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Colorectal cancer (CRC) development is a gradual process defined by the accumulation of numerous genetic mutations and epigenetic alterations leading to the adenoma-carcinoma sequence. Despite significant advances in the diagnosis and treatment of CRC, it continues to be a leading cause of cancer-related deaths worldwide. Even in the presence of oxygen, CRC cells bypass oxidative phosphorylation to produce metabolites that enable them to proliferate and survive—a phenomenon known as the “Warburg effect”. Understanding the complex glucose metabolism in CRC cells may support the development of new diagnostic and therapeutic approaches. Here we discuss the most recent findings on genetic mutations and epigenetic modulations that may positively or negatively regulate the Warburg effect in CRC cells. We focus on the non-coding RNA (ncRNA)-based epigenetics, and we present a perspective on the therapeutic relevance of critical molecules and ncRNAs mediating the Warburg effect in CRC cells. All the relevant studies were identified and assessed according to the genes and enzymes mediating the Warburg effect. The findings summarized in this review should provide a better understanding of the relevance of genetic mutations and the ncRNA-based epigenetic alterations to CRC pathogenesis to help overcome chemoresistance.
Batoul Abi Zamer; Wafaa Abumustafa; Mawieh Hamad; Azzam A. Maghazachi; Jibran Sualeh Muhammad. Genetic Mutations and Non-Coding RNA-Based Epigenetic Alterations Mediating the Warburg Effect in Colorectal Carcinogenesis. Biology 2021, 10, 847 .
AMA StyleBatoul Abi Zamer, Wafaa Abumustafa, Mawieh Hamad, Azzam A. Maghazachi, Jibran Sualeh Muhammad. Genetic Mutations and Non-Coding RNA-Based Epigenetic Alterations Mediating the Warburg Effect in Colorectal Carcinogenesis. Biology. 2021; 10 (9):847.
Chicago/Turabian StyleBatoul Abi Zamer; Wafaa Abumustafa; Mawieh Hamad; Azzam A. Maghazachi; Jibran Sualeh Muhammad. 2021. "Genetic Mutations and Non-Coding RNA-Based Epigenetic Alterations Mediating the Warburg Effect in Colorectal Carcinogenesis." Biology 10, no. 9: 847.
Objective: Herceptin (trastuzumab) is an approved drug for treating HER2+ breast cancer patients, but its use for other diseases is not established. We sought to investigate the effects of Herceptin on ameliorating experimental autoimmune encephalomyelitis (EAE) and to examine its effects on the expression of various genes. Methods: We used in-silico analysis of publicly available data, qRT-PCR, and immunohistochemistry (IHC) to determine the expression of HER2+ cells in the brains of EAE mice. IHC was also utilized to determine the anti-inflammatory effects of Herceptin. The ability of Herceptin to alleviate the EAE clinical score was measured in these mice. Bioinformatics analysis of publicly available data and qRT-PCR were performed to investigate the differentially expressed genes that were either up-regulated or down-regulated during the high clinical score (HCS) of the disease. Results: We observed that HER2/Erbb2, the receptor for Herceptin is upregulated in the brains of EAE mice when the brains were examined at the HCS stage. Further, we demonstrated that Herceptin ameliorates the EAE disease, increasing re-myelination, reducing brain inflammation, CD3+ T cell accumulation, and HER2+ cells in the brains of these mice. Molecular analysis demonstrated the expression of different genes that were either up-regulated or down-regulated during the HCS of the disease. Our combined bioinformatics and qRT-PCR analyses show increased mRNA expression of Atp6v0d2, C3, C3ar1, Ccl3, Ccl6, Cd74, Clec7a, Cybb, H2-Aa, Hspb1, Lilr4b, Lilrb4a, Mpeg1, Ms4a4a, Ms4a6c, Saa3, Serpina3n and Timp1, at HCS. Except for the mRNA levels of Cd74 and Clec7a which were increased at HCS when Herceptin was used in both prophylactic and therapeutic regimens, the levels of other described mRNAs were reduced. Conclusion: These novel findings show that Herceptin ameliorates the clinical score in EAE mice and are the first to investigate in detail the differential gene expression post-treatment with the drug.
Mena Al-Ani; Noha Mousaad Elemam; Ibrahim Y Hachim; Tom K Raju; Jibran Sualeh Muhammad; Mahmood Y Hachim; Riyad Bendardaf; Azzam A Maghazachi. Molecular Examination of Differentially Expressed Genes in the Brains of Experimental Autoimmune Encephalomyelitis Mice Post Herceptin Treatment. Journal of Inflammation Research 2021, ume 14, 2601 -2617.
AMA StyleMena Al-Ani, Noha Mousaad Elemam, Ibrahim Y Hachim, Tom K Raju, Jibran Sualeh Muhammad, Mahmood Y Hachim, Riyad Bendardaf, Azzam A Maghazachi. Molecular Examination of Differentially Expressed Genes in the Brains of Experimental Autoimmune Encephalomyelitis Mice Post Herceptin Treatment. Journal of Inflammation Research. 2021; ume 14 ():2601-2617.
Chicago/Turabian StyleMena Al-Ani; Noha Mousaad Elemam; Ibrahim Y Hachim; Tom K Raju; Jibran Sualeh Muhammad; Mahmood Y Hachim; Riyad Bendardaf; Azzam A Maghazachi. 2021. "Molecular Examination of Differentially Expressed Genes in the Brains of Experimental Autoimmune Encephalomyelitis Mice Post Herceptin Treatment." Journal of Inflammation Research ume 14, no. : 2601-2617.
Chemokines are soluble mediators that are expressed on immune and non-immune cells in various species, and are critical for their survival and homeostasis. They are key players in the development, function and migration of innate and adaptive immune cells including macrophages, neutrophils, dendritic cells, natural killer cells, B and T cells. In viral, bacterial and parasitic infections, chemokines try to recruit immune cells in order to induce inflammation and promote pathogen clearance. However, some chemokines were found to be detrimental and cause excessive inflammation and pathologies.
Noha Mousaad Elemam; Bariaa A. Khalil; Azzam A. Maghazachi. Chemokines and Chemokine Receptors. Reference Module in Biomedical Sciences 2021, 1 .
AMA StyleNoha Mousaad Elemam, Bariaa A. Khalil, Azzam A. Maghazachi. Chemokines and Chemokine Receptors. Reference Module in Biomedical Sciences. 2021; ():1.
Chicago/Turabian StyleNoha Mousaad Elemam; Bariaa A. Khalil; Azzam A. Maghazachi. 2021. "Chemokines and Chemokine Receptors." Reference Module in Biomedical Sciences , no. : 1.
In March 2020, COVID-19 infection caused by SARS-CoV-2 has been declared to be a global pandemic, where its complications, severity and mortality are reported to be due to the released inflammatory cytokines or the so-called cytokine storm. This is quite similar to that observed in the autoimmune and chronic inflammatory rheumatic disease, rheumatoid arthritis (RA). It was hypothesized that RA patients are at a higher risk of acquiring COVID-19; however, recent studies reported that they are not when compared to the rest of the population. In this review, we aim to highlight the mutual pathological features, cytokine profiles and risk factors between COVID-19 and RA. Also, many researchers are currently working to explore therapeutic agents that could aid in the eradication of COVID-19 infection. Due to the similarity between the inflammation status in COVID-19 and RA, many anti-rheumatic drugs such as hydroxychloroquine, tocilizumab, baricitinib and anakinra were proposed to be therapeutic modalities for COVID-19 infection.
Noha Mousaad Elemam; Azzam A. Maghazachi; Suad Hannawi. COVID-19 infection and rheumatoid arthritis: mutual outburst cytokines and remedies. Current Medical Research and Opinion 2021, 37, 929 -938.
AMA StyleNoha Mousaad Elemam, Azzam A. Maghazachi, Suad Hannawi. COVID-19 infection and rheumatoid arthritis: mutual outburst cytokines and remedies. Current Medical Research and Opinion. 2021; 37 (6):929-938.
Chicago/Turabian StyleNoha Mousaad Elemam; Azzam A. Maghazachi; Suad Hannawi. 2021. "COVID-19 infection and rheumatoid arthritis: mutual outburst cytokines and remedies." Current Medical Research and Opinion 37, no. 6: 929-938.
Multiple sclerosis (MS) is a chronic autoimmune disease that affects the myelination of the neurons present in the central nervous system (CNS). The exact etiology of MS development is unclear, but various environmental and genetic factors might play a role in initiating the disease. Experimental autoimmune encephalomyelitis (EAE) is a mouse model that is used to study the pathophysiology of MS disease as well as the effects of possible therapeutic agents. In addition, autoreactive immune cells trigger an inflammatory process upon the recognition of CNS antigens, which leads to destruction of the neurons. These include innate immune cells such as macrophages, dendritic cells, and natural killer cells. Additionally, the activation and extravasation of adaptive immune cells such as CD4+ T cells into the CNS may lead to further exacerbation of the disease. However, many studies revealed that immune cells could have either a protective or pathological role in MS. In this review, we highlight the roles of innate and adaptive immune cellular and soluble players that contribute to the pathogenesis of MS and EAE, which may be used as potential targets for therapy.
Sarah Dhaiban; Mena Al-Ani; Noha Elemam; Mahmood Al-Aawad; Zeinab Al-Rawi; Azzam Maghazachi. Role of Peripheral Immune Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis. Sci 2021, 3, 12 .
AMA StyleSarah Dhaiban, Mena Al-Ani, Noha Elemam, Mahmood Al-Aawad, Zeinab Al-Rawi, Azzam Maghazachi. Role of Peripheral Immune Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis. Sci. 2021; 3 (1):12.
Chicago/Turabian StyleSarah Dhaiban; Mena Al-Ani; Noha Elemam; Mahmood Al-Aawad; Zeinab Al-Rawi; Azzam Maghazachi. 2021. "Role of Peripheral Immune Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis." Sci 3, no. 1: 12.
Chemokines are crucial inflammatory mediators needed during an immune response to clear pathogens. However, their excessive release is the main cause of hyperinflammation. In the recent COVID-19 outbreak, chemokines may be the direct cause of acute respiratory disease syndrome, a major complication leading to death in about 40% of severe cases. Several clinical investigations revealed that chemokines are directly involved in the different stages of SARS-CoV-2 infection. Here, we review the role of chemokines and their receptors in COVID-19 pathogenesis to better understand the disease immunopathology which may aid in developing possible therapeutic targets for the infection.
Bariaa A. Khalil; Noha Mousaad Elemam; Azzam A. Maghazachi. Chemokines and chemokine receptors during COVID-19 infection. Computational and Structural Biotechnology Journal 2021, 19, 976 -988.
AMA StyleBariaa A. Khalil, Noha Mousaad Elemam, Azzam A. Maghazachi. Chemokines and chemokine receptors during COVID-19 infection. Computational and Structural Biotechnology Journal. 2021; 19 ():976-988.
Chicago/Turabian StyleBariaa A. Khalil; Noha Mousaad Elemam; Azzam A. Maghazachi. 2021. "Chemokines and chemokine receptors during COVID-19 infection." Computational and Structural Biotechnology Journal 19, no. : 976-988.
Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by varying degrees of demyelination of uncertain etiology, and is associated with specific environmental and genetic factors. Upon recognition of CNS antigens, the immune cells initiate an inflammatory process which leads to destruction and deterioration of the neurons. Innate immune cells such as macrophages, dendritic cells and natural killer cells are known to play critical roles in the pathogenesis of MS. Also, the activation of peripheral CD4+ T cells by CNS antigens leads to their extravasation into the CNS causing damages that exacerbates the disease. This could be accompanied by dysregulation of T regulatory cells and other cell types functions. Experimental autoimmune encephalomyelitis (EAE) is a mouse model used to study the pathophysiology of MS disease. In this review, we highlight the roles of innate and adaptive immune players in the pathogenesis of MS and EAE.
Sarah Dhaiban; Mena Al-Ani; Noha Mousaad Elemam; Mahmood H Al-Aawad; Zeinab Al-Rawi; Azzam A. Maghazachi. Role of Immune Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis. 2020, 1 .
AMA StyleSarah Dhaiban, Mena Al-Ani, Noha Mousaad Elemam, Mahmood H Al-Aawad, Zeinab Al-Rawi, Azzam A. Maghazachi. Role of Immune Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis. . 2020; ():1.
Chicago/Turabian StyleSarah Dhaiban; Mena Al-Ani; Noha Mousaad Elemam; Mahmood H Al-Aawad; Zeinab Al-Rawi; Azzam A. Maghazachi. 2020. "Role of Immune Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis." , no. : 1.
COVID-19 infection caused by the newly discovered coronavirus severe acute respiratory distress syndrome virus-19 (SARS-CoV-2) has become a pandemic issue across the globe. There are currently many investigations taking place to look for specific, safe and potent anti-viral agents. Upon transmission and entry into the human body, SARS-CoV-2 triggers multiple immune players to be involved in the fight against the viral infection. Amongst these immune cells are NK cells that possess robust antiviral activity, and which do not require prior sensitization. However, NK cell count and activity were found to be impaired in COVID-19 patients and hence, could become a potential therapeutic target for COVID-19. Several drugs, including glatiramer acetate (GA), vitamin D3, dimethyl fumarate (DMF), monomethyl fumarate (MMF), natalizumab, ocrelizumab, and IFN-β, among others have been previously described to increase the biological activities of NK cells especially their cytolytic potential as reported by upregulation of CD107a, and the release of perforin and granzymes. In this review, we propose that such drugs could potentially restore NK cell activity allowing individuals to be more protective against COVID-19 infection and its complications.
Mena Al-Ani; Noha Mousaad Elemam; Jennifer Elisabeth Hundt; Azzam A Maghazachi. Drugs for Multiple Sclerosis Activate Natural Killer Cells: Do They Protect Against COVID-19 Infection? Infection and Drug Resistance 2020, ume 13, 3243 -3254.
AMA StyleMena Al-Ani, Noha Mousaad Elemam, Jennifer Elisabeth Hundt, Azzam A Maghazachi. Drugs for Multiple Sclerosis Activate Natural Killer Cells: Do They Protect Against COVID-19 Infection? Infection and Drug Resistance. 2020; ume 13 ():3243-3254.
Chicago/Turabian StyleMena Al-Ani; Noha Mousaad Elemam; Jennifer Elisabeth Hundt; Azzam A Maghazachi. 2020. "Drugs for Multiple Sclerosis Activate Natural Killer Cells: Do They Protect Against COVID-19 Infection?" Infection and Drug Resistance ume 13, no. : 3243-3254.
Multiple sclerosis (MS) is an immune-mediated and neurodegenerative disorder that results in inflammation and demyelination of the central nervous system (CNS). MS symptoms include walking difficulties, visual weakening, as well as learning and memory impairment, thus affecting the quality of the patient’s life. Chemokines and chemokine receptors are expressed on the immune cells as well as the CNS resident cells. Several sets of chemokine receptors and their ligands tend to be pathogenic players in MS, including CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL17, CCL19, CCL21, CCL22, CXCL1, CXCL8, CXCL9, CXCL10, CXCL11, and CXCL16. Furthermore, current modulatory drugs that are used in the treatment of MS and its animal model, the experimental autoimmune encephalomyelitis (EAE), affect the expression of several chemokine and chemokine receptors. In this review, we highlight the pathogenic roles of chemokines and their receptors as well as utilizing them as potential therapeutic targets through selective agents, such as specific antibodies and receptor blockers, or indirectly through MS or EAE immunomodulatory drugs.
Sarah Dhaiban; Mena Al-Ani; Noha Mousaad Elemam; Azzam A Maghazachi. Targeting Chemokines and Chemokine Receptors in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis. Journal of Inflammation Research 2020, ume 13, 619 -633.
AMA StyleSarah Dhaiban, Mena Al-Ani, Noha Mousaad Elemam, Azzam A Maghazachi. Targeting Chemokines and Chemokine Receptors in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis. Journal of Inflammation Research. 2020; ume 13 ():619-633.
Chicago/Turabian StyleSarah Dhaiban; Mena Al-Ani; Noha Mousaad Elemam; Azzam A Maghazachi. 2020. "Targeting Chemokines and Chemokine Receptors in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis." Journal of Inflammation Research ume 13, no. : 619-633.
The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy.
Israa Shihab; Bariaa A. Khalil; Noha Mousaad Elemam; Ibrahim Y. Hachim; Mahmood Yaseen Hachim; Rifat A. Hamoudi; Azzam A. Maghazachi. Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment. Cancers 2020, 12, 2226 .
AMA StyleIsraa Shihab, Bariaa A. Khalil, Noha Mousaad Elemam, Ibrahim Y. Hachim, Mahmood Yaseen Hachim, Rifat A. Hamoudi, Azzam A. Maghazachi. Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment. Cancers. 2020; 12 (8):2226.
Chicago/Turabian StyleIsraa Shihab; Bariaa A. Khalil; Noha Mousaad Elemam; Ibrahim Y. Hachim; Mahmood Yaseen Hachim; Rifat A. Hamoudi; Azzam A. Maghazachi. 2020. "Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment." Cancers 12, no. 8: 2226.
Current guidelines for COVID-19 management recommend the utilization of various repurposed drugs. Despite ongoing research toward the development of a vaccine against SARS-CoV-2, such a vaccine will not be available in time to contribute to the containment of the ongoing pandemic. Therefore, there is an urgent need to develop a framework for the rapid identification of novel targets for diagnostic and therapeutic interventions. We analyzed publicly available transcriptomic datasets of SARS-CoV infected humans and mammals to identify consistent differentially expressed genes then validated in SARS-CoV-2 infected epithelial cells transcriptomic datasets. Comprehensive toxicogenomic analysis of the identified genes to identify possible interactions with clinically proven drugs was carried out. We identified IFITM3 as an early upregulated gene, and valproic acid was found to enhance its mRNA expression as well as induce its antiviral action. These findings indicate that analysis of publicly available transcriptomic and toxicogenomic data represents a rapid approach for the identification of novel targets and molecules that can modify the action of such targets during the early phases of emerging infections like COVID-19.
Mahmood Hachim; Saba Al Heialy; Ibrahim Yaseen Hachim; Rabih Halwani; Abiola C. Senok; Azzam Maghazachi; Qutayba Hamid. Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells. Frontiers in Immunology 2020, 11, 1372 .
AMA StyleMahmood Hachim, Saba Al Heialy, Ibrahim Yaseen Hachim, Rabih Halwani, Abiola C. Senok, Azzam Maghazachi, Qutayba Hamid. Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells. Frontiers in Immunology. 2020; 11 ():1372.
Chicago/Turabian StyleMahmood Hachim; Saba Al Heialy; Ibrahim Yaseen Hachim; Rabih Halwani; Abiola C. Senok; Azzam Maghazachi; Qutayba Hamid. 2020. "Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells." Frontiers in Immunology 11, no. : 1372.
Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases, while its molecular triggers are not fully understood. A few studies have shown that natural killer (NK) cells may play either a pathogenic or a protective role in RA. In this study, we sought to explore NK cell markers that could be plausibly used in evaluating the differences among healthy controls and RA patients. Publicly available transcriptome datasets from RA patients and healthy volunteers were analyzed, in order to identify differentially expressed genes (DEGs) between 1. different immune cells as compared to NK cells, and 2. NK cells of RA patients and healthy controls. The identified DEGs were validated using 16 healthy controls and 17 RA patients. Peripheral blood mononuclear cells (PBMCs) were separated by Ficoll density gradient method, while NK cells were isolated using RosetteSep technique. RNA was extracted and gene expression was assessed using RT-qPCR. All selected genes were differentially expressed in NK cells compared to PBMCs. CD56, CXCL16, PECAM-1, ITGB7, BTK, TLR10, and IL-1β were significantly upregulated, while CCL2, CCR4, RELA and IBTK were downregulated in the NK cells of RA patients when compared to healthy controls. Therefore, these NK specific genes might be used as promising biomarkers for RA diagnosis.
Noha Mousaad Elemam; Mahmood Yaseen Hachim; Suad Hannawi; Azzam A. Maghazachi. Differentially Expressed Genes of Natural Killer Cells Can Distinguish Rheumatoid Arthritis Patients from Healthy Controls. Genes 2020, 11, 492 .
AMA StyleNoha Mousaad Elemam, Mahmood Yaseen Hachim, Suad Hannawi, Azzam A. Maghazachi. Differentially Expressed Genes of Natural Killer Cells Can Distinguish Rheumatoid Arthritis Patients from Healthy Controls. Genes. 2020; 11 (5):492.
Chicago/Turabian StyleNoha Mousaad Elemam; Mahmood Yaseen Hachim; Suad Hannawi; Azzam A. Maghazachi. 2020. "Differentially Expressed Genes of Natural Killer Cells Can Distinguish Rheumatoid Arthritis Patients from Healthy Controls." Genes 11, no. 5: 492.
Background: Insulin-like growth factor 1 receptor (IGF1R) activation triggers multiple signaling pathways involved in proliferation and anti-apoptosis in breast cancer (BC). Materials and Methods: Immunohistochemistry for IGF1R was performed on 50 BC cases; expression was assessed for staining intensity and localization pattern (mixed, membranous, and cytoplasmic) which was correlated to hormone receptor status. Results: Of estrogen receptor-positive (ER+) cases, 97.2% were IGF1R+ (48.6% mixed, 43.2% membranous, and 5.4% cytoplasmic pattern) compared to ER− cases (38.5%, 7.7% and 30.8%, respectively) (p=0.003). In progesterone receptor-positive (PR+) cases, 97.2% were IGF1R+, (47.2%, 41.7% and 8.3%, respectively) compared to PR− ones (42.9%, 14.3% and 21.4%, respectively) (p=0.036). For human epidermal growth factor receptor 2-negative (HER2−) cases, 88.8% were IGF1R+ (44.4%, 8.3% and 36.1%, respectively). All HER2+ cases were IGF1R+ (71.4%, 7.1% and 21.4%, respectively) (p=0.015). In conclusion, hormone receptor-positive HER2− cases showed membranous and mixed IGF1R localization. However, hormone receptor-negative and HER2+ showed cytoplasmic or diminished IGF1R expression. Conclusion: These luminal subtypes may benefit from targeted IGFR therapy in the future.
Noura Alkhayyal; Iman Talaat; Arya Vinodnadat; Azzam Maghazachi; Salah Abusnana; Kari Syrjänen; Riyad Bendardaf. Correlation of Insulin-like Growth Factor 1 Receptor Expression With Different Molecular Subtypes of Breast Cancer in the UAE. Anticancer Research 2020, 40, 1555 -1561.
AMA StyleNoura Alkhayyal, Iman Talaat, Arya Vinodnadat, Azzam Maghazachi, Salah Abusnana, Kari Syrjänen, Riyad Bendardaf. Correlation of Insulin-like Growth Factor 1 Receptor Expression With Different Molecular Subtypes of Breast Cancer in the UAE. Anticancer Research. 2020; 40 (3):1555-1561.
Chicago/Turabian StyleNoura Alkhayyal; Iman Talaat; Arya Vinodnadat; Azzam Maghazachi; Salah Abusnana; Kari Syrjänen; Riyad Bendardaf. 2020. "Correlation of Insulin-like Growth Factor 1 Receptor Expression With Different Molecular Subtypes of Breast Cancer in the UAE." Anticancer Research 40, no. 3: 1555-1561.
Objective: To investigate, in detail, the effects of rituximab (RTX), an off-label drug for treating multiple sclerosis (MS) disease on preventing and/or ameliorating experimental autoimmune encephalomyelitis (EAE). Methods: Using bioinformatics analysis of publicly available transcriptomics data, we determined the accumulation of B cells, plasma cells and T cells in different compartments of multiple sclerosis patients (MS) and healthy individual brains. Based on these observations and on the literature search, we dosed RTX in EAE mice either orally, or injected intraperitoneally (IP). The latter route was used either prophylactically (asymptomatic stage; upon the induction of the disease), or therapeutically (acute stage; upon the appearance of the first sign of the disease). Further, we used RTX as a preventive drug either as a single agent or in combination with other routes of administration. Results: Because no complete recovery was observed when RTX was used prophylactically or therapeutically, we devised another protocol of injecting this drug before the onset of the disease and designated this regiment as prevention. We demonstrated that the 20 μg/mouse prevention completely reduced the EAE clinical score, impaired infiltration of T and B cells into the perivascular space of mice brains, along with inhibiting the inflammation and demyelination. However, the 5 and 10 μg/mouse doses although reduced all aspects of inflammation in these mice, their effects were not as potent as the 20 μg/mouse RTX dose. Finally, we combined the 5 μg/mouse prevention treatment with either the prophylactic or therapeutic regimen and observed a robust effect. Conclusion: We observed that combinatorial regimens resulted in further reduction of inflammation, T and B cell extravasation into the brains of EAE mice and improved the re-myelination.
Mena R Al-Ani; Tom K Raju; Mahmood Y Hachim; Ibrahim Y Hachim; Noha M Elemam; Maha Guimei; Riyad Bendardaf; Azzam A Maghazachi. Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens. Journal of Inflammation Research 2020, ume 13, 151 -164.
AMA StyleMena R Al-Ani, Tom K Raju, Mahmood Y Hachim, Ibrahim Y Hachim, Noha M Elemam, Maha Guimei, Riyad Bendardaf, Azzam A Maghazachi. Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens. Journal of Inflammation Research. 2020; ume 13 ():151-164.
Chicago/Turabian StyleMena R Al-Ani; Tom K Raju; Mahmood Y Hachim; Ibrahim Y Hachim; Noha M Elemam; Maha Guimei; Riyad Bendardaf; Azzam A Maghazachi. 2020. "Rituximab Prevents the Development of Experimental Autoimmune Encephalomyelitis (EAE): Comparison with Prophylactic, Therapeutic or Combinational Regimens." Journal of Inflammation Research ume 13, no. : 151-164.
Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases and a prototypic inflammatory disease, affecting the small joints of the hands and feet. Chemokines and chemokine receptors play a critical role in RA pathogenesis via immune cells recruitment. Several chemokines and chemokine receptors are abundant in the peripheral blood and in the local inflamed joints of RA. Furthermore, synthetic and biologics disease modifying anti rheumatic drugs have been reported to affect chemokines expression. Thus, many studies have focused on targeting chemokines and chemokine receptors, where some have shown positive promising results. However, most of the chemokine blockers in human trials of RA treatment displayed some failures that can be attributed to several reasons in their structures and binding affinities. Nevertheless, targeting chemokines will continue to be under development, in order to improve their therapeutic potentials in RA and other autoimmune diseases. In this review we provide an up-to-date knowledge regarding the role of chemokines and chemokine receptors in RA with an emphasis on their activities on immune cells. We also discussed the effects of drugs targeting those molecules in RA. This knowledge might provide impetus for developing new therapeutic modalities to treat this chronic disease.
Noha Mousaad Elemam; Suad Hannawi; Azzam A Maghazachi. Role of Chemokines and Chemokine Receptors in Rheumatoid Arthritis. ImmunoTargets and Therapy 2020, ume 9, 43 -56.
AMA StyleNoha Mousaad Elemam, Suad Hannawi, Azzam A Maghazachi. Role of Chemokines and Chemokine Receptors in Rheumatoid Arthritis. ImmunoTargets and Therapy. 2020; ume 9 ():43-56.
Chicago/Turabian StyleNoha Mousaad Elemam; Suad Hannawi; Azzam A Maghazachi. 2020. "Role of Chemokines and Chemokine Receptors in Rheumatoid Arthritis." ImmunoTargets and Therapy ume 9, no. : 43-56.
Pyroptosis is a newly discovered programmed cell death with inflammasome formation. Pattern recognition receptors that identify repetitive motifs of prospective pathogens such as LPS of gram‐negative bacteria are crucial to pyroptosis. Upon stimulation by pathogen‐associated molecular patterns or damage‐associated molecular patterns, proinflammatory cytokines, mainly IL‐1 family members IL‐1β and IL‐18, are released through pyroptosis specific pore‐forming protein, gasdermin D. Even though IL‐1 family members are mainly involved in innate immunity, they can be factors in adaptive immunity. Given the importance of IL‐1 family members in health and diseases, deciphering the role of pyroptosis in the regulation of innate and adaptive immunity is of great importance, especially with the recent progress in identifying the exact mechanism of such a pathway. In this review, we will focus on how the innate inflammatory mediators can regulate the adaptive immune system and vice versa via pyroptosis.
Mahmood Hachim; Bariaa A. Khalil; Noha Mousaad Elemam; Azzam A. Maghazachi. Pyroptosis: The missing puzzle among innate and adaptive immunity crosstalk. Journal of Leukocyte Biology 2020, 108, 323 -338.
AMA StyleMahmood Hachim, Bariaa A. Khalil, Noha Mousaad Elemam, Azzam A. Maghazachi. Pyroptosis: The missing puzzle among innate and adaptive immunity crosstalk. Journal of Leukocyte Biology. 2020; 108 (1):323-338.
Chicago/Turabian StyleMahmood Hachim; Bariaa A. Khalil; Noha Mousaad Elemam; Azzam A. Maghazachi. 2020. "Pyroptosis: The missing puzzle among innate and adaptive immunity crosstalk." Journal of Leukocyte Biology 108, no. 1: 323-338.
Introduction: Although natural killer (NK) are major cells used to treat cancer patients, recent clinical trials showed that NK92 cells can be also used for the same purpose due to their high anti-tumor activity. Here, we examined whether these cells might be inflammatory due to the release of interleukin-1β (IL-1β), and whether the anti-inflammatory molecules dimethyl fumarate (DMF), or monomethyl fumarate (MMF) impair this activity. Methods: NK92 cells were examined for the synthesis and release of IL-1β utilizing RT-PCR and ELISA assay, respectively. The expression of hydroxy-carboxylic acid receptors (HCA)1, HCA2 and HCA3 was detected by immunoblotting, flow cytometry, immunofluorescence and RT-PCR assays. The activation of caspase-1 and Gasdermin D (GSDMD) was evaluated by immunoblot assay. Pyroptosis was demonstrated by immunofluorescence imaging. Expression of DNA methyltransferases (DNMTs) mRNA was determined by whole transcriptome and immunoblot analyses. Results: LPS-induced the release of IL-1β from NK92 cells, whereas DMF or MMF inhibited this induction. The effect of these drugs was due to inhibiting the conversion of procaspase-1 into active caspase-1. NK92 cells highly expressed GSDMD, a pyroptotic-mediated molecule. However, LPS induced the distribution of GSDMD into the cell membranes, corroborated with the presence of pyroptotic bodies, an activity that was inhibited by DMF or MMF. These molecule also inhibited the generation of GSDMD through DNMT-mediated hypermethylation of the promoter region of GSDMD gene. These results were supported by increased expression of DNMTs mRNA as determined by whole transcriptome analysis. Discussion: Our results are the first to show that NK92 cells utilize GSDMD pathway to release IL-1β. Further, DMF and MMF which were previously shown to enhance NK cell cytotoxicity, also inhibit the inflammatory effects of these cells, making them most suitable for treating cancer patients.
Jibran Sualeh Muhammad; Manju Nidagodu Jayakumar; Noha Mousaad Elemam; Thenmozhi Venkatachalam; Tom Kalathil Raju; Rifat Akram Hamoudi; Azzam A. Maghazachi. Gasdermin D Hypermethylation Inhibits Pyroptosis And LPS-Induced IL-1β Release From NK92 Cells. ImmunoTargets and Therapy 2019, ume 8, 29 -41.
AMA StyleJibran Sualeh Muhammad, Manju Nidagodu Jayakumar, Noha Mousaad Elemam, Thenmozhi Venkatachalam, Tom Kalathil Raju, Rifat Akram Hamoudi, Azzam A. Maghazachi. Gasdermin D Hypermethylation Inhibits Pyroptosis And LPS-Induced IL-1β Release From NK92 Cells. ImmunoTargets and Therapy. 2019; ume 8 ():29-41.
Chicago/Turabian StyleJibran Sualeh Muhammad; Manju Nidagodu Jayakumar; Noha Mousaad Elemam; Thenmozhi Venkatachalam; Tom Kalathil Raju; Rifat Akram Hamoudi; Azzam A. Maghazachi. 2019. "Gasdermin D Hypermethylation Inhibits Pyroptosis And LPS-Induced IL-1β Release From NK92 Cells." ImmunoTargets and Therapy ume 8, no. : 29-41.
We recently reported that pretreatment of IL-2 activated human natural killer (NK) cells with the drugs dimethyl fumarate (DMF) and monomethyl fumarate (MMF) upregulated the expression of surface chemokine receptor CCR10. Ligands for CCR10, namely CCL27 and CCL28, induced the chemotaxis of these cells. Here, we performed a bioinformatics analysis to see which chemokines might be expressed by the human HCT-116 colorectal cancer cells. We observed that, in addition to CCL27 and CCL28, HCT-116 colorectal cancer cells profoundly express CXCL16 which binds CXCR6. Consequently, NK92 cells were treated with DMF and MMF for 24 h to investigate in vitro chemotaxis towards CXCL16, CCL27, and CCL28. Furthermore, supernatants collected from HCT-116 cells after 24 or 48 h incubation induced the chemotaxis of NK92 cells. Similar to their effects on human IL-2-activated NK cells, MMF and DMF enhanced the expression of CCR10 and CXCR6 in NK92 cells. Neutralizing anti-CXCL16 or anti-CCL28 inhibited the chemotactic effects of 24 and 48 supernatants, whereas anti-CCL27 only inhibited the 48 h supernatant activity, suggesting that 24 h supernatant contains CXCL16 and CCL28, whereas HCT-116 secretes all three chemokines after 48 h in vitro cultures. CXCL16, CCL27, and CCL28, as well as the supernatants collected from HCT-116, induced the mobilization of (Ca)2+ in NK92 cells. Cross-desensitization experiments confirmed the results of the chemotaxis experiments. Finally, incubation of NK92 cells with HCT-116 induced the lysis of the tumor cells. In summary, these results might have important implications in directing the anti-tumor effectors NK cells towards tumor growth sites.
Noha Mousaad Elemam; Zaidoon Al-Jaderi; Mahmood Hachim; Azzam A. Maghazachi. HCT-116 colorectal cancer cells secrete chemokines which induce chemoattraction and intracellular calcium mobilization in NK92 cells. Cancer Immunology, Immunotherapy 2019, 68, 883 -895.
AMA StyleNoha Mousaad Elemam, Zaidoon Al-Jaderi, Mahmood Hachim, Azzam A. Maghazachi. HCT-116 colorectal cancer cells secrete chemokines which induce chemoattraction and intracellular calcium mobilization in NK92 cells. Cancer Immunology, Immunotherapy. 2019; 68 (6):883-895.
Chicago/Turabian StyleNoha Mousaad Elemam; Zaidoon Al-Jaderi; Mahmood Hachim; Azzam A. Maghazachi. 2019. "HCT-116 colorectal cancer cells secrete chemokines which induce chemoattraction and intracellular calcium mobilization in NK92 cells." Cancer Immunology, Immunotherapy 68, no. 6: 883-895.
Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system is common amongst young adults, leading to major personal and socioeconomic burdens. However, it is still considered complex and challenging to understand and treat, in spite of the efforts made to explain its etiopathology. Despite the discovery of many genetic and environmental factors that might be related to its etiology, no clear answer was found about the causes of the illness and neither about the detailed mechanism of these environmental triggers that make individuals susceptible to MS. In this review, we will attempt to explore the major contributors to MS autoimmunity including genetic, epigenetic and ecological factors with a particular focus on toxins, chemicals or drugs that may trigger, modify or prevent MS disease.
Mahmood Y. Hachim; Noha M. Elemam; Azzam A. Maghazachi. The Beneficial and Debilitating Effects of Environmental and Microbial Toxins, Drugs, Organic Solvents and Heavy Metals on the Onset and Progression of Multiple Sclerosis. Toxins 2019, 11, 147 .
AMA StyleMahmood Y. Hachim, Noha M. Elemam, Azzam A. Maghazachi. The Beneficial and Debilitating Effects of Environmental and Microbial Toxins, Drugs, Organic Solvents and Heavy Metals on the Onset and Progression of Multiple Sclerosis. Toxins. 2019; 11 (3):147.
Chicago/Turabian StyleMahmood Y. Hachim; Noha M. Elemam; Azzam A. Maghazachi. 2019. "The Beneficial and Debilitating Effects of Environmental and Microbial Toxins, Drugs, Organic Solvents and Heavy Metals on the Onset and Progression of Multiple Sclerosis." Toxins 11, no. 3: 147.
Innate lymphoid cells (ILCs) are an emerging group of immune cells that provide the first line of defense against various pathogens as well as contributing to tissue repair and inflammation. ILCs have been classically divided into three subgroups based on their cytokine secretion and transcription factor profiles. ILC nomenclature is analogous to that of T helper cells. Group 1 ILCs composed of natural killer (NK) cells as well as IFN-γ secreting ILC1s. ILC2s have the capability to produce TH2 cytokines while ILC3s and lymphoid tissue inducer (LTis) are subsets of cells that are able to secrete IL-17 and/or IL-22. A recent subset of ILC known as ILC4 was discovered, and the cells of this subset were designated as NK17/NK1 due to their release of IL-17 and IFN-γ. In this review, we sought to explain the subclasses of ILCs and their roles as mediators of lytic enzymes and inflammation.
Noha Mousaad Elemam; Suad Hannawi; Azzam A. Maghazachi. Innate Lymphoid Cells (ILCs) as Mediators of Inflammation, Release of Cytokines and Lytic Molecules. Toxins 2017, 9, 398 .
AMA StyleNoha Mousaad Elemam, Suad Hannawi, Azzam A. Maghazachi. Innate Lymphoid Cells (ILCs) as Mediators of Inflammation, Release of Cytokines and Lytic Molecules. Toxins. 2017; 9 (12):398.
Chicago/Turabian StyleNoha Mousaad Elemam; Suad Hannawi; Azzam A. Maghazachi. 2017. "Innate Lymphoid Cells (ILCs) as Mediators of Inflammation, Release of Cytokines and Lytic Molecules." Toxins 9, no. 12: 398.