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Article ; Online: Evaluation of CO

Abdallah, Lamiaa / El-Shennawy, Tarek

Euro-Mediterranean journal for environmental integration

2020 Volume 5, Issue 3, Page(s) 49

Abstract: Energy-related ... ...

Abstract	Energy-related CO
Keywords	covid19
Language	English
Publishing date	2020-09-21
Document type	Journal Article
ZDB-ID	2843155-8
ISSN	2365-7448 ; 2365-6433
ISSN (online)	2365-7448
ISSN	2365-6433
DOI	10.1007/s41207-020-00184-w
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Article ; Online: Mathematical Modelling for the Role of CD4

Makhlouf, Ahmed M / El-Shennawy, Lamiaa / Elkaranshawy, Hesham A

Computational and mathematical methods in medicine

2020 Volume 2020, Page(s) 7187602

Abstract: Mathematical modelling has been used to study tumor-immune cell interaction. Some models were proposed to examine the effect of circulating lymphocytes, natural killer cells, and ... ...

Abstract	Mathematical modelling has been used to study tumor-immune cell interaction. Some models were proposed to examine the effect of circulating lymphocytes, natural killer cells, and CD8
MeSH term(s)	Antineoplastic Agents/administration & dosage ; CD4-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/cytology ; Computer Simulation ; Humans ; Immunotherapy/methods ; Immunotherapy, Adoptive ; Killer Cells, Natural/cytology ; Models, Theoretical ; Neoplasms/drug therapy ; Neoplasms/immunology ; Neoplasms/pathology ; Tomography, X-Ray Computed
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2020-02-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2252430-7
ISSN	1748-6718 ; 1748-670X ; 1027-3662
ISSN (online)	1748-6718
ISSN	1748-670X ; 1027-3662
DOI	10.1155/2020/7187602
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Article ; Online: Mathematical Modelling for the Role of CD4+T Cells in Tumor-Immune Interactions

Ahmed M. Makhlouf / Lamiaa El-Shennawy / Hesham A. Elkaranshawy

Computational and Mathematical Methods in Medicine, Vol

2020 Volume 2020

Abstract: Mathematical modelling has been used to study tumor-immune cell interaction. Some models were proposed to examine the effect of circulating lymphocytes, natural killer cells, and CD8+T cells, but they neglected the role of CD4+T cells. Other models were ... ...

Abstract	Mathematical modelling has been used to study tumor-immune cell interaction. Some models were proposed to examine the effect of circulating lymphocytes, natural killer cells, and CD8+T cells, but they neglected the role of CD4+T cells. Other models were constructed to study the role of CD4+T cells but did not consider the role of other immune cells. In this study, we propose a mathematical model, in the form of a system of nonlinear ordinary differential equations, that predicts the interaction between tumor cells and natural killer cells, CD4+T cells, CD8+T cells, and circulating lymphocytes with or without immunotherapy and/or chemotherapy. This system is stiff, and the Runge–Kutta method failed to solve it. Consequently, the “Adams predictor-corrector” method is used. The results reveal that the patient’s immune system can overcome small tumors; however, if the tumor is large, adoptive therapy with CD4+T cells can be an alternative to both CD8+T cell therapy and cytokines in some cases. Moreover, CD4+T cell therapy could replace chemotherapy depending upon tumor size. Even if a combination of chemotherapy and immunotherapy is necessary, using CD4+T cell therapy can better reduce the dose of the associated chemotherapy compared to using combined CD8+T cells and cytokine therapy. Stability analysis is performed for the studied patients. It has been found that all equilibrium points are unstable, and a condition for preventing tumor recurrence after treatment has been deduced. Finally, a bifurcation analysis is performed to study the effect of varying system parameters on the stability, and bifurcation points are specified. New equilibrium points are created or demolished at some bifurcation points, and stability is changed at some others. Hence, for systems turning to be stable, tumors can be eradicated without the possibility of recurrence. The proposed mathematical model provides a valuable tool for designing patients’ treatment intervention strategies.
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7
Subject code	570
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Dose-dependent reproductive toxicity of sodium benzoate in male rats: Inflammation, oxidative stress and apoptosis.

El-Shennawy, Lamiaa / Kamel, Maher Abd El-Naby / Khalaf, Asmaa Hassan Younis / Yousef, Mokhtar Ibrahim

Reproductive toxicology (Elmsford, N.Y.)

2020 Volume 98, Page(s) 92–98

Abstract: The synthetic food preservative sodium benzoate (SB) is widely used in both food and pharmaceutical industries. A growing body of evidence highlights the adverse effects of SB on human health; however, effect of the prolonged intake of SB on the ... ...

Abstract	The synthetic food preservative sodium benzoate (SB) is widely used in both food and pharmaceutical industries. A growing body of evidence highlights the adverse effects of SB on human health; however, effect of the prolonged intake of SB on the reproductive system is not fully elucidated. The current study investigates the effect of different doses of SB (0-1000 mg/kg BW) on the reproductive system of male rats administered oral SB for 90 consecutive days. Results revealed that increasing doses of SB significantly altered the weight of reproductive organs, decreased sperm count and motility and enhanced the percentage of abnormal sperms. This was concomitant with significant decline in plasma testosterone and FSH levels, increase in plasma LH and decrease in the activities of 17β-HSD and 17-KSR enzymes in the testes. Inflammation and oxidative stress were induced as indicated by the significant increase in TNF-α and IL-6 levels, inhibition of antioxidant enzymes activity and levels of GSH, increase in the levels of NO and TBARS and enhanced protein expression of mtTFA and UCP2 in the testes. Interestingly, p53 expression and caspase-3 activity were upregulated in the testes suggesting induction of apoptosis. Histopathological examination of the testes confirmed apoptosis and revealed degenerative alterations of the testes' architecture and perturbation of spermatogenesis. Based upon these findings, the no-observed-adverse-effect level of SB on the reproductive system was determined to be less than 1 mg/kg BW/day, highlighting the risks of long-term exposure to low as well as high doses of SB on male reproductive health.
MeSH term(s)	Administration, Oral ; Animals ; Apoptosis/drug effects ; Dose-Response Relationship, Drug ; Follicle Stimulating Hormone/blood ; Food Preservatives/toxicity ; Glutathione Transferase/metabolism ; Inflammation/chemically induced ; Inflammation/metabolism ; Inflammation/pathology ; Luteinizing Hormone/blood ; Male ; Mitochondria/drug effects ; Oxidative Stress/drug effects ; Oxidoreductases/metabolism ; Rats, Wistar ; Reproduction/drug effects ; Sodium Benzoate/toxicity ; Sperm Count ; Spermatozoa/drug effects ; Testis/drug effects ; Testis/metabolism ; Testis/pathology ; Testosterone/blood
Chemical Substances	Food Preservatives ; Testosterone (3XMK78S47O) ; Luteinizing Hormone (9002-67-9) ; Follicle Stimulating Hormone (9002-68-0) ; Oxidoreductases (EC 1.-) ; Glutathione Transferase (EC 2.5.1.18) ; Sodium Benzoate (OJ245FE5EU)
Language	English
Publishing date	2020-09-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	639342-1
ISSN	1873-1708 ; 0890-6238
ISSN (online)	1873-1708
ISSN	0890-6238
DOI	10.1016/j.reprotox.2020.08.014
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Article: Physics-driven structural docking and protein language models accelerate antibody screening and design for broad-spectrum antiviral therapy.

bioRxiv : the preprint server for biology

2024

Abstract: Therapeutic antibodies have become one of the most influential therapeutics in modern medicine to fight against infectious pathogens, cancer, and many other diseases. However, experimental screening for highly efficacious targeting antibodies is labor- ... ...

Abstract	Therapeutic antibodies have become one of the most influential therapeutics in modern medicine to fight against infectious pathogens, cancer, and many other diseases. However, experimental screening for highly efficacious targeting antibodies is labor-intensive and of high cost, which is exacerbated by evolving antigen targets under selective pressure such as fast-mutating viral variants. As a proof-of-concept, we developed a machine learning-assisted antibody generation pipeline that greatly accelerates the screening and re-design of immunoglobulins G (IgGs) against a broad spectrum of SARS-CoV-2 coronavirus variant strains. These viruses infect human host cells via the viral spike protein binding to the host cell receptor angiotensin-converting enzyme 2 (ACE2). Using over 1300 IgG sequences derived from convalescent patient B cells that bind with spike's receptor binding domain (RBD), we first established protein structural docking models in assessing the RBD-IgG-ACE2 interaction interfaces and predicting the virus-neutralizing activity of each IgG with a confidence score. Additionally, employing Gaussian process regression (also known as Kriging) in a latent space of an antibody language model, we predicted the landscape of IgGs' activity profiles against individual coronaviral variants of concern. With functional analyses and experimental validations, we efficiently prioritized IgG candidates for neutralizing a broad spectrum of viral variants (wildtype, Delta, and Omicron) to prevent the infection of host cells
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.01.582176
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Article ; Online: Unique molecular signatures sustained in circulating monocytes and regulatory T cells in convalescent COVID-19 patients.

Clinical immunology (Orlando, Fla.)

2023 Volume 252, Page(s) 109634

Abstract: Over two years into the COVID-19 pandemic, the human immune response to SARS-CoV-2 during the active disease phase has been extensively studied. However, the long-term impact after recovery, which is critical to advance our understanding SARS-CoV-2 and ... ...

Abstract	Over two years into the COVID-19 pandemic, the human immune response to SARS-CoV-2 during the active disease phase has been extensively studied. However, the long-term impact after recovery, which is critical to advance our understanding SARS-CoV-2 and COVID-19-associated long-term complications, remains largely unknown. Herein, we characterized single-cell profiles of circulating immune cells in the peripheral blood of 100 patients, including convalescent COVID-19 and sero-negative controls. Flow cytometry analyses revealed reduced frequencies of both short-lived monocytes and long-lived regulatory T (Treg) cells within the patients who have recovered from severe COVID-19. sc-RNA seq analysis identifies seven heterogeneous clusters of monocytes and nine Treg clusters featuring distinct molecular signatures in association with COVID-19 severity. Asymptomatic patients contain the most abundant clusters of monocytes and Tregs expressing high CD74 or IFN-responsive genes. In contrast, the patients recovered from a severe disease have shown two dominant inflammatory monocyte clusters featuring S100 family genes: one monocyte cluster of S100A8 & A9 coupled with high HLA-I and another cluster of S100A4 & A6 with high HLA-II genes, a specific non-classical monocyte cluster with distinct IFITM family genes, as well as a unique TGF-β high Treg Cluster. The outpatients and seronegative controls share most of the monocyte and Treg clusters patterns with high expression of HLA genes. Surprisingly, while presumably short-lived monocytes appear to have sustained alterations over 4 months, the decreased frequencies of long-lived Tregs (high HLA-DRA and S100A6) in the outpatients restore over the tested convalescent time (≥ 4 months). Collectively, our study identifies sustained and dynamically altered monocytes and Treg clusters with distinct molecular signatures after recovery, associated with COVID-19 severity.
MeSH term(s)	Humans ; Monocytes ; COVID-19/metabolism ; T-Lymphocytes, Regulatory ; Pandemics ; SARS-CoV-2
Language	English
Publishing date	2023-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2023.109634
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Article ; Online: EGFR inhibition blocks cancer stem cell clustering and lung metastasis of triple negative breast cancer.

Liu, Xia / Adorno-Cruz, Valery / Chang, Ya-Fang / Jia, Yuzhi / Kawaguchi, Madoka / Dashzeveg, Nurmaa K / Taftaf, Rokana / Ramos, Erika K / Schuster, Emma J / El-Shennawy, Lamiaa / Patel, Dhwani / Zhang, Youbin / Cristofanilli, Massimo / Liu, Huiping

Theranostics

2021 Volume 11, Issue 13, Page(s) 6632–6643

Abstract: Triple-negative breast cancer (TNBC) is one of the most aggressive and metastatic breast cancer subtypes lacking targeted therapy. Our recent work demonstrated that circulating tumor cell (CTC) clusters and polyclonal metastasis of TNBC are driven by ... ...

Abstract	Triple-negative breast cancer (TNBC) is one of the most aggressive and metastatic breast cancer subtypes lacking targeted therapy. Our recent work demonstrated that circulating tumor cell (CTC) clusters and polyclonal metastasis of TNBC are driven by aggregation of CD44
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents, Immunological/immunology ; Antineoplastic Agents, Immunological/therapeutic use ; Cell Aggregation/drug effects ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/immunology ; ErbB Receptors/physiology ; Erlotinib Hydrochloride/therapeutic use ; Female ; Genes, Reporter ; Humans ; Hyaluronan Receptors/antagonists & inhibitors ; Hyaluronan Receptors/physiology ; Lung Neoplasms/prevention & control ; Lung Neoplasms/secondary ; Mice ; MicroRNAs/genetics ; Molecular Targeted Therapy ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/physiology ; Neoplastic Cells, Circulating/drug effects ; Neoplastic Stem Cells/drug effects ; RNA/genetics ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/pathology ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; Antineoplastic Agents, Immunological ; CD44 protein, human ; Hyaluronan Receptors ; MIRN30b microRNA, human ; MicroRNAs ; Neoplasm Proteins ; RNA, recombinant ; RNA (63231-63-0) ; Erlotinib Hydrochloride (DA87705X9K) ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2021-04-30
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2592097-2
ISSN	1838-7640 ; 1838-7640
ISSN (online)	1838-7640
ISSN	1838-7640
DOI	10.7150/thno.57706
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Article ; Online: The Arabian camel, Camelus dromedarius interferon epsilon: Functional expression, in vitro refolding, purification and cytotoxicity on breast cancer cell lines.

Abdel-Fattah, Manal / Saeed, Hesham / El-Shennawy, Lamiaa / Shalaby, Manal / Embaby, Amira / Ataya, Farid / Mahmoud, Hoda / Hussein, Ahmed

PloS one

2019 Volume 14, Issue 9, Page(s) e0213880

Abstract: The current study highlights, for the first time, cloning, overexpression and purification of the novel interferon epsilon (IFNƐ), from the Arabian camel Camelus dromedaries. The study then assesses the cytotoxicity of IFNε against two human breast ... ...

Abstract	The current study highlights, for the first time, cloning, overexpression and purification of the novel interferon epsilon (IFNƐ), from the Arabian camel Camelus dromedaries. The study then assesses the cytotoxicity of IFNε against two human breast cancer cell lines MDA-MB-231 and MCF-7. Full-length cDNA encoding interferon epsilon (IFNε) was isolated and cloned from the liver of the Arabian camel, C. dromedarius using reverse transcription-polymerase chain reaction. The sequence analysis of the camel IFNε cDNA showed a 582-bp open reading frame encoding a protein of 193 amino acids with an estimated molecular weight of 21.230 kDa. A BLAST search analysis revealed that the C. dromedarius IFNε shared high sequence identity with the IFN genes of other species, such as Camelus ferus, Vicugna pacos, and Homo sapiens. Expression of the camel IFNε cDNA in Escherichia coli gave a fusion protein band of 24.97 kDa after induction with either isopropyl β-D-1-thiogalactopyranoside or lactose for 5 h. Recombinant IFNε protein was overexpressed in the form of inclusion bodies that were easily solubilized and refolded using SDS and KCl. The solubilized inclusion bodies were purified to apparent homogeneity using nickel affinity chromatography. We examined the effect of IFNε on two breast cancer cell lines MDA-MB-231 and MCF-7. In both cell lines, IFNε inhibited cell survival in a dose dependent manner as observed by MTT assay, morphological changes and apoptosis assay. Caspase-3 expression level was found to be increased in MDA-MB-231 treated cells as compared to untreated cells.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Camelus/genetics ; Cell Survival/drug effects ; Cloning, Molecular ; Humans ; Interferons/chemistry ; Interferons/genetics ; Interferons/metabolism ; Interferons/pharmacology ; MCF-7 Cells ; Male ; Protein Folding ; Sequence Homology
Chemical Substances	Antineoplastic Agents ; Interferons (9008-11-1)
Language	English
Publishing date	2019-09-06
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0213880
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Article ; Online: Physics-driven structural docking and protein language models accelerate antibody screening and design for broad-spectrum antiviral therapy

bioRxiv

Abstract	Therapeutic antibodies have become one of the most influential therapeutics in modern medicine to fight against infectious pathogens, cancer, and many other diseases. However, experimental screening for highly efficacious targeting antibodies is labor-intensive, which is exacerbated by evolving antigen targets under selective pressure such as fast-mutating viral variants. As a proof-of-concept, we developed a machine learning-assisted antibody generation pipeline that greatly accelerates the screening and re-design of immunoglobulins G (IgGs) against a broad spectrum of coronavirus variants. Using over 1300 IgG sequences derived from patient B cells bound with the viral spike9s receptor binding domain (RBD), we first established protein structural docking models in assessing the IgG-RBD-ACE2 interaction interfaces and predicting their viral neutralizing activities with a confidence score. The confidence score is calculated as a fraction of IgG-blocking RBD binding sites versus all ACE2-interacting sites. Additionally, employing Gaussian process regression (also known as Kriging) in a latent space of an antibody language model, we predicted the IgGs9 activity profiles against viral strains. Using functional analyses and experimental validations, we subsequently prioritized IgG candidates for neutralizing a broad spectrum of viral variants (wildtype, Delta, and Omicron) and preventing the infection of host cells in vitro and hACE2 transgenic mice in vivo. To further improve the blockade efficacy for the Delta strain (B.1.617), we rationally redesigned the IgG clones with single amino acid substitutions at the RBD-binding interface. Our work expedites applications of artificial intelligence in low-data regimes when limited data is available, including protein language models (using unlabeled data) and Kriging (using few labeled data) for antibody sequence analysis, activity prediction, and efficacy improvement, which are aided by physics-driven protein docking models for antibody-antigen interface structure analyses.
Keywords	covid19
Language	English
Publishing date	2024-03-04
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.03.01.582176
Database	COVID19

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Article ; Online: NFκB affects estrogen receptor expression and activity in breast cancer through multiple mechanisms.

Frasor, Jonna / El-Shennawy, Lamiaa / Stender, Joshua D / Kastrati, Irida

Molecular and cellular endocrinology

2015 Volume 418 Pt 3, Page(s) 235–239

Abstract: Estrogen receptor (ER) and NFκB are two widely expressed, pleiotropic transcription factors that have been shown to interact and affect one another's activity. While the ability of ER to repress NFκB activity has been extensively studied and is thought ... ...

Abstract	Estrogen receptor (ER) and NFκB are two widely expressed, pleiotropic transcription factors that have been shown to interact and affect one another's activity. While the ability of ER to repress NFκB activity has been extensively studied and is thought to underlie the anti-inflammatory activity of estrogens, how NFκB signaling affects ER activity is less clear. This is a particularly important question in breast cancer since activation of NFκB in ER positive tumors is associated with failure of endocrine and chemotherapies. In this review, we provide an update on the multiple mechanisms by which NFκB can influence ER activity, including down-regulation of ER expression, enhanced ER recruitment to DNA, and increased transcriptional activity of both liganded and unliganded ER. Additionally, a novel example of NFκB potentiation of ER-dependent gene repression is reviewed. Together, these mechanisms can alter response to endocrine therapies and may underlie the poor outcome for women with ER positive tumors that have active NFκB signaling.
MeSH term(s)	Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Down-Regulation ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; NF-kappa B/metabolism ; Receptors, Estrogen/genetics ; Receptors, Estrogen/metabolism ; Signal Transduction ; Tamoxifen/therapeutic use ; Transcription, Genetic
Chemical Substances	NF-kappa B ; Receptors, Estrogen ; Tamoxifen (094ZI81Y45)
Language	English
Publishing date	2015-12-15
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2014.09.013
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