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  • 1
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-7-15)
    Abstract: Marburg virus (MARV) is one of the most harmful zoonotic viruses with deadly effects on both humans and nonhuman primates. Because of its severe outbreaks with a high rate of fatality, the world health organization put it as a risk group 4 pathogen and focused on the urgent need for the development of effective solutions against that virus. However, up to date, there is no effective vaccine against MARV in the market. In the current study, the complete proteome of MARV (seven proteins) was analyzed for the antigenicity score and the virulence or physiological role of each protein where we nominated envelope glycoprotein (Gp), Transcriptional activator (VP30), and membrane-associated protein (VP24) as the candidates for epitope prediction. Following that, a vaccine construct was designed based on CTL, HTL, and BCL epitopes of the selected protein candidates and to finalize the vaccine construct, several amino acid linkers, β-defensin adjuvant, and PADRE peptides were incorporated. The generated potential vaccine was assessed computationally for several properties such as antigenicity, allergenicity, stability, and other structural features where the outcomes of these assessments nominated this potential vaccine to be validated for its binding affinity with two molecular targets TLR-8 and TLR-4. The binding score and the stability of the vaccine-receptor complex, which was deeply studied through molecular docking-coupled dynamics simulation, supported the selection of our designed vaccine as a putative solution for MARV that should be validated through future wet-lab experiments. Here, we describe the computational approach for designing and analysis of this potential vaccine.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 2
    Online Resource
    Online Resource
    Jaypee Brothers Medical Publishing ; 2014
    In:  World Journal of Dentistry Vol. 5, No. 2 ( 2014-06), p. 81-86
    In: World Journal of Dentistry, Jaypee Brothers Medical Publishing, Vol. 5, No. 2 ( 2014-06), p. 81-86
    Abstract: Advanced glycosylated end products (AGEs) in type II diabetic patients are usually precipitated on the periodontallyaffected root surfaces. The presence of periodontopathic microbes, at the same time, may also add a negative impact on the prognosis of the regenerative periodontal surgery. This in vitro study aimed to evaluate the effect of chemical conditioning on surface characteristics of periodontally-affected roots of diabetic patients. Methods Three groups (n = 25) of freshly-extracted teeth were collected from the outpatient clinics, College of Dentistry, King Khalid University. In group 1, teeth were collected from healthy individuals for orthodontic purpose. Teeth of group 2 were collected from healthy patients with chronic periodontitis, while those of group 3 were collected from diabetic patients with chronic periodontitis. Roots of the collected teeth were examined using the scanning electron microscope (SEM) before and after mechanical surface planning and chemical treatment using normal saline, EDTA gel, Tetracycline HCL (TC) or citric acid (CA) each for 4 minutes (n = 5 from each group). Results Interpretation of SEM images revealed undesirable etching effect of the chemicals used on the surfaces of healthy roots. Although EDTA showed an effective cleanse of the smear debris, it seemed to have no power on surface cuticles existed on roots of diabetic individuals. Tetracycline HCl provided acceptable conditioning of periodontally-affected root surfaces. Citric acid showed a powerful removal of both smear debris and cuticle layers off the periodontally-affected roots of diabetic individuals. Conclusion Topical application of EDTA, TC or CA shows sensible effect on the periodontally affected root surfaces. However, each of these chemicals exhibits different conditioning power. Citric acid is a promising agent to biomodify the periodontally-affected root surfaces of diabetic patients. Clinical relevance Citric acid is an acceptable biomodifier for the periodontally-affected root surfaces. This approach may improve the prognosis of periodontal therapies especially in type II diabetic patients. How to cite this article Abdelaziz KM, Eid HA, Eid RA. Effect of Bioconditioning on Surface Characteristics of Periodontally- affected Roots of Diabetic Patients. World J Dent 2014;5(2):81-86.
    Type of Medium: Online Resource
    ISSN: 0976-6006 , 0976-6014
    Language: English
    Publisher: Jaypee Brothers Medical Publishing
    Publication Date: 2014
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  • 3
    In: Current Issues in Molecular Biology, MDPI AG, Vol. 44, No. 5 ( 2022-05-23), p. 2387-2400
    Abstract: In severe cases of sepsis, endotoxin-induced cardiomyopathy can cause major damage to the heart. This study was designed to see if Vitamin C (Vit C) could prevent lipopolysaccharide-induced heart damage. Eighteen Sprague Dawley male rats (n = 6) were divided into three groups. Rats received 0.5 mL saline by oral gavage in addition to a standard diet (Control group), rats received one dose of endotoxin on day 15 (lipopolysaccharide) (LPS) (6 mg/kg), which produced endotoxemia (Endotoxin group), and rats that received 500 mg/Kg BW of Vit C by oral gavage for 15 days before LPS administration (Endotoxin plus Vit C group). In all groups, blood and tissue samples were collected on day 15, six hours after LPS administration, for histopathological and biochemical analysis. The LPS injection lowered superoxide dismutase (SOD) levels and increased malondialdehyde in tissues compared with a control group. Furthermore, the endotoxin group showed elevated inflammatory biomarkers, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Both light and electron microscopy showed that the endotoxic-treated group’s cardiomyocytes, intercalated disks, mitochondria, and endothelial cells were damaged. In endotoxemic rats, Vit C pretreatment significantly reduced MDA levels and restored SOD activity, minimized biomarkers of inflammation, and mitigated cardiomyocyte damage. In conclusion: Vit C protects against endotoxin-induced cardiomyopathy by inhibiting oxidative stress cytokines.
    Type of Medium: Online Resource
    ISSN: 1467-3045
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2090836-2
    SSG: 12
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  • 4
    In: British Journal of Biomedical Science, Frontiers Media SA, Vol. 79 ( 2022-3-18)
    Abstract: Context: Intermittent short-duration re-oxygenation attenuates cardiac changes in response to hypoxia. Objective: To see if intermittent short-duration re-oxygenation may protect the heart muscle from hypoxia damage. Materials and Methods: Eighteen albino rats were used to carry out the study. Rats divided into: (normoxia); rats exposed to room air as a control, second (hypoxic) group; rats subjected to a pressure of 405 mmHg in a hypobaric chamber to simulate hypoxia at 5,000 m, and third (intermittent short-duration re-oxygenation); rats exposed to room air three times per day. Experiments were all 14 days long. Results: Hypoxia enhanced the oxidative stress biomarker malondialdehyde while lowering the antioxidant superoxide dismutase . The levels of tumour necrosis factor (TNF-α) and interleukin-6 (IL-6) in the myocardium were elevated in hypoxic hearts. The hypoxic rats’ cardiac myofibrils showed disarray of muscle fibres, vacuolation of the sarcoplasm, pyknosis of the nucleus, and expansion of intercellular gaps on histological examination. In addition, cardiomyocytes showed degenerative defects in ventricular myocardial cells on ultrastructural analysis. Myofibril thinning and degenerative mitochondrial changes affected intercalated discs with fascia adherent, desmosomes, and gap junction. Intermittent short-duration re-oxygenation improve cardiac histological, ultrastructural and oxidant/antioxidant parameters changes during hypoxia. Conclusion: Hypoxia showed a substantial impact on myocardial architecture, as well as increased oxidative stress and pro-inflammatory cytokines. Intermittent short-duration re-oxygenation significantly decreases hypoxia-induced cardiac changes.
    Type of Medium: Online Resource
    ISSN: 2474-0896
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2241762-X
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  • 5
    In: Biomedicines, MDPI AG, Vol. 11, No. 8 ( 2023-08-11), p. 2254-
    Abstract: Cyclin dependent kinase inhibitor 2A (CDKN2A) is a well-known tumor suppressor gene as it functions as a cell cycle regulator. While several reports correlate the malfunction of CDKN2A with the initiation and progression of several types of human tumors, there is a lack of a comprehensive study that analyzes the potential effect of CDKN2A genetic alterations on the human immune components and the consequences of that effect on tumor progression and patient survival in a pan-cancer model. The first stage of the current study was the analysis of CDKN2A differential expression in tumor tissues and the corresponding normal ones and correlating that with tumor stage, grade, metastasis, and clinical outcome. Next, a detailed profile of CDKN2A genetic alteration under tumor conditions was described and assessed for its effect on the status of different human immune components. CDKN2A was found to be upregulated in cancerous tissues versus normal ones and that predicted the progression of tumor stage, grade, and metastasis in addition to poor prognosis under different forms of tumors. Additionally, CDKN2A experienced different forms of genetic alteration under tumor conditions, a characteristic that influenced the infiltration and the status of CD8, the chemokine CCL4, and the chemokine receptor CCR6. Collectively, the current study demonstrates the potential employment of CDKN2A genetic alteration as a prognostic and immunological biomarker under several types of human cancers.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2720867-9
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  • 6
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 22 ( 2022-11-15), p. 14102-
    Abstract: Several recent studies have pointed out that arc GTPase activating protein 1 (RACGAP1) is a putative oncogene in many human tumors. However, to date, no pan-cancer analysis has been performed to study the different aspects of this gene expression and behavior in tumor tissues. Here, we applied several bioinformatics tools to perform a comprehensive analysis for RACGAP1. First, we assessed the expression of RACGAP1 in several types of human tumors and tried to correlate that with the stage of the tumors analyzed. We then performed a survival analysis to study the correlation between RACGAP1 upregulation in tumors and the clinical outcome. Additionally, we investigated the mutation forms, the correlation with several immune cell infiltration, the phosphorylation status of the interested protein in normal and tumor tissues, and the potential molecular mechanisms of RACGAP1 in cancerous tissue. The results demonstrated that RACGAP1, a highly expressed gene across several types of tumors, correlated with a poor prognosis in several types of human cancers. Moreover, it was found that RACGAP1 affects the tumor immune microenvironment by influencing the infiltration level of several immune cells. Collectively, the current study provides a comprehensive overview of the oncogenic roles of RACGAP1, where our results nominate it as a potential prognostic biomarker and a target for antitumor therapy development.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 7
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 17 ( 2021-08-28), p. 9330-
    Abstract: Nipah virus is one of the most harmful emerging viruses with deadly effects on both humans and animals. Because of the severe outbreaks, in 2018, the World Health Organization focused on the urgent need for the development of effective solutions against the virus. However, up to date, there is no effective vaccine against the Nipah virus in the market. In the current study, the complete proteome of the Nipah virus (nine proteins) was analyzed for the antigenicity score and the virulence role of each protein, where we came up with fusion glycoprotein (F), glycoprotein (G), protein (V), and protein (W) as the candidates for epitope prediction. Following that, the multitope vaccine was designed based on top-ranking CTL, HTL, and BCL epitopes from the selected proteins. We used suitable linkers, adjuvant, and PADRE peptides to finalize the constructed vaccine, which was analyzed for its physicochemical features, antigenicity, toxicity, allergenicity, and solubility. The designed vaccine passed these assessments through computational analysis and, as a final step, we ran a docking analysis between the designed vaccine and TLR-3 and validated the docked complex through molecular dynamics simulation, which estimated a strong binding and supported the nomination of the designed vaccine as a putative solution for Nipah virus. Here, we describe the computational approach for design and analysis of this vaccine.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-12-9)
    Abstract: A deep understanding of the causes of liability to SARS-CoV-2 is essential to develop new diagnostic tests and therapeutics against this serious virus in order to overcome this pandemic completely. In the light of the discovered role of antimicrobial peptides [such as human b-defensin-2 (hBD-2) and cathelicidin LL-37] in the defense against SARS-CoV-2, it became important to identify the damaging missense mutations in the genes of these molecules and study their role in the pathogenesis of COVID-19. Methods We conducted a comprehensive analysis with multiple in silico approaches to identify the damaging missense SNPs for hBD-2 and LL-37; moreover, we applied docking methods and molecular dynamics analysis to study the impact of the filtered mutations. Results The comprehensive analysis reveals the presence of three damaging SNPs in hBD-2; these SNPs were predicted to decrease the stability of hBD-2 with a damaging impact on hBD-2 structure as well. G51D and C53G mutations were located in highly conserved positions and were associated with differences in the secondary structures of hBD-2. Docking-coupled molecular dynamics simulation analysis revealed compromised binding affinity for hBD-2 SNPs towards the SARS-CoV-2 spike domain. Different protein–protein binding profiles for hBD-2 SNPs, in relation to their native form, were guided through residue-wise levels and differential adopted conformation/orientation. Conclusions The presented model paves the way for identifying patients prone to COVID-19 in a way that would guide the personalization of both the diagnostic and management protocols for this serious disease.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 9
    In: Clinical and Experimental Pharmacology and Physiology, Wiley, Vol. 46, No. 12 ( 2019-12), p. 1111-1123
    Abstract: This study investigates the effect of chronic consumption of a high‐fat diet rich in corn oil ( CO ‐ HFD ) on atrial cells ultrastructure, antioxidant levels and markers of intrinsic cell death of both control and type 1 diabetes mellitus (T1 DM )‐induced rats. Adult male rats (10 rats/group) were divided into four groups: control fed standard diet ( STD ) (3.82 kcal/g, 9.4% fat), CO ‐ HFD (5.4 kcal/g, 40% fat), T1 DM fed STD , and T1 DM  +  CO ‐ HFD . CO ‐ HFD and T1 DM alone or in combination impaired systolic and diastolic functions of rats and significantly reduced levels of GSH and the activity of SOD , enhanced lipid peroxidation, increased protein levels of P53, Bax, cleaved caspase‐3, and ANF and decreased levels of Bcl‐2 in their atria. Concomitantly, atrial cells exhibited fragmentation of the myofibrils, disorganized mitochondria, decreased number of atrionatriuretic factor ( ANF ) granules, and loss of gap junctions accompanied by changes in capillary walls. Among all treatments, the severity of all these findings was more severe in T1 DM and most profound in the atria of T1 DM  +  CO ‐ HFD . In conclusion, chronic consumption of CO ‐ HFD by T1 DM ‐induced rats elicits significant biochemical and ultrastructural damage to rat atrial cells accompanied by elevated oxidative stress and mitochondria‐mediated cell death.
    Type of Medium: Online Resource
    ISSN: 0305-1870 , 1440-1681
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2020033-X
    SSG: 15,3
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  • 10
    In: Biomedicines, MDPI AG, Vol. 10, No. 1 ( 2021-12-24), p. 39-
    Abstract: Insecticides and toxicants abound in nature, posing a health risk to humans. Concurrent exposure to many environmental contaminants has been demonstrated to harm myocardial performance and reduce cardiac oxidative stress. The purpose of this research was to study the protective effect of vitamin C (Vit C) on quinalphos (QP)-induced cardiac tissue damage in rats. Eighteen albino male rats were randomly categorised into three groups (n = 6). Control, QP group: rats received distilled water. QP insecticide treatment: an oral administration of QP incorporated in drinking water. QP + Vit C group: rats received QP and Vit C. All the experiments were conducted for ten days. Decline of cardiac antioxidant biomarkers catalase (CAT) and reduced glutathione (GPx) along with increased proinflammatory markers tumour necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) indicated oxidative and inflammatory damage to the heart following administration of QP when compared to control rats. The light microscopic and ultrastructure appearance of QP-treated cardiomyocytes exhibited cardiac damage. Administration of Vit C showed decreased oxidative and inflammatory biomarkers, confirmed with histological and electron microscopic examination. In conclusion, Vit C protected the heart from QP-induced cardiac damage due to decreased inflammation and oxidative stress.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720867-9
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