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Background The extensive genetic heterogeneity found in the B cell precursor acute lymphoblastic leukemia (BCP-ALL) subtype of childhood ALL represents a potential repository of biomarkers. To explore this potential, we have carried out in silico analysis of publicly available ALL datasets to identify genetic biomarkers for childhood BCP-ALL, which could be used either individually or in combination as markers for early detection, risk stratification, and prognosis. Methods To explore novel genes that show promising clinical and molecular signatures, we examined the cBioPortal online tool for publicly available datasets on lymphoid cancers. Three studies on lymphoblastic and lymphoid leukemia with 1706 patients and 2144 samples of which were identified. Only B-Lymphoblastic Leukemia/Lymphoma samples (n = 1978) were selected for further analysis. Chromosomal changes were assessed to determine novel genomic loci to analyze clinical and molecular profiles for the leukemia of lymphoid origin using cBioPortal tool. Results ADAM6 gene homozygous deletions (HOM:DEL) were present in 59.60% of the profiled patients and were associated with poor ten years of overall patients’ survival. Moreover, patients with ADAM6 HOM:DEL showed a distinguished clinical and molecular profile with higher Central Nervous System (CNS) sites of relapse. In addition, ADAM6 HOM:DEL was significantly associated with unique microRNAs gene expression patterns. Conclusion ADAM6 has the potential to be a novel biomarker for the development and progress of BCP- ALL.
Laila Alsuwaidi; Mahmood Hachim; Abiola Senok. Novel Markers in Pediatric Acute Lymphoid Leukemia: The Role of ADAM6 in B Cell Leukemia. Frontiers in Cell and Developmental Biology 2021, 9, 1 .
AMA StyleLaila Alsuwaidi, Mahmood Hachim, Abiola Senok. Novel Markers in Pediatric Acute Lymphoid Leukemia: The Role of ADAM6 in B Cell Leukemia. Frontiers in Cell and Developmental Biology. 2021; 9 ():1.
Chicago/Turabian StyleLaila Alsuwaidi; Mahmood Hachim; Abiola Senok. 2021. "Novel Markers in Pediatric Acute Lymphoid Leukemia: The Role of ADAM6 in B Cell Leukemia." Frontiers in Cell and Developmental Biology 9, no. : 1.
In asthma, most of the identified biomarkers pertain to the Th2 phenotype and no known biomarkers have been verified for severe asthmatics. Therefore, identifying biomarkers using the integrative phenotype-genotype approach in severe asthma is needed. The study aims to identify novel biomarkers as genes or pathways representing the core drivers in asthma development, progression to the severe form, resistance to therapy, and tissue remodeling regardless of the sample cells or tissues examined. Comprehensive reanalysis of publicly available transcriptomic data that later was validated in vitro, and locally recruited patients were used to decipher the molecular basis of asthma. Our in-silicoanalysis revealed a total of 10 genes (GPRC5A, SFN, ABCA1, KRT8, TOP2A, SERPINE1, ANLN, MKI67, NEK2, and RRM2) related to cell cycle and proliferation to be deranged in the severe asthmatic bronchial epithelium and fibroblasts compared to their healthy counterparts. In vitro, RT qPCR results showed that (SERPINE1 and RRM2) were upregulated in severe asthmatic bronchial epithelium and fibroblasts, (SFN, ABCA1, TOP2A, SERPINE1, MKI67, and NEK2) were upregulated in asthmatic bronchial epithelium while (GPRC5A and KRT8) were upregulated only in asthmatic bronchial fibroblasts. Furthermore, MKI76, RRM2, and TOP2A were upregulated in Th2 high epithelium while GPRC5A, SFN, ABCA1 were upregulated in the blood of asthmatic patients. SFN, ABCA1 were higher, while MKI67 was lower in severe asthmatic with wheeze compared to nonasthmatics with wheezes. SERPINE1 and GPRC5A were downregulated in the blood of eosinophilic asthmatics, while RRM2 was upregulated in an acute attack of asthma. Validation of the gene expression in PBMC of locally recruited asthma patients showed that SERPINE1, GPRC5A, SFN, ABCA1, MKI67, and RRM2 were downregulated in severe uncontrolled asthma. We have identified a set of biologically crucial genes to the homeostasis of the lung and in asthma development and progression. This study can help us further understand the complex interplay between the transcriptomic data and the external factors which may deviate our understanding of asthma heterogeneity.
Mahmood Yaseen Hachim; Noha Mousaad Elemam; Rakhee K. Ramakrishnan; Laila Salameh; Ronald Olivenstein; Ibrahim Yaseen Hachim; Thenmozhi Venkatachalam; Bassam Mahboub; Saba Al Heialy; Qutayba Hamid; Rifat Hamoudi. Derangement of cell cycle markers in peripheral blood mononuclear cells of asthmatic patients as a reliable biomarker for asthma control. Scientific Reports 2021, 11, 1 -24.
AMA StyleMahmood Yaseen Hachim, Noha Mousaad Elemam, Rakhee K. Ramakrishnan, Laila Salameh, Ronald Olivenstein, Ibrahim Yaseen Hachim, Thenmozhi Venkatachalam, Bassam Mahboub, Saba Al Heialy, Qutayba Hamid, Rifat Hamoudi. Derangement of cell cycle markers in peripheral blood mononuclear cells of asthmatic patients as a reliable biomarker for asthma control. Scientific Reports. 2021; 11 (1):1-24.
Chicago/Turabian StyleMahmood Yaseen Hachim; Noha Mousaad Elemam; Rakhee K. Ramakrishnan; Laila Salameh; Ronald Olivenstein; Ibrahim Yaseen Hachim; Thenmozhi Venkatachalam; Bassam Mahboub; Saba Al Heialy; Qutayba Hamid; Rifat Hamoudi. 2021. "Derangement of cell cycle markers in peripheral blood mononuclear cells of asthmatic patients as a reliable biomarker for asthma control." Scientific Reports 11, no. 1: 1-24.
Purpose: Microbial coinfections in COVID-19 patients carry a risk of poor outcomes. This study aimed to characterize the clinical and microbiological profiles of coinfections in patients with COVID-19. Methods: A retrospective review of the clinical and laboratory records of COVID-19 patients with laboratory-confirmed infections with bacteria, fungi, and viruses was conducted. Only adult COVID-19 patients hospitalized at participating health-care facilities between February 1 and July 31, 2020 were included. Data were collected from the centralized electronic system of Dubai Health Authority hospitals and Sheikh Khalifa General Hospital Umm Al Quwain. Results: Of 29,802 patients hospitalized with COVID-19, 392 (1.3%) had laboratory-confirmed coinfections. The mean age of patients with coinfections was 49.3± 12.5 years, and a majority were male (n=330 of 392, 84.2%). Mean interval to commencement of empirical antibiotics was 1.2± 3.6) days postadmission, with ceftriaxone, azithromycin, and piperacillin–tazobactam the most commonly used. Median interval between admission and first positive culture (mostly from blood, endotracheal aspirates, and urine specimens) was 15 (IQR 8– 25) days. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli were predominant in first positive cultures, with increased occurrence of Stenotrophomonas maltophilia, methicillin-resistant Staphylococcus aureus, Acinetobacter baumannii, Candida auris, and Candida parapsilosis in subsequent cultures. The top three Gram-positive organisms were Staphylococcus epidermidis, Enterococcus faecalis, and Staphylococcus aureus. There was variability in levels of sensitivity to antibiotics and isolates harboring mecA, ESBL, AmpC, and carbapenemase-resistance genes were prevalent. A total of 130 (33.2%) patients died, predominantly those in the intensive-care unit undergoing mechanical ventilation or extracorporeal membrane oxygenation. Conclusion: Despite the low occurrence of coinfections among patients with COVID-19 in our setting, clinical outcomes remained poor. Predominance of Gram-negative pathogens, emergence of Candida species, and prevalence of isolates harboring drug-resistance genes are of concern.
Abiola Senok; Mubarak Alfaresi; Hamda Khansaheb; Rania Nassar; Mahmood Hachim; Hanan Al Suwaidi; Majed Almansoori; Fatma Alqaydi; Zuhair Afaneh; Aalya Mohamed; Shahab Qureshi; Ayman Ali; Abdulmajeed Alkhajeh; Alawi Alsheikh-Ali. Coinfections in Patients Hospitalized with COVID-19: A Descriptive Study from the United Arab Emirates. Infection and Drug Resistance 2021, ume 14, 2289 -2296.
AMA StyleAbiola Senok, Mubarak Alfaresi, Hamda Khansaheb, Rania Nassar, Mahmood Hachim, Hanan Al Suwaidi, Majed Almansoori, Fatma Alqaydi, Zuhair Afaneh, Aalya Mohamed, Shahab Qureshi, Ayman Ali, Abdulmajeed Alkhajeh, Alawi Alsheikh-Ali. Coinfections in Patients Hospitalized with COVID-19: A Descriptive Study from the United Arab Emirates. Infection and Drug Resistance. 2021; ume 14 ():2289-2296.
Chicago/Turabian StyleAbiola Senok; Mubarak Alfaresi; Hamda Khansaheb; Rania Nassar; Mahmood Hachim; Hanan Al Suwaidi; Majed Almansoori; Fatma Alqaydi; Zuhair Afaneh; Aalya Mohamed; Shahab Qureshi; Ayman Ali; Abdulmajeed Alkhajeh; Alawi Alsheikh-Ali. 2021. "Coinfections in Patients Hospitalized with COVID-19: A Descriptive Study from the United Arab Emirates." Infection and Drug Resistance ume 14, no. : 2289-2296.
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.
Background: The COVID-19 pandemic varies between countries, with suggestions that weather might contribute to the transmission mode, disease presentation, severity, and clinical outcomes. Yet the exact link between climate and COVID-19 is still not well-explored. Objectives: This study aimed to evaluate the effect of hot geographical region weather [like United Arab Emirates (UAE)] on COVID-19 clinical profile and outcomes. Temperature, wind speed, cloud cover, precipitation, and other weather-related variables were studied concerning COVID-19 patients outcomes and laboratory results. Methodology: A total of 434 COVID-19 positive patients admitted between January and June 2020, were recruited from Al Kuwait Hospital, Dubai, UAE. Temperature, wind speed, cloud cover, and precipitation rate were retrieved from history+ for the day when COVID-19 patients presented to the hospital. These weather parameters were correlated with COVID-19 clinical and laboratory parameters. Results: Our results showed that patients needed admission in days with higher temperatures, higher solar radiation, and less humidity were associated with higher deaths. This association can be linked to the association of these weather parameters with age at diagnosis; higher C-reactive protein (CRP), neutrophil count, white cell count (WCC), aspartate aminotransferase (AST), and alkaline phosphatase (ALP); and lower lymphocyte count, estimated glomerular filtration rate (eGFR), hemoglobin (Hb), Na, and albumin, all of which are considered poor prognostic factors for COVID-19. Conclusion: Our study highlighted the importance of weather-related variables on the dynamics of mortality and clinical outcomes of COVID-19. The hot weather might makes some people, especially those with comorbidities or older ages, develop aggressive inflammation that ends up with complications and mortality.
Mahmood Yaseen Hachim; Ibrahim Y. Hachim; Kashif Naeem; Haifa Hannawi; Issa Al Salmi; Suad Hannawi. Higher Temperatures, Higher Solar Radiation, and Less Humidity Is Associated With Poor Clinical and Laboratory Outcomes in COVID-19 Patients. Frontiers in Public Health 2021, 9, 618828 .
AMA StyleMahmood Yaseen Hachim, Ibrahim Y. Hachim, Kashif Naeem, Haifa Hannawi, Issa Al Salmi, Suad Hannawi. Higher Temperatures, Higher Solar Radiation, and Less Humidity Is Associated With Poor Clinical and Laboratory Outcomes in COVID-19 Patients. Frontiers in Public Health. 2021; 9 ():618828.
Chicago/Turabian StyleMahmood Yaseen Hachim; Ibrahim Y. Hachim; Kashif Naeem; Haifa Hannawi; Issa Al Salmi; Suad Hannawi. 2021. "Higher Temperatures, Higher Solar Radiation, and Less Humidity Is Associated With Poor Clinical and Laboratory Outcomes in COVID-19 Patients." Frontiers in Public Health 9, no. : 618828.
Both canonical and non-canonical Wnt signaling pathway alterations have been documented in pulmonary disease pathogenesis and progression; therefore, they can be an attractive target for pharmaceutical management of severe asthma. Wnt/β-catenin signaling was shown to link early embryonic lung development impairment to later in life asthmatic airway remodeling. Here we explored the changes in Wnt signaling associated with asthma initiation and progression in epithelial and fibroblasts using a comprehensive approach based onin silicoanalysis and followed byin vitrovalidation. In summary, thein silicoanalysis showed that the bronchial epithelium of severe asthmatic patients showed a deranged balance between Wnt enhancer and Wnt inhibitors. A Th2-high phenotype is associated with upregulated Wnt-negative regulators, while inflammatory and neutrophilic severe asthmatics showed higher canonical Wnt signaling member enrichment. Most of these genes are regulators of healthy lung development early in life and, if disturbed, can make people susceptible to developing asthma early in life and prone to developing a severe phenotype. Most of the Wnt members are secreted, and their effect can be in an autocrine fashion on the bronchial epithelium, paracrine on nearby adjacent structural cells like fibroblasts and smooth muscles, or systemic in blood. Our results showed that canonical Wnt signaling is needed for the proper response of cells to proliferative stimuli, which puts cells under stress. Cells in response to this proliferative stress will activate the senescence mechanism, which is also dependent on Wnt signaling. Inhibition of Wnt signaling using FH535 inhibits both proliferation and senescence markers in bronchial fibroblasts compared to DMSO-treated cells. In fibroblasts from asthmatic patients, inhibition of Wnt signaling did not show that effect as the Wnt signaling is deranged besides other pathways that might be non-functional.
Mahmood Yaseen Hachim; Noha Mousaad Elemam; Rakhee K. Ramakrishnan; Khuloud Bajbouj; Ronald Olivenstein; Ibrahim Yaseen Hachim; Saba Al Heialy; Qutayba Hamid; Hauke Busch; Rifat Hamoudi. Wnt Signaling Is Deranged in Asthmatic Bronchial Epithelium and Fibroblasts. Frontiers in Cell and Developmental Biology 2021, 9, 1 .
AMA StyleMahmood Yaseen Hachim, Noha Mousaad Elemam, Rakhee K. Ramakrishnan, Khuloud Bajbouj, Ronald Olivenstein, Ibrahim Yaseen Hachim, Saba Al Heialy, Qutayba Hamid, Hauke Busch, Rifat Hamoudi. Wnt Signaling Is Deranged in Asthmatic Bronchial Epithelium and Fibroblasts. Frontiers in Cell and Developmental Biology. 2021; 9 ():1.
Chicago/Turabian StyleMahmood Yaseen Hachim; Noha Mousaad Elemam; Rakhee K. Ramakrishnan; Khuloud Bajbouj; Ronald Olivenstein; Ibrahim Yaseen Hachim; Saba Al Heialy; Qutayba Hamid; Hauke Busch; Rifat Hamoudi. 2021. "Wnt Signaling Is Deranged in Asthmatic Bronchial Epithelium and Fibroblasts." Frontiers in Cell and Developmental Biology 9, no. : 1.
Purpose. Asthma is one of the most common obstructive pulmonary diseases worldwide. Epigenetic alterations, including DNA methylation and histone modifications, have been reported to contribute to asthma pathogenesis. Since the inflammation mediator and remodeling trigger, IL-13, is known to play a central role in the pathophysiology of asthma, this study was aimed to identify novel IL-13-regulated epigenetic modifiers in asthma that may contribute to subepithelial fibrosis. Methods. Publicly available transcriptomic datasets from Gene Expression Omnibus (GEO) were used to identify differentially expressed genes on an epigenetic level upon IL-13 exposure in lung fibroblasts. Bronchial fibroblasts isolated from healthy and asthmatic individuals were assessed for the gene and protein expression levels of the identified gene at baseline and upon IL-13 treatment using qRT-PCR and western blotting, respectively. Its subcellular localization and tissue distribution were examined in bronchial fibroblasts as well as bronchial biopsies by immunofluorescence and immunohistochemical analysis, respectively. Results. Bioinformatic analysis revealed the differential expression of the histone demethylase JMJD2B/KDM4B, a well-known epigenetic modulator that leads to the demethylation of different lysine residues on histones, in IL-13-treated lung fibroblasts. The baseline expression levels of JMJD2B were higher in asthmatic fibroblasts and in bronchial biopsies in comparison to healthy ones. There was also an increase in JMJD2B activity as evidenced by the demethylation of its downstream target, H3K36me3. Furthermore, IL-13 stimulation induced JMJD2B expression and further demethylation of H3K36me3 in asthmatic fibroblasts. This was accompanied by increased translocation of JMJD2B into the nucleus. Conclusion. This study highlights the novel pathological involvement of the histone demethylase JMJD2B/KDM4B in asthmatic airway fibroblasts that are regulated by IL-13. Clinical implications. Given that there is no single therapeutic medicine to effectively treat the various subtypes of asthma, this study provides promising insights into JMJD2B as a new therapeutic target that could potentially improve the treatment and management of asthma.
Khuloud Bajbouj; Mahmood Y. Hachim; Rakhee K. Ramakrishnan; Huwaida Fazel; Jumana Mustafa; Shahed Alzaghari; Mahmoud Eladl; Jasmin Shafarin; Ronald Olivenstein; Qutayba Hamid. IL-13 Augments Histone Demethylase JMJD2B/KDM4B Expression Levels, Activity, and Nuclear Translocation in Airway Fibroblasts in Asthma. Journal of Immunology Research 2021, 2021, 1 -10.
AMA StyleKhuloud Bajbouj, Mahmood Y. Hachim, Rakhee K. Ramakrishnan, Huwaida Fazel, Jumana Mustafa, Shahed Alzaghari, Mahmoud Eladl, Jasmin Shafarin, Ronald Olivenstein, Qutayba Hamid. IL-13 Augments Histone Demethylase JMJD2B/KDM4B Expression Levels, Activity, and Nuclear Translocation in Airway Fibroblasts in Asthma. Journal of Immunology Research. 2021; 2021 ():1-10.
Chicago/Turabian StyleKhuloud Bajbouj; Mahmood Y. Hachim; Rakhee K. Ramakrishnan; Huwaida Fazel; Jumana Mustafa; Shahed Alzaghari; Mahmoud Eladl; Jasmin Shafarin; Ronald Olivenstein; Qutayba Hamid. 2021. "IL-13 Augments Histone Demethylase JMJD2B/KDM4B Expression Levels, Activity, and Nuclear Translocation in Airway Fibroblasts in Asthma." Journal of Immunology Research 2021, no. : 1-10.
Patients with rheumatoid arthritis (RA) represent one of the fragile patient groups that might be susceptible to the critical form of the coronavirus disease − 19 (COVID-19). On the other side, RA patients have been found not to have an increased risk of COVID-19 infection. Moreover, some of the Disease-Modifying Anti-Rheumatic Drugs (DMARDS) commonly used to treat rheumatic diseases like Hydroxychloroquine (HCQ) were proposed as a potential therapy for COVID-19 with a lack of full understanding of their molecular mechanisms. This highlights the need for the discovery of common pathways that may link both diseases at the molecular side. In this research, we used the in silico approach to investigate the transcriptomic profile of RA synovium to identify shared molecular pathways with that of severe acute respiratory syndrome-corona virus-2 (SARS-COV-2) infected lung tissue. Our results showed upregulation of chemotactic factors, including CCL4, CCL8, and CCL11, that all shared CCR5 as their receptor, as a common derangement observed in both diseases; RA and COVID-19. Moreover, our results also highlighted a possible mechanism through which HCQ, which can be used as a monotherapy in mild RA or as one of the triple-DMARDs therapy (tDMARDs; methotrexate, sulphasalazine, and HCQ), might interfere with the COVID-19 infection. This might be achieved through the ability of HCQ to upregulate specific immune cell populations like activated natural killer (NK) cells, which were found to be significantly reduced in COVID-19 infection. In addition to its ability to block CCR5 rich immune cell recruitment that also was upregulated in the SARS-COV-2 infected lungs. This might explain some of the reports that showed beneficial effects.
Mahmood Y. Hachim; Ibrahim Y. Hachim; Kashif Bin Naeem; Haifa Hannawi; Issa Al Salmi; Suad Hannawi. C-C chemokine receptor type 5 links COVID-19, rheumatoid arthritis, and Hydroxychloroquine: in silico analysis. Translational Medicine Communications 2020, 5, 1 -12.
AMA StyleMahmood Y. Hachim, Ibrahim Y. Hachim, Kashif Bin Naeem, Haifa Hannawi, Issa Al Salmi, Suad Hannawi. C-C chemokine receptor type 5 links COVID-19, rheumatoid arthritis, and Hydroxychloroquine: in silico analysis. Translational Medicine Communications. 2020; 5 (1):1-12.
Chicago/Turabian StyleMahmood Y. Hachim; Ibrahim Y. Hachim; Kashif Bin Naeem; Haifa Hannawi; Issa Al Salmi; Suad Hannawi. 2020. "C-C chemokine receptor type 5 links COVID-19, rheumatoid arthritis, and Hydroxychloroquine: in silico analysis." Translational Medicine Communications 5, no. 1: 1-12.
Patients with rheumatoid arthritis (RA) represent one of the fragile patient groups that might be susceptible to the critical form of the coronavirus disease -19 (COVID-19) . On the other side, RA patients have been found not to have an increased risk of COVID-19 infection. Moreover, some of the Disease-Modifying Anti-Rheumatic Drugs (DMARDS) commonly used to treat rheumatic diseases like Hydroxychloroquine (HCQ) were proposed as a potential therapy for COVID-19 with a lack of full understanding of their molecular mechanisms. This highlights the need for the discovery of common pathways that may link both diseases at the molecular side. In this research, we used the in silico approach to investigate the transcriptomic profile of RA synovium to identify shared molecular pathways with that of severe acute respiratory syndrome-corona virus-2 (SARS-COV-2) infected lung tissue. Our results showed upregulation of chemotactic factors, including CCL4, CCL8, and CCL11, that all shared CCR5 as their receptor, as a common derangement observed in both diseases; RA and COVID-19. Moreover, our results also highlighted a possible mechanism through which HCQ, which can be used as a monotherapy in mild RA or as one of the triple-DMARDs therapy (tDMARDs; methotrexate, sulphasalazine, and HCQ), might interfere with the COVID-19 infection. This might be achieved through the ability of HCQ to upregulate specific immune cell populations like activated natural killer (NK) cells, which were found to be significantly reduced in COVID-19 infection. In addition to its ability to block CCR5 rich immune cell recruitment that also was upregulated in the SARS-COV-2 infected lungs. This might explain some of the reports that showed beneficial effects.
Mahmood Yaseen Hachim; Ibrahim Hachim; Kashif Naeem; Haifa Hannawi; Issa Al Salmi; Suad Hannawi. C-C chemokine receptor type 5 links COVID-19, Rheumatoid arthritis, and Hydroxychloroquine: In silico analysis . 2020, 1 .
AMA StyleMahmood Yaseen Hachim, Ibrahim Hachim, Kashif Naeem, Haifa Hannawi, Issa Al Salmi, Suad Hannawi. C-C chemokine receptor type 5 links COVID-19, Rheumatoid arthritis, and Hydroxychloroquine: In silico analysis . . 2020; ():1.
Chicago/Turabian StyleMahmood Yaseen Hachim; Ibrahim Hachim; Kashif Naeem; Haifa Hannawi; Issa Al Salmi; Suad Hannawi. 2020. "C-C chemokine receptor type 5 links COVID-19, Rheumatoid arthritis, and Hydroxychloroquine: In silico analysis ." , no. : 1.
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.
Cellular entry of SARS-CoV-2 is thought to occur through the binding of viral spike S1 protein to ACE2. The entry process involves priming of the S protein by TMPRSS2 and ADAM17, which collectively mediate the binding and promote ACE2 shedding. In this study, microarray and RNA-sequencing (RNA-seq) expression data were utilized to profile the expression pattern of ACE2, ADAM17, and TMPRSS2 in type 2 diabetic (T2D) and non-diabetic human pancreatic islets. Our data show that pancreatic islets express all three receptors irrespective of diabetes status. The expression of ACE2 was significantly increased in diabetic/hyperglycemic islets compared to non-diabetic/normoglycemic. Islets from female donors showed higher ACE2 expression compared to males; the expression of ADAM17 and TMPRSS2 was not affected by gender. The expression of the three receptors was statistically similar in young (≤40 years old) versus old (≥60 years old) donors. Obese (BMI > 30) donors have significantly higher expression levels of ADAM17 and TMPRSS2 relative to those from non-obese donors (BMI < 25). TMPRSS2 expression correlated positively with HbA1c and negatively with age, while ADAM17 and TMPRSS2 correlated positively with BMI. The expression of the three receptors was statistically similar in muscle and subcutaneous adipose tissues obtained from diabetic and nondiabetic donors. Lastly, ACE2 expression was higher in sorted pancreatic β-cell relative to other endocrine cells. In conclusion, ACE2 expression is increased in diabetic human islets. More studies are required to investigate whether variations of ACE2 expression could explain the severity of COVID-19 infection-related symptoms between diabetics and non-diabetic patients.
Jalal Taneera; Waseem El-Huneidi; Mawieh Hamad; Abdul Mohammed; Esraa Elaraby; Mahmood Hachim. Expression Profile of SARS-CoV-2 Host Receptors in Human Pancreatic Islets Revealed Upregulation of ACE2 in Diabetic Donors. Biology 2020, 9, 215 .
AMA StyleJalal Taneera, Waseem El-Huneidi, Mawieh Hamad, Abdul Mohammed, Esraa Elaraby, Mahmood Hachim. Expression Profile of SARS-CoV-2 Host Receptors in Human Pancreatic Islets Revealed Upregulation of ACE2 in Diabetic Donors. Biology. 2020; 9 (8):215.
Chicago/Turabian StyleJalal Taneera; Waseem El-Huneidi; Mawieh Hamad; Abdul Mohammed; Esraa Elaraby; Mahmood Hachim. 2020. "Expression Profile of SARS-CoV-2 Host Receptors in Human Pancreatic Islets Revealed Upregulation of ACE2 in Diabetic Donors." Biology 9, no. 8: 215.
Despite all the advances in the management of breast cancer (BC), patients with distance metastasis are still considered incurable with poor prognosis. For that reason, early detection of the metastatic lesions is crucial to improve patients’ life span as well as quality of life. Many markers were proposed to be used as biomarkers for metastatic BC lesions, however many of them lack organ specificity. This highlights the need for novel markers that are more specific in detecting disseminated BC lesions. Here, we investigated mammaglobin-1 expression as a potential and specific marker for metastatic BC lesions using our patient cohort consisting of 30 newly diagnosed BC patients. For all patients, bone marrow (BM) aspiration, BM biopsy stained by H&E and BM immunohistochemically stained for mammaglobin-1 were performed. In addition, the CA15-3 in both serum and bone marrow plasma was also evaluated for each patient. Indeed, mammaglobin-1 immuno-staining was able to detect BM micrometastases in 16/30 patients (53.3%) compared to only 5/30 patients (16.7%) in BM biopsy stained by H&E and no cases detected by BM aspirate (0%). In addition, our results showed a trend of association between mammaglobin-1 immunoreactivity and the serum and BM plasma CA15-3. Further validation was done using large publicly available databases. Our results showed that mammaglobin-1 gene expression to be specifically upregulated in BC patients’ samples compared to normal tissue as well as samples from other cancers. Moreover, our findings also showed mammaglobin-1 expression to be a marker of tumour progression presented as lymph nodes involvement and distant metastasis. These results provide an initial evidence for the use of mammaglobin-1 (SCGB2A2) immunostaining in bone marrow as a tool to investigate early BM micrometastases in breast cancer.
Iman Mamdouh Talaat; Mahmood Hachim; Ibrahim Yaseen Hachim; Ramez Abd El-Razak Ibrahim; Mohamed Abd El Rahman Ahmed; Hanan Yehia Tayel. Bone marrow mammaglobin-1 (SCGB2A2) immunohistochemistry expression as a breast cancer specific marker for early detection of bone marrow micrometastases. Scientific Reports 2020, 10, 1 -12.
AMA StyleIman Mamdouh Talaat, Mahmood Hachim, Ibrahim Yaseen Hachim, Ramez Abd El-Razak Ibrahim, Mohamed Abd El Rahman Ahmed, Hanan Yehia Tayel. Bone marrow mammaglobin-1 (SCGB2A2) immunohistochemistry expression as a breast cancer specific marker for early detection of bone marrow micrometastases. Scientific Reports. 2020; 10 (1):1-12.
Chicago/Turabian StyleIman Mamdouh Talaat; Mahmood Hachim; Ibrahim Yaseen Hachim; Ramez Abd El-Razak Ibrahim; Mohamed Abd El Rahman Ahmed; Hanan Yehia Tayel. 2020. "Bone marrow mammaglobin-1 (SCGB2A2) immunohistochemistry expression as a breast cancer specific marker for early detection of bone marrow micrometastases." Scientific Reports 10, no. 1: 1-12.
Background: Patients with rheumatoid arthritis (RA) represent one of the fragile patient groups that might be susceptible to coronavirus disease -19 (COVID-19) and its severe form. On the other side, RA patients have been found not to have an increased risk of COVID19 infection. Moreover, some of the Disease-Modifying Anti-Rheumatic Drugs (DMARDS) commonly used to treat rheumatic diseases like Hydroxychloroquine (HCQ) were proposed as a potential therapy for COVID19 with a lack of full understanding of their molecular mechanisms. This highlights the need for the discovery of common pathways that may link both diseases at the molecular side Methods: We used the in silico approach to investigate the transcriptomic profile of RA synovium compared to osteoarthritis and healthy controls to identify RA specific molecular pathways shared with that of severe acute respiratory syndrome-corona virus-2 (SARS-COV-2) infected lung tissue. Results: Our results showed upregulation of chemotactic factors, including CCL4, CCL8, and CCL11, that all shared CCR5 as their receptor, as a common derangement observed in both diseases; RA and COVID-19. Moreover, our results also highlighted that HCQ might interfere with the COVID-19 infection through its ability to upregulate specific immune cell populations like activated natural killer (NK) cells, besides blocking CCR5 rich immune cell recruitment to the SARS-COV-2 infected lungs Conclusion: Our results might explain some of the reports that showed beneficial effects and indicate the need for proper patients stratification on their immune profile before selecting the therapeutic protocol or clinical trial enrollment. Keyword COVID-19, SARS-COV-2, Hydroxychloroquine, rheumatoid arthritis
Mahmood Yaseen Hachim; Ibrahim Hachim; Kashif Naeem; Haifa Hannawi; Issa Al Salmi; Suad Hannawi. C-C chemokine receptor type 5 links COVID-19, Rheumatoid arthritis, and Hydroxychloroquine. 2020, 1 .
AMA StyleMahmood Yaseen Hachim, Ibrahim Hachim, Kashif Naeem, Haifa Hannawi, Issa Al Salmi, Suad Hannawi. C-C chemokine receptor type 5 links COVID-19, Rheumatoid arthritis, and Hydroxychloroquine. . 2020; ():1.
Chicago/Turabian StyleMahmood Yaseen Hachim; Ibrahim Hachim; Kashif Naeem; Haifa Hannawi; Issa Al Salmi; Suad Hannawi. 2020. "C-C chemokine receptor type 5 links COVID-19, Rheumatoid arthritis, and Hydroxychloroquine." , no. : 1.
Phosphatidylinositol-specific phospholipase C X domain 3 (PLCXD3) has been shown to influence pancreatic β-cell function by disrupting insulin signaling. Herein, we investigated two genetic variants in the PLCXD3 gene in relation to type 2 diabetes (T2D) or metabolic syndrome (MetS) in the Emirati population. In total, 556 adult Emirati individuals (306 T2D and 256 controls) were genotyped for two PLCXD3 variants (rs319013 and rs9292806) using TaqMan genotyping assays. The frequency distribution of minor homozygous CC genotype of rs9292806 and GG genotype of rs319013 were significantly higher in subjects with MetS compared to Non-MetS (p < 0.01). The minor homozygous rs9292806-CC and rs319013-GG genotypes were significantly associated with increased risk of MetS (adj. OR 2.92; 95% CI 1.61–5.3; p < 0.001) (adj. OR 2.62; 95% CI 1.42–4.83; p = 0.002), respectively. However, no associations were detected with T2D. In healthy participants, the homozygous minor genotypes of both rs9292806 and rs319013 were significantly higher fasting glucose (adj. p < 0.005), HbA1c (adj. p < 0.005) and lower HDL-cholesterol (adj. p < 0.05) levels. Data from T2D Knowledge Portal database disclosed a nominal association of rs319013 and rs9292806 with T2D and components of MetS. Bioinformatics prediction analysis showed a deleterious effect of rs9292806 on the regulatory regions of PLCXD3. In conclusion, this study identifies rs319013 and rs9292806 variants of PLCXD3 as additional risk factors for MetS in the Emirati population.
Hayat Aljaibeji; Abdul Khader Mohammed; Sami Alkayyali; Mahmood Yaseen Hachim; Hind Hasswan; Waseem El-Huneidi; Jalal Taneera; Nabil Sulaiman. Genetic Variants of the PLCXD3 Gene Are Associated with Risk of Metabolic Syndrome in the Emirati Population. Genes 2020, 11, 1 .
AMA StyleHayat Aljaibeji, Abdul Khader Mohammed, Sami Alkayyali, Mahmood Yaseen Hachim, Hind Hasswan, Waseem El-Huneidi, Jalal Taneera, Nabil Sulaiman. Genetic Variants of the PLCXD3 Gene Are Associated with Risk of Metabolic Syndrome in the Emirati Population. Genes. 2020; 11 (6):1.
Chicago/Turabian StyleHayat Aljaibeji; Abdul Khader Mohammed; Sami Alkayyali; Mahmood Yaseen Hachim; Hind Hasswan; Waseem El-Huneidi; Jalal Taneera; Nabil Sulaiman. 2020. "Genetic Variants of the PLCXD3 Gene Are Associated with Risk of Metabolic Syndrome in the Emirati Population." Genes 11, no. 6: 1.
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.
Since the outbreak of the novel coronavirus disease (COVID-19) at the end of 2019, the clinical presentation of the disease showed a great heterogeneity with a diverse impact between different subpopulations. Emerging evidence from different parts of the world showed significantly poor outcome among males compared to female patients. A better understanding of the molecular mechanisms behind this difference might be a fundamental step for a more effective and targeted response to the outbreak. For that reason, here we try to investigate the molecular basis of the gender variations in mortality rates related to COVID-19 infection. To achieve this, we used our in-house pipeline to process publicly available lung transcriptomic data from 141 females compared to 286 males. After excluding Y specific genes, our results showed a shortlist of 73 genes that are differentially expressed between the two groups. Our results showed downregulation of a group of genes that are involved in the regulation of hydrolase activity including (AGTR1, CHM, DDX3X, FGFR3, SFRP2, and NLRP2), which is also believed to be essential for lung immune response and antimicrobial activity in the lung tissues in males compared to females. In contrast, our results showed an upregulation of angiotensin II receptor type 1 (AGTR1), a member of the renin-angiotensin system (RAS) that plays a role in angiotensin-converting enzyme 2 (ACE2) activity modulation. Interestingly, recent reports and experimental animal models highlight an important role of this receptor in SARS-Coronavirus lung damage as well as pulmonary edema, suggesting a possible role of its blockers like losartan and olmesartan as potential therapeutic options for COVID-19 infection. Finally, our results also showed a differential expression of different genes that are involved in the immune response including the NLRP2 and PTGDR2, further supporting the notion of the sex-based immunological differences. Taken together, our results provide an initial evidence of the molecular mechanisms that might be involved in the differential outcomes observed between both genders during the COVID-19 outbreak. This might be essential for the discovery of new targets and more precise therapeutic options to treat COVID-19 patients from different clinical and epidemiological characteristics with the aim of improving their outcome.
Ibrahim Y. Hachim; Mahmood Y. Hachim; Iman Mamdouh Talaat; Vanessa M. López-Ozuna; Narjes Saheb Sharif-Askari; Rabih Halwani; Qutayba Hamid. The Molecular Basis of Gender Variations in Mortality Rates Associated with the Novel Coronavirus (COVID-19) Outbreak. 2020, 1 .
AMA StyleIbrahim Y. Hachim, Mahmood Y. Hachim, Iman Mamdouh Talaat, Vanessa M. López-Ozuna, Narjes Saheb Sharif-Askari, Rabih Halwani, Qutayba Hamid. The Molecular Basis of Gender Variations in Mortality Rates Associated with the Novel Coronavirus (COVID-19) Outbreak. . 2020; ():1.
Chicago/Turabian StyleIbrahim Y. Hachim; Mahmood Y. Hachim; Iman Mamdouh Talaat; Vanessa M. López-Ozuna; Narjes Saheb Sharif-Askari; Rabih Halwani; Qutayba Hamid. 2020. "The Molecular Basis of Gender Variations in Mortality Rates Associated with the Novel Coronavirus (COVID-19) Outbreak." , no. : 1.
The accumulation of fibroblasts, their synthesis of extracellular matrix (ECM) proteins and their innate resistance to apoptosis are characteristics of subepithelial fibrosis observed in severe asthma. Interleukin-17 (IL-17) is an important regulator of airway remodeling in asthma. However, the contribution of IL-17 to the pro-fibrotic phenotype of bronchial fibroblasts is not well-characterized. In this study, we investigated whether IL-17 induced autophagy regulates mitochondrial and pro-fibrotic function in bronchial fibroblasts. The primary cultured bronchial fibroblasts isolated from non-asthmatic (NHBF) and severe asthmatic (DHBF) subjects were treated with IL-17 in order to ascertain its effect on mitochondrial function, mitochondrial quality control, and apoptosis using immunoblotting and flow cytometric analyses. At baseline, DHBF exhibited higher levels of mitophagy and mitochondrial biogenesis compared to NHBF. Immunohistochemical evaluation of bronchial biopsies showed intense PINK1 immunoreactivity in severe asthma than in control. IL-17 intensified the mitochondrial dysfunction and impaired the mitochondrial quality control machinery in NHBF and DHBF. Moreover, IL-17 augmented a pro-fibrotic and anti-apoptotic response in both group of fibroblasts. Inhibition of autophagy using bafilomycin-A1 reduced PINK1 expression in NHBF and restored the IL-17 mediated changes in PINK1 to their basal levels in DHBF. Bafilomycin-A1 also reversed the IL-17 associated fibrotic response in these fibroblasts, suggesting a role for IL-17 induced autophagy in the induction of fibrosis in bronchial fibroblasts. Taken together, our findings suggest that IL-17 induced autophagy promotes mitochondrial dysfunction and fibrosis in bronchial fibroblasts from both non-asthmatic and severe asthmatic subjects. Our study provides insights into the therapeutic potential of targeting autophagy in ameliorating fibrosis, particularly in severe asthmatic individuals.
Rakhee K. Ramakrishnan; Khuloud Bajbouj; Saba Al Heialy; Bassam Mahboub; Abdul Wahid Ansari; Ibrahim Y. Hachim; Surendra Rawat; Laila Salameh; Mahmood Hachim; Ronald Olivenstein; Rabih Halwani; Rifat Hamoudi; Qutayba Hamid. IL-17 Induced Autophagy Regulates Mitochondrial Dysfunction and Fibrosis in Severe Asthmatic Bronchial Fibroblasts. Frontiers in Immunology 2020, 11, 1002 .
AMA StyleRakhee K. Ramakrishnan, Khuloud Bajbouj, Saba Al Heialy, Bassam Mahboub, Abdul Wahid Ansari, Ibrahim Y. Hachim, Surendra Rawat, Laila Salameh, Mahmood Hachim, Ronald Olivenstein, Rabih Halwani, Rifat Hamoudi, Qutayba Hamid. IL-17 Induced Autophagy Regulates Mitochondrial Dysfunction and Fibrosis in Severe Asthmatic Bronchial Fibroblasts. Frontiers in Immunology. 2020; 11 ():1002.
Chicago/Turabian StyleRakhee K. Ramakrishnan; Khuloud Bajbouj; Saba Al Heialy; Bassam Mahboub; Abdul Wahid Ansari; Ibrahim Y. Hachim; Surendra Rawat; Laila Salameh; Mahmood Hachim; Ronald Olivenstein; Rabih Halwani; Rifat Hamoudi; Qutayba Hamid. 2020. "IL-17 Induced Autophagy Regulates Mitochondrial Dysfunction and Fibrosis in Severe Asthmatic Bronchial Fibroblasts." Frontiers in Immunology 11, no. : 1002.
Patients with renal cell carcinoma (RCC), the most common malignant renal epithelial tumor, usually present with advanced disease and unpredicted clinical behavior. The receptor tyrosine kinase, ephrin type-A receptor 2 (EphA2) was found to be overexpressed in several malignancies and its expression was found to be associated with poor prognostic features. Our study is an observational study with the aim of investigating the prognostic value of EphA2 in RCC patients and its association with clinicopathological parameters as well as Ki-67 expression, which is a well-known proliferative and prognostic marker in RCC. EphA2 and Ki-67 immunohistochemical staining was performed on whole sections representative of 50 patients diagnosed with primary RCC from 2013 to 2018. In addition, the association between EphA2 mRNA expression and clinicopathological parameters as well as the patients’ outcome was also evaluated using two large publicly available databases. Our results showed a significant association between EphA2 immunohistochemical expression and tumor size, nuclear grade, tumor stage, patients’ outcome and Ki-67 expression (P < .05 for all). The same trend was also observed with EphA2 mRNA expression using larger patients’ cohorts in 2 publicly available databases. Notably, EphA2 protein expression showed higher levels of co-expression with the proliferative marker Ki-67. Our results suggested that higher expression of EphA2 and Ki-67 in tumor tissues predicts a locally aggressive behaviour and poor outcome of patients with RCC. Moreover, our results give a rationale for the potential benefits of using novel therapeutic strategies with the aim of targeting EphA2 receptor in RCC patients that might help in improving their outcome.
Iman Mamdouh Talaat; Israa Sobhy Okap; Tamer Abou Youssif; Ibrahim Yaseen Hachim; Mahmood Hachim; Samar Mohamed El Sheikh. The prognostic value of ephrin type-A2 receptor and Ki-67 in renal cell carcinoma patients. Medicine 2020, 99, e20191 .
AMA StyleIman Mamdouh Talaat, Israa Sobhy Okap, Tamer Abou Youssif, Ibrahim Yaseen Hachim, Mahmood Hachim, Samar Mohamed El Sheikh. The prognostic value of ephrin type-A2 receptor and Ki-67 in renal cell carcinoma patients. Medicine. 2020; 99 (19):e20191.
Chicago/Turabian StyleIman Mamdouh Talaat; Israa Sobhy Okap; Tamer Abou Youssif; Ibrahim Yaseen Hachim; Mahmood Hachim; Samar Mohamed El Sheikh. 2020. "The prognostic value of ephrin type-A2 receptor and Ki-67 in renal cell carcinoma patients." Medicine 99, no. 19: e20191.
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.
The United Arab Emirates National Diabetes and Lifestyle Study (UAEDIAB) has identified obesity, hypertension, obstructive sleep apnea, and dyslipidemia as common phenotypic characteristics correlated with diabetes mellitus status. As these phenotypes are usually linked with genetic variants, we hypothesized that these phenotypes share single nucleotide polymorphism (SNP)-clusters that can be used to identify causal genes for diabetes. We explored the National Human Genome Research Institute-European Bioinformatics Institute Catalog of Published Genome-Wide Association Studies (NHGRI-EBI GWAS) to list SNPs with documented association with the UAEDIAB-phenotypes as well as diabetes. The shared chromosomal regions affected by SNPs were identified, intersected, and searched for Enriched Ontology Clustering. The potential SNP-clusters were validated using targeted DNA next-generation sequencing (NGS) in two Emirati diabetic patients. RNA sequencing from human pancreatic islets was used to study the expression of identified genes in diabetic and non-diabetic donors. Eight chromosomal regions containing 46 SNPs were identified in at least four out of the five UAEDIAB-phenotypes. A list of 34 genes was shown to be affected by those SNPs. Targeted NGS from two Emirati patients confirmed that the identified genes have similar SNP-clusters. ASAH1, LRP4, FES, and HSD17B12 genes showed the highest SNPs rate among the identified genes. RNA-seq analysis revealed high expression levels of HSD17B12 in human islets and to be upregulated in type 2 diabetes (T2D) donors. Our integrative phenotype-genotype approach is a novel, simple, and powerful tool to identify clinically relevant potential biomarkers in diabetes. HSD17B12 is a novel candidate gene for pancreatic β-cell function.
Mahmood Y. Hachim; Hayat Aljaibeji; Rifat A. Hamoudi; Ibrahim Y. Hachim; Noha M. Elemam; Abdul Khader Mohammed; Albert Salehi; Jalal Taneera; Nabil Sulaiman. An Integrative Phenotype–Genotype Approach Using Phenotypic Characteristics from the UAE National Diabetes Study Identifies HSD17B12 as a Candidate Gene for Obesity and Type 2 Diabetes. Genes 2020, 11, 461 .
AMA StyleMahmood Y. Hachim, Hayat Aljaibeji, Rifat A. Hamoudi, Ibrahim Y. Hachim, Noha M. Elemam, Abdul Khader Mohammed, Albert Salehi, Jalal Taneera, Nabil Sulaiman. An Integrative Phenotype–Genotype Approach Using Phenotypic Characteristics from the UAE National Diabetes Study Identifies HSD17B12 as a Candidate Gene for Obesity and Type 2 Diabetes. Genes. 2020; 11 (4):461.
Chicago/Turabian StyleMahmood Y. Hachim; Hayat Aljaibeji; Rifat A. Hamoudi; Ibrahim Y. Hachim; Noha M. Elemam; Abdul Khader Mohammed; Albert Salehi; Jalal Taneera; Nabil Sulaiman. 2020. "An Integrative Phenotype–Genotype Approach Using Phenotypic Characteristics from the UAE National Diabetes Study Identifies HSD17B12 as a Candidate Gene for Obesity and Type 2 Diabetes." Genes 11, no. 4: 461.