Khairy M.A. Zoheir
King Saud University
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Featured researches published by Khairy M.A. Zoheir.
Immunobiology | 2015
Sheikh F. Ahmad; Mushtaq Ahmad Ansari; Khairy M.A. Zoheir; Saleh A. Bakheet; Hesham M. Korashy; Ahmed Nadeem; Abdelkader E. Ashour; Sabry M. Attia
Histamine 4 receptor (H4R) is a novel target for the pharmacological modulation of histamine-mediated immune signals during inflammatory diseases. The purpose of this study was to assess the effects of the H4R agonist 4-methylhistamine dihydrochloride (4-MeH) and antagonist JNJ7777120 (JNJ) in the inflamed rat knee. Animals were fasted for 18h before a single dose of 4-MeH or JNJ (30mg/kg) was administered intraperitoneally (i.p.), both followed by intra-articular (i.a.) injection of LPS 2h later. Blood and synovial fluid were collected after a short incubation period and TNF-α, NF-κB, and IkB-α levels were measured via flow cytometry. Additionally, we assessed the effects of H4R engagement on the expression of IL-1β, TNF-α, and NF-κB mRNAs and the protein levels of TNF-α, NF-κB, JAK-1, and STAT-3 in the inflamed knee tissue. These results revealed increased TNF-α and NF-κB expression and decreased IkB-α levels in both the LPS alone and 4-MeH treated groups in whole blood and synovial fluid. Further, IL-1β, TNF-α, and NF-κB mRNA levels were significantly increased and western blot analysis confirmed increased expression of TNF-α, NF-κB, JAK-1, and STAT-3 in both LPS and 4-MeH treatment groups. Furthermore, these increases were completely inhibited in the inflamed knee tissue of the JNJ-treated group. Thus, the inhibition of inflammatory mediators and signaling pathways by the H4R antagonist JNJ suggests the anti-arthritic importance of this molecule.
Pharmacological Research | 2015
Ahmed Nadeem; Naif O. Al-Harbi; Mohamed M. Al-Harbi; Ahmed M. El-Sherbeeny; Sheikh F. Ahmad; Nahid Siddiqui; Mushtaq Ahmad Ansari; Khairy M.A. Zoheir; Sabry M. Attia; Khaled A. Al-Hosaini; Shakir D. Al-Sharary
Psoriasis is one of the most common skin disorders characterized by erythematous plaques that result from hyperproliferative keratinocytes and infiltration of inflammatory leukocytes into dermis and epidermis. Recent studies suggest that IL-23/IL-17A/IL-22 cytokine axis plays an important role in the pathogenesis of psoriasis. The small molecule bromodomain and extraterminal domain (BET) inhibitors, that disrupt interaction of BET proteins with acetylated histones have recently demonstrated efficacy in various models of inflammation through suppression of several pathways, one of them being synthesis of IL-17A/IL-22 which primarily depends on transcription factor, retinoic acid receptor-related orphan receptor C (RORC). However, the efficacy and mechanistic aspect of a BET inhibitor in mouse model of skin inflammation has not been explored previously. Therefore, this study investigated the role of BET inhibitor, JQ-1 in mouse model of psoriasis-like inflammation. Mice were topically applied imiquimod (IMQ) to develop psoriasis-like inflammation on the shaved back and ear followed by assessment of skin inflammation (myeloperoxidase activity, ear thickness, and histopathology), RORC and its signature cytokines (IL-17A/IL-22). JQ-1 suppressed IMQ-induced skin inflammation as reflected by a decrease in ear thickness/myeloperoxidase activity, and RORC/IL-17A/IL-22 expression. Additionally, a RORα/γ agonist SR1078 was utilized to investigate the role of RORC in BET-mediated skin inflammation. SR1078 reversed the protective effect of JQ-1 on skin inflammation at both histological and molecular levels in the IMQ model. The current study suggests that BET bromodomains are involved in psoriasis-like inflammation through induction of RORC/IL-17A pathway. Therefore, inhibition of BET bromodomains may provide a new therapy against skin inflammation.
Molecular Neurobiology | 2017
Sheikh F. Ahmad; Khairy M.A. Zoheir; Mushtaq Ahmad Ansari; Ahmed Nadeem; Saleh A. Bakheet; Laila Al-Ayadhi; Mohammad Zeed Alzahrani; Othman A. Al-Shabanah; Mohammed M. Al-Harbi; Sabry M. Attia
Autism is a neurodevelopmental disorder characterized by stereotypic repetitive behaviors, impaired social interactions, and communication deficits. Numerous immune system abnormalities have been described in individuals with autism including abnormalities in the ratio of Th1/Th2/Th17 cells; however, the expression of the transcription factors responsible for the regulation and differentiation of Th1/Th2/Th17/Treg cells has not previously been evaluated. Peripheral blood mononuclear cells (PBMCs) from children with autism (AU) or typically developing (TD) control children were stimulated with phorbol-12-myristate 13-acetate (PMA) and ionomycin in the presence of brefeldin A. The expressions of Foxp3, RORγt, STAT-3, T-bet, and GATA-3 mRNAs and proteins were then assessed. Our study shows that children with AU displayed altered immune profiles and function, characterized by a systemic deficit of Foxp3+ T regulatory (Treg) cells and increased RORγt+, T-bet+, GATA-3+, and production by CD4+ T cells as compared to TD. This was confirmed by real-time PCR (RT-PCR) and western blot analyses. Our results suggest that autism impacts transcription factor signaling, which results in an immunological imbalance. Therefore, the restoration of transcription factor signaling may have a great therapeutic potential in the treatment of autistic disorders.
International Immunopharmacology | 2013
Sheikh F. Ahmad; Khairy M.A. Zoheir; Hala E. Abdel-Hamied; Abdelkader E. Ashour; Saleh A. Bakheet; Sabry M. Attia; Adel R.A. Abd-Allah
Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation of the synovial joints, joint malformations, and disability. The continuous use of conventional anti-inflammatory drugs is associated with severe adverse effects. Grape seed proanthocyanidin extract (GSPE) is considered to have protective effects against several diseases. In this study based on the mouse adjuvant-induced-arthritis (AIA) model, we examined the effects of GSPE on the key mediators of arthritic inflammation, namely T cell subsets, glucocorticoid-induced tumour necrosis factor receptor (GITR) expressing cells, CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells, Th17 cells, Th1/Th2 cytokines, and inflammatory mediator gene expression. We treated BALB/c mice with 25, 50, or 100 mg/kg GSPE or saline daily (14 days) per orally (p.o.) at the onset of AIA. At the peak phase of AIA (day 14), the heparinised whole blood and ankle joints of all groups were collected and tested. GSPE-treated mice showed a substantial reduction in the levels of T cell subsets, GITR-expressing cells, and Th1 cytokines as well as the inflammatory mediators (MCP-1, MIP-2, and ICAM-1) that induce them compared with the vehicle-treated (saline) and arthritic mice. However, GSPE significantly upregulated the number of Tregs and Th2 cytokine producing cell number or it also induced Th17/Treg rebalance and orchestrated various pro-inflammatory and anti-inflammatory cytokines and the gene expression of their mediators that mediate cellular infiltration into the joints. This might, contribute to its anti-arthritic activity. Our results suggest that p.o. treatment with GSPE attenuated AIA in mice might offer a promising alternative/adjunct treatment for RA.
Cytokine | 2014
Sheikh F. Ahmad; Khairy M.A. Zoheir; Saleh A. Bakheet; Abdelkader E. Ashour; Sabry M. Attia
Rheumatoid arthritis (RA) is one of the major autoimmune diseases of global prevalence. Irrespective of much research in RA disease, no drugs with capable safety profiles are yet available. Poly(ADP-ribose) polymerase-1 (PARP-1) synthesizes and transfers ADP ribose polymers to target proteins, and regulates DNA repair and genomic integrity maintenance. PARP-1 also plays a crucial role in the progression of the inflammatory response, and its inhibition confers protection in several models of inflammatory disorders. We investigated the possible anti-arthritic effects of the PARP-1 inhibitor 5-aminoisoquinolinone (5-AIQ) in a mouse model of adjuvant induced arthritis (AIA). In this study, we examined the effects of 5-AIQ on the key mediators of arthritic inflammation, namely, edema and arthritic score, T cell subsets, regulatory T (Treg) cells, IL-17A, GITR expressing cells, NF-kB p65, IkB-α and pro and anti-inflammatory mediators mRNA expression levels. PARP-1 inhibition 5-AIQ treatment significantly attenuated the severity of AIA, reduced the arthritis scores, a substantial reduction in the levels of T cell subsets, IL-17A, NF-kB p65, GITR expressing cells, and as well as the pro-inflammatory mediators. However, 5-AIQ significantly up-regulated the number of Tregs cells, IkB-α levels and mRNA expression of anti-inflammatory mediators. Our results suggest that treatment with 5-AIQ attenuated AIA in mice might offer a promising alternative/adjunct treatment for RA.
Cellular Immunology | 2014
Sheikh F. Ahmad; Khairy M.A. Zoheir; Hala E. Abdel-Hamied; Abdelkader E. Ashour; Saleh A. Bakheet; Sabry M. Attia; Adel R.A. Abd-Allah
Naringin, a well-known flavanone glycoside found in grapefruit and other citrus fruits, was determined to be an effective anti-inflammatory compound. We investigated the effect of naringin on the key mediators of arthritic inflammation, namely T cell subsets, CD4(+)GITR(+) expressing cells, CD4(+)CD25(+)Foxp3(+) (Treg), Th1/Th2 cytokines and inflammatory mediators. We treated Balb/c mice (p.o.) with naringin (20, 40 and 80 mg/kg) for 14 days. Compared with the vehicle-treated and arthritic-control mice, the naringin treatment demonstrated a considerable decrease in the level of T cells, CD4(+)GITR(+), Th1 cytokine and inflammatory mediator expressions. In contrast, naringin treatment resulted in significantly up-regulated Treg and Th2 cytokine levels. Therefore, the naringin-induced inhibition of the T cells, various pro-inflammatory cytokines and inflammatory mediators that facilitate cellular infiltration into the joints might have contributed to its anti-arthritic activity. Our data suggest that naringin diminished the AIA in mice and it could be a potential alternative/adjunct treatment for RA.
Immunological Investigations | 2016
Naif O. Al-Harbi; Faisal Imam; Mohammed M. Al-Harbi; Mushtaq Ahmad Ansari; Khairy M.A. Zoheir; Hesham M. Korashy; Mohamed M. Sayed-Ahmed; Sabry M. Attia; Othman A. Shabanah; Sheikh F. Ahmad
ABSTRACT Dexamethasone (DEX) is a synthetic glucocorticoid with potent anti-inflammatory effects that is widely used to treat inflammatory diseases. The aim of the present study was to investigate the possible protective effect of DEX on the lipopolysaccharides (LPS)-induced acute lung injury (ALI) in a mouse model. Animals were pretreated with DEX (5 and 10 mg/kg, i.p.) for seven days and acute lung injury was induced by intranasal (i.n.) administration of LPS on day 7. In the present study, administration of LPS resulted in significant increase in neutrophils and lymphocytes count whereas a substantial reduction in T cell subsets (CD3+ and CD4+) and pro-inflammatory (IL-6 and TNF-α) cytokines occurred, which were reversed by DEX treatment. RT-PCR analysis revealed an increased mRNA expression of IL-6, TNF-α, COX-2, iNOS, and NF-κB p65 and decreased IL-10 in the LPS group, which were reversed by treatment with DEX in lung tissues. Western blot analysis revealed an increased expression of COX-2, iNOS and NF-κB p65 in the LPS-group, which was reduced by treatment with DEX. Compared with the LPS group, the DEX treatment also demonstrated a considerable increase in the protein expression level of IL-10 cytokine. Administration of LPS resulted in marked increase in malondialdehyde (MDA) levels and myeloperoxidase (MPO) activity whereas noticeable decrease in glutathione (GSH) content. These changes were significantly reversed by treatment with DEX. The histological examinations revealed protective effect of DEX while LPS group aggravated lung injury. The present findings demonstrate the potent anti-inflammatory action of the DEX against acute lung injury induced by LPS.
Animal Reproduction Science | 2010
Khairy M.A. Zoheir; Ahmed A. Allam
This study aimed to detect the sex of bovine embryo by adding ethidium bromide (EB) or 5 microl of CuSO(4) at different concentrations (0.5 M, 1 M, 1.5 M, 2 M, 3 M and 5 M) to the product of loop-mediated isothermal amplification (LAMP) reaction. The result of these additions was a colour change and a precipitate. This allows detection with the naked eye without the use of electrophoresis or a turbidity meter. The in vitro produced bovine embryos were divided into one to eight pieces using a microblade attached to a micromanipulator. The cell number in each piece was counted before sexing. Sexing of DNA samples extracted from one to five biopsies cells was performed by LAMP. After biopsy, the remaining part of the embryos was used to confirm the sex by polymerase chain reaction (PCR). The time for the whole procedure was about 45 min. LAMP is a novel DNA amplification method which amplifies a target sequence specifically under isothermal condition. We used this method to examine 58 bovine embryos and the accuracy of sex prediction was 100% when the blastomeres dissociated from a morula exceeds three. This study showed that the present method can be applied in bovine breeding programs to facilitate manipulation of the sex ratio of offspring. The aim of this study is to develop an improved embryo sexing technique based on the LAMP reaction. This new method is economic and more suitable for field application without turbidity meter or electrophoresis.
Pharmacological Research | 2015
Faisal Imam; Naif O. Al-Harbi; Mohammed M. Al-Harbi; Mushtaq Ahmad Ansari; Khairy M.A. Zoheir; Muzaffar Iqbal; Md. Khalid Anwer; Ali R. Al Hoshani; Sabry M. Attia; Sheikh F. Ahmad
Diosmin, a natural flavonoid glycoside present abundantly in the pericarp of various citrus fruits. Because of its anti-inflammatory and antioxidant properties, it can be used in many diseases. In this study, we investigated the possible protective mechanisms of the diosmin on LPS-induced lung injury through inhibition of T cell receptors, pro-inflammatory cytokines and NF-κB activation. Animals were pretreated with diosmin (50 and 100mg/kg, p.o.) for seven days prior to lipopolysaccharides (LPS) treatment. LPS administration increased neutrophils, monocytes, lymphocytes, total leukocyte count (TLC) and platelets which were decreased by diosmin. We observed that mice exposed to LPS showed increased malondialdehyde level and MPO activity whereas marked decrease in glutathione content. These changes were significantly reversed by treatment with diosmin in a dose dependent manner. Diosmin treatment showed a substantial reduction in T cell (CD4(+) and CD8(+)) receptors and pro-inflammatory (IL-2(+) and IL-17(+)) cytokines in whole blood. In addition, RT-PCR analysis revealed increased mRNA expression of IL-6, IL-17, TNF-α, and NF-κB in the LPS group, while reduced by treatment with diosmin. Western blot analysis confirmed the increased protein expression of IL-1β, TNF-α and NF-κB p65 in the LPS group and treatment of animals with diosmin reversed these effects. The levels of cytoplasmic p-IκB-α and p-NF-κB p65 expression also were mitigated by diosmin. The histological examinations revealed protective effect of diosmin while LPS group aggravated lung injury. These results support the potential for diosmin to be investigated as a potential agent for the treatment of lung injury and inflammatory diseases.
Molecular Immunology | 2015
Sheikh F. Ahmad; Khairy M.A. Zoheir; Mushtaq Ahmad Ansari; Hesham M. Korashy; Saleh A. Bakheet; Abdelkader E. Ashour; Othman A. Al-Shabanah; Mohammed M. Al-Harbi; Sabry M. Attia
Increasing indication is unveiling a role for poly(ADP-ribose) polymerase (PARP)-1 in the regulation of inflammatory/immune responses. The aim of the present study was to determine the potential anti-inflammatory effects of PARP-1 inhibitor 5-aminoisoquinolinone (5-AIQ) to explore the role of PARP-1 inhibitor in a mouse model of carrageenan-induced lung inflammation. A single dose of 5-AIQ (1.5mg/kg) was administered intraperitoneally (i.p.) 1h before λ-carrageenan (Cg) administration. We assessed the effects of 5-AIQ treatment on CD25(+), GITR(+), CD25(+)GITR(+), IL-17(+) and Foxp3(+) cells which were investigated using flowcytometry in pleural exudates and heparinized blood. We also evaluated mRNA expressions of IL-6, TNF-α, IL-1β, IL-10, CD11a, l-selectin (CD62L), ICAM-1, MCP-1, iNOS and COX-2 in the lung tissue. We further examined the effects of 5-AIQ on the key mediators of inflammation, namely COX-2, STAT-3, NF-kB p65, PARP-1, IkB-α and IL-4 protein expression in the lung tissue using western blotting. The results illustrated that the numbers of T cell subsets, IL-17(+) cytokine levels were markedly increased and Foxp3(+) production decreased in the Cg group. Furthermore, Cg-induced up-regulation of adhesion molecules, pro-inflammatory mediators and chemokine expressions. Western blot analysis revealed an increased protein expressions of COX-2, STAT-3 NF-kB p65 and PARP-1 and decreased IkB-α and IL-4 in the Cg group. PARP-1 inhibitor via 5-AIQ treatment reverses the action significantly of all the previously mentioned effects. Moreover, histological examinations revealed anti-inflammatory effects of 5-AIQ, whereas Cg-group aggravated Cg-induced inflammation. Present findings demonstrate the potent anti-inflammatory action of the PARP-1 inhibitor in acute lung injury induced by carrageenan.