Selim, A. M., Y. A. Elsabagh, M. M. El-Sawalhi, N. A. Ismail, and M. A. Senousy, "Association of integrin-β2 polymorphism and expression with the risk of rheumatoid arthritis and osteoarthritis in Egyptian patients.", BMC medical genomics, vol. 16, issue 1, pp. 204, 2023. Abstract

BACKGROUND: The genetic architecture of rheumatoid arthritis (RA) and osteoarthritis (OA) are still unclear. Although RA and OA have quite different causes, they share synovial inflammation, risk factors, and some disease-associated genes, including the integrin subunit β2 (ITGB2)/CD18 gene involved in extracellular matrix interactions and immune cell signaling. However, the functional role of ITGB2 genetic variants, its circulating expression pattern, and their clinical usefulness in RA and OA remain unexplored. Our study appraised the association of ITGB2 rs2070946 single nucleotide polymorphism with the vulnerability to RA and OA and its influence on ITGB2 mRNA expression, along with the potential of serum ITGB2 expression in RA and OA diagnosis.

METHODS: This study included 70 RA patients, 70 primary OA patients, and 60 healthy volunteers. Genotyping and gene expression analysis were performed using qPCR. Bioinformatics analysis was employed to construct the protein-protein interaction (PPI) network of ITGB2.

RESULTS: Serum ITGB2 mRNA expression was upregulated in both RA and OA compared to healthy controls. ITGB2 rs2070946 was associated with escalating risk of both diseases. RA patients harboring the rs2070946 CC or TC + CC genotypes had higher serum ITGB2 expression than the TT genotype carriers. Likewise, OA patients having the minor homozygote CC genotype had higher serum ITGB2 expression than those carrying the TT, TC or TT + TC genotypes. Serum ITGB2 expression showed profound diagnostic potential for RA and OA in receiver-operating characteristic analysis. In RA, serum ITGB2 expression positively correlated with rheumatoid factor and disease activity score 28 (DAS28). The ITGB2-PPI network enriched in cell-cell adhesion, ICAM-3 receptor activity, T-cell activation, leukocyte adhesion, complement binding, and NF-κB, tumor necrosis factor, and interleukin signaling pathways.

CONCLUSION: These findings embrace the impact of ITGB2 rs2070946 as a novel genetic biomarker of both RA and OA, which could alter the ITGB2 expression. Serum ITGB2 expression could aid in timely diagnosis of RA and OA.

Attia, M. S., H. A. Ewida, M. A. Abdel Hafez, S. A. EL-Maraghy, and M. M. El-Sawalhi, "Altered Lnc-EGFR, SNHG1, and LincRNA-Cox2 Profiles in Patients with Relapsing-Remitting Multiple Sclerosis: Impact on Disease Activity and Progression.", Diagnostics (Basel, Switzerland), vol. 13, issue 8, 2023. Abstract

Relapsing-remitting multiple sclerosis (RRMS) is the most prevalent MS subtype. Ample evidence has indicated that long noncoding RNAs (lncRNAs) are crucial players in autoimmune and inflammatory disorders. This study investigated the expression of lnc-EGFR, SNHG1, and lincRNA-Cox2 in RRMS patients during active relapses and in remission. Additionally, the expression of FOXP3, a master transcription factor for regulatory T cells, and NLRP3-inflammasome-related genes were determined. Relationships between these parameters and MS activity and annualized relapse rate (ARR) were also evaluated. The study included 100 Egyptian participants: 70 RRMS patients (35 during relapse and 35 in remission) and 30 healthy controls. RRMS patients showed significant downregulation of lnc-EGFR and FOXP3 and dramatic upregulation of SNHG1, lincRNA-Cox2, NLRP3, ASC, and caspase-1 compared to controls. Lower serum TGF-β1 and elevated IL-1β levels were observed in RRMS patients. Notably, patients during relapses displayed more significant alterations than those in remission. Lnc-EGFR was positively correlated with FOXP3 and TGF-β1 and negatively correlated with ARR, SNHG1, lincRNA-Cox2, and NLRP3 inflammasome components. Meanwhile, SNHG1 and lincRNA-Cox2 were positively correlated with ARR, NLRP3, ASC, caspase-1, and IL-1β. Excellent diagnostic performance for lnc-EGFR, FOXP3, and TGF-β1 was demonstrated, while all biomarkers exhibited strong prognostic potential for predicting relapses. Finally, the differential expression of lnc-EGFR, SNHG1, and lincRNA-Cox2 in RRMS patients, especially during relapses, suggests their involvement in RRMS pathogenesis and activity. Correlation between their expression and ARR implies relationships to disease progression. Our findings also highlight their promising roles as biomarkers for RRMS.

El-Sawalhi, M. M., and L. A. Ahmed, "Exploring the protective role of apocynin, a specific NADPH oxidase inhibitor, in cisplatin-induced cardiotoxicity in rats", Chemico-biological interactions, vol. 207: Elsevier, pp. 58–66, 2014. Abstract
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El-Sawalhi, M. M., H. A. Darwish, M. N. Mausouf, and A. A. Shaheen, "Modulation of age-related changes in oxidative stress markers and energy status in the rat heart and hippocampus: a significant role for ozone therapy", Cell biochemistry and function, vol. 31, no. 6, pp. 518–525, 2013. Abstract
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Ismail, N. A., A. A. Shaheen, M. M. El-Sawalhi, and Y. M. Megahed, "Effect of calcium channel antagonists in modifying the inhibitory influence of adenosine on insulin secretion.", Arzneimittel-forschung, vol. 45, no. 8, pp. 865–868, 1995. Abstract
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Arab, H. H., and M. M. El-Sawalhi, "Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: modulation of oxidative stress and inflammatory mediators", Toxicology and applied pharmacology, vol. 268, no. 2: Academic Press, pp. 241–248, 2013. Abstract
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EL-Maraghy, S. A., S. M. Rizk, M. M. El-Sawalhi, and others, "Hepatoprotective potential of crocin and curcumin against iron overload-induced biochemical alterations in rat", Afr J Biochem Res, vol. 3, no. 5, pp. 215–21, 2009. Abstract
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Abd-El-Fattah, A. A., M. M. El-Sawalhi, E. R. Rashed, and M. A. El-Ghazaly, "Possible role of vitamin E, coenzyme Q10 and rutin in protection against cerebral ischemia/reperfusion injury in irradiated rats", International journal of radiation biology, vol. 86, no. 12: Taylor & Francis, pp. 1070–1078, 2010. Abstract
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AbdEl-Gawad, H. M., and M. M. El-Sawalhi, "Nitric oxide and oxidative stress in brain and heart of normal rats treated with doxorubicin: role of aminoguanidine", Journal of Biochemical and Molecular Toxicology, vol. 18, no. 2: Wiley Subscription Services, Inc., A Wiley Company Hoboken, pp. 69–77, 2004. Abstract
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Gad, M. Z., M. M. El-Sawalhi, M. F. Ismail, and N. D. El-Tanbouly, "Biochemical study of the anti-diabetic action of the Egyptian plants Fenugreek and Balanites", Molecular and cellular Biochemistry, vol. 281: Kluwer Academic Publishers, pp. 173–183, 2006. Abstract
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