combating breast cancer.
Role of peroxiredoxin of the AhpC/TSA family in antioxidant defense mechanisms of Francisella tularensis
Francisella tularensis is a Gram-negative, facultative intracellular pathogen and the causative agent of a lethal human disease known as tularemia. Due to its extremely high virulence and potential to be used as a bioterror agent, F. tularensis is classified by the CDC as a Category A Select Agent. As an intracellular pathogen, F. tularensis during its intracellular residence encounters a number of oxidative and nitrosative stresses. The roles of the primary antioxidant enzymes SodB, SodC and KatG in oxidative stress resistance and virulence of F. tularensis live vaccine strain (LVS) have been characterized in previous studies. However, very fragmentary information is available regarding the role of peroxiredoxin of the AhpC/TSA family (annotated as AhpC) of F. tularensis SchuS4; whereas the role of AhpC of F. tularensis LVS in tularemia pathogenesis is not known. This study was undertaken to exhaustively investigate the role of AhpC in oxidative stress resistance of F. tularensis LVS and SchuS4. We report that AhpC of F. tularensis LVS confers resistance against a wide range of reactive oxygen and nitrogen species, and serves as a virulence factor. In highly virulent F. tularensis SchuS4 strain, AhpC serves as a key antioxidant enzyme and contributes to its robust oxidative and nitrosative stress resistance, and intramacrophage survival. We also demonstrate that there is functional redundancy among primary antioxidant enzymes AhpC, SodC, and KatG of F. tularensis SchuS4. Collectively, this study highlights the differences in antioxidant defense mechanisms of F. tularensis LVS and SchuS4.
Family planning under sociocultural influence: evaluating knowledge, access, and utilization in Al Baha, Saudi Arabia
Unmet need for contraception remains a persistent global reproductive health challenge. In Saudi Arabia, national estimates indicate moderate contraceptive uptake; however, region-specific data on awareness, accessibility, and utilization of family planning (FP) services remain limited, particularly in semi-rural settings such as Al-Baha. To evaluate awareness, access, and utilization of family planning and reproductive health services and to identify perceived barriers and sociodemographic determinants among adult women in Al-Baha, Saudi Arabia. A population-based cross-sectional study was conducted using a 23-item online questionnaire administered to female residents aged ≥18 years between December 2024 and February 2025 through convenience sampling. Descriptive statistics summarized participant characteristics and FP-related variables. Associations between categorical variables were assessed using chi-square ( ²) tests. Univariable and multivariable logistic regression analyses were performed to estimate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Statistical significance was set at a two-sided  < 0.05. Ethical approval was obtained from the Deanship of Scientific Research, Al-Baha University (Approval No. 46110701-20241117), and electronic informed consent was secured prior to participation. A total of 892 women participated (mean age 38 ± 10.5 years). Awareness of FP initiatives was reported by 24%, and 18% had previously received FP consultation/services. Although 94% reported geographic access to a healthcare facility within 30 min, routine reproductive health service utilization remained limited, with 53% reporting infrequent visits. Current contraceptive use was reported by 42%, predominantly oral contraceptive pills (15%) and intrauterine methods (9%). Overall, 32% reported at least one barrier to contraception access, with \"other barriers\" (14%) and limited availability (11%) cited most frequently. Several outcomes demonstrated significant sociodemographic variation (  < 0.05). In multivariable analysis, age >30 years independently predicted current contraceptive use (aOR 3.97; 95% CI 2.64-5.98;  < 0.001). Despite reported geographic accessibility, awareness and counselling uptake remain suboptimal in Al-Baha. Targeted, culturally responsive primary care-based interventions and strengthened service availability are warranted to improve informed reproductive health decision-making.
Circulation of Dengue Virus Serotype 2 in Humans and Mosquitoes During an Outbreak in El Quseir City, Egypt Corrigendum
El-Kady AM, Osman HA, Alemam MF, et al. Infect Drug Resist. 2022;15:2713-2721. The authors have advised that the acknowledgment statement on page 2719 is incorrect. The text “This research was supported by Princess Nourah Bint Abdulrahman University Project number (PNURSP2022R39), Riyadh, Saudi Arabia” should read “This research was supported by Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2022R39), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia”. The authors apologize for this error.
Circulation of Dengue Virus Serotype 2 in Humans and Mosquitoes During an Outbreak in El Quseir City, Egypt
In recent decades, the rate of infection with dengue virus (DENV) has risen significantly, now affecting nearly 400 million individuals annually. Dengue fever among humans is caused via specific mosquito vectors bites. Sporadic cases have been reported in Egypt. The goal of this study was to identify the serotype of the DENV outbreak in both human and mosquito vector along the coast of the Red Sea, Upper Egypt, in 2017. Identification of the serotype of the virus may help identify its source and assist in applying epidemiological and control measures. The current study was carried out in El Quseir City, Red Sea Governorate, Upper Egypt, on 144 patients complaining of symptoms indicative of dengue fever at the time of the 2017 Egypt outbreak. Human blood samples and the mosquito reservoirs were identified as having dengue virus infection serologically and molecularly. Overall, 97 (67.4%) patients were positive for dengue virus IgM antibodies. Molecular examination of the human samples and pools of mosquitoes revealed that DENV-2 virus was the serotype responsible for the outbreak. Only one pool of female mosquitoes containing was infected with dengue fever virus (DENV-2). This was the first serotyping of the DENV responsible for dengue virus outbreak in Egypt in 2017. Determining the serotype of dengue virus can help to avoid and monitor outbreaks. The serotype identified in this study was DENV-2, while DENV-1 was the serotype found in the previous outbreak in 2015 in the province of Assiut. This study thus raises concerns that a new dengue serotype could have been introduced into Egypt. It is necessary for a comprehensive risk assessment to be carried out in the country, including an entomological survey, to assess the presence and potential geographical expansion of mosquito vectors there.
Characterization of the Role of Transcriptional Regulator of AraC/XylS Family in Tularemia Pathogenesis
The Tier 1 Select Agent, Francisella tularensis causes an acute and fatal disease known as tularemia. Many studies have devoted enormous efforts to understand how F. tularensis avoids host defense mechanisms, replicates within an extremely secure immune system, and eventually causes the deadly disease tularemia. The extremely high virulence of Francisella depends on its ability to manipulate gene expression according to the surrounding environment. This process requires the involvement of unique transcriptional regulators. Francisella possesses very few transcriptional regulators, and a majority of them characterized to-date have been shown to regulate genes involved in virulence and cellular functions. The role of a transcriptional regulator of F. tularensis belonging to the AraC/XylS in gene regulation and virulence remains uncharacterized to-date. This study characterized the role of AraC in gene regulation, intramacrophage survival, and virulence of F. tularensis.In specific aim 1, we generated a deletion mutant (ΔaraC) of FTL_0689 gene encoding AraC of F. tularensis Live Vaccine Strain (LVS), and its transcomplemented strain (ΔaraC+paraC). Characterization of the ΔaraC mutant demonstrated that AraC does not regulate genes involved in arabinose utilization. Genomic organization of the araC gene suggested that it may have a role in the regulation of a unique multidrug efflux pump (MEP) located downstream of it. Our results revealed that the phenotype of the ΔaraC mutant mirrors that of the emrA1 and the silC mutants, the components of the MEP. However, these phenotypic similarities are not due to the direct regulation of MEP genes by AraC. Further characterization revealed that AraC is involved in providing resistance against oxidative stress.In specific aim 2, we investigated the role of AraC as a global transcriptional regulator in F. tularensis LVS strain. We studied gene expression profiles of the wild type F. tularensis LVS and the ΔaraC mutant under normal and oxidative stress conditions. The results revealed that AraC serves as a transcriptional regulator only when the bacteria are exposed to oxidative stress conditions. AraC is involved in the regulation of virulence genes encoded on Francisella Pathogenicity Island, stress response genes, energy production, genes encoding enzymes in the tricarboxylic acid (TCA) cycle, metabolism and regulatory proteins indicating its role as a global regulator. The differential expression of these genes also impaired the ability of the ΔaraC mutant to survive in macrophages and attenuated its virulence in mice.Collectively, this study identified and characterized a novel transcription factor, AraC, required for adaptation of Francisella to oxidative stress conditions encountered outside or within a host.
Identification of Toxoplasma gondii Genes Important for Conversion to Cysts
Toxoplasma gondii is an obligate intracellular Apicomplexa parasite. It causes the disease toxoplasmosis, estimated to be the second leading cause of food borne death in the United States. The disease is usually asymptomatic or can cause flu like symptoms in healthy individuals but it can be lethal in immunocompromised patients or to the fetus following congenital transmission. The main route of transmission is fecal oral, mainly by ingestion of under-cooked meet contaminated with bradyzoites containing cysts or by the consumption of the oocysts that contain sporozoites. In the United States approximately 25% of the adult population is seropositive for the parasite. The current findings of this study suggest that these three genes contribute to parasite survival in exogenous stress conditions and conversion to the chronic cyst stage both in vitro and in vivo.
On the Use of Radar and Optical Satellite Imagery for the Monitoring of Flood Hazards on Heritage Sites in Southern Sinai, Egypt
This study focuses on the use of radar and optical satellite imagery for flood hazard mapping and monitoring around the archaeological sites of the Wadi Baba area, situated at Sinai (Egypt) and well known for its heritage treasures belonging to diverse historical periods and civilizations from the Pharaonic, Nabateans, Christian, and Islamic eras. Although this area is located in an arid to semi-arid climatic region, it is intermittently flooded due to torrential rainstorms. To assess the amount of rainfall expected and its impacts on heritage sites, satellite Sentinel-1 (C-Band) and Tropical Rainfall Monitoring Mission (TRMM) data were jointly used with measurements from meteorological stations and the Digital Elevation Model (DEM) from Shuttle Radar Topography Mission (SRTM). Envi5.1, ArcGIS 10.4.1, Snap 6.0, and the GEE platform were used to process optical and radar data, which were further analysed using the ArcHydro model. In this study, the TRMM accumulated rainfall data acquired on 17 January 2010, Sentinel-1 radar images between 2017 and 2019, and Sentinel-1 data captured from 1 to 30 March 2020 processed by GEE platform were chosen to assess the effects of flood events on the archaeological sites in the study area. The results indicated that the study area is exposed to flood risk that significantly threatens these heritage sites. Based on that, mitigation strategies were devised and recommended to mitigate the flood hazard impact around the archaeological areas.