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Article ; Online: The Role of Systems Biology in Deciphering Asthma Heterogeneity

Mahmood Yaseen Hachim / Fatma Alqutami / Ibrahim Yaseen Hachim / Saba Al Heialy / Hauke Busch / Rifat Hamoudi / Qutayba Hamid

Life, Vol 12, Iss 10, p

2022 Volume 1562

Abstract: Asthma is one of the most common and lifelong and chronic inflammatory diseases characterized by inflammation, bronchial hyperresponsiveness, and airway obstruction episodes. It is a heterogeneous disease of varying and overlapping phenotypes with many ... ...

Abstract	Asthma is one of the most common and lifelong and chronic inflammatory diseases characterized by inflammation, bronchial hyperresponsiveness, and airway obstruction episodes. It is a heterogeneous disease of varying and overlapping phenotypes with many confounding factors playing a role in disease susceptibility and management. Such multifactorial disorders will benefit from using systems biology as a strategy to elucidate molecular insights from complex, quantitative, massive clinical, and biological data that will help to understand the underlying disease mechanism, early detection, and treatment planning. Systems biology is an approach that uses the comprehensive understanding of living systems through bioinformatics, mathematical, and computational techniques to model diverse high-throughput molecular, cellular, and the physiologic profiling of healthy and diseased populations to define biological processes. The use of systems biology has helped understand and enrich our knowledge of asthma heterogeneity and molecular basis; however, such methods have their limitations. The translational benefits of these studies are few, and it is recommended to reanalyze the different studies and omics in conjugation with one another which may help understand the reasons for this variation and help overcome the limitations of understanding the heterogeneity in asthma pathology. In this review, we aim to show the different factors that play a role in asthma heterogeneity and how systems biology may aid in understanding and deciphering the molecular basis of asthma.
Keywords	asthma ; systems biology ; multi-omics ; Science ; Q
Subject code	501
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells

Mahmood Yaseen Hachim / Saba Al Heialy / Ibrahim Yaseen Hachim / Rabih Halwani / Abiola C. Senok / Azzam A. Maghazachi / Qutayba Hamid

Frontiers in Immunology, Vol

2020 Volume 11

Abstract: 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 ... ...

Abstract	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.
Keywords	COVID-19 ; SARS-CoV-2 ; interferon-induced transmembrane proteins ; valproic acid ; antiviral immunity ; Immunologic diseases. Allergy ; RC581-607 ; covid19
Subject code	570
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Diagnostic accuracy of fine-needle aspiration cytology in patients presented with thyroid nodules in Al-Ain city, UAE

Dina Ali Alawlaqi / Ibrahim Yaseen Hachim / Jamal Al Deen Alkoteesh / Abdulghani Elomami / Mohammad Ahmad Alfalasi

Hamdan Medical Journal, Vol 13, Iss 4, Pp 203-

2020 Volume 207

Abstract: Background: Thyroid diseases are a common health problem affecting 5% of the general world population. Thyroid nodules represent one of the main clinical presentations of many of the thyroid diseases, including benign and malignant lesions. Fine-needle ... ...

Abstract	Background: Thyroid diseases are a common health problem affecting 5% of the general world population. Thyroid nodules represent one of the main clinical presentations of many of the thyroid diseases, including benign and malignant lesions. Fine-needle aspiration cytology (FNAC) is considered one of the main techniques used for the evaluation of thyroid nodules. Objectives: The aim of this study is to investigate the accuracy of fineneedle aspiration (FNA) biopsy in the diagnosis and evaluation of thyroid nodules. Patients and Methods: The study is a retrospective study that involves 131 patients presented with a thyroid nodule and attended the surgical departments in Tawam Hospital. Results: Our results showed that the majority of patients (68.6%) were younger than 45 years. Females were pre-dominant, with 88.4% compared to males (11.6%). According to the Bethesda system, 4.87% of the cases were classified as Category I, 32.92% as Category II, 21.95% as Category III, 10.97% as Category IV, 14.63% as Category V and 14.63% as Category VI. Final pathological reports revealed that all the 4 cases of Category II (benign) (100%) were confirmed to be non-cancerous. In addition, 8/18 of cases (44.4%) classified as Category III (atypia of undetermined significance) were confirmed to be malignant and one (5.6%) diagnosed with the atypical follicular lesion, whereas the other cases were diagnosed with non-cancerous lesions. In contrast, all cases 9/9 suspicious for follicular neoplasm (Category IV) were confirmed to be malignant. Similarly, all cases 12/12 with Category V (suspicious for malignancy), and all cases categorised as malignant (VI) in FNA were also confirmed to be malignant. Conclusion: The results highlighted the importance of using a combined approach that consists of clinical, radiological as well as pathological approaches for a more accurate evaluation of the thyroid lesions. In addition, the results also showed that FNAC is a sensitive tool that can detect malignant thyroid nodules.
Keywords	diagnosis ; fine-needle aspiration ; sensitivity ; thyroid nodules ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Wolters Kluwer Medknow Publications
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction

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

Scientific Reports, Vol 11, Iss 1, Pp 1-

Derangement of cell cycle markers in peripheral blood mononuclear cells of asthmatic patients as a reliable biomarker for asthma control

2021 Volume 2

Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Wnt Signaling Is Deranged in Asthmatic Bronchial Epithelium and Fibroblasts

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

Frontiers in Cell and Developmental Biology, Vol

2021 Volume 9

Abstract: 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 ...

Abstract	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 on in silico analysis and followed by in vitro validation. In summary, the in silico analysis 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.
Keywords	asthma ; Wnt/b-catenin ; remodeling ; in silco analysis ; transcriptome ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Derangement of cell cycle markers in peripheral blood mononuclear cells of asthmatic patients as a reliable biomarker for asthma control

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 24

Abstract: Abstract 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 ... ...

Abstract	Abstract 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 ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Combination of obesity and co-morbidities leads to unfavorable outcomes in COVID-19 patients

Saba Al Heialy / Mahmood Yaseen Hachim / Ibrahim Yaseen Hachim / Kashif Bin Naeem / Haifa Hannawi / Jeyaseelan Lakshmanan / Issa Al Salmi / Suad Hannawi

Saudi Journal of Biological Sciences, Vol 28, Iss 2, Pp 1445-

2021 Volume 1450

Abstract: Objective: Obesity has been described as a significant independent risk factors of COVID-19. We aimed to study the association between obesity, co-morbidities and clinical outcomes of COVID-19. Methods: Clinical data from 417 patients were collected ... ...

Abstract	Objective: Obesity has been described as a significant independent risk factors of COVID-19. We aimed to study the association between obesity, co-morbidities and clinical outcomes of COVID-19. Methods: Clinical data from 417 patients were collected retrospectively from the Al Kuwait Hospital, Ministry of Health and Prevention (MOHAP), Dubai, United Arab Emirates, who were admitted between March and June 2020. Patients were divided according to their body mass index (BMI). Various clinical outcomes were examined: presenting symptoms, severity, major co-morbidities, ICU admission, death, ventilation, ARDS, septic shock and laboratory parameters. Results: The average BMI was 29 ± 6.2 kg/m2. BMI alone was not associated with the outcomes examined. However, class II obese patients had more co-morbidities compared to other groups. Hypertension was the most significant co-morbidity associated with obesity. Patients with BMI above the average BMI (29 kg/m2) and presence of underlying co-morbidities showed significant increase in admission to ICU compared to patients below 29 kg/m2 and underlying co-morbidities (21.7% Vs. 9.2%), ARDS development (21.7% Vs. 10.53%), need for ventilation (8.3% Vs. 1.3%), and mortality (10% Vs. 1.3%). Conclusions: Our data suggests that presence of underlying co-morbidities and high BMI work synergistically to affect the clinical outcomes of COVID-19.
Keywords	Obesity ; COVID-19 ; Co-morbidities ; Severity ; Biology (General) ; QH301-705.5
Subject code	610 ; 616
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Bone marrow mammaglobin-1 (SCGB2A2) immunohistochemistry expression as a breast cancer specific marker for early detection of bone marrow micrometastases

Iman Mamdouh Talaat / Mahmood Yaseen Hachim / Ibrahim Yaseen Hachim / Ramez Abd El-Razak Ibrahim / Mohamed Abd El Rahman Ahmed / Hanan Yehia Tayel

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 12

Abstract: Abstract 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’ ... ...

Abstract	Abstract 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.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Blood and Salivary Amphiregulin Levels as Biomarkers for Asthma

Frontiers in Medicine, Vol

2020 Volume 7

Abstract: Background: Amphiregulin (AREG) expression in asthmatic airways and sputum was shown to increase and correlate with asthma. However, no studies were carried out to evaluate the AREG level in blood and saliva of asthmatic patients.Objective: To measure ... ...

Abstract	Background: Amphiregulin (AREG) expression in asthmatic airways and sputum was shown to increase and correlate with asthma. However, no studies were carried out to evaluate the AREG level in blood and saliva of asthmatic patients.Objective: To measure circulating AREG mRNA and protein concentrations in blood, saliva, and bronchial biopsies samples from asthmatic patients.Methods: Plasma and Saliva AREG protein concentrations were measured using ELISA while PBMCs, and Saliva mRNA expression was measured by RT qPCR in non-severe, and severe asthmatic patients compared to healthy controls. Primary asthmatic bronchial epithelial cells and fibroblasts were assessed for AREG mRNA expression and released soluble AREG in their conditioned media. Tissue expression of AREG was evaluated using immunohistochemistry of bronchial biopsies from asthmatic patients and healthy controls. Publicly available transcriptomic databases were explored for the global transcriptomic profile of bronchial epithelium, and PBMCs were explored for AREG expression in asthmatic vs. healthy controls.Results: Asthmatic patients had higher AREG protein levels in blood and saliva compared to control subjects. Higher mRNA expression in saliva and primary bronchial epithelial cells plus higher AREG immunoreactivity in bronchial biopsies were also observed. Both blood and saliva AREG levels showed positive correlations with allergic rhinitis status, atopy status, eczema status, plasma periostin, neutrophilia, Montelukast sodium use, ACT score, FEV1, and FEV1/FVC. In silico analysis showed that severe asthmatic bronchial epithelium with high AREG gene expression is associated with higher neutrophils infiltration.Conclusion: AREG levels measured in a minimally invasive blood sample and a non-invasive saliva sample are higher in non-allergic severe asthma.Clinical ImplicationsThis is the first report to show the higher level of AREG levels in blood and saliva of non-allergic severe asthma.
Keywords	asthma ; biomarkers ; saliva ; amphiregulin (AREG) ; non-invasive ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Intranasal administration of abatacept enhances IL-35+ and IL-10+ producing Bregs in lung tissues of ovalbumin-sensitized asthmatic mice model.

Maha Fahad Alenazy / Fatemeh Saheb Sharif-Askari / Mohammed S El-Wetidy / Narjes Saheb Sharif-Askari / Ibrahim Yaseen Hachim / Mohammad-Hani Temsah / Basema Saddik / Roua Al-Kufaidy / Maha A Omair / Yasser A Alshawakir / Amany Adulgadel Fathaddin / Suad Hannawi / Qutayba Hamid / Mohammed A Omair / Saleh Al-Muhsen / Rabih Halwani

PLoS ONE, Vol 17, Iss 9, p e

2022 Volume 0271689

Abstract: Backgrounds Treating asthmatic rheumatoid arthritis patients with abatacept has been shown to associate with better control of asthma symptoms. However, the mechanism behind that is not investigated. Methods Ovalbumin (OVA)- sensitized BALB/c female mice ...

Abstract	Backgrounds Treating asthmatic rheumatoid arthritis patients with abatacept has been shown to associate with better control of asthma symptoms. However, the mechanism behind that is not investigated. Methods Ovalbumin (OVA)- sensitized BALB/c female mice were treated intranasally (IN) or intraperitoneally (IP) with abatacept 4 hrs before the OVA challenge. The effects of abatacept IN or IP on the lungs and blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and ELISA assay. Results Treating OVA- sensitized asthmatic mice model with abatacept, IN or IP, reduced lung inflammation. IN treatment with abatacept increased the frequency of IL-35 and IL-10 producing Bregs in the lung tissues to a higher level compared to IP treatment. Moreover, the frequency of lungs LAG3+ Tregs was significantly increased following treatment. This was also associated with a reduction in lung tissue and serum IL-17 levels of treated mice. Conclusions These results suggest that abatacept by enhancing IL-35+IL-10+ Bregs and LAG3+ Tregs might reverse IL-17 induced lung inflammation during asthma.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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