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  • 1
    Online Resource
    Online Resource
    DataSheet_1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-7-12)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-7-12)
    Abstract: Advanced stage cancers are aggressive and difficult to treat with mono-therapeutics, substantially decreasing patient survival rates. Hence, there is an urgent need to develop unique therapeutic approaches to treat cancer with superior potency and efficacy. This study investigates a new approach to develop a potent combinational therapy to treat advanced stage leukemia. Biologically active α-amino amide analogs (RS)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylpropiolamide (α-AAA-A) and (RS)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylbut2-enamide (α-AAA-B) were synthesized using linear Ugi multicomponent reaction. Cytotoxicities and IC 50 values of α-AAA-A and α-AAA-B against leukemia cancer cell lines (HL-60 and K562) were analyzed though MTT assay. Cytotoxic assay analyzed percent killing of leukemia cell lines due to the effect of γδ T cells alone or in combination with α-AAA-A or α-AAA-B. Synthesized biologically active molecule α-AAA-A exhibited increased cytotoxicity of HL-60 (54%) and K562 (44%) compared with α-AAA-B (44% and 36% respectively). Similarly, α-AAA-A showed low IC 50 values for HL-60 (1.61 ± 0.11 μM) and K562 (3.01 ± 0.14 μM) compared to α-AAA-B (3.12 ± 0.15 μM and 6.21 ± 0.17 μM respectively). Additive effect of amide analogs and γδ T cells showed significantly high leukemia cancer cell killing as compared to γδ T cells alone. A unique combinational therapy with γδ T cells and biologically active anti-cancer molecules (α-AAA-A/B), concomitantly may be a promising cancer therapy.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.706586
    DOI: 10.3389/fonc.2021.706586.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 2
    Online Resource
    Online Resource
    Seroprevalence of Anti-S1-RBD Antibodies in Pre-pandemic and Pandemic Subjects From Hail Region, KSA
    Frontiers Media SA ; 2022
    In:  Frontiers in Public Health Vol. 10 ( 2022-6-9)
    Details
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 10 ( 2022-6-9)
    Abstract: Two years into the pandemic, yet the threat of new SARS-CoV-2 variants continues to loom large. Sustained efforts are required to fully understand the infection in asymptomatic individuals and those with complications. Identification, containment, care, and preventative strategies rely on understanding the varied humoral immune responses. Methods An in-house ELISA was developed and standardized to screen for serum IgG antibodies against the SARS-CoV-2 S1-RBD protein as an antigen. This study aims to investigate the seroprevalence of serum antibodies against S1-RBD antigen in pre-pandemic ( n = 120) and during the early pandemic period ( n = 120) in subjects from the Hail region, KSA and to correlate it with clinical and demographic factors. Results Samples collected from both male ( n = 60) and female ( n = 60) subjects during the pandemic in the age groups of 20–40 (0.31 ± 0.029 and 0.29 ± 0.024, respectively) and 41–60 years (0.35 ± 0.026 and 0.30 ± 0.025, respectively) showed significantly higher levels of serum antibodies against S-RBD antigen than the age-matched pre-pandemic samples [male ( n = 60) and female ( n = 60)]. Pandemic subjects exhibited significantly ( p & lt; 0.01) higher inhibition (80–88%) than age-matched pre-pandemic subjects (32–39%). Antibodies against S1-RBD antigen were detected in approximately 10% of the total pre-pandemic population (males and females). However, subjects & gt; 60 years did not show antibodies. Conclusion Antibody levels increased in samples collected during the pandemic, even though these subjects were not clinically COVID-19 positive. A small number of pre-pandemic subjects showed serum antibodies, suggesting prior exposure to other coronaviruses in the region. With dwindling neutralizing antibody levels and reduced vaccine efficacy against newer variants, it remains crucial to develop better assays for surveillance, management, and future research.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    URL: Article
    DOI: 10.3389/fpubh.2022.874741
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711781-9
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  • 3
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    Online Resource
    Table_9.csv
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-3-29)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-3-29)
    Abstract: Selective cancer cell recognition is the most challenging objective in the targeted delivery of anti-cancer agents. Extruded specific cancer cell membrane coated nanoparticles, exploiting the potential of homotypic binding along with certain protein-receptor interactions, have recently proven to be the method of choice for targeted delivery of anti-cancer drugs. Prediction of the selective targeting efficiency of the cancer cell membrane encapsulated nanoparticles (CCMEN) is the most critical aspect in selecting this strategy as a method of delivery. Materials and methods A probabilistic model based on binding scores and differential expression levels of Glioblastoma cancer cells (GCC) membrane proteins (factors and receptors) was implemented on python 3.9.1. Conditional binding efficiency (CBE) was derived for each combination of protein involved in the interactions. Selective propensities and Odds ratios in favour of cancer cells interactions were determined for all the possible combination of surface proteins for ‘k’ degree of interaction. The model was experimentally validated by two types of Test cultures. Results Several Glioblastoma cell surface antigens were identified from literature and databases. Those were screened based on the relevance, availability of expression levels and crystal structure in public databases. High priority eleven surface antigens were selected for probabilistic modelling. A new term, Break-even point (BEP) was defined as a characteristic of the typical cancer cell membrane encapsulated delivery agents. The model predictions lie within ±7% of the experimentally observed values for both experimental test culture types. Conclusion The implemented probabilistic model efficiently predicted the directional preference of the exposed nanoparticle coated with cancer cell membrane (in this case GCC membrane). This model, however, is developed and validated for glioblastoma, can be easily tailored for any type of cancer involving CCMEN as delivery agents for potential cancer immunotherapy. This probabilistic model would help in the development of future cancer immunotherapeutic with greater specificity.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
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    URL: Article
    DOI: 10.3389/fimmu.2023.1162213
    DOI: 10.3389/fimmu.2023.1162213.s001
    DOI: 10.3389/fimmu.2023.1162213.s002
    DOI: 10.3389/fimmu.2023.1162213.s003
    DOI: 10.3389/fimmu.2023.1162213.s004
    DOI: 10.3389/fimmu.2023.1162213.s005
    DOI: 10.3389/fimmu.2023.1162213.s006
    DOI: 10.3389/fimmu.2023.1162213.s007
    DOI: 10.3389/fimmu.2023.1162213.s008
    DOI: 10.3389/fimmu.2023.1162213.s009
    DOI: 10.3389/fimmu.2023.1162213.s010
    DOI: 10.3389/fimmu.2023.1162213.s011
    DOI: 10.3389/fimmu.2023.1162213.s012
    DOI: 10.3389/fimmu.2023.1162213.s013
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 4
    Online Resource
    Online Resource
    Editorial: Immunotherapy and small molecule inhibitors as combinational cancer therapeutics
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-8-22)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-8-22)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2023.1270182
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 5
    Online Resource
    Online Resource
    Presence of Circulatory Autoantibodies Against ROS-Modified Histone H1 Protein in Lymphoma Patients
    Frontiers Media SA ; 2022
    In:  Frontiers in Genetics Vol. 13 ( 2022-5-25)
    Details
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-5-25)
    Abstract: Lymphoma is a chronic inflammatory disease in which the immune system is highly affected. Increased oxidative stress is one of the common conditions of cancer and affects macromolecules. Histone modifications affect the chromatin structure and functions. In this study, histone H1 (His-H1) protein was modified by reactive oxygen species (ROS), and structural and chemical changes were studied. Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients were selected, and oxidative stress markers, inflammatory cytokines, and serum autoantibodies were analyzed using biochemical and immunological assays. Furthermore, the formation of antigen-antibody immune complexes was assessed by the Langmuir plot. ROS-modified His-H1 (ROS-His-H1) showed substantial structural perturbation in protein (UV-hyperchromicity and increased intrinsic fluorescence) compared to the native His-H1 protein. A possible explanation for the changes is suggested by the exposure of the aromatic chromophore to the solvent. In-depth structural analysis by circular dichroism (CD) exhibited major changes in α-helix (−21.43%) and turns (+33%), reflecting changes in the secondary structure of histone H1 protein after ROS exposure. ELISA and competitive ELISA findings revealed high recognitions of serum autoantibodies to ROS-His-H1 from NHL, followed by HL subjects. Healthy controls showed negligible binding. Non-modified His-H1 did not show any binding with serum samples from either cohort. High apparent association constants (ACCs) were calculated for ROS-His-H1 using purified IgGs from NHL (1.46 × 10 –6  M) compared to HL (1.33 × 10 –6  M) patients. Non-modified His-H1 exhibited a hundred times less ACC for NHL (2.38 × 10 –8  M) and HL (2.46 × 10 –8  M) patients. Thus, ROS modifications of histone H1 cause structural changes and expose cryptic neo-epitopes on the protein against which autoantibodies were generated. These perturbations might affect the histone DNA interaction dynamics and potentially be correlated with gene dysregulation. These subtle molecular changes with an immune imbalance might further aggravate the disease.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    URL: Article
    DOI: 10.3389/fgene.2022.909903
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606823-0
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