13 results on '"Omari Sa"'
Search Results
2. Transient receptor potential Vanilloid 1 (TRPV1) in haematological malignancies
- Author
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Omari, SA
- Abstract
Transient receptor potential vanilloid-1 (TRPV1) is a member of the TRP family of channels that are responsible for nociceptive, thermal and mechanical sensations. It is primarily associated with neuronal cells, but has been detected in different non-neuronal cells, including leukocytes. Capsaicin (CAP), the active ingredient of hot chilli peppers, is one of a number of related endogenous and plant-derived compounds (broadly termed 'vanilloid-like agents') that have been shown to induce apoptosis and inhibit cell proliferation in some cancer cells, through both TRPV1-dependent and -independent mechanisms. The expression and function of TRPV1 in haematological malignancies however, has not been extensively investigated. Specific targeting by vanilloid-like agents toward TRPV1 on cancerous cells in patients with haematological malignancies may represent a novel therapeutic approach to treating these diseases. This thesis investigated the expression and function of TRPV1 in haematological malignancies, using both blood cancer cell lines and blood samples obtained from patients with different blood cancers. The specific aims were to; 1) study the effect of TRPV1 agonists and antagonists on the viability of THP-1, U266B1 and U937 haematological malignant cell lines, 2) validate and optimise Western blotting and flow cytometry protocols to detect TRPV1 expression in leukocytes, 3) investigate TRPV1 expression in THP-1, U266B1 and U937 cells, and 4) compare TRPV1 expression in leukocytes obtained from patients with blood cancers to normal subjects. The thesis begins with a comprehensive review and discussion on TRPV1 structure and function, as well as its expression and role in health and disease. In particular, there is a focus on the role of TRPV1 in cancer, including haematological malignancies (Chapter 1). In Chapter 2, the effect of CAP on the metabolic activity of three malignant haematological cell lines, THP-1, U266B1 and U937, was investigated. Metabolic activity assays were performed using the alamarBlue¬¨vÜ method. CAP induced cytotoxicity in all three cell lines in a concentration-dependent manner. A biphasic effect on metabolic activity was observed on THP-1 cells [EC50, IC50 (95% CI) = 32.9 (19.9-54.3), 219 (144-246) ˜í¬¿M]. U266B1 cells were more resistant to CAP-induced death than THP-1 and U937 cells. TRPV1 and CB1 antagonists (SB452533 and AM251, respectively) suppressed the CAP-induced increase in THP-1 cell metabolic activity (P
- Published
- 2023
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3. Dysregulation of PAX5 causes uncommitted B cell development and tumorigenesis in mice
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Cho, Helian K, Barthel N, Adria Closa, Hannes Bergmann, Carla M. Roots, Lisa A. Miosge, Eduardo Eyras, Joanne H. Reed, Ian A. Cockburn, Mehmet Yabas, Brigette Boast, Xi Li, Stephen L. Nutt, Anselm Enders, Henry J. Sutton, Omari Sa, Christopher C. Goodnow, Nadine Hein, Young C, T. Andrews, and Katherine M. Hannan
- Subjects
Mutation ,education.field_of_study ,biology ,Population ,medicine.disease_cause ,CD19 ,Malignant transformation ,medicine.anatomical_structure ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Cancer research ,biology.protein ,PAX5 ,education ,Carcinogenesis ,Transcription factor ,B cell - Abstract
PAX5 is the master transcription factor controlling B cell identity. In humans, mutations in PAX5 account for 30% of B cell acute lymphoblastic leukemia (B-ALL) cases. Investigating the causal effects of PAX5 mutations has however been difficult due to the premature lethality of Pax5−/− mice. Here we describe a novel mouse strain with a premature STOP mutation in Pax5 (Y351*) that produces a truncated protein and reduction in protein function, yet still allows for some B cell development to occur. A population of uncommitted and multipotent CD19+B220− B cells develops in the bone marrow of homozygous mice leading to the development of B-ALL. We show that the tumors frequently acquire secondary mutations in Jak3, and Ptpn11 highlighting key pathways interacting with PAX5 during malignant transformation. Analysis of the PAX5Y351* mice provide insight not only into the functional consequence of reduced PAX5 activity on B cell development and identity, but also provides an avenue in which to study PAX5-driven B-ALL in mice.One Sentence SummaryReduction in PAX5 function in mice induces the development of uncommitted B cells that have multipotent and malignant potential.
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- 2021
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4. Health and well-being of older populations affected by humanitarian crises in low- and middle-income countries: a scoping review of peer-reviewed literature.
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Omari SA, McCall SJ, Hneiny L, and Sibai AM
- Abstract
Background: The convergence of global demographic changes and rising humanitarian crises in low- and middle-income countries (LMICs) has raised the number of affected older people (OP). These individuals face the challenges of aging and the adverse conditions of disasters, particularly pronounced in LMICs. This review aims to explore literature on the health and well-being of older populations during humanitarian crises in LMICs., Methods: This scoping review included primary studies on the health and well-being of older populations in humanitarian crises in LMIC. A search was conducted in five bibliographic databases last updated in 2023. A numerical summary and thematic analysis of study characteristics and themes were executed and findings were narratively synthesized., Results: A total of 84 eligible studies were included. The majority of studies were quantitative (n = 56), followed by qualitative (n = 22) and mixed-methods (n = 6). Most literature focuses on the high burden of mental health conditions and their determinants, such as depression, anxiety, and Post-Traumatic Stress Disorder (PTSD). The second most common theme is physical health, discussing high levels of mortality, disability, some non-communicable diseases, and limited evidence on the poor nutritional status. OP lack access to routine healthcare due to cost barriers. The key gaps in the literature are in mental and psychosocial health, especially pertaining to vulnerabilities and risk factors, and to contextualized interventions. Physical health research is relatively narrow lacking a wider range of chronic diseases while no research was performed on communicable diseases other than COVID-19., Conclusions: Findings show the complex vulnerabilities of OP in humanitarian crises which exacerbate their physical, mental, and psychosocial health outcomes. There is a need to strengthen evidence on the effectiveness of interventions, and to investigate determinants of health, especially mental and psychosocial health, across different contexts. Research should also explore cross-cutting issues like gender, access to livelihoods, and equitable access to humanitarian assistance., Competing Interests: Declarations. Ethical approval: Since this is a scoping review of previously published studies, ethical approval for this study is not needed. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
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- 2024
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5. Direct Z-scheme heterojunction impregnated MoS 2 -NiO-CuO nanohybrid for efficient photocatalyst and dye-sensitized solar cell.
- Author
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Dharmalingam K, Bojarajan AK, Gopal R, Thangavel E, Burhan Al Omari SA, and Sangaraju S
- Abstract
In this present work, the preparation of ternary MoS
2 -NiO-CuO nanohybrid by a facile hydrothermal process for photocatalytic and photovoltaic performance is presented. The prepared nanomaterials were confirmed by physio-chemical characterization. The nanosphere morphology was confirmed by electron microscopy techniques for the MoS2 -NiO-CuO nanohybrid. The MoS2 -NiO-CuO nanohybrid demonstrated enhanced crystal violet (CV) dye photodegradation which increased from 50 to 95% at 80 min; The degradation of methyl orange (MO) dye increased from 56 to 93% at 100 min under UV-visible light irradiation. The trapping experiment was carried out using different solvents for active species and the Z-Scheme photocatalytic mechanism was discussed in detail. Additionally, a batch series of stability experiments were carried out to determine the photostability of materials, and the results suggest that the MoS2 -NiO-CuO nanohybrid is more stable even after four continuous cycles of photocatalytic activity. The MoS2 -NiO-CuO nanohybrid delivers photoconversion efficiency (4.92%) explored efficacy is 3.8 times higher than the bare MoS2 (1.27%). The overall results indicated that the MoS2 -NiO-CuO nanohybrid nanostructure could be a potential candidate to be used to improve photocatalytic performance and DSSC solar cell applications as well., (© 2024. The Author(s).)- Published
- 2024
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6. In vitro and in vivo modelling of mutant JAK3/STAT5 signaling in leukemia.
- Author
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Omari SA, Kosasih HJ, Chung T, and de Bock CE
- Abstract
Mutations within the IL7-R-JAK-STAT signaling pathway are important drivers of T-cell acute lymphoblastic leukemia (T-ALL). Here we describe the important steps required to generate retroviral particles for the stable expression of mutant JAK3 constructs that induce constitutive JAK/STAT signaling. These are subsequently used for the viral transduction of the IL-3 cytokine-dependent Ba/F3 cell line or murine hematopoietic stem and progenitor cells (HSPCs) for in vitro and in vivo modelling of cytokine-independent growth or leukemia initiation respectively., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)
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- 2023
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7. Optimized flow cytometric detection of transient receptor potential vanilloid-1 (TRPV1) in human hematological malignancies.
- Author
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Omari SA, Geraghty DP, Khalafallah AA, Venkat P, Shegog YM, Ragg SJ, de Bock CE, and Adams MJ
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- Child, Flow Cytometry, Humans, Leukocytes, Mononuclear metabolism, Male, Prostate metabolism, TRPV Cation Channels genetics, TRPV Cation Channels metabolism, Antineoplastic Agents, Hematologic Neoplasms, Tongue Neoplasms
- Abstract
The ectopic overexpression of transient receptor potential vanilloid-1 (TRPV1) has been detected in numerous solid cancers, including breast, prostate, pancreatic, and tongue epithelium cancer. However, the expression of TRPV1 in hematological malignancies remains unknown. Here we show through in silico analysis that elevated TRPV1 mRNA expression occurs in a range of hematological malignancies and presents an optimized flow cytometry method to rapidly assess TRPV1 protein expression for both cell lines and primary patient samples. Three anti-TRPV1 antibodies were evaluated for intracellular TRPV1 detection using flow cytometry resulting in an optimized protocol for the evaluation of TRPV1 in hematological malignant cell lines and patients' peripheral blood mononuclear cells (PBMC). Overexpression of TRPV1 was observed in THP-1 (acute monocytic leukemia) and U266B1 (multiple myeloma, MM), but not U937 (histiocytic lymphoma) compared to healthy PBMC. TRPV1 was also detected in all 49 patients including B-cell non-Hodgkin's lymphoma (B-NHL), MM, and others and 20 healthy controls. TRPV1 expression was increased in 8% of patients (MM = 2, B-NHL = 2). In conclusion, we provide an optimized flow cytometry method for routine expression analysis of clinical samples and show that TRPV1 is increased in a subset of patients with hematological malignancies., (© 2022. The Author(s).)
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- 2022
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8. Antimicrobial resistance in the protracted Syrian conflict: halting a war in the war.
- Author
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Osman M, Rafei R, Ismail MB, Omari SA, Mallat H, Dabboussi F, Cazer C, Karah N, Abbara A, and Hamze M
- Subjects
- Armed Conflicts, Europe, Health Policy, Refugees, Syria, Anti-Bacterial Agents pharmacology, Drug Resistance, Bacterial
- Abstract
The Syrian conflict has damaged key infrastructure and indirectly affected almost all parts of the Middle East and Europe, with no end in sight. Exhausting conditions created by the Syrian crisis and related massive displacement promote the emergence of numerous public health problems that fuel antimicrobial resistance (AMR) development. Here, we explore the current situation of the Syrian displaced population, and AMR inside Syria and among refugees in host countries. We then suggest a roadmap of selected key interventions and strategies to address the threat of AMR in the context of the Syrian crisis. These recommendations are intended to urge health policy-makers in governments and international health organizations to optimize and push for implementing an effective policy taking into consideration the current obstacles.
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- 2021
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9. A Point Mutation in IKAROS ZF1 Causes a B Cell Deficiency in Mice.
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Boast B, Miosge LA, Kuehn HS, Cho V, Athanasopoulos V, McNamara HA, Sontani Y, Mei Y, Howard D, Sutton HJ, Omari SA, Yu Z, Nasreen M, Andrews TD, Cockburn IA, Goodnow CC, Rosenzweig SD, and Enders A
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- Animals, Antibody Formation, HEK293 Cells, Haploinsufficiency, Heat Shock Transcription Factors genetics, Heat Shock Transcription Factors metabolism, Humans, Ikaros Transcription Factor metabolism, Immunoglobulins metabolism, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, NIH 3T3 Cells, B-Lymphocytes immunology, Common Variable Immunodeficiency genetics, Ikaros Transcription Factor genetics, Point Mutation genetics
- Abstract
IKZF1 (IKAROS) is essential for normal lymphopoiesis in both humans and mice. Previous Ikzf1 mouse models have demonstrated the dual role for IKZF1 in both B and T cell development and have indicated differential requirements of each zinc finger. Furthermore, mutations in IKZF1 are known to cause common variable immunodeficiency in patients characterized by a loss of B cells and reduced Ab production. Through N -ethyl- N -nitrosourea mutagenesis, we have discovered a novel Ikzf1 mutant mouse with a missense mutation (L132P) in zinc finger 1 (ZF1) located in the DNA binding domain. Unlike other previously reported murine Ikzf1 mutations, this L132P point mutation ( Ikzf1
L132P ) conserves overall protein expression and has a B cell-specific phenotype with no effect on T cell development, indicating that ZF1 is not required for T cells. Mice have reduced Ab responses to immunization and show a progressive loss of serum Igs compared with wild-type littermates. IKZF1L132P overexpressed in NIH3T3 or HEK293T cells failed to localize to pericentromeric heterochromatin and bind target DNA sequences. Coexpression of wild-type and mutant IKZF1, however, allows for localization to pericentromeric heterochromatin and binding to DNA indicating a haploinsufficient mechanism of action for IKZF1L132P Furthermore, Ikzf1+/L132P mice have late onset defective Ig production, similar to what is observed in common variable immunodeficiency patients. RNA sequencing revealed a total loss of Hsf1 expression in follicular B cells, suggesting a possible functional link for the humoral immune response defects observed in Ikzf1L132P/L132P mice., (Copyright © 2021 by The American Association of Immunologists, Inc.)- Published
- 2021
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10. COVID-19 in children: Could pertussis vaccine play the protective role?
- Author
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Ismail MB, Omari SA, Rafei R, Dabboussi F, and Hamze M
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- Animals, Bordetella pertussis, Child, Humans, Immunity, Heterologous immunology, Lymphocytes virology, Models, Theoretical, Preventive Medicine methods, Public Health, Respiratory System virology, COVID-19 epidemiology, COVID-19 prevention & control, Pertussis Toxin therapeutic use, Pertussis Vaccine
- Abstract
While COVID-19 continues to spread across the globe, diligent efforts are made to understand its attributes and dynamics to help develop treatment and prevention measures. The paradox pertaining to children being the least affected by severe illness poses exciting opportunities to investigate potential protective factors. In this paper, we propose that childhood vaccination against pertussis (whooping cough) might play a non-specific protective role against COVID-19 through heterologous adaptive responses in this young population. Pertussis is a vaccine-preventable infectious disease of the respiratory tract and it shares many similarities with COVID-19 including transmission and clinical features. Although pertussis is caused by a bacterium (Bordetella pertussis) while COVID-19 is a viral infection (SARS-CoV-2), previous data showed that cross-reactivity and heterologous adaptive responses can be seen with unrelated agents of highly divergent groups, such as between bacteria and viruses. While we build the arguments of this hypothesis on theoretical and previous empirical evidence, we also outline suggested lines of research from different fields to test its credibility. Besides, we highlight some concerns that may arise when attempting to consider such an approach as a potential public health preventive intervention against COVID-19., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2020
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11. TRPV1 Channels in Immune Cells and Hematological Malignancies.
- Author
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Omari SA, Adams MJ, and Geraghty DP
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- Animals, Humans, Mice, Hematologic Neoplasms pathology, Inflammation pathology, TRPV Cation Channels metabolism
- Abstract
Transient receptor potential vanilloid-1 (TRPV1) is a member of the TRP family of channels that are responsible for nociceptive, thermal, and mechanical sensations. Originally associated exclusively with sensory neurons, TRPV1 is now known to be present in almost all organs, including cells of the immune system, where TRPV1 has been shown to play a pivotal role in inflammation and immunity. Monocytes, macrophages, and dendritic cells express TRPV1, with both mouse and human studies suggesting that TRPV1 activation protects against endotoxin-induced inflammation. In contrast, TRPV1 (and other TRP channels) appears to be required for T-cell receptor activation by mitogens. Additionally, studies in cell lines derived from hematological and other malignancies suggest altered expression/function of TRPV1 might serve as a target for novel cytotoxic therapies., (© 2017 Elsevier Inc. All rights reserved.)
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- 2017
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12. Capsaicin-Induced Death of Human Haematological Malignant Cell Lines Is Independent of TRPV1 Activation.
- Author
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Omari SA, Adams MJ, Kunde DA, and Geraghty DP
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- Cannabinoid Receptor Antagonists pharmacology, Cell Death drug effects, Cell Line, Tumor, Humans, Indoles pharmacology, Oxazines metabolism, Piperidines pharmacology, Pyrazoles pharmacology, TRPV Cation Channels antagonists & inhibitors, Xanthenes metabolism, Capsaicin pharmacology, Hematologic Neoplasms metabolism
- Abstract
The effect of the plant-derived vanilloid, capsaicin (CAP), on the metabolic activity of THP-1, U266B1 and U937 hematological malignancy cells was determined. CAP reduced metabolic activity in a concentration-dependent manner in the three cell lines. A biphasic effect was observed on THP-1 cells (EC50: IC50 (95% CI) 32.9 (19.9-54.3)/219 (144-246) µmol/l). U266B1 cells were more resistant to CAP than THP-1 and U937. Metabolic activity was significantly inhibited by CAP in U937 compared to U266B1 cells (IC50: 197 versus 431 µmol/l, respectively, p < 0.008). Transient receptor potential vanilloid-1 (TRPV1) and CB1 antagonists (SB452533 and AM251, respectively) suppressed the CAP-induced increase in THP-1 cell metabolic activity (p < 0.001). AM251 and SB452533 appeared to act as partial agonists and displayed a synergistic effect with CAP in U937 cells. CAP inhibits the metabolic activity of malignant hematological cells through non-TRPV1-dependent mechanisms., (© 2016 S. Karger AG, Basel.)
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- 2016
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13. Influence of substitutions on asymmetric dihydroxychlorins with regard to intracellular uptake, subcellular localization and photosensitization of Jurkat cells.
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Rancan F, Wiehe A, Nöbel M, Senge MO, Omari SA, Böhm F, John M, and Röder B
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- Apoptosis drug effects, Biological Transport, Humans, Jurkat Cells, Molecular Structure, Necrosis, Phospholipids metabolism, Photosensitizing Agents pharmacology, Photosensitizing Agents toxicity, Porphyrins pharmacology, Porphyrins toxicity, Stereoisomerism, Hydroxides chemistry, Photosensitizing Agents chemistry, Photosensitizing Agents metabolism, Porphyrins chemistry, Porphyrins metabolism
- Abstract
The search for new efficient sensitizers for photodynamic therapy (PDT) points to improve photophysical properties like absorption in the red region and singlet oxygen quantum yield as well as to control the localization of the sensitizer within the tumour cell. Depending on their physicochemical properties and their uptake mechanism, sensitizers can reach different intracellular concentrations and localize in different subcellular compartments. Moreover, the preferential localization of a sensitizer in target organelles, like mitochondria or lysosomes, could determine the cell death mechanism after PDT. This study aimed to investigate the influence of substitutions on dihydroxychlorins with regard to intracellular uptake, subcellular localization and cell death pathway. Moreover, the effect of a liposome-based delivery system was tested. The intracellular uptake was found to be strictly dependent on the sensitizer molecular structure and the means of its delivery. The most polar sensitizer in this study (compound 3) had, depending on incubation time, an intracellular concentration 2-8 times higher than the unsubstituted chlorin 1. All investigated photosensitizers localize predominantly in lysosomes but after longer incubation times weak fluorescence intensity was also detected in mitochondria and Golgi apparatus. The cell death pathway was found to be influenced by the sensitizer intracellular concentration and the applied light doses. In general, the increasing amphiphilicity of the sensitizer molecules is correlated with an increased sensitizer uptake and an increased rate of necrotic cells after irradiation.
- Published
- 2005
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