Hamza Hanieh

Hamza Hanieh
Al-Hussein Bin Talal University | AHU · Department of Medical Analysis

Doctor of Philosophy

About

63
Publications
12,166
Reads
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1,387
Citations
Introduction
-Docking-based drug design and evaluation for currently uncured diseases including autoimmunity and cancer. -Post-transcriptional regulation of mRNA stability in acute inflammation and chronic inflammation (Autoimmunity). - Epigenetic regulation of pathogenesis of inflammatory and autoimmune diseases by Ahr/microRNAs axis. - The role of microRNAs in cell signaling and differentiation Pro- and anti-inflammatory T cells. - Transcriptional regulation of Ahr on microRNAs in immune responses.

Publications

Publications (63)
Article
Multiple sclerosis (MS) is a degenerative autoimmune disease attacks the myelin sheath of the central nervous system (CNS) neurons causing different disabilities. According to recent evidence, the main bioactive component in Enicostema axillare , the Swrtiamarin (SM) has been found to exert anti-inflammatory and antioxidant activities against sever...
Article
Full-text available
The role of oxidative injury and inflammatory response in cardiovascular diseases and heart failure has been well-acknowledged. This study evaluated the protective effect of umbelliferone (UMB), a coumarin with promising radical scavenging and anti-inflammatory activities, on myocardial injury induced by isoproterenol (ISO) in rats. Rats received 5...
Article
Background: Despite the significant advances in diagnosis and treatment, breast cancer remains the most common malignancy and the second cause of death in women. Increasingly, preclinical evidence has suggested aryl hydrocarbon receptor (Ahr), a ligand activated transcription factor, a promising therapeutic target in breast cancer. Purpose: This st...
Article
The short non-coding microRNAs (miRNAs) have emerged as reliable modulators of various pathological conditions including autoimmune diseases in mammals. The current study, aims to identify new potential differential expressed miRNAs and their downstream mRNA targets of the autoimmune disease, Multiple sclerosis (MS). The study identifies a new set...
Article
Full-text available
Kirenol (KRL) is a biologically active substance extracted from Herba Siegesbeckiae. This natural type of diterpenoid has been widely adopted for its important anti-inflammatory and anti-rheumatic properties. Despite several studies claiming the benefits of KRL, its cardiac effects have not yet been clarified. Cardiotoxicity remains a key concern a...
Preprint
Full-text available
The short non-coding microRNAs (miRNAs), have emerged as reliable modulators of various pathological conditions including autoimmune diseases in mammals. The current study, aims to identify new potential differential expressed miRNAs and their downstream mRNA targets of the autoimmune disease, Multiple sclerosis (MS). First, we used a computational...
Article
Full-text available
Multiple sclerosis (MS) is an autoimmune disease that involves demyelination of axons in the central nervous system (CNS) and affects patients worldwide. It has been demonstrated that ligand-activated aryl hydrocarbon receptor (Ahr) ameliorates experimental autoimmune encephalomyelitis (EAE), a murine model of MS, by increasing CD4⁺FoxP3⁺ T cells....
Article
Full-text available
The lipopolysaccharide (LPS)–induced endocytosis of Toll-like receptor 4 (TLR4) is an essential step in the production of interferon-β (IFN-β), which activates the transcription of antiviral response genes by STAT1 phosphorylated at Tyr ⁷⁰¹ . Here, we showed that STAT1 regulated proinflammatory cytokine production downstream of TLR4 endocytosis ind...
Article
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Cyclophosphamide (CP) is a widely used chemotherapeutic agent; however, its clinical application is limited because of its multi-organ toxicity. Galangin (Gal) is a bioactive flavonoid with promising biological activities. This study investigated the hepatoprotective effect of Gal in CP-induced rats. Rats received Gal (15, 30 and 60 mg/kg/day) for...
Article
Full-text available
Immune cells infiltrate adipose tissues and provide a framework to regulate energy homeostasis. However, the precise underlying mechanisms and signaling by which the immune system regulates energy homeostasis in metabolic tissues remain poorly understood. Here, we show that the AT-rich interactive domain 5A (Arid5a), a cytokine-induced nucleic acid...
Article
Sex-determining region Y-related (SRY) high-mobility group box 4 (SOX4) is a member of the group C subfamily of SOX transcription factors and promotes tumorigenesis by endowing cancer cells with survival, migratory, and invasive capacities. Emerging evidence has highlighted an unequivocal role for this transcription factor in mediating various sign...
Article
Full-text available
Senescence and autophagy play important roles in homeostasis. Cellular senescence and autophagy commonly cause several degenerative processes, including oxidative stress, DNA damage, telomere shortening, and oncogenic stress; hence, both events are known to be interrelated. Autophagy is well known for its disruptive effect on human diseases, and it...
Article
Full-text available
Background Multiple sclerosis (MS) is a widespread neurological autoimmune disease that includes episodes of demyelination in the central nervous system (CNS). The accumulated evidence has suggested that aryl hydrocarbon receptor (Ahr), a ligand-activated transcription factor, is a promising treatment target for MS. Thus, the current study aimed to...
Data
High levels of GA show toxic effects. (A and B) The CD4+CD62L+ T cells were isolated from the spleen and cultured under Th17-polarizing conditions, and peritoneal macrophages were cultured in presence of LPS. Cell viability of (A) differentiating Th17 and (B) peritoneal macrophages 48 hr after stimulation in presence of GA (20–120 μmol/L). (C and D...
Data
GA suppresses AChE activity in CD4+ T cells and macrophages. AChE catalytic activity in culture supernatant of (A) CD4+ T cells isolated from naive mice and stimulated with PHA and (B) peritoneal macrophages were stimulated with LPS. The PHA-stimulated CD4+ T cells and LPS-stimulated macrophages were electroporated with antisense (as)-miR-132, and...
Data
In silico molecular modeling of mouse Ahr PAS-B domain. A) Superimposition of predicted 3D structure of mouse Ahr PAS-B domain with the human C-terminal PAS domain of HIF2a (PDB ID: 1p97). (B) Ramachandran plot of predicted mouse Ahr PAS-B domain. (PDF)
Data
Efficiency of cell stimulation milieus. The CD4+CD62L+ T cells were isolated from the spleen and cultured under Th17-, Treg or Tr1-polarizing conditions, and peritoneal macrophages were cultured in presence of LPS. The mRNA expression of Rorc, Il6, FoxP3 and Il10 were assessed by quantitative real‐time PCR and normalized to Gapdh mRNA. (A) Relative...
Article
Full-text available
AT-rich interactive domain-containing protein 5a (Arid5a) is an RNA-binding protein (RBP) required for autoimmunity via stabilization of interleukin-6 (Il6) and signal transducer and activator of transcription 3 (STAT3) mRNAs. However, the roles of Arid5a in Th17 cells and its association with autoimmunity remain unknown. Here, we show that the lev...
Article
Full-text available
Atorvastatin is a lipid lowering agent and widely used to treat hypercholestermia. However following oral administration, the bioavailability of the drug is only 12% due to extensive first pass metabolism. The aim of the current research was to formulate ATO- transdermal patches utilizing various polymers combinations. Hydroxypropyl methylcellulose...
Article
AT-rich interactive domain-containing protein 5a (Arid5a) is an RNA-binding protein (RBP) required for autoimmunity via stabilization of interleukin-6 (Il6) and signal transducer and activator of transcription 3 (STAT3) mRNAs. However, the roles of Arid5a in Th17 cells and its association with autoimmunity remains unknown. Here, we show that the le...
Article
Full-text available
Background: Chronic inflammation in ulcerative colitis (UC) patients is the major risk factor for colitis-associated colon cancer (CAC). Recent evidences have shown that microRNAs (miRNAs) are implicated in CAC pathogenesis. However, the interaction of miRNAs with the transcription factors that alleviate CAC has not been reported. Methods: 2,3,7...
Article
Pinocembrin (5, 7- dihydroxy flavanone) is the most abundant chiral flavonoid found in propolis, exhibiting antioxidant, antimicrobial and anti-inflammatory properties. However, the effect of Pinocembrin on allergic response is unexplored. Thus, current study aimed at investigating the effects of Pinocembrin on IgE-mediated allergic response in vit...
Article
Full-text available
The AT-rich interactive domain-containing protein 5a (Arid5a) plays a critical role in autoimmunity by regulating the half-life of Interleukin-6 (IL-6) mRNA. However, the signaling pathways underlying Arid5a-mediated regulation of IL-6 mRNA stability are largely uncharacterized. Here, we found that during the early phase of lipopolysaccharide (LPS)...
Article
Full-text available
Background Despite the remarkable progress to fight against breast cancer, metastasis remains the dominant cause of treatment failure and recurrence. Therefore, control of invasiveness potential of breast cancer cells is crucial. Accumulating evidences suggest Aryl hydrocarbon receptor (Ahr), a helix-loop-helix transcription factor, as a promising...
Data
Sox4 mitigates the inhibitory effects of Flavipin on migration of breast cancer cells. Sox4-expressing or empty vector and incubated for 6 h to recover. The cell were seeded in 6-well plate in a complete medium and allowed to attach overnight, then treated with DMSO or Flavipin (200 μmol/L) in the charcoal-stripped medium for 24 h. A line was made...
Data
Amino acid composition of human Ahr PAS-B domain. (DOCX)
Data
The in silico docking of Lonchophorcol A binding potential to human Ahr. Lonchophorcol A binds to Ahr at Thr264 and Ala119. The yellow-dotted lines indicates the hydrogen bonds. (JPG)
Data
The in silico molecular modeling of human Ahr PAS-B. (A) Superimposition of predicted 3D structure of Ahr PAS-B with the Arnt PAS-B. (B) The Ramachandran plot of predicted Ahr PAS-B and Arnt PAS-B. (TIF)
Data
Flavipin suppresses adhesion of breast cancer cells. The T47D and MDA-MB-231 cells were seeded in 6-well plate and incubated overnight in complete medium to attach, then washed with PBS to remove the non-adherent cells. Cells were then treated with DMSO or Flavipin (200 μmol/L) in the charcoal-stripped medium for 48 h, and washed two times with PBS...
Data
Molecular docking of Ahr agonist candidates. (DOCX)
Data
Procheck statistics of 3D structure human Ahr PAS-B domain. (DOCX)
Data
Flavipin suppresses ITGA4 in breast cancer cells. The T47D and MDA-MB-231 cells were seeded in 10 cm plate and incubated overnight in complete medium to attach, then treated with DMSO or Flavipin (200 μmol/L) in the charcoal-stripped medium for 48 h. The T47D medium contained 10 nmol/L E2. (A) ITGA4 mRNA. The mRNA was quantified by real-time PCR us...
Data
Sox4 mitigates the inhibitory effects of Flavipin on invasion of breast cancer cells. The cells were transfected by electroporation with Sox4-expressing or empty vector and incubated for 6 h to recover. Cell invasion was studied using Boyden chamber. The cells were suspended in serum-free medium and placed in the trans-well, the lower well containe...
Data
Primary structural properties of human Ahr PAS-B domain. (DOCX)
Article
Full-text available
Adenine-thymine (AT)-rich interactive domain containing protein 5a (Arid5a) is an RNA-binding protein that has been shown to play an important immune regulatory function via the stabilization of IL-6 and STAT3 mRNA. However, the role of Arid5a in the overwhelming and uncontrolled immune response that leads to septic shock is unknown. Here, we repor...
Article
Full-text available
Balance in signal transducer and activator of transcription (STAT) activation is a key factor in regulating the fate of naive CD4 + T cells. Here, we demonstrate that AT-rich interactive domain-containing protein 5a (Arid5a) in T cells directs naive CD4 + T cells to differentiate into inflammatory CD4 + T cells, especially Th17 cells, through selec...
Article
Full-text available
Background: MicroRNAs (miRNAs) are a class of short non-coding RNAs that pave a new avenue for understanding immune responses and cancer progression. Although the miRNAs are involved in breast cancer development, their axis with the transcription factors that show therapeutic potential in breast cancer is largely unknown. Previous studies showed a...
Article
Full-text available
Aryl hydrocarbon receptor (Ahr), a transcription factor, plays a critical role in autoimmune inflammation of the intestine. In addition, microRNAs (miRNAs), small non-coding oligonucleotides, mediate pathogenesis of inflammatory bowel diseases (IBD). However, the precise mechanism and interactions of these molecules in IBD pathogenesis have not yet...
Article
Full-text available
The discovery of microRNAs (miRNAs) is one of the most significant breakthroughs in recent decades. miRNAs are a class of small, endogenous, non-coding RNAs (19–24 nt) that negatively regulate the expression of target genes by binding to their 39 untranslated region and are involved in various biological processes. Three main approaches that are gl...
Article
Full-text available
The immune system is regulated by distinct signaling pathways that control the development and function of the immune cells. Accumulating evidence suggest that ligation of aryl hydrocarbon receptor (Ahr), an environmentally responsive transcription factor, results in multiple cross talks that are capable of modulating these pathways and their downs...
Article
Full-text available
MicroRNAs (miRNAs) are a small group of RNAs that are emerging as a new avenue by which autoimmune diseases may be modulated. Accumulating evidence shows that miRNAs are involved in the pathogenesis of MS; however, the interaction of miRNAs with environmentally responsive transcription factors that play prominent roles in MS is unexplored. The acti...
Article
Full-text available
Aryl hydrocarbon receptor (AHR) plays critical roles in various autoimmune diseases such as multiple sclerosis by controlling interleukin-17 (IL-17)-producing T-helper (TH17) and regulatory T cells. Although various transcription factors and cytokines have been identified as key participants in TH17 generation, the role of microRNAs in this process...
Article
Full-text available
A number of recent studies have examined the functions of aryl hydrocarbon receptor (Ahr) in the immune system. Also known as dioxin receptor, Ahr is a ligand-activated transcription factor that serves as a receptor for various environmental toxins. The functions of Ahr in T cells depend on the specific ligand bound to the receptor. For instance, b...
Article
Full-text available
Polymorphisms in the genes encoding CYP2C9 enzyme and VKORC1 reductase significantly influence the dose variability of coumarinic oral anticoagulants (COAs). Substantial inter- and intraethnic variability exists in the frequencies of CYP2C9 (∗) 2 and (∗) 3 and VKORC1 -1639A alleles. However, the prevalence of CYP2C9 and VKORC1 genetic variants is l...
Article
We previously described that supplementary garlic, onion and purple sweet potato (PSP) enhance humoral immune response in White Leghorn chickens. In the present in vitro study, we investigated the effects of garlic (GE), onion (OE) and PSP (PSPE) extracts on proliferation, interleukin (IL)-2 and interferon (INF)-γ gene expression of stimulated lymp...
Article
Macrophages play a pivotal role in innate immune responses to pathogens via toll-like receptors. We previously demonstrated that aryl hydrocarbon receptor (Ahr) in combination with signal transducer and activator of transcription 1 (Stat1) negatively regulates pro-inflammatory cytokine production by inhibiting nuclear factor-κB activation in macrop...
Article
Full-text available
The contributions of aryl hydrocarbon receptor (Ahr) to the pathogenesis of rheumatoid arthritis have not been elucidated. Here, we show that Ahr deficiency ameliorated collagen-induced arthritis, a mouse model of RA. Collagen-immunized Ahr KO mice showed decreased serum levels of such proinflammatory cytokines as IL-1β and IL-6. The Th17 and Th1 c...
Article
This study aimed at investigating the effects of dietary Allium sativum (garlic, G) and Allium cepa (onion, O) on immune functions in White Leghorn chicken. One-week-old chicks, were fed diets without (control) or with Alliums (GL and OL, 10 g or GH and OH, 30 g/kg diet). Chickens were immunized with Newcastle disease virus (NDV), sheep red blood c...
Article
Full-text available
This study was intended to determine the modulatory effects of dietary supplementation of purple sweet potato (Ipomoea batats Poir., PSP) on the immune response of chickens. PSP was included in a basal starter diet by 1% (PSP(L)) or 3% (PSP(H)) and continually fed. Newcastle disease (NDV) vaccine, Brucella abortus (BA) and sheep red blood cells (SR...
Article
Flow cytometric analysis and immunohistochemical observation were used to qualitatively and quantitatively clarify the nature of B cell differentiation in the bursa of Fabricius of chick embryos and to determine the timing of antibody class switching in chicken spleens based on positivity of IgM and IgG on and in the cells. In the bursa, the sIgM-p...
Article
The signaling pathways leading to the activation of extracellular signal-regulated kinase (ERK) by phorbol 12-myristate 13-acetate (PMA), formyl-methionylleucyl-phenylalanine (fMLP) and lipopolysaccharide (LPS) in chicken heterophils were examined. To determine the mechanism of ERK's activation and its relation with the influx of calcium ions, hete...
Article
Full-text available
This study aimed to evaluate the effect of sugar alcohol as an energy source for cecal microbes on digestibility, cecotrophy (i.e. reingestion of microbial products of cecum, cecotrophs) and performance in rabbits. Thus, we fed rabbits an experimental diet that included 5% of D-mannitol, and collected hard feces and cecotrophs to be analyzed for cr...

Questions

Question (1)
Question
Does anyone has advices or explanation for the following? I have three cells line MCF-7, T47D and MDA231, when I received these cells in 25 cm flasks from friend's laboratory, they were adherent and look very healthy. I trypsinized them and transfer to 75 cm flask at 70 % conflu. in the mediums recommended by ATCC. The T47D cells kept growing well for three passages then started to detach and grow slowly. The MCF-7 and MDA231 started to detach next day and growth and adherence stopped. The laboratory who provided us with these cells uses DMEM/F-12 medium without insulin, so I changed to this medium for all cells, but no significant difference, the cells have been cultured for more than one week, and the medium is changed every two days, but no significant advancement. Can any one help me to solve this problem?

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